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12,300 | 25,681,239 | Subgroup analyses showed that this effect was strongest in colorectal surgery and that IOWI with antibiotic solutions had a stronger effect than irrigation with PVP-I or saline .
Conclusion These results suggest that IOWI before skin closure represents a pragmatic and economical approach to reduce postoperative SSI after abdominal surgery and that antibiotic solutions seem to be more effective than PVP-I solutions or simple saline , and it might be worth to re-evaluate their use for specific indications | Purpose Surgical site infection ( SSI ) remains to be one of the most frequent infectious complications following abdominal surgery .
Prophylactic intra-operative wound irrigation ( IOWI ) before skin closure has been proposed to reduce bacterial wound contamination and the risk of SSI .
However , current recommendations on its use are conflicting especially concerning antibiotic and antiseptic solutions because of their potential tissue toxicity and enhancement of bacterial drug resistances . | BACKGROUND Postoperative surgical site infections are one of the most frequent complications after open abdominal surgery , and triclosan-coated sutures were developed to reduce their occurrence . The aim of the PROUD trial was to obtain reliable data for the effectiveness of triclosan-coated PDS Plus sutures for abdominal wall closure , compared with non-coated PDS II sutures , in the prevention of surgical site infections . METHODS This multicentre , r and omised controlled group-sequential superiority trial was done in 24 German hospitals . Adult patients ( aged ≥18 years ) who underwent elective midline abdominal laparotomy for any reason were eligible for inclusion . Exclusion criteria were impaired mental state , language problems , and participation in another intervention trial that interfered with the intervention or outcome of this trial . A central web-based r and omisation tool was used to r and omly assign eligible participants by permuted block r and omisation with a 1:1 allocation ratio and block size 4 before mass closure to either triclosan-coated sutures ( PDS Plus ) or uncoated sutures ( PDS II ) for abdominal fascia closure . The primary endpoint was the occurrence of superficial or deep surgical site infection according to the Centers for Disease Control and Prevention criteria within 30 days after the operation . Patients , surgeons , and the outcome assessors were masked to group assignment . Interim and final analyses were by modified intention to treat . This trial is registered with the German Clinical Trials Register , number DRKS00000390 . FINDINGS Between April 7 , 2010 , and Oct 19 , 2012 , 1224 patients were r and omly assigned to intervention groups ( 607 to PDS Plus , and 617 to PDS II ) , of whom 1185 ( 587 PDS Plus and 598 PDS II ) were analysed by intention to treat . The study groups were well balanced in terms of patient and procedure characteristics . The occurrence of surgical site infections did not differ between the PDS Plus group ( 87 [ 14·8 % ] of 587 ) and the PDS II group ( 96 [ 16·1 % ] of 598 ; OR 0·91 , 95 % CI 0·66 - 1·25 ; p=0·64 ) . Serious adverse events also did not differ between the groups-146 of 583 ( 25·0 % ) patients treated with PDS Plus had at least one serious adverse event , compared with 138 of 602 ( 22·9 % ) patients treated with PDS II ; p=0·39 ) . INTERPRETATION Triclosan-coated PDS Plus did not reduce the occurrence of surgical site infection after elective midline laparotomy . Innovative , multifactorial strategies need to be developed and assessed in future trials to reduce surgical site infections . FUNDING Johnson & Johnson Medical Limited A r and omized controlled trail in 374 patients requiring emergency appendicectomy to determine the value of topical ampicillin and antiseptic solution of chlorhexidine and cetyl trimethyl ammonium bromide ( Savlon ) in preventing wound infection is reported . The application of 1 g of ampicillin powder to the wound significantly reduced wound infection in perforated appendicitis , but not in unperforated appendicitis . Wound irrigation with 1 per cent cetyl trimethyl ammonium bromide was ineffective in preventing wound infection in all grade s of appendicitis . When wound contamination is difficult to avoid , as in perforated appendicitis , topical ampicillin should be used to reduce the rate of wound infection Objective To determine the clinical effectiveness of wound edge protection devices in reducing surgical site infection after abdominal surgery . Design Multicentre observer blinded r and omised controlled trial . Participants Patients undergoing laparotomy at 21 UK hospitals . Interventions St and ard care or the use of a wound edge protection device during surgery . Main outcome measures Surgical site infection within 30 days of surgery , assessed by blinded clinicians at seven and 30 days and by patient ’s self report for the intervening period . Secondary outcomes included quality of life , duration of stay in hospital , and the effect of characteristics of the patient and operation on the efficacy of the device . Results 760 patients were enrolled with 382 patients assigned to the device group and 378 to the control group . Six patients in the device group and five in the control group did not undergo laparotomy . Fourteen patients , seven in each group , were lost to follow-up . A total of 184 patients experienced surgical site infection within 30 days of surgery , 91/369 ( 24.7 % ) in the device group and 93/366 ( 25.4 % ) in the control group ( odds ratio 0.97 , 95 % confidence interval 0.69 to 1.36 ; P=0.85 ) . This lack of benefit was consistent across wound assessment s performed by clinicians and those reported by patients and across all secondary outcomes . In the secondary analyses no subgroup could be identified in which there was evidence of clinical benefit associated with use of the device . Conclusions Wound edge protection devices do not reduce the rate of surgical site infection in patients undergoing laparotomy , and therefore their routine use for this role can not be recommended . Trial registration Current Controlled Trials IS RCT N This study sought to determine in a district general hospital ( a ) the frequency and nature of bacterial contamination at operation , ( b ) the incidence of consequent infection and ( c ) the prophylactic effect , if any , of inter‐parietal povidone‐iodine against postoperative wound infection This study compared the efficacy of a single intravenous dose of Cefazolin alone or combined with an antibiotic containing preclosure-irrigation solution in patients undergoing cesarean section . A total of 308 patients were prospect ively assigned to two groups by r and omization . Group I received two grams of Cefazolin IV and abdomino-peritoneal irrigation with saline . Group II received one gram of Cefazolin IV and one gram in the saline irrigation solution . The rate of total postoperative morbidity was 2.3 times higher in Group I compared to Group II ( 16/154 or 10.4 % vs 7/154 or 4.5 % ) and morbidity at the operative site was six times higher ( 13/154 or 8.4 % vs 2/154 or 1.3 % ) One hundred ninety patients with peritonitis at the time of abdominal surgery were allocated at r and om to systemic antibiotic treatment alone or systemic antibiotic treatment combined with topical application of antibiotics in the wound at the time of wound closure . The overall wound infection rate was 17 percent without significant difference between the two treatment groups ( P>0.80 ) To evaluate syringe pressure irrigation of the surgical wound to decrease its infection after appendectomy , we design ed a r and omized control trial at the Emergency Department of Mexico City General Hospital , including 350 patients with acute abdomen suggestive of appendicitis , without any other infection clinical ly evident . The trial was r and omized into 2 groups . Group I patients received prophylactic systemic antibiotics before surgery . Group II patients received the same prophylactic systemic antibiotics plus syringe pressure irrigation of the surgical wound with 300 ml of saline solution using a 20-ml syringe with 19-gauge intravenous ( IV ) catheter to measure the incidence of postoperative wound infection . In our results , 283 patients had appendicitis . Of these , 188 were uncomplicated ( 66.4 % ) and 95 ( 33.6 % ) were complicated . Of the complicated cases , 40 were assigned to group I , and of these , 29 ( 72.5 % ) developed wound infection . In group II there were 55 patients and only 9 ( 16.3 % ) developed wound infection after syringe pressure irrigation [ p= 0.000001 ; 95 % confidence interval ( CI ) = 0.02–0.22 ] . We conclude that syringe pressure irrigation of the surgical wound after appendectomy contributes significantly to decrease the incidence of postoperative wound infection in complicated cases . It is a cheap , safe , and accessible method in any surgical room In this prospect i ve , r and omized study of 187 patients undergoing a variety of general surgical procedures , no significant difference could be demonstrated between those patients whose wounds were irrigated with normal saline solution and those whose wounds were irrigated with povidone-iodine . The potential of an alpha or a beta error is discussed No carefully controlled trial of the use of topical ampicillin in cholecystectomy wounds has been described . A series of 100 consecutive cholecystecomies performed by one surgeon using this drug in a double‐blind manner is reported . The efficacy of topical ampicillin in lowering the wound‐infection rate as shown by other authors is not confirmed The wound-infection rate after abdominal operations was compared in 113 patients r and omly allocated to an untreated control group , a group receiving preoperative lincomycin and tobramycin , or a group receiving local instillation of povidone-iodine . The wound-infection rate was 8.1 % in 37 patients receiving antibiotics , 42.1 % in 38 untreated controls , and 39.5 % in 38 patients in the povidone-iodine group The effect of povidone iodine on wound sepsis following gastrointestinal surgery was studied in a trial involving 153 patients of whom 72 had their wounds sprayed with povidone iodine dry powder ( Disadine DP ) and 81 acted as a control group . The infection rate of 9·9 per cent in the patients treated with povidone iodine was significantly lower than that of 24·4 per cent in the control group ( P<0·05 ) . Bacterial contamination of the wound at the time of operation was shown to be of importance , being associated with a 52 per cent infection rate in the control group . However , spraying of contaminated wounds with povidone iodine reduced the infection rate to the significantly lower level of 11 per cent ( P<0·05 ) . We conclude that povidone iodine is a safe and effective means of reducing wound sepsis following gastrointestinal surgery A r and omized stratified clinical trial of topical povidone‐iodine in 627 patients undergoing abdominal procedures demonstrated a reduction in postoperative wound sepsis in female patients , in patients receiving subcutaneous low dose heparin and during the first quarter of the trial when the infection rate in control subjects was high . Overall , there was no significant reduction in wound sepsis after administration of povidone‐iodine due mainly to a high infection rate in povidone‐iodine treated male appendix operations where , by chance , there was an increased incidence of contamination with Bacteroides fragilis Single doses of clindamycin hydrochloride and gentamicin sulfate given preoperatively , combined with intraoperative topical application of povidone-iodine were given to patients with perforated or gangrenous appendicitis . The incidence of wound sepsis was reduced from 36 % to 5 % ; severe infections were reduced from 25 % to 0 % when compared with a control untreated group of patients . When used alone , povidone-iodine had little effect in these patients . No toxic effects of the antibiotics or antiseptic were recorded nor were any resistant strains of pathogenic organisms grown from cultures OBJECTIVE To evaluate whether saline wound irrigation decreases the incidence of wound infection following abdominal gynecologic surgery . METHOD In this prospect i ve r and omized study , 104 patients underwent wound irrigation before wound closure following abdominal gynecologic surgery and 102 patients did not . RESULTS There were no significant differences between the 2 groups in patient characteristics or in factors influencing the incidence of wound infection after abdominal gynecologic surgery . The incidence of wound infection was 10.6 % among women who underwent wound irrigation and 9.8 % among those who did not , and the difference was not statistically significant . CONCLUSION Saline wound irrigation before abdominal wall closure is not helpful in decreasing the incidence of wound infection after abdominal gynecologic surgery In a prospect i ve blind trial in patients undergoing intraabdominal surgery , instillation of povodone iodine ( PVI ) solution into the wound failed to reduce the incidence of wound sepsis The effect of using topical povidone-iodine spray in addition to a single dose of intravenous metronidazole was studied in a clinical trial involving 200 patients undergoing appendicectomy . Despite the metronidazole , patients with perforated or gangrenous appendices still had an unacceptably high rate of wound infection . Overall , no benefit result ed from the addition of the povidone-iodine spray . Sub-dividing the patients according to the macroscopic state of the appendix , the degree of bacterial contamination of the operative wound or the depth of subcutaneous fat also failed to reveal any advantage gained by using the antiseptic The aim of this prospect i ve r and omised study was to estimate the effect of saline wound irrigation before wound closure in the prevention of infection following caesarean delivery . Participants with indications for elective or emergency caesarean section were r and omly allocated to two groups . A total of 260 women who underwent wound irrigation before wound closure and 260 did not . No demographic differences were identified between the groups . There were also no significant differences between the groups in terms of factors known to influence wound infection . The incidence of wound infection was 7.3 % for the control group and 6.5 % for the saline group ; however , the difference was not significant ( relative risk : 0.88 ; 95 % confidence interval : 0.45–1.74 ; p = 0.86 ) . In conclusion , saline wound irrigation before wound closure did not reduce the infection rate in patients undergoing caesarean delivery Background : Surgical-site infection is a common postoperative nosocomial infection . Surgeons frequently treat operative patients with protective antibiotics and often choose cefazolin as the drug . Treatment schemes include both preoperative intravenous dosing and intraoperative dosing by irrigation . This study was design ed to measure cefazolin concentrations both in serum and in wound drain fluid after intravenous dosing and after irrigation . Methods : The authors conducted an institutional review board – approved study involving r and omized allocation of breast reduction patients to group 1 ( preoperative intravenous dosing ) or group 2 ( intraoperative dosing by irrigation ) . Each patient had serum and wound drainage specimens measured over time for cefazolin concentrations . Cefazolin dosing was based on preparations commonly used in the authors ’ hospital . Results from 24 patients are reported . Results : Patients treated by conventional preoperative intravenous dosing displayed the expected serum degradation curve . These patients also demonstrated wound drainage concentrations ( peak , 22.49 & mgr;g/ml ) for approximately 4 to 5 hours . Measured concentrations were above the minimum therapeutic concentration ( 8 & mgr;g/ml ) for Staphylococcus aureus . Patients treated by wound irrigation also demonstrated serum concentrations above minimum therapeutic concentration . In addition , these patients ’ wound drain fluid demonstrated very high cefazolin concentrations ( peak , 4185.93 & mgr;g/ml ) , which remained high for 24 hours . Conclusions : Protective cefazolin concentrations in the wound can be achieved by both intravenous and irrigation delivery . Wound irrigation produces higher concentrations for longer periods of time Sequential analysis of a double-blind , fixed dose , controlled clinical trial comprising 64 patients treated by truncal vagotomy and pyloroplasty demonstrated a statistically significant reduction of postoperative wound infections by topical application of ampicillin in the wound Three hundred and fifteen patients with appendicitis were r and omized into two groups . One group received pre‐operative systemic gentamicin and metronidazole while the other group received 1 per cent topical povidone – iodine solution in addition to the antibiotics . For early appendicitis including normal and acutely inflamed appendices , only one dose of antibiotics was used . The postoperative wound sepsis was very low in both groups of patients and there was no statistical difference between them . For late appendicitis including gangrenous and perforated appendices , the antibiotics were continued for 7 days . Eight out of 51 patients who had the topical agent developed wound sepsis compared with one out of 52 patients who received no topical agent . This difference is statistically significant ( P = 0·03 ) . All wound infections presented within 2 weeks of operation and were deep . Povidone – iodine , 1 per cent , adversely affects the wound infection rate in late appendicitis and should not be used Whether or not topical application of ampicillin is necessary in patients undergoing elective colorectal operations was investigated . After mechanical preparation , 193 patients received 2 grams of cefotaxime administered intravenously from the start of the operation ; patients received two more doses within the next 12 hours . In addition , patients were r and omized to receive or not receive prophylaxis against infection of 2 grams of ampicillin in the site of the incision at closure . Twenty-three patients did not complete the study . Wound infection occurred in five of 81 patients who had topical application of ampicillin compared with six of 89 patients who did not receive prophylaxis ; the difference was not significant . There were no significant differences in rates of wound dehiscence , intra-abdominal abscess or anastomotic leakage . Escherichia coli and Bacteroides fragilis were the predominant microorganisms isolated . Thus , topical application of ampicillin did not lower the wound infection rate when there was a preoperative antibiotic administered intravenously The effects of intrarectal metronidazole and intraincisional povidone iodine on sepsis after emergency appendicectomy were compared in a double-blind r and omised controlled trial in 496 patients . Wound sepsis occurred in 12.3 % of metronidazole-treated patients compared with 24 % in the povidone-iodine group and 23.5 % in an untreated control group . The metronidazole-treated patients left hospital approximately 2 days earlier than patients in the other two groups . They returned to work sooner and receiver fewer visits from the district nursing service . A short six-dose course of metronidazole significantly reduces the wound-infection rate in patients over the age of 12 undergoing emergency appendicectomy . If the clinical and economic benefits of metronidazole shown by this study are confirmed , the drug should be considered for routine use in emergency appendicectomy The effect of topical ampicillin on the rate of wound infection after emergency appendicectomy was studied in a prospect i ve controlled trial of 200 patients . Sixteen per cent of patients in the control group developed a wound injection compared with 3 per cent of those receiving ampicillin powder in the wound ( P<0.01 ) . When patients with peritonitis were considered , 64 per cent of the 14 patients in the control group developed a wound infection compared with 13 per cent of the 15 patients in the ampicillin group Intermittent intraoperative antibiotic irrigation from the beginning of an operative procedure to its completion is a valuable supplement to hospital and operating room cleanliness and to good surgical technique . A prospect i ve , r and omized , double-blind study of 200 patients undergoing clean-contaminated operations on the gastrointestinal tract demonstrated a marked reduction in the incidence of postoperative wound infection and absolute prevention of postoperative peritonitis In a prospect i ve , r and omized trial , prophylactic use of topical antibiotics in addition to systemic prophylaxis was studied in patients undergoing abdominoperineal amputation of the rectum . All patients received gentamicin 80 mg and metronidazole 500 mg intravenously at induction of anesthesia , followed by the same dose 8 hourly for 48 hours . In accordance with the r and omization , half of the patients were additionally given gentamicin 160 mg + metronidazole 400 mg topically into the perineal wound at closure . Perineal wound infection appeared in 19 of the 41 patients who received both systemic and topical prophylaxis , and in 18 of the 38 with only systemic antibiotics . Cell-mediated immunity was preoperatively assessed with a skin test ( Multitest ) in all but three patients . Impairment of cell-mediated immunity was associated with significantly heightened rate of wound infection , and these patients did not benefit from topical antibiotics Wound healing following elective laparotomy was studied in 220 patients . The patients were divided into two groups ; the first group received preoperative skin disinfection with alcohol 70 % and iodine-tincture 2 % and , before skin suturing , disinfection with iodine . The second group received preoperative skin disinfection with povidone-iodine 10 % ( Betadine ) and , before skin closure , a 10 % povidone-iodine solution was applied to the subcutis and skin edges . Complicated wound healing was seen in 21 % of the first and 24 % of the second group ; wound sepsis rate was 13 % and 16 % respectively , in the majority of cases following colorectal surgery The effect of topical ampicillin sodium and polyglycolic acid and silk sutures on the recurrence of an existing hernia or an incisional hernia and on infection rates in clean abdominal wounds ( herniotomies and simple cholecystectomies ) was studied in a triple-blind , r and omized trial with 398 consecutive patients . One infection , three suture sinuses , and two incisional hernias occurred among 113 patients with cholecystectomies , while the corresponding rates in 285 patients with hernia repairs were 11 infections , no suture sinuses , and three recurrent hernias . No effect of ampicillin could be demonstrated , nor was any difference between polyglycolic acid and silk sutures shown . No interaction between the antibiotic and suture material was found , and no side effects were observed . Wound infection was significantly more frequent in patients with postoperative seromas or hematomas A prospect i ve , r and omized trial of prophylaxis against wound infection in acute abdominal surgery was conducted in 210 patients comparing systemic administration of 2 antibiotics active against bowel organisms , topical administration of povidone iodine to the wound , and no prophylactic treatment . Prophylactic treatment was given only on the day of operation . There was a significant decrease in wound infection following both types of prophylactic treatment compared to no treatment . There was no significant difference in results between systemic treatment with antibiotics and povidone iodine sprayed into the wound . The advantage of topical treatment with povidone iodine over antibiotic treatment is that development of bacterial resistance is not a hazard . RésuméUne étude prospect i ve r and omisée de l'infection des plaies après chirurgie abdominale d'urgence a comparé , chez 210 malades , les effets de l'administration systématique de deux antibiotiques actifs contre les germes intestinaux , de l'application d'iodure de povidone dans la plaie et de l'absence de tout traitement prophylactique . Les antibiotiques ont été administrés uniquement le jour de l'opération . Par rapport à l'absence de traitement , les deux types de prophylaxie réduisent de façon significative la fréquence des infections . Mais il n'y a pas de différence significative entre les effets des antibiotiques et ceux de l'iodure de povidone in loco . Par rapport aux antibiotiques , l'iodure de povidone offre un avantage : il n'y a pas de risque de développement d'une résistance bactérienne Prophylactic use of topical ampicillin in addition to intravenous ampicillin and metronidazole was studied in a r and omized trial including 203 consecutive patients undergoing elective colorectal surgery . All received ampicillin , 1g × 3 , and metronidazole , 0.5g × 3 , intravenously for at least three days from induction of anesthesia , and 105 also received topical ampicillin , 1 g , in each of the surgical wounds . Deep wound infection or dehiscence was seen in 12 of 105 having both administrations of antibiotics , and in nine of 98 having only intravenous antibiotics . The two groups were similar according to distribution of sex , age , type of surgery , and efficiency of bowel preparation . Topical ampicillin should be omitted in elective colorectal surgery when systemic prophylaxis with ampicillin and metronidazole is used Two hundred forty-six patients with acute appendicitis were r and omly assigned to one of two groups . One group of 120 patients received systemic clindamycin preoperatively . Another group of 126 patients received , in addition to systemic clindamycin , a solution of topical ampicillin applied to subcutaneous tissues . No differences were found in the characteristics of the two groups . Combined prophylaxis with clindamycin and ampicillin significantly reduced wound infection to 4 % , compared with clindamycin alone ( p less than 0.02 ) . A decrease in the surgical wound infection rate in the group treated with clindamycin and ampicillin was mainly observed in patients with advanced ( gangrenous and perforated ) appendicitis ( p less than 0.05 ) . A significant decrease in wound infection rates in patients with positive culture results was also found . We conclude that prophylaxis with a combination of systemic clindamycin and topical ampicillin solution , when compared with clindamycin alone , more effectively prevents wound infection after emergency appendectomy , especially in patients with serious wound contamination BACKGROUND The reported incidence of surgical site infection after abdominal surgery in morbidly obese patients is high ( about 15 % in most studies ) , and this is associated with considerable disability and an increased economic burden . Topical antibiotics may reduce the incidence of serious infections . METHODS St and ard techniques for the prevention of surgical site infections were used along with the introduction of kanamycin into the subcutaneous space of morbidly obese patients at the time of closure and allowing it to dwell for 2 h. Eight hundred thirty-seven evaluable patients were followed for the development of site complications for at least six weeks postoperatively . RESULTS One of the 65 patients with a revisional procedure had a primary deep incisional surgical site infection , as did one of the 772 patients with a primary operation . Secondary deep incisional surgical site infections occurred in four patients , two after spontaneous evacuation of a seroma , one from excessive superficial contamination , and one following separation of a nonhealing surgical site . Additionally , 21 patients had minor surgical site complications including incisional separation and stitch-related infections , which required no significant expenditure of re sources . CONCLUSIONS Prolonged contact ( 2 h ) of topical kanamycin solution with the surgical site greatly reduces the incidence of primary infections in the deep subcutaneous space of laparotomy sites in morbidly obese patients |
12,301 | 19,160,269 | Behavioural interventions of general advice only are not effective and may reduce abstinence .
Individualized interventions , very low calorie diets , and CBT may be effective and not reduce abstinence .
Exercise interventions are not associated with reduced weight gain at end of treatment , but may be associated with worthwhile reductions in weight gain in the long term , Bupropion , fluoxetine , nicotine replacement therapy , and probably varenicline all reduced weight gain while being used .
Although this effect was not maintained one year after quitting for bupropion , fluoxetine , and nicotine replacement , the evidence is insufficient to exclude a modest long-term effect . | BACKGROUND Most people who stop smoking gain weight , on average about 7 kg in the long term .
There are some interventions that have been specifically design ed to tackle smoking cessation whilst also limiting weight gain .
Many smoking cessation pharmacotherapies and other interventions may also limit weight gain .
OBJECTIVES This review is divided into two parts . ( | Sixty subjects were run in a study comparing the use of nicotine gum with placebo gum during cessation from smoking . Subjects were given clinic support and chewed the gum ad libitum . A survival analysis showed the two groups differed significantly in successful abstinence over time ( p less than .03 ) . Differences between groups appeared early ( within weeks ) and , at six months , a 28 % superiority of nicotine over placebo gum was demonstrated with mean success rates of 48 % and 20 % , respectively . Between six months and one year , relapse in the nicotine group accounted for the 30 % vs. 20 % success rates for nicotine and placebo observed at one year . In a pilot study ( " dispensary " ) testing the efficacy of the two gums when intervention was minimal , subjects in both groups resumed smoking within the first two weeks . The enhanced short-term success rates with nicotine gum in the clinic study are attributed to an effective interaction between use of the active preparation and clinic support . Long-term cessation may require extended maintenance procedures and /or an identification of optimal gum use A non-combustible nicotine inhaler , administered orally , has been developed for treatment of smokers . The inhaler allows weaning from nicotine while maintaining partial reinforcement of the ritual/sensory phenomena of smoking . Subjects were r and omly assigned to active ( n = 112 ) and placebo ( n = 111 ) groups . Some behavioral intervention occurred as a function of participation . Strict abstinence ( primary outcome criterion ) was defined by CO < or = 8 ppm with no slips allowed at any time and cotinine values < or = 14 at 1 year . Survival analysis showed active inhaler was superior to placebo ( p < 0.01 ) . Active vs. placebo success rates were : 63 % vs. 47 % ( day 3 ) , 46 % vs. 28 % ( week 1 ) , 36 % vs. 19 % ( week 2 ) , 33 % vs. 16 % ( week 3 ) , 29 % vs. 14 % ( week 6 ) , 24 % vs. 10 % ( 3 months ) , 17 % vs. 9 % ( 6 months ) and 13 % vs. 8 % ( 1 year ) . chi 2 analyses were significant through 3 months but not at 6 months ( p < 0.08 ) or 1 year . Craving was relieved with active inhalers at day 3 and week 1 . Subjects averaged six inhalers/day . Cotinine levels were 57 - 61 % of smoking levels . Common side effects included throat/mouth irritation and coughing . Failure was predicted by early slips . The inhaler is clearly useful for short-term smoking cessation with potential for long-term efficacy . Extended access to the inhaler and relapse prevention training could improve success rates . Another promising approach would be to combine the inhaler with a nicotine patch BACKGROUND Altering the macronutrient composition of the diet influences hunger and satiety . Studies have compared high- and low-protein diets , but there are few data on carbohydrate content and ketosis on motivation to eat and ad libitum intake . OBJECTIVE We aim ed to compare the hunger , appetite , and weight-loss responses to a high-protein , low-carbohydrate [ ( LC ) ketogenic ] and those to a high-protein , medium-carbohydrate [ ( MC ) nonketogenic ] diet in obese men feeding ad libitum . DESIGN Seventeen obese men were studied in a residential trial ; food was provided daily . Subjects were offered 2 high-protein ( 30 % of energy ) ad libitum diets , each for a 4-wk period-an LC ( 4 % carbohydrate ) ketogenic diet and an MC ( 35 % carbohydrate ) diet-r and omized in a crossover design . Body weight was measured daily , and ketosis was monitored by analysis of plasma and urine sample s. Hunger was assessed by using a computerized visual analogue system . RESULTS Ad libitum energy intakes were lower with the LC diet than with the MC diet [ P=0.02 ; SE of the difference ( SED ) : 0.27 ] at 7.25 and 7.95 MJ/d , respectively . Over the 4-wk period , hunger was significantly lower ( P=0.014 ; SED : 1.76 ) and weight loss was significantly greater ( P=0.006 ; SED : 0.62 ) with the LC diet ( 6.34 kg ) than with the MC diet ( 4.35 kg ) . The LC diet induced ketosis with mean 3-hydroxybutyrate concentrations of 1.52 mmol/L in plasma ( P=0.036 from baseline ; SED : 0.62 ) and 2.99 mmol/L in urine ( P<0.001 from baseline ; SED : 0.36 ) . CONCLUSION In the short term , high-protein , low-carbohydrate ketogenic diets reduce hunger and lower food intake significantly more than do high-protein , medium-carbohydrate nonketogenic diets The authors examine weight gains associated with smoking cessation in the Lung Health Study ( 1986 - 1994 ) over a 5-year follow-up period . A cohort of 5,887 male and female smokers in the United States and Canada , aged 35 - 60 years , were r and omized to either smoking intervention or usual care . Among participants who achieved sustained quitting for 5 years , women gained a mean of 5.2 ( st and ard error , 5.0 ) kg in year 1 and a mean of 3.4 ( st and ard error , 5.5 ) kg in years 1 - 5 . Men gained a mean of 4.9 ( st and ard error , 4.9 ) kg in year 1 and a mean of 2.6 ( st and ard error , 5.8 ) kg in years 1 - 5 . In regression analyses , smoking-change variables were the most potent predictors of weight change . Participants going from smoking to quit-smoking in a given year had mean weight gains of 2.95 kg/year ( 3.61 % ) in men and 3.09 kg/year ( 4.69 % ) in women . Over 5 years , 33 % of sustained quitters gained > or = 10 kg compared with 6 % of continuing smokers . Also among sustained quitters , 7.6 % of men and 19.1 % of women gained > or = 20 % of baseline weight ; 60 % of the gain occurred in year 1 , although significant weight gains continued through year 5 . The average gains and the high proportions of sustained and intermittent quitters who gained excessive weight suggest the need for more effective early interventions that address both smoking cessation and weight control Three smoking cessation interventions design ed for use by general practitioners ( GPs ) within the routine consultation were evaluated in a field setting using 26 GPs throughout metropolitan Sydney . A total of 450 smoking patients were allocated to either Structured Behavioral Change with nicotine gum ( Group SBCN ) , Structured Behavioral Change without nicotine gum ( Group SBC ) , or GP advice with nicotine gum ( Group AN ) . Although significant differences in the percentage of abstainers were observed between Groups SBCN and SBC three weeks after treatment ( 39 % vs. 26 % ) , the point prevalence abstinence rate for patients at 12 months declined to 19 , 18 , and 12 % for Groups SBCN , SBC , and AN , respectively . Continuous abstinence to the end of the 12-month period was 9 % for Groups SBCN and SBC , and 6 % for Group AN . Forty-eight percent of the 450 patients made an attempt to stop smoking , and 89 % reduced their cigarette consumption at some point during the study . Examination of 132 self- selecting patients who fully participated in the three interventions and attended all scheduled visits , revealed significantly larger proportions of abstainers within Groups SBCN ( 34 % ) and SBC ( 33 % ) than in Group AN ( 15 % ) at the 12-month follow-up BACKGROUND St John 's wort is an effective antidepressant that can reduce tobacco withdrawal symptoms , but it is not known whether it assists cessation . Chromium assists weight loss and might limit post cessation weight gain . METHODS In a factorial design , we r and omised smokers stopping smoking to 900 mg St John 's wort ( SJW ) active or placebo and also r and omised them to 400 microm chromium or placebo daily . Treatment started 2 weeks prior to quit day and continued for 14 weeks . Participants and research ers were blind to treatment allocation . All participants received weekly behavioural support . The primary endpoints were biochemically confirmed prolonged abstinence and mean weight gain in abstinent smokers 4 weeks after quitting . RESULTS 6/71 ( 8.5 % ) participants on active SJW and 9/72 ( 12.5 % ) on placebo achieved prolonged abstinence at 4 weeks , an odds ratio ( OR ) ( 95 % confidence interval ) of 0.65 ( 0.22 - 1.92 ) . At 6 months , 3 ( 4.2 % ) SJW active and 6 ( 8.3 % ) SJW placebo participants were still abstinent , an OR of 0.49 ( 0.12 - 2.02 ) . Among these participants , the mean difference in weight gain between active chromium and placebo was -0.8 1 kg ( -3.79 to 2.18 ) at 4 weeks and -3.88 kg ( -12.13 to 4.38 ) at 6 months . CONCLUSIONS Taking together the absolute quit rates , the small difference between active and placebo , and lack of effects on withdrawal shows that SJW is ineffective for smoking cessation . Insufficient people stopped smoking to properly test the efficacy of chromium in preventing weight gain , but the point estimate indicates a potentially worthwhile benefit BACKGROUND Nicotine replacement therapies are efficacious for treating nicotine dependence . However , limited data exist on benefits of different NRTs and predictors of treatment outcome . This study compared the effectiveness of transdermal nicotine vs. nicotine lozenge for smoking cessation and identified predictors of treatment response . METHODS A r and omized , open-label effectiveness trial was conducted at 12 medical sites participating in the National Cancer Institute 's Community Clinical Oncology Program . The sample consisted of 642 treatment-seeking smokers r and omized to 12 weeks of transdermal nicotine or nicotine lozenge . RESULTS Smoker characteristics were assessed at baseline , and 24-h point prevalence abstinence confirmed with breath carbon monoxide ( CO ) was evaluated at end of treatment ( EOT ) and at a 6-month follow-up . There was a trend for higher quit rates for transdermal nicotine vs. nicotine lozenge at EOT ( 24.3 % vs. 18.7 % , p=.10 ) and 6 months ( 15.6 % vs. 10.9 % , p=.10 ) . A logistic regression model of EOT quit rates showed smokers who preferred transdermal nicotine , were not reactive to smoking cues , and did not use nicotine to alleviate distress or stimulate cognitive function had higher quit rates on transdermal nicotine . A logistic regression model of 6-month quit rates showed smokers who preferred transdermal nicotine had higher quit rates on transdermal nicotine , and smokers who used nicotine to alleviate distress or stimulate cognitive processes had lower quit rates on nicotine lozenge . CONCLUSIONS Transdermal nicotine may be more effective than nicotine lozenge for smokers who prefer transdermal nicotine and do not smoke to alleviate emotional distress or stimulate cognitive function BACKGROUND Cigarette smoking is an established predictor of incident type 2 diabetes mellitus , but the effects of smoking cessation on diabetes risk are unknown . OBJECTIVE To test the hypothesis that smoking cessation increases diabetes risk in the short term , possibly owing to cessation-related weight gain . DESIGN Prospect i ve cohort study . SETTING The ARIC ( Atherosclerosis Risk in Communities ) Study . PATIENTS 10,892 middle-aged adults who initially did not have diabetes in 1987 to 1989 . MEASUREMENTS Smoking was assessed by interview at baseline and at subsequent follow-up . Incident diabetes was ascertained by fasting glucose assays through 1998 and self-report of physician diagnosis or use of diabetes medications through 2004 . RESULTS During 9 years of follow-up , 1254 adults developed type 2 diabetes . Compared with adults who never smoked , the adjusted hazard ratio of incident diabetes in the highest tertile of pack-years was 1.42 ( 95 % CI , 1.20 to 1.67 ) . In the first 3 years of follow-up , 380 adults quit smoking . After adjustment for age , race , sex , education , adiposity , physical activity , lipid levels , blood pressure , and ARIC Study center , compared with adults who never smoked , the hazard ratios of diabetes among former smokers , new quitters , and continuing smokers were 1.22 ( CI , 0.99 to 1.50 ) , 1.73 ( CI , 1.19 to 2.53 ) , and 1.31 ( CI , 1.04 to 1.65 ) , respectively . Further adjustment for weight change and leukocyte count attenuated these risks substantially . In an analysis of long-term risk after quitting , the highest risk occurred in the first 3 years ( hazard ratio , 1.91 [ CI , 1.19 to 3.05 ] ) , then gradually decreased to 0 at 12 years . LIMITATION Residual confounding is possible even with meticulous adjustment for established diabetes risk factors . CONCLUSION Cigarette smoking predicts incident type 2 diabetes , but smoking cessation leads to higher short-term risk . For smokers at risk for diabetes , smoking cessation should be coupled with strategies for diabetes prevention and early detection 1,218 smokers able to quit smoking for 48 hr were r and omly assigned to one of 12 cells in a 4 x 3 fully crossed factorial experiment . A pharmacologic factor contained four levels : nicotine polacrilex ( gum ) delivered ad lib or on a fixed regimen , placebo gum , and no gum . A self-guided behavioral treatment factor contained three levels : self-selected relapse prevention modules , r and omly administered modules , and no modules . Those receiving nicotine gum were more likely to be abstinent at the 2- and 6-month follow-ups . The fixed regimen accounted for most of the effect for gum . There was no effect for the relapse prevention module factor . Men and women showed a differential treatment response . Men who received nicotine gum were more likely to be abstinent at each follow-up ( 2 , 6 , and 12 months ) . No treatment was significantly better among women . We conclude that research on different gum chewing regimens is warranted and that further examination of possible gender differences in response to replacement therapy is needed Objectives . To determine the safety and efficacy of the nicotine patch and gum for adolescents who want to quit smoking . Design . Double-blind , double-dummy , r and omized , 3-arm trial with a nicotine patch ( 21 mg ) , nicotine gum ( 2 and 4 mg ) , or a placebo patch and gum ; all participants received cognitive-behavioral group therapy . Setting . Inner-city , outpatient clinic on the East Coast . Subjects . Thirteen- to 17-year-old adolescents who smoked ≥10 cigarettes per day ( CPD ) , scored ≥5 on the Fagerström Test of Nicotine Dependence , and were motivated to quit smoking . Intervention . Twelve weeks of nicotine patch or gum therapy with cognitive-behavioral therapy , with a follow-up visit at 6 months ( 3 months after the end of treatment ) . Main Outcome Measures . Safety assessed on the basis of adverse event reports for all 3 groups , prolonged abstinence , assessed through self-report and verified with exhaled carbon monoxide ( CO ) levels of ≤6 ppm , in intent-to-treat analyses , and smoking reduction ( CPD and thiocyanate concentrations ) among trial completers . Results . A total of 120 participants were r and omized ( 72 % white , 70 % female ; age : 15.2 ± 1.33 years ; smoking : 18.8 ± 8.56 CPD ; Fagerström Test of Nicotine Dependence score : 7.04 ± 1.29 ) from 1999 to 2003 . Participants started smoking at 11.2 ± 1.98 years of age and had been smoking daily for 2.66 ± 1.56 years ; 75 % had at least 1 current psychiatric diagnosis . Mean compliance across groups was higher for the patch ( mean : 78.4–82.8 % ) than for the gum ( mean : 38.5–50.7 % ) . Both the patch and gum were well tolerated , and adverse events were similar to those reported in adult trials . Changes in mean saliva cotinine concentrations throughout treatment were not statistically significant . Intent-to-treat analyses of all r and omized participants showed CO-confirmed prolonged abstinence rates of 18 % for the active-patch group , 6.5 % for the active-gum group , and 2.5 % for the placebo group ; the difference between the active-patch and placebo arms was statistically significant . There was no significant effect of patch versus gum or gum versus placebo on cessation outcomes . Abstinence rates at the 3-month follow-up assessment were sustained but were not significantly associated with treatment group . Mean smoking rates , but not CO or thiocyanate concentrations , decreased significantly in all 3 arms but not as a function of treatment group . Conclusions . Nicotine patch therapy combined with cognitive-behavioral intervention was effective , compared with placebo , for treatment of tobacco dependence among adolescent smokers . Decreases in the numbers of cigarettes smoked appeared to be offset by compensatory smoking . Additional study of nicotine gum , with enhanced instructional support , is needed to assess its efficacy among adolescent smokers Smoking cessation is an arduous process because nicotine withdrawal syndrome , which occurs following sudden interruption of nicotine use in long-term smokers , frequently prevents them from giving up the habit . Nicotine supplement systems may relieve smokers ' nicotine withdrawal symptoms and , thus , help in the process of abstinence from smoking . The purpose of the present study was to investigate the effectiveness and safety of a 30-mg transdermal nicotine patch in a smoking cessation program for Chinese smokers . In this r and omized , double-blind , placebo-controlled study , 30 heavy smokers , who had smoked more than 20 cigarettes per day for more than a year , were treated with 30-mg transdermal nicotine patches , and 32 heavy smokers were given placebo patches during a 6-week smoking cessation program . The clinical characteristics of the two groups were similar . After 6 weeks , the use of the transdermal nicotine patch was associated with markedly reduced nicotine dependence and severity of withdrawal symptoms . Nineteen ( 63 % , 95 % confidence interval , CI , 46%-80 % ) of the smokers treated with the transdermal nicotine patch had successfully quit smoking at the end of the program ( 6 weeks ) and nine ( 30 % , 95 % CI 14%-46 % ) remained abstinent 1 year later . In contrast , only 11 ( 34 % , 95 % CI 18%-50 % ) of the smokers in the placebo group had successfully stopped smoking after 6 weeks , and three remained abstinent 1 year later ( 9 % , 95 % CI 0%-19 % ) . However , there was no statistically significant difference between the two groups of smokers after 1 year of follow-up ( p = 0.08 ) . Side-effects were minimal and did not affect the efficacy of the skin patch . The results indicate that the transdermal nicotine patch is an effective aid in smoking cessation programs AIM To examine the association between weight change and baseline body mass index ( BMI ) over 8 years in a cohort of continuing and quitting smokers . DESIGN Prospect i ve cohort . SETTING Oxfordshire general practice s nicotine patch/placebo trial with 8-year follow-up . PARTICIPANTS Eighty-five participants were biochemically proven abstinent at 3 , 6 , 12 months and 8 years ( abstainers ) . A total of 613 smoked throughout the 8 years ( smokers ) , 26 quit for a whole year but were smoking again by 8 years ( relapsed ) ; 116 smoked for the first year but were abstinent at 8 years ( late abstainers ) . MEASUREMENTS Weight and BMI was measured at baseline and at 8 years . Regression models were used to examine weight gain by smoking status and the association of BMI at the time of quitting . FINDINGS Abstainers gained 8.79 kg [ st and ard deviation ( SD ) 6.36 ; 95 % confidence interval ( CI ) 7.42 , 10.17 ] . Smokers gained 2.24 kg ( SD 6.65 ; 95 % CI 1.7 , 2.77 ) . Relapsed smokers gained 3.28 kg ( SD 7.16 ; 95 % CI 0.328 , 6.24 ) . Late abstainers gained 8.33 kg ( SD 8.04 ; 95 % CI 6.85 , 9.81 ) . The association between baseline BMI and weight change was modified by smoking status . In smokers there was a negative linear association of BMI , while in abstainers a J-shaped curve fitted best . These models estimated weight change over 8 years in abstainers of + 9.8 kg , + 7.8 kg , + 10.2 kg , + 19.4 kg and in smokers of + 3.9 kg , + 2.6 kg , 1.0 kg and -0.8 kg , where BMI was 18 , 23 , 29 and 36 , respectively . CONCLUSION Obese smokers gain most weight on quitting smoking , while obese continuing smokers are likely to remain stable or lose weight . Obese quitters have the greatest need for interventions to ameliorate weight gain Smokers ( N = 126 ) were r and omly assigned to 6-session smoking cessation treatments consisting of 1 of 2 counseling strategies ( skills training or support ) and 1 of 2 nicotine exposure strategies ( nicotine gum or rapid smoking ) . Counseling and nicotine strategies were completely crossed ; all four combinations result ed in equivalent 1-year abstinence rates . Skills training produced higher initial cessation and more coping responses posttreatment than did support . Rapid smoking , but not nicotine gum , produced tachycardia to the taste of cigarettes posttreatment , consistent with cigarette aversion . The treatments were differentially effective among sub population s of smokers : Subjects high in pretreatment negative affect responded best to support counseling ; those low in pretreatment negative affect responded best to skills training . Self-reports of pretreatment craving predicted response to the nicotine exposure treatments This study examined the efficacy of transdermal nicotine in postmenopausal smokers , and whether a history of depression or hormone replacement therapy ( HRT ) moderated smoking cessation outcomes . Postmenopausal smokers ( N=152 ) received intensive smoking cessation counseling and were r and omly assigned to use either a 21-mg nicotine patch for 3 months , with a 1-month taper , or a placebo patch . The primary outcome was biochemically vali date d 7-day point prevalence smoking abstinence during treatment ( i.e. , 1 , 2 , 6 , and 12 weeks after the quit date ) and 1 year after study medication was discontinued . Subjects who received transdermal nicotine were significantly more likely than placebo-treated subjects to remain abstinent from smoking during treatment , but not at the 1-year follow-up . The majority of subjects ( > 50 % ) in both groups accurately identified their treatment assignment . History of depression was associated with a decreased likelihood to abstain from smoking throughout the study . HRT did not moderate smoking outcomes . These data indicate that transdermal nicotine may provide short-term benefits for smoking cessation in postmenopausal women . However , efforts are needed to improve long-term abstinence rates and smoking outcomes among women with a history of depression Signal detection methods were used to develop an algorithm useful in distinguishing those at risk for late relapse from those likely to maintain abstinence . Four subgroups with 24-month survival ( nonrelapse ) rates ranging from 79 % to 33 % were identified . Among participants whose depression symptoms decreased from baseline to the end of treatment , lower levels of nicotine dependence were associated with less relapse at the 24-month follow-up ( odds ratio = 2.77 ; 95 % confidence interval : 1.36 - 5.62 ) . Among participants whose depression symptoms increased from baseline to the end of treatment , greater weight gain was associated with less relapse at follow-up ( odds ratio = 2.90 ; 95 % confidence interval : 1.41 - 5.96 ) . This study suggested that it may become possible to use both baseline and treatment information to " titrate " interventions Nicotine replacement by transdermal patches is more effective than placebo in smoking cessation , but has a low success rate after one year ( 9 - 18 % ) . We tested whether this was attributed to insufficient nicotine replacement . We conducted a r and omized trial to investigate the effect on outcome of different doses of transdermal nicotine replacement after stratification according to baseline plasma cotinine values . Two hundred and ninety seven adult smokers were enrolled . Those with baseline cotinine < or = 250 ng.ml-1 ( low cotinine ) were r and omly assigned to placebo ( LC-P ) or to 15 mg 16 h nicotine patches ( LC-15 ) , and those with baseline cotinine > 250 ng.mL-1 ( high cotinine ) were r and omly assigned to 15 mg ( HC-15 ) or 25 mg ( HC-25 ) 16 h nicotine patches . Plasma nicotine and cotinine values , expired carbon monoxide and withdrawal symptoms were measured at scheduled intervals during treatment . Smokers in the LC-15 group had a significantly higher success rate than placebo ( 28 vs 9 % ) . Smokers with high baseline cotinine had lower success rates , and a high dose of nicotine did not increase success rate ( HC-25 9 % vs HC-15 11 % ) . Subjects in the HC-15 group had the lowest percentage of nicotine replacement and a higher prevalence of withdrawal symptoms than the HC-25 group . Replacement was similar in groups LC-15 and HC-25 , but the success rate was significantly lower in HC-25 group , despite similar levels of withdrawal symptoms . We conclude that a higher success rate was obtained after one year in smokers with low baseline plasma cotinine values . Determination of plasma cotinine values may be , thus , helpful in identifying smokers who could benefit from transdermal nicotine replacement The purpose of this study was to examine the effectiveness of different practice -based approaches to assist patients of primary care physicians to quit smoking and sustain cessation . Forty-four nonsmoking general practitioners volunteered for the study . After a period of training , they r and omized 923 smoking clients , unselected for motivation toward quitting , to four different intervention groups : ( i ) minimal intervention , consisting of one single counselling session and a brief h and out on quitting techniques ; ( ii ) repeated counselling including reinforcing sessions at Months 1 , 3 , 6 , and 9 ; ( iii ) repeated counselling and use of nicotine gum ; and ( iv ) repeated counselling and spirometry . Biochemically vali date d smoking status was assessed at six and 12 months after recruitment . The proportion of verified quitters at 12 months was 4.8 percent among subjects r and omized to the minimal intervention group , compared to 5.5 percent , 7.5 percent , and 6.5 percent among those r and omized to the three repeated-counselling groups . In no treatment group was the outcome significantly different from that for one-time counselling at the ( P<0.05 ) level . Lack of power , contamination , and low attendance at reinforcing sessions should be taken into account in interpreting the results The transdermal administration of nicotine by means of a transdermal nicotine system ( TNS ) affords a novel way of nicotine replacement to alleviate smoking cessation . The plasma levels of nicotine maintained with the TNS are in the range of the footpoint concentrations observed in smokers . The efficacy of the TNS was investigated in two placebo-controlled double-blind smoking cessation programs with minimal contact and minimal psychological support . A total of 311 smokers were treated for 3 months or 9 weeks . The abstinence rates at the end of the treatment and weaning periods were almost doubled in the TNS groups ( 36 % and 39 % ) as compared to the placebo groups ( 23 % and 20 % ) with a significant difference for both studies ( p<0.05 ) . These data suggest that the TNS can also improve the smoking cessation rates under the conditions of general medical advice , making it suitable for use outside of specialized smoking cessation centers OBJECTIVE The purpose of this study was to evaluate the efficacy of long-term use of bupropion sustained release ( SR ) , the nicotine patch , and the combination of these 2 treatments in patients who initially failed treatment . METHODS This was a post hoc analysis of a multicenter , double-blind , r and omized , placebo-controlled clinical trial in 893 smokers . Patients were r and omly assigned to 9 weeks of treatment with placebo ( n = 160 ) , bupropion SR ( n = 244 ) , nicotine patch ( n = 244 ) , or a combination of nicotine patch and bupropion SR ( n = 245 ) . The study was originally design ed with a follow-up period of 52 weeks . In this analysis , short-term success was defined as smoking cessation after 14 or 21 days of therapy and long-term success was defined as smoking cessation after > 21 days of therapy . Patients who did not achieve short-term success were evaluated for long-term success at week 9 ( end of treatment ) , 6 months , and 1 year after the start of the study . RESULTS The mean age of the smokers was 44 years . The majority ( 93 % ) of patients were white , and 52 % were female . The study subjects smoked an average of 27 cigarettes per day . Among the 467 patients who initially failed treatment in the first 3 weeks , treatment with bupropion SR alone and in combination with the nicotine patch produced significant increases in successful smoking cessation rates from weeks 4 to 9 ( 19 % bupropion SR or combination , 7 % nicotine patch , 7 % placebo ) , at month 6 ( 11 % bupropion SR , 13 % combination , 2 % nicotine patch , 3 % placebo ) , and at month 12 ( 10 % bupropion SR , 7 % combination , 2 % nicotine patch , 1 % placebo ) ( P < 0.05 for bupropion SR and combination vs nicotine patch or placebo ) . CONCLUSION Among patients who initially failed treatment , continued therapy with bupropion SR , either alone or in combination with the nicotine patch , result ed in significantly higher short- and long-term smoking cessation rates than treatment with the nicotine patch alone or placebo Smokers ( n = 315 ) who wished to quit were r and omly assigned in a double-blind manner to groups using either nicotine or placebo gum . Self-reported and observed symptoms of tobacco withdrawal were collected before cessation and at follow-ups of 1 to 2 weeks , 1 month , and 6 months . Self-reported and /or observed anger , anxiety , craving , difficulty concentrating , hunger , impatience , and restlessness were the most prominent symptoms of tobacco withdrawal . These symptoms had returned to precessation levels by 1 month except increased weight , hunger , and craving continued for 6 months in many smokers . Nicotine gum decreased most symptoms , including craving and hunger but not weight . Abstinent smokers with more intense withdrawal were not more likely to relapse . Abstinent smokers who gained more weight were less likely to relapse This study reports findings from an investigation of the efficacy of high-dose nicotine patch ( NP ) therapy for heavy smokers with a past history of alcohol dependence . One hundred thirty participants were r and omly assigned to 42 mg or 21 mg of transdermal nicotine for 4 weeks , followed by an 8-week dose titration . Follow-up assessment s were conducted at 4 and 12 weeks . Differences between dose conditions were nonsignificant , although unexpectedly , outcomes favored participants in the 21-mg NP condition . Nicotine abstinence at follow-up was related to longer length of alcohol abstinence at time of enrollment . Future research should investigate ways to improve smoking quit rates in this population , including more frequent counseling sessions and /or other pharmacotherapies . These investigations should focus primarily on smokers in early alcohol recovery Recent research has demonstrated there is a high prevalence of weight concerns in smokers and that smokers with weight concerns may respond poorly to treatment for tobacco dependence . Most studies have focused only on females or have consisted of small sample s. In this study of a 12-week r and omized trial of nicotine inhaler , bupropion or both for smoking cessation , 50 % of the 1012 female smokers and 26 % of the 680 male smokers , at study entry , were weight concerned . In examining the impact of weight concerns on the 12-week point-prevalence smoking abstinence , 26 % of non-weight-concerned smokers quit smoking compared to 22 % of weight-concerned smokers ( p=0.06 ) . This study , which includes a large sample of both genders , provides further evidence that approximately half of females who are seeking smoking cessation treatment are weight concerned and that one quarter of male smokers are weight concerned . Additionally , being weight concerned may impact the short-term success rates of stopping smoking using pharmacotherapy BACKGROUND This study was undertaken to assess the safety and efficacy of a treatment involving brief counseling and the nicotine patch among hospital in patients and to identify variables associated with long-term smoking cessation following hospitalization . METHODS One hundred eighty-five patients were r and omly assigned to one of three smoking cessation interventions : ( 1 ) A Minimal Care ( MC ) condition , consisting of a brief physician-delivered motivational message to stop smoking , ( 2 ) a Counseling + Active Nicotine Patch ( CAP ) condition in which patients received the motivational message , a 6-week supply of nicotine patches , and extended bedside and telephone counseling , and ( 3 ) a Counseling + Placebo Patch ( CPP ) condition identical to the CAP condition except the supplied patches contained no nicotine . RESULTS At 6-month follow-up , abstinence rates for the three treatments were 4.9 , 6.5 , and 9.7 % for the MC , CPP , and CAP treatments , respectively . These differences were not statistically significant . Patients admitted for respiratory disease were more likely to quit than patients with any other diagnosis . The nicotine patch was well tolerated by hospital in patients . CONCLUSIONS The initiation of nicotine patch therapy during hospitalization appears to be safe when used among patients carrying a wide range of diagnoses . Our study provided no evidence of the superiority of nicotine patches versus placebo , but this does not preclude the possibility that future research using larger sample s might detect differences between patch groups . Hospital interventions for smoking cessation may be most effective among patients hospitalized for a smoking-related illness such as respiratory disease OBJECTIVE We assessed the safety of long-term varenicline administration for smoking cessation . METHODS In this r and omized , double-blind , multicenter trial , eligible adult smokers ( 18 - 75 years ) who smoked an average of > or = 10 cigarettes/day were r and omized to either varenicline 1 mg twice daily ( BID ) or placebo for 52 weeks . Subjects made weekly clinic visits until week 8 , and then every 4 weeks until week 52 , with a follow-up visit at week 53 . The target quit date was the morning of the week 1 clinic visit . Brief counseling was provided at each visit , and vital signs , adverse events ( AEs ) , and smoking status were documented . Other laboratory measures were collected at specified visits . RESULTS A total of 251 subjects were r and omized to varenicline and 126 to placebo . Approximately half of the subjects in each arm completed the study ( 53.8 % varenicline ; 46.8 % placebo ) . Treatment-emergent AEs were observed in 96.4 % of varenicline- and 82.5 % of placebo-treated subjects during the study . Common varenicline-associated AEs were nausea ( 40.2 % ) , abnormal dreams ( 22.7 % ) , and insomnia ( 19.1 % ) . Most AEs were considered mild or moderate in intensity . AEs leading to discontinuation of varenicline treatment included nausea ( 7.6 % ) , insomnia ( 3.2 % ) , and abnormal dreams ( 2.4 % ) . A single varenicline-related serious AE , bilateral subcapsular cataracts , was observed . At week 52 , 7-day point prevalence abstinence rates were 36.7 % ( varenicline ) and 7.9 % ( placebo ) . CONCLUSIONS Varenicline 1 mg BID can be safely administered for up to 1 year . Varenicline was also a more effective smoking cessation aid than placebo throughout the study , supporting both its short- ( 12-week ) and long-term ( 52-week ) efficacy Rationale Cigarette smokers weigh less than nonsmokers , and smokers often gain weight when they quit . This is a major barrier to smoking cessation , especially among women . However , strict dieting is not recommended during smoking cessation out of concern that it might promote relapse . This concern derives , in part , from the observation that calorie restriction increases self-administration of drugs of abuse in animals . This relationship has never been experimentally demonstrated in humans . Objectives To evaluate whether calorie restriction increases cigarette smoking in humans . Methods Seventeen ( nine males , eight females ) healthy , normal-weight smokers not attempting to quit were cycled in partially counterbalanced order , double-blind , through four diets — normal calorie ( 2,000–2,800 kcal/day ) , low calorie ( 700 kcal/day deficit ) , low-carbohydrate (CHO)/normal-calorie , and low-CHO/low-calorie — for 6 days per diet in an inpatient research ward . Smoking was assessed by cigarette counts , breath carbon monoxide ( CO ) levels , and cigarette craving . Results Compared with the normal-calorie diet , while on the low-calorie diet , subjects smoked 8 % more cigarettes ( P<0.02 ) and had 11 % higher breath CO levels ( P<0.01 ) . The low-CHO/normal-calorie diet showed no significant effect on either variable , but there was a 15 % increase in breath CO levels ( P<0.05 ) on the low-CHO/low-calorie diet . There were no changes in self-reported cigarette craving or mood . Conclusions Consistent with animal studies , moderate calorie restriction was associated with a small but statistically significant increase in cigarette smoking , with no independent effect of CHO deprivation . These findings suggest that dieting may increase smoking behavior and could impede smoking-cessation attempts Differences among adult women smokers with differing levels of concern about post-cessation weight gain were investigated in a national r and om-digit-dialing survey . To avoid defining weight concerns in terms of possible etiologies or contributory factors , respondents were stratified using a single item querying concern about post-cessation weight gain ; 39 % described themselves as very concerned ( VC ) , 28 % as somewhat concerned ( SC ) , and 33 % as not concerned ( NC ) . Significant between-groups differences were detected for measures of weight and body image , eating patterns and weight control practice s , and nicotine dependence , but not for depression . Differences , primarily between VC and NC , were also detected for several weight-related smoking variables , including importance of weight as a factor in initiation , smoking as a weight control strategy , increased appetite and weight gain as withdrawal symptoms , willingness to gain weight upon quitting , self-efficacy about relapse in the face of weight gain , and readiness to quit smoking . Most differences persisted even after adjusting for body mass index and nicotine dependence . Although the importance of thinness was rated higher by weight-concerned women , the difference did not reach significance . Rather , what differentiated groups was the importance of overall body image , suggesting a larger pattern of preoccupation with body image that may not be captured by queries about weight concerns alone . We conclude that weight-concerned women smokers will be especially unlikely to seek treatment or attempt self-quitting ; and that redirecting attention to other aspects of body image is likely to be more helpful than attempting to divert attention away from body image Our data and that of research ers in the area clearly provide evidence for nicotine-specific withdrawal and its relief with nicotine gum . In addition , outcome efficacy is enhanced when nicotine gum is combined with behavioral treatment . Nicotine gum appears to be valuable both as a systematic tool and as a means of combatting short- and long-term nicotine seeking that contribute to maintenance of smoking and the inability to quit This study reports findings from an investigation of the efficacy of high-dose nicotine patch ( NP ) therapy for heavy smokers with a history of alcohol dependence . One hundred thirty participants were r and omly assigned to 42 or 21 mg of transdermal nicotine . Follow-up assessment s were conducted at 4 , 12 , 24 , and 36 weeks . Differences between dose conditions were nonsignificant , although , unexpectedly , outcomes favored participants in the 21-mg NP condition . Nicotine abstinence rates in the 21- and 42-mg NP conditions on Week 36 follow-up were 16.9 % and 9.2 % , respectively . Patch condition did not interact with severity of nicotine dependence . However , nicotine abstinence at follow-up was related to a longer length of alcohol abstinence . No evidence was found for better outcomes as a function of the percentage of baseline cotinine replaced by NPs . Future research should focus primarily on investigating ways to improve smoking quit rates for smokers in early alcohol recovery The authors evaluated the efficacy of fluoxetine hydrochloride ( Prozac ; Eli Lilly and Company , Indianapolis , IN ) as an adjunct to behavioral treatment for smoking cessation . Sixteen sites r and omized 989 smokers to 3 dose conditions : 10 weeks of placebo , 30 mg , or 60 mg fluoxetine per day . Smokers received 9 sessions of individualized cognitive-behavioral therapy , and biologically verified 7-day self-reported abstinence follow-ups were conducted at 1 , 3 , and 6 months posttreatment . Analyses assuming missing data counted as smoking observed no treatment difference in outcomes . Pattern-mixture analysis that estimates treatment effects in the presence of missing data observed enhanced quit rates associated with both the 60-mg and 30-mg doses . Results support a modest , short-term effect of fluoxetine on smoking cessation and consideration of alternative models for h and ling missing data Rationale Fluoxetine improves affect in clinical syndromes such as depression and premenstrual dysphoric disorder . Little is known about fluoxetine ’s influence on mood changes after quitting smoking , which often resemble sub- clinical depression . Objectives The present study , a re- analysis of previously published data ( Niaura et al. 2002 ) , examined fluoxetine ’s effect on changes in negative and positive affect following quitting smoking . Methods Adult smokers ( n=175 ) without clinical ly significant depression were r and omized on a double-blind basis to receive fluoxetine hydrochloride ( 30 or 60 mg daily ) or placebo for 10 weeks in combination with cognitive-behavioral therapy ( CBT ) for smoking cessation . We postulated that fluoxetine would beneficially influence post-cessation changes in positive and negative affect . Results Mood change across treatment was analyzed using mixed linear modeling controlling for initial level of nicotine dependence , plasma fluoxetine metabolites , and change in cotinine ( a nicotine metabolite ) at each visit . Relative to placebo , those on 60 mg fluoxetine experienced an elevation in positive affect that increased across time [ t(526)=2.50 , P=0.01 ] , and a reduction in negative affect that returned to baseline across time [ t(524)=2.26 , P=0.02 ] . There were no differences between 30 mg and placebo on changes in positive or negative affect . Conclusions Results indicate that 60 mg of fluoxetine improves both positive and negative mood states after quitting smoking and that diminished positive affect may be an overlooked affective response to smoking cessation Patterns of smoking cessation using 6- and 12-month follow-up data are reported for 1,261 primary care patients r and omized to 3 physician-delivered smoking interventions : advice only ( AO ) , counseling ( CI ) , and counseling plus availability of nicotine-containing gum ( CI + NCG ) . One-week-point-prevalence cessation rates at 12 months did not differ among the interventions : AO ( 15.2 % ) , CI ( 12.9 % ) and CI + NCG ( 16.7 % ) . However , maintained cessation rates ( abstinent at both 6 and 12 months ) increased with intervention intensity : AO ( 6.0 % ) , CI ( 7.8 % ) and CI + NCG ( 10.0 % ) : Test of trend chi 2 = 5.06 , p = .02 . CI + NCG was significantly higher than AO ( p = .02 ) . The findings support the following conclusions : Brief physician-delivered intervention with availability of nicotine-containing gum can have a beneficial long-term effect on smoking cessation , and cohort data as well as point-prevalence rates are important when assessing the long-term impact of lifestyle interventions Many smokers perceive that smoking controls their body weight and that stopping smoking leads to weight gain . This study examined characteristics associated with weight concerns in 72 male smokers enrolled in a controlled trial for smoking cessation . Motivation to quit smoking was found to be significantly lower in those with weight concerns ( P < .001 ) . Further investigation is needed to enable the tailoring of interventions for weight-concerned male smokers Fluoxetine 's effect ( 30 mg , 60 mg , and placebo ) on postcessation weight gain was studied among participants from a r and omized , double-blind 10-week smoking cessation trial who met strict criteria for abstinence and drug levels . It was hypothesized that ( a ) fluoxetine would dose-dependently suppress postcessation weight gain and ( b ) drug discontinuation would produce dose-dependent weight rebound . During the on-drug phase , placebo participants gained weight linearly ( M = 2.61 kg ) . exceeding both fluoxetine groups ( 30-mg group M = 1.33 kg , 60-mg group M = 1.25 kg ) . Weight suppression was initially greater for 60 mg than 30 mg , but both were followed by weight gain . Six months off drug produced greater dose-dependent weight rebound for 60 mg than 30 mg or placebo . Considering both on- and off-drug phases , weight gain for 60 mg of fluoxetine ( M = 6.5 kg ) was comparable with that for placebo ( M = 4.7 kg ) but greater than that for 30 mg ( M = 3.6 kg ) . Fluoxetine appears to forestall postcessation weight gain , allowing time for the weight-conscious smoker to focus on quitting smoking rather than on preventing weight gain AIM Using nicotine gum can reduce the amount of weight gained when quitting . Here we examine the relationship between weight gain and use of adequate amounts of gum . To mitigate the confounders associated with correlational analyses , we contrast the effects of active gum and placebo , and analyze outcomes prospect ively . DESIGN AND SETTING R and omized double-blind placebo-controlled trial of nicotine gum . Participants were instructed to use nine to 15 pieces of gum/day for the first 2 months of treatment . PARTICIPANTS Participants ( n = 103 ) were r and omized to either active ( 2 mg or 4 mg ) or placebo gum . MEASUREMENTS We examined the effect on weight gain of the interaction between treatment ( active versus placebo ) and daily gum use [ ≥9 pieces/day ( compliant use ) versus < 9 pieces/day ] . FINDINGS After 30 days of abstinence , smokers treated with active gum had not gained significantly less weight than those on placebo ( 1.1 kg versus 1.6 kg , P = 0.175 ) . However , a significant compliance-treatment interaction was observed ( P = 0.005 ) : active gum users who used ≥9 pieces/day during the first 14 days of treatment had gained less weight at follow-up ( 0.6 kg versus 1.6 kg for those who used < 9 pieces/day , P = 0.017 ) , but participants r and omized to the placebo group saw no such benefit from compliant use . A similar compliance-treatment interaction ( P = 0.046 ) was also observed when the effect of compliance was examined within active treatment ( 2 mg versus 4 mg ) . CONCLUSIONS When smokers are quitting , those who use more pieces of nicotine gum experience less weight gain in the first 30 days . This relationship is not seen for smokers on placebo gum The authors examined the effect of 24-hour nicotine patches in smoking cessation among over-the-counter customers in Denmark , based on a r and omized double-blind placebo-controlled trial . Participants were consecutive customers to whom nicotine patches were offered as the only treatment . Forty-two pharmacies in the areas of Aarhus and Copenhagen in Denmark participated in the trial , and 522 customers who smoked 10 or more cigarettes per day were r and omized to either nicotine patches or placebo from January to March 1994 . Customers with chronic diseases and pregnant or breastfeeding women were excluded from the trial . Twenty-four-hour patches were offered free of charge during a 3-month period . Those smoking 20 or more cigarettes per day started on a dose of 21-mg/day patches . Customers who smoked less started on patches of 14 mg/day ; and for all of the participants , the dose was gradually reduced to 7-mg/day patches during the study period . Smoking behavior and compliance were recorded by means of self-administered question naires and telephone interviews . Smoking status was recorded in intervals of 4 weeks , which was fixed to be a treatment period , and 26 weeks after inclusion . There was a significant increase in smoking cessation rates after 8 weeks of follow-up but only among smokers who started on 21-mg/day patches . There was a marked placebo effect at each time of contact during the trial , especially in those smoking fewer than 20 cigarettes per day . Although the noncompliance rate was high overall due to discontinuation in the use of patches by relapsed smokers , noncompliance among successful quitters was low . More side effects were seen in the nicotine group than in the placebo group , but none of the reported side effects were serious . It appears that regular healthy smokers who were customers of nonprescribed nicotine patches and who received 21-mg/day nicotine patches benefited from the active treatment ( 44.1 % stopped smoking after 4 weeks ) , but almost as many stopped smoking in the placebo group ( 37.3 % after 4 weeks ) . No significant differences in smoking cessation rates were seen among smokers who started with the low-dose nicotine or placebo patches In this double-blind , placebo-controlled smoking cessation treatment study , 608 participants were r and omly assigned to receive active bupropion and active 4-mg gum ( AA , n = 228 ) , active bupropion and placebo gum ( AP , n = 224 ) , or placebo bupropion and placebo gum ( PP , n = 156 ) . Relative to the PP group , the AA and AP groups were each significantly more likely to be abstinent at 1 week , end of treatment , and 6 months but not at 12 months postquit . After the first week postquit there were no differences in abstinence rates between the AA and AP groups . We found no significant individual difference variables that moderated outcome beyond 1 week postquit OBJECTIVES Weight gain is a consistent sequela of smoking cessation . A successful intervention might attract smokers who fear weight gain . If the gain causes smoking relapse , such an intervention might reduce smoking relapse risk . METHODS Using a sample of 158 smokers who completed a 2-week smoking treatment program , we compared an innovative weight gain prevention intervention with both a nonspecific treatment and st and ard treatment . Subjects were assessed on weight and smoking behavior and followed for 1 year . RESULTS A disturbing , unexpected finding was that subjects in both the innovative and nonspecific conditions had a higher risk of smoking relapse than did st and ard treatment subjects . Some differences were observed between abstinent and smoking subjects in weight gain by treatment condition . CONCLUSIONS Both active interventions may have been so complicated that they detracted from nonsmoking . Also , caloric restriction may increase the reinforcing value of nicotine , a psychoactive drug , thereby increasing smoking relapse risk . The magnitude of weight gain after smoking cessation may not merit interventions that increase smoking risk . Perhaps attitudinal modifications are the most appropriate A double-blind trial on the effect of nicotine-containing chewing gum compared with a placebo gum in smoking cessation was organized in connection with smoking cessation course activity in North Karelia , Finl and . During the three-week course 70 % of the active group ( N = 84 ) and 54 % of the placebo group ( N = 76 ) stopped smoking ( P < 0.05 ) . A difference was found also after six months ( 35 % vs 28 % ) , although no more statistically significant . There were no major differences between the groups in the amount of withdrawal symptoms or side-effects BACKGROUND The purpose of this study was , to identify predictors of quitting following general practitioners ' ( GP ) anti-smoking counseling . METHODS We studied determinants ( characterized following the Precede framework ) of successful quitting ( 1 year sustained abstinence , biochemically confirmed at 6- and 12-month follow-up ) among 861 smokers r and omized to the intervention groups based on repeated counseling ( RC ) , RC + spirometric testing , and RC + nicotine gum , in a smoking cessation trial carried out in Turin , Italy . RESULTS GPs ' intervention worked best for male ( OR = 2.30 ; 95 % CI , 1.13 - 4.52 ) and married ( OR = 3.63 ; 95 % CI , 1.37 - 9.59 ) smokers , for smokers who had maintained abstinence for at least 1 month in the past ( OR = 6.78 ; 95 % CI , 1.56 - 29.52 ) or at their first quit attempt ( OR = 10.91 ; 95 % CI , 2.37 - 50.13 ) , and for those who spontaneously reduced their coffee consumption ( OR = 3.30 ; 95 % CI , 1.59 - 6.82 ) ; heavy smokers ( > = 20 cig/day OR = 0.48 ; 95 % CI , 0.24 - 0.93 ) and those living with other smokers ( > = 1 smokers in the household : OR = 0.44 ; 95 % CI , 0.22 - 0.90 ) were less likely to give up . Previous antismoking advice by the GP represented a strong barrier to success for healthy smokers ( OR = 0.19 ; 95 % CI , 0.07 - 0.52 ) , but not for those reporting symptoms of shortness of breath ( OR = 0.63 ; 95 % CI , 0.39 - 9.20 ) . There were no interactions between predictors and treatment conditions . CONCLUSIONS Assessment of factors influencing quitting would allow GPs to tailor their message to address existing barriers and to help patients utilize their re sources for change Few research ers have studied whether weight gain has an impact on short-term relapse to smoking . The authors of this study investigated predictors of relapse among 989 participants ( 60 % women ) in a r and omized , double-blind , 10-week multicenter trial to determine the effect of fluoxetine ( 30 or 60 mg ) versus placebo in combination with behavioral counseling for smoking cessation . Medication compliance and smoking status were biochemically verified . At Visit 2 , participants were asked to set a quit date within the subsequent 2 visits . A proportional hazards regression model was used to predict risk of relapse within the first 3 months of quitting . Weight gain predicted relapse , but for men only . Female gender also predicted relapse . The results led the authors to question whether postcessation weight gain interventions should be restricted to women smokers BACKGROUND AND METHODS Use of nicotine-replacement therapies and the antidepressant bupropion helps people stop smoking . We conducted a double-blind , placebo-controlled comparison of sustained-release bupropion ( 244 subjects ) , a nicotine patch ( 244 subjects ) , bupropion and a nicotine patch ( 245 subjects ) , and placebo ( 160 subjects ) for smoking cessation . Smokers with clinical depression were excluded . Treatment consisted of nine weeks of bupropion ( 150 mg a day for the first three days , and then 150 mg twice daily ) or placebo , as well as eight weeks of nicotine-patch therapy ( 21 mg per day during weeks 2 through 7 , 14 mg per day during week 8 , and 7 mg per day during week 9 ) or placebo . The target day for quitting smoking was usually day 8 . RESULTS The abstinence rates at 12 months were 15.6 percent in the placebo group , as compared with 16.4 percent in the nicotine-patch group , 30.3 percent in the bupropion group ( P<0.001 ) , and 35.5 percent in the group given bupropion and the nicotine patch ( P<0.001 ) . By week 7 , subjects in the placebo group had gained an average of 2.1 kg , as compared with a gain of 1.6 kg in the nicotine-patch group , a gain of 1.7 kg in the bupropion group , and a gain of 1.1 kg in the combined-treatment group ( P<0.05 ) . Weight gain at seven weeks was significantly less in the combined-treatment group than in the bupropion group and the placebo group ( P<0.05 for both comparisons ) . A total of 311 subjects ( 34.8 percent ) discontinued one or both medications . Seventy-nine subjects stopped treatment because of adverse events : 6 in the placebo group ( 3.8 percent ) , 16 in the nicotine-patch group ( 6.6 percent ) , 29 in the bupropion group ( 11.9 percent ) , and 28 in the combined-treatment group ( 11.4 percent ) . The most common adverse events were insomnia and headache . CONCLUSIONS Treatment with sustained-release bupropion alone or in combination with a nicotine patch result ed in significantly higher long-term rates of smoking cessation than use of either the nicotine patch alone or placebo . Abstinence rates were higher with combination therapy than with bupropion alone , but the difference was not statistically significant BACKGROUND Transdermal nicotine therapy is widely used to aid smoking cessation , but there is uncertainty about its safety in patients with cardiac disease . METHODS In a r and omized , double-blind , placebo-controlled trial at 10 Veterans Affairs medical centers , we r and omly assigned 584 out patients ( of whom 576 were men ) with at least one diagnosis of cardiovascular disease to a 10-week course of transdermal nicotine or placebo as an aid to smoking cessation . The subjects were monitored for a total of 14 weeks for the primary end points of the study ( death , myocardial infa rct ion , cardiac arrest , and admission to the hospital due to increased severity of angina , arrhythmia , or congestive heart failure ) ; the secondary end points ( admission to the hospital for other reasons and outpatient visits necessitated by increased severity of heart disease ) ; any side effects of therapy ; and abstinence from smoking . RESULTS There were 48 primary and 78 secondary end points noted in a total of 95 subjects . At least one of the primary end points was reached by 5.4 percent of the subjects in the nicotine group and 7.9 percent of the subjects in the placebo group ( difference , 2.5 percent ; 95 percent confidence interval , -1.6 to 6.5 percent ; P=0.23 ) . In the nicotine group , 11.9 percent of the subjects had at least one of the secondary end points , as compared with 9.7 percent in the placebo group ( difference , 2.2 percent ; 95 percent confidence interval , -2.2 to 7.4 percent ; P= 0.37 ) . After 14 weeks the rate of abstinence from smoking was 21 percent in the nicotine group , as compared with 9 percent in the placebo group ( P=0.001 ) , but after 24 weeks the abstinence rates were not significantly different ( 14 percent vs. 11 percent , P= 0.67 ) . CONCLUSIONS Transdermal nicotine does not cause a significant increase in cardiovascular events in high-risk out patients with cardiac disease . However , the efficacy of transdermal nicotine as an aid to smoking cessation in such patients is limited and may not be sustained over time Laboratory trials have demonstrated the efficacy of nicotine replacement in smoking cessation but absolute success rates are low . For many , nicotine gum is hard to use and transdermal nicotine is slow-acting and passive . A new , faster-acting nicotine nasal spray ( NNS ) can provide easily self-administered relief from cigarette withdrawal . The NNS was tested for safety and efficacy in smoking cessation . Two hundred and fifty-five smokers were r and omized to NNS or a piperine placebo . Drug use was limited to 8 - 32 doses/day for 6 months . Subjects were tested while smoking and at post-cessation daily ( week 1 ) with follow-up at weeks 2 , 3 , 6 and at 3 months , 6 months and 1 year . Continuous abstinence analyses ( CO < or = 8 ppm ; no slips ) showed that NNS significantly enhanced success rates over placebo overall ( p < 0.001 ) and at all test intervals . Differences at key intervals between active and placebo were : 63 % vs. 40 % ( day 5 ) , 51 % vs. 30 % ( week 3 ) , 43 % vs. 20 % ( 6 weeks ) , 34 % vs. 13 % ( 3 months ) , 25 % vs. 10 % ( 6 months ) and 18 % vs. 8 % ( 1 year ) . Side effects were common but tolerable . Cotinine measures showed that replacement of nicotine approximated 30 % of smoking levels . Hazard functions revealed relapse risks peaked at day 1 , day 5 and 3 weeks for strict abstinence . It is concluded NNS is safe , efficacious and a viable alternative treatment for smoking cessation |
12,302 | 26,898,781 | Some previously described food patterns , specifically the Mediterranean Food Pattern , the Alternative Healthy Eating Index , the Prudent diet or the Provegetarian Food Pattern may be effective to reduce the future risk of depression .
Among them , only the Mediterranean Food Pattern has been tested for primary prevention in a large r and omised trial , but the inverse association found was not statistically significant .
Notwithst and ing , this field is promising and , according to large and well-conducted observational studies , food patterns potentially associated with reduced risk of depression are those emphasising seafood , vegetables , fruits and nuts . | An emerging field of research in nutritional epidemiology is the assessment of several links between nutritional quality and mental health .
Specifically , some studies have pointed out that several food patterns could be associated with a reduced risk of depression among adults .
This association seems to be consistent across countries , cultures and population s according to several systematic review s and meta-analyses of observational studies . | Background A few observational studies have found an inverse association between adherence to a Mediterranean diet and the risk of depression . R and omized trials with an intervention based on this dietary pattern could provide the most definitive answer to the findings reported by observational studies . The aim of this study was to compare in a r and omized trial the effects of two Mediterranean diets versus a low-fat diet on depression risk after at least 3 years of intervention . Methods This was a multicenter , r and omized , primary prevention field trial of cardiovascular disease ( Prevención con Dieta Mediterránea ( PREDIMED Study ) ) based on community-dwelling men aged 55 to 80 years and women aged 60 to 80 years at high risk of cardiovascular disease ( 51 % of them had type 2 diabetes ; DM2 ) attending primary care centers affiliated with 11 Spanish teaching hospitals . Primary analyses were performed on an intention-to-treat basis . Cox regression models were used to assess the relationship between the nutritional intervention groups and the incidence of depression . Results We identified 224 new cases of depression during follow-up . There was an inverse association with depression for participants assigned to a Mediterranean diet supplemented with nuts ( multivariate hazard ratio ( HR ) 0.78 ; 95 % confidence interval ( CI ) 0.55 to 1.10 ) compared with participants assigned to the control group , although this was not significant . However , when the analysis was restricted to participants with DM2 , the magnitude of the effect of the intervention with the Mediterranean diet supplemented with nuts did reach statistical significance ( multivariate HR = 0.59 ; 95 % CI 0.36 to 0.98 ) . Conclusions The result suggest that a Mediterranean diet supplemented with nuts could exert a beneficial effect on the risk of depression in patients with DM2.Trial registration This trial has been registered in the Current Controlled Trials with the number IS RCT N BACKGROUND Although individual nutrients have been investigated in relation to depression risk , little is known about the overall role of diet in depression . OBJECTIVE We examined whether long-term dietary patterns derived from a food-frequency question naire ( FFQ ) predict the development of depression in middle-aged and older women . DESIGN We conducted a prospect i ve study in 50,605 participants ( age range : 50 - 77 y ) without depression in the Nurses ' Health Study at baseline ( 1996 ) who were followed until 2008 . Long-term diet was assessed by using FFQs every 4 y since 1986 . Prudent ( high in vegetables ) and Western ( high in meats ) patterns were identified by using a principal component analysis . We used 2 definitions for clinical depression as follows : a strict definition that required both a reported clinical diagnosis and use of antidepressants ( 3002 incident cases ) and a broad definition that further included women who reported either a clinical diagnosis or antidepressant use ( 7413 incident cases ) . RESULTS After adjustment for age , body mass index , and other potential confounders , no significant association was shown between the diet patterns and depression risk under the strict definition . Under the broad definition , women with the highest scores for the Western pattern had 15 % higher risk of depression ( 95 % CI : 1.04 , 1.27 ; P-trend = 0.01 ) than did women with the lowest scores , but after additional adjustment for psychological scores at baseline , results were no longer significant ( RR : 1.09 ; 95 % CI : 0.99 , 1.21 ; P-trend = 0.08 ) . CONCLUSION Overall , results of this large prospect i ve study do not support a clear association between dietary patterns from factor analysis and depression risk BACKGROUND Studies of diet and depression have focused primarily on individual nutrients . AIMS To examine the association between dietary patterns and depression using an overall diet approach . METHOD Analyses were carried on data from 3486 participants ( 26.2 % women , mean age 55.6 years ) from the Whitehall II prospect i ve cohort , in which two dietary patterns were identified : ' whole food ' ( heavily loaded by vegetables , fruits and fish ) and ' processed food ' ( heavily loaded by sweetened desserts , fried food , processed meat , refined grains and high-fat dairy products ) . Self-reported depression was assessed 5 years later using the Center for Epidemiologic Studies - Depression ( CES-D ) scale . RESULTS After adjusting for potential confounders , participants in the highest tertile of the whole food pattern had lower odds of CES-D depression ( OR = 0.74 , 95 % CI 0.56 - 0.99 ) than those in the lowest tertile . In contrast , high consumption of processed food was associated with an increased odds of CES-D depression ( OR = 1.58 , 95 % CI 1.11 - 2.23 ) . CONCLUSIONS In middle-aged participants , a processed food dietary pattern is a risk factor for CES-D depression 5 years later , whereas a whole food pattern is protective BACKGROUND Adherence to a Mediterranean diet may improve longevity , but relevant data are limited . METHODS We conducted a population -based , prospect i ve investigation involving 22,043 adults in Greece who completed an extensive , vali date d , food-frequency question naire at base line . Adherence to the traditional Mediterranean diet was assessed by a 10-point Mediterranean-diet scale that incorporated the salient characteristics of this diet ( range of scores , 0 to 9 , with higher scores indicating greater adherence ) . We used proportional-hazards regression to assess the relation between adherence to the Mediterranean diet and total mortality , as well as mortality due to coronary heart disease and mortality due to cancer , with adjustment for age , sex , body-mass index , physical-activity level , and other potential confounders . RESULTS During a median of 44 months of follow-up , there were 275 deaths . A higher degree of adherence to the Mediterranean diet was associated with a reduction in total mortality ( adjusted hazard ratio for death associated with a two-point increment in the Mediterranean-diet score , 0.75 [ 95 percent confidence interval , 0.64 to 0.87 ] ) . An inverse association with greater adherence to this diet was evident for both death due to coronary heart disease ( adjusted hazard ratio , 0.67 [ 95 percent confidence interval , 0.47 to 0.94 ] ) and death due to cancer ( adjusted hazard ratio , 0.76 [ 95 percent confidence interval , 0.59 to 0.98 ] ) . Associations between individual food groups contributing to the Mediterranean-diet score and total mortality were generally not significant . CONCLUSIONS Greater adherence to the traditional Mediterranean diet is associated with a significant reduction in total mortality Introduction Recent research suggests that diet quality influences depression risk ; however , a lack of experimental evidence leaves open the possibility that residual confounding explains the observed relationships . The aim of this study was to document the cross-sectional and longitudinal associations between dietary patterns and symptoms of depression and to undertake a detailed examination of potential explanatory factors , particularly socioeconomic circumstances , in the diet-depression relationship . Methods Data were drawn from the Personality and Total Health ( PATH ) Through Life Study , a longitudinal community study following three age cohorts ( 20 + ; 40 + ; 60+yrs ) from south-eastern Australia over three assessment periods ( n = 3663 ) . Regression analyses evaluated the cross-sectional and longitudinal relationships between dietary patterns , depressive symptoms , age , detailed measures of socioeconomic circumstances , other health behaviours , and cardiovascular risk factors . Results The lowest tertile of prudent ( healthy ) dietary pattern and the highest tertile of western ( unhealthy ) dietary pattern were associated with an increased likelihood of depressive symptoms . However , these contemporaneous associations were explained by adjustment for detailed measures of socioeconomic circumstances and physical activity . In prospect i ve analyses , lower scores on the healthy dietary pattern and higher scores on the unhealthy dietary pattern independently predicted increased depressive symptoms across time , before and after adjustment for potential confounders and baseline depressive symptoms , but only for those in the oldest cohort . Dietary patterns did not explain the relationship between socioeconomic position and depressive symptoms . Conclusion The results of this study confirm that the relationship between habitual dietary intake and depressive symptoms is somewhat explained by socioeconomic circumstances and other health behaviours , but suggest that long term exposure to unhealthy dietary habits independently predisposes to depression over the lifecourse Emerging evidence relates some nutritional factors to depression risk . However , there is a scarcity of longitudinal assessment s on this relationship . Objective To evaluate the association between fatty acid intake or the use of culinary fats and depression incidence in a Mediterranean population . Material and Methods Prospect i ve cohort study ( 1999–2010 ) of 12,059 Spanish university graduates ( mean age : 37.5 years ) initially free of depression with permanently open enrolment . At baseline , a 136-item vali date d food frequency question naire was used to estimate the intake of fatty acids ( saturated fatty acids ( SFA ) , polyunsaturated fatty acids ( PUFA ) , trans unsaturated fatty acids ( TFA ) and monounsaturated fatty acids ( MUFA ) and culinary fats ( olive oil , seed oils , butter and margarine ) During follow-up participants were classified as incident cases of depression if they reported a new clinical diagnosis of depression by a physician and /or initiated the use of antidepressant drugs . Cox regression models were used to calculate Hazard Ratios ( HR ) of incident depression and their 95 % confidence intervals ( CI ) for successive quintiles of fats . Results During follow-up ( median : 6.1 years ) , 657 new cases of depression were identified . Multivariable-adjusted HR ( 95 % CI ) for depression incidence across successive quintiles of TFA intake were : 1 ( ref ) , 1.08 ( 0.82–1.43 ) , 1.17 ( 0.88–1.53 ) , 1.28 ( 0.97–1.68 ) , 1.42 ( 1.09–1.84 ) with a significant dose-response relationship ( p for trend = 0.003 ) . Results did not substantially change after adjusting for potential lifestyle or dietary confounders , including adherence to a Mediterranean Dietary Pattern . On the other h and , an inverse and significant dose-response relationship was obtained for MUFA ( p for trend = 0.05 ) and PUFA ( p for trend = 0.03 ) intake . Conclusions A detrimental relationship was found between TFA intake and depression risk , whereas weak inverse associations were found for MUFA , PUFA and olive oil . These findings suggest that cardiovascular disease and depression may share some common nutritional determinants related to subtypes of fat intake BACKGROUND Previous studies on diet and coronary heart disease ( CHD ) focused primarily on individual nutrients or foods . OBJECTIVE We examined whether overall dietary patterns derived from a food-frequency question naire ( FFQ ) predict risk of CHD in men . DESIGN This was a prospect i ve cohort study of 44875 men aged 40 - 75 y without diagnosed cardiovascular disease or cancer at baseline in 1986 . RESULTS During 8 y of follow-up , we documented 1089 cases of CHD ( nonfatal myocardial infa rct ion and fatal CHD ) . Using factor analysis , we identified 2 major dietary patterns using dietary data collected through a 131-item FFQ . The first factor , which we labeled the " prudent pattern , " was characterized by higher intake of vegetables , fruit , legumes , whole grains , fish , and poultry , whereas the second factor , the " Western pattern , " was characterized by higher intake of red meat , processed meat , refined grains , sweets and dessert , French fries , and high-fat dairy products . After adjustment for age and CHD risk factors , the relative risks from the lowest to highest quintiles of the prudent pattern score were 1.0 , 0 . 87 , 0.79 , 0.75 , and 0.70 ( 95 % CI : 0.56 , 0.86 ; P : for trend = 0.0009 ) . In contrast , the relative risks across increasing quintiles of the Western pattern score were 1.0 , 1.21 , 1.36 , 1.40 , and 1.64 ( 95 % CI : 1.24 , 2.17 ; P : for trend < 0.0001 ) . These associations persisted in subgroup analyses according to cigarette smoking , body mass index , and parental history of myocardial infa rct ion . CONCLUSIONS These data suggest that major dietary patterns derived from the FFQ predict risk of CHD , independent of other lifestyle variables Background : It has been suggested that dietary patterns are associated with future risk of depressive symptoms . However , there is a paucity of prospect i ve data that have examined the temporality of this relation . Objective : We examined whether adherence to a healthy diet , as defined by using the Alternative Healthy Eating Index ( AHEI ) , was prospect ively associated with depressive symptoms assessed over a 5-y period . Design : Analyses were based on 4215 participants in the Whitehall II Study . AHEI scores were computed in 1991–1993 and 2003–2004 . Recurrent depressive symptoms were defined as having a Center for Epidemiologic Studies Depression Scale score ≥16 or self-reported use of antidepressants in 2003–2004 and 2008–2009 . Results : After adjustment for potential confounders , the AHEI score was inversely associated with recurrent depressive symptoms in a dose-response fashion in women ( P-trend < 0.001 ; for 1 SD in AHEI score ; OR : 0.59 ; 95 % CI : 0.47 , 0.75 ) but not in men . Women who maintained high AHEI scores or improved their scores during the 10-y measurement period had 65 % ( OR : 0.35 % ; 95 % CI : 0.19 % , 0.64 % ) and 68 % ( OR : 0.32 % ; 95 % CI : 0.13 % , 0.78 % ) lower odds of subsequent recurrent depressive symptoms than did women who maintained low AHEI scores . Among AHEI components , vegetable , fruit , trans fat , and the ratio of polyunsaturated fat to saturated fat components were associated with recurrent depressive symptoms in women . Conclusion : In the current study , there was a suggestion that poor diet is a risk factor for future depression in women Introduction Dietary patterns are culturally specific and there is limited data on the association of dietary patterns with late-life depression in Chinese . This study examined the associations between dietary patterns and baseline and subsequent depressive symptoms in community-dwelling Chinese older people in Hong Kong . Methods Participants aged ≥65 year participating in a cohort study examining the risk factors for osteoporosis completed a vali date d food frequency question naire at baseline between 2001 and 2003 . Factor analysis was used to identify three dietary patterns : “ vegetables-fruits ” pattern , “ snacks-drinks-milk products ” pattern , and “ meat-fish ” pattern . Depressive symptoms were measured at baseline and 4-year using the vali date d Geriatric Depression Scale . Multiple logistic regression was used for cross-sectional analysis ( n = 2,902 ) to assess the associations between dietary patterns and the presence of depressive symptoms , and for longitudinal analysis ( n = 2,211 ) on their associations with 4-year depressive symptoms , with adjustment for socio-demographic and lifestyle factors . Results The highest quartile of “ vegetables-fruits ” pattern score was associated with reduced likelihood of depressive symptoms [ Adjusted OR = 0.55 ( 95 % CI : 0.36–0.83 ) , ptrend = 0.017 ] compared to the lowest quartile at baseline . Similar inverse trend was observed for the highest quartile of “ snacks-drinks-milk products ” pattern score [ Adjusted OR = 0.41 ( 95 % CI : 0.26–0.65 ) , ptrend<0.001 ] compared to the lowest quartile . There was no association of “ meat-fish ” pattern with the presence of depressive symptoms at baseline . None of the dietary patterns were associated with subsequent depressive symptoms at 4-year . Conclusion Higher “ vegetables-fruits ” and “ snacks-drinks-milk products ” pattern scores were associated with reduced likelihood of baseline depressive symptoms in Chinese older people in Hong Kong . The longitudinal analyses failed to show any causal relationship between dietary patterns and depressive symptoms in this population Background Longitudinal studies assessing the long-term association between alcohol intake and depression are scarce . The type of beverage may also be important . Therefore we aim ed to prospect ively evaluate the influence of alcohol intake on incident depression in a Mediterranean cohort . Methods We assessed 13,619 university graduates ( mean age : 38 years , 42 % men ) participating in a Spanish prospect i ve epidemiological cohort ( the SUN Project ) , initially free of depression . They were recruited between 1999–2008 and biennially followed-up during 2001–2010 . At baseline , a 136-item vali date d food – frequency question naire was used to assess alcohol intake . Wine was the preferred beverage . Participants were classified as incident cases of depression if they reported a new clinical diagnosis of depression by a physician and /or initiated the use of antidepressant drugs . Cox regression and restricted cubic splines analyses were performed over 82,926 person-years . Results Only among women , an U-shaped relationship between total alcohol intake and depression risk was found ( P=0.01 ) . Moderate alcohol intake ( 5–15 g/day ) was associated with lower risk ( Hazard Ratio : 0.62 ; 95 % Confidence Interval : 0.43 - 0.89 ) . No association was apparent for higher intakes of alcohol or for any specific type of alcoholic beverage . Conclusions Moderate alcohol intake might protect against depression among women . Further confirmatory studies are needed Background Alcoholic beverages are widely consumed . Depression , the most prevalent mental disorder worldwide , has been related to alcohol intake . We aim ed to prospect ively assess the association between alcohol intake and incident depression using repeated measurements of alcohol intake . Methods We followed-up 5,505 high-risk men and women ( 55 to 80 y ) of the PREDIMED Trial for up to seven years . Participants were initially free of depression or a history of depression , and did not have any history of alcohol-related problems . A 137-item vali date d food frequency question naire administered by a dietician was repeated annually to assess alcohol intake . Participants were classified as incident cases of depression when they reported a new clinical diagnosis of depression , and /or initiated the use of antidepressant drugs . Cox regression analyses were fitted over 23,655 person-years . Results Moderate alcohol intake within the range of 5 to 15 g/day was significantly associated with lower risk of incident depression ( hazard ratio ( HR ) and 95 % confidence interval ( 95 % CI ) = 0.72 ( 0.53 to 0.98 ) versus abstainers ) . Specifically , wine consumption in the range of two to seven drinks/week was significantly associated with lower rates of depression ( HR ( 95 % CI ) = 0.68 ( 0.47 to 0.98 ) ) . Conclusions Moderate consumption of wine may reduce the incidence of depression , while heavy drinkers seem to be at higher risk BACKGROUND The associations between different sources of dietary n-3 ( omega-3 ) and n-6 ( omega-6 ) fatty acids and the risk of depression have not been prospect ively studied . OBJECTIVE The objective was to examine the relation between different n-3 and n-6 types with clinical depression incidence . DESIGN We prospect ively studied 54,632 US women from the Nurses ' Health Study who were 50 - 77 y of age and free from depressive symptoms at baseline . Information on diet was obtained from vali date d food-frequency question naires . Clinical depression was defined as reporting both physician-diagnosed depression and regular antidepressant medication use . RESULTS During 10 y of follow-up ( 1996 - 2006 ) , 2823 incident cases of depression were documented . Intake of long-chain n-3 fatty acids from fish was not associated with depression risk [ relative risk ( RR ) for 0.3-g/d increment : 0.99 ; 95 % CI : 0.88 , 1.10 ] , whereas α-linolenic acid ( ALA ) intake was inversely associated with depression risk ( multivariate RR for 0.5-g/d increment : 0.82 ; 95 % CI : 0.71 , 0.94 ) . The inverse association between ALA and depression was stronger in women with low linoleic acid ( LA ) intake ( P for interaction = 0.02 ) : a 0.5-g/d increment in ALA was inversely associated with depression in the first , second , and third LA quintiles [ RR ( 95 % CI ) : 0.57 ( 0.37 , 0.87 ) , 0.62 ( 0.41 , 0.93 ) , and 0.68 ( 0.47 , 0.96 ) , respectively ] but not in the fourth and fifth quintiles . CONCLUSIONS The results of this large longitudinal study do not support a protective effect of long-chain n-3 from fish on depression risk . Although these data support the hypothesis that higher ALA and lower LA intakes reduce depression risk , this relation warrants further investigation In the present study , we examined longitudinal changes in self-reported depressive symptoms ( and related domains ) in relation to baseline intakes of n-3 fatty acids ( absolute and relative to n-6 fatty acids ) . Sex-specific associations were evaluated in a prospect i ve cohort of adults ( n = 2,053 ) from Baltimore , Maryl and , who were 30 - 64 years of age at baseline and were followed for a mean of 4.65 ( st and ard deviation , 0.93 ) years ( 2004 - 2013 ) . Using mean intakes of n-3 and n-6 fatty acids reported on two 24-hour dietary recalls , we estimated the ratios of n-3 to n-6 fatty acids for both highly unsaturated fatty acids ( ≥20 carbon atoms ) ( HUFAs ) and polyunsaturated fatty acids ( ≥18 carbon atoms ) ( PUFAs ) . Outcomes included total and domain-specific scores on the 20-item Center for Epidemiologic Studies -Depression scale . Based on mixed-effects regression models , among women , both higher n-3 HUFA : n-6 PUFA and n-3 PUFA : n-6 PUFA ratios were associated with a slower rate of increase in total Center for Epidemiologic Studies -Depression scores over time . Higher n-3 HUFA : n-6 HUFA ratios were associated with slower increases in somatic complaints in men , whereas among women , higher n-3 HUFA : n-6 PUFA and n-3 PUFA : n-6 PUFA ratios were both linked to putative longitudinal improvement in positive affect over time . Among US adults , n-3:n-6 dietary fatty acid ratio was associated with longitudinal changes in depressive symptoms , with a higher ratio linked to a slower increase in depressive symptoms over time , particularly among women OBJECTIVES To identify dietary and lifestyle variables that may affect cognitive function in the elderly . DESIGN Population -based prospect i ve cohort study . SETTING General community residing in Athens and the surrounding Attica region of Greece . SUBJECTS A total of 732 men and women , 60 years or older , participating in the EPIC-Greece cohort ( European Prospect i ve Investigation into Cancer and Nutrition ) and residing in the Attica region had sociodemographic , anthropometric , medical , dietary and lifestyle variables ascertained at enrolment ( 1993 - 1999 ) . Six to 13 years later , cognitive function was evaluated through the Mini-Mental State Examination ( MMSE ) score and affective state through the Geriatric Depression Scale ( GDS ) . RESULTS MMSE score was positively associated with years of formal education , height and physical activity and inversely with age , diabetes mellitus and GDS score ( P < 0.05 for all ) . Among dietary variables , intake of PUFA was inversely associated with cognitive function and this association was largely accounted for by a similar association with seed oils . Adherence to the Mediterranean diet , as well as intake of olive oil , MUFA and SFA exhibited weakly positive but not significant associations . CONCLUSION Physical activity and early life factors as reflected in height are significant predictors of cognitive function in the elderly . Seed oil consumption may adversely affect cognition , whereas other nutritional factors do not appear to have a quantitatively large effect Background Very long chain omega-3 fatty acids ( w-3 PUFA ) intake and fish consumption have been suggested as protective factors against neuropsychiatric disorders but there is scarcity of large cohort studies assessing this association . Aim of the study To assess the association between w-3-PUFA intake and fish consumption and mental disorders . Methods A prospect i ve cohort study was performed in 7,903 participants . W-3 PUFA intake and fish consumption were ascertained through a vali date d semi-quantitative food frequency question naire . The outcomes after 2 years of follow-up were : ( 1 ) Incident mental disorder ( depression , anxiety , or stress ) , ( 2 ) incident depression , and ( 3 ) incident anxiety . Logistic regression models and generalized additive models were fit to assess the relationship between w-3 PUFA intake or fish consumption and the incidence of these outcomes . Odds ratios ( OR ) and their 95 % confidence intervals ( CI ) were calculated . Results 173 cases of depression , 335 cases of anxiety , and 4 cases of stress were observed during 2-year follow-up . ORs ( 95 % CI ) of mental disorder for successive quintiles of energy-adjusted w-3 PUFA intake were 1 ( reference ) , 0.72 ( 0.52–0.99 ) , 0.79 ( 0.58–1.08 ) , 0.65 ( 0.47–0.90 ) , and 1.04 ( 0.78–1.40 ) . Subjects with a moderate consumption of fish ( third and fourth quintiles of consumption : median of each quintile 83.3 and 112 g/day , respectively ) had a relative risk reduction higher than 30 % . Conclusions A potential benefit of w-3 PUFA intake on total mental disorders is suggested , although no linear trend was apparent BACKGROUND Inflammation is considered as a mechanism leading to depression , but the association between inflammatory dietary pattern and depression risk is unknown . METHODS Using reduced-rank regression , we identified a dietary pattern that was related to plasma levels of inflammatory markers ( C-reactive protein , interleukin-6 , tumor necrosis factor α receptor 2 ) , and we conducted a prospect i ve analysis of the relationship of this pattern and depression risk among participants in the Nurses ' Health Study . A total of 43,685 women ( aged 50 - 77 ) without depression at baseline ( 1996 ) were included and followed up until 2008 . Diet information was obtained from food frequency question naires completed between 1984 through 2002 and computed as cumulative average of dietary intakes with a 2-year latency applied . We used a strict definition of depression that required both self-reported physician-diagnosed depression and use of antidepressants , and a broader definition that included women who reported either clinical diagnosis or antidepressant use . RESULTS During the 12-year follow-up , we documented 2594 incident cases of depression using the stricter definition and 6446 using the broader definition . After adjustment for body mass index and other potential confounders , relative risks comparing extreme quintiles of the inflammatory dietary pattern were 1.41 ( 95 % confidence interval [ CI ] , 1.22 , 1.63 ; P-trend<.001 ) for the strict definition and 1.29 ( 95 % CI , 1.18 , 1.41 ; P-trend<.001 ) for the broader definition of depression . CONCLUSIONS The inflammatory dietary pattern is associated with a higher depression risk . This finding suggests that chronic inflammation may underlie the association between diet and depression OBJECTIVE We compared the effect on mood of a moderate sodium Dietary Approaches to Stop Hypertension-type diet , which included lean red meat ( vitality diet [ VD ] ) , with a healthy diet ( HD ; decreased fat and increased wholegrain breads and cereal ) . METHODS In a r and omized , parallel intervention study , postmenopausal women were assigned to the VD or HD for 14 wk . Mood was measured every 2 wk by the Profile of Mood States . Dietary adherence was assessed using 24-h urine collection s. Data were analyzed using one-way between-groups multivariate analysis of variance and correlations . RESULTS Forty-six subjects completed the VD and 49 completed the HD . The two groups showed an improvement in anger , confusion , depression , fatigue , tension , vigor , and the Profile of Mood States global score over the length of the intervention ( P < 0.01 for time ) , but there was a significant diet group by time effect for anger ( P < 0.05 ) , such that anger improved more in the VD compared with the HD group . For the two groups combined , urinary sodium excretion was associated with the Profile of Mood States global score , such that a low sodium intake was associated with a better mood ( r = 0.267 , P < 0.05 ) . In addition , red meat consumption ( a component of the VD ) was associated with a decrease in depression ( r = -0.21 , P < 0.05 ) and an increase in fruit consumption was associated with a decrease in confusion ( r = -0.26 , P < 0.05 ) . CONCLUSION In addition to the health benefits of a moderate-sodium Dietary Approaches to Stop Hypertension diet on blood pressure and bone health , this diet had a positive effect on improving mood in postmenopausal women In a prospect i ve epidemiological investigation aim ing to identify dietary lipids potentially associated with affective state and depression , 610 healthy men and women aged 60 years or older , participating in the EPIC-Greece cohort and residing in the Attika region had dietary , sociodemographic , anthropometric , medical and lifestyle variables ascertained at enrollment . Six to 13 years later , affective state was evaluated through the 15-point geriatric depression scale ( GDS ) score along with cognitive function and medical variables . In multivariate linear regression analysis , while adjusting for potential confounders , GDS score was negatively associated with dietary intake of monounsaturated lipids ( MUFA ) and their main source , olive oil , and positively associated with intake of polyunsaturated lipids ( PUFA ) and one of their principal sources , seed oils . Intake of calories , total lipids , fish and seafood or saturated lipids did not exhibit significant association with GDS . Potential non-linearities were assessed by quantile multivariate regression analysis : The median GDS score was positively associated with PUFA and seed oils intake , while other lipid groups showed no appreciable associations . The 90th percentile of the GDS score ( towards the high end ) exhibited significant negative associations with MUFA and olive oil , weaker positive associations with PUFA and seed oils and no appreciable association with other lipid group dietary intakes . We conclude that among Attika elders , lower intake of seed oils and higher intake of olive oil prospect ively predict a healthier affective state . Olive oil intake , in particular , predicts a lower chance of scoring in the highest part of the GDS BACKGROUND Previous studies assessing the role of dietary factors in depression have mainly focused on nutrients , while the association between dietary patterns and depression is less studied . OBJECTIVE The aim was to assess the role of dietary patterns in depression in both cross-sectional and prospect i ve analyses . DESIGN The study population consisted of 1003 Finnish middle-aged or older men from the Kuopio Ischemic Heart Disease Risk Factor Study . Food consumption was assessed by food frequency question naire in 1991 - 1993 and dietary patterns from 25 predefined food groups were extracted by factor analysis . Depressive symptoms were assessed with the self-administered Human Population Laboratory Depression Scale , cut-off point of five or more indicating elevated depressive symptoms . RESULTS Altogether 72 ( 7.2 % ) subjects had elevated depressive symptoms . Three dietary patterns were identified : " prudent " , " Western " and " mixed " . In cross-sectional analysis , after adjustments for age , examination year , BMI , smoking , alcohol consumption , education , marital status , leisure-time physical activity , history of mental illness and cardiovascular disease the prudent dietary pattern was associated with a 25 % lower prevalence of elevated depressive symptoms ( OR : 0.75 ; 95 % CI : 0.57 , 0.99 ; P=0.036 ) , whereas the Western dietary pattern was associated with increased prevalence of elevated depressive symptoms ( OR : 1.41 ; 95 % CI : 1.08 , 1.84 ; P=0.011 ) . In the prospect i ve analysis ( 16.5 follow-up years ) , the prudent dietary pattern was inversely associated with the risk of getting a hospital discharge diagnosis of depression ( HR : 0.66 ; 95 % CI 0.47 , 0.93 ; P=0.018 ) . CONCLUSIONS Adherence to healthy dietary pattern is associated with lower risk of getting a hospital discharge diagnosis of depression CONTEXT Adherence to the Mediterranean dietary pattern ( MDP ) is thought to reduce inflammatory , vascular , and metabolic processes that may be involved in the risk of clinical depression . OBJECTIVE To assess the association between adherence to the MDP and the incidence of clinical depression . DESIGN Prospect i ve study that uses a vali date d 136-item food frequency question naire to assess adherence to the MDP . The MDP score positively weighted the consumption of vegetables , fruit and nuts , cereal , legumes , and fish ; the monounsaturated- to saturated-fatty-acids ratio ; and moderate alcohol consumption , whereas meat or meat products and whole-fat dairy were negatively weighted . SETTING A dynamic cohort of university graduates ( Seguimiento Universidad de Navarra/University of Navarra Follow-up [ SUN ] Project ) . PARTICIPANTS A total of 10 094 initially healthy Spanish participants from the SUN Project participated in the study . Recruitment began on December 21 , 1999 , and is ongoing . MAIN OUTCOME MEASURE Participants were classified as having incident depression if they were free of depression and antidepressant medication at baseline and reported a physician-made diagnosis of clinical depression and /or antidepressant medication use during follow-up . RESULTS After a median follow-up of 4.4 years , 480 new cases of depression were identified . The multiple adjusted hazard ratios ( 95 % confidence intervals ) of depression for the 4 upper successive categories of adherence to the MDP ( taking the category of lowest adherence as reference ) were 0.74 ( 0.57 - 0.98 ) , 0.66 ( 0.50 - 0.86 ) , 0.49 ( 0.36 - 0.67 ) , and 0.58 ( 0.44 - 0.77 ) ( P for trend < .001 ) . Inverse dose-response relationships were found for fruit and nuts , the monounsaturated- to saturated-fatty-acids ratio , and legumes . CONCLUSIONS Our results suggest a potential protective role of the MDP with regard to the prevention of depressive disorders ; additional longitudinal studies and trials are needed to confirm these findings |
12,303 | 20,976,727 | Two large western r and omized trials , meta-analyses and a recent systematic review were unable to demonstrate overall benefit from extended lymphadenectomy . | The extent of lymphadenectomy during therapeutic gastrectomy for gastric cancer remains a protracted and controversial issue .
While traditionally extended lymphadenectomy is performed in Eastern Asia , limited lymphadenectomy is advocated by most western surgeons . | Abstract Background : Although early gastric cancer ( T1 , NX ) in Japan has been reported to have an excellent prognosis , the experience with this cancer in the United States is limited . The treatment of these tumors in Japan is becoming less aggressive as “ good prognostic factors ” are increasingly recognized . Our objective was to identify predictors of nodal disease and survival in a large cohort of Western patients with T1 tumors . Methods : A retrospective review of our prospect i ve data base from July 1985 to March 1998 revealed 165 patients undergoing surgical resection for T1 gastric tumors . Clinicopathological factors analyzed and compared included presence of positive nodes , tumor size ( 4.5 vs.,4.5 cm ) , depth ( mucosal vs. submucosal ) , grade ( poor vs. moderate and well ) , and tumor site ( proximal vs. distal ) , presence of venous or perineural invasion , and Lauren ’s classification . Factors predicting lymph node involvement and disease-specific survival were evaluated by univariate and multivariate analysis . Results : Median follow-up time was 36 months . The actuarial 5-year survival was 88 % . Thirteen patients ( 8 % ) died of disease . Lymph node involvement was present in 31 tumors ( 19 % ) , with a 5-year survival of 91 % with negative nodes vs. 78 % with positive nodes . On univariate and multivariate analysis , the presence of tumor submucosal invasion ( P,.05 ) , venous invasion ( P 5.02 ) , and size of 4.5 cm and larger ( P 5.02 ) was significantly associated with an increased risk for nodal positivity . On univariate analysis of survival , node-positive tumors ( P 5.02 ) and tumors 4.5 cm and larger ( P 5.008 ) were significantly associated with decreased survival . On multivariate analysis , only node-positive tumors were significantly ( P 5.01 ) associated with decreased survival . Those tumors that were limited to the mucosa and less than 4.5 cm in size ( n = 47 ) had a 4 % rate of positive nodes . In contrast , those tumors that were 4.5 cm and larger and had penetrated into the submucosa ( n = 16 ) had a 56 % chance of positive nodes . Conclusions : Early gastric carcinoma in North America has an excellent prognosis , similar to that in Japan . Tumors that are limited to the mucosa and smaller than 4.5 cm could be considered for limited resection without lymphadenectomy BACKGROUND In Japan the surgical approach to treatment of potentially curable gastric cancer , including extended lymphadenectomy , seems in retrospective surveys to give better results than the less radical procedures favoured in Western countries . There has , however , been no evidence from r and omised trials that extended lymphadenectomy ( D2 gastric resection ) confers a survival advantage . This question was addressed in a trial involving thirty-two surgeons in Europe . METHODS In a prospect i ve r and omised controlled trial , D1 resection ( level 1 lymphadenectomy ) was compared with D2 resection ( levels 1 and 2 lymphadenectomy ) . Central r and omisation ( 200 patients in each arm ) followed a staging laparotomy . FINDINGS The D2 group had greater postoperative hospital mortality ( 13 % vs 6.5 % ; p=0.04 [ 95 % Cl 9 - 18 % for D2 , 4 - 11 % for D1 ] and higher overall postoperative morbidity ( 46 % vs 28 % ; p<0.001 ) ; their postoperative stay was also longer . The excess postoperative morbidity and mortality in the D2 group was accounted for by distal pancreaticosplenectomy and splenectomy . In the whole group ( 400 patients ) , survival beyond three years was 30 % in patients whose gastrectomy included en-bloc pancreatico-splenic resection versus 50 % in the remainder . INTERPRETATION D2 gastric resections are followed by higher morbidity and mortality than D1 resections . These disadvantages are consequent upon additional pancreatectomies and distal splenectomies , and in long-term follow-up the higher mortality when the pancreas and spleen are resected may prove to nullify any survival benefit from D2 procedures The contention that the R2 radical gastrectomy for localized and potentially curable gastric carcinoma may be superior to gastrectomy without lymphadenectomy ( R1 ) was assessed by r and omized trial . Five years after commencement 403 patients have been evaluated at surgery and only 43 ( 11 per cent ) found eligible ( S0–2 , P0 , H0 , N0–1 ) , 22 of whom underwent R1 and 21 R2 gastrectomy . Seven patients had final histological stages in excess of the protocol . The R2 group had a longer operating time ( P<0.005 ) , a greater blood transfusion requirement ( P<0.005 ) , a longer hospital stay ( 0.05>P>0.025 ) and required reoperation in four cases . There were no postoperative deaths . Four patients have died from the disease in the R1 group and five in the R2 group , there being no difference in the probability of survival at a median follow‐up of 3.1 years . The small proportion of patients suitable for radical R2 surgery , the high associated morbidity and the fact that survival advantage has yet to be proven in trial suggest that this procedure should not yet be performed outside of controlled clinical trials This prospect i ve r and omized study compared the survival of patients with tumour node metastasis ( TNM ) stage T2 N1–2 gastric cancer treated by gastrectomy alone or gastrectomy followed by uracil – tegafur BackgroudApplication of laparoscopy-assisted distal gastrectomy ( LADG ) for early gastric cancer ( EGC ) is still controversial because of scant evidence of long-term safety and feasibility . We evaluated the long-term outcome of LADG compared with conventional open distal gastrectomy ( ODG ) for EGC . Methods Between March 1999 and July 2006 , 106 patients underwent LADG and 105 patients underwent ODG for EGC . Clinicopathologic characteristics , postoperative outcomes , hospital course , postoperative morbidity , postoperative mortality , and long-term outcomes , including cancer recurrence and survival , were retrospectively compared between the two groups . Survival of all patients was confirmed with 55-month median follow-up . Results Postoperative recovery was significantly faster in the LADG group ; passing flatus occurred earlier , starting a liquid diet began sooner , and postoperative hospital stay was shorter ( p < 0.05 ) . Mean operation time was significantly longer in the LADG group . Postoperative complications in the LADG group occurred less frequently compared with in the ODG group ( 4.7 % versus 13.3 % , p = 0.046 ) . Tumor recurrence occurred in two cases ( 0.9 % ) and death related to recurrence occurred in only one patient ( 0.5 % ) . Overall 5-year survival rate ( 5-YSR ) of all patients was 95.5 % , while disease-specific 5-YSR was 98.8 % . There was no significant difference in survival rates between the two groups ; overall 5-YSR of the ODG and LADG groups was 94.9 % and 95.9 % , respectively . Conclusions Our data suggest that LADG for EGC is feasible and safe . We expect the results of the present study to be confirmed by prospect i ve r and omized analysis Curative resection is the treatment of choice for potentially curable gastric cancer . Two major Western studies in the 1990s failed to show a benefit from D2 dissection . They showed extremely high postoperative mortality after D2 dissection , and were criticised for the potential inadequacy of the pretrial training in the new technique of D2 dissection , prior to the phase III studies being initiated . The inclusion of pancreatectomy and splenectomy in D2 dissection was associated with increased morbidity and mortality . Following these results , we started a phase II trial to evaluate the safety and efficacy of pancreas-preserving D2 dissection . The results of this trial regarding the safety of pancreas preserving D2 dissection were published in 1998 . In this paper , we present the survival results of this phase II trial to confirm the rationale of carrying out a phase III study comparing D1 vs D2 dissection for curable gastric cancer . Italian patients with histologically proven gastric adenocarcinoma were registered in the Italian Gastric Cancer Study Group Multicenter trial . The study was carried out based on the General Rules of the Japanese Research Society for Gastric Cancer . A strict quality control system was achieved by a supervising surgeon of the reference centre who had stayed at the National Cancer Center Hospital , Tokyo , to learn the st and ard D2 gastrectomy and the postoperative management . The st and ard procedure entailed removal of the first and second tier lymph nodes . During total gastrectomy , the pancreas was preserved according to the Maruyama technique . Complete follow-up was available to death or 5 years in 100 % of patients and the median follow-up time was 4.38 years . Out of 297 consecutive patients registered , 191 patients were enrolled in the study between May 1994 and December 1996 . The overall morbidity rate was 20.9 % . The postoperative in-hospital mortality was 3.1 % . The overall 5-year survival rate among all eligible patients was 55 % . Survival was strictly related to stage , depth of wall invasion , lymph node involvement and type of gastrectomy ( distal vs total).Our results suggest a survival benefit for pancreas-preserving D2 dissection in Italian patients with gastric cancer if performed in experienced centres . A phase III trial among exclusively experienced centres is urgently needed BACKGROUND A multicenter , r and omized , clinical trial was initiated to evaluate the possible benefits of extended D2 ( D2 + ) lymphadenectomy after potentially curative resection of gastric cancer . METHODS St and ard D2 lymphadenectomy was defined according to the Japanese Gastric Cancer Association classification . D2 + lymph node dissection additionally included the removal of para-aortic nodes . RESULTS Of 781 patients screened , 275 were r and omized to st and ard D2 ( n = 141 ) or extended D2 + ( n = 134 ) lymphadenectomy . The overall morbidity rates were comparable in D2 ( 27.7 % ; 95 % confidence interval [ CI ] , 20.3 - 35.1 ) and D2 + ( 21.6 % ; 95 % CI , 13.7 - 29.5 ) groups ( P = .248 ) . Pre-existing cardiac disease , splenectomy , and excessive blood loss were identified as risk factors for overall and nonsurgical complications . Postoperative mortality rates were 4.9 % ( 95 % CI , 1.4 - 8.5 ) and 2.2 % ( 95 % CI , 0 - 4.7 ) , respectively ( P = .376 ) . CONCLUSIONS The interim safety analysis failed to show any significant difference with regard to the extent of lymph node dissection . The surgical outcome was not different between the 2 surgeries Background The prognosis of patients with gastric cancer and para-aortic lymph node ( PALN ) metastasis is poor . Recent Japanese r and omized trials concluded that prophylactic PALN dissection is not effective for curable advanced gastric cancer . However , the value of curative resection in patients with pathologically positive PALN is not determined yet . Methods We retrospectively identified 178 patients with pathologically positive PALN who underwent curative resection at the Cancer Institute Hospital from 1980 to 2004 . Patient characteristics were analyzed and independent prognostic factors for death were identified by Cox proportional hazard model . Results Partial gastrectomy was the most frequently performed procedure ( 142 of 178 ) . Postoperative morbidity and mortality rates were 30 and 2 % , respectively , with a 5-year survival rate of 13.0 % . Multivariate analysis revealed the total number of positive nodes ( hazard ratio , 1.804 ; 95 % confidence interval , 1.221–2.665 ) and macroscopic type ( hazard ratio , 1.697 ; 95 % confidence interval , 1.138–2.530 ) as independent prognostic factors , while age , sex , histology , pathological tumor depth , and degree of PALN dissection were not statistically significant . The 5-year survival rate increased to 28.6 % in patients with ≤15 positive nodes and macroscopic type other than type 4 . Conclusions Prophylactic PALN dissection can not be justified in curable advanced gastric cancer . However , R0 resection including PALN retrieval might be beneficial in patients with pathologically positive PALN , providing patients are carefully selected and operations are performed safely BACKGROUND / AIMS A r and omized study was performed to evaluate morbidity and mortality after D2 ( level 1 and 2 lymphadenectomy ) and D4 ( D2 plus lymphadenectomy of para-aortic lymph nodes ) dissection for advanced gastric cancer . METHODOLOGY Two hundred and fifty-six patients with advanced gastric adenocarcinoma were enrolled ( 128 to each group ) . Patients were r and omly allocated into D2 ( N = 128 ) or D4 ( N = 128 ) group . The first and second tiers of lymph nodes are removed in D2 dissection . In D4 gastrectomy , the paraaortic lymph nodes were additionally removed . RESULTS There was no indication of significant distribution bias with regard to age , sex , T- grade , and N- grade between the two groups . Operation time of D4 gastrectomy ( 369 + /- 120 min ) was significantly longer than that of D2 gastrectomy ( 273 + /- 1103 min ) , and blood loss of the D4 group ( 872 + /- 683 mL ) was significantly greater than that of the D2 group 571 + /- 527 mL ( P < 0.001 ) . Five ( 4 % ) and two ( 2 % ) medical complications developed in the D2 and D4 groups , respectively . Surgical complications developed in 28 ( 22 % ) and 48 patients ( 38 % ) after D2 and D4 gastrectomy . The most common complications were anastomotic leakage , pancreatic fistula , and abdominal abscess . Pancreatic fistula developed in 6 ( 19 % ) of 32 patients after D4 plus pancreatosplenectomy , but the incidence of pancreatic fistula after D2 gastrectomy plus pancreatosplenectomy was low ( 6 % , 1/16 ) . Two patients died within 30 days of operation ( 0.8 % , 2/256 ) , and each patient belonged to the D2 and D4 group . CONCLUSIONS Although there is a significantly higher surgical complication rate in D4 dissection , D4 dissection can be done safely as D2 dissection when performed by well-trained surgeons PURPOSE Possible causes underlying the substantial differences in gastric cancer survival rates observed between Japan and the West were examined in a r and omized trial comparing the Western R1 resection with limited lymphadenectomy and the Japanese R2 resection with extended lymphadenectomy . PATIENTS AND METHODS The effect of four factors associated with lymphadenectomy on microscopic tumor-node-metastasis ( TNM ) staging , and on stage-specific survival rates was assessed in 473 curatively resected patients . RESULTS After application of extended lymphadenectomy , additional information on N status was available , only in R2 resections with up-staging to N2 status in 30 % of patients . The calculated effect of this stage migration on known 5-year survival rates was as follows : an increase of 1 % in TNM stage Ia , 2 % in Ib , 7 % in II , 15 % in IIIa , and 15 % in IIIb . A further increase in survival was observed by stage migration to N3 or N4 status , due to selective extension of lymphadenectomy to clinical ly overt metastases located outside the allocated level of clearance ( contamination ) . Incomplete lymphadenectomy of N1- or N2-level stations indicated for dissection ( noncompliance ) demonstrates that more migration can occur when strictly adhering to the protocol . Examining more nodes per N level ( diligence ) induces even more migration , since the number of nodes that were histologically examined per N level correlated significantly with nodal status ( lymph node-negative [ N- ] or lymph node-positive [ N+ ] ) . CONCLUSION These factors explain , at least partially , superior stage-specific survival rates after R2 compared with R1 resections , without a real survival benefit in individual patients Background This study was conducted to evaluate the leaning curve of D2 lymph node dissection for patients with gastric cancer in a high-volume center . Methods The authors prospect ively review ed the data of all patients who underwent total gastrectomy with D2 lymph node dissection during a 4-year period . Retrieved lymph node number was used as a surrogate marker of oncological outcome . The retrieved lymph node number cut-off value required for satisfactory D2 lymph node dissection was defined as > 25 . Cumulative sum analysis was used to examine the learning curves of individual surgeons at target accuracy rates of 85 % , 90 % , 92.5 % , 95 % , and 98 % . Results Two junior staff surgeons performed 198 curative-intent total gastrectomies with D2 lymph node dissections during the study period ; their success rates exceeded 90 % . Operating time decreased with operative experience ( Pearson correlation coefficient = −0.515 , P < 0.001 ) . The learning period for total gastrectomy with D2 lymph node dissection for these two junior members of staff was calculated as 23–35 cases , presuming a 92.5 % success rate . Conclusions The current study suggests that the surgical learning period for D2 lymph node dissection extends to at least 23 cases or 8 months . In clinical trials containing gastric cancer surgery , the learning curve for qualified surgery from the st and point of oncological outcome should be considered to minimize bias due to surgeon-associated factors PURPOSE The extent of lymph node dissection appropriate for gastric cancer is still under debate . We have conducted a r and omized trial to compare the results of a limited ( D1 ) and extended ( D2 ) lymph node dissection in terms of morbidity , mortality , long-term survival and cumulative risk of relapse . We have review ed the results of our trial after follow-up of more than 10 years . PATIENTS AND METHODS Between August 1989 and June 1993 , 1,078 patients with gastric adenocarcinoma were r and omly assigned to undergo a D1 or D2 lymph node dissection . Data were collected prospect ively , and patients were followed for more than 10 years . RESULTS A total of 711 patients ( 380 in the D1 group and 331 in the D2 group ) were treated with curative intent . Morbidity ( 25 % v 43 % ; P < .001 ) and mortality ( 4 % v 10 % ; P = .004 ) were significantly higher in the D2 dissection group . After 11 years there is no overall difference in survival ( 30 % v 35 % ; P = .53 ) . Of all subgroups analyzed , only patients with N2 disease may benefit of a D2 dissection . The relative risk ratio for morbidity and mortality is significantly higher than one for D2 dissections , splenectomy , pancreatectomy , and age older than 70 years . CONCLUSION Overall , extended lymph node dissection as defined in this study generated no long-term survival benefit . The associated higher postoperative mortality offsets its long-term effect in survival . For patients with N2 disease an extended lymph node dissection may offer cure , but it remains difficult to identify patients who have N2 disease . Morbidity and mortality are greatly influenced by the extent of lymph node dissection , pancreatectomy , splenectomy and age . Extended lymph node dissections may be of benefit if morbidity and mortality can be avoided A 3‐year prospect i ve study of the learning curve for D2 gastrectomy was carried out by one surgeon beginning to perform the operation independently after intensive specialist training . Some 38 patients were treated ; there were four postoperative deaths and 22 patients had complications . Postoperative morbidity decreased significantly with time ( rs= ‐0·38 , P = 0·02 , 95 per cent confidence interval ‐ 0·62 to ‐ 0·07 ) . The physiological component of POSSUM ( Physiological and Operative Severity Score for the enumeration of Mortality and morbidity ) was significantly lower in the third year ( median value 15 , 16 and 14 for years 1 , 2 and 3 , n = 31 , χ2 = 7·5 , 2 d.f . , P = 0·02 , Kruskal‐Wallis test ) , but the operative POSSUM scores and the number of lymph nodes found were not decreased ( median operative POSSUM score 19 , 18 and 21 , n = 31 , χ2 = 0·2 , 2 d.f . , P = 0·91 , Kruskal‐Wallis test ) . The results suggest a learning curve lasting about 18–24 months or 15 to 25 procedures before a plateau is reached . Improved results were associated with changes in case selection and operative tactics but not with reduced extent of lymphadenectomy . D2 gastrectomy should be restricted to specialist centres where adequate training and supervision can be provided during the learning curve BACKGROUND Gastrectomy with D2 lymphadenectomy is the st and ard treatment for curable gastric cancer in eastern Asia . Whether the addition of para-aortic nodal dissection ( P AND ) to D2 lymphadenectomy for stage T2 , T3 , or T4 tumors improves survival is controversial . We conducted a r and omized , controlled trial at 24 hospitals in Japan to compare D2 lymphadenectomy alone with D2 lymphadenectomy plus P AND in patients undergoing gastrectomy for curable gastric cancer . METHODS Between July 1995 and April 2001 , 523 patients with curable stage T2b , T3 , or T4 gastric cancer were r and omly assigned during surgery to D2 lymphadenectomy alone ( 263 patients ) or to D2 lymphadenectomy plus P AND ( 260 patients ) . We did not permit any adjuvant therapy before the recurrence of cancer . The primary end point was overall survival . RESULTS The rates of surgery-related complications among patients assigned to D2 lymphadenectomy alone and those assigned to D2 lymphadenectomy plus P AND were 20.9 % and 28.1 % , respectively ( P=0.07 ) . There were no significant differences between the two groups in the frequencies of anastomotic leakage , pancreatic fistula , abdominal abscess , pneumonia , or death from any cause within 30 days after surgery ( the rate of death was 0.8 % in each group ) . The median operation time was 63 minutes longer and the median blood loss was 230 ml greater in the group assigned to D2 lymphadenectomy plus P AND . The 5-year overall survival rate was 69.2 % for the group assigned to D2 lymphadenectomy alone and 70.3 % for the group assigned to D2 lymphadenectomy plus P AND ; the hazard ratio for death was 1.03 ( 95 % confidence interval [ CI ] , 0.77 to 1.37 ; P=0.85 ) . There were no significant differences in recurrence-free survival between the two groups ; the hazard ratio for recurrence was 1.08 ( 95 % CI , 0.83 to 1.42 ; P=0.56 ) . CONCLUSIONS As compared with D2 lymphadenectomy alone , treatment with D2 lymphadenectomy plus P AND does not improve the survival rate in curable gastric cancer . ( Clinical Trials.gov number , NCT00149279 . BACKGROUND The survival benefit and morbidity after nodal dissection for gastric cancer remains controversial . We aim ed to do a single-institution r and omised trial to compare D1 ( ie , level 1 ) lymphadenectomy with that of D3 ( ie , levels 1 , 2 , and 3 ) dissection for gastric cancer in terms of overall survival and disease-free survival . METHODS From Oct 7 , 1993 , to Aug 12 , 1999 , 335 patients were registered . 221 patients were eligible , 110 of whom were r and omly assigned D1 surgery and 111 of whom were r and omly assigned D3 surgery , both with curative intent . Three participating surgeons had done at least 25 independent D3 dissections before the start of the trial , and every procedure was verified by pathological analyses . The primary endpoints were 5-year overall survival and 5-year disease-free survival . We also analysed risk of recurrence . Main analyses were done by intention to treat . This trial is registered at the US National Institute of Health website . FINDINGS Median follow-up for the 110 ( 50 % ) survivors was 94.5 months ( range 62.9 - 135.1 ) . Overall 5-year survival was significantly higher in patients assigned D3 surgery than in those assigned D1 surgery ( 59.5 % [ 95 % CI 50.3 - 68.7 ] vs 53.6 % [ 44.2 - 63.0 ] ; difference beteween groups 5.9 % [ -7.3 to 19.1 ] , log-rank p=0.041 ) . 215 patients who had R0 resection ( ie , no microscopic evidence of residual disease ) had recurrence at 5 years of 50.6 % [ 41.1 - 60.2 ] for D1 surgery and 40.3 % [ 30.9 - 49.7 ] for D3 surgery ( difference between groups 10.3 % [ -3.2 to 23.7 ] , log-rank p=0.197 ) . INTERPRETATION D3 nodal dissection , compared with that of D1 , offers a survival benefit for patients with gastric cancer when done by well trained , experienced surgeons Extended lymphadenectomy ( D2 ) provides accurate nodal staging of gastric cancer . The aim of this study was to clarify the degree of stage migration seen with D2 combined with para‐aortic lymph node dissection for gastric cancer invading the subserosa , the serosa and adjacent structures ( T2ss–4 ) in patients considered not to have distant metastases ( M0 ) BACKGROUND Classic surgical treatment of upper third gastric carcinoma is based on an extended total gastrectomy , including splenectomy . The purpose of this study was to perform a prospect i ve r and omized clinical trial comparing the early and late results of total gastrectomy ( TG ) versus total gastrectomy plus splenectomy ( TGS ) . METHODS One hundred eighty-seven patients with gastric carcinoma were included . In all patients a D2 total gastrectomy was performed . During surgery they were r and omized to 1 of 2 operative options . They were monitored to their death or to 5 years later if they were alive . RESULTS Operative mortality was similar after both operations ( 3 % after TG and 4 % after TGS ) . Septic complications after surgery were higher after TGS compared with TG ( P < .04 ) . Five-year survival rates were not statistically different between groups or in subset analysis according to stage of disease . CONCLUSIONS On the basis of the results of the present prospect i ve r and omized trial , splenectomy is not necessary in early stages of disease . A low operative mortality rate ( less than 3 % ) must be achieved to obtain good long-term results BACKGROUND / AIMS Preoperative chemotherapy is considered an effective treatment option for patients with gastric cancer . We retrospectively evaluated neoadjuvant chemotherapy with oxaliplatin , leucovorin and 5-flurouracil ( OLF ) in patients with locally advanced gastric cancer to determine its feasibility , as well as impact on the curative resection rate and patients ' survival . METHODOLOGY A total of 87 patients with locally advanced gastric cancer that underwent preoperative chemotherapy combined with surgery or surgery alone were r and omly matched according to the clinical TNM stage . The clinical responses to chemotherapy were assessed . The curative rate , postoperative complications and patients ' survival between both groups were compared . RESULTS The two groups were well matched . Complete or partial response was observed in 51.7 % ( 15/29 ) of patients in the OLF group , and three ( 10.3 % ) of them had complete pathologic response . The curative resection rates were 89.7 % in the OLF group and 77.6 % in the surgery alone group . The postoperative complications were equal for both groups . The mean survival is 20.6 months in the OLF group vs. 19.9 months in the surgery alone group ( p=0.02 ) . CONCLUSIONS Neoadjuvant chemotherapy using OLF combination is active in gastric cancer and the toxicity level is acceptable . This treatment improves the curative resection rate and patients ' survival in locally advanced gastric cancer Background Laparoscopy-assisted distal gastrectomy ( LADG ) with st and ard D2 dissection is a complex procedure usually performed only by experienced surgeons , and the feasibility of this procedure still remains unclear . Method Patients who underwent LADG at the Cancer Institute Hospital between April 2006 and October 2008 were recruited for this study . Early surgical outcomes were compared between patients who underwent complete D2 dissection ( complete D2 group ; n = 42 ) and those who underwent D1 + beta dissection ( D1 + beta group ; n = 179 ) to determine the feasibility of laparoscopic D2 lymph node dissection . Results In complete D2 group , the operation time was longer ( 253 ± 10 vs 224 ± 4 min ; P = 0.005 ) , and the number of retrieved lymph nodes was larger ( 41 ± 2 vs 35 ± 1 ; P = 0.002 ) compared with those in D1 + beta group . The other early surgical outcomes monitored for the two groups were not different between groups . Conclusions LADG with complete D2 lymph node dissection can be performed safely if the procedure is st and ardized and an experienced laparoscopic surgeon performs the surgery . To be accepted as a st and ard treatment for advanced gastric cancer , well- design ed prospect i ve trial is necessary Background The survival of patients with advanced gastric cancer after D2 dissection is still poor . Asian surgeons have proposed a more radical lymph node dissection , design ated as D4 dissection , where paraaortic lymph nodes are removed in combination with D2 dissection . To evaluate the survival benefit of D4 dissection , a multi-institutional r and omized trial of D2 vs D4 gastrectomy was conducted . Methods Patients enrolled in the study had potentially curable gastric adenocarcinoma at an advanced stage . Patients were r and omized to undergo either D2 or D4 gastrectomy . Results Two hundred and ninety-three patients were registered and 269 patients were eligible ; 135 patients were allocated to the D2 group and 134 to the D4 group . Five-year survival was 52.6 % after D2 surgery and 55.0 % after D4 gastrectomy . There was no significant difference in survival between the D2 and D4 groups ( χ2 = 0.064 ; P = 0.801 ) . Hospital deaths occurred in 1 patients ( 0.7 % ) in the D2 group and 5 in the D4 group D4 gastrectomy is a more risky surgery than D2 dissection . Seven patients ( 5.2 % ) in the D2 and 15 ( 11.2 % ) in the D4 group died of causes other than gastric cancer recurrence . Sixty-three patients ( 46.7 % ) in the D2 group and 52 ( 38.8 % ) in the D4 group had disease recurrence . Conclusion Prophylactic D4 dissection is not recommended for patients with potentially curable advanced gastric cancer Objective The authors determined if more radical surgery with extended lymphadenectomy improves the results of gastrectomy in patients with adenocarcinoma of the gastric antrum . Summary Background Data The overall survival in patients with gastric cancer is disappointing . Improved survival has been reported by Japanese authors . Whether this is because of a higher number of early gastric cancers in the Japanese series , different biologic behavior in Asians , or the adoption of radical surgery with lymphadenectomy remains unclear . Methods R1 subtotal gastrectomy with omentectomy and R3 total gastrectomy ( omentectomy , splenectomy , distal pancreatectomy , lymphatic clearance of the celiac axis , and skeletonization of vessels in the porta hepatis ) were evaluated in a prospect i ve , r and omized comparison . Results Fifty-five patients were r and omized—25 to the R1 group and 30 to the R3 group . The two groups were comparable for age , sex , tumor size , TNM stage , and length of follow-up . The R3 group had a longer operating time ( 140 vs. 260 min ; p < 0.05 ) , a greater transfusion requirement ( 0 vs. 2 units , p < 0.05 ) and a longer hospital stay ( 8 vs. 16 days ; p < 0.05 ) ( medians ; Mann-Whitney U test ) . The only postoperative death was in the R3 group and was caused by intra-abdominal sepsis . Fourteen patients in the R3 group developed left subphrenic abscesses . There were no major complications in the R1 group . Overall survival was significantly better in the R1 group ( median survival estimated by Kaplan-Meier method , 1511 vs. 922 days , p < 0.05 , log-rank test ) . Conclusions R3 total gastrectomy can be performed with a low mortality , but it has a high morbidity because of intra-abdominal sepsis . The data do not support the routine use of R3 total gastrectomy for treatment of patients with antral cancer BACKGROUND Japanese surgeons have been actively performing extended lymphadenectomy ( D2 , removal of perigastric nodes and nodes along the left gastric , common hepatic , celiac and splenic arteries ; or D3 , D2 plus removal of nodes in the hepatoduodenal ligament , in the retropancreatic space and along the vessels of the transverse mesocolon ) . In recent years interest has exp and ed to superextended lymphadenectomy ( D4 ) of nodes around abdominal aorta ( para-aortic lymph nodes from aortic hiatus to aortic bifurcation ) . Because the therapeutic value of this D4 procedure remains controversial , we initiated a prospect i ve study to compare D3 and D4 lymphadenectomy . METHODS Seventy patients with T3 or T4 gastric cancer and without macroscopic metastasis to the para-aortic nodes treated by potentially curative total gastrectomy were r and omized to D4 ( group A , n = 35 ) and D3 ( group B , n = 35 ) lymphadenectomies . RESULTS Metastases to para-aortic nodes were found in 4 patients . Postoperative survival after D4 resection was not statistically significant between the groups . Postoperative morbidity for group A was greater . In group A 4 patients had postoperative retention of intra-abdominal fluid ( lymphorrhea ) and 4 others had prolonged diarrhea . One patient in each group died of postoperative complications . CONCLUSIONS Surgical treatment of microscopic disease in grossly normal para-aortic lymph nodes may generate occasional long-term survivors . Selecting appropriate c and i date s who might benefit from D4 resections needs to be refined . On the basis of this study , a nationwide study should be considered BACKGROUND The disadvantages of D2 gastrectomy have been mostly related to splenopancreatectomy . Unlike two large European trials , we have recently showed the safety of D2 dissection with pancreas preservation in a one-arm phase I-II trial . This new r and omised trial was set up to compare post-operative morbidity and mortality and survival after D1 and D2 gastrectomy among the same experienced centres that participated into the previous trial . METHODS In a prospect i ve multicenter r and omised trial , D1 gastrectomy was compared to D2 gastrectomy . Central r and omisation was performed following a staging laparotomy in 162 patients with potentially curable gastric cancer . FINDINGS Of 162 patients r and omised , 76 were allocated to D1 and 86 to D2 gastrectomy . The two groups were comparable for age , sex , site , TNM stage of tumours , and type of resection performed . The overall post-operative morbidity rate was 13.6 % . Complications developed in 10.5 % of patients after D1 and in 16.3 % of patients after D2 gastrectomy . This difference was not statistically significant ( p<0.29 ) . Reoperation rate was 3.4 % after D2 and 2.6 % after D1 resection . Post-operative mortality rate was 0.6 % ( one death ) ; it was 1.3 % after D1 and 0 % after D2 gastrectomy . INTERPRETATION Our preliminary data confirm that in very experienced centres morbidity and mortality after extended gastrectomy can be as low as those showed by Japanese authors . They also suggest that D2 gastrectomies with pancreas preservation are not followed by significantly higher morbidity and mortality than D1 resections BACKGROUND A regimen of epirubicin , cisplatin , and infused fluorouracil ( ECF ) improves survival among patients with incurable locally advanced or metastatic gastric adenocarcinoma . We assessed whether the addition of a perioperative regimen of ECF to surgery improves outcomes among patients with potentially curable gastric cancer . METHODS We r and omly assigned patients with resectable adenocarcinoma of the stomach , esophagogastric junction , or lower esophagus to either perioperative chemotherapy and surgery ( 250 patients ) or surgery alone ( 253 patients ) . Chemotherapy consisted of three preoperative and three postoperative cycles of intravenous epirubicin ( 50 mg per square meter of body-surface area ) and cisplatin ( 60 mg per square meter ) on day 1 , and a continuous intravenous infusion of fluorouracil ( 200 mg per square meter per day ) for 21 days . The primary end point was overall survival . RESULTS ECF-related adverse effects were similar to those previously reported among patients with advanced gastric cancer . Rates of postoperative complications were similar in the perioperative-chemotherapy group and the surgery group ( 46 percent and 45 percent , respectively ) , as were the numbers of deaths within 30 days after surgery . The resected tumors were significantly smaller and less advanced in the perioperative-chemotherapy group . With a median follow-up of four years , 149 patients in the perioperative-chemotherapy group and 170 in the surgery group had died . As compared with the surgery group , the perioperative-chemotherapy group had a higher likelihood of overall survival ( hazard ratio for death , 0.75 ; 95 percent confidence interval , 0.60 to 0.93 ; P=0.009 ; five-year survival rate , 36 percent vs. 23 percent ) and of progression-free survival ( hazard ratio for progression , 0.66 ; 95 percent confidence interval , 0.53 to 0.81 ; P<0.001 ) . CONCLUSIONS In patients with operable gastric or lower esophageal adenocarcinomas , a perioperative regimen of ECF decreased tumor size and stage and significantly improved progression-free and overall survival . ( Current Controlled Trials number , IS RCT N93793971 [ controlled-trials.com ] . ) A r and omized comparison of D1 ( level 1 lymphadenectomy ) and D3 ( levels 1 , 2 and 3 lymphadenectomy ) dissection was performed to evaluate morbidity and effects on survival from gastric cancer BACKGROUND Advanced gastric cancer can respond to S-1 , an oral fluoropyrimidine . We tested S-1 as adjuvant chemotherapy in patients with curatively resected gastric cancer . METHODS Patients in Japan with stage II or III gastric cancer who underwent gastrectomy with extended ( D2 ) lymph-node dissection were r and omly assigned to undergo surgery followed by adjuvant therapy with S-1 or to undergo surgery only . In the S-1 group , administration of S-1 was started within 6 weeks after surgery and continued for 1 year . The treatment regimen consisted of 6-week cycles in which , in principle , 80 mg of oral S-1 per square meter of body-surface area per day was given for 4 weeks and no chemotherapy was given for the following 2 weeks . The primary end point was overall survival . RESULTS We r and omly assigned 529 patients to the S-1 group and 530 patients to the surgery-only group between October 2001 and December 2004 . The trial was stopped on the recommendation of the independent data and safety monitoring committee , because the first interim analysis , performed 1 year after enrollment was completed , showed that the S-1 group had a higher rate of overall survival than the surgery-only group ( P=0.002 ) . Analysis of follow-up data showed that the 3-year overall survival rate was 80.1 % in the S-1 group and 70.1 % in the surgery-only group . The hazard ratio for death in the S-1 group , as compared with the surgery-only group , was 0.68 ( 95 % confidence interval , 0.52 to 0.87 ; P=0.003 ) . Adverse events of grade 3 or grade 4 ( defined according to the Common Toxicity Criteria of the National Cancer Institute ) that were relatively common in the S-1 group were anorexia ( 6.0 % ) , nausea ( 3.7 % ) , and diarrhea ( 3.1 % ) . CONCLUSIONS S-1 is an effective adjuvant treatment for East Asian patients who have undergone a D2 dissection for locally advanced gastric cancer . ( Clinical Trials.gov number , NCT00152217 [ Clinical Trials.gov ] . ) Locally advanced gastric cancer with extensive lymph node metastasis is usually considered unresectable and so treated by chemotherapy . This trial explored the safety and efficacy of preoperative chemotherapy followed by extended surgery in the management of locally advanced gastric adenocarcinoma Summary Controversy still exists on the optimal surgical resection for potentially curable gastric cancer . Much better long-term survival has been reported in retrospective/non-r and omized studies with D2 resections that involve a radical extended regional lymphadenectomy than with the st and ard D1 resections . In this paper we report the long-term survival of patients entered into a r and omized study , with follow-up to death or 3 years in 96 % of patients and a median follow-up of 6.5 years . In this prospect i ve trial D1 resection ( removal of regional perigastric nodes ) was compared with D2 resection ( extended lymphadenectomy to include level 1 and 2 regional nodes ) . Central r and omization followed a staging laparotomy . Out of 737 patients with histologically proven gastric adenocarcinoma registered , 337 patients were ineligible by staging laparotomy because of advanced disease and 400 were r and omized . The 5-year survival rates were 35 % for D1 resection and 33 % for D2 resection ( difference –2 % , 95 % CI = –12%–8 % ) . There was no difference in the overall 5-year survival between the two arms ( HR = 1.10 , 95 % CI 0.87–1.39 , where HR > 1 implies a survival benefit to D1 surgery ) . Survival based on death from gastric cancer as the event was similar in the D1 and D2 groups ( HR = 1.05 , 95 % CI 0.79–1.39 ) as was recurrence-free survival ( HR = 1.03 , 95 % CI 0.82–1.29 ) . In a multivariate analysis , clinical stages II and III , old age , male sex and removal of spleen and pancreas were independently associated with poor survival . These findings indicate that the classical Japanese D2 resection offers no survival advantage over D1 surgery . However , the possibility that D2 resection without pancreatico-splenectomy may be better than st and ard D1 resection can not be dismissed by the results of this trial |
12,304 | 25,418,417 | Results from five small studies , with low method ological quality , indicated ESWL is less effective for kidney stones than PCNL but not significantly different from RIRS .
Hospital stay and duration of treatment was less with ESWL . | BACKGROUND Stones in the urinary tract are a common medical problem in the general population .
At present , the great expansion in minimally invasive techniques has led to the decrease in open surgery .
Extracorporeal shock wave lithotripsy ( ESWL ) has been introduced as an alternative approach which disintegrates stones in the kidney and upper urinary tract through the use of shock waves .
Nevertheless , as there are limitations with the success rate in ESWL , other minimally invasive modalities for kidney stones such as percutaneous nephrolithotomy ( PCNL ) and retro grade intrarenal surgery ( RIRS ) are also widely applied .
This is an up date of a review first published in 2009 .
OBJECTIVES This review aim ed to assess the effectiveness and complications of ESWL for kidney stones compared with PCNL or RIRS . | PURPOSE We determined the preferred treatment of staghorn calculi . MATERIAL S AND METHODS Between January 1992 and December 1994 we performed a prospect i ve , r and omized , single center study involving 50 kidneys with complete staghorn calculi : 27 renal units were treated with extracorporeal shock wave lithotripsy ( ESWL ) monotherapy ( group 1 ) and 23 were treated with combined ( initial ) percutaneous nephrostolithotomy with ESWL ( group 2 ) . The 2 treatment groups were compared regarding stone size , grade of collecting system dilatation and urine culture at presentation . The number of treatment sessions , narcotic doses , renal colic episodes , septic complications , unplanned ancillary procedures , length of hospitalization , total treatment duration and stone-free rate at 6 months were recorded and compared . RESULTS At the conclusion of therapy the stone-free rate was significantly greater in group 2 than in group 1 ( 74 versus 22 % , respectively , p = 0.0005 ) . The complication rate was significantly greater in group 1 , with 15 septic complications ( fever greater than 38.5C for longer than 3 days ) in 10 patients compared to only 2 episodes in group 2 ( p = 0.007 ) . The unplanned ancillary procedure rate was significantly greater in group 1 ( 8 procedures in 7 patients versus 1 procedure in group 2 , p = 0.03 ) . The overall treatment length was significantly shorter in group 2 ( 1 versus 6 months , p = 0.0006 ) . There was no significant difference in the number of procedures performed with anesthesia or in the number of hospitalization days between the 2 treatment groups . CONCLUSIONS Combined percutaneous nephrostolithotomy and ESWL should be recommended as the first line treatment choice for most patients with staghorn stones PURPOSE We compared the efficacy of shock wave lithotripsy and ureteroscopy for treatment of distal ureteral calculi . MATERIAL S AND METHODS A total of 64 patients with solitary , radiopaque distal ureteral calculi 15 mm . or less in largest diameter were r and omized to treatment with shock wave lithotripsy ( 32 ) using an HM3 lithotriptor ( Dornier MedTech , Kennesaw , Georgia ) or ureteroscopy ( 32 ) . Patient and stone characteristics , treatment parameters , clinical outcomes , patient satisfaction and cost were assessed for each group . RESULTS The 2 groups were comparable in regard to patient age , sex , body mass index , stone size , degree of hydronephrosis and time to treatment . Procedural and operating room times were statistically significantly shorter for the shock wave lithotripsy compared to the ureteroscopy group ( 34 and 72 versus 65 and 97 minutes , respectively ) . In addition , 94 % of patients who underwent shock wave lithotripsy versus 75 % who underwent ureteroscopy were discharged home the day of procedure . At a mean followup of 21 and 24 days for shock wave lithotripsy and ureteroscopy , respectively , 91 % of patients in each group had undergone imaging with a plain abdominal radiograph , and all studies showed resolution of the target stone . Minor complications occurred in 9 % and 25 % of the shock wave lithotripsy and ureteroscopy groups , respectively ( p value was not significant ) . No ureteral perforation or stricture occurred in the ureteroscopy group . Postoperative flank pain and dysuria were more severe in the ureteroscopy than shock wave lithotripsy group , although the differences were not statistically significant . Patient satisfaction was high , including 94 % for shock wave lithotripsy and 87 % for ureteroscopy ( p value not significant ) . Cost favored ureteroscopy by $ 1,255 if outpatient treatment for both modalities was assumed . CONCLUSIONS Ureteroscopy and shock wave lithotripsy were associated with high success and low complication rates . However , shock wave lithotripsy required significantly less operating time , was more often performed on an outpatient basis , and showed a trend towards less flank pain and dysuria , fewer complications and quicker convalescence . Patient satisfaction was uniformly high in both groups . Although ureteroscopy and shock wave lithotripsy are highly effective for treatment of distal ureteral stones , we believe that HM3 shock wave lithotripsy , albeit slightly more costly , is preferable to manipulation with ureteroscopy since it is equally efficacious , more efficient and less morbid BACKGROUND To establish the best treatment modality in our hospitals for patients with proximal-ureteral calculi 5 to 10 mm , we compared the treatment outcome in those who underwent primary ureteroscopy ( URS ) with that in patients who underwent primary in-situ SWL . The primary endpoints were stone-free rates at 3 weeks and 3 months and the subjective patient experience . PATIENTS AND METHODS The study was a prospect i ve patient-preference trial . From September 2002 to May 2005 , 80 patients were included , of whom 71 could be evaluated . Thirty-three patients were treated with SWL and 38 with semirigid or flexible URS . Stone status was evaluated with excretory urography or noncontrast helical CT . The bother score of urinary-tract symptoms was recorded on a visual analog scale . RESULTS The stone-free rate at 3 weeks was 58 % and 78 % ( P = 0.061 ) and at 3 months 88 % and 89 % ( P = 1 ) for SWL and URS , respectively . The percentage of patients in need of analgesics was 30 % and 49 % ( P = 0.118 ) at 3 weeks and 9 % and 21 % ( P = 0.181 ) at 3 months for the SWL and the URS group , respectively . The bother score regarding dysuria , hematuria , and flank pain were statistically significant in favor of SWL . CONCLUSION Ureteroscopy tends to make patients stone free faster , but SWL is preferred by most patients because there is less discomfort after treatment OBJECTIVES To conduct a prospect i ve and r and omized trial to compare the efficiency quotient and cost-effectiveness index of shock wave lithotripsy ( SWL ) and ureteroscopic lithotripsy ( URSL ) for the treatment of large upper third ureteral stones . METHODS A total of 35 male patients and 7 female patients with a solitary , radiopaque upper ureteral stone , 15 mm or more in diameter , who underwent SWL or URSL were enrolled in this study . The mean patient age was 53.1 + /- 14.5 years . The endpoint of the study was for the patient to be stone free or to have insignificant residual stone ( 3 mm or less ) within the kidney . RESULTS The mean stone length + /- SD was 17.9 + /- 3.9 cm in the SWL group and 18.5 + /- 2.9 cm in the URSL group ( P > 0.05 ) . The efficiency quotient for SWL and URSL was 0.61 and 0.63 , respectively . The cost-effectiveness index , treatment time , pain score , and hospital stay were greater in the URSL group . However , the degree of hydronephrosis significantly influenced the success rate of SWL . All patients with severe hydronephrosis in the SWL group needed auxiliary surgical procedures to become stone free . CONCLUSIONS The efficiency quotients of SWL and URSL were comparable in the treatment of large upper third ureteral stones . However , SWL should not be recommended as the first-line treatment option for the management of upper third ureteral stones larger than 1.5 cm with severe hydronephrosis . Underst and ing the cost-effectiveness , success rate , pain score , and patient satisfaction score for the two different approaches constitutes the indispensable requisites for choosing the optimal first-line therapeutic strategy PURPOSE We determined the natural course and compared the deleterious effects in kidneys of shock wave lithotripsy , percutaneous nephrolithotomy and observation for asymptomatic lower caliceal stones . MATERIAL S AND METHODS Between April 2007 and August 2008 patients with asymptomatic lower caliceal calculi were enrolled in the study . To assess stone status noncontrast abdominal helical computerized tomography was done 3 and 12 months after intervention . All patients were evaluated by dimercapto-succinic acid renal scintigraphy 6 weeks and 12 months after intervention . RESULTS A total of 94 patients were prospect ively r and omized to percutaneous nephrolithotomy ( 31 ) , shock wave lithotripsy ( 31 ) and observation ( 32 ) . Mean + /- SD followup was 19.3 + /- 5 months ( range 12 to 29 ) . In the percutaneous nephrolithotomy group all patients were stone-free at month 12 . Scintigraphy revealed a scar in 1 patient ( 3.2 % ) on month 3 followup imaging . In the shock wave lithotripsy group the stone-free rate was 54.8 % . Scintigraphy revealed scarring in 5 patients ( 16.1 % ) . In the observation group 7 patients ( 18.7 % ) required intervention during followup . Median time to intervention was 22.5 + /- 3.7 months ( range 18 to 26 ) . One patient ( 3.1 % ) had spontaneous stone passage . Scintigraphy did not reveal scarring in any patient . CONCLUSIONS Stone related events were noted in more than 20 % of patients with asymptomatic lower caliceal stones observed expectantly . To manage lower caliceal stones percutaneous nephrolithotomy has a significantly higher stone-free rate with less renal scarring than shock wave lithotripsy . Thus , patients with asymptomatic lower caliceal stones must be informed in detail about all management options , especially focusing on percutaneous nephrolithotomy with its outst and ing outcome PURPOSE The efficacy of shock wave lithotripsy and percutaneous stone removal for the treatment of symptomatic lower pole renal calculi was determined . MATERIAL S AND METHODS A prospect i ve r and omized , multicenter clinical trial was performed comparing shock wave lithotripsy and percutaneous stone removal for symptomatic lower pole only renal calculi 30 mm . or less . RESULTS Of 128 patients enrolled in the study 60 with a mean stone size of 14.43 mm . were r and omized to percutaneous stone removal ( 58 treated , 2 awaiting treatment ) and 68 with a mean stone size of 14.03 mm . were r and omized to shock wave lithotripsy ( 64 treated , 4 awaiting treatment ) . Followup at 3 months was available for 88 % of treated patients . The 3-month postoperative stone-free rates overall were 95 % for percutaneous removal versus 37 % lithotripsy ( p < 0.001 ) . Shock wave lithotripsy results varied inversely with stone burden while percutaneous stone-free rates were independent of stone burden . Stone clearance from the lower pole following shock wave lithotripsy was particularly problematic for calculi greater than 10 mm . in diameter with only 7 of 33 ( 21 % ) patients becoming stone-free . Re-treatment was necessary in 10 ( 16 % ) lithotripsy and 5 ( 9 % ) percutaneous cases . There were 9 treatment failures in the lithotripsy group and none in the percutaneous group . Ancillary treatment was necessary in 13 % of lithotripsy and 2 % percutaneous cases . Morbidity was low overall and did not differ significantly between the groups ( percutaneous stone removal 22 % , shock wave lithotripsy 11 % , p = 0.087 ) . In the shock wave lithotripsy group there was no difference in lower pole anatomical measurements between kidneys in which complete stone clearance did or did not occur . CONCLUSIONS Stone clearance from the lower pole following shock wave lithotripsy is poor , especially for stones greater than 10 mm . in diameter . Calculi greater than 10 mm . in diameter are better managed initially with percutaneous removal due to its high degree of efficacy and acceptably low morbidity PURPOSE We compared the long-term impact on renal function after shock wave lithotripsy , percutaneous nephrolithotomy or the 2 techniques combined in patients with a solitary kidney . MATERIAL S AND METHODS A total of 45 women and 38 men 15 to 86 years old ( mean age 56.1 ) with a solitary kidney were treated with shock wave lithotripsy ( 53 ) , percutaneous nephrolithotomy ( 18 ) or the 2 techniques combined ( 12 ) . Before and after treatment serum creatinine , blood pressure and the calculated glomerular filtration rate were determined , and raw and calculated data were compared by the Kruskal-Wallis , Fisher exact and Wilcoxon rank sum tests , and the Spearman correlation coefficient . Followup was 1 to 166.5 months ( mean 53.0 , median 46.9 ) overall and statistically equivalent in the 3 treatment arms . RESULTS Treatment groups were comparable in regard to patient age , sex distribution , weight , blood pressure and pretreatment serum creatinine . There was no significant difference in any evaluated pretreatment or posttreatment parameters and no difference in the change in any parameter after treatment . Stratifying patients to pretreatment serum creatinine less or greater than 2 mg./dl . likewise revealed no significant difference in the impact on long-term renal function . However , pretreatment serum creatinine positively and strongly correlated with a positive change in the glomerular filtration rate after therapy . CONCLUSIONS In this study there was no evidence that any of these 3 treatment modalities result ed in the deterioration of renal function even at long-term followup . This finding implies that shock wave lithotripsy , percutaneous nephrolithotomy and the 2 therapies combined are equally efficacious for preserving renal function when performed in patients with a solitary kidney Our aim was to evaluate the hypothesis that relief of renal obstruction lowers the arterial blood pressure if the procedure of stone removal does not injure the kidney itself . Sixty patients with unilateral renal stone were evaluated at baseline and 3 months after electrical shockwave lithotripsy ( ESWL , n=30 ) or Gil-Vernet intrasinus pyelolithotomy ( n=30 ) . Blood pressures were measured noninvasively and renal vascular resistances were obtained from radionuclide measurements of renal blood flow . At baseline , the renal vascular resistance of the obstructed kidney was 2 and 2.5 times greater than of the unobstructed kidney in the ESWL and pyelolithotomy groups , respectively . After 3 months in operated patients , the blood pressure decreased ( from 87 to 81 mm Hg , P=0.002 , in case of diastolic , and from 140 to 132 mm Hg , P<0.0001 , in case of systolic pressure ) , while the vascular resistances of both kidneys were equal and normal . In contrast , in the ESWL group the blood pressures and vascular resistances of the treated kidney did not differ from the baseline values . Surgical relief of renal obstruction chronically lowers the arterial blood pressure , possibly by normalizing the renal vascular resistance . ESWL does not change the blood pressure or renal vascular resistance , which could reflect a balance between the relief of obstruction and kidney lesions induced by shock waves Introduction : The aim of this study is to assess the efficiency of extracorporeal shock wave lithotripsy ( ESWL ) as initial therapy for isolated lower pole kidney stones smaller than 20 mm . Patients and Methods : During a 24-month period 116 patients with previously untreated single stones under 20 mm in diameter were treated with a Dornier lithotripter S. They were analyzed with regard to stone site and size , number of ESWL sessions , auxiliary measures , retreatment rates , complications and the time taken for stone clearance . Results : 76 patients ( 65.5 % ) became stone free , 50 of them ( 43.1 % ) within 3 months after ESWL . Depending on stone size the stone-free rates were 67.1 % for patients with a stone diameter of < 10 mm ( 59 of 88 patients ) , and 60.7 % for stone diameters between 10 and 20 mm ( 17 of 28 patients ) . Complications during and after treatment were rare , i.e. the necessity of ureteral stent insertion due to colic ( n = 10 ) , endoscopic stone removal ( n = 2 ) , acute pyelonephritis ( n = 1 ) , stonestreet ( n = 1 ) and 1 case of hematoma not requiring intervention . The recurrence rate during follow-up ( 13.2–36.9 , mean 25.0 months ) was low : 16 patients ( 13.8 % ) had recurrent or persistent stones , and 74 patients ( 63.8 % ) had no evidence of urolithiasis . Conclusions : ESWL is a safe and efficient first-line therapy for treatment of isolated small lower pole kidney stones with acceptable stone-free rates , low morbidity , few complications and a low stone recurrence rate This study was design ed to compare different methods of treating renal calculi in order to establish which was the most cost effective and successful . Of 1052 patients with renal calculi , 350 underwent open surgery , 350 percutaneous nephrolithotomy , 328 extracorporeal shockwave lithotripsy ( ESWL ) , and 24 both percutaneous nephrolithotomy and ESWL . Treatment was defined as successful if stones were eliminated or reduced to less than 2 mm after three months . Success was achieved in 273 ( 78 % ) patients after open surgery , 289 ( 83 % ) after percutaneous nephrolithotomy , 301 ( 92 % ) after ESWL , and 15 ( 62 % ) after percutaneous nephrolithotomy and ESWL . Comparative total costs to the NHS were estimated as 3500 pounds for open surgery , 1861 pounds for percutaneous nephrolithotomy , 1789 pounds for ESWL , and 3210 pounds for both ESWL and nephrolithotomy . ESWL caused no blood loss and little morbidity and is the cheapest and quickest way of returning patients to normal life PURPOSE We performed a prospect i ve r and omized study to determine appropriate first line treatment for distal ureteral stones . MATERIAL AND METHODS Between January 1996 and October 1997 , 80 patients with distal ureteral stones ( 40 smaller than 5 mm . and 40 larger than 5 mm . ) were r and omized and treated with extracorporeal shock wave lithotripsy or ureteroscopy with a 9.5 or 6.5F semirigid ureteroscope . RESULTS Ureteroscopy was significantly better in terms of operative time , fluoroscopy time and time to achieve a stone-free state . The smaller the stones , the greater the difference between the 2 treatment modalities . CONCLUSIONS For distal ureteral stones we recommend ureteroscopy as first line treatment To evaluate percutaneous nephrolithotomy ( PNL ) and extracorporeal shock wave lithotripsy ( ESWL ) for their clinical effects , their cost effectiveness , their complication rates , and the patients ' experiences , 55 consecutive patients were r and omised to have one or other operation between October 1986 and October 1988 . Six patients were excluded , 21 were treated with PNL and 28 with ESWL as primary treatment . Mean hospital stay and length of treatment were longer for PNL than for ESWL . Since 1 July 1987 all patients having ESWL have been treated without anaesthesia ( n = 15 ) , whereas epidural anaesthesia was used for all PNL . Slightly more of the ESWL patients experienced some pain during treatment . Minor complications or pain were more common after ESWL during the first 10 days after discharge from hospital . If patients with stone fragments of 4 mm or less were regarded as having a successful outcome , the success rates after one year were 94 % for PNL and 77 % for ESWL . The overall total cost was lower for ESWL than for PNL , the cost per successfully treated patient being 2172 pounds for PNL and 1810 pounds for ESWL . Medium sized kidney stones ( 6 - 30 mm , or 2 - 3 stones of 20 mm or less ) can be efficiently and cheaply treated by both PNL and ESWL , though the cost of ESWL is lower . Even if effects other than cost ( such as complications and patients ' experience ) are borne in mind , ESWL was superior to PNL for this group of patients PURPOSE The optimal management of lower pole renal calculi is controversial . We compared shock wave lithotripsy ( SWL ) and ureteroscopy ( URS ) for the treatment of patients with small lower pole stones in a prospect i ve , r and omized , multicenter trial . MATERIAL S AND METHODS A total of 78 patients with 1 cm or less isolated lower pole stones were r and omized to SWL or URS . The primary outcome measure was stone-free rate on noncontrast computerized tomography at 3 months . Secondary outcome parameters were length of stay , complication rates , need for secondary procedures and patient derived quality of life measures . RESULTS A total of 67 patients r and omized to SWL ( 32 ) or URS ( 35 ) completed treatment . The 2 groups were comparable with respect to age , sex , body mass index , side treated and stone surface area . Operative time was significantly shorter for SWL than URS ( 66 vs 90 minutes ) . At 3 months of followup 26 and 32 patients who underwent SWL and URS had radiographic followup that demonstrated a stone-free rate of 35 % and 50 % , respectively ( p not significant ) . Intraoperative complications occurred in 1 SWL case ( unable to target stone ) and in 7 URS cases ( failed access in 5 and perforation in 2 ) , while postoperative complications occurred in 7 SWL and 7 URS cases . Patient derived quality of life measures favored SWL . CONCLUSIONS This study failed to demonstrate a statistically significant difference in stone-free rates between SWL and URS for the treatment of small lower pole renal calculi . However , SWL was associated with greater patient acceptance and shorter convalescence STUDY OBJECTIVE : To compare extracorporeal shock wave lithotripsy and percutaneous nephrolithotomy for efficacy in treating renal calculi . DESIGN : Non-r and omised multicentre cohort study with 3 month follow up and 13 month data collection period . SETTING : Lithotripter centre in London , tertiary referral hospital , and urological clinics in several secondary and tertiary care centres . PATIENTS : 933 of 1001 patients treated by lithotripsy at the lithotripter centre were compared with 195 treated by nephrolithotomy . Missing patients were due to incomplete collection of data . Age and sex distributions and characteristics of the stones were similar in the two treatment groups . Two patients died in the lithotripsy group . Three month follow up was achieved in about 84 % of both groups ( 783/933 for lithotripsy ; 163/195 for nephrolithotomy ) . INTERVENTIONS : The nephrolithotomy group had surgical nephrolithotomy alone . In the lithotripsy group 83 % ( 774/933 ) had lithotripsy alone , 11 % ( 103/933 ) had combined lithotripsy and nephrolithotomy , and 6 % ( 56/933 ) had lithotripsy plus ureteroscopy . Single and combined lithotripter treatments were analysed as one group and compared with nephrolithotomy . END POINT : Presence of stones three months after treatment . MEASUREMENTS AND MAIN RESULTS : Presence of residual stones was assessed by plain radiography , ultrasonography , or intravenous urography . After adjustment for age and size and position of stone for patients with single stones the likelihood of being free of stones three months after treatment was significantly greater in the nephrolithotomy group than the lithotripsy group ( odds ratio 6.6 ; 95 % confidence interval 3.0 to 14.6 ) and the response was particularly pronounced with staghorn calculi ( 62 % ( 8/13 ) v 15 % ( 141/96 ) patients free of stones after nephrolithotomy and lithotripsy , respectively ) . OTHER FINDINGS : 19%(146/775 ) of patients who had had lithotripsy had to be readmitted within three months after treatment compared with 14%(23/162 ) who had nephrolithotomy ; and 64%(94/146 ) of readmissions after lithotripsy were for complications compared with 30%(7/23 ) of readmissions after nephrolithotomy . CONCLUSIONS : Nephrolithotomy may be preferable to lithotripsy for treating renal stones and it may not be wise to invest heavily in lithotripsy facilities PURPOSE We assess the efficacy of extracorporeal shock wave lithotripsy monotherapy for isolated lower pole nephrolithiasis , and compare it to that for isolated middle and upper caliceal calculi . MATERIAL S AND METHODS We treated 714 renal units in 687 patients with isolated caliceal stones using a Lithostar lithotriptor ( Siemens Medical Systems , Erlangen , Germany ) . The stones were localized in the lower , mid and upper calices in 455 , 104 and 128 patients , respectively . Stone load was recorded in cm.2 . Patients were stratified into 3 groups based on stone burden . The energy and shock waves , use of anesthesia , number of treatment sessions , auxiliary measures and complications were noted . Patients were evaluated with intravenous urogram or plain film of kidneys , ureters and bladder , and ultrasonography when stone-free , or clinical ly significant residual fragment status , including nonobstructive and noninfectious insignificant fragments 4 mm . or less , was noted at the fluoroscopic control 2 to 4 weeks after the last session . Final clinical ly significant residual fragment decision was made 10 to 12 weeks after the last session . Extracorporeal shock wave lithotripsy was considered a failure if no fragmentation was noted after session 3 and continued if fragmentation was noted . Results regarding caliceal localization were compared . RESULTS Complete data were available on 591 renal units . Auxiliary procedures were used in 81 ( 14 % ) units before treatment . Anesthesia was given to 101 ( 17 % ) patients . The mean number of shock waves and energy used were 2,022 and 17.4 kV. , respectively . The difference in shock wave , energy and treatment rate among 3 caliceal locations reached statistical significance only for energy delivered to the lower and upper calices . The effectiveness quotient of extracorporeal shock wave lithotripsy was 36 % , 46 % and 41 % for lower , middle and upper pole stone disease , respectively ( p = 0.4 ) . There was a highly significant correlation between stone-free and re-treatment rates , and stone burden . The overall stone-free rate was 66 % , and 63 % , 73 % and 71 % for lower , middle and upper caliceal stones , respectively ( p = 0.1 ) . For the group with stones greater than 2 cm.2 overall stone-free rate decreased to 49 % , and 53 % , 60 % and 23 % in lower , middle and upper caliceal locations , respectively . Overall , extracorporeal shock wave lithotripsy monotherapy failed in 46 ( 7.7 % ) renal units . Steinstrasse developed in 39 ( 6.5 % ) patients who were then treated with repeat lithotripsy . CONCLUSIONS Extracorporeal shock wave lithotripsy appears to be successful for management of isolated caliceal stone disease . Treatment efficacy was not significantly different among stones localized in lower , middle and upper poles . We recommend it as the primary treatment of choice for stones less than 2.0 cm.2 in all caliceal locations . Treatment should be individualized for management of caliceal stones greater than 2.0 cm.2 until large prospect i ve r and omized trials comparing shock wave lithotripsy and percutaneous nephrolithotomy are available OBJECTIVE The gold st and ard for removal of renal stones more than 2 cm in diameter is percutaneous nephrolithotripsy ( PCNL ) . Retro grade intrarenal surgery ( RIRS ) has become more and more fashionable because of its high safety and repeatability , especially in smaller stones . Many retrospective studies have proved its efficacy and safety in larger calculi , however . We decided to compare prospect ively both procedures in terms of safety and efficacy in renal pelvic stones more than 2 cm in diameter . PATIENTS AND METHODS This was a r and omized single tertiary care center trial with two arms ( 32 patients in each arm ) . The first group comprised patients who underwent PCNL , while in the second group , there were patients in whom RIRS with a semirigid ureteroscope was used . The primary end points were hematocrit and hemoglobin drop after surgery as equivalents of safety and stone disintegration rate in terms of efficacy . The secondary end points comprised operating room time , visual analogue scale of pain , pain treatment , and hospital stay . RESULTS The mean hematocrit drop after the procedure was lower in the second group . Similarly , operating room time and hospital stay were significantly shorter after RIRS in comparison with PCNL . In the second group , patients had favorable features in terms of pain intensity and treatment after the procedure . PCNL showed higher efficacy ( 94 % ) in comparison with RIRS ( 75 % ) . The power of 83 % was calculated for the primary end point . CONCLUSION The efficacy of RIRS is acceptable and , emphasizing its high safety , it should be considered as a valuable alternative option for management of renal pelvic stones more than 2 cm in diameter AIM To compare the efficacy and complications of extracorporeal shock-wave lithotripsy ( SWL ) and pneumatic ureteroscopic lithotripsy ( URS ) in the treatment of lower ureteral calculi . METHODS From August 1997 to June 1999 , 210 patients with calculi in the distal third of the ureter were treated with SWL and the other 180 with URS . The stones were fragmented with either HB-ESWL-V lithotripter or JML-93 pneumatic lithotripter through Wolf 7.5 approximately 9.0 Fr ureteroscope . The outcome was assessed in terms of stone clearance rate , re-treatment rate and complication incidence . RESULTS The stone clearance rate was 78.1 % with SWL and 93.3 % with URS ( P<0.05 ) . SWL had a re-treatment rate of 11.9 % , vs 2.2 % in the URS group ( P<0.05 ) . URS caused ureteral perforation in 3.3 % of patients , while it was 0 with SWL ( P<0.05 ) . The differences in the incidence of other complications such as infection and stricture between the two groups were insignificant . CONCLUSION Though the selection of these two options depends on equipments available and the expertise of the operator , we recommend URS as the optimal treatment for distal ureteral calculi PURPOSE We compared the safety and efficacy of percutaneous ante grade ureterolithotripsy with retro grade ureterolithotripsy for large impacted proximal ureter stones in a prospect i ve r and omized manner . MATERIAL S AND METHODS A total of 91 patients with large impacted proximal ureteral stones , defined as stones > 1 cm in size located between the ureteropelvic junction and the lower border of the fourth lumbar vertebra , were prospect ively r and omized for ante grade ( 44 ) or retro grade ( 47 ) ureterolithotripsy . Failure of the procedure ( conversion to an open procedure ) , intraoperative and postoperative morbidity , operative time , hospital stay , stone clearance at discharge home , and follow-up were analyzed in each group . RESULTS The main complications were bleeding ( 2.3 % ; 1 of 43 ) for the ante grade procedure and ureteral injury ( 2.3 % ; 1 of 44 ) for the retro grade procedure . Percutaneous ante grade ureterolithotripsy was associated with longer operative times ( 75.4+/-11.8 v 30.6+/-7.8 minutes ; P<0.001 ) , longer hospital stay ( 6.3+/-0.5 v 2.1+/-0.4 days ; P<0.001 ) , and a longer interval to return to normal activities ( 7.8+/-0.7 v 2.7+/-0.6 days ; P<0.001 ) . Nevertheless , the percutaneous ante grade procedure had a higher stone-free rate both at discharge home ( 95.3 % v 79.5 % ; P=0.027 ) , and 1 month post-procedure ( 100 % v 86.4 % ; P=0.026 ) . CONCLUSIONS Percutaneous ante grade ureterolithotripsy is a valuable treatment modality for impacted proximal ureteral calculi larger than 1 cm , and achieves higher stone-free rates than those of retro grade ureteroscopy with holmium : YAG laser lithotripsy . The drawbacks of the ante grade procedure are longer operative time and hospital stay PURPOSE Contemporary treatment of lower pole renal calculi includes extracorporeal shock wave lithotripsy , percutaneous nephrostolithotomy and retro grade ureteropyeloscopy . Success rates for shock wave lithotripsy are reduced in this setting , especially for stones greater than 1 cm . and /or in patients with anatomical variants . Percutaneous treatment , although effective , subjects the patient to increased morbidity . We studied the safety and efficacy of retro grade ureteroscopic treatment of lower pole intrarenal calculi . MATERIAL S AND METHODS We evaluated 90 stone burdens localized to the lower pole and treated with a small diameter , actively deflectable , flexible ureteropyeloscope and a 200 micron holmium laser fiber . Stone burdens were classified as group 1 - -10 or less , group 2 - -11 to 20 and group 3 - -greater than 20 mm . in largest diameter . Patients with calculi less than 2.5 cm . were treated as out patients unless concurrent medical conditions required hospitalization . Larger stones and partial staghorn calculi ( group 3 ) frequently required 2-stage endoscopic procedures with retro grade intrarenal irrigation for 36 hours to clear debris . An acceptable immediate surgical outcome was defined as complete fragmentation reducing the stone burden to dust and 2 mm . or less fragments . Success was defined as clear imaging ( that is stone-free ) on renal sonography with minimum 3-month followup . Extreme anatomical variants , including a long infundibulum , acute infundibulopelvic angle and a dilated collecting system , were noted and correlated with surgical failures . RESULTS Endoscopic access and complete stone fragmentation were achieved in 94 , 95 and 45 % of groups 1 , 2 and 3 , respectively . After a second treatment the success rate increased to 82 % in group 3 , with an overall rate of 91 % . Of the 19 surgical failures 8 were secondary to inability to access the lower pole and 11 were secondary to inability to render the patient stone-free . In 2 of the 19 cases infundibular strictures hindered ureteroscopic access . In addition , of the anatomical variants a long lower pole infundibulum was the most statistically significant predictor of failure . Mean operative time ranged from 38 minutes for small to 126 for the largest calculi . There were no major complications . Overall stone-free rates with minimum 3-month followup were 82 , 71 and 65 % in groups 1 , 2 and 3 , respectively , and 88 , 77 and 81 % , respectively , in patients with an acceptable initial surgical outcome ( that is excluding those with access failures from analysis ) . CONCLUSIONS Retro grade ureteropyeloscopy is a safe and effective surgical treatment for lower pole intrarenal calculi OBJECTIVE To compare the outcomes of percutaneous nephrolithotomy ( PNL ) and extracorporeal shock wave lithotripsy ( ESWL ) for moderate sized ( 1 - 2 cm ) upper and middle pole renal calculi in regards to stone clearance rate , morbidity , and quality of life . METHODS All patients diagnosed with moderate sized upper and middle pole kidney stones by computed tomography ( CT ) were offered enrollment . They were r and omized to receive either ESWL or PNL . The SF-8 quality of life survey was administered preoperatively and at 1 week and 3 months postoperatively . Abdominal radiograph at 1 week and CT scan at 3 months were used to determine stone-free status . All complications and outcomes were recorded . RESULTS PNL established a stone-free status of 95 % and 85 % at 1 week and 3 months , respectively , whereas ESWL established a stone-free status of 17 % and 33 % at 1 week and 3 months , respectively . Retreatment in ESWL was required in 67 % of cases , with 0 % retreatment in PNL . Stone location , stone density , and skin-to-stone distance had no impact on stone-free rates at both visits , irrespective of procedure . Patient-reported outcomes , including overall physical and mental health status , favored a better quality of life for patients who had PNL performed . CONCLUSION PNL more often establishes stone-free status , has a more similar complication profile , and has similar reported quality of life at 3 months when compared with ESWL for moderate-sized kidney stones . PNL should be offered as a treatment option to all patients with moderate-sized kidney stones in centers with experienced endourologists PURPOSE There is theoretical concern that stone recurrence rates may be higher following extracorporeal shock wave lithotripsy ( ESWL ) compared to other techniques because of residual stone debris . MATERIAL S AND METHODS We documented all new stone formations in 298 consecutive patients who initially achieved a stone-free status following ESWL for renal calculi less that 2 cm in largest dimension , and compared the findings to those of 62 patients treated with percutaneous nephrolithotomy without ultrasonic fragmentation . Stone-free status was assessed by a central ly review ed plain abdominal film and renal tomograms at 3 months . A plain abdominal film was repeated at 12 and 24 months to detect recurrence . RESULTS New stones formed in 22.2 % of patients after ESWL and 4.2 % after percutaneous nephrolithotomy at 1 year ( p = 0.004 ) , and in 34.8 % versus 22.6 % , respectively , at 2 years ( p = 0.190 ) . Furthermore , more new stones recurred in the lower and mid calices compared to baseline location in the ESWL group ( chi-square < 0.0001 ) , which was not observed in the percutaneous nephrolithotomy group . CONCLUSIONS Our data support a trend toward higher stone recurrence rates in ESWL treated patients , which may be due to microscopic s and particles migrating to dependent calices and acting as a nidus for new stone formation |
12,305 | 30,781,797 | Skipping breakfast was associated with a worse lipid profile , blood pressure levels , insulin-resistance , and metabolic syndrome .
This review supports skipping breakfast as an easy marker of the risk of OW/OB and metabolic diseases , whether or not it is directly involved in causality . | The incidence of skipping breakfast in pediatric subjects is rising , and a relationship with overweight ( OW ) and obesity ( OB ) has been shown .
Associations with cardiovascular outcomes and skipping breakfast in adults have been reported .
The purpose of this systematic review was to summarize the association of skipping breakfast with body weight and metabolic outcomes in the pediatric population . | OBJECTIVE The circadian clock regulates glucose metabolism by mediating the activity of metabolic enzymes , hormones , and transport systems . Breakfast skipping and night eating have been associated with high HbA1c and postpr and ial hyperglycemia after lunch and dinner . Our aim was to explore the acute effect of breakfast consumption or omission on glucose homeostasis and clock gene expression in healthy individuals and individuals with type 2 diabetes . RESEARCH DESIGN AND METHODS In a crossover design , 18 healthy volunteers and 18 volunteers with 14.5 ± 1.5 years diabetes , BMI 30.7 ± 1.1 kg/m2 , and HbA1c 7.6 ± 0.1 % ( 59.6 ± 0.8 mmol/mol ) were r and omly assigned to a test day with breakfast and lunch ( YesB ) and a test day with only lunch ( NoB ) . Postpr and ial clock and clock-controlled gene expression , plasma glucose , insulin , intact glucagon-like peptide 1 ( iGLP-1 ) , and dipeptidyl peptidase IV ( DPP-IV ) plasma activity were assessed after breakfast and lunch . RESULTS In healthy individuals , the expression level of Per1 , Cry1 , Rorα , and Sirt1 was lower ( P < 0.05 ) but Clock was higher ( P < 0.05 ) after breakfast . In contrast , in individuals with type 2 diabetes , Per1 , Per2 , and Sirt1 only slightly , but significantly , decreased and Rorα increased ( P < 0.05 ) after breakfast . In healthy individuals , the expression level of Bmal1 , Rorα , and Sirt1 was higher ( P < 0.05 ) after lunch on YesB day , whereas the other clock genes remained unchanged . In individuals with type 2 diabetes , Bmal1 , Per1 , Per2 , Rev-erbα , and Ampk increased ( P < 0.05 ) after lunch on the YesB day . Omission of breakfast altered clock and metabolic gene expression in both healthy and individuals with type 2 diabetes . CONCLUSIONS Breakfast consumption acutely affects clock and clock-controlled gene expression leading to normal oscillation . Breakfast skipping adversely affects clock and clock-controlled gene expression and is correlated with increased postpr and ial glycemic response in both healthy individuals and individuals with diabetes Background There is no data on diet- and activity-related behaviors associated with overweight and obesity among Pakistani school-aged children . The study aim ed to explore dietary behaviors , physical activity and sedentary lifestyle associated with overweight and obesity , and their socio-demographic correlates , among Pakistani primary school children . Methods A population -based cross-sectional study was conducted with a representative multistage r and om cluster sample of 1860 children aged five to twelve years in Lahore , Pakistan . Overweight ( > + 1 SD ) and obesity ( > + 2 SD ) were defined using the World Health Organization reference 2007 . Chi-square test was used as the test of trend . Linear regression was used to examine the predictive power of independent variables in relation to body mass index ( BMI ) . Logistic regression was used to quantify the independent predictors and adjusted odds ratios ( aOR ) with 95 % confidence intervals ( CI ) were obtained . Statistical significance was considered at P < 0.05 . Results Children skipping breakfast ( 8 % ) , eating fast food and snacks ≥ once a week ( 43 % ) and being involved in sedentary lifestyle > one hour a day ( 49 % ) were significantly more likely to be overweight and obese while those participating in physical activity > twice a week ( 53 % ) were significantly less likely to be overweight and obese ( all P < 0.01 ) . Skipping breakfast ( P < 0.001 ) , eating fast food and snacks ( P = 0.001 ) and sedentary lifestyle ( P < 0.001 ) showed an independent positive association with BMI while physical activity showed an independent inverse association ( P = 0.001 ) . Skipping breakfast ( aOR 1.82 , 95 % CI 1.22 - 2.71 ) , eating fast food and snacks ≥ once a week ( OR 1.41 , 95 % CI 1.07 - 1.86 ) , physical activity > twice a week ( aOR 0.49 , 95 % CI 0.34 - 0.70 ) and sedentary lifestyle > one hour a day ( aOR 1.56 , 95 % CI 1.19 - 2.03 ) were independent predictors of being overweight . Skipping breakfast had independent inverse association with physical activity ( aOR 0.63 , 95 % CI 0.45 - 0.89 ) and eating fast food and snacks had independent positive association with sedentary lifestyle ( aOR 1.79 , 95 % CI 1.49 - 2.16 ) . Female gender was independently associated with skipping breakfast ( aOR 1.50 , 95 % CI 1.04 - 2.16 ) . Male gender ( aOR 1.64 , 95 % CI 1.33 - 2.02 ) , urban area with high SES ( aOR 5.09 , 95 % CI 3.02 - 8.60 ) and higher parental education ( aOR 1.74 , 95 % CI 1.12 - 2.68 ) were significant independent predictors of eating fast food and snacks ≥ once a week . Living in the rural area was independently associated ( aOR 2.51 , 95 % CI 1.71 - 3.68 ) with physical activity > twice a week . Male gender ( aOR 1.60 , 95 % CI 1.31 - 1.95 ) , urban area with low SES ( aOR 1.46 , 95 % CI 1.02 - 2.09 ) , high-income neighborhoods ( aOR 1.52 , 95 % CI 1.02 - 2.25 ) , higher parental education ( aOR 1.55 , 95 % CI 1.03 - 2.34 ) and fewer siblings ( aOR 1.38 , 95 % CI 1.10 - 1.73 ) were independent predictors of sedentary lifestyle > one hour a day . Conclusions Dietary behaviors , physical activity and sedentary lifestyle are independent predictors of overweight and higher BMI among Pakistani primary school children , and are significantly affected by the child 's socio-demographic characteristics . These findings support the urgent need to develop a National strategy for diet and physical activity and to implement culturally relevant behavioral interventions in the re source -poor developing country setting OBJECTIVE To assess the prospect i ve associations of breakfast , lunch , and dinner skipping at age 4 years with body fat ( ie , percent fat mass , body mass index [ BMI ] , and weight status ) at age 6 years . STUDY DESIGN Data were analyzed from 5913 children participating in the Generation R Study , a population -based prospect i ve cohort study in Rotterdam , The Netherl and s. Meal-skipping behaviors were assessed through parent-report question naires . Children 's weight and height were objective ly measured and converted to BMI SDSs . Weight status ( ie , overweight or normal weight ) was defined according to age- and sex-specific cutoff points . At age 6 years , percent fat mass was assessed by dual-energy X-ray absorptiometry . Linear and logistic regression analyses were performed , adjusting for covariates and BMI at age 4 years . RESULTS Breakfast skipping at age 4 years was associated with a higher percent fat mass at age 6 years ( β = 1.38 ; 95 % CI , 0.36 - 2.40 ) . No associations were found with BMI or weight status . Furthermore , no associations were found between lunch and dinner skipping at age 4 years and body fat at age 6 years . CONCLUSION Breakfast skipping at age 4 years is associated with a higher percent fat mass at age 6 years . Further prospect i ve studies , including intervention studies , are warranted to extend the evidence base on the directionality and causality of this association Introduction The study aim was to evaluate risk factors of obesity in Polish children aged 7 to 9 years . Material and methods A representative group of 2571 children ( 1268 girls and 1303 boys ) was r and omly selected according to the European Childhood Obesity Group protocol . Weight and height were measured and body mass index ( BMI ) was calculated . A question naire was completed by the children 's parents with respect to behavioural and family-related risk factors of obesity . International Obesity Task Force criteria were used for classification of children 's obesity . Results Obesity was found in 3.7 % of girls and 3.6 % of boys . There was a statistically significant association between the prevalence of obesity in girls and their mother 's obesity : OR = 5.06 ( 1.96–13.05 ) , p < 0.001 , father 's obesity : OR = 5.19 ( 1.96–13.69 ) , p < 0.001 , and both parents ’ obesity : OR = 5.43 ( 1.39–21.29 ) , p = 0.01 . Obesity in boys was significantly associated with mother 's obesity : OR = 5.6 ( 2.6–12.02 ) , p < 0.001 , father 's obesity : OR = 6.21 ( 2.89–13.37 ) , p < 0.001 , and both parents ’ obesity : OR = 7.22 ( 2.44–31.33 ) , p < 0.001 . Skipping or irregular eating of breakfast was a risk factor for obesity in girls with OR = 2.71 ( 1.33–5.51 ) , p = 0.005 . Neither family income nor parents ’ education level was related to their offspring 's obesity . TV watching , physical activity level and eating in fast food places were not significant risk factors for obesity . Conclusions Eating breakfast regularly seems to protect girls from obesity development while low physical activity is not a significant obesity risk factor in this age group for either boys or girls . This finding stresses the more important role of healthy diet than physical activity promotion in obesity prevention in prepubertal children Background / Objectives : Childhood obesity is prevalent , and dietary habits are a key determinant . Some children skip breakfast for weight control , but studies have shown mixed results . Therefore , we assessed the association between breakfast skipping and body mass index ( BMI ) among young Chinese children in Hong Kong . Design /Subjects and Methods : A cohort of 113 457 primary 4 participants of the Department of Health Student Health Service in 1998–2000 was followed up for 2 years , with 68 606 ( 60.5 % ) participants available for analysis in primary 6 . The sociodemographic characteristics for traced and untraced participants were similar . At baseline and follow-up , students reported breakfast habit ( consumed vs skipped ) and other lifestyle characteristics using a st and ardized question naire . BMI was derived using height and weight measured by trained nurses . Multivariable linear regression was used to examine the cross-sectional relationship between breakfast habit and BMI , as well as the prospect i ve association between baseline breakfast habit and change in BMI . Models adjusted for demographic , socioeconomic and lifestyle characteristics . Results : A total of 1805 ( 5.3 % ) boys and 1793 ( 5.2 % ) girls skipped breakfast at baseline . In cross-sectional analyses , breakfast skippers had a higher mean BMI than did eaters among both primary 4 ( β=0.77 , 95 % confidence interval ( 95 % CI ) : 0.67–0.87 ) ( P<0.001 ) and primary 6 children ( β=0.86 , 95 % CI : 0.78–0.95 ) ( P<0.001 ) . Compared with eaters , baseline breakfast skippers experienced a greater increase in BMI in the subsequent 2 years ( β=0.11 , 95 % CI : 0.07–0.16 ) ( P<0.001 ) , and this association was stronger among lunch skippers than eaters ( P for interaction=0.04 ) . Conclusion : Our study provided prospect i ve evidence that skipping breakfast predicts a greater increase in BMI among Hong Kong children . As breakfast is a modifiable dietary habit , our results may have important implication s for weight control . However , the underlying mechanism of this effect warrants further BACKGROUND Breakfast is associated with lower body weight in observational studies . Public health authorities commonly recommend breakfast consumption to reduce obesity , but the effectiveness of adopting these recommendations for reducing body weight is unknown . OBJECTIVE We tested the relative effectiveness of a recommendation to eat or skip breakfast on weight loss in adults trying to lose weight in a free-living setting . DESIGN We conducted a multisite , 16-wk , 3-parallel-arm r and omized controlled trial in otherwise healthy overweight and obese adults [ body mass index ( in kg/m² ) between 25 and 40 ] aged 20 - 65 y. Our primary outcome was weight change . We compared weight change in a control group with weight loss in experimental groups told to eat breakfast or to skip breakfast [ no breakfast ( NB ) ] . R and omization was stratified by prer and omization breakfast eating habits . A total of 309 participants were r and omly assigned . RESULTS A total of 283 of the 309 participants who were r and omly assigned completed the intervention . Treatment assignment did not have a significant effect on weight loss , and there was no interaction between initial breakfast eating status and treatment . Among skippers , mean ( ±SD ) baseline weight- , age- , sex- , site- , and race-adjusted weight changes were -0.71 ± 1.16 , -0.76 ± 1.26 , and -0.61 ± 1.18 kg for the control , breakfast , and NB groups , respectively . Among breakfast consumers , mean ( ±SD ) baseline weight- , age- , sex- , site- , and race-adjusted weight changes were -0.53 ± 1.16 , -0.59 ± 1.06 , and -0.71 ± 1.17 kg for the control , breakfast , and NB groups , respectively . Self-reported compliance with the recommendation was 93.6 % for the breakfast group and 92.4 % for the NB group . CONCLUSIONS A recommendation to eat or skip breakfast for weight loss was effective at changing self-reported breakfast eating habits , but contrary to widely espoused views this had no discernable effect on weight loss in free-living adults who were attempting to lose weight Background Skipping breakfast was found to be associated with abdominal obesity in primary school children . The aim of this research was to examine factors associated with skipping breakfast in primary school children in order to develop targeted preventive measures . Methods Baseline data assessment ( 2010 ) of a cluster-r and omized controlled trial for the evaluation of a school-based health promotion program in primary school children in the state of Baden-Württemberg , Germany . Anthropometric measures of 1,943 primary school children aged 7.1 ± 0.6 years ( 51.2 % boys ) were conducted according to ISAK-st and ards ( International St and ard for Anthropometric Assessment ) by trained staff . Further information on the health and living conditions of the children and their parents were assessed in parental question naires . Generalized linear mixed regression analysis was calculated to define correlates for skipping breakfast in terms of odds ratios ( OR ) and 95 % confidence intervals ( CI ) . Results According to the final regression models , significant correlates of skipping breakfast can be divided into modifiable behavioral components ( high consumption of soft drinks ( OR 2.49 , 95 % CI 1.81 ; 3.43 ) , screen media ( OR 2.48 , 95 % CI 1.77 ; 3.46 ) and high levels of physical activity ( OR 0.64 , 95 % CI 0.44 ; 0.93 ) ) on the one h and , and more or less static socio-economic factors ( migration background ( OR 2.81 , 95 % CI 2.02 ; 3.91 ) , single parenting ( OR 2.13 , 95 % CI 1.34 ; 3.40 ) , and high family education level ( OR 0.42 , 95 % CI 0.28 ; 0.64 ) ) on the other h and , and finally individual factors ( female gender ( OR 1.43 , 95 % CI 1.03 ; 1.99 ) and having a percentage of body fat at or above the 95th percentile ( OR 1.47 , 95 % CI 1.00 ; 2.17 ) ) . Conclusion Targeted prevention should aim at health-related behaviors accompanying the habit of skipping breakfast . Focusing on vulnerable groups , characterized by not so easily modifiable socio-economic as well as individual factors , may improve results . Interventions should synergistically promote children ’s health and involve their parents in order to be successful . To reach all children and to avoid skipping breakfast , schools should offer regular breakfast at the start of a school day . Policy makers should support healthy eating habits at all times Introduction A balanced diet is at the heart of healthy growth and development of children and youth , whereas inappropriate eating habits considerably influence the incidence of disorders connected with nutrition , including overweight and obesity . This paper aims at study ing nutritional factors of 18-year-old secondary school youth in the urban environment and their effect on the incidence of overweight and obesity . Material s and methods The survey was conducted among 1,999 secondary school students chosen at r and om . The research tool consisted an original survey question naire . The measurements of respondents ’ height and body mass provided data for calculating the body mass index . Results and conclusion The percentage of youth with deficient body mass was estimated at 8.4 % . The percentage of normal weight students in the surveyed group was estimated at 77.6 % . Overweight and obesity characterized 14.0 % of the total number . As many as 21.8 % of overweight and obese respondents would eat one or two meals as opposed to 16.8 % of normal weight students . Three-fourths of the surveyed students would eat breakfast regardless of their nutritional habits . Lunch is eaten by 52.9 % of normal weight 18-year-olds and 46.1 % of overweight and obese students . The analysis of mealtimes suggests that overweight and obese students would have their breakfast and dinner at later hours than the rest of the surveyed . More than half of the participating students failed to eat lunch ( 53.9 % ) , and one in four students within this group resigned from supper . Girls would eat fruit and vegetables more frequently than boys several times a day . The percentage of persons in the surveyed groups who would eat fast foods on a daily basis was similar regardless of their nutritional status . Sweetened carbonated beverages would be drunk more often by overweight and obese boys ( 81.2 % ) as compared with boys with proper body mass ( 75.8 % ) . The same type of beverages would be popular with two-thirds of girls , and this result was similar regardless of their nutritional status . About 44.2 % of overweight and obese girls and 20 % of girls with proper body mass attempted to lose weight , and 5.7 % of boys tried to go on a diet . Eating limitations were declared by 16.5 % of overweight and obese boys and ca . 3 % of normal weight boys . Conclusion Within the surveyed group of youth , it was possible to indicate eating errors primarily consisting in irregular eating , too low a number of meals during the day , particularly skipping breakfast , which took place more frequently among overweight and obese students rather than normal weight ones . The survey points to the insufficient intake of vegetables and fruit as opposed to salty and sweet meals . It is essential to convey the knowledge on the causes of overweight and obesity as well as rules of a healthy diet as factors preventing civilization diseases |
12,306 | 31,553,360 | Evidence of low quality indicates that adjustable slings are effective for treating post-prostatectomy urinary incontinence , with frequency of adverse events similar to the surgical option considered gold st and ard ( the artificial urinary sphincter implant ) | ABSTRACT Urinary incontinence after prostatectomy has a significant negative impact on the quality of life of the patient .
The surgical treatment includes several models of male slings , such as adjustable slings .
The objective of this study was to evaluate the effectiveness and safety of adjustable sling in the treatment of post-prostatectomy urinary incontinence .
This is a systematic review of literature . | AIMS To review the patient choice , clinical outcomes and satisfaction rate between adjustable and non-adjustable male sling ( MS ) with a minimum follow up of 24 months . METHODS A prospect i ve review of clinical parameters in all male patients who underwent MS surgery between January 2009 and December 2011 was undertaken . Vali date d instruments were utilized in the follow-up survey . RESULTS A total of 44 MS were inserted with 25 men choosing adjustable Argus ( Promedon , Cordoba , Argentina ) and 19 men received non-adjustable AdVance ( American Medical Systems , Minnetonka , MN ) MS . The mean age and follow-up for men in the Argus group were 65.4 years and 36.2 months , and in AdVance group were 63.8 years and 33.1 months . Revision surgery was performed in six Argus MS for recurrent urinary incontinence . Social continence ( defined as 0 to 1 urinary pad use ) was achieved in 23 patients ( 92 % ) with Argus MS and 16 patients ( 84 % ) with AdVance MS ( P = 0.45 ) . The overall satisfaction rate on a 5-point scale was 4.5 in Argus and 4.3 in AdVance patients , and there was no significant difference in the PGI-I score between the two groups ( P = 0.36 ) . Kaplan-Meier analysis of urinary continence and patient satisfaction rates were not statistically significant between Argus and AdVance slings ( P = 0.76 and P = 0.38 ) . CONCLUSIONS Given the choice between the two types of MS , more men chose adjustable Argus over non-adjustable AdVance sling . There was no significant difference in the clinical outcome , social continence and overall patient satisfaction rates between the two types of MS in the short term . Neurourol . Urodynam . 35:482 - 486 , 2016 . © 2015 Wiley Periodicals , OBJECTIVE To evaluate the efficacy and safety of the adjustable suburethral sling Remeex ® in the treatment of male stress urinary incontinence ( SUI ) . PATIENTS AND METHODS Single-center prospect i ve study of patients treated for SUI after radical prostatectomy or transurethral resection of prostate . The severity of incontinence was evaluated by the number of pads used per day . Success rate , complications and number of adjustments were studied . RESULTS From February 2011 to May 2015 , Remeex ® was implanted in 25 patients . The average preoperative number of pads used per day was 3,8 ( ±1,8 ) . Sling tension has been adjusted the day after surgery in all patients . Mean follow-up was 31 months ( ±15 ) . During follow-up , 6 patients did not need any readjustment ( 24 % ) and 15 patients ( 60 % ) had to be readjusted . One Remeex system had to be completely removed because of a sub-occlusive syndrome . Three patients had early infection requiring partial system removal ( Varitensor ) . At the end of follow-up , 9 patients were cured ( 36 % ) , 9 patients ( 36 % ) were significantly improved and 7 patients ( 28 % ) were not improved . Five patients are waiting for a new readjustment . CONCLUSION In this short series of patients who had prostatic surgery , at mid-term follow-up , the placement of a BSUA-R was associated with an improvement or cure of urinary incontinence symptoms in two-thirds of cases . LEVEL OF EVIDENCE 4 PURPOSE To report long-term results of the Argus T adjustable system for treatment of post-prostatectomy urinary incontinence ( PPI ) . MATERIAL S AND METHODS From October 2007 to August 2008 , 37 patients with PPI were included in a prospect i ve , single-arm , multicenter trial of treatment with the Argus T adjustable system ( Promedon , Argentina ) . Preoperative evaluation included urine culture , urethrocystoscopy , urodynamic testing , 24-h pad weight test ( PWT ) and quality of life question naires . Patients were stratified according to baseline degree of incontinence ( mild-moderate or severe ) . Postoperative evaluation included immediate PWT , quality of life question naires and daily use of pads at 1 , 12 and 30 months . RESULTS AND CONCLUSIONS One patient was lost to follow-up . At the 30-month follow-up , 24/31 patients ( 77 % ) were dry , 3/31 ( 10 % ) improved and 4/31 ( 13 % ) were failures . In particular , in the mild-moderate group , 8/8 ( 100 % ) patients were dry . In the severe group , 20/28 patients ( 71 % ) were dry , 3/28 ( 11 % ) improved and 5/28 ( 18 % ) were failures . Median visual analogue scale ( VAS ) scores dropped from 9 ( 4 - 10 ) to 0.5 ( 0 - 10 ) and International Consultation on Incontinence Question naire Short Form scores from ( ICIQ-SF ) 19 ( 12 - 21 ) to 1 ( 0 - 10 ) . Retro grade leak point pressure increased from 18 ( 5 - 29 ) to 35 ( 22 - 45 ) cm H2O after intraoperative adjustment . Complications included immediate postoperative infection in 2/36 patients ( 6 % ) and transient inguinal and /or perineal pain in 22/36 patients ( 61 % ) . Argus T has a long-term high success rate ( 86 % cure + improvement at the 30-month follow-up ) . Good outcomes were achieved even in severe incontinence cases and maintained for over 30 months PURPOSE We report on our initial experience in terms of efficacy and safety with a new , self-anchoring adjustable transobturator male system ( A.M.I. ® ATOMS System ) for the treatment of male stress urinary incontinence after prostate surgery . MATERIAL S AND METHODS In this prospect i ve , nonr and omized single center study conducted between March and December 2009 , patients with stress urinary incontinence secondary to prostatic surgery were treated with the ATOMS device . Urethroscopy , filling and voiding cystometry were performed preoperatively for all patients . In addition , incontinence symptoms were assessed , and a physical examination , 24-hour pad test and 24-hour pad count were performed before and after surgery . RESULTS A total of 38 patients were included in the study ( 36 after radical prostatectomy , 2 after benign prostatic hyperplasia surgery ) . No intraoperative complications occurred . Mean number of adjustments during followup was 3.97 ( range 0 to 9 ) . At a mean followup of 16.9 months ( range 13 to 21 ) the overall success rate was 84.2 % . Of the successful cases 60.5 % were considered dry ( 0 to 1 pad and less than 15 ml/24-hour pad test ) and 23.7 % improved ( more than 1 pad per 24 hours but more than 50 % decrease in pad use and less than 100 ml per 24-hour pad test ) . In 15.8 % of the patients the treatment was considered to have failed ( more than 2 pads daily and greater than 100 ml on 24-hour pad test ) . CONCLUSIONS The treatment of male stress urinary incontinence with the ATOMS is safe and effective . It is an excellent first or second line treatment for mild to moderate male stress urinary incontinence , even after external irradiation . The option of long-term , minimally invasive adjustment to respond to patient needs is a significant advantage of this new implant AIMS We explored re- interventions and short and long term adverse events associated with procedures for male incontinence among Medicare beneficiaries . METHODS All inpatient and outpatient cl aims for a simple r and om sample of Medicare beneficiaries for 2000 - 2011 were queried to identify patients of interest . All male patients with an International Classification of Diseases , 9th Edition ( ICD-9 ) diagnosis code for stress incontinence or mixed incontinence were included . Artificial urinary sphincter recipients , patients who underwent a sling operation and those receiving an injection of a bulking agent were identified with Current Procedure Terminology ( CPT-4 ) and ICD-9 Procedure Codes . RESULTS The entire cohort of 1,246 patients were operated on between 2001 and 2011 . 34.9 % of them received an artificial urinary sphincter ( AUS ) , 28.7 % with a bulking agent , and 36.4 % with a sling . There were no statistically significant differences in demographics or comorbidities between the treatment groups , except that more sling patients were obese ( P = 0.006 ) and fewer bulk patients had diabetes ( P = 0.007 ) . There are , however , significant changes in procedures selected over time ( P < 0.001 ) . In the first year and over the entire follow-up after surgery , patients treated with bulking agents had the most subsequent interventions ( 40.1 % and 52.9 % ) , followed by sling ( 10.4 % and 15.5 % ) , and AUS ( 2.3 % and 20 % ) ( P < 0.001 ) . Post-operative and 90 day complications were low . CONCLUSIONS All three treatments seem to be safe among Medicare beneficiaries with multiple comorbidities . The urological , infectious , and neurological complication occurrences were low PURPOSE Many investigators have used the number of pads to determine the severity of post-prostatectomy incontinence and yet the accuracy of this tool remains unproven . We determined whether the patient perception of pad use and urine loss reflects actual urine loss . We also identified a quality of life measure that distinguishes patients by severity of incontinence . MATERIAL S AND METHODS We prospect ively enrolled 235 men from a total of 18 sites 6 months or more after radical prostatectomy who had incontinence requiring protection . Patients completed a question naire on the perception of pad number , size and wetness , a quality of life question , several st and ardized incontinence question naires and a 24-hour pad test that assessed pad number , size and weight . SPSS ® was used for statistical analysis . RESULTS Perception of the number of pads used closely agreed with the number of pads collected during a 24-hour pad test . Perceived and actual pad size had excellent concordance ( 76 % , p < 0.001 ) . Patients with wet and soaked pads had statistically and clinical ly significantly different pad weights that were uniquely different from each other and from those of patients who were almost dry and slightly wet . Response to the quality of life question separated the men into 4 statistically significantly different groups based on mean 24-hour pad weight . CONCLUSIONS Patients accurately described the number , size and degree of wetness of pads collected during a 24-hour pad test . These values correlated well with actual urine loss . The single question , " To what extent does urine loss affect your quality of life ? " separated men into distinct categories PURPOSE We prospect ively assessed the role of nerve sparing surgery on urinary continence after open radical retropubic prostatectomy . MATERIAL S AND METHODS We evaluated a consecutive series of 536 patients who underwent open radical retropubic prostatectomy with attempted bilateral , unilateral or no nerve sparing , as defined by the surgeon , without prior radiotherapy at a minimum followup of 1 year with documented assessment of urinary continence status . Because outlet obstruction may influence continence rates , its incidence and management was also evaluated . RESULTS One year after surgery 505 of 536 patients ( 94.2 % ) were continent , 27 ( 5 % ) had grade I stress incontinence and 4 ( 0.8 % ) had grade II stress incontinence . Incontinence was found in 1 of 75 ( 1.3 % ) , 11 of 322 ( 3.4 % ) and 19 of 139 patients ( 13.7 % ) with attempted bilateral , attempted unilateral and without attempted nerve sparing , respectively . The proportional differences were highly significant , favoring a nerve sparing technique ( p < 0.0001 ) . On multiple logistic regression analysis attempted nerve sparing was the only statistically significant factor influencing urinary continence after open radical retropubic prostatectomy ( OR 4.77 , 95 % CI 2.18 to 10.44 , p = 0.0001 ) . Outlet obstruction at the anastomotic site in 33 of the 536 men ( 6.2 % ) developed at a median of 8 weeks ( IQR 4 to 12 ) and was managed by dilation or an endoscopic procedure . CONCLUSIONS The incidence of incontinence after open radical retropubic prostatectomy is low and continence is highly associated with a nerve sparing technique . Therefore , nerve sparing should be attempted in all patients if the principles of oncological surgery are not compromised ABSTRACT Objective To compare the results of two slings , Argus T ® and Advance ® , for the treatment of postprostatectomy urinary incontinence ( PPUI ) . Material and Methods : From December 2010 to December 2011 , 22 patients with PPUI were r and omized as follows : 11 ( mean age 62.09(±5.30 ) ) underwent treatment with Advance ® and 11 ( mean age 62.55(±8.54 ) ) with Argus T ® . All patients were evaluated preoperatively with urodynamic testing , quality of life question naire ( ICIQ-SF ) , voiding diary and 24-hour pad test . Exclusion criteria were : neurological diseases , severe detrusor overactivity and urethral stenosis . Evaluation was performed at 6 , 12 and 18 months after the surgery . After implantation of the Argus T ® sling , patients who experienced urine leakage equal to or greater than the initial volume underwent adjustment of the sling tension . Results were statistically analyzed using the Fisher ’s test , Kolmogorov-Smirnov test , Friedman ’s non-parametric test or the Mann-Whitney test . Results Significant improvement of the 24-hour pad test was observed with the Argus T ® sling ( p=0.038 ) , With regard to the other parameters , there was no significant difference between the two groups . Removal of the Argus T ® device due to perineal pain was performed in one patient ( 9 % ) . Despite non uniform results , both devices were considered useful to improve quality of life ( ICIQ-SF ) : Argus T ® ( p=0.018 ) and Advance ® ( p=0.017 ) . Conclusions Better results were observed in the 24h pad test and in levels of satisfaction with the Argus T ® device . Both slings contributed to improve quality of life ( ICIQ-SF ) , with acceptable side effects OBJECTIVE To evaluate the effectiveness of a readjustable sling for the treatment of male stress urinary incontinence ( SUI ) . MATERIAL S AND METHODS Between October 2002 and August 2005 , 51 male patients with mild to severe SUI were prospect ively operated with the use of a readjustable sling ( MRS ) at seven different European hospitals : Spain ( 2 ) , Italy ( 2 ) , Greece ( 1 ) , Germany ( 1 ) , and Portugal ( 1 ) . The origin of incontinence was radical prostatectomy in 43 cases , TUR in 4 , and open prostatectomy in another 4 . Duration of incontinence ranged from 1 to 10 yr with an average of 3.5 yr . RESULTS All patients but 5 were regulated during the early postoperative period ; 44 patients ( including all 5 not regulated during the early period ) required a second regulation under local anaesthesia between 1 to 4 mo after surgery , and 17 other patients required more than one delayed regulation . After that , 33 patients ( 64.7 % ) were considered cured ( 25 of them wore no pads at all , and 8 used small pads or sanitary napkins for security but normally remained dry ) ; another 10 cases showed important improvement ( 19.6 % ) ; and only 8 patients remain unchanged ( 15.7 % ) . The average follow-up time was 32 mo ( range : 16 - 50 ) . The mesh was removed in 1 case owing to urethral erosion and the varitensor in 2 cases owing to infection . There were five ( 9.8 % ) uneventful intraoperative bladder perforations at the postoperative period , and there were three mild perineal haematomas ( 5.9 % ) . Most patients felt perineal discomfort or pain , which was easily treated with oral medications . CONCLUSIONS The MRS((R ) ) allowed postoperative readjustment of the suburethral sling pressure at the immediate or midterm postoperative period , which allowed the achievement of good midterm results in almost 85 % of patients without significant postoperative complications OBJECTIVE To communicate long-term results of the multicentre phase III trial post-prostatectomy urinary incontinence ( PPI ) treated with an adjustable male sling . PATIENTS AND METHODS 48 PPI patients were included in this trial from April 2003 to September 2004 . 39 post radical prostatectomy and 9 post adenomectomy . 19 wore 5 pads per day ( 3 - 8 ) each weight 83 gr ( 17 - 198 ) . 29 wore condom catheter or penile clamp The Argus was implanted through perineal approach . Using needles , the sling was transferred to the abdominal wall where it was adjusted by washers . The adjustment was done with retro grade urethral pressure from 45 to 55 cm water . Clinical data were up date d till September 2007 . The mean follow-up was 45 months ( 36 - 54 ) and median age was 67 years ( 52 - 77 ) . The evaluation was : the ICIQ-SF score and qualification as Dry : no pads , Improved : 1 pad and Failed : 2 or more pads in 24 hr , including those with slings removed . RESULTS 47 were evaluated , result ing : 31 ( 66 % ) Dry , 6 ( 12.8 % ) Improved and 10 ( 21 % ) Failed . The ICIQ-SF score changed from 19.5 to 6 . Of the 31 dry pts , 5 required one adjustment . 10 pts failed , 9 after sling removal , 6 due to erosion and 3 for infection . One patient failed with the sling in place , 6 erosions were registered : 4 in the urethra , 1 into the bladder and 1 through the abdominal wall . Perineal pain persisted in 2 . One patient was excluded , died in September 2006 . CONCLUSIONS Argus has demonstrated its efficacy in long- term follow-up . The social continence rate was about 80 % . The important complication was erosion or infection Introduction The objective of this study was to report outcome measures with third-generation pre-attached scrotal port adjustable transobturator male system ( ATOMS ) for male stress urinary incontinence ( SUI ) after radical prostatectomy . Methods A prospect i ve open study was conducted on consecutive patients . Evaluation included cough test , urethroscopy , filling and voiding cystometry , 24-h pad count and pad test , patient-reported outcomes ( ICIQ-SF , IIQ-7 , PGI , GRA , and VAS ) , complications according to the Clavien – Dindo system , operative results , number of adjustments , and filling of the system . Results Thirty-four patients with median pad test 510 ( 170–1225 ) ml were operated on . Preoperative SUI was mild ( 5.9 % ) , moderate ( 17.6 % ) , and severe ( 76.5 % ) . At median 18.5 ( 12–26 ) months follow-up distribution of SUI was none ( 85.3 % ) , mild ( 8.8 % ) , and moderate ( 5.9 % ) . Median intraoperative filling was 14 ( 8–17 ) ml , number of adjustments 1 ( 0–5 ) , and total filling 17.5 ( 11–33.5 ) ml . At 3 months , median ICIQ-SF ( p = 0.0001 ) and IIQ-7 ( p < 0.0001 ) decreased . At 12 months , 24-h pad count and pad test decreased ( both p < 0.0001 ) , residual volume slightly increased ( p = 0.018 ) , PGI-I was 1 ( 1–3 ) , GRA 6 ( 3–6 ) , and 97 % were satisfied with treatment . Continence ( p = 0.016 ) and satisfaction ( p = 0.09 ) were worse in irradiated patients . Median operative time was 67 ( 35–120 ) min , hospital stay 1 ( 1–3 ) days , and VAS for pain on postoperative day 1 was 0 ( 0–2 ) . Complications presented in 14.7 % ( 8.8 % grade I and 5.9 % grade III ) . Conclusion Treatment of severe male SUI after radical prostatectomy with pre-attached scrotal port ATOMS is safe and very effective in the short term . A positive cough test before implant and intraoperative overfilling of the system may optimize patient selection and results Objectives : The study aims to investigate and evaluate the influence of 2 different methods of implantation of the Argus transobturator ( Argus-T ) adjustable male sling on complication rate and short-term efficacy . Methods : A prospect i ve mono-center evaluation was conducted on consecutive patients treated for persistent post-radical prostatectomy incontinence . Thirty-six patients were implanted with the Argus-T adjustable male sling - 18 by inguinal-perineal incision ( IPI ) and 18 by single-perineal incision ( SPI ) . Measurements included 24-hour frequency volume micturition list , 24-hour pad test , 24-hour pad count , Visual Analogue Scale for continence and satisfaction , flowmetry and residual voided urine . Results : Cure rate for IPI and SPI at 1 , 6 and 12 months was 67 , 75 , 62 % and 59 , 63 , 63 % , respectively ( no statistically significant difference ) . Although more clinical ly significant complications were seen in the IPI group , a statistical significant difference was observed only for wound infection between the IPI and the SPI groups ( 33 vs. 0 % , p = 0.019 ) . Conclusions : The Argus-T male sling SPI suspension operation is a minimally invasive and safe procedure for the management of male postoperative stress incontinence which is highly appreciated by the patients OBJECTIVE To evaluate prospect ively the efficacy and the safety of the ArgusT in male patients with persistent stress urinary incontinence . METHODS A prospect i ve 2-center evaluation was conducted on consecutive patients treated for persistent stress incontinence . Forty-two patients were implanted with the ArgusT male sling system with no associated surgery . Measurements included daily pad usage , 24-hour pad weight test , International Quality of Life question naire , International Consultation on Incontinence Question naire short form , and the Patient Global Impression of Improvement . Postoperative complications were assessed using the Clavien-Dindo classification . The definitions used were cured , 0 - 5 g in 24-hour pad weight test ; improved , reduction of urine loss in 24-hour pad weight test > 50 % ; and failed , all others . RESULTS After a mean follow-up of 28.8 months ( 20 - 38 months ) , 26 patients were dry ( 61.9 % ) with a pad test of 0 - 5 g/24 hours . Eleven patients ( 26.2 % ) improved . Five patients are considered failures . Overall daily pad use , urine loss in the 24-hour pad test , and quality of life scores improved significantly after sling implantation . Median adjustment rate was 1.7 . There were no perioperative complications . Postoperative complications were mainly grade I and II complications according to the Clavien-Dindo classification . CONCLUSION The ArgusT sling system offers an effective and safe treatment option for male patients with moderate to severe stress urinary incontinence in a follow-up > 2 years , even after radiotherapy To evaluate the efficacy and safety of a new adjustable bulbourethral sling ( Argus ® , Promedon SA , Cordoba , Argentina ) in the treatment of male stress urinary incontinence ( SUI ) after prostate surgery PURPOSE We prospect ively examined whether the fixed urethral resistance of the perineal male sling for the treatment of stress incontinence causes significant bladder outlet obstruction or de novo voiding dysfunction . MATERIAL S AND METHODS A total of 22 patients ( average age 67 years old ) were evaluated before and after surgery with videourodynamics , the self-administered UCLA Prostate Cancer Index incontinence section and pad score . RESULTS Mean followup was 25 months ( range 6 to 42 ) . All patients complained of a moderate to severe problem before surgery . After surgery 16 ( 73 % ) reported a very small problem/no problem , 3 ( 14 % ) a moderate problem and 3 ( 14 % ) reported a big problem . Average pad use + /- SD decreased from 4.6 + /- 2.5 to 0.74 + /- 1.0 pads ( p < 0.01 ) . Median UCLA Prostate Cancer Index incontinence score increased from 82 to 313 , p < 0.001 . Mean retro grade leak point pressure ( RLPP ) increased from 30.4 + /- 15.9 to 59.9 + /- 9.7 cm water . Bladder outlet obstruction did not develop in any patients after surgery . Average maximum flow rate did not change significantly ( 17.7 + /- 6.5 vs 19.2 + /- 9.7 ml per second , p = 0.6 ) . Nor was there a significant change in detrusor pressure at maximum flow rate ( 40.3 + /- 9.2 vs 45.8 + /- 14.7 cm water , p = 0.3 ) . While de novo urgency or urge incontinence did not develop in any patients , 2 of 5 patients with a moderate/big leakage problem demonstrated postoperative detrusor overactivity on cystometry . Both individuals requiring more than 3 pads daily had a postoperative RLPP of less than 50 cm water . CONCLUSIONS Pad use , leak point pressure and urinary incontinence scores are significantly improved after sling surgery . Fixed resistance does not lead to bladder outlet obstruction . Postoperative RLPP less than 50 cm water and urodynamic detrusor overactivity are associated with increased pad use and bother study characteristics will help limit selection bias . Second , the outcome measures should be clinical ly relevant and collected prospect ively.2 Ideally , the use of health-related quality of life measures will help strengthen the value of the case series . Finally , a high follow-up rate is imperative.2 If a large number of patients are dropping out of a study , the validity of the treatment or study protocol must be question ed . Unfortunately , even the best design ed clinical trials can lose patients to follow-up . In such situations , it is important that the authors state the reasons for the loss to follow-up |
12,307 | 32,258,079 | The flapless surgery and conventional approach had comparable clinical performance over three years or more .
The guided or free-h and technique does not significantly affect the long-term outcomes of flapless surgery | BACKGROUND The conventional implant approach involves flap elevation , which may result in increased soft tissue and bone loss and postoperative morbidity .
The flapless surgical technique , aided by three-dimensional medical imaging equipment , is regarded as a possible alternative to the conventional approach to alleviate the above issues .
Several studies have been performed regarding the role of flapless implant surgery .
However , the results are inconsistent and there is no robust synthesis of long-term evidence to better inform surgeons regarding which type of surgical technique is more beneficial to the long-term prognosis of patients in need of implant insertion .
AIM To compare the long-term clinical performance after flapless implant surgery to that after the conventional approach with flap elevation . | PURPOSE The literature reports that flapless compared with traditional implant surgery can be associated with several advantages , including the maintenance of peri-implant hard tissues . This study investigated vertical bone resorption during long-term follow-up after implant placement with flapless versus traditional surgery . MATERIAL AND METHODS In this prospect i ve , r and omized controlled clinical trial , 40 patients underwent implant placement at the Maxillofacial Department Surgery of the Istituto Stomatologico Italiano Hospital in Milan , Italy . Patients were r and omly assigned to the control or experimental group . The control group had implants placed with open flap surgery ( traditional surgery ) , whereas the experimental group had implants placed with flapless surgery . The distance between the first implant thread and the marginal crestal bone level was measured at the basal , loading , and long-term control points . The basal recording was performed just after implant placement . The loading measurement was recorded at the time of implant loading , after 2 months of healing for the lower jaw and after 3 months of healing for the upper jaw , and the long-term control record was registered 36 months after implant placement . Statistical analysis was performed using mean values and st and ard deviations based on bone resorption in the 2 groups . To detect statistical differences , the Student t test was applied . Differences were considered significant if P values were less than .05 . RESULTS The control group ( open flap surgery ) was comprised of 19 patients , and the experimental group ( flapless surgery ) was comprised of 21 patients . No statistical differences were found in peri-implant bone resorption between the 2 groups at the basal , implant loading , and 3-year control recordings . CONCLUSION According to this study , the approach to implant surgery does not seem to influence peri-implant bone resorption in humans , at least for the period measured in this study PURPOSE To compare the efficacy of immediate functionally loaded implants placed with a flapless procedure ( test group ) versus implants placed after flap elevation and conventional load-free healing ( control group ) in partially edentulous patients . MATERIAL S AND METHODS Forty patients were r and omized : 20 to the flapless immediately loaded group and 20 to the conventional group . To be immediately loaded , implants had to be inserted with a minimum torque > 45 Ncm . Implants in the immediately loaded group were provided with full acrylic resin temporary restorations the same day . Implants in the conventional group were submerged ( anterior region ) or left unsubmerged ( posterior region ) and were left load-free for 3 months ( m and ibles ) or 4 months ( maxillae ) . Provisional restorations were replaced with definitive single metal-ceramic crowns 1 month postloading . Outcome measures were prosthesis and implant failures , biological and prosthetic complications , postoperative edema , pain , and use of analgesics . Independent sample chi2 tests , Mann-Whitney tests , t tests , and paired t tests were used with a significance level of .05 . RESULTS Fifty-two implants were placed in the flapless group and 56 in the conventionally loaded group . In the flapless group , 1 flap had to be raised to control the direction of the bur and 1 implant did not reach the planned primary stability and was treated as belonging to the conventional group . After 3 years no dropouts or failures occurred . There was no statistically significant difference for complications ; however , patients in the conventional group had significantly more postoperative edema and pain and consumed more analgesics than those in the flapless group . Osstell values were significantly higher at baseline in the flapless group ( P = .033 ) . When comparing baseline data with years 1 , 2 , and 3 within each group , mean Osstell values of the flapless group did not increase , whereas there were statistically significant increases in the Periotest values . CONCLUSIONS Implants can be successfully placed flapless and loaded immediately without compromising success rates ; the procedure decreases treatment time and patient discomfort PURPOSE The purpose of this 2-year r and omized controlled clinical trial was to assess the differences in implant survival rates , soft tissue preservation , patient centered outcome and crestal bone changes applying the minimally invasive ( MI ) flapless approach for single implant placement compared to flapped implant surgery ( FS ) . MATERIAL S AND METHODS Subjects eligible for this study were r and omly assigned into two groups : MI or FS . Items of evaluation were the following : implant installation position , soft tissue healing , post-surgical pain , soft tissue outcome , marginal bone loss ( MBL ) , and implant survival rate . RESULTS Forty subjects ( 14 women and 26 men , 20 in MI group and 20 in FS group with a mean of 39 ± 13.2 years old ) were included in the study . None of the implants demonstrated dehiscence or loss during the follow-up . Subjects in MI group showed significantly lower post-surgical pain and significantly less wound healing index scores at 1-week follow-up . The width of keratinized mucosa decreased from a mean of 4.2 ± 1.6 mm pre-surgically to 3.7 ± 1.1 mm at crown delivery but remained stable at 2-year follow-up in MI group . At every appointment in the study , no statistical significant difference of PD and MBL was found between the two groups . CONCLUSION Compared with FS , single implants placed applying the MI technique in selected subjects showed advantages in improving patient comfort and decreasing post-implant placement soft tissue reaction . Meanwhile , implants with MI approach have the same level of MBL and high success rates as FS procedure at 2-year follow-up . The deduction of keratinized mucosa is very limited and the width of KM remained stable with MI approach at 2-year follow-up PURPOSE The aim of this prospect i ve clinical study was to evaluate the 3-year outcome of fixed partial prostheses supported by implants with immediate provisionalization without occlusal contacts inserted in predominantly soft bone with flap and flapless protocol s. MATERIAL S AND METHODS Forty-one patients partially rehabilitated with 72 NobelSpeedy implants ( 51 maxillary ; 21 m and ibular ) were consecutively included and treated with a flapless surgical protocol ( n = 20 patients ; 32 implants ) and flapped surgical protocol ( n = 21 patients ; 40 implants ) . Primary outcome measure was implant survival ; secondary outcome measures were marginal bone resorption ( comparing the bone levels at 1 and 3 years with baseline ) and the incidence of biological , mechanical , and esthetic complications . Survival was computed through life tables ; descriptive statistics were applied to the remaining variables of interest . RESULTS Eight patients with eight implants dropped out of the study . One implant failed in one patient ( flapless group ) giving an overall cumulative survival rate ( CSR ) of 98.6 % . No failures were noted with the flapped protocol ( CSR 100 % ) , while for the implants placed with the flapless surgical technique , a 96.9 % CSR was registered . The overall average marginal bone resorption at 3 years was 1.37 mm ( SD = 0.94 mm ) , with 1.14 mm ( SD = 0.49 mm ) and 1.60 mm ( SD = 1.22 mm ) for the flap and flapless groups , respectively . Mechanical complications occurred in nine patients ( n = 5 patients in the flapless group ; n = 4 patients in the flap group ) . Implant infection was registered in three implants and three patients ( flapless group ) , who exhibited inadequate oral hygiene levels . CONCLUSIONS Partial edentulism rehabilitation through immediate provisionalization fixed prosthesis supported by dental implants inserted through flap or flapless surgical techniques in areas of predominantly soft bone was viable at 3 years of follow-up . The limitations and risks of the " free-h and " method in flapless surgery should be considered when planning implant-supported fixed prosthetic reconstructions In this issue , we answer three questions with respect to loss to follow-up in a clinical trial : How important is loss to follow-up ? How is loss to follow-up calculated ? How many patients can be lost to follow-up without mistrusting the results ? 1 . How important is loss to follow-up ? The simple answer to this question is “ very important ” because loss to follow-up can severely compromise a study 's validity . Incomplete follow-up biases the results when either : The dropout rates are different between study groups ; or The patients who drop out are different from those who do not drop out . Why do these situations make a difference ? Because in each situation , those lost to follow-up often have a different prognosis than those who complete the study . For example , patients who receive treatment for cervical myelopathy may not return for follow-up because they became asymptomatic and felt no need to return to see the surgeon . Conversely , some patients may not return because they had a particularly bad outcome ( worse pain or function ) or complication , or because they died . In either case , bias can affect the validity of the inferences drawn from the study . 2 . How is loss to follow-up calculated ? There is much confusion about how to determine the proportion of patients lost to follow-up . In order to correctly calculate the follow-up rate , one needs to know the denominator . In a r and omized controlled trial ( RCT ) , the denominator for each group is the number of patients who were r and omized , not the number who received the treatment . For example , suppose we have an RCT comparing two treatment groups , Group A and Group B. The investigators evaluate 178 patients and r and omize 120 ; 61 to Group A and 59 to Group B ( Fig 1 ) . Following the figure , we note that 49 patients received treatment A and 52 received treatment B. At the final follow-up 40 were analyzed in Group A and 41 in Group B. How many were considered lost to follow-up ? Many would consider the loss to follow-up rate to be 9 ( 18 % ) of 49 in treatment A and 11 ( 21 % ) of 52 in treatment B using as the denominator only those that were treated . However , the real proportion lost to follow-up must consider those who were r and omly assigned , even if they did not receive treatment . In the present example , this is calculated as 21 ( 34 % ) of 61 for treatment A and 18 ( 31 % ) of 59 for treatment B. Fig 1 Hypothetical example of patients lost to follow-up in a r and omized controlled trial . When calculating loss to follow-up in a retrospective cohort study , all individuals receiving treatment during the study period should be used as the denominator , not just those with complete data . For example , let 's say you want to compare decompression plus lumbar fusion with decompression alone in disc herniation and the data available are all patients receiving either treatment in the last 5 years ( N = 275 ) . However , the data base from which the data are obtained is incomplete and only 190 have the necessary data available . Since the investigators stated as part of the inclusion criteria that only those patients with complete data are included , they consider the follow-up to be 100 % ( 190/190 ) . This conclusion is wrong . The denominator should include all patients who underwent the surgery irrespective of completeness of data . The follow-up rate for this example is 69 % ( 190/275 ) . 3 . How many patients can be lost to follow-up without mistrusting the results ? Some have suggested that 20 % poses serious threats to validity 1 . This may be a good rule of thumb , but keep in mind that even small proportions of patients lost to follow-up can cause significant bias 2 . One way to determine if loss to follow-up can seriously affect results is to assume a worst-case scenario with the missing data and look to see if the results would change . Here is an example : Let 's assume a multicenter study enrolled 500 patients into each arm of a study comparing artificial disc replacement ( ADR ) with fusion , and the end point is adjacent segment disease ( ASD ) . The trial numbers are found in Fig 2 . Fig 2 Hypothetical example of the effect of loss to follow-up considering a worst-case scenario . ADR indicates artificial disc replacement ; ASD , adjacent segment disease . The proportion of patients with ASD in the ADR group is half as much versus the fusion group , 25 % ( 100/400 ) compared with 50 % ( 200/400 ) . If we assume that the 100 lost to follow-up in the ADR group had ASD and the 100 lost to follow-up in the fusion group did not , then the rate of ASD in each group would be 40 % ( 200/500 ) . In this case , adopting the worst-case scenario for the intervention group with respect to those lost to follow-up causes the results to change significantly from half the rate of ASD with ADR to the same rate . When this happens , loss to follow-up can threaten the internal validity of the trial . Only when the worst case does not change the inferences derived from the results is lost to follow-up not a problem PURPOSE To compare outcomes for immediately loaded one-piece implants ( OPI ) , placed flapless , and conventionally loaded two-piece implants ( TPI ) , placed after two-stage flapped surgery . MATERIAL S AND METHODS Thirty-eight participants were r and omised to receive either one OPI ( 19 participants , OPI group ) or one TPI ( 19 participants , TPI group ) inserted in the posterior m and ible with a torque of at least 35 Ncm according to a parallel group design . OPI were immediately loaded with non-occluding temporary crowns . After 3 months , TPI were exposed and implants in both groups were occlusally loaded with zirconia crowns . Outcome measures were implant failure , prosthesis failure , any complication and changes of probing pocket depth ( PPD ) , plaque index ( PI ) , gingiva index ( GI ) , and peri-implant marginal bone level , recorded by unblinded assessors . RESULTS Three years after occlusal loading , three participants dropped out from the TPI group . There were no statistically significant differences between the groups with regard to participants with implant failure ( OPI group 1/19 ; TPI group 0/16 ; difference in proportions ( DIP ) , -5.3 % ; 95 % confidence interval ( CI ) -15.3 to 4.8 ; P = 1.000 ) , prosthesis failure ( OPI group 3/19 , TPI group 5/16 ; DIP , 15.5 % ; 95 % CI -12.6 to 43.5 ; P = 0.424 ) , any complication ( OPI group 6/19 , TPI group 5/16 ; DIP , -0.3 % ; 95 % CI -31.2 to 30.5 ; P = 1.000 ) , or changes of PPD ( P = 0.174 ) , PI ( P = 0.222 ) , or GI ( P = 0.415 ) . Veneer chipping accounted for most prosthesis failures and complications . On average OPI and TPI lost 1.34 mm and 0.67 mm of marginal bone , respectively , the difference between groups being statistically significant ( mean difference , 0.66 mm ; 95 % CI -0.02 to 1.34 ; P = 0.024 ) in favour of TPI implants . CONCLUSIONS Both implant procedures might be viable in the short term , but statistically significantly more bone loss might be indicative of future problems with OPI . Because of the high incidence of chipping , veneered zirconia crowns can not be recommended on posterior implants . Conflict-of-interest statement : The authors are grateful to Nobel Biocare for providing the study material s free of charge . Money received from the manufacturer was used to reimburse participants for regular attendance at follow-up appointments and to finance data management . The authors declare no conflict of interest The purpose of the current study was to determine the survival rates and to measure marginal bone changes and peri-implant conditions 8.5 years after placement of one-piece implants with an anodically oxidized surface ( AOS ) . A total of 52 subjects who received a one-piece implant with an AOS using a flapless or flap protocol and completed a previous r and omized clinical trial were contacted for a recall visit 8.5 years after implant placement ( T8.5 ) . Implant success and survival rates , probing pocket depth ( PPD ) , presence of bleeding on probing ( BoP ) , papilla level , and incidence of complications and peri-implant disease were assessed by a single , blinded examiner . A second blinded examiner evaluated marginal bone level changes . Results for 8.5 years were compared to those at the time of implant placement , implant loading ( 0.5 year ) , and 1 and 1.5 years follow-up . The results based on 28 patients who attended the follow-up visit ( half had flapless and half a flap protocol ) showed a 100 % implant survival rate and a 96.4 % implant success rate 8.5 years after implant placement using one-piece implants , with no difference in survival and success rates between the flapless and the flap protocol . During the same follow-up period , a significant increase in crestal bone height from 1.5 to 8.5 years was observed . Analysis suggested decreasing mean levels of bone loss with time ( P < .001 ) . Moreover , there was 0.8 to 1.0 mm of bone loss through year 1.5 , which decreased to 0.3 mm at 8.5 years ( P < .05 ) . There was no statistically significant difference in PPD or BoP over time . Similar mean levels of PPD were found in flap and flapless groups ( mean [ SD ] = 2.4 [ 0.3 ] and 2.2 [ 0.4 ] mm , respectively [ P = .18 ] ) , as well as similar rates of BoP ( 22.8 % vs 17.9 % , respectively ) . Papilla levels increased during the first year after implant loading . However , there was little additional change between 1.5 and 8.5 years . A total of eight fractured porcelain crowns and three crown loosenings were reported . One-piece implants with an AOS showed high survival rates and stable marginal bone and periimplant soft tissue levels regardless of whether a flapless or flap protocol was used PURPOSE To evaluate the survival rate and marginal bone loss ( MBL ) of a calcium phosphate-blasted titanium implant inserted by a flap or flapless technique and to study the morphochemical characteristics of the implant surface . MATERIAL S AND METHODS Sixty out of 85 patients who received one or more implants were selected as eligible for this prospect i ve longitudinal cohort clinical study . Titanium implants ( n = 132 ) were placed in human healthy subjects using either a flap or flapless technique , selected on the basis of the best practice . The survival rate and MBL were evaluated after 3 months ( preloading stress-free healing period ) and after 6 , 12 , 24 , and 36 months in relation to implant diameter , location , sex , and smoking habits . Surface morphochemical analyses were performed by environmental scanning electron microscopy connected with energy-dispersive x-ray ( ESEM/EDX ) . RESULTS The overall survival rate was 97.72 % . After 3 and 36 months , MBL was 0.36 ± 0.66 mm and 1.09 ± 1.10 mm for the flapless group and 0.29 ± 0.51 mm and 1.03 ± 0.92 mm for the flap group . MBL showed a statistically significant increase with time ( P = .0001 ) , and differences were found at all times since 6 months . No statistical differences between the flapless and flap groups and sex were observed at any time , while MBL was significantly higher in the maxillary versus m and ibular location ( 6 , 12 , and 24 months ) and in smokers versus nonsmokers ( 6 months ) . Higher MBL in both groups was found for a smaller diameter ( 3.5 mm ) than larger diameter ( 4.1 , 5 mm ) . The surface showed a Ti-Al-V alloy displaying a uniform nanotexture . CONCLUSION The implant system showed a high survival rate and markedly lower MBL considering the limits for acceptable progression . Flapless and flap techniques demonstrated similar results of MBL at the preloading healing period and at the 6 months to 3 years postloading periods . Both surgical procedures induced an early MBL during the preloading stress-free period . Implant diameter , m and ibular/maxillary location , preloading stress-free period , and smoking habits affect MBL more than the type of surgery after both short- and long-term follow-up PURPOSE The aim of this study was to compare the pain experienced after implant placement with 2 different surgical procedures : a flapless surgical procedure using an image-guided system based on a template and an open-flap procedure . MATERIAL S AND METHODS The study population consisted of 60 patients who were referred for implant placement . One group consisted of 30 patients who were referred for the placement of 80 implants and treated with a flapless procedure . The other group consisted of 30 patients who were referred for the placement of 72 implants with a conventional procedure . Patients were selected r and omly . They were requested to fill out a question naire using a visual analog scale ( VAS ) to assess the pain experienced and to indicate the number of analgesic tablets taken every postoperative day from the day of the surgery ( DO ) to 6 days after surgery ( D6 ) . RESULTS The results showed a significant difference in pain measurements , with higher scores on the VAS with open-flap surgery ( P < .01 ) . Pain decreased faster with the flapless procedure ( P = .05 ) . The number of patients who felt no pain ( VAS = 0 ) was higher with the flapless procedure ( 43 % at DO versus 20 % ) . With the flapless procedure , patients took fewer pain tablets ( P = .03 ) and the number of tablets taken decreased faster ( P = .04 ) . DISCUSSION Minimally invasive procedures may be requested by patients to reduce their anxiety and the pain experienced and thus increase the treatment acceptance rate . CONCLUSION With the flapless procedure , patients experienced pain less intensely and for shorter periods of time PURPOSE To evaluate the efficacy of flapless versus open flap implant placement in partially edentulous patients . MATERIAL S AND METHODS Forty patients with two separate edentulous areas characterised by residual bone at least 5 mm thick and 10 mm in height had these sites r and omised following a split-mouth design to receive at least one implant to each side after flap elevation or not . Implants were first placed in one site , and after 2 weeks in the other site freeh and . Implants inserted with a torque > 48 Ncm were immediately loaded with full occluding acrylic temporary restorations . Definitive single cemented crowns or screw-retained metal ceramic fixed dental prostheses were delivered after 2 months . Outcome measures were prosthesis and implant failures , complications , postoperative swelling and pain , consumption of analgesics , patient preference , surgical time , marginal bone level changes , and implant stability quotient ( ISQ ) values . RESULTS Seventy-six implants were placed flapless and 67 after flap elevation . In the flapless group , four flaps had to be raised to control the direction of the bur , whereas one haemorrhage and one fracture of the buccal bone occurred in two patients of the flap elevation group . Four implants did not reach the planned stability ( three belonging to the flapless group ) and they were all immediately replaced by larger diameter ones . After 1 year , no drop-outs occurred . Two definitive bridges could not be placed when planned ( one in each group ) and two crowns had to be remade ( one in each group ) . Two implants failed in each group , all in different patients . There were no statistically significant differences for prosthetic and implant failures , complications , ISQ values and marginal bone levels between groups . However , flapless implant placement required significantly less operation time ( 17 minutes less , saving almost two-thirds of the time for implant placement ) , induced less postoperative pain , swelling , analgesic consumption and was preferred by patients . Mean ISQ values of both groups significantly decreased over time . CONCLUSIONS Implants can be successfully placed flapless and loaded immediately , reducing treatment time and patient discomfort PURPOSE This 5-year prospect i ve multicenter study compared implant survival and success , peri-implant health and soft tissue responses , crestal bone level stability , and complication rates following immediate loading of single OsseoSpeed implants placed in anterior maxillary healed ridges or extraction sockets . MATERIAL S AND METHODS Individuals requiring anterior tooth replacement with single implants were treated and immediately provisionalized . Definitive all-ceramic crowns were placed at 12 weeks . Implant survival , bone levels , soft tissue levels , and peri-implant health were monitored for 5 years . RESULTS One hundred thirteen patients received implants in fresh sockets ( 55 ) and healed ridges ( 58 ) . After 5 years , 45 and 49 patients remained for evaluation , respectively . During the first year , three implants failed in the extraction socket group ( 94.6 % survival ) and one implant failed in the healed ridge group ( 98.3 % survival ) ; this difference was not significant . No further implant failures were recorded . After 5 years , the interproximal crestal bone levels were located a mean of 0.43 ± 0.63 mm and 0.38 ± 0.62 mm from the reference points of implants in sockets and healed ridges ( not a significant difference ) . In both groups , papillae increased over time and peri-implant mucosal zenith positions were stable from the time of definitive crown placement in sockets and healed ridges . Compared to flap surgery for implants in healed ridges , flapless surgery result ed in increased peri-implant mucosal tissue dimension ( average , 0.78 ± 1.34 mm vs 0.19 ± 0.79 mm ) . CONCLUSION After 5 years , the bone and soft tissue parameters that characterize implant success and contribute to dental implant esthetics were similar following the immediate provisionalization of implants in sockets and healed ridges . The overall tissue responses and reported implant survival support the immediate provisionalization of dental implants in situations involving healed ridges and , under ideal circumstances , extraction sockets PURPOSE Some initial loss of bone around dental implants is generally expected . There is reason to believe that reflecting a mucoperiosteal flap promotes crestal bone loss in the initial phase after an implant has been inserted . The objective of this study was to compare the effect of flapless implant insertion on initial bone loss with that of conventional placement after elevation of a mucoperiosteal flap . MATERIAL S AND METHODS Eighty patients were r and omly assigned either to the flapless group ( test ) or to the group with a full-thickness flap ( control ) . In total , 195 implants were included in the study : 95 of these were inserted flapless ( test group ) , and 100 were inserted by raising a mucoperiosteal flap ( control group ) . Healing occurred unsubmerged for both groups . To assess changes in the peri-implant bone level , the height of the mesial and distal peri-implant bone was measured on digitally calibrated radiographs taken at the time of implant placement and 12 months afterward . RESULTS After 1 year , a mean cumulative crestal bone loss of 0.24 ± 0.62 mm was measured . A mean bone loss of 0.55 ± 0.57 mm was found in the group with the mucoperiosteal flap , while a slight mean gain in bone height of 0.09 ± 0.49 mm was found in the test group , a statistically significant difference ( P < .001 ) . CONCLUSION Flapless implant insertion caused less peri-implant bone loss than implant insertion with flap preparation . Therefore , the flapless procedure represents a protective and promising method in implant surgery BACKGROUND Based on three-dimensional implant planning software for computed tomographic ( CT ) scan data , customized surgical templates and final dental prostheses could be design ed to ensure high precision transfer of the implant treatment planning to the operative field and an immediate rigid splinting of the installed implants , respectively . PURPOSE The aim of the present study was to ( 1 ) evaluate a concept including a treatment planning procedure based on CT scan images and a prefabricated fixed prosthetic reconstruction for immediate function in upper jaws using a flapless surgical technique and ( 2 ) vali date the universality of this concept in a prospect i ve multicenter clinical study . MATERIAL S AND METHODS Twenty-seven consecutive patients with edentulous maxillae were included . Treatments were performed according to the Teeth-in-an-Hour concept ( Nobel Biocare AB , Göteborg , Sweden ) , which includes a CT scan-derived customized surgical template for flapless surgery and a prefabricated prosthetic suprastructure . RESULTS All patients received their final prosthetic restoration immediately after implant placement , that is , both the surgery and the prosthesis insertion were completed within approximately 1 hour . In the 24 patients followed for 1 year , all prostheses and individual implants were recorded as stable . CONCLUSION The present prospect i ve multicenter study indicates that the prefabrication , on the basis of models derived from three-dimensional oral implant planning software , of both surgical templates for flapless surgery and dental prostheses for immediate loading is a very reliable treatment option . It is evident that the same approach could be used for staged surgery and in partial edentulism BACKGROUND Despite several reports on the clinical outcomes of flapless implant surgery , limited information exists regarding the clinical conditions after flapless implant surgery . OBJECTIVE The objective of this study was to evaluate the soft tissue conditions and marginal bone changes around dental implants 1 year after flapless implant surgery . STUDY DESIGN For the study , 432 implants were placed in 241 patients by using a flapless 1-stage procedure . In these patients , peri-implant soft tissue conditions and radiographic marginal bone changes were evaluated 1 year after surgery . RESULTS None of the implants were lost during follow-up , giving a success rate of 100 % . The mean probing depth was 2.1 mm ( SD 0.7 ) , and the average bleeding on probing index was 0.1 ( SD 0.3 ) . The average gingival index score was 0.1 ( SD 0.3 ) , and the mean marginal bone loss was 0.3 mm ( SD 0.4 mm ; range 0.0 - 1.1 mm ) . Ten implants exhibited bone loss of > 1.0 mm , whereas 125 implants experienced no bone loss at all . CONCLUSION The results of this study demonstrate that flapless implant surgery is a predictable procedure . In addition , it is advantageous for preserving crestal bone and mucosal health surrounding dental implants AIM The aim of this experimental study is to compare the effect of mini-incision flapless versus flap technique of implant placement on the amount of vascular structures and blood vessel elements in peri-implant soft tissue , using immunohistochemical analysis . METHOD The experiment was conducted on five domestic pigs . Each animal received six implants in m and ible according to the split-mouth design . On one r and omly chosen jaw side , mini-incision flapless surgery was performed , whereas on the opposite jaw side , flap was raised . After 3 months of implant healing through submerged approach , the experimental animals were sacrificed and sample s for immunohistochemical analyses were taken from the buccal side of peri-implant mucosa next to the neck of implants , from three levels . The study outcome was the presence of vascular structures and elements of the blood vessels in the peri-implant mucosa per microscopic field , estimated through ordinal scores from 0 to 2 . Effects of surgical approach , site of implantation , and their interaction on vascular scores of peri-implant mucosa were assessed by Brunner and Langer nonparametric analysis of longitudinal data . RESULTS Statistically significant effect of surgical approach on vascularity of peri-implant mucosa has been revealed in the second mucosal layer , where flapless approach provided higher vascularity compared with flap approach ( P = 0.002 ) . In the remaining two layers , surgical approach did not affect mucosal vascularity significantly ( layer 1 : P = 0.071 ; layer 3 : P = 0.433 ) . CONCLUSION The flapless surgical implant placement approach using mini-incision provides better vascularization of peri-implant mucosa after 3 months of healing compared with flap surgery BACKGROUND Flapless implant surgery is mostly performed using guided surgical protocol s , however , long-term studies on free-h and ed flapless surgery for single implants are lacking . PURPOSE This prospect i ve study evaluates bone level changes , peri-implant health , and complications of solitary implants placed using a conventional flap ( F ) or flaplessly ( FL ) after 6 - 9 years . MATERIAL S AND METHODS Fifty-three single TiUnite Brånemark implants were originally inserted in 49 patients using an one-stage delayed loading protocol with flap ( n = 27 , F ) or flaplessly ( n = 26 , FL ) based on available bone volume and surgeon 's decision-making . Thirty-six patients with 37 implants participated in the prospect i ve follow-up investigation 6 - 9 years later whereby survival , bone level changes , peri-implant health , and complications were assessed . RESULTS After 88 months ( range 76 - 107 ) , all implants were survived . For F and FL combined , the overall average radiographic bone level was above the first implant thread , 1.26 mm apical of the implant-abutment junction ( SD 1.08 ; 0 - 4.9 ) and statistically comparable . Bone loss from time of loading was 0.49 mm ( SD 1.1 ; -1.3 to 2.8 ) for F and -0.89 mm ( SD 1.0 ; -2.8 to 0.7 ) for FL ( P < .01 ) , suggesting regrowth of bone in FL due to initial countersinking . One implant ( 2.7 % ) had a probing depth above 5 mm . CONCLUSION Free-h and ed flapless implant surgery for single implants with neighboring teeth is a predictable long-term treatment provided when there is sufficient bone volume OBJECTIVES Flapless implant surgery is fast gaining popularity because of several advantages , such as reduced surgical time , postoperative bleeding , and swelling . Studies have shown that flap elevation results in some amount of bone loss . The aim of the current study was to compare the amount of bone loss in procedures using the flapless technique and those where flap elevation was done . Papillary fill was also compared in both techniques , which is unique to this study . STUDY DESIGN Forty patients , selected according to certain inclusion and exclusion criteria , were r and omly assigned to 1 of 2 groups : Flap ( F ) , or Flapless ( FL ) . The amount of crestal bone loss was measured from st and ardized radiographs at baseline , 6 months , 1 year , and 2 years after implant placement . Papillary fill was evaluated using the Papillary presence index , which was measured 6 months after loading . RESULTS The bone loss was greater for the F group during all time periods and the mean papillary fill was greater for the FL group . CONCLUSIONS In conclusion , the results of the current study show that flapless implant surgery results in less crestal bone loss both during the healing period and after loading . In addition , it can produce better papillary fill . The cases selected for this study were ideal cases in terms of bone volume and the operator was well experienced , however . Care should be taken during case selection for flapless implant surgery |
12,308 | 28,708,579 | mCRC Patients with left-sided , wild type Kras have a better prognosis than those with right-sided diseases when treated with cetuximab . | OBJECTIVE To assess the prognostic role of primary tumor location along with Kras status in metastatic colorectal cancer ( mCRCs ) treated with cetuximab . | BACKGROUND Since the 1990s , fluorouracil-based adjuvant chemotherapy has significantly reduced the risk of tumour recurrence in patients with stage III colon cancer . We aim ed to assess whether the addition of cetuximab to st and ard adjuvant oxaliplatin , fluorouracil , and leucovorin chemotherapy ( FOLFOX4 ) in patients with stage III colon cancer improved disease-free survival ( DFS ) . METHODS For this open-label , r and omised phase 3 study done in nine European countries , we enrolled patients through an interactive voice response system to the central r and omisation centre , with a central stratified permuted block r and omisation procedure . We r and omly assigned patients with resected ( R0 ) stage III disease ( 1:1 ) to receive 12 cycles of FOLFOX4 twice a week with or without cetuximab . Patients were stratified by N-status ( N1 vs N2 ) , T-status ( T1 - 3 vs T4 ) , and obstruction or perforation status ( no obstruction and no perforation vs obstruction or perforation or both ) . A protocol amendment ( applied in June , 2008 , after 2096 patients had been r and omly assigned to treatment-restricted enrolment to patients with tumours wild-type at codons 12 and 13 in exon 2 of the KRAS gene ( KRAS exon 2 wild-type ) . The primary endpoint was DFS . Analysis was intention to treat in all patients with KRAS exon 2 wild-type tumours . The study is registered at EudraCT , number 2005 - 003463 - 23 . FINDINGS Between Dec 22 , 2005 , and Nov 5 , 2009 , 2559 patients from 340 sites in Europe were r and omly assigned . Of these patients , 1602 had KRAS exon 2 wild-type tumours ( intention-to-treat population ) , 791 in the FOLFOX4 plus cetuximab group and 811 in the FOLFOX4 group . Median follow-up was 3·3 years ( IQR 3·2 - 3·4 ) . In the experimental and control groups , DFS was similar in the intention-to-treat population ( hazard ratio [ HR ] 1·05 ; 95 % CI 0·85 - 1·29 ; p=0·66 ) , and in patients with KRAS exon 2/BRAF wild-type ( n=984 , HR 0·99 ; 95 % CI 0·76 - 1·28 ) or KRAS exon 2-mutated tumours ( n=742 , HR 1·06 ; 95 % CI 0·82 - 1·37 ) . We noted heterogeneous responses to the addition of cetuximab in preplanned subgroup analyses . Grade 3 or 4 acne-like rash ( in 209 of 785 patients [ 27 % ] vs four of 805 [ < 1 % ] ) , diarrhoea ( 113 [ 14 % ] vs 70 [ 9 % ] ) , mucositis ( 63 [ 8 % ] vs 10 [ 1 % ] ) , and infusion-related reactions ( 55 [ 7 % ] vs 30 [ 4 % ] ) were more frequent in patients treated with FOLFOX4 plus cetuximab than in those patients who received FOLFOX4 alone . INTERPRETATION The addition of cetuximab to FOLFOX4 did not improve DFS compared with FOLFOX4 alone in patients with KRAS exon 2 wild-type resected stage III colon cancer . This trial can not conclude on the benefit of cetuximab in the studied population , but the heterogeneity of response suggests that further investigation of the role of FOLFOX4 plus cetuximab in specific patient subgroups is warranted . FUNDING Fédération Francophone de Cancérologie Digestive ( FFCD ) , Merck KGaA , and Sanofi-Aventis |
12,309 | 29,162,558 | This study may provide surgical treatment effects evidence for SHFC . | BACKGROUND The treatment of supracondylar humerus fracture in children ( SHFC ) is associated with complications such as functional deficit , residual deformity , and iatrogenic neurological damage .
The st and ard treatment is closed reduction and percutaneous Kirschner wire fixation with different configurations .
Despite this fact , there is still no consensus on the most effective technique for the treatment of these fractures .
OBJECTIVE The aim of this systematic review will be to evaluate the effect of surgical interventions on the treatment of Gartl and type II and III SHFC by assessing function , complications , and error as primary outcomes .
Clinical outcomes such as range of motion and pain and radiographic outcomes will also be judged . | A linear analogue for rating pain with 10 , 15 and 20 cm lines is significantly less variable than a 5 cm line ( mean error of 15 cm line is 0 - 19 % , 95 % confidence limits for the group + /- 2 % and an inood correlation between repeated ratins of a recalled pain distant in time . The variance of the rating is significantly less than the repeated rating of a r and om mark . The linear analogue rating of a constant pain stimulus is reproducible and changes in rating are likely to be real changes of opinion . Pethidine 150 mg intramuscularly had no significant effect , tested 30 minutes after the administration , on the accuracy or reproducibility of the analogue rating . A linear analogue seems a suitable method of recording the patient 's opion of a severe pain such as that of labour Controversy exists concerning pin placement for supracondylar humerus fractures in children . Both crossed pin and lateral only pin configurations have shown good results ; however , prospect i ve studies are lacking . We present a prospect i ve , surgeon-r and omized study comparing crossed pin ( group A , n = 20 ) versus preferential lateral only pin ( group B , n = 20 ) fixation for displaced supracondylar humerus fractures . There was no difference in Baumann 's angle ( P>0.75 ) , the humerotrochlear angle ( P>0.85 ) , or final elbow range of motion ( P>0.25 ) . Both groups had stable reductions and clinical ly normal alignment . The only complication in both groups was a transient ulnar nerve irritation , despite no intraoperative evidence of nerve violation with a nerve stimulator . One patient in each group required modification of the operative plan . In group B , one patient had a medial pin inserted because of medial comminution extending proximally limiting available lateral pin placement . In group A , the surgeon elected to use lateral pins only because of an obviously subluxating ulnar nerve . In conclusion , we recommend orthopedic surgeons treating unstable pediatric supracondylar humerus fractures be facile with both medial and lateral pin placement INTRODUCTION Closed reduction and percutaneous pinning are the most widely used treatment options for displaced supracondylar humerus fractures in children , but there is still no consensus concerning the most preferred technique in injuries of the extension type . OBJECTIVE The aim of this study was to compare three common orthopaedic procedures in the treatment of displaced extension type supracondylar humerus fractures in children . METHODS Total of 93 consecutive patients ( 66 boys and 27 girls ) referred to our hospital with Gartl and type II or III extension supracondylar humeral fractures were prospect ively included in the study over a six-year period . At initial presentation 48 patients were classified as Gartl and type II and 45 as Gartl and type III fractures . The patients were subdivided into three groups based on the following treatment modality : closed reduction with percutaneous pinning , open reduction with Kirschner wires ( K-wires ) fixation , and closed reduction with cast immobilisation . The treatment outcome and clinical characteristics were compared among groups , as well as evaluated using Flynn 's criteria . RESULTS Excellent clinical outcome was reported in 70.3 % of patients treated with closed reduction with percutaneous pinning and in 64.7 % of patients treated with open reduction with K-wire fixation . The outcome was significantly worse in children treated with closed reduction and cast immobilisation alone , as excellent outcome is achieved in just 36.4 % of cases ( p = 0.011 ) . CONCLUSION Closed reduction with percutaneous pinning is the method of choice in the treatment of displaced pediatric supracondylar humeral fracture , while open reduction with K-wire fixation is as a good alternative in cases with clear indications |
12,310 | 26,831,727 | Conclusion Professionally applied 5 % sodium fluoride varnish can remineralise early enamel caries and 38 % silver diamine fluoride is effective in arresting dentine caries | Background As a low-cost and easily operated treatment , the use of professionally applied topical fluoride was approved for preventing dental caries and remineralising early enamel caries or white spot lesions .
It is also used to arrest dentine caries .
The aim of this study is to investigate the clinical efficacy of professional fluoride therapy in remineralising and arresting caries in children . | PURPOSE This study 's purpose was to test silver diammine fluoride ( SDF ) in arresting incipient occlusal caries in erupting permanent first molars and to compare it with other approaches . METHODS Sixty-six first erupting permanent molars were r and omly divided into 3 groups : cross tooth-brushing technique ( CTT ) , application of SDF , and glass ionomer fissure sealant ( GIC ) . The clinical procedures were conducted by the same dentist . Teeth were assessed clinical ly by 1 blinded examiner using visual inspection at baseline and after 3 , 6 , 12 , 18 , and 30 months and radiographically at 6- , 12- , and 30-month follow-up evaluations . The Kruskall-Wallis test was used to compare noninvasive treatments , and the Friedman test was performed to evaluate differences for each group during different follow-up periods . RESULTS A reduced number of active caries lesions was noted in all groups . After 3 and 6 months , SDF showed a significantly greater capacity for arresting caries lesions than CTT and GIC . At 18- and 30-month evaluations , no differences were observed among the 3 groups . All groups showed differences between baseline and all follow-up re-examinations . CONCLUSIONS All the tested techniques are equally efficient in controlling initial occlusal caries in erupting permanent first molars after 30-months of follow-up The aim of this double-blind r and omized clinical trial was to evaluate the efficacy of 1.23 % APF gel application on the arrest of active incipient carious lesions in children . Sixty 7- to 12-year-old children , with active incipient lesions were included in the study . Children were divided r and omly into 2 groups : 1.23 % APF gel and placebo gel applications . Each group received 8 weekly applications of treatment . The lesions were re-evaluated at the 4th and 8th appointments . Poisson regression analysis was used to estimate relative risks of the presence of active white spot lesions . Groups showed similar results ( PR = 1.67 ; CI 95 % 0.69 - 3.98 ) . The persistence of at least 1 active lesion was associated with a higher number of lesions in the baseline ( PR = 2.67 ; CI 95 % 1.19 - 6.03 ) , but not with sugar intake ( PR = 1.06 ; CI 95 % 0.56 - 2.86 ) and previous exposure to fluoride dentifrice ( PR = 1.26 ; CI 95 % 0.49 - 2.29 ) . The trial demonstrates the equivalence of the treatments . The use of the APF gel showed no additional benefits in this sample of children exposed to fluori date d water and dentifrice . The professional dental plaque removal in both groups may also account for the result ing equivalence of the treatments OBJECTIVE To compare the effectiveness of annual topical application of silver diamine fluoride ( SDF ) solution , semi-annual topical application of SDF solution , and annual application of a flowable high fluoride-releasing glass ionomer in arresting active dentine caries in primary teeth . METHODS A total of 212 children , aged 3 - 4 years , were r and omly allocated to one of three groups for treatment of carious dentine cavities in their primary teeth : Gp1-annual application of SDF , Gp2-semi-annual application of SDF , and Gp3-annual application of glass ionomer . Follow-up examinations were carried out every six months to assess whether the treated caries lesions had become arrested . RESULTS After 24 months , 181 ( 85 % ) children remained in the study . The caries arrest rates were 79 % , 91 % and 82 % for Gp1 , Gp2 and Gp3 , respectively ( p=0.007 ) . In the logistic regression model using GEE to adjust for clustering effect , higher caries arrest rates were found in lesions treated in Gp2 ( OR=2.98 , p=0.007 ) , those in anterior teeth ( OR=5.55 , p<0.001 ) , and those in buccal/lingual smooth surfaces ( OR=15.6 , p=0.004 ) . CONCLUSION Annual application of either SDF solution or high fluoride-releasing glass ionomer can arrest active dentine caries . Increasing the frequency of application to every 6 months can increase the caries arrest rate of SDF application . CLINICAL SIGNIFICANCE Arrest of active dentine caries in primary teeth by topical application of SDF solution can be enhanced by increasing the frequency of application from annually to every 6 months , whereas annual paint-on of a flowable glass ionomer can also arrest active dentine caries and may provide a more aesthetic outcome Background Dental caries is a major public health problem in many countries . Since the last territority-wide dental survey of Hong Kong preschool children was conducted in 2001 , a survey to up date the information is necessary . This study aim ed to describe the dental caries experience of preschool children in Hong Kong and factors affecting their dental caries status . Methods A stratified r and om sample of children from seven kindergartens in Hong Kong was surveyed in 2009 . Ethical approval from IRB and parental consent was obtained . Clinical examinations of the children were performed by two calibrated examiners using disposable dental mirrors , an intra-oral LED light and ball-ended periodontal probes . A question naire to investigate possible explanatory factors for caries status was completed by the children ’s parents . Caries experience was recorded using the dmft index . Multifactor-ANOVA was used to study the relationship between dental caries experience , and the background and oral health-related behaviours of the children . Results Seven hundred children ( 53 % boys ) , mean age 5.3 ± 0.7 years were examined . The mean dmft score of the surveyed children was 2.2 and 51 % of them had no caries experience ( dmft = 0 ) . Most ( > 95 % ) of the decayed teeth were untreated . Statistically significant correlations were found between dental caries experience of the children and their oral health-related habits , family income , parental education level and parental dental knowledge . Conclusions Early childhood dental caries was prevalent among the preschool children in Hong Kong . Their caries experience was associated with their oral health-related behaviours , socio-economic background , and parental education and dental knowledge Arresting Caries Treatment ( ACT ) has been proposed to manage untreated dental caries in children . This prospect i ve r and omized clinical trial investigated the caries-arresting effectiveness of a single spot application of : ( 1 ) 38 % silver diamine fluoride ( SDF ) with tannic acid as a reducing agent ; ( 2 ) 38 % SDF alone ; ( 3 ) 12 % SDF alone ; and ( 4 ) no SDF application in primary teeth of 976 Nepalese schoolchildren . The a priori null hypothesis was that the different treatments have no effect in arresting active cavitated caries . Only the single application of 38 % SDF with or without tannic acid was effective in arresting caries after 6 months ( 4.5 and 4.2 mean number of arrested surfaces ; p < 0.001 ) , after 1 year ( 4.1 and 3.4 ; p < 0.001 ) , and after 2 years ( 2.2 and 2.1 ; p < 0.01 ) . Tannic acid conferred no additional benefit . ACT with 38 % SDF provides an alternative when restorative treatment for primary teeth is not an option The aim of this r and omized clinical trial study was to evaluate the therapeutic effect of two varnish formulations ( G1 = 5 % NaF , G2 = 6 % NaF + 6 % CaF(2 ) ) on the remineralization of white spot lesions ( WSL ) . The sample was composed of 15 ( 7- to 12-year-old ) children with 45 active WSL in anterior permanent teeth . The children were r and omly divided into two groups providing 22 lesions for G1 and 23 for G2 . The children were su bmi tted to weekly varnish applications 4 times . The WSL were evaluated twice : baseline and on week 4 . Maximum lesion dimensions ( mesiodistal and incisogingival ) were measured in millimeters and classified in four grade s of size . WSL were also assessed regarding lesion activity by one calibrated examiner . The Pearson chi-square and Fisher 's exact tests were used ( P < 0.01 ) . WSL reductions were observed in both varnish groups ( Chi-square = 0.15 , d.f . = 1 , P = 0.90 ) , and with similar magnitude ( in mm ) : 1.19 and 1.29 for G1 and G2 , respectively . Thirty-six WSL ( 15 in G1 and 21 in G2 ) were classified as inactive on week 4 , reaching an overall value of 80 % . No difference was observed between G1 and G2 regarding activity scores ( Fisher 's exact test , p > 0.01 ) . It was concluded that after 4 applications the two varnish formulations tested produced similar clinical effects , indicating the reduction and the control of carious activity in most WSL AIM The aim of this study is to assess the effects of fluoride varnishes on enamel caries lesions on permanent dentition . MATERIAL S AND METHODS 92 children from primary school ( Vasil Shanto , Tirana , Albania ) aged 11 - 12 years were divided into varnish ( experimental ) and control group . The experiment group received the first fluoride varnish application ( Fluoridin , Voco ) at baseline , the second application after 3 months and the third application at 6 months from baseline , while the children in the control group received no professional fluoride application . Examinations were performed at baseline and after 7 months . RESULTS We observed a slight increase in caries prevalence in the control group compared with the varnish group at the 7 month interval ( P < 0.1 for DMFT and P < 0.5 for DMFS and DS ) . When enamel lesions were included the mean of DeMFT , DeMFS , DeS the caries prevalence was significantly lower in the varnish group after 7 months ( P < 0.001 for DeMFT , DeMFS ) . CONCLUSION Fluoride varnish is an effective mean for arresting early enamel lesions . It is a safe , convenient and well accepted method by patients The aim of this study was to assess in vivo the therapeutic effect of three fluoride varnishes available in the Brazilian market on the performance of white spot lesions ( WSL ) . The sample included 36 children aged 7 to 13 years old , with a total of 67 active WSL in permanent anterior teeth . The children were r and omly divided into 3 groups , according to fluoride varnish used : FL- Fluorniz ( n=24 ) , DUO - Duofluorid XII ( n=22 ) and DF - Durafluor ( n=21 ) . Maximum WSL dimensions ( mesiodistal and incisogingival ) were measured in millimeters by a previously calibrated single examiner using a periodontal probe . WSL were also assessed regarding lesion activity . Initial and final S-OHI ( Simplified Oral Hygiene Index ) scores were recorded . Pearson 's chi-square test revealed no statistically significant differences ( p>0.05 ) in the performance of the varnishes . At the end of the 5th week , FL had 6 active and 18 inactive WSL ; DUO had 7 active and 15 inactive WSL ; and DL had 6 active and 15 inactive WSL . Taking into account all lesions , there was a 45.7 % reduction in WSL dimensions . Paired Student 's t-test revealed a statistically significant difference ( p<0.05 ) between the initial size ( 1.88 ) and final size ( 1.02 ) . After four applications , all varnishes obtained similar clinical results Objective To describe the dental caries status of preschool children in Hong Kong and factors which affect their caries status . Design 658 preschool children aged 4 to 6 years from six r and omly selected kindergartens in Hong Kong were surveyed in December 1997 . A question naire to investigate possible explanatory variables for caries status was completed by their parents . Dental caries was diagnosed according to the criteria recommended by the World Health Organization ( 1997 ) . Result Caries experience as measured by the mean number of decayed , missing and filled primary teeth ( dmft ) of the 4- , 5- , and 6-year-old children were found to be 0.9 , 1.8 , and 3.3 respectively . Overall , 61 % of the children had a zero dmft score . Children born in Mainl and China had a higher mean dmft score ( 4.6 ) than those born in Hong Kong ( 1.4 ) . Statistically significant correlations were found between the children 's dental caries status and their oral health practice s as well as their socio-economic background . Parents ' education level , dental knowledge and attitudes were also associated with the children 's dental caries experience . Conclusion In general , the caries status of Hong Kong Chinese preschool children was similar to that of children in industrialised countries and was better than that of children in the nearby areas . However , special dental programmes should be made available to children from lower socio-economic classes and new immigrants from Mainl and China because they are the high risk groups for caries in Hong Kong BACKGROUND Plaque control and caries arrest still remain a challenge for dentists . OBJECTIVE This study was conducted to assess the effect of the combined use of chlorhexidine varnish and fluoride varnish on the visible plaque index ( VPI ) and white spot lesion ( WS ) remineralization in primary dentition . METHODS A total of 80 caries-active preschool children ( 3 - 5 years ) were r and omly divided into four groups . Group 1 received a chlorhexidine varnish application every week during 4 weeks . Group 2 received a fluoride varnish application every week during 4 weeks . Group 3 received alternated applications of chlorhexidine and fluoride varnish during 4 weeks . Group 4 served as control ( without any type of cariostatic agent ) . RESULTS There was no statistically significant difference in the VPI and WS remineralization among the groups after 1 month . However , 3 months follow-up demonstrated that group 3 ( chlorhexidine + fluoride ) showed significantly better results for both VPI and WS remineralization . CONCLUSION The combined application of chlorhexidine and fluoride varnishes is more effective on plaque and remineralization of incipient caries after 3 months than the same agents applied separately The aim of this study was to apply the quantitative light-induced fluorescence ( QLF ) method in a r and omised controlled study , comparing treatment with fluoride varnish and professional tooth cleaning for remineralisation of white spot lesions in caries-active adolescents . In the fluoride varnish group ( n = 13 ; 32 lesions ) , professional tooth-cleaning was followed by application of fluoride varnish at the beginning of the study , after 1 wk , and then once every 6 wk for 6 months . The other group ( n = 18 ; 30 lesions ) underwent professional tooth-cleaning once every 6 wk for 6 months . Enamel fluorescence was measured at baseline and at each visit . In the fluoride varnish group there was a significant change over time ( baseline : 6 months ) for both lesion area : and average change in fluorescence ( decreased lesion area and increased fluorescence radiance ) . The corresponding changes in the professional tooth-cleaning group were not significant . There was a significant difference in average change in fluorescence between the two test groups . For lesion area , there was no significant difference , but a tendency towards a difference between the test groups . It was concluded that ( a ) the QLF method is a sensitive method , suitable for longitudinal quantification of incipient caries lesions on smooth surfaces ; and ( b ) that repeated fluoride applications had a favourable effect on the remineralisation of white spot lesions as measured after 6 months BACKGROUND Silver diamine fluoride ( SDF ) is an effective agent for the arrest of caries in children , is easy to apply and can be used outside the clinical environment . Interim restorative treatment ( IRT ) using glass ionomer cement has also been cl aim ed to be a simple and effective method to arrest caries in deciduous teeth . OBJECTIVE To examine whether , for underprivileged schoolchildren with cavities , treatment with 30 % SDF gives better results than IRT for carries arrest . METHOD This r and omised controlled study compares the effect of IRT ( FUJI IX ) with 30 % SDF in 91 children aged 5 - 6 years . RESULTS After 1 year , treatment with SDF was more effective [ relative risk ( RR ) = 66.9 % ] than IRT ( RR = 38.6 % ) for the arrest of caries ; this was statistically significant ( P < 0.05 ) . CONCLUSION The SDF technique showed better results than IRT for the arrest of cavities in deciduous teeth , indicating that its use for underprivileged communities may justify a paradigm shift in paediatric dentistry The purpose of this study was to determine the efficacy of fluoride varnish ( 5 % sodium fluoride , Duraphat ® , Colgate ) in reverting white spot lesions ( WSLs ) after fixed orthodontic treatment . This study was a r and omized , parallel group , controlled clinical trial . Using saline solution as control , 110 participants ( mean age ± st and ard deviation : 16.6 ± 3.2 years ) ranging from 12 to 22 years old were r and omly assigned to either the test group ( group 1 ) or the control group ( group 2 ) . Application of fluoride varnish or saline was applied onto tooth surfaces with WSLs every month during the first 6 months after debonding . The labial ( buccal ) surfaces of the teeth were assessed by the use of a DIAGNOdent pen ( DD ) at the baseline , 3- and 6-month follow-up visits . After 6 months , 96 subjects with a total of 209 study teeth ( 47 subjects , 104 teeth in group 1 ; 49 subjects , 105 teeth in group 2 ) remained . The WSLs had a mean DD reading at baseline of 17.66 ± 5.36 in group 1 and 16.19 ± 5.70 in group 2 , which decreased by 5.78 and 2.44 , respectively , at the 3-month follow-up visit and decreased by 7.56 and 3.09 , respectively , at the 6-month follow-up visit . The mean baseline DD readings in the two groups were similar ( t test , P > 0.05 ) . There was statistically significant differences between the mean DD readings of the two groups at the 3-month ( P < 0.05 ) and at the 6-month follow-up visits ( P < 0.01 ) . Topical fluoride varnish application is effective in reversing WSLs after debonding and should be advocated as a routine caries prevention measure after orthodontic treatment Untreated dental caries in Chinese pre-school children is common . This prospect i ve controlled clinical trial investigated the effectiveness of topical fluoride applications in arresting dentin caries . Three hundred seventy-five children , aged 3 - 5 years , with carious upper anterior teeth were divided into five groups . Children in the first and second groups received annual applications of silver diamine fluoride solution ( 44,800 ppm F ) . Sodium fluoride varnish ( 22,600 ppm F ) was applied every three months to the lesions of children in the third and fourth groups . For children in the first and third groups , soft carious tissues were removed prior to fluoride application . The fifth group was the control . Three hundred eight children were followed for 30 months . The respective mean numbers of arrested carious tooth surfaces in the five groups were 2.5 , 2.8 , 1.5 , 1.5 , and 1.3 ( p < 0.001 ) . Silver diamine fluoride was found to be effective in arresting dentin caries in primary anterior teeth in pre-school children BACKGROUND The aim of this study was to evaluate the effect of fluoride varnish on enamel caries progression in the primary dentition . METHODS One hundred forty-two children in Head Start schools ( 3 to 5 years old ) were r and omized into the varnish and control groups . Children in the varnish group received fluoride varnish ( Duraphat , Colgate-Palmolive Co. ) at baseline and after four months , and children in the control group received no professional fluoride applications . Two calibrated examiners performed the examinations at baseline and at nine months . RESULTS At nine months , the authors found that in the control group , 37.8 percent of active enamel lesions on occlusal , buccal and lingual surfaces became inactive , 3.6 percent progressed and 36.9 percent did not change . In the varnish group , 81.2 percent became inactive , 2.4 percent progressed and 8.2 percent did not change . The difference between the groups was statistically significant ( P < .0001 ) . The mean decayed surfaces , or ds , value in the varnish group was significantly lower after nine months than it was at baseline ( P < .0001 ) . When enamel lesions were included in the data analysis ( along with dentinal lesions ) , the decayed with initial enamel lesions , missing and filled surfaces , or dEmfs , values ; decayed with initial enamel lesions , missing and filled teeth , or dEmft , values ; and decayed surfaces with initial enamel lesions , or dEs , values were significantly lower in the varnish group after nine months than they were at baseline ( P < .0001 ) . CONCLUSIONS These results suggest that fluoride varnish applications may be an effective measure in reversing active pit- and -fissure enamel lesions in the primary dentition . CLINICAL IMPLICATION S Fluoride varnishes are safe , easy to apply and well-accepted by patients . This study shows that fluoride varnish may offer an efficient , nonsurgical alternative for the treatment of decay in children We hypothesized that the six-monthly application of silver diamine fluoride ( SDF ) can arrest the development of caries in the deciduous dentition of six-year-old schoolchildren and prevent caries in their first permanent molars . A prospect i ve controlled clinical trial was conducted on the efficacy of a 38 % SDF solution for caries reduction . Four hundred and twenty-five six-year-old children were divided into two groups : One group received SDF solution in primary canines and molars and first permanent molars every 6 mos for 36 mos . The second group served as controls . The 36-month follow-up was completed by 373 children . The mean number of new decayed surfaces appearing in primary teeth during the study was 0.29 in the SDF group vs. 1.43 in controls . The mean of new decayed surfaces in first permanent molars was 0.37 in the SDF group vs. 1.06 in controls . The SDF solution was found to be effective for caries reduction in primary teeth and first permanent molars in schoolchildren OBJECTIVE To describe the prevalence of dental caries among Jordanian preschool children and risk factors for caries . DESIGN Preschool children aged 1 to 5 years from r and omly selected nurseries and kindergartens in Amman were surveyed in September 2001 . A question naire to investigate factors that might have affected dental caries level was completed by parents . Dental caries was diagnosed as recommended by the World Health Organization . RESULTS The mean dmft scores at 1 , 2 , 3 , 4 , and 5 years were 0.19 , 1.15 , 1.7 , 2.13 , and 3.22 respectively . Overall , 52 % of children were caries-free . Caries level was significantly related to feeding practice s , snacking habits , oral health practice s and pattern of dental visiting as well as to socio-economic background , parents , education level and awareness . CONCLUSION The dental caries level was slightly higher than that of children in industrialised countries but lower than that of children in the neighbouring Arab countries . However , the early caries development seen in children from the lower socio-economic classes , because they are at high risk for caries in Jordan , reinforces the need for preventive programmes before eruption of the teeth . Access to dental care must be improved to enable any preventive strategies to be implemented Objectives : Fluoride varnish ( FV ) is efficacious in caries prevention although its effects among different tooth surfaces are poorly understood . This study sought to determine the extent to which caries-preventive effects of a community intervention that included FV application among preschool-aged children varied according to primary tooth anatomy and baseline tooth pathology . Methods : Secondary analysis was undertaken of data from a community-r and omized controlled trial among 543 3- to 5-year-old Aboriginal children in 30 Northern Territory Australian communities . Children in intervention communities received community health promotion and FV application once every 6 months . Net caries ( d3mfs ) risk and 95 % confidence limits ( CL ) were estimated for the control and intervention arms , and stratified according to tooth anatomy/location and baseline pathology ( sound , enamel opacity , hypoplastic defect or precavitated carious lesion ) . The intervention ’s efficacy was quantified using generalized estimating equation modeling accounting for study design and clustering . The assumption of efficacy homogeneity was tested using a Wald χ2 test with a p < 0.2 criterion and post hoc pairwise comparisons . Results : The intervention result ed in a 25 % reduction ( relative risk , RR = 0.75 ; 95 % CL = 0.71 , 0.80 ) in the 2-year surface-level caries risk . There was substantial heterogeneity in FV efficacy by baseline surface pathology : RRs were 0.73 for sound , 0.77 for opaque , 0.90 for precavitated , and 0.92 for hypoplastic surfaces . Among sound surfaces , maxillary anterior facials received significantly more benefit ( RR = 0.62 ) compared to pits and fissures ( RR = 0.78 ) . Conclusion : The intervention had greatest efficacy on surfaces that were sound at baseline . Among those sound surfaces , maxillary anterior facials received most caries-preventive benefit Dental caries in Chinese pre-school children is common , and restorative treatment is not readily available . This prospect i ve controlled clinical trial investigated the effectiveness of topical fluoride applications in arresting dentin caries . We divided 375 children ( aged 3 - 5 yrs ) with carious upper anterior teeth into five groups . Children in the first and second groups received annual applications of silver diamine fluoride solution ( 44,800 ppm F ) . NaF varnish ( 22,600 ppm F ) was applied every three months onto the lesions of children in the third and fourth groups . For children in the first and third groups , soft carious tissues were removed prior to fluoride application . The fifth group was the control . We followed 341 children for 18 months . The mean numbers of new caries surfaces in the five groups were 0.4 , 0.4 , 0.8 , 0.6 , and 1.2 , respectively ( p = 0.001 ) . The respective mean numbers of arrested carious tooth surfaces were 2.8 , 3.0 , 1.7 , 1.5 , and 1.0 ( p < 0.001 ) BACKGROUND Untreated dental caries in children remains a public health challenge in poor communities . OBJECTIVES This prospect i ve controlled clinical trial investigated the effectiveness of a new anti-caries agent , Nano Silver Fluoride ( NSF ) , applied once a year to arrest caries in children . METHODS One hundred thirty decayed primary teeth were r and omly divided into two groups : NSF as the experimental agent and water as the control group . Teeth were clinical ly diagnosed and treated by one masked examiner and followed up at seven days and five and 12 months by another calibrated examiner who was blinded to the type of treatment . The criteria of the ICDAS II were followed to determine the activity of lesion and the diagnosis of caries . The Pearson 's chi-square test was used to compare the groups during different follow-up exams . RESULTS At seven days , 81 % of teeth in the NSF group exhibited arrested caries , whereas in controls , no teeth had arrested decay ( p<0.001 ) [ PF , prevented fraction=81 % ] . After five months , the NSF group had 72.7 % with arrested decay , and the control group had 27.4 % ( p<0.001 ) [ PF=62.5 % ] . At 12 months , 66.7 % of the lesions treated with NSF were still arrested , while the control group had 34.7 % remaining arrested ( p=0.003 ) [ PF=50 % ] . The number need to treat ( NNT ) at five months was two , and at 12 months , the number was three . CLINICAL SIGNIFICANCE The NSF formulation is effective to arrest active dentine caries and not stain teeth . CONCLUSIONS NSF was demonstrated to be effective in arresting caries in children in poor communities |
12,311 | 27,150,294 | It was not possible to discern any association between particular intervention characteristics and family carer outcomes .
Current evidence is limited , but overall suggests face-to-face educational interventions supported by written and /or other re sources have potential to improve carers ' knowledge and self-efficacy for pain management . | BACKGROUND Family carers play a significant role in managing pain and associated medicines for people with advanced cancer .
Research indicates that carers often feel inadequately prepared for the tasks involved , which may impact on carers ' and patients ' emotional state as well as the achievement of optimal pain control .
However , little is known about effective methods of supporting family carers with cancer pain medicines .
AIMS To systematic ally identify and review studies of interventions to help carers manage medicines for pain in advanced cancer .
To identify implication s for practice and research . | Objective To evaluate the process of implementation of the modified London Stroke Carers Training Course ( LSCTC ) in the Training Caregivers After Stroke ( TRACS ) cluster r and omised trial and contribute to the interpretation of the TRACS trial results . The LSCTC was a structured competency-based training programme design ed to help develop the knowledge and skills ( eg , patient h and ling or transfer skills ) essential for the day-to-day management of disabled survivors of stroke . The LSCTC comprised 14 components , 6 were m and atory ( and delivered to all ) and 8 non-m and atory , to be delivered based on individual assessment of caregiver need . Design Process evaluation using non-participant observation , documentary analysis and semistructured interviews . Participants Patients with stroke ( n=38 ) , caregivers ( n=38 ) , stroke unit staff ( n=53 ) . Setting s 10 of the 36 stroke units participating in the TRACS trial in four English regions ( Yorkshire , North West , South East and South West , Peninsula ) . Results Preparatory cascade training on delivery of the LSCTC did not reach all staff and did not lead to multidisciplinary team ( MDT ) wide underst and ing of , engagement with or commitment to the LSCTC . Although senior therapists in most intervention units observed developed ownership of the LSCTC , MDT working led to separation rather than integration of delivery of LSCTC elements . Organisational features of stroke units and professionals ’ patient-focused practice s limited the involvement of caregivers . Caregivers were often invited to observe therapy or care being provided by professionals but had few opportunities to make sense of , or to develop knowledge and stroke-specific skills provided by the LSCTC . Where provided , caregiver training came very late in the inpatient stay . Assessment and development of caregiver competence was not commonly observed . Conclusions Context ual factors including service improvement pressures and staff perceptions of the necessity for and work required in caregiver training impacted negatively on implementation of the caregiver training intervention . Structured caregiver training programmes such as the LSCTC are unlikely to be practical in setting s with short inpatient stays . Stroke units where early supported discharge is in place potentially offer a more effective vehicle for introducing competency based caregiver training . LINKED TRACS Cluster r and omised controlled trial number IS RCT N49208824 The adoption of evidence -based hierarchies and research methods from other disciplines may not completely translate to complex palliative care setting s. The heterogeneity of the palliative care population , complexity of clinical presentations , and fluctuating health states present significant research challenges . The aim of this narrative review was to explore the debate about the use of current evidence -based approaches for conducting research , such as r and omized controlled trials and other study design s , in palliative care , and more specifically to ( 1 ) describe key myths about palliative care research ; ( 2 ) highlight substantive challenges of conducting palliative care research , using case illustrations ; and ( 3 ) propose specific strategies to address some of these challenges . Myths about research in palliative care revolve around evidence hierarchies , sample heterogeneity , r and om assignment , participant burden , and measurement issues . Challenges arise because of the complex physical , psychological , existential , and spiritual problems faced by patients , families , and service providers . These challenges can be organized according to six general domains : patient , system/organization , context / setting , study design , research team , and ethics . A number of approaches for dealing with challenges in conducting research fall into five separate domains : study design , sampling , conceptual , statistical , and measures and outcomes . Although r and omized controlled trials have their place whenever possible , alternative design s may offer more feasible research protocol s that can be successfully implemented in palliative care . Therefore , this article highlights " outside the box " approaches that would benefit both clinicians and research ers in the palliative care field . Ultimately , the selection of research design s is dependent on a clearly articulated research question , which drives the research process The aim of this editorial is to highlight several research priorities and key implication s for policy and practice that inform an agenda to improve family carer support . The development of systematic approaches to identify carers who are at risk of poor psychosocial outcomes is a priority . Family caregiving should not be pathologised as an inherently negative experience ; however , it would be a breach of care if more than 40 % of carers who appear to meet the criteria for psychological distress1 are not offered suitable supports . Related to this is the urgent need for greater investment in bereavement research ; while bereavement support is integral to palliative care , it is typically under-re source d , under-investigated and not systematic ally applied . We know that routine intervention for all bereaved carers is not warranted . The challenge is to discern those carers who are ‘ at risk ’ prior to the death of the patient and to identify suitable evidence -based strategies to assist them . Research indicates that carer re sources , rather than patient diagnosis or illness severity , are the primary predictors of carer burden and other carer outcomes . This implies that although the specific content may need to vary to suit the context , the core elements of family carer interventions may be relevant across disease groups . It is also apparent that the perceived quality of social support is more important than the size of the social network in improving carer outcomes .2 Current indications are that palliative care providers should assist carers by targeting social support and re sources and provide education that focuses on coping strategies and preparation for the carer role . In many countries , family carers are well prepared for the beginning of life when , for example , prospect i ve parents are routinely offered parenting classes . It is also not uncommon to assist carers prepare for and support relatives having major heart surgery . However , preparation for supporting a relative/ friend at the end of their life is not routinely offered . Carers typically want to know what the role entails , how to manage symptoms , signs of imminent death and re sources and strategies to sustain their own well-being . Given the majority of patients want to be cared for in their home environment , initiatives that assist carers to achieve this are needed . The period of time most people receive palliative care services is typically quite short ; hence , the challenge is to design interventions that are as brief as possible , readily accessible and easily delivered . The significant number of carers who support patients in the hospital/hospice setting should also not be neglected ; their needs are often hidden . Other valuable insights regarding how we deliver interventions are surfacing . For example , the conception that face-to-face carer support is the gold st and ard is being challenged . Emerging evidence suggests that telephone and video phone support may be equally effective in some circumstances.1,3 Emphasis on the development of a strategic , coordinated and priority-driven family carer research agenda is also important.4 The role of formal research collaborations may be a vehicle to foster this . Much of the carer research seems to be first-world centric . More attention needs to be directed towards family caregiving in under-re source d countries and in other under-represented population s such as ethnic minority groups . Several important policy and clinical matters warrant consideration if palliative care is to foster improved carer support . One of the core questions for policymakers and clinicians is whether or not it is feasible for palliative care to be expected to meet the needs of the patients ’ entire family . It has been recommended that given re source constraints , the focus should be on the primary family carer ( as identified by the patient ) and where possible extended to other family members.5 Consideration might also be given to revising expectations about the goal of family support . The current World Health Organization definition of palliative care advocates that families ’ quality of life be improved ; perhaps a more realistic objective may be to aim to reduce the psychosocial burden of primary family carers . A related question is how to effectively legitimise family carer support . Most family carers do not want to discuss their needs and concerns in front of their relative ; they therefore need one-to-one time with healthcare and socialcare professionals . It is also clear that many healthcare workers find supporting carers challenging . Hence , where pertinent , consideration should be given to the potential merits of officially recognising family carers as ‘ care recipients ’ ; therefore , they are formally acknowledged as ‘ worthy ’ within the healthcare system . This may help justify much needed re sources and allow healthcare workers to allocate time and where pertinent offer interventions . In 488855 PMJ27710.1177/0269216313488855Palliative MedicineEditorial CONTEXT Concerns about pain medications are major barriers to pain management in hospice , but few studies have focused on systematic methods to address these concerns . OBJECTIVES The objective of this study was to test the preliminary efficacy of the Effective Management of Pain : Overcoming Worries to Enable Relief ( EMPOWER ) intervention , which included hospice staff education , staff screening of barriers to pain management at admission , and discussion about misunderst and ings regarding pain management with family caregivers and patients . METHODS We conducted a pilot , cluster r and omized , controlled trial with four hospices . One hundred twenty-six family caregivers ( 55 interventions and 71 controls ) were interviewed at two weeks after admission . If patients survived three months after admission , caregivers were reinterviewed . RESULTS At two weeks , caregivers in the intervention group reported better knowledge about pain management ( P = 0.001 ) , fewer concerns about pain and pain medications ( P = 0.008 ) , and lower patient pain over the past week ( P = 0.014 ) and trended toward improvement in most other areas under study . Exploratory analyses suggest that EMPOWER had a greater effect for black subjects ( vs. whites ) on reducing concern about stigma . At three months , the intervention group trended better on most study outcomes . CONCLUSION EMPOWER is a promising model to reduce barriers to pain management in hospice The shift of health care burden from acute to chronic conditions is strongly linked to lifestyle and behaviour . As a consequence , health services are attempting to develop strategies and interventions that can attend to the complex interactions of social and biological factors that shape both . In this paper we trace one of the most influential incarnations of this ‘ turn to the complex ’ : the Medical Research Council ( MRC ) guidance on developing and evaluating complex interventions . Through an analysis of the key publications , and drawing on social scientific approaches to what might constitute complexity in this context , we suggest that such initiatives need to adjust their conceptualisation of ‘ the complex ’ . We argue that complexity needs to be understood as a dynamic , ecological system rather than a stable , albeit complicated , arrangement of individual elements . Crucially , in contrast to the experimental logic embedded in the MRC guidance , we question whether the R and omised Controlled Trial ( RCT ) is the most appropriate method through which to engage with complexity and establish reliable evidence of the effectiveness of complex interventions Background Being a family carer to a patient nearing the end of their life is a challenging and confronting experience . Studies show that caregiving can have negative consequences on the health of family carers including fatigue , sleep problems , depression , anxiety and burnout . One of the goals of palliative care is to provide psychosocial support to patients and families facing terminal illness . A systematic review of interventions for family carers of cancer and palliative care patients conducted at the start of this millennium demonstrated that there was a dearth of rigorous inquiry on this topic and consequently limited knowledge regarding the types of interventions likely to be effective in meeting the complex needs of family carers . We wanted to discern whether or not the evidence base to support family carers has improved . Furthermore , undertaking this review was acknowledged as one of the priorities for the International Palliative Care Family Carer Research Collaboration http://www.centreforpallcare.org . Methods A systematic review was undertaken in order to identify developments in family carer support that have occurred over the last decade . The focus of the review was on interventions that targeted improvements in the psychosocial support of family carers of palliative care patients . Studies were grade d to assess their quality . Results A total of fourteen studies met the inclusion criteria . The focus of interventions included psycho-education , psychosocial support , carer coping , symptom management , sleep promotion and family meetings . Five studies were r and omised controlled trials , three of which met the criteria for the highest quality evidence . There were two prospect i ve studies , five pre-test/post-test projects and two qualitative studies . Conclusions The systematic review identified a slight increase in the quality and quantity of psychosocial interventions conducted for family carers in the last decade . More rigorous intervention research is required in order to meet the supportive care needs of family carers of palliative care patients PURPOSE / OBJECTIVES To examine the impact of pain education on family members providing home care to elderly patients with cancer . DESIGN Quasiexperimental . SETTING Homes of selected patients from two California medical centers . SAMPLE Fifty family caregivers of patients experiencing cancer-related pain . METHODS The pain education program included three components : pain assessment , pharmacologic interventions , and nonpharmacologic interventions . Patients and their family caregivers were evaluated prior to initiation of the program and at one and three weeks following the interventions . MAIN RESEARCH VARIABLES Quality of life ( QOL ) ; knowledge and attitudes about pain ; and caregiver burden . FINDINGS Findings based on measures of QOL and caregiver burden demonstrated the physical and psychological impact of family caregiving and pain management . Comparison between elderly patients with cancer and family caregivers revealed the pain experience 's significant impact on family members caring for a loved one in pain . CONCLUSIONS The pain education program was effective in improving knowledge and attitudes regarding pain management . IMPLICATION S FOR NURSING PRACTICE Pain management is a priority for nurses , and use of interventions such as structured pain education improves QOL outcomes for elderly patients and their family caregivers 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 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 CONTEXT Despite the increasing complexity of medication regimens for persistent cancer pain , little is known about how oncology out patients and their family caregivers manage pain medications at home . OBJECTIVES To describe the day-to-day management of pain medications from the perspectives of oncology out patients and their family caregivers who participated in a r and omized clinical trial of a psychoeducational intervention called the Pro-Self ( © ) Plus Pain Control Program . In this article , we focus on pain medication management in the context of highly individualized home environments and lifestyles . METHODS This qualitative study was conducted as part of a r and omized clinical trial , in which an embedded mixed methods research design was used . Audio-recorded dialogue among patients , family caregivers , and intervention nurses was analyzed using qualitative research methods . RESULTS Home and lifestyle context s for managing pain medications included highly individualized home environments , work and recreational activities , personal routines , and family characteristics . Pain medication management processes particularly relevant in these context s included underst and ing , organizing , storing , scheduling , remembering , and taking the medications . With the exception of their interactions with the intervention nurses , most study participants had little involvement with clinicians as they worked through these processes . CONCLUSION Pain medication management is an ongoing multidimensional process , each step of which has to be mastered by patients and their family caregivers when cancer treatment and supportive care are provided on an outpatient basis . Realistic patient- and family-centered skill-building interventions are needed to achieve effective and safe pain medication management in the context s of individual home environments and lifestyles Patient attitudes and knowledge regarding cancer pain and strong opioid analgesia can sometimes be a barrier to good pain control . Educational interventions that address these barriers are effective in oncology out patients but have not been evaluated in patients with more advanced disease . We assessed the feasibility of a r and omized , controlled clinical trial evaluating a brief DVD-based educational intervention for cancer pain in palliative care patients . Participants were shown DVD at baseline ( V1 ) and at 1 week ( V2 ) . Outcomes were assessed using Brief Pain Inventory ( BPI ) and Patient Pain Question naire ( PPQ ) before intervention , and at V2 and V3 ( 4 weeks later ) . Fifteen patients and 10 carers were recruited . Between V1 and V2 , total BPI and PPQ scores improved significantly by 9.6 % ( p = 0.02 ) and 17 % ( p = 0.04 ) respectively with no further improvements at V3 . Our findings suggest that this intervention is feasible and potentially effective between 7—30 days follow up . A multicentre clinical trial is now needed to evaluate this intervention further 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 OBJECTIVE To determine the efficacy in overcoming attitudinal barriers to reporting cancer pain and using analgesics of an educational intervention presented to patients accompanied by a significant other ( SO ) as compared with patients alone . DESIGN Patient-SO pairs ( N = 161 ) were r and omized to the dyad condition ( patient and SO received the intervention ) , solo condition ( patient received the intervention ) , or care as usual . Dyad and solo conditions received the intervention at baseline ( T1 ) and 2 and 4 weeks later . MAIN OUTCOME MEASURES Patients ' and SOs ' attitudes about analgesic use and patients ' pain outcomes ( pain severity , pain relief , interference with life , negative mood , and global quality of life [ QOL ] ) at T1 , 5 weeks later ( T2 ) , and 9 weeks later ( T3 ) . RESULTS Completers ' analyses revealed no significant differences between groups at T2 . At T3 , patients in the dyad and the solo groups showed greater decreases in attitudinal barriers as compared with controls . T1-T3 changes in patients ' barriers mediated between the dyad and solo interventions and pain severity , pain relief , pain interference , negative mood , and global QOL . CONCLUSION The intervention was no more efficacious when it was presented to dyads than to patients alone . Conditions under which SOs should be included in interventions need to be determined Background : The majority of cancer treatment is provided in outpatient setting s. Family caregivers ’ ( FCs ’ ) knowledge and beliefs about pain and its management are critical components of effective care . Objective : This study ’s aim was to evaluate the efficacy of a psychoeducational intervention , compared with control , to increase FCs ’ knowledge of cancer pain management . Intervention/ Methods : Family caregivers of oncology out patients were r and omized together with the patients into the PRO-SELF Pain Control Program ( n = 58 ) or a control group ( n = 54 ) . Family caregivers completed a demographic question naire and the Family Pain Question naire ( FPQ ) at the beginning and end of the study to assess their knowledge about pain and its management . The intervention consisted of nurse coaching , home visits , and phone calls that occurred over 6 weeks . Results : One hundred twelve FCs ( 60 % female ) with a mean age of 63 ( SD , 10.7 ) years participated . Compared with FCs in the control group , FCs in the PRO-SELF group had significantly higher knowledge scores on all of the single items on the FPQ , except for the item “ cancer pain can be relieved , ” as well as for the total FPQ score . Conclusion : The use of a knowledge and attitude survey like the FPQ , as part of a psychoeducational intervention provides an effective foundation for FC education about cancer pain management . Implication s for Practice : Oncology nurses can use FCs ’ responses to the FPQ to individualize teaching and spend more time on identified knowledge deficits . This individualized approach to FC education may save staff time and improve patient outcomes This article reports the first phase of a three-phase study to develop and test a pain education programme for family carers of patients with advanced cancer . The purpose of this phase was to develop the pain education programme . Interviews were conducted with 19 family carers to elicit their perceptions about the components , content , amount and timing of an educational programme that might be useful in educating them about pain management . Interviews were taped , transcribed and content analysed . Family carers reported knowledge deficits regarding pain , medications , comfort therapies and general comfort measures . Strategies for learning were described . Findings from these interviews together with results published in the literature were structured into a formal pain management programme . This programme has been pilot tested and evaluated using a r and omized clinical trial This preliminary study tested the efficacy of a partner-guided cancer pain management protocol for patients who are at the end of life . Seventy-eight advanced cancer patients meeting criteria for hospice eligibility and their partners were r and omly assigned to a partner-guided pain management training intervention , or usual care control condition . The partner-guided pain management training protocol was a three-session intervention conducted in patients ' homes that integrated educational information about cancer pain with systematic training of patients and partners in cognitive and behavioral pain coping skills . Data analyses revealed that the partner-guided pain management protocol produced significant increases in partners ' ratings of their self-efficacy for helping the patient control pain and self-efficacy for controlling other symptoms . Partners receiving this training also showed a trend to report improvements in their levels of caregiver strain . Overall , the results of this preliminary study suggest that a partner-guided pain management protocol may have benefits in the context of cancer pain at the end of life . Given the significance of pain at the end of life , future research in this area appears warranted |
12,312 | 21,660,557 | The combined results from 13 trials ( n = 589 ) determined that calcitonin significantly reduced the severity of acute pain in recent OVCFs .
Side effects were mild , with enteric disturbances and flushing reported most frequently .
Although calcitonin has proven efficacy in the management of acute back pain associated with a recent OVCF , there is no convincing evidence to support the use of calcitonin for chronic pain associated with older fractures of the same origin | Vertebral collapse is a common fracture associated with osteoporosis .
Subsequent pain may be severe and often requires medications and bed rest .
Several studies have suggested the use of calcitonin for the treatment of fracture pain .
We sought to determine the analgesic efficacy of calcitonin for acute and chronic pain of osteoporotic vertebral compression fractures ( OVCF ) . | Summary Back pain due to vertebral collapse is the main symptom of postmenopausal osteoporosis . The clinical picture in these crush fractures varies , depending on the type and the location of fracture , but in general , a new vertebral crush fracture gives rise to severe pain that immobilizes the patient and necessitates bedrest . In this double-blind controlled clinical trial , 56 patients who had recently ( within the last 3 days ) suffered an osteoporotic vertebral fracture were hospitalized for a period of 14 days . Salmon calcitonin ( 100 IU ) or placebo injections were given daily . Pain was rated daily on a 10-point scale by the same observers . Blood and urinary parameters were also evaluated . The results showed a significant ( P<0.001 ) difference in pain intensity between the calcitonin group and the placebo group . This beneficial effect was generally apparent from the second day of treatment onward , and over the following 2 weeks , the patients were able to sit and st and , and gradually started to walk again . A significant decrease in urinary hydroxyproline and urinary calcium was also noted in the calcitonin group . It is concluded that calcitonin exerts a beneficial effect on back pain following a vertebral crush fracture The aim of this study was to investigate the effect of nasal calcitonin on chronic back pain and disability attributed to osteoporosis . The study design involved three groups of osteoporotic postmenopausal women suffering from chronic back pain . Group I consisted of 40 women with vertebral fractures , group II of 30 women with degenerative disorders and group III of 40 patients with non specific chronic back pain and without abnormality on plain X-rays . Pain intensity was measured using a numerical rating scale ( NRS ) and disability due to back pain was measured using the Oswestry disability question naire . The patients were r and omly assigned to receive , for three months , either 200 IU intranasal salmon calcitonin and 1,000 mg of oral calcium daily ( groups IA , IIA , IIIA ) or 1,000 mg of oral calcium daily ( groups IB , IIB , IIIB ) . Repeated measures ANOVA showed that there were no significant time , group or interaction effects for pain intensity and disability in any of the groups studied . Mean Oswestry and NRS scores were reduced during the follow-up period in the groups IA , IIIA , but the differences between the two time points were not statistically significant . Intranasal calcitonin has no effect on chronic back pain intensity and functional capacity of osteoporotic women regardless of the presence of fractures , degenerative disorders or chronic back pain of non-specific etiology The purpose of this study was to evaluate the efficacy of calcitonin on β-endorphin levels in female patients experiencing back pain associated with postmenopausal osteoporosis . The secondary purpose was to assess the pain and quality of life in these patients . There were 30 patients with a mean age of 58.2±5.4 years in the treatment group and 26 patients with a mean age of 58.8±5.2 years in the placebo group in this r and omized , placebo-controlled study . The patients subcutaneously received 100 IU salmon calcitonin or placebo injections and 1,000 mg elementary calcium for 2 weeks . Baseline plasma β-endorphin levels were measured and repeated after 2 weeks . Patients ’ pain and quality of life ( QOL ) were evaluated by using the Visual Analogue Scale , Modified Face Scale , Beck Depression Index , and Nottingham Health Profile . Patients ’ global assessment of disease activity was also performed at baseline and at the end of the first and second week . We found that plasma β-endorphin levels in the treatment group were significantly higher than the placebo group at the end of the second week ( p<0.001 ) . Although pain and QOL scores were improved at the end of the second week in both groups ( p<0.05 ) , the improvement in the treatment group was more significant when compared with the placebo group ( p<0.05 ) . Therefore , calcitonin is an analgesic agent , as it increases the plasma β-endorphin levels in patients with postmenopausal osteoporosis , which consequently improves QOL Our aim was to compare the analgesic efficacy of pamidronate ( PAM ) and synthetic human calcitonin ( CT ) in intravenous infusion for recent painful benign vertebral compression in a r and omised prospect i ve double-blind study . Twenty-seven patients aged 49–85 years with painful benign non-traumatic vertebral compression were included in the study . They received either PAM ( 1 mg/kg ) or synthetic human CT ( 1.5 mg ) as an intravenous infusion . Pain and functional disability were evaluated before infusion , and 4 and 30 days afterwards . The pain score assessed on a visual analogue scale at day 0 was 5.94±2.47 in patients treated with PAM and 6.27±2.50 in patients treated with CT ( p=0.74 ) ; at day 4 , 4.8±2.80 with PAM vs 3.9±2.68 with CT ( p=0.37 ) ; and at day 30 , 3.6±3.13 with PAM vs 3.10±2.76 with CT ( p=0.70 ) . Spinal function scores were 18.21±3.17 at day 0 in patients treated with PAM vs 17.23±4.42 in patients treated with CT ( p=0.69 ) and at day 30 , 13.7±5.36 with PAM vs 12.33±3.22 with CT ( p=0.68 ) . We found no advantage of PAM over CT in a single intravenous infusion for the treatment of painful recent benign vertebral compression . Since CT is ten times less costly , its use should be preferred Summary A placebo-controlled , double-blind study was carried out over 4 months to evaluate two doses of synthetic human calcitonin ( 0.25 and 0.125 mg ) given s.c . three times per week . Enrolled were 60 women , aged 56–82 years , who had experienced a vertebral fracture due to low-energy trauma within the preceding year . During active treatment there was within the first month a dose-dependent decrease of the indices of bone resorption ( fasting urinary calcium and hydroxyproline excretions ) , whereas only the higher dose and a treatment period of 4 months produced a reduction of bone formation ( serum osteocalcin ) . The bone mineral content ( BMC ) of the nondominant forearm was unchanged . Treatment with calcitonin also had significant , dosedependent , analgetic effects . The amelioration of pain was , in multivariate analyses , related to a reduction in parameters felt to be markers for bone resorption . In the placebo group there was a significant reduction of the BMC of the forearm but no changes of any of the biochemical markers for bone turnover and no improvement of pain . In conclusion , treatment with two low doses of calcitonin induced changes of the biochemical markers of bone turnover in a dosedependent manner . The analgetic properties of calcitonin were also of salient clinical importance . The knowledge derived from this study could be adapted to the dosage schedule in long-term trials in osteoporosis Radiographically detected vertebral fractures ( hereafter referred to as vertebral fractures ) are a hallmark of postmenopausal osteoporosis and an important end point in clinical trials of osteoporosis treatment . Women with vertebral fractures have low bone mass compared with women without these fractures and , independently of bone mass , have an increased risk for additional vertebral and other fractures [ 1 - 4 ] . Vertebral fractures are common : Five percent of 50-year-old white women and 25 % of 80-year-old women have had at least one vertebral fracture [ 5 ] . Surprisingly , however , the manner in which vertebral fractures affect health remains uncertain . Cross-sectional studies in community-derived sample s of older women have demonstrated only a modest association [ 6 - 8 ] or no association [ 9 - 11 ] between prevalent vertebral fractures and back pain or disability . Cross-sectional studies do not distinguish more recent fractures from older vertebral fractures and may fail to capture transient increases in pain or disability [ 12 ] , a limitation that may underestimate the clinical effect of these fractures [ 13 ] . Back pain is common among elderly women [ 14 ] , and frequent causes of back pain , such as degenerative disc disease , facet joint osteoarthritis , spinal stenosis , and scoliosis , may obscure the impact of vertebral fracture . Only about one third of new vertebral fractures come to medical attention [ 15 , 16 ] , suggesting that most vertebral fractures are asymptomatic . However , attitudes toward back pain in older women and access to health care may also play a role in determining whether vertebral fractures come to medical attention . We examined the effect of incident vertebral fractures on back pain and back-related functional limitations in a large community-based sample of elderly women who underwent serial spinal radiography and annual assessment s of back pain and disability over the same period . Methods Participants Study patients were participants in the Study of Osteoporotic Fractures , a cohort recruited from population -based listings in four U.S. metropolitan areas . Details of the design of this study are published elsewhere [ 17 ] . Lateral spine radiographs were obtained for 9677 white women between the ages of 65 and 99 years ( median age , 70 years ) who underwent baseline examination between 1986 and 1988 . Repeated spinal radiographs suitable for morphometry were obtained for 7223 women ( 75 % of the original cohort ) at a follow-up clinic visit held an average of 3.7 years ( range , 1.3 to 5.1 years ) later . All participants gave informed consent . Vertebral Morphometry Lateral radiographs of the thoracic and lumbar spine were obtained in accordance with current guidelines [ 18 ] . Quantitative vertebral morphometry was performed using six-point digitization as described elsewhere [ 3 , 19 ] to calculate the anterior ( Ha ) , mid- ( Hm ) , and posterior ( Hp ) height for each vertebral body from T4 to L4 . A system of triage of radiographs , described elsewhere [ 3 , 20 ] , was used to reduce the number of radiographs requiring morphometric measurements . Briefly , trained technicians separated sets of radiographs into normal , uncertain , or probably fractured groups on the basis of a limited semiquantitative grading scheme that categorized women by the most abnormal vertebral level [ 20 ] . Uncertain grade s were further categorized by the study radiologist as normal or probably fractured . Morphometry was done on the radiograph pairs that were categorized as probably fractured ( 42 % ) . In a r and om sample of 503 women whose radiographs were triaged and then digitized , triage missed no incident fractures according to the study definition . Definition of Vertebral Fracture A vertebra was classified as having a prevalent fracture on the baseline radiograph if any of the following ratios were more than 3 SDs ( > 4 SDs for severe fractures ) below the normal mean for that vertebral level : ( Ha/Hp ) , ( Hm/Hp ) , or a combination of ( H/H [ ] 1 ) and ( Hai/Hai 1 ) [ 3 , 21 ] . A new ( incident ) fracture was identified if any of the three vertebral heights ( Ha , Hm , or Hp ) on follow-up radiographs decreased by 20 % or more and by at least 4 mm compared with the baseline height . Incident fractures identified by morphometry were review ed by a radiologist to exclude imaging artifacts or such conditions as osteophytosis and Scheuermann disease ; 7 % of vertebrae meeting the morphometric criteria for incident fracture were reclassified as not fractured . Incident Clinical Fractures We used previously described methods [ 22 ] to assess the occurrence of clinical fractures of any bone during follow-up . Women were considered to have a clinical vertebral fracture if they reported a new diagnosis of spinal fracture and a clinical radiology report confirmed that a vertebral fracture was present . Measurements of Pain , Disability , and Limited Activity We evaluated outcome measures by using a previously described question naire [ 7 , 23 ] that asked about back pain and back-related disability in the past 12 months and the number of days of limited activity due to back pain . The question naire was administered at baseline and at three annual follow-up contacts held before assessment of vertebral fractures . The third follow-up contact coincided with follow-up radiography . Back pain was assessed on scales of frequency ( 0 , never or rarely ; 1 , some of the time ; 2 , most of the time ; or 3 , all of the time ) and severity ( 0 , no pain ; 1 , mild pain ; 2 , moderate pain ; or 3 , severe pain ) . The two pain questions had high internal consistency ( Cronbach = 0.81 ) and were summed for a total score that could range from 0 to 6 . We defined clinical ly significant back pain as pain that was experienced most or all of the time or pain that was moderate or severe . Women without significant back pain at baseline were considered to have increased back pain if clinical ly significant pain had developed between any follow-up contacts . For women with clinical ly significant back pain at baseline , increased back pain was defined as an increase in total pain score of at least two points . Both types of increase had a similar association with incident fractures and thus were combined for a single outcome . Back-related disability was assessed with questions about the degree of difficulty ( 0 , no difficulty ; 1 , some difficulty ; 2 , much difficulty ; or 3 , unable to perform activity ) in six activities of daily living that involved the back ( bending down to pick up light-weight objects , lifting a 10-pound object from the floor , reaching for objects just above the head , putting on socks or stockings , getting in and out of an automobile , and st and ing for 2 hours ) . These measures were combined in a back-related disability score ranging from 0 to 18 . As reported elsewhere [ 7 ] , this scale has high internal consistency ( Cronbach = 0.82 ) and is highly correlated ( Spearman r = 0.73 ) with a more extensive instrument used to assess disability caused by low back pain [ 24 ] . We defined clinical ly significant disability as much difficulty or unable in one or more of the six activities . Women without significant disability at baseline were considered to have increased disability if clinical ly significant disability had developed between any follow-up contacts . For women with clinical ly significant disability at baseline , increased disability was defined as an increase in disability score of at least three points . Both types of increase had a similar association with incident fractures and thus were combined for a single outcome . We also asked participants if they had limited their activities because of back pain since the last contact ; if the answer was yes , we asked for the number of days they had stayed in bed and the number of days on which activity was limited ( not including days in bed ) because of back pain . Questions were adapted from previous surveys [ 25 , 26 ] . For all follow-up contacts , we summed the number of days of bed rest and , in a separate measure , the number of days of limited activity ; we then divided these numbers by the total years of follow-up to estimate the average number of affected days per year . Other Measurements The baseline question naire assessed potential confounding factors that may be associated with the risk for incident vertebral fracture and with back pain or disability , including smoking ( current or past smoker ) ; inactivity , defined as walking less than one block daily ( yes or no ) ; a previous physician diagnosis of osteoporosis or spinal fracture ( yes or no ) ; current use of estrogen ( yes or no ) ; hip pain in the past 12 months ( yes or no ) ; and height at 25 years of age . At the baseline examination , we assessed height and weight and calculated body mass index ( kg/m2 ) . We assessed grip strength by using an isometric dynamometer ( Jamar Hydraulic H and Dynamometer , JA Preston , Jackson , Mississippi ) at baseline and at the follow-up examination and calculated change in grip strength between the two measurements . A r and om sample of 16 % of baseline spine radiographs was assessed for spinal disc degeneration by using previously published methods [ 27 ] . Statistical Analysis Unless otherwise indicated , analyses were done separately in groups stratified by the presence of one or more baseline prevalent vertebral fractures . Descriptive and bivariate associations were assessed by using the t-test for continuous variables and the chi-square test for dichotomous variables . The association between incident vertebral fractures and dichotomous outcomes ( increased back pain and increased back disability ) was analyzed with logistic regression techniques . We analyzed the association of incident vertebral fracture with days of bed rest and days of limited activity per year by using Poisson regression . The distribution of days of bed rest ( mean SD , 0.44 5.15 ) and limited-activity days ( 16.3 53.7 ) indicate that considerable overdispersion is present . Poisson regression allowing for this overdispersion provides a good estimation and inferential scheme [ Health-related quality of life ( HRQOL ; “ QOL ” hereafter ) was evaluated in Japanese osteoporotic patients using three question naires ; the SF-36 ( MOS 36-Item Short-Form Health Survey ; generic , profile-type ) , the EQ-5D ( Euro Qol-5 Dimensions ; generic , preference-based ) , and the JOQOL ( Japanese Osteoporosis Quality of Life 1999 ; disease-targeted ) . The eight subscales and two summary scores of the SF-36 were impaired in these patients even after correction for age and sex . The scores on the EQ-5D and JOQOL correlated well with the subscales of the SF-36 that represent the physical aspects of physical function and bodily pain , which suggests that physical aspects are important determinants of overall QOL status in osteoporotic patients . Although the QOL scores did not correlate with bone mineral density , they were markedly influenced by the presence of vertebral fractures . In particular , the presence of two or more vertebral fractures greatly decreased the QOL scores . We then evaluated the QOL scores before and after treatment . The patients were either given calcium supplementation alone or calcium plus once-weekly elcatonin ( Elcitonin , Asahi Kasei Pharma , Tokyo , Japan ) injection . Elcatonin treatment markedly improved diverse aspects of the QOL , whereas calcium alone did not . The current data suggest that osteoporosis , especially in the presence of vertebral fracture , is associated with compromised QOL , and therapeutic intervention for osteoporosis should be evaluated in terms of QOL , as well as in terms of increases in bone mineral density and fracture prevention Abstract . The aim of this study was to assess the efficacy and safety of nasal spray and subcutaneous formulations of salmon calcitonin . Two-hundred-four patients , 27 males and 177 females , aged 72 years on average , with a recent , painful , vertebral crush fracture were given either 50 IU/day of subcutaneous salmon calcitonin ( SCSCT , 102 patients ) or 200 IU/day of intranasal salmon calcitonin ( INSCT , 102 patients ) for 30 consecutive days , according to a double-blind , double-placebo design . The two-sided 95 % confidence interval of the difference between the two formulations for the pain on D30 assessed by Huskisson 's Visual Analogue Scale ( VAS ) [ −5.3 mm , 7.9 mm ] was included in the [ −10 mm , 10 mm ] reference interval . Equivalence of the two formulations , was demonstrated . At the end of the study , the 95 % confidence intervals of VAS of both treatment groups were included in the [ 0 mm , 30 mm ] interval , which is considered to be clinical ly pertinent . Relief was obtained in less than 10 days for more than 50 % of patients . The urinary hydroxyproline/creatinine and calcium/creatinine ratios remained constant between D1 and D30 with both formulations . General safety was comparable between the two formulations . Local safety of INSCT was similar to that of its placebo Abstract Vertebral fractures are associated with back pain and disability . There are , however , few prospect i ve data looking at back pain and disability following identification of radiographic vertebral fracture . The aim of this analysis was to determine the impact of radiographically identified vertebral fracture on the subsequent occurrence of back pain and disability . Women aged 50 years and over were recruited from population registers in 18 European centers for participation in the European Prospect i ve Osteoporosis Study . Participants completed an interviewer-administered question naire which included questions about back pain in the past year and various activities of daily living , and they had lateral spine radiographs performed . Participants in these centers were followed prospect ively and had repeat spine radiographs performed a mean of 3.7 years later . In addition they completed a question naire with the same baseline questions concerning back pain and activities of daily living . The presence of prevalent and incident vertebral fracture was defined using established morphometric criteria . The data were analyzed using logistic regression with back pain or disability ( present or absent ) at follow-up as the outcome variable with adjustment made for the baseline value of the variable . The study included 2,260 women , mean age 62.2 years . The mean time between baseline and follow-up survey was 5.0 years . Two hundred and forty participants had prevalent fractures at the baseline survey , and 85 developed incident fractures during follow-up . After adjustment for age , center , and the baseline level of disability , compared with those without baseline prevalent fracture , those with a prevalent fracture ( odds ratio [OR]=1.4 ; 95 % confidence interval [ CI ] 1.0 to 2.0 ) or an incident fracture ( OR=1.7 ; 95 % CI , 0.9 to 3.2 ) were more likely to report disability at follow-up , though the confidence intervals embraced unity . Those with both a prevalent and incident fracture , however , were significantly more likely to report disability at follow-up ( OR=3.1 ; 95 % CI , 1.4 to 7.0 ) . After adjustment for age , center , and frequency of back pain at baseline , compared with those without baseline vertebral fracture , those with a prevalent fracture were no more likely to report back pain at follow-up ( OR=1.2 ; 95%CI , 0.8 to 1.7 ) . There was a small increased risk among those with a preexisting fracture who had sustained an incident fracture during follow-up ( OR=1.6 ; 95%CI , 0.6 to 4.1 ) though the confidence intervals embraced unity . In conclusion , although there was no significant increase in the level of back pain an average of 5 years following identification of radiographic vertebral fracture , women who suffered a further fracture during follow-up experienced substantial levels of disability with impairment in key physical functions of independent living Summary Forty-five postmenopausal osteoporotic women with at least one osteoporotic vertebral crush fracture were r and omized into three treatment groups . Each patient was on calcitonin , 50 U , on alternate days for 2 weeks monthly ( 350 U/month ) , and 500 mg/day oral calcium supplementation . In group II , this therapy was supplemented with phosphate ( 750 mg/day ) , and in group III , nor and rostenolone decanoate ( 50 mg/month ) was added to the calcitonin + calcium therapy . Bone mineral content , by single photon absorptiometry , of the radius midshaft and distal site ( 3 cm ) , as well as the lumbar and metacarpal radiomorphometrical indices were estimated semiannually . The therapeutic trial lasted 36 months except in the phosphate supplementation group , where , due to unfavorable results , treatment was discontinued after 24 months . Calcitonin practically prevented further bone loss for 24 months even in this relatively small and intermittent dosage . Phosphate supplementation was without benefit ; however , according to the majority of the examined parameters , combination of calcitonin with the anabolic steroid nor and rostenolone decanoate extended efficacy up to 36 months . This latter combination seems to be a promising , relatively inexpensive therapeutic regimen in the treatment of established postmenopausal osteoporosis Fifty-nine consecutive patients ( 19 men , 40 women , mean age 60.8 [ 27 - 80 ] years ) with primary osteoporosis were studied to see if there was any significant gain in bone mass after treatment with salmon calcitonin . All the patients were given 1 g calcium by mouth every morning . Group 1 ( n = 20 ) received no other specific medication while group 2 ( n = 19 ) were given 100 I.U. calcitonin subcutaneously every second evening and group 3 ( n = 20 ) received the same dose every evening . The pain reported by the patients was subdivided into four severity grade s , and analgesic consumption was recorded . In group 1 there was a nonsignificant decrease in pain , but in groups 2 and 3 there was a highly significant diminution in pain ( P less than 0.005 ) and in analgesic intake ( P less than 0.01 ) . Measurements of bone density carried out by photon absorption at the end of 12 months showed a 5.5 % increase in the distal radius in group 2 ( P = 0.0001 ) and a 7.1 % increase in group 3 ( P = 0.0001 ) , while in group 1 mineral content had decreased by 4.3 % ( nonsignificant ) . These results show that a significant gain in bone mass can be achieved by administration of calcitonin , either daily or on alternate days . The incidence of extravertebral fractures and of new or progressive vertebral deformity tended to be lower in groups 2 and 3 than in group 1 OBJECTIVE To evaluate the analgesic efficacy of calcitonin suppositories ( 200 IU ) in comparison with bed rest and paracetamol tablets , as a rescue analgesic . DESIGN A prospect i ve , double-blind , r and omized , placebo-controlled , clinical trial . PATIENTS Forty patients ( 8 men and 32 postmenopausal women ) , who had recently ( within the last 5 days ) suffered a nontraumatic osteoporotic vertebral fracture . SETTING AND INTERVENTIONS All patients were admitted to the hospital , divided r and omly into two groups and received either one calcitonin or placebo suppository once a day , respectively , for 28 days . All patients were allowed to take paracetamol tablets ( 500 mg ) , with a maximum dose of six tablets daily . OUTCOME MEASURES Spinal pain evaluation was performed at the beginning of the study ( before the initiation of treatment ) and then daily until the end of the study ( day 28 ) using the Huskinsson 's visual analog scale ( VAS ) and a painmeter device , by direct pressure on the fractured vertebra . Pain was evaluated with the patients attempting or performing four different locomotor functions , e.g. , bed rest , sitting , st and ing , and walking functions . Biochemical urine and plasma measurements were carried out before the initiation of treatment and on days 14 and 28 . RESULTS All calcitonin-treated patients experienced an overall statistically significant ( all p values < 0.001 ) decrease of spinal pain as assessed by the VAS and the painmeter device . Pain relief allowed for early mobilization and the gradual restoration of the locomotive functions in the calcitonin-treated group . Placebo-treated patients remained in bed for almost the whole of the observation period . At the end of the study ( 28th day ) , fasting osteocalcin , hydroxyproline/creatinine , and calcium/creatinine ratio values were statistically significantly ( all p values < 0.001 ) , lower in the calcitonin-treated than in the placebo-treated patients . In the placebo group these values showed a gradual increase . In the calcitonin-treated group side effects mainly included dizziness and enteric irritation caused by the suppositories . Enteric irritation was also present in the placebo-treated group . CONCLUSIONS Salmon calcitonin suppositories ( 200 IU daily ) caused a dramatic decrease in spinal pain in patients with recent osteoporotic vertebral fractures and influenced the early mobilization and the gradual restoration of their locomotor functions Spinal collapse is a painful complication of osteoporosis . In this study , the analgesic effect of salmon calcitonin , administered intranasally ( 200 IU per day ) , was assessed in 18 patients with acute collapse of one to four vertebrae . Pain was evaluated by a descriptive pain scale ( ie , Keele 's ) as well as by the daily consumption of analgesic drugs . When compared with placebo , intranasal salmon calcitonin significantly relieved pain and occasioned a decrease in the consumption of analgesic drugs . No major side effects were reported by the patients under study The aim of this study was to examine the effect of intranasal administration of salmon calcitonin to a group of 24 postmenopausal women with severe , established osteoporosis ( t score < -2.5 SD ) and more than one vertebral fracture . The patients were treated with 200 IU of nasal salmon calcitonin daily for 2 months with a subsequent pause of 2 months ( 3 cycles ) and 500 mg calcium daily over a total of 12 months in an open r and omized study . The patients were compared with an age matched control group of 18 women of a similar clinical status who were treated with calcium and vitamin D only . In the nasal calcitonin treatment group an increase in the trabecular axial bone density of 2.8 % was achieved , as well as increase in trabecular appendicular ( forearm ) bone density of 1.6 % , together with a cortical bone density increase of 1.8 % axial and 1 % appendicular . Initially , elevated values of urinary deoxypyridinoline were found in 12 women in the nasal calcitonin treatment group ; these levels returned to normal under salmon calcitonin nasal therapy and documented the inhibition of increased osteoclastic activity . Cyclic intermittent calcitonin nasal therapy led to a general increase in trabecular and cortical axial and appendicular bone density , marked alleviation of the subjective sensation of pain , and a reduction in the daily dose of accompanying nonsteroidal anti-inflammatory drugs by 50 % Examinations were performed in 20 adult male and female patients ( pts ) suffering from acute back pain due to vertebral compression fracture secondary to osteoporosis proved by lateral X-rays of the dorso-lumbar spine ( Th3-L5 ) , and bone mineral density with the method of dual energy X-ray absorptiometry . The synthetic human calcitonin ( SUC ) ( 0.5 mg ) was injected I.M. every day during 28 days . Analgesic effect was evaluated on 0 , 3 , 7 , 14 , 21 and 28th day by patient 's assessment of functional capacity , and physician 's assessment of pain and mobility . On the same days biochemical variables of Ca-P homeostasis were determined . Treatment with calcitonin result ed in a positive analgesic effect . The functional capacity and mobility of pts increased with diminution of pain . No significant alterations of Ca-P homeostasis was observed . Mild and transient side effects as nausea and tachycardia were negligible . SHC appears to have a significant analgesic effect in treatment of primary osteoporosis The present study was planned to assess the safety , tolerability and efficacy on bone mineral density ( BMD ) , pain , quality of life and fracture risk of alendronate , calcitonin and calcium treatments . A total of 151 postmenopausal women with lumbar spine BMD 2 SD or more below the young adult mean were r and omly assigned to one of three groups : 51 patients received oral alendronate 10 mg and calcium 1000 mg ( alendronate group ) , 50 patients intranasal salmon calcitonin 100 IU and oral calcium 1000 mg ( calcitonin group ) , and 50 patients oral calcium 1000 mg ( calcium group ) daily for one year . BMD was assessed by dual energy X-ray absorbtiometry , pain by a visual analogue scale , and quality of life by the Nottingham health profile . Significant increases in BMD at all sites were obtained in the calcitonin and alendronate groups , but not in the calcium group . Pain and quality of life improved significantly in both the calcitonin and alendronate groups , but not in the calcium group . New vertebral fractures were seen in 31.58 % of the alendronate , 37.5 % of the calcitonin , and 40 % of the calcium groups , representing no statistical difference . No serious side-effects were seen in any of the patients during follow-up We examined the analgesic effect of nasal salmon calcitonin in patients with acute pain due to recent , nontraumatic osteoporotic vertebral crush fractures . 32 men and 68 postmenopausal women were studied using a prospect i ve , double-blind , placebo-controlled clinical design . Men and women taking 200 IU of nasal salmon calcitonin daily for a period of 28 days had a dramatic decrease of spinal pain . This analgesic effect was accompanied by early mobilization and gradual restoration of the locomotor functions , such as sitting , st and ing and walking . Patients receiving the placebo nasal spray remained in bed for almost the entire period of observation . The consumption of high doses of paracetamol did not help placebo patients to get out of bed during the 4 weeks of hospitalization . Nasal salmon calcitonin and early mobilization also reduced hydroxyproline excretion , thus preventing massive bone loss during the period of bedrest In a multicentre open trial 530 patients suffering from primary osteoporosis , secondary osteoporosis and Sudeck 's disease were enrolled to assess synthetic human calcitonin efficacy on bone pain relief . Spontaneous pain , pain on movement , provoked pain , functional impairment and patient 's assessment were recorded . During the first 30 days of treatment , all the parameters significantly improved ( p < 0·01 ) and the tolerability was satisfactory . Four hundred and ten patients entered a follow-up study , this number gradually decreasing over a 6-month period due to a satisfactory outcome . Efficacy on bone pain remained very high in most of the patients , many of whom continued to improve . These results suggest that synthetic human calcitonin is highly effective on pain and functional impairment in bone disease and is well tolerated Different types of calcitonin ( porcine , human , salmon ) are used in the management of bone diseases characterized by a high bone turnover , such as post-menopausal osteoporosis and Paget ’s disease ; recently , salmon calcitonin has become clinical ly available as an intranasal ( i.n . ) spray . An analgesic effect has also been described for calcitonins , both in experimental animals and humans , but only a few studies in humans were placebo controlled . The aim of this study was to compare the analgesic efficacy of i.n . and intramuscular ( i.m . ) salmon calcitonin ( sCT ) and of placebo in women affected by painful post-menopausal osteoporosis , in a double-blind , double-placebo trial . Twenty-eight women were r and omly allocated to one of the following treatments : 1 ) i.n . sCT 200 U/day plus i.m . placebo ; 2 ) i.n . placebo plus i.m . sCT 100 U/day ; and 3 ) i.n . and i.m . placebo . Each treatment lasted four weeks , and the pain score was evaluated weekly by means of a visual analogic scale ( VAS ) . Twenty-four women completed the trial ; with i.n . sCT , the pain score decreased significantly by the second week of treatment ( p<0.05 ) ; with i.m . sCT and with placebo , the pain score decreased significantly only by the fourth week ( p<0.05 ) , so that the final pain scores obtained with the three treatments were not different . We conclude that i.n . sCT was probably more rapid , but not more effective than i.m . sCT or placebo in decreasing pain in post-menopausal osteoporosis . ( Aging Clin . Exp . Res . 6 : 459 - 463 , 1994 Intramuscular and intranasal synthetic salmon calcitonin ( sCT ) has long been used in the treatment of involutional osteoporosis . A new suppository formulation was developed and many studies demonstrated that rectally administered sCT is efficacious and well tolerated . Thirty postmenopausal women , who had a bone mineral density at the lumbar spine below the mean of age-matched women , were enrolled in this study . Using an open balanced , r and omized design , the patients were allocated to two groups of treatment : sCT suppositories at the dose of 100 UI/day or 200 UI every other day for six months . Treatment with sCT suppositories caused a statistically significant decrease of pain in both study groups . Bone mineral density at lumbar spine showed an increase in both study groups with significant difference respect the basal value for the patients treated with sCT on alternate day . Based on the results of this study , we can thus conclude that sCT in suppository formulation is effective in reducing pain sintomatology , bone loss and turnover in involutional osteoporosis Carbocalcitonin spray administered for 12 months at a daily dosage of 80 U MRC according to five schedules has been tested on 150 normal spontaneous postmenopausal women for its influence on bone mineral density ( BMD ) , bone metabolism and osteoarticular pain . BMD was monitored before and at the end of treatment in comparison with BMD of untreated control women . Metabolic markers ( serum alkaline phosphatase , serum osteocalcin and urinary hydroxyproline ) were also evaluated before and during treatment ( at the 9th or 10th month of treatment ) . Osteoarticular pain was assessed by an analogic visual scale . Intranasal carbocalcitonin , administered according to cyclic schedules at a high frequency dosage , was able to maintain bone mass only in the earlier postmenopausal women . BMD percent increase after 12 months of treatment was 1.10 and 1.31 in women with low ( < 0.870 mg/cm2 ) and high baseline BMD ( > or = 0.870 mg/cm2 ) , respectively . In advanced menopause the maintaining effect of carbocalcitonin on BMD seemed evident only if the baseline bone mass was lower than the BMD of the age matched control group . At least six months of treatment/year is necessary for effective therapy . Both systemic and local tolerance were optimal . No significant side-effects were detected A prospect i ve study was performed to clarify the therapeutic effect on calcitonin in the patients with osteoporosis using patient-based outcome measures . A total of 67 patients with primary osteoporosis who complained back pain were included in this study . All patients were administered calcitonin 20 Unit/week intramuscularly . The therapeutic effects were assessed using various patient-based outcome measures before treatment , 2 , 4 weeks and 3 months after treatment . We used Short form 12 for measuring general well-being , Rol and Morris disability question naire for functional status associated with back pain , and visual analogue scale for pain intensity . Statistic analysis was performed using paired-t test . Pain intensity and functional status were significantly recovered at 2 weeks follow-up time and the effects were continued at 3 months follow-up time . Physical component summary ( PCS ) was recovered at 3 months follow-up tme , whereas mental component summary ( MCS ) was improved at 2 weeks follow-up time . These facts suggest that improvement of back pain using calcitonin correlates directly with recovery in functional status , indirectly with recovery in general well being STUDY OBJECTIVE To determine the amount of change in pain severity , as measured by a visual analog scale , that constitutes a minimum clinical ly significant difference . METHODS Patients 18 years of age or older who presented with acute pain result ing from trauma were enrolled in this prospect i ve , descriptive study . The setting was an urban county hospital emergency department with a Level 1 trauma center . In the course of a brief interview , patients were asked to indicate their current pain severity with a single mark through a st and ard 100-mm visual analog scale . At intervals of 20 minutes for the next 2 hours , patients were asked to repeat this measurement and , in addition , to contrast their present pain severity with that at the time of the previous measurement . They were to indicate whether they had " much less , " " a little less , " " about the same , " " a little more , " or " much more " pain . All contrasts were made without reference to prior visual analog scale measurements . A maximum of six measurements of pain change were recorded per patient . Measurements ended when the patient left the ED or when the patient reported a pain score of zero . The minimum clinical ly significant change in visual analog scale pain score was defined as the mean difference between current and preceding visual analog scale scores when the subject noted a little less or a little more pain . RESULTS Forty-eight subjects were enrolled , and 248 pain contrasts were recorded . Of these contrasts , 41 were rated as a little less and 39 as a little more pain . The mean difference between current and preceding visual analog scale scores in these 80 contrasts was 13 mm ( 95 % confidence interval , 10 to 17 mm ) . CONCLUSION The minimum clinical ly significant change in patient pain severity measured with a 100-mm visual analog scale was 13 mm . Studies of pain experience that report less than a 13-mm change in pain severity , although statistically significant , may have no clinical importance Summary In most countries , calcitonin is available in the form of injections , and less frequently as an intranasal spray . An oral route of administration should improve compliance . In a preliminary feasibility study , we have compared the acute biological action of injectable salmon calcitonin ( 50 IU ) , with the injectable calcitonin analogue ASC 710 ( 0.2 mg ) and oral ASC 710 ( 20 mg ) in 6 patients suffering from active Paget 's disease of bone . The intensity and duration of the biological response were not significantly different in the 3 modes of therapy . In conclusion , the oral calcitonin analogue ASC 710 possesses an antiresorbing activity in Paget 's disease comparable to that of an injection of salmon calcitonin which demonstrates that it can cross the intestinal barrier Summary Using prospect i ve data from the Canadian Multicentre Osteoporosis Study ( CaMos ) , we compared health utilities index ( HUI ) scores after 5 years of follow-up among participants ( 50 years and older ) with and without incident clinical fractures . Incident fractures had a negative impact on HUI scores over time . Introduction This study examined change in health-related quality of life ( HRQL ) in those with and without incident clinical fractures as measured by the HUI . Methods The study cohort was 4,820 women and 1,783 men ( 50 years and older ) from the CaMos . The HUI was administered at baseline and year 5 . Participants were sub-divided into incident fracture groups ( hip , rib , spine , forearm , pelvis , other ) and were compared with those without these fractures . The effects of both time and fracture type on HUI scores were examined in multivariable regression analyses . Results Men and women with hip fractures , compared to those without , had lower HUI measures that ranged from −0.05 to −0.25 . Both women and men with spine fractures had significant deficits on the pain attributes ( −0.07 to −0.12 ) . In women , self-care ( −0.06 ) , mobility and ambulation ( −0.05 ) were also negatively impacted . Women with rib fractures had deficits similar to women with spine fractures , and these effects persisted over time . In men , rib fractures did not significantly affect HUI scores . Pelvic and forearm fractures did not substantially influence HUI scores . Conclusion The HUI was a sensitive measure of HRQL change over time . These results will inform economic analyses evaluating osteoporosis therapies |
12,313 | 28,704,792 | Similarly , shorter telomere length was found among smokers compared to non‐smokers , and among current smokers compared to never or former smokers .
Dose‐response meta‐ analysis suggested an inverse trend between pack‐years of smoking and telomere length .
Conclusion Shorter telomeres among ever smokers compared to those who never smoked may imply mechanisms linking tobacco smoke exposure to ageing‐related disease .
Telomere length was shorter in ever smokers compared to never smokers .
Among ever smokers , current smokers had shorter mean telomeres than former smokers .
An inverse trend was indicated between pack‐years of smoking and telomere length | Background Cigarette smoking is a risk factor for ageing‐related disease , but its association with biological ageing , indicated by telomere length , is unclear . | Inconsistent associations between smoking and telomere length ( TL ) have been reported in epidemiologic studies , perhaps because of the time-varying nature of smoking behaviors . We estimated the associations of TL , which was measured by quantitative polymerase chain reaction using saliva DNA , with concurrent and past smoking status reported biennially for up to 16 years before TL measurement in 5,624 participants in the Health and Retirement Study ( 1992 - 2008 ) . Smoking was associated with reduced TL when we used prospect i ve data on smoking statuses among men and women , but the association was strongly attenuated among men in cross-sectional analyses . This attenuation was largely due to a higher rate of smoking cessation during the study period among men with shorter TL than among men with longer TL . Short TL was also associated with poorer overall health in men , which suggests that male smokers with short TL were more likely to quit smoking because of poor health . Analyses of years since cessation , smoking duration , and pack-years of smoking all support the hypothesis that increased cigarette use shortens TL . Our results provide a potential explanation for the inconsistent associations between smoking and TL reported in previous cross-sectional studies . Time-varying associations should be considered in future studies of smoking behavior , TL , aging , and disease risk Background : Within-person variability in biomarkers results in r and om error that can attenuate estimates of association . Little information on such variability is available for a number of nutrition-related biomarkers . Methods : Blood sample s obtained 2 to 4 weeks apart were analyzed for tocopherols , carotenoids , ascorbate , lipids , cotinine , C-reactive protein , and oxidative stress . Subjects ( n = 206 men and women , mean age 45.4 years ) were either smokers or passively exposed to smoke . We calculated intraindividual and interindividual variability and the number of measurements required to reduce attenuation . Results : For most biomarkers , 2 measurements would be required to limit the attenuation of correlation coefficients to no lower than 90 % of the true correlation . If only one measurement were obtained , observed correlations would be approximately 80–88 % of true correlations . For regression coefficients , 3 or 4 measures would be required . Exceptions were ascorbic acid and malondialdehyde , for which a single measure result ed in little attenuation . Conclusions : For most serum markers , collection of 2 or more measurements per person is desirable to increase the ability to detect associations between biomarkers and health-related variables . If only one measure is possible , sample sizes should be planned to permit detection of associations that are likely to be observed , not the theoretical true associations . The results of this study , in which measurements were obtained 2 to 4 weeks apart , are relevant for epidemiologic research in which the exposure of interest is the subject ’s baseline or current status . It is likely that within-person variability would be greater over a period of months or years |
12,314 | 19,239,469 | There is no strong evidence of a protective effect of exclusive breastfeeding for at least 3 months against AD , even among children with a positive family history | BACKGROUND Breastfeeding is undisputedly preferable to formula feeding for infant nutrition because of its nutritional , immunological and psychological benefits .
However , studies on the association between breastfeeding and development of atopic dermatitis ( AD ) have shown inconsistent results .
OBJECTIVES To examine the association between exclusive breastfeeding for at least 3 months after birth and the development of AD in childhood . | Objective : To evaluate whether levels of n-6 long chain polyunsaturated fatty acids ( LCPs ) in human breast milk are related to the mother ’s atopic constitution , and whether a decreased level can be restored by gamma-linolenic acid supplementation . Design : Cross-sectional study and dietary supplementation trial . Subjects : 20 atopic mothers and 20 non-atopic mothers ( controls ) , all lactating . Setting : General population . Interventions : The atopic mothers were r and omly assigned to low ( n=10 ) or high ( n=10 ) dosage oral supplementation with oral borage oil for one week ( 230 or 460 mg gamma-linolenic acid ( 18:3n-6 ) per day).Main outcome measures : Essential fatty acid composition of the breast milk total fat fraction , determined by gas liquid chromatography . Results : Arachidonic acid ( 20:4n-6 ) was lower in breast milk of atopic mothers compared with non-atopic mothers ( 0.39 wt% vs 0.46 wt% , difference −0.07 % wt% ( 95 % confidence limits −0.13 , −0.01 wt% ; P<0.05 ) . The ratio between linoleic acid and the sum of n-6 derivatives did not differ between these groups , indicating no difference in delta-6-desaturase ( D6D ) activity . Supplementation of the atopic mothers significantly increased the levels of gamma-linolenic acid and dihomo-gamma-linolenic acid in breast milk in a dose-related way , but the level of arachidonic acid was not increased . Conclusion : We found a decreased level of arachidonic acid in breast milk in atopic compared to non-atopic mothers , but no indication that the rate-limiting enzymatic step ( D6D ) is involved . Supplementation increased the precursor pool but did not restore the level of arachidonic acid . We conclude that atopy is related to a metabolic disturbance beyond the D6D enzymatic step . A low level of arachidonic acid in breast milk may be a risk factor for the development of atopy in the infant , especially when the possible underlying metabolic disturbance of EFA metabolism is inherited by the child . Sponsorship : F Hoffman-La Roche ( Basel , Switzerl and ) and Friesl and Dairy Foods ( Leeuwarden , The Netherl and s).European Journal of Clinical Nutrition ( 2000 ) 54 , BACKGROUND There is controversy regarding the relationship of the effect of breast-feeding on markers of allergy such as total serum IgE in childhood . OBJECTIVE This study , using longitudinal data , tested the hypothesis that the relation of breast-feeding to IgE in childhood differs depending on maternal total IgE level . METHODS Total serum IgE was assessed with the paper radioimmunosorbent test at 4 ages in nonselected children enrolled at birth into the prospect i ve Tucson Children 's Respiratory Study . Children were classified as never breast-fed , breast-fed less than 4 months , or breast-fed 4 months or longer , on the basis of physician report or question naires completed by parents by the time the child was 18 months old . A longitudinal r and om effects model was used to test for group differences and temporal trends in IgE for children classified with reference to maternal IgE ( high tertile vs all others ) and breast-feeding history . A total of 664 children with 1457 observations were included . RESULTS Among children whose mothers were in the 2 lower tertiles of IgE , breast-feeding was associated with lower total serum IgE at age 6 years ( 24.2 vs 44.3 IU/mL for never breast-fed children ; P < .02 ) ; similar trends existed at age 11 years . In contrast , for children whose mothers were in the highest tertile of IgE , breast-feeding of 4 months or longer was associated with higher IgE levels in the child compared with those never breast-fed or breast-fed less than 4 months ( 97.0 vs 38.9 IU/mL ; P < . 005 ) . These cross-sectional analyses were confirmed with the longitudinal r and om effects model , which also showed no effect of confounders . Paternal IgE showed no similar relation with child IgE. CONCLUSION Breast-feeding appears to have paradoxic relations with IgE in childhood , depending on maternal IgE level . These findings may help explain the contradictory results found in other investigations of the relation of breast-feeding to allergic symptoms and markers BACKGROUND Opinions and recommendations about the optimal duration of exclusive breastfeeding have been strongly divided , but few published studies have provided direct evidence on the relative risks and benefits of different breastfeeding duration s in recipient infants . OBJECTIVE We examined the effects on infant growth and health of 3 compared with 6 mo of exclusive breastfeeding . DESIGN We conducted an observational cohort study nested within a large r and omized trial in Belarus by comparing 2862 infants exclusively breastfed for 3 mo ( with continued mixed breastfeeding through > /= 6 mo ) with 621 infants who were exclusively breastfed for > /= 6 mo . Regression to the mean , within-cluster correlation , and cluster- and individual-level confounding variables were accounted for by using multilevel regression analyses . RESULTS From 3 to 6 mo , weight gain was slightly greater in the 3-mo group [ difference : 29 g/mo ( 95 % CI : 13 , 45 g/mo ) ] , as was length gain [ difference : 1.1 mm ( 0.5 , 1.6 mm ) ] , but the 6-mo group had a faster length gain from 9 to 12 mo [ difference : 0.9 mm/mo ( 0.3 , 1.5 mm/mo ) ] and a larger head circumference at 12 mo [ difference : 0.19 cm ( 0.07 , 0.31 cm ) ] . A significant reduction in the incidence density of gastrointestinal infection was observed during the period from 3 to 6 mo in the 6-mo group [ adjusted incidence density ratio : 0.35 ( 0.13 , 0.96 ) ] , but no significant differences in risk of respiratory infectious outcomes or atopic eczema were apparent . CONCLUSIONS Exclusive breastfeeding for 6 mo is associated with a lower risk of gastrointestinal infection and no demonstrable adverse health effects in the first year of life The aim of this study was to assess the preventive effect of exclusive breast-feeding and early solid food avoidance on atopic dermatitis ( AD ) in infancy . This study is part of a dietary clinical trial in a prospect i ve cohort of healthy term newborns at risk of atopy . It was recommended to breast-feed for at least 4 months and to avoid solid food in the same time-period . Eight hundred and sixty-five infants exclusively breast-fed , and 256 infants partially or exclusively formula-fed , were followed-up until the end of the first year following birth . AD and sensitization to milk and egg were considered as study end-points . The 1-year incidence of AD was compared between the two study groups . Adjusted odds ratios ( OR ) with 95 % confidence intervals ( CI ) were calculated by multiple logistic regression . The incidence of AD was calculated in relation to age at introduction of solid food and amount of food given . In the breast-fed group , the adjusted OR for AD was 0.47 ( 95 % CI 0.30 - 0.74 ) . The strongest risk factor was the occurrence of AD in the subject 's core family . The risk of infants with AD to be sensitized to milk was four times higher , and to egg eight times higher , than in infants without AD . Age at first introduction of solid food and diversity of solid food showed no effect on AD incidence . We conclude that in infants at atopic risk , exclusive breast-feeding for at least 4 months is effective in preventing AD in the first year of life PURPOSE To identify factors that might be targeted for intervention to increase breastfeeding among black mothers . DESIGN Secondary analysis of the 1988 National Maternal Infant Health Survey . PARTICIPANTS Black mothers ( N = 5,142 ) from a nationally representative sample of mothers who had births in 1988 . MAIN OUTCOME MEASURES Breastfeeding rates RESULTS Factors associated with breastfeeding included a mother 's plan to breastfeed ; Women , Infants and Children ( WIC ) advice , or advice from a prenatal-care provider on breastfeeding ; and discussion of breastfeeding practice s at prenatal birth classes . CONCLUSIONS The results suggest that the prenatal period may be a critical time to influence a prospect i ve black mother 's decision to breastfeed her infant Abstract . One hundred and twenty‐one women with history of a previous child with atopic disease were r and omly allocated during the next pregnancy to antigen avoidance or control groups . Dietary advice consisted of almost complete exclusion of milk and dairy products , egg , fish , beef and peanut throughout pregnancy and lactation . A total of 109 completed the study . Maternal antigen avoidance was associated with reduced occurrence of atopic eczema and the skin involvement was less extensive and milder . The beneficial effect was observed mainly in the breast‐fed group . Among the fifty‐five who completed the trial of antigen avoidance , seventeen infants developed atopic eczema , five out of thirty‐five who were breast‐fed and twelve out of twenty who were formula‐fed . Among the offspring of fifty‐four control mothers given no dietary restriction , eczema was observed in twenty‐four infants , eleven out of thirty‐six breast‐fed and thirteen of eighteen formula‐fed . Avoidance of common dietary allergens during pregnancy and lactation enhanced the preventive beneficial effect of exclusive breast feeding on the incidence of atopic eczema among infants at high risk ABSTRACT A prospect i ve case‐control study is presented to assess an allergy prevention programme in children up to 36 months of age . Infants born at three maternity hospitals were followed from birth : 279 infants with high atopic risk ( intervention group ) were compared with 80 infants with similar atopic risk but no intervention ( non‐intervention group ) . The intervention programme included dietary measures ( exclusive and prolonged milk feeding diet followed by a hypoantigenic weaning diet ) and environmental measures ( avoidance of parental smoking in the presence of the babies , day care > 2 years of life ) . Mothers in this group who had insufficient breast milk were r and omly assigned to one of two coded formulas : either a hydrolysed milk formula ( Nidina HA , Nestlé ) or a conventional adapted formula ( Nan , Nestlé ) . Other environmental measures remained the same as for the breastfeeding mothers . The non‐intervention group were either breastfed or received the usual Italian milk feeding and weaning diet , without environmental advice . The main outcome measures were anthropometric measurements and allergic disease manifestations . Normal anthropometric data were observed both in the intervention group and in the nonintervention group . The incidence of allergic manifestations was much lower in the intervention group than in the nonintervention group at 1 year ( 11.5 versus 54.4 % , respectively ) and at 2 years ( 14.9 versus 65.6 % ) and 3 years ( 20.6 versus 74.1 % ) . Atopic dermatitis and recurrent wheezing were found in both the intervention group and the non‐intervention group from birth up to the second year of life , while urticaria and gastrointestinal disorders were only present in the non‐intervention group in the first year of life . Conjunctivitis and rhinitis were present after the second year in both the intervention group and the non‐intervention group . Relapse of the same allergic symptom was less in the intervention group ( 13.0 % ) than in the non‐intervention group ( 36.9 % ) . In comparison to the non‐intervention group , there were fewer intervention group cases with two or more different allergic symptoms ( 8.7 versus 32.6 % ) , and they were more likely to avoid steroid treatment ( 0 versus 10.8 % ) and hospital admission ( 0 versus 6.5 % ) . Babies in the non‐intervention group fed with adapted formula were more likely to develop allergies than breastfed babies in the same group . In the intervention group the breastfed infants had the lowest incidence of allergic symptoms , followed by the infants fed the hydrolysed formula ( ns ) . Infants in the intervention group fed the adapted formula had significantly more allergies than the breastfed and hydrolysed milk fed infants , although less than their counterparts in the non‐intervention group . Of the affected subjects in the intervention group , 80.4 % were RAST and /or Prick positive to food or inhalant allergens . Total serum IgE values detected at birth in the intervention group were not predictive , but at 1 and 2 years of age , IgE values more than 2 SD above the mean in asymptomatic babies were found to predictive for later allergy . In breastfed babies the total IgE level at 1 and 2 years of age was lower than in the other two feeding groups . Of the various factors tested in the non‐intervention group , the following were the most important in the pathogenesis of allergic symptoms : ( i ) formula implementation begun in the first week of life ; ( ii ) early weaning ( < 4 months ) ; ( iii ) feeding beef ( < 6 months ) ; ( iv ) early introduction of cow 's milk ( < 6 months ) ; and ( v ) parental smoking in the presence of the babies and early day care admission ( < 2 years of life ) . All the preventive measures used in this study ( exclusive breastfeeding and /or hydrolysed milk feeding , delayed and selective introduction of solid foods , and environmental advice ) were effective at the third year of follow‐up , greatly reducing allergic manifestations in high atopic risk babies in comparison with those not receiving these interventions IN 1953 Glaser and Johnstone1 reported on the use of soybean milk as an aid in the prophylaxis of allergic disease in children . They concluded that if one withheld cow 's milk , beef , egg and wheat from the diets of potentially allergic children from the time of birth until the age of six to nine months , only one quarter as many of these children acquired major respiratory allergies compared to their siblings and another nonrelated control group . They also reported that the incidence of atopic eczema in infants on the restricted diet was only one fourth as great as in the . . 54 babies who had been solely breast-fed for more than 6 months , 77 babies who had been breast-fed for 2 - -6 months , and 105 babies who had been weaned to cow's-milk-based formulas at less than 2 months were followed for the first 3 years of life . All the babies had the same pattern of solid food intake until 1 year of age . Compared with formula feeding , prolonged breast-feeding result ed in a lower incidence of severe or obvious atopic disease particularly in babies with family history of atopy We examined the relationship of diet to the development of atopic manifestations in a group of infants with an immediate family history of atopy , followed prospect ively from birth for up to 20 months of age . There was no relationship between the development of atopic dermatitis , rhinitis and wheeze and either 2 or 4 months exclusive breast feeding , or the introduction of cow 's milk or solids in the first 4 months of life . In addition there was no relationship between the introduction of milk , egg or wheat into the diet and the development of skin‐test positivity to these foods . In fact , five infants developed positive skin tests to the food prior to its introduction into the diet , suggesting exposure via maternal breast milk . Thus we have been unable to show a protective effect of either breast feeding or cow 's milk or solid avoidance on the development of atopic disease in infancy BACKGROUND The relationship between infant feeding and childhood asthma is controversial . This study tested the hypothesis that the relation between breast feeding and childhood asthma is altered by the presence of maternal asthma . METHODS Healthy non-selected newborn infants ( n=1246 ) were enrolled at birth . Asthma was defined as a physician diagnosis of asthma plus asthma symptoms reported on ⩾2 question naires at 6 , 9 , 11 or 13 years . Recurrent wheeze ( ⩾4 episodes in the past year ) was reported by question naire at seven ages in the first 13 years of life . Duration of exclusive breast feeding was based on prospect i ve physician reports or parental question naires completed at 18 months . Atopy was assessed by skin test responses at the age of 6 years . RESULTS The relationship between breast feeding , asthma , and wheeze differed with the presence or absence of maternal asthma and atopy in the child . After adjusting for confounders , children with asthmatic mothers were significantly more likely to have asthma if they had been exclusively breast fed ( OR 8.7 , 95 % CI 3.4 to 22.2 ) . This relationship was only evident for atopic children and persisted after adjusting for confounders . In contrast , the relation between recurrent wheeze and breast feeding was age dependent . In the first 2 years of life exclusive breast feeding was associated with significantly lower rates of recurrent wheeze ( OR 0.45 , 95 % CI 0.2 to 0.9 ) , regardless of the presence or absence of maternal asthma or atopy in the child . Beginning at the age of 6 years , exclusive breast feeding was unrelated to prevalence of recurrent wheeze , except for children with asthmatic mothers in whom it was associated with a higher odds ratio for wheeze ( OR 5.7 , 95 % CI 2.3 to 14.1 ) , especially if the child was atopic . CONCLUSION The relationship between breast feeding and asthma or recurrent wheeze varies with the age of the child and the presence or absence of maternal asthma and atopy in the child . While associated with protection against recurrent wheeze early in life , breast feeding is associated with an increased risk of asthma and recurrent wheeze beginning at the age of 6 years , but only for atopic children with asthmatic mothers ABSTRACT . The influence of a family history of atopy on atopic morbidity , and relationships between diet in infancy and allergic manifestations at the ages of one and five years were prospect ively studied in 91 children . A control group consisted of 72 children with no family history of atopy . At the age of one year , atopic manifestations were found in 19 % of 163 children , in 23 % of those with a family history of atopy and in 14 % of those with no such history . Skin problems were more common in children with a family history of atopy ( 43 % ) than in the control children ( 19 % ) . Of the children with a family history of atopy , 23 % had prolonged rhinorrhoea during infancy . The corresponding figure in children with no family history of atopy was 10 % . Prolonged rhinorrhoea during infancy correlated with parental smoking only in children with a family history of atopy ( 47 % vs. 18 % ) . At the age of five years , atopic disease was found in 17 % of 128 children , 24 % of those with a family history of atopy and 9 % of those with no such history . Atopic eczema was more common in children with a family history of atopy , irrespective of the diet consumed during infancy . Atopic signs were found in about half of all the children with a family history of atopy . If atopy had been present in the family , the child usually exhibited the same manifestation . Onset of atopic manifestations was not prevented or delayed Abstract The preventive effect of maternal avoidance of cow 's milk and eggs on the development of atopic dermatitis and sensitization to food allergens was studied in a prospect i ve trial with families at high risk for atopy . intervention included encouraging exclusive breast feeding for at least 3 months and delaying the controlled introduction of solid foods . In addition , one group received a maternal diet with the complete avoidance of milk and eggs in the last trimester of pregnancy and during the period of exclusive breast feeding , another group had the same diet starting after delivery , and mothers of the third group had no dietary restrictions . The period prevalences of atopic dermatitis as well as the rates of specific sensitization to eggs and milk at 6 and 12 months were not significantly different between groups . We were unable to demonstrate a significant preventive effect of maternal diet . Conclusion While breast feeding should be promoted for children at risk for atopy , mothers can be encouraged to stay on normal diet during pregnancy and the breast feeding period BACKGROUND Atopic dermatitis ( AD ) is the collection of the cutaneous inflammatory manifestations which are chronic or repetitive associated with the other atopic diseases . The prevalence of the AD varies from one country to another . AIM The aims of this work in to study the allergolicol , clinical and epidemiological profile of the AD in the south of Tunisia . METHODS our study is prospect i ve about 100 cases reported in a period of 18 months . The diagnostic was carried on the criteria of Hanifin and Radjka . For every patient we studied the biographical data and the clinical manifestations of AD . Allergoloigical explorations ( pricks-tests ) were carried out . RESULTS the overage of the patients was 104 months with extremes of 5 moths and 43 years . 65 % of our patients were men . At the beginning the average was 61 months with extremes of 2 months and 37 years . 55 patients had antecedents of family allergy and 34 had antecedents of personal allergy . The former preceded the AD in 28 cases . We did n't note any significant relation between the existence of familial allergy and the severity of the AD . In the statement , the principal factor was the contact with the house dust ( 33 cases ) , the duration of maternal breastfeeding ( overage 13.7 months ) did n't influence neither the SCORAD , nor the beginning age of the AD . The date of beginning of food diversity ( overage 6.16 months ) did n't significantly influence the severity of the illness . The clinical aspect was a sharp eczema in 71 % of the cases according . To the SCORAD score . The AD was judged to be weak in 5 cases , moderate in 68 cases and severe in 27 cases . The number of rise per year varied from one rise ( 75 cases ) , to more then 6 rises per year ( 6 cases ) . The evolution was chronic in 6 cases . The pricks test showed to be positive for the accariens in the group of aeroallergen in 9 cases among the 35 cases tested , and positive for the whole egg in the group of trophallergen in 5 cases among the 13 cases tested It has been reported that the feeding of cow 's milk may enhance the development of atopy in predisposed infants . A prospect i ve study following children from birth through 15 years of age in a private pediatric practice was design ed to determine if the food ingested during the first months of life is related to the development of atopy in the offspring of allergic families . Each of 328 children with a positive family history of allergy was assigned to one of three groups . according to the feeding preference of the parents : 48 were fed breast milk ; 79 , soy-based formula ; and 201 , cow 's milk formula . All groups had egg , citrus , tomato , and wheat restrictions as well as inhalant allergen avoidance . These were compared to a control group of 580 children with no family history of allergy . Breast fed infants were found to have approximately one-half the incidence of atopy of cow 's milk or soy formula fed infants from atopic families when followed for up to 15 years . Soy feeding produced no advantage over cow 's milk in the prophylaxis of allergic disease . There was a threefold increase in clinical ly apparent atopic disease in offspring of allergic families when compared to controls but only a two-fold increase if the infant was breast fed . These results support the hypothesis that breast feeding and delay of exposure to known allergens may reduce the frequency of clinical allergic disease in the offspring of allergic families To evaluate factors associated with initiation and duration of breastfeeding in Italy , 1601 ( 73 % ) respondents among 2192 r and omly selected mothers were interviewed within 1 mo of delivery . Mothers who started breastfeeding ( 85 % ) were followed‐up for 12 mo . A compliance rate of 100 % was obtained . At multiple logistic regression analysis , mother having been breastfed herself ( p<0.01 ) , nursing guidance in the maternity ward ( p= 0.01 ) and higher social class ( p= 0.03 ) were positively associated with initiation of breastfeeding . We found that 42 % , 19 % , 10 % and 4 % mothers were still breastfeeding at 3 , 6 , 9 and 12 mo after delivery , respectively . Cox multiple regression analysis showed a negative association between duration of breastfeeding and pacifier use ( p<0.01 ) , and a positive association with a higher level of maternal education ( p= 0.04 ) . Formula supplementation in the maternity ward ( given to 30 % of infants ) was associated with a shorter duration of exclusive breastfeeding ( p = 0.03 ) . Mothers need support with breastfeeding , particularly those from lower social background s and with lower levels of education . Early use of the pacifier should be discouraged BACKGROUND The literature regarding the association between breast-feeding and atopic diseases has been contradictory . OBJECTIVE We have assessed the relationship between breast-feeding and atopic disorders in a cohort followed into middle age . METHODS The Tasmanian Asthma Study is a population -based prospect i ve cohort study that has followed participants from the age of 7 to 44 years . Exclusive breast-feeding in the first 3 months of life was examined as a risk factor for atopic diseases by using multiple logistic regression and generalized estimating equation analyses . RESULTS At age 7 years , exclusively breast-fed children with a maternal history of atopy had a marginally lesser risk of current asthma than those not exclusively breast-fed ( odds ratio [ OR ] , 0.8 ; 95 % CI , 0.6 - 1.0 ) . However , after age 7 years , the risk reversed , and exclusively breast-fed children had an increased risk of current asthma at 14 ( OR , 1.46 ; 95 % CI , 1.02 - 2.07 ) , 32 ( OR , 1.84 ; 95 % CI , 1.06 - 3.3 ) , and 44 ( OR , 1.57 ; 95 % CI , 1.15 - 2.14 ) years . Exclusively breast-fed children also had a reduced risk of food allergy at age 7 years but an increased risk of food allergy ( OR , 1.26 ; 95 % CI , 1.1 - 1.5 ) and allergic rhinitis ( OR , 1.2 ; 95 % CI , 1.0 - 1.3 ) at 44 years . CONCLUSION Exclusively breast-fed babies with a maternal history of atopy were less likely to develop asthma before the age of 7 years , but more likely to develop asthma after the age of 7 years . CLINICAL IMPLICATION S The current recommendation to breast-feed high-risk infants for protection against early wheezing illness can be confirmed . However , the recommendation should be reconsidered for protection against allergic asthma and atopy in the longer term CONTEXT Current evidence that breastfeeding is beneficial for infant and child health is based exclusively on observational studies . Potential sources of bias in such studies have led to doubts about the magnitude of these health benefits in industrialized countries . OBJECTIVE To assess the effects of breastfeeding promotion on breastfeeding duration and exclusivity and gastrointestinal and respiratory infection and atopic eczema among infants . DESIGN The Promotion of Breastfeeding Intervention Trial ( PROBIT ) , a cluster-r and omized trial conducted June 1996-December 1997 with a 1-year follow-up . SETTING Thirty-one maternity hospitals and polyclinics in the Republic of Belarus . PARTICIPANTS A total of 17 046 mother-infant pairs consisting of full-term singleton infants weighing at least 2500 g and their healthy mothers who intended to breastfeed , 16491 ( 96.7 % ) of which completed the entire 12 months of follow-up . INTERVENTIONS Sites were r and omly assigned to receive an experimental intervention ( n = 16 ) modeled on the Baby-Friendly Hospital Initiative of the World Health Organization and United Nations Children 's Fund , which emphasizes health care worker assistance with initiating and maintaining breastfeeding and lactation and postnatal breastfeeding support , or a control intervention ( n = 15 ) of continuing usual infant feeding practice s and policies . MAIN OUTCOME MEASURES Duration of any breastfeeding , prevalence of predominant and exclusive breastfeeding at 3 and 6 months of life and occurrence of 1 or more episodes of gastrointestinal tract infection , 2 or more episodes of respiratory tract infection , and atopic eczema during the first 12 months of life , compared between the intervention and control groups . RESULTS Infants from the intervention sites were significantly more likely than control infants to be breastfed to any degree at 12 months ( 19.7 % vs 11.4 % ; adjusted odds ratio [ OR ] , 0.47 ; 95 % confidence interval [ CI ] , 0.32 - 0.69 ) , were more likely to be exclusively breastfed at 3 months ( 43.3 % vs 6.4 % ; P<.001 ) and at 6 months ( 7.9 % vs 0.6 % ; P = .01 ) , and had a significant reduction in the risk of 1 or more gastrointestinal tract infections ( 9.1 % vs 13.2 % ; adjusted OR , 0.60 ; 95 % CI , 0.40 - 0.91 ) and of atopic eczema ( 3.3 % vs 6.3 % ; adjusted OR , 0.54 ; 95 % CI , 0.31 - 0.95 ) , but no significant reduction in respiratory tract infection ( intervention group , 39.2 % ; control group , 39.4 % ; adjusted OR , 0.87 ; 95 % CI , 0.59 - 1.28 ) . CONCLUSIONS Our experimental intervention increased the duration and degree ( exclusivity ) of breastfeeding and decreased the risk of gastrointestinal tract infection and atopic eczema in the first year of life . These results provide a solid scientific underpinning for future interventions to promote breastfeeding Aims : To investigate the effect of breast feeding on allergic disease in infants up to 2 years of age . Methods : A birth cohort of 4089 infants was followed prospect ively in Stockholm , Sweden . Information about various exposures was obtained by parental question naires when the infants were 2 months old , and about allergic symptoms and feeding at 1 and 2 years of age . Duration of exclusive and partial breast feeding was assessed separately . Symptom related definitions of various allergic diseases were used . Odds ratios ( OR ) and 95 % confidence intervals ( CI ) were estimated in a multiple logistic regression model . Adjustments were made for potential confounders . Results : Children exclusively breast fed during four months or more exhibited less asthma ( 7.7 % v 12 % , ORadj = 0.7 , 95 % CI 0.5 to 0.8 ) , less atopic dermatitis ( 24 % v 27 % , ORadj = 0.8 , 95 % CI 0.7 to 1.0 ) , and less suspected allergic rhinitis ( 6.5 % v 9 % , ORadj = 0.7 , 95 % CI 0.5 to 1.0 ) by 2 years of age . There was a significant risk reduction for asthma related to partial breast feeding during six months or more ( ORadj = 0.7 , 95 % CI 0.5 to 0.9 ) . Three or more of five possible allergic disorders — asthma , suspected allergic rhinitis , atopic dermatitis , food allergy related symptoms , and suspected allergic respiratory symptoms after exposure to pets or pollen — were found in 6.5 % of the children . Exclusive breast feeding prevented children from having multiple allergic disease ( ORadj = 0.7 , 95 % CI 0.5 to 0.9 ) during the first two years of life . Conclusion : Exclusive breast feeding seems to have a preventive effect on the early development of allergic disease — that is , asthma , atopic dermatitis , and suspected allergic rhinitis , up to 2 years of age . This protective effect was also evident for multiple allergic disease The protective effect of breast feeding against atopic disease ( AD ) has been confirmed in several prospect i ve studies , while some retrospective studies have yielded controversial results . We have evaluated the prophylactic effect of prolonged breast feeding on the development of AD in 101 newborns at hereditary risk for allergic disease . The study design also included a strict dietary avoidance regimen of the nursing mothers . Our data demonstrate that breast feeding or breast feeding supplemented with soy milk exert a prophylactic effect on the development of AD in these at-risk infants . Mechanisms by which breast feeding protects from atopy are discussed Breast feeding ( BF ) provides many advantages to the offspring ; however , at present there is an ongoing debate as to whether or not it prevents allergic diseases . The aim of the current study was to investigate the effect of duration of BF on eczema in the first year of life . A birth cohort of 1128 infants was followed prospect ively from 5 months of pregnancy . Data were collected using question naires , a medical examination and blood tests for allergy at the age of 1 yr . Breast feeding was not statistically significant associated with eczema in the first year of life [ adj ORs with 95 % CIs : 0.8 ( 0.4 - 1.3 ) , 0.8 ( 0.5 - 1.3 ) and 1.0 ( 0.6 - 1.5 ) for BF duration of 1 - 6 wk , 7 - 12 wk and > or = 13 wk , respectively ] . Eczema was positively associated with atopy and educational level of the mother , use of antibiotics in pregnancy and passive smoking by the child during the first 12 months . Regular postnatal contact of the infants with dogs was inversely associated with eczema . Breast feeding was positively associated with eczema among children with non-atopic parents [ adj ORs with 95 % CIs : 2.1 ( 0.4 - 10.6 ) , 2.2 ( 0.4 - 11.3 ) and 1.9 ( 0.4 - 8.5 ) for BF duration of 1 - 6 wk , 7 - 12 wk and > or = 13 wk , respectively ] , whereas an inverse association was found among children with atopic parents [ adj ORs with 95 % CIs : 0.6 ( 0.3 - 1.3 ) , 0.7 ( 0.3 - 1.4 ) and 0.9 ( 0.5 - 1.7 ) for the same BF duration s ] . However , these associations were not statistically significant . Breast feeding has no significant effect on the prevalence of eczema in the first year of life . The effect of BF on eczema in children depends on parental atopy BACKGROUND A number of studies have observed an association between breast-feeding and increased risk of development of asthma and eczema . It has been proposed that these results might be due to early signs of atopic disease in the infant causing mothers to prolong breast-feeding . OBJECTIVE We sought to determine whether early symptoms of atopic disease ( eczema , food reaction , or asthma ) or positive skin prick test responses reduce the likelihood of ceasing breast-feeding . METHODS A prospect i ve birth cohort of 620 infants from Melbourne , Australia , was used . Telephone interviews every 4 weeks were conducted until 64 weeks and then again at 78 and 104 weeks to determine duration of breast-feeding ( both exclusive and total ) and evidence of atopic disease . Because of the varying time of onset of atopic symptoms , they were modeled as time-varying covariates in Cox models . RESULTS Only 52 ( 8.4 % ) infants did not establish breast-feeding , whereas an additional 103 ( 25.0 % ) did not establish exclusive breast-feeding . Early signs of atopic disease or sensitization were independently associated with an approximately 28 % reduction in risk of ceasing exclusive breast-feeding ( adjusted hazard ratio , 0.72 ; 95 % CI , 0.53 - 0.97 ) ; P=.029 ) , but there was no evidence for a relationship with risk of ceasing breast-feeding completely ( adjusted hazard ratio , 1.12 ; 95 % CI , 0.92 - 1.37 ; P=.262 ) . CONCLUSION Early signs of atopic disease might prolong the duration of exclusive breast-feeding . This could mask a protective effect of breast-feeding or even result in breast-feeding appearing to be a risk factor for the development of atopic diseases . Future investigation of the relationship between breast-feeding and atopic diseases should consider this possibility |
12,315 | 24,370,993 | Conclusions This meta- analysis showed that certain interventions can reduce the risk of sports injuries . | Background The effects of methods to prevent injuries have been studied in several systematic review s. However , no meta- analysis taking into account all r and omised controlled intervention trials aim ing at the prevention of sports injuries has been published .
Objective To summarise the effects of sports injury prevention interventions . | Background A protective effect on injury risk in youth sports through neuromuscular warm-up training routines has consistently been demonstrated . However , there is a paucity of information regarding the quantity and quality of coach-led injury prevention programmes and its impact on the physical performance of players . Objective The aim of this cluster-r and omised controlled trial was to assess whether different delivery methods of an injury prevention programme ( FIFA 11 + ) to coaches could improve player performance , and to examine the effect of player adherence on performance and injury risk . Method During the 2011 football season ( May – August ) , coaches of 31 tiers 1–3 level teams were introduced to the 11 + through either an unsupervised website or a coach-focused workshop with and without additional on-field supervisions . Playing exposure , adherence to the 11 + , and injuries were recorded for female 13-year-old to 18-year-old players . Performance testing included the Star Excursion Balance Test ( SEBT ) , single-leg balance , triple hop and jumping-over-a-bar tests . Results Complete preseason and postseason performance tests were available for 226 players ( 66.5 % ) . Compared to the unsupervised group , single-leg balance ( OR=2.8 ; 95 % CI 1.1 to 4.6 ) and the anterior direction of the SEBT improved significantly in the onfield supervised group of players ( OR=4.7 ; 95 % CI 2.2 to 7.1 ) , while 2-leg jumping performance decreased ( OR=−5.1 ; 95 % CI −9.9 to −0.2 ) . However , significant improvements in 5 of 6 reach distances in the SEBT were found , favouring players who highly adhered to the 11 + . Also , injury risk was lower for those players ( injury rate ratio , IRR=0.28 , 95 % CI 0.10 to 0.79 ) . Conclusions Different delivery methods of the FIFA 11 + to coaches influenced players ’ physical performance minimally . However , high player adherence to the 11 + result ed in significant improvements in functional balance and reduced injury risk BACKGROUND Ankle injuries account for 30 to 60 % of all parachuting injuries . This study was design ed to determine if outside-the-boot ankle braces could reduce ankle sprains during Army paratrooper training . METHODS The r and omized trial involved 777 volunteers from the U.S. Army Airborne School , Fort Benning , Ga. Of this group , 745 completed all study requirements ( 369 brace-wearers and 376 non-brace-wearers ) . Each volunteer made five parachute jumps , for a total of 3,674 jumps . RESULTS The incidence of inversion ankle sprains was 1.9 % in non-brace-wearers and 0.3 % in brace-wearers ( risk ratio , 6.9 ; p = 0.04 ) . Other injuries appeared unaffected by the brace . Overall , 5.3 % of the non-brace group and 4.6 % of the brace group experienced at least one injury . The risk ratio for injured individuals was 1.2:1 ( non-brace to brace groups ; p = 0.65 ) . CONCLUSION Inversion ankle sprains during parachute training can be significantly reduced by using an outside-the-boot ankle brace , with no increase in risk for other injuries Background This study was conducted to investigate whether the most common injuries in soccer could be prevented , and to determine if a simple question naire could identify players at increased risk . Hypothesis Introduction of targeted exercise programs to male soccer players with a history of previous injury or reduced function in the ankle , knee , hamstring , or groin will prevent injuries . Study Design R and omized controlled trial ; Level of evidence , 2 . Methods A total of 508 players representing 31 teams were included in the study . A question naire indicating previous injury and /or reduced function as inclusion criteria was used to divide the players into high-risk ( HR ) ( 76 % ) and low-risk ( LR ) groups . The HR players were r and omized individually into an HR intervention group or HR control group . Results A total of 505 injuries were reported , sustained by 56 % of the players . The total injury incidence was a mean of 3.2 ( 95 % confidence interval [ CI ] , 2.5–3.9 ) in the LR control group , 5.3 ( 95 % Cl , 4.6–6.0 ) in the HR control group ( P = .0001 vs the LR control group ) , and 4.9 ( 95 % Cl , 4.3–5.6 ) in the HR intervention group ( P = .50 vs the HR control group ) . For the main outcome measure , the sum of injuries to the ankle , knee , hamstring , and groin , there was also a significantly lower injury risk in the LR control group compared with the 2 other groups , but no difference between the HR intervention group and the HR control group . Compliance with the training programs in the HR intervention group was poor , with only 27.5 % in the ankle group , 29.2 % in the knee group , 21.1 % in the hamstring group , and 19.4 % in the groin defined as having carried out the minimum recommended training volume . Conclusion The players with a significantly increased risk of injury were able to be identified through the use of a question naire , but player compliance with the training programs prescribed was low and any effect of the intervention on injury risk could not be detected BACKGROUND Shock-absorbing and biomechanic shoe orthoses are frequently used in the prevention and treatment of back and lower extremity problems . One review concludes that the former is clinical ly effective in relation to prevention , whereas the latter has been tested in only 1 r and omized clinical trial , concluding that stress fractures could be prevented . OBJECTIVES To investigate if biomechanic shoe orthoses can prevent problems in the back and lower extremities and if reducing the number of days off-duty because of back or lower extremity problems is possible . DESIGN Prospect i ve , r and omized , controlled intervention trial . STUDY SUBJECTS One female and 145 male military conscripts ( aged 18 to 24 years ) , representing 25 % of all new conscripts in a Danish regiment . METHOD Health data were collected by question naires at initiation of the study and 3 months later . Custom-made biomechanic shoe orthoses to be worn in military boots were provided to all in the study group during the 3-month intervention period . No intervention was provided for the control group . Differences between the 2 groups were tested with the chi-square test , and statistical significance was accepted at P < .05 . Risk ratio ( RR ) , risk difference ( ARR ) , numbers needed to prevent ( NNP ) , and cost per successfully prevented case were calculated . OUTCOME VARIABLES Outcome variables included self-reported back and /or lower extremity problems ; specific problems in the back or knees or shin splints , Achilles tendonitis , sprained ankle , or other problems in the lower extremity ; number of subjects with at least 1 day off-duty because of back or lower extremity problems and total number of days off-duty within the first 3 months of military service because of back or lower extremity problems . RESULTS Results were significantly better in an actual-use analysis in the intervention group for total number of subjects with back or lower extremity problems ( RR 0.7 , ARR 19 % , NNP 5 , cost 98 US dollars ) ; number of subjects with shin splints ( RR 0.2 , ARR 19 % , NNP 5 , cost 101 US dollars ) ; number of off-duty days because of back or lower extremity problems ( RR 0.6 , ARR < 1 % , NNP 200 , cost 3750 US dollars ) . In an intention-to-treat analysis , a significant difference was found for only number of subjects with shin splints ( RR 0.3 , ARR 18 % , NNP 6 cost 105 US dollars ) , whereas a worst-case analysis revealed no significant differences between the study groups . CONCLUSIONS This study shows that it may be possible to prevent certain musculoskeletal problems in the back or lower extremities among military conscripts by using custom-made biomechanic shoe orthoses . However , because care-seeking for lower extremity problems is rare , using this method of prevention in military conscripts would be too costly . We also noted that the choice of statistical approach determined the outcome 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 Abstract . This prospect i ve r and omized intervention investigated whether training on a balance board could reduce the amount of traumatic injuries of the lower extremities in female soccer players . A total of 221 female soccer players from 13 different teams playing in the second and third Swedish divisions volunteered to participate in the study . Seven teams ( n=121 ) were r and omized to an intervention group and six teams ( n=100 ) to a control group and were followed during one outdoor season ( April – October ) . Before and after the season muscle flexibility and balance/postural sway of the lower extremities were measured in the players . There were no significant differences in age , height , weight , muscle flexibility and balance/postural sway of the lower extremities between the intervention and the control group . During the season the players in the intervention group performed a special training program consisting of 10–15 min of balance board training in addition to their st and ard soccer practice and games . After a 37 % drop-out the intervention group consisted of 62 players and the control group of 78 players . The results showed no significant differences between the groups with respect either to the number , incidence , or type of traumatic injuries of the lower extremities . The incidence rate of " major " injuries was higher in the intervention group than in the control group . Four of five anterior cruciate ligament injuries occurred in the intervention group , which means that we could not prevent severe knee injuries in female soccer players with balance board training . However , among the players who had been injured during the 3-month period prior to this investigation there were significantly more players from the control group than from the intervention group who sustained new injuries during the study period BACKGROUND Concussion is a serious problem in many contact sports , including rugby union football . The study 's primary aim was to measure the efficacy of padded headgear in reducing the rates of head injury or concussion . METHODS A cluster r and omized controlled trial with three arms was conducted with rugby union football teams as the unit of r and omization . Teams consisted of males participating in under 13- , 15- , 18- , and 20-yr age group competitions . The interventions were " st and ard " and " modified " padded headgear . Headgear wearing and injury were measured for each study team at each game over two seasons . RESULTS Eighty-two teams participated in year 1 and 87 in year 2 . A total of 1493 participants ( 10,040 player hours ) were in the control group , 1128 participants ( 8170 player hours ) were assigned to the st and ard headgear group , and 1474 participants ( 10,650 player hours ) were assigned to the modified headgear group . The compliance rates were low in all groups , but 46 % of participants wore st and ard headgear . An intention-to-treat analysis showed no differences in the rates of head injury or concussion between controls and headgear arms . Incidence rate ratios for st and ard headgear wearers referenced to controls were 0.95 and 1.02 for game and missed game injuries . Analyses of injury rates based on observed wearing patterns also showed no significant differences . Incidence rate ratios for st and ard headgear wearers referenced to nonwearers were 1.11 and 1.10 for game and missed game injuries . CONCLUSIONS Padded headgear does not reduce the rate of head injury or concussion . The low compliance rates are a limitation . Although individuals may choose to wear padded headgear , the routine or m and atory use of protective headgear can not be recommended Objective To evaluate the effectiveness of neuromuscular training in reducing the rate of acute knee injury in adolescent female football players . Design Stratified cluster r and omised controlled trial with clubs as the unit of r and omisation . Setting 230 Swedish football clubs ( 121 in the intervention group , 109 in the control group ) were followed for one season ( 2009 , seven months ) . Participants 4564 players aged 12 - 17 years ( 2479 in the intervention group , 2085 in the control group ) completed the study . Intervention 15 minute neuromuscular warm-up programme ( targeting core stability , balance , and proper knee alignment ) to be carried out twice a week throughout the season . Main outcome measures The primary outcome was rate of anterior cruciate ligament injury ; secondary outcomes were rates of severe knee injury ( > 4 weeks ’ absence ) and any acute knee injury . Results Seven players ( 0.28 % ) in the intervention group , and 14 ( 0.67 % ) in the control group had an anterior cruciate ligament injury . By Cox regression analysis according to intention to treat , a 64 % reduction in the rate of anterior cruciate ligament injury was seen in the intervention group ( rate ratio 0.36 , 95 % confidence interval 0.15 to 0.85 ) . The absolute rate difference was −0.07 ( 95 % confidence interval −0.13 to 0.001 ) per 1000 playing hours in favour of the intervention group . No significant rate reductions were seen for secondary outcomes . Conclusions A neuromuscular warm-up programme significantly reduced the rate of anterior cruciate ligament injury in adolescent female football players . However , the absolute rate difference did not reach statistical significance , possibly owing to the small number of events . Trial registration Clinical trials NCT00894595 Background : Sport is the leading cause of injury requiring medical attention among adolescents . We studied the effectiveness of a home-based balance-training program using a wobble board in improving static and dynamic balance and reducing sports-related injuries among healthy adolescents . Methods : In this cluster r and omized controlled trial , we r and omly selected 10 of 15 high schools in Calgary to participate in the fall of 2001 . We then recruited students from physical education classes and r and omly assigned them , by school , to either the intervention ( n = 66 ) or the control ( n = 61 ) group . Students in the intervention group participated in a daily 6-week and then a weekly 6-month home-based balance-training program using a wobble board . Students at the control schools received testing only . The primary outcome measures were timed static and dynamic balance , 20-m shuttle run and vertical jump , which were measured at baseline and biweekly for 6 weeks . Self-reported injury data were collected over the 6-month follow-up period . Results : At 6 weeks , improvements in static and dynamic balance were observed in the intervention group but not in the control group ( difference in static balance 20.7 seconds , 95 % confidence interval [ CI ] 10.8 to 30.6 seconds ; difference in dynamic balance 2.3 seconds , 95 % CI 0.7 to 4.0 seconds ) . There was evidence of a protective effect of balance training in over 6 months ( relative risk of injury 0.2 , 95 % CI 0.05 to 0.88 ) . The number needed to treat to avoid 1 injury over 6 months was 8 ( 95 % CI 4 to 35 ) . Interpretation : Balance training using a wobble board is effective in improving static and dynamic balance and reducing sports-related injuries among healthy adolescents In a r and omized prospect i ve study among 390 recruits , the hypothesis that improved shoe shock attenuation could lessen the incidence of overuse injuries was tested . During the 14 weeks of training , 90 % of the recruits sustained overuse injuries . Recruits training in a modified basketball shoe had a statistically significant lower incidence of metatarsal stress fractures and foot overuse injuries , compared with st and ard infantry boots , but their overall incidence of overuse injuries was not reduced . The effect of improved shoe shock attenuation was limited to those overuse injuries result ing from vertical impact loads Young female players in European h and ball have a very high injury incidence , up to 50 injuries per 1000 hours of game . More than half of these injuries happen without any external cause . The aim of the study was to investigate the effect of an intervention programme design ed to reduce the number of injuries in young female players in European h and ball , with special emphasis on injuries in the lower extremities . The programme was created using elite athlete training programmes and those design ed for rehabilitation of injured athletes with functional instability of their ankles and rupture of the anterior cruciate ligament . It included the use of an ankle disk for 10 - 15 min at all practice sessions , for one 10-month season ( August 1995-May 1996 ) . Twenty-two teams participated in the study , and were r and omly assigned to the intervention or control group . Eleven teams with 111 players were r and omised to the intervention group and 11 teams with 126 players to the control group . Data were analysed using a t-test for continuous variables , chi2- analysis and Fisher 's exact test for dichotomous variables and multivariate methods to determine odds-ratios . The results indicated that using the intervention programme decreased the numbers of both traumatic and overuse injuries significantly . The differences in injuries between the groups were 80 % during games and 71 % during practice . In addition , the players in the control group had a 5.9 times higher risk of acquiring an injury than the players in the intervention group A study was undertaken to evaluate the effect of a semi rigid ankle orthosis ( Sport-Stirrup ) on the incidence of ankle sprains in soccer players during 1 playing season . Senior soccer players were divided into 2 groups : play ers with previous ankle sprains ( N = 258 ) and players without such history ( N = 246 ) . The players in these groups were each r and omly allocated to either a semi rigid orthosis or a control group at the start of the playing season . All subsequent injuries during the season and the total number of playing hours were documented . There was a significant reduction in the incidence of ankle sprains ( injuries/1 000 playing hours ) by ankles in the orthosis group with previous sprains ( 0.14 ) com pared with the nonbraced group with previous sprains ( 0.86 ) . The incidence of ankle sprains was significantly higher in the nonbraced group with previous sprains ( 0.86 ) compared with the nonbraced group without pre vious sprains ( 0.46 ) . Thus , in this study , a semirigid or thosis significantly reduced the incidence of recurrent ankle sprains in soccer players with previous history of ankle sprains Background The incidence rate of soccer injuries is among the highest in sports , particularly for adult male soccer players . Purpose To investigate the effect of the ‘ The11 ’ injury prevention programme on injury incidence and injury severity in adult male amateur soccer players . Study design Cluster-r and omised controlled trial . Methods Teams from two high-level amateur soccer competitions were r and omly assigned to an intervention ( n=11 teams , 223 players ) or control group ( n=12 teams , 233 players ) . The intervention group was instructed to perform The11 in each practice session during one soccer season . The11 focuses on core stability , eccentric training of thigh muscles , proprioceptive training , dynamic stabilisation and plyometrics with straight leg alignment . All participants of the control group continued their practice sessions as usual . Results In total , 427 injuries were recorded , affecting 274 of 456 players ( 60.1 % ) . Compliance with the intervention programme was good ( team compliance=73 % , player compliance=71 % ) . Contrary to the hypothesis , injury incidences were almost equal between the two study groups : 9.6 per 1000 sports hours ( 8.4–11.0 ) for the intervention group and 9.7 ( 8.5–11.1 ) for the control group . No significant differences were found in injury severity , but a significant difference was observed in the location of the injuries : players in the intervention group sustained significantly less knee injuries . Conclusions This study did not find significant differences in the overall injury incidence or injury severity between the intervention and control group of adult male soccer players . More research is recommended , focusing on injury aetiology and risk factors in adult male amateur soccer players OBJECTIVE To study the effects of a school-based injury prevention program on physical activity injury incidence and severity . DESIGN Cluster r and omized controlled trial performed from January 1 , 2006 , through July 31 , 2007 . SETTING Forty Dutch primary schools . PARTICIPANTS A total of 2210 children ( aged 10 - 12 years ) . INTERVENTION Schools were r and omized to receive either the regular curriculum or an intervention program that targeted physical activity injuries . OUTCOME MEASURES Incidence and severity of physical activity injuries per 1000 hours of physical activity participation . RESULTS A total of 100 injuries in the intervention group and 104 injuries in the control group were registered . Nonresponse at baseline or follow-up was minimal ( 8.7 % ) . The Cox regression analyses adjusted for clustering showed a small nonsignificant intervention effect on total ( HR , 0.81 ; 95 % confidence interval [ CI ] , 0.41 - 1.59 ) , sports club ( 0.69 ; 0.28 - 1.68 ) , and leisure time injuries ( 0.75 ; 0.36 - 1.55 ) . However , physical activity appeared to be an effect modifier . In those who were less physically active , the intervention had a larger effect . The intervention reduced the total and leisure time injury incidence ( HR , 0.47 ; 95 % CI , 0.21 - 1.06 ; and 0.43 ; 0.16 - 1.14 ; respectively ) . Sports club injury incidence was significantly reduced ( HR , 0.23 ; 95 % CI , 0.07 - 0.75 ) . CONCLUSION We found a substantial and relevant reduction in physical activity injuries , especially in children in the low active group , because of the intervention . This school-based injury prevention program is promising , but future large-scale research is needed BACKGROUND The benefits of sport are well recognized , but many activities carry a sport-specific injury risk . Snowboarding has become an increasingly popular winter sport in Austria in recent years , with an estimated 900,000 participants annually . Roughly 6,000 of these suffer from injury and up to 2,000 sustain moderate or severe wrist injuries ( mainly fractures of the distal radius and epiphysiolyses ) . METHODS We conducted a prospect i ve , r and omized , controlled trial to test the protective effect of a wrist protector , which differs in position , stiffness , length , and fixation from conventional protectors . Seven hundred twenty-one snowboarders were r and omized into two groups . The risk factors and the injuries that occurred were registered by question naires and , in case of medical treatment , by medical reports . Time until injury ( in half-days ) was compared by the proportional hazards model . RESULTS Nine severe wrist injuries were sustained in the unprotected control group and only one in the protected group ( hazard ratio , 0.13 ; 95 % confidence limits , 0.02 , 1.04 ) . Twelve snowboarders of the protector group secretly discarded their protectors during the trial ( including the snowboarder who suffered the one and only severe wrist injury of this group ) . A per- protocol analysis was therefore performed , which demonstrated a more accentuated result ( p = 0.003 ) . There was no statistically significant increase in the incidence of other types of injury . Experience was shown to be a further protective factor . CONCLUSION We recommend the use of a wrist protector , particularly for novices participating in this sport . As in other domains of medicine , preventive measures can decrease morbidity also in terms of sport injuries Background It is unknown whether an exercise program can prevent overuse injuries in the lower extremity . An often encountered and important risk factor for the development of lower extremity overuse injuries is an abrupt increase in activity level . Hypothesis A preventive training program based on a literature review of intrinsic risk factors , and performed concurrent with an increase in physical activity , can reduce the incidence of overuse knee injuries and medial tibial stress syndrome , as well as increase running distance . Study Design R and omized controlled trial ; Level of evidence , 1 . Methods A total of 1020 soldiers aged 20.9 years ( range , 19–26 years ) undergoing 3 months of basic military training consecutively enrolled from December 2004 to December 2005 . The prevention program consisted of an exercise program of 15 minutes ’ duration 3 times a week , including 5 exercises for strength , flexibility , and coordination ; the placebo program consisted of 5 exercises for the upper body . Results During the observation period , 223 subjects sustained an injury , with 50 and 48 of these fulfilling the study criteria for overuse knee injuries or medial tibial stress syndrome , respectively . There were no significant differences in incidence of injury between the prevention group and the placebo group ( incidence , 0.22 vs 0.19 ; P = .162 ; relative risk = 1.05 [ range , 0.98–1.11 ] ) . The soldiers in the prevention group had the greater improvement in running distance in 12-minute run tests ( 82 vs 43 m ; P = .037 ) . Conclusion An exercise program with an emphasis on muscular strengthening , coordination , and flexibility based on intrinsic risk factors identified through a literature review did not influence the risk of developing overuse knee injuries or medial tibial stress syndrome in subjects undergoing an increase in physical activity . The program increased maximal running distance in a 12-minute test Abstract Despite various attempts at prevention , injury in downhill skiing continues to be a worrisome recreational problem . The purpose of this study was to test the effect of an instructional ski video on the behaviour and injuries of 763 downhill skiers . They were enrolled in two study groups , based on whether or not an instructional video had been shown in their bus on the way to a skiing resort . The video focussed on information regarding how to get started in downhill skiing and injury prevention . The outcome parameters , behaviour ( binding test and adjustment ) , injury risk , type and consequence , were registered on the return trip 8 days later by a question naire . In the intervention group all outcome parameters changed significantly . The binding test was performed by 86 % in the intervention group and by only 59 % in the control group ( P < 0.05 ) . Adjustment of the bindings was done by 22 % in the intervention group vs 14 % in the control group . Regarding injury risk , 205 injuries were seen in 158 persons ( 20.7 % ) which is 26 injured skiers per 1000 skier-days and 33.6 injuries per 1000 skier-days . In the intervention group 16 % of all skiers were injured vs 23 % in the control group , yielding a reduction in injury risk of 30 % ( P < 0.05 ) . Injuries caused by falls were seen in 12.6 % in the intervention group vs 16.2 % in the control group ( P < 0.05 ) . Injuries caused by collision were seen in 6 % of the intervention group vs 12 % in the control group ( P < 0.05 ) . The overall mean injury risk was 16 injuries per 1000 falls . Knee injuries made up 32.6 % of the total . For inexperienced skiers the knee injury risk was significantly lower if the bindings had been tested ( P < 0.05 ) . Therefore , an instructional ski video can change the behaviour of downhill skiers and reduce the injury risk and consequences significantly Background The rapidly increasing number of activity-induced musculoskeletal injuries among adolescents and young adults is currently a true public health burden . The objective of this study was to investigate whether a neuromuscular training programme with injury prevention counselling is effective in preventing acute musculoskeletal injuries in young men during military service . Methods The trial design was a population -based , r and omised study . Two successive cohorts of male conscripts in four companies of one brigade in the Finnish Defence Forces were first followed prospect ively for one 6-month term to determine the baseline incidence of injury . After this period , two new successive cohorts in the same four companies were r and omised into two groups and followed prospect ively for 6 months . Military service is compulsory for about 90 % of 19-year-old Finnish men annually , who comprised the cohort in this study . This r and omised , controlled trial included 968 conscripts comprising 501 conscripts in the intervention group and 467 conscripts in the control group . A neuromuscular training programme was used to enhance conscripts ' motor skills and body control , and an educational injury prevention programme was used to increase knowledge and awareness of acute musculoskeletal injuries . The main outcome measures were acute injuries of the lower and upper limbs . Results In the intervention groups , the risk for acute ankle injury decreased significantly compared to control groups ( adjusted hazards ratio ( HR ) = 0.34 , 95 % confidence interval ( 95 % CI ) = 0.15 to 0.78 , P = 0.011 ) . This risk decline was observed in conscripts with low as well as moderate to high baseline fitness levels . In the latter group of conscripts , the risk of upper-extremity injuries also decreased significantly ( adjusted HR = 0.37 , 95 % CI 0.14 to 0.99 , P = 0.047 ) . In addition , the intervention groups tended to have less time loss due to injuries ( adjusted HR = 0.55 , 95 % CI 0.29 to 1.04 ) . Conclusions A neuromuscular training and injury prevention counselling programme was effective in preventing acute ankle and upper-extremity injuries in young male army conscripts . A similar programme could be useful for all young individuals by initiating a regular exercise routine . Trial registration Clinical Trials.gov identifier number NCT00595816 Background The injury rate in soccer is high , and effective injury prevention methods are needed . Purpose To test the effect of a video-based awareness program on the incidence of acute injuries in soccer . Study Design R and omized control trial ; Level of evidence , 1 . Methods Participants were elite male soccer players from the top 2 divisions in Icel and . Fifteen of 20 teams completed the study : 7 intervention teams ( 127 players ) and 8 control teams ( 144 players ) chosen by r and om . Just before the start of the 2000soccer season , the intervention teams were visited with an intervention program . The program included a 15-minutepresentation with information on the injury risk of playing elite soccer , typical injuries , and their mechanisms . Then the players workedtogether in pairs and analyzed video sequences to develop preventive strategies . The 12 video sequences were selected fromthe previous Icel and ic soccer season , representing 3 typical injury mechanisms that accounted for more than half of all incidentsrecorded . During the season , team physical therapists prospect ively recorded all acute injuries , and coaches recorded trainingexposure on a special form . Injury incidence was compared between groups and between the 1999 and 2000 seasons for teamsthat participated in both seasons . Results No difference was observed in injury incidence between the intervention ( 6.6 ± 0.7 injuries per 1000 player hours ) and control groups ( 6.6 ± 0.7 injuries per 1000 player hours ) . Furthermore , there was no difference in injury location or type . Conclusion The video-based injury awareness program showed no effect on injury rate Injuries of the wrist are common among snowboarders and in-line skaters . Wrist protectors have been developed to protect against injury . Some studies support the use of such wrist protection , but others emphasize the fact that wrist protectors may transfer the injury to other locations in the forearm . We conducted a prospect i ve , r and omized , clinical study of 5029 snowboarders , 2515 in a braced group and 2514 in a control group . The primary endpoint was fracture or sprain of the wrist with loss of range of motion and pain of at least a 3-day duration . Concomitant injuries were also recorded . Eight wrist injuries occurred in the braced group and 29 occurred in the control group . This was a significant difference . Beginners ( first 5 days on a snowboard ) and snowboarders with rented equipment were more prone to injury than others . No injuries could be related to the use of the wrist brace . We conclude that wrist braces are effective in protecting snowboarders against wrist injury . Beginners are a high-risk group Abstract Objective To investigate the effect of a structured warm-up programme design ed to reduce the incidence of knee and ankle injuries in young people participating in sports . Design Cluster r and omised controlled trial with clubs as the unit of r and omisation . Setting 120 team h and ball clubs from central and eastern Norway ( 61 clubs in the intervention group , 59 in the control group ) followed for one league season ( eight months ) . Participants 1837 players aged 15 - 17 years ; 958 players ( 808 female and 150 male ) in the intervention group ; 879 players ( 778 female and 101 male ) in the control group . Intervention A structured warm-up programme to improve running , cutting , and l and ing technique as well as neuromuscular control , balance , and strength . Main outcome measure The rate of acute injuries to the knee or ankle . Results During the season , 129 acute knee or ankle injuries occurred , 81 injuries in the control group ( 0.9 ( SE 0.09 ) injuries per 1000 player hours ; 0.3 ( SE 0.17 ) in training v 5.3 ( SE 0.06 ) during matches ) and 48 injuries in the intervention group ( 0.5 ( SE 0.11 ) injuries per 1000 player hours ; 0.2 ( SE 0.18 ) in training v 2.5 ( SE 0.06 ) during matches ) . Fewer injured players were in the intervention group than in the control group ( 46 ( 4.8 % ) v ( 76 ( 8.6 % ) ; relative risk intervention group v control group 0.53 , 95 % confidence interval 0.35 to 0.81 ) . Conclusion A structured programme of warm-up exercises can prevent knee and ankle injuries in young people playing sports . Preventive training should therefore be introduced as an integral part of youth sports programmes PURPOSE To investigate the effectiveness of a multistation proprioceptive exercise program for the prevention of ankle injuries in basketball players using a prospect i ve r and omized controlled trial in combination with biomechanical tests of neuromuscular performance . METHODS A total of 232 players participated in the study and were r and omly assigned to a training or control group following the CONSORT statement . The training group performed a multistation proprioceptive exercise program , and the control group continued with their normal workout routines . During one competitive basketball season , the number of ankle injuries was counted and related to the number of sports participation sessions using logistic regression . Additional biomechanical pre – post tests ( angle reproduction and postural sway ) were performed in both groups to investigate the effects on neuromuscular performance . RESULTS In the control group , 21 injuries occurred , whereas in the training group , 7 injuries occurred . The risk for sustaining an ankle injury was significantly reduced in the training group by approximately 65 % . [ corrected ] The corresponding number needed to treat was 7 . Additional biomechanical tests revealed significant improvements in joint position sense and single-limb stance in the training group . CONCLUSIONS The multistation proprioceptive exercise program effectively prevented ankle injuries in basketball players . Analysis of number needed to treat clearly showed the relatively low prevention effort that is necessary to avoid an ankle injury . Additional biomechanical tests confirmed the neuromuscular effect and confirmed a relationship between injury prevention and altered neuromuscular performance . With this knowledge , proprioceptive training may be optimized to specifically address the dem and s in various athletic activities Background Ankle sprains are frequent injuries in soccer . Several strategies can be used to prevent further ankle sprains in athletes : the most common are proprioceptive training , strength training , and orthoses . Objective To investigate which of these 3 interventions is the most effective in preventing ankle sprains in athletes with previous ankle inversion sprain . Study Design R and omized controlled trial ; Level of evidence , 1 . Methods and Measures Eighty male soccer players ( age , 24.6 ± 2.63 years ; height , 175.60 ± 4.36 cm ; weight , 64.26 ± 8.37 kg ) in the first division of a men 's league who had experienced previous ankle inversion sprain were r and omly selected from an original population of 120 players . The subjects were individually and r and omly assigned to 4 study groups : group 1 ( n = 20 ) followed the proprioceptive program , group 2 ( n = 20 ) followed the strength program , group 3 ( n = 20 ) used orthoses , and group 4 ( n = 20 ) was the control group . Data on the frequency of ankle sprain reinjury were collected at the end of the session . Results There were no significant differences among the groups in the number of exposures . The incidence of ankle sprains in players in the proprioception training group was significantly lower than in the control group ( relative risk of injury , 0.13 ; 95 % confidence interval , 0.003 - 0.93 ; P = .02 ) . The findings with respect to the strength and orthotic groups in comparison with the control group were not significant ( relative risk of injury , 0.5 ; 95 % confidence interval , 0.11 - 1.87 ; P = .27 for strength ; relative risk of injury , 0.25 ; 95 % confidence interval , 0.03 - 1.25 ; P = .06 for orthotic group ) . Conclusion Proprioceptive training , compared with no intervention , was an effective strategy to reduce the rate of ankle sprains among male soccer players who suffered ankle sprain A set of exercises -- the " 11"--have been selected to prevent football injuries . The purpose of this cluster-r and omized controlled trial was to investigate the effect of the " 11 " on injury risk in female youth football . Teams were r and omized to an intervention ( n=59 teams , 1091 players ) or a control group ( n=54 teams , 1001 players ) . The intervention group was taught the " 11 , " exercises for core stability , lower extremity strength , neuromuscular control and agility , to be used as a 15-min warm-up program for football training over an 8-month season . A total of 396 players ( 20 % ) sustained 483 injuries . No difference was observed in the overall injury rate between the intervention ( 3.6 injuries/1000 h , confidence interval ( CI ) 3.2 - 4.1 ) and control group ( 3.7 , CI 3.2 - 4.1 ; RR=1.0 , CI 0.8 - 1.2 ; P=0.94 ) nor in the incidence for any type of injury . During the first 4 months of the season , the training program was used during 60 % of the football training sessions , but only 14 out of 58 intervention teams completed more than 20 prevention training sessions . In conclusion , we observed no effect of the injury prevention program on the injury rate , most likely because the compliance with the program was low Objective : To examine the effectiveness of a sport-specific balance training program in reducing injury in adolescent basketball . Design : Cluster r and omized controlled trial . Setting : Twenty-five high schools in Calgary and surrounding area . Subjects : Nine hundred and twenty high school basketball players ( ages 12 - 18 ) . Intervention : Subjects were r and omly allocated by school to the control ( n = 426 ) and training group ( n = 494 ) . Both groups were taught a st and ardized warm-up program . The training group was also taught an additional warm-up component and a home-based balance training program using a wobble board . Main Outcome Measures : All injuries occurring during basketball that required medical attention and /or caused a player to be removed from that current session and /or miss a subsequent session were then recorded and assessed by a team therapist who was blinded to training group allocation . Results : A basketball-specific balance training program was protective of acute-onset injuries in high school basketball [ RR = 0.71 ( 95 % CI ; 0.5 - 0.99 ) ] . The protective effect found with respect to all injury [ RR = 0.8 ( 95 % CI ; 0.57 - 1.11 ) ] , lower-extremity injury [ RR = 0.83 ( 95 % CI ; 0.57 - 1.19 ) ] , and ankle sprain injury [ RR = 0.71 ( 95 % CI ; 0.45 - 1.13 ) ] were not statistically significant . Self-reported compliance to the intended home-based training program was poor ( 298/494 or 60.3 % ) . Conclusions : A basketball-specific balance training program was effective in reducing acute-onset injuries in high school basketball . There was also a clinical ly relevant trend found with respect to the reduction of all , lower-extremity , and ankle sprain injury . Future research should include further development of neuromuscular prevention strategies in addition to further evaluation of methods to increase compliance to an injury-prevention training program in adolescents Objectives There is no consensus on the aetiology and prevention of running-related injuries in runners . Preconditioning studies among different athlete population s show positive effects on the incidence of sports injuries . Hypothesis A 4-week preconditioning programme in novice runners will reduce the incidence of running-related injuries . Study design R and omised controlled clinical trial ; level of evidence , 1 . Methods Novice runners ( N=432 ) prepared for a four-mile recreational running event . Participants were allocated to the 4-week preconditioning ( PRECON ) group ( N=211 ) or the control group ( N=221 ) . The PRECON group started a 4-week training programme , prior to the running programme , with walking and hopping exercises . After the 4-week period both groups started a 9-week running programme . In both groups information was registered on running exposure and running-related injuries ( RRIs ) using an internet-based running log . Primary outcome measure was RRIs per 100 runners . An RRI was defined as any musculoskeletal complaint of the lower extremity or lower back causing restriction of running for at least a week . Results The incidence of RRIs was 15.2 % in the PRECON group and 16.8 % in the control group . The difference in RRIs between the groups was not significant ( χ2=0.161 , df=1 , p=0.69 ) . Conclusion This prospect i ve study demonstrated that a 4-week PRECON programme with walking and hopping exercises had no influence on the incidence of RRIs in novice runners OBJECTIVE To determine the effectiveness of coach-led neuromuscular warm-up on reducing lower extremity ( LE ) injuries in female athletes in a mixed-ethnicity , predominantly low-income , urban population . DESIGN Cluster r and omized controlled trial . SETTING Chicago public high schools . PARTICIPANTS Of 258 coaches invited to participate , 95 ( 36.8 % ) enrolled ( 1558 athletes ) . Ninety coaches and 1492 athletes completed the study . INTERVENTIONS We r and omized schools to intervention and control groups . We trained intervention coaches to implement a 20-minute neuromuscular warm-up . Control coaches used their usual warm-up . MAIN OUTCOME MEASURES Coach compliance was tracked by self-report and direct observation . Coaches reported weekly athlete exposures ( AEs ) and LE injuries causing a missed practice or game . Research assistants interviewed injured athletes . Injury rates were compared between the control and intervention groups using χ(2 ) and Fisher exact tests . Significance was set at P < .05 . Poisson regression analysis adjusted for clustering and covariates in an athlete subset reporting personal information ( n = 855 ; 57.3 % ) . RESULTS There were 28 023 intervention AEs and 22 925 control AEs . Intervention coaches used prescribed warm-up in 1425 of 1773 practice s ( 80.4 % ) . Intervention athletes had lower rates per 1000 AEs of gradual-onset LE injuries ( 0.43 vs 1.22 , P < .01 ) , acute-onset noncontact LE injuries ( 0.71 vs 1.61 , P < .01 ) , noncontact ankle sprains ( 0.25 vs 0.74 , P = .01 ) , and LE injuries treated surgically ( 0 vs 0.17 , P = .04 ) . Regression analysis showed significant incidence rate ratios for acute-onset noncontact LE injuries ( 0.33 ; 95 % CI , 0.17 - 0.61 ) , noncontact ankle sprains ( 0.38 ; 95 % CI , 0.15 - 0.98 ) , noncontact knee sprains ( 0.30 ; 95 % CI , 0.10 - 0.86 ) , and noncontact anterior cruciate ligament injuries ( 0.20 ; 95 % CI , 0.04 - 0.95 ) . CONCLUSION Coach-led neuromuscular warm-up reduces noncontact LE injuries in female high school soccer and basketball athletes from a mixed-ethnicity , predominantly low-income , urban population . TRIAL REGISTRATION CLINICAL TRIALS.ORG IDENTIFIER : NCT01092286 Background : The incidence of acute hamstring injuries is high in several sports , including the different forms of football . Purpose : The authors investigated the preventive effect of eccentric strengthening of the hamstring muscles using the Nordic hamstring exercise compared with no additional hamstring exercise on the rate of acute hamstring injuries in male soccer players . Study Design : R and omized controlled trial ; Level of evidence , 1 . Methods : Fifty Danish male professional and amateur soccer teams ( 942 players ) were allocated to an intervention group ( 461 players ) or a control group ( 481 players ) . Players in the intervention group conducted a 10-week progressive eccentric training program followed by a weekly seasonal program , whereas players in the control group followed their usual training program . The main outcome measures were numbers of overall , new , and recurrent acute hamstring injuries during 1 full soccer season . Results : Fifty-two acute hamstring injuries in the control group compared with 15 injuries in the intervention group were registered . Comparing intervention versus the control group , overall acute hamstring injury rates per 100 player seasons were 3.8 versus 13.1 ( adjusted rate ratio [ RR ] , 0.293 ; 95 % confidence interval [ CI ] , 0.150 - 0.572 ; P < .001 ) . New injury rates per 100 player seasons were 3.1 versus 8.1 ( RR , 0.410 ; 95 % CI , 0.180 - 0.933 ; P = .034 ) , whereas recurrent injury rates per 100 player seasons were 7.1 versus 45.8 ( RR , 0.137 ; 95 % CI , 0.037 - 0.509 ; P = .003 ) . Number needed to treat [ NNT ] to prevent 1 acute hamstring injury ( new or recurrent ) is 13 ( 95 % CI , 9 - 23 ) players . The NNT to prevent 1 new injury is 25 ( 95 % CI , 15 - 72 ) players , and NNT to prevent 1 recurrent injury is 3 ( 95 % CI , 2 - 6 ) players . Conclusion : In male professional and amateur soccer players , additional eccentric hamstring exercise decreased the rate of overall , new , and recurrent acute hamstring injuries The purpose of this prospect i ve , r and omized study was to determine the efficacy of a prophylactic knee brace to reduce the frequency and severity of acute knee injuries in football in an athletic environment in which the athletic shoe , playing surface , athlete-exposure , knee injury history , and brace assignment were either statistically or experimentally controlled . The partici pants in the study were 1396 cadets at the United States Military Academy , West Point , New York , who experienced a total of 21,570 athlete-exposures in the 1986 and 1987 fall intramural tackle football seasons . The use of prophylactic knee braces significantly re duced the frequency of knee injuries , both in the total number of subjects injured and in the total number of medial collateral ligament injuries incurred . However , the reduction in the frequency of knee injuries ( total and medial collateral ligament ) was dependent on player position . Defensive players who wore prophylactic knee braces had statistically fewer knee injuries than players who served as controls . This was not true of offensive players who served as controls ; they had statistically no difference in the number of knee injuries from players who wore prophylactic knee braces . The severity of medial collateral ligament and anterior cruciate ligament knee injuries was not significantly reduced with the use of prophylactic knee braces Objective To evaluate the effectiveness of an unsupervised proprioceptive training programme on recurrences of ankle sprain after usual care in athletes who had sustained an acute sports related injury to the lateral ankle ligament . Design R and omised controlled trial , with one year follow-up . Setting Primary care . Participants 522 athletes , aged 12 - 70 , who had sustained a lateral ankle sprain up to two months before inclusion ; 256 ( 120 female and 136 male ) in the intervention group ; 266 ( 128 female and 138 male ) in the control group . Intervention Both groups received treatment according to usual care . Athletes allocated to the intervention group additionally received an eight week home based proprioceptive training programme . Main outcome measure Self reported recurrence of ankle sprain . Results During the one year follow-up , 145 athletes reported a recurrent ankle sprain : 56 ( 22 % ) in the intervention group and 89 ( 33 % ) in the control group . Nine athletes needed to be treated to prevent one recurrence ( number needed to treat ) . The intervention programme was associated with a 35 % reduction in risk of recurrence . Cox regression analysis showed significantly fewer recurrent ankle sprains in the intervention than in the control group . This effect was found for self reported recurrent ankle sprains ( relative risk 0.63 , 95 % confidence interval 0.45 to 0.88 ) , recurrent ankle sprains leading to loss of sports time ( 0.53 , 0.32 to 0.88 ) , and recurrent ankle sprains result ing in healthcare costs or lost productivity costs ( 0.25 , 0.12 to 0.50 ) . No significant differences were found between medically treated athletes in the intervention group and medically treated controls . Athletes in the intervention group who were not medically treated had a significantly lower risk of recurrence than controls who were not medically treated . Conclusions The use of a proprioceptive training programme after usual care of an ankle sprain is effective for the prevention of self reported recurrences . This proprioceptive training was specifically beneficial in athletes whose original sprain was not medically treated . Trial registration Ankle sprains are often complicated by functional instability and repeated sprains . Rehabilitation with wobble boards in patients with functional instability has been tested , and significant improvement has been found compared to no training . The aim of this study was to investigate whether the number of patients with residual symptoms following ankle sprains could be reduced by training on a wobble board during 12-week recovery period . In addition , the influence of training in the time course reduction of edema was investigated . We performed a prospect i ve study including 61 patients , all active in sports for more than 2 hours a week with primary ankle sprains . The effect of a 12-week training program with wobble board was compared with no training . Forty-eight patients completed the study . In the follow-up period ( mean X = 230 days ) , we found significantly fewer recurrent sprains , and significantly fewer patients in the training group had functional instability of the ankle compared with the no training group . There were no differences in the two groups in the time which elapsed before patients were painless at walking , during running , or at sports . Volumetric measurements revealed no difference in the speed of reduction of hematoma and edema of the ankle and foot between the two groups . We conclude that training on a wobble board early after primary stage 2 ankle sprains is effective in reducing residual symptoms following this lesion and that training does not seem to affect the time course reduction in edema Lower limb overuse injuries are common among people who are exposed to physical stress . Orthotic shoe insoles are widely used to prevent lower limb overuse injuries . Here , we conducted a r and omized-controlled study to examine whether the use of orthotic insoles prevents lower limb overuse injuries . Participants ( n=228 ) were r and omly assigned to use ( n=73 ) or not to use ( n=147 ) orthotic insoles . The insoles were molded to the shape of the foot to provide support during physical activity . The main outcome measure in the present study was the physician-diagnosed lower limb overuse injury . Thirty-four ( 46.6 % ) subjects in the insole group were diagnosed with a lower limb overuse injury compared with 56 ( 38.1 % ) in the control group ( P=0.29 ) during the 6-month study period . When body mass index and the results of a 12-min running test and muscle strength were adjusted in a Cox 's regression model , the hazard ratio for lower limb overuse injury in the insole group was 1.3 ( 95 % confidence intervals : 0.8 - 2.1 ) compared with the control group . Use of orthotic insoles was not associated with a decrease in lower limb overuse injuries . Our findings suggest that routine use of orthotic insoles does not prevent physical-stress-related lower limb injuries in healthy young male adults Background Neuromuscular and proprioceptive training programs can decrease noncontact anterior cruciate ligament injuries ; however , they may be difficult to implement within an entire team or the community at large . Hypothesis A simple on-field alternative warm-up program can reduce noncontact ACL injuries . Study Design R and omized controlled trial ( clustered ) ; Level of evidence , 1 . Methods Participating National Collegiate Athletic Association Division I women 's soccer teams were assigned r and omly to intervention or control groups . Intervention teams were asked to perform the program 3 times per week during the fall 2002 season . All teams reported athletes ’ participation in games and practice s and any knee injuries . Injury rates were calculated based on athlete exposures , expressed as rate per 1000 athlete exposures . A z statistic was used for rate ratio comparisons . Results Sixty-one teams with 1435 athletes completed the study ( 852 control athletes ; 583 intervention ) . The overall anterior cruciate ligament injury rate among intervention athletes was 1.7 times less than in control athletes ( 0.199 vs 0.340 ; P = .198 ; 41 % decrease ) . Noncontact anterior cruciate ligament injury rate among intervention athletes was 3.3 times less than in control athletes ( 0.057 vs 0.189 ; P = .066 ; 70 % decrease ) . No anterior cruciate ligament injuries occurred among intervention athletes during practice versus 6 among control athletes ( P = .014 ) . Game-related noncontact anterior cruciate ligament injury rates in intervention athletes were reduced by more than half ( 0.233 vs 0.564 ; P = .218 ) . Intervention athletes with a history of anterior cruciate ligament injury were significantly less likely to suffer another anterior cruciate ligament injury compared with control athletes with a similar history ( P = .046 for noncontact injuries ) . Conclusion This program , which focuses on neuromuscular control , appears to reduce the risk of anterior cruciate ligament injuries in collegiate female soccer players , especially those with a history of anterior cruciate ligament injury This r and omized clinical study was design ed to pro spectively determine the efficacy of a semirigid ankle stabilizer in reducing the frequency and severity of acute ankle injuries in basketball . Athletic shoe , playing surface , athlete-exposure , ankle injury history , and brace assignment were either statistically or experimen tally controlled . Participants in the study were 1601 United States Military Academy cadets with no prepar ticipation , clinical , functional , or radiographic evidence of ankle instability . Subjects experienced a total of 13,430 athlete-exposures in the 1990 and 1991 intra mural basketball seasons . Ankle injury was defined as acute trauma to the ankle ligaments that result ed in an athlete 's inability to participate in basketball 1 day after the injury . Use of ankle stabilizers significantly reduced the frequency of ankle injuries . Reduction in ankle in juries , however , depended on the nature of injury ( fewer contact injuries occurred among those who wore braces ) . Injury severity was not statistically reduced , and wearing the ankle stabilizer did not affect the fre quency of knee injuries . Attitude toward ankle stabilizer use improved as use of the stabilizer increased Background Ankle sprains are the most common musculoskeletal injuries that occur in athletes , and they have a profound impact on health care costs and re sources . Hypothesis A balance training program can reduce the risk of ankle sprains in high school athletes . Study Design R and omized controlled clinical trial ; Level of evidence , 1 . Methods Seven hundred and sixty-five high school soccer and basketball players ( 523 girls and 242 boys ) were r and omly assigned to either an intervention group ( 27 teams , 373 subjects ) that participated in a balance training program or to a control group ( 28 teams , 392 subjects ) that performed only st and ard conditioning exercises . On-site athletic trainers recorded athlete exposures and sprains . Results The rate of ankle sprains was significantly lower for subjects in the intervention group ( 6.1 % , 1.13 of 1000 exposures vs 9.9 % , 1.87 of 1000 exposures ; P = .04 ) . Athletes with a history of an ankle sprain had a 2-fold increased risk of sustaining a sprain ( risk ratio , 2.14 ) , whereas athletes who performed the intervention program decreased their risk of a sprain by one half ( risk ratio , 0.56 ) . The ankle sprain rate for athletes without previous sprains was 4.3 % in the intervention group and 7.7 % in the control group , but this difference was not significant ( P = .059 ) . Conclusion A balance training program will significantly reduce the risk of ankle sprains in high school soccer and basketball players In a prospect i ve study of stress fractures the hypothesis that a shock-absorbing orthotic device worn within military boots could lessen the incidence of stress fractures was tested . The incidence of metatarsal , tibial , and femoral stress fractures was lower in the orthotic group , but only the latter difference was statistically significant . The time of onset and the location of stress fractures between orthotic and nonorthotic users did not differ . These findings suggest that the incidence of femoral stress fractures , which are the most dangerous type of stress fracture because of their high risk of developing into displaced fractures , can be reduced by an orthotic device Background Soccer injuries are common , and athletes returning to play after injury are especially at risk . Few studies have investigated how to prevent reinjury . Hypothesis The rate of reinjury is reduced using a coach-controlled rehabilitation program . Study Design R and omized controlled trial ; Level of evidence , 1 . Methods Twenty-four male amateur soccer teams were r and omized into an intervention ( n = 282 ) and control group ( n = 300 ) . The intervention was implemented by team coaches and consisted of information about risk factors for reinjury , rehabilitation principles , and a 10-step progressive rehabilitation program including return to play criteria . During the 2003 season , coaches reported individual exposure and all time loss injuries were evaluated by a doctor and a physiotherapist . Four teams ( n = 100 ) withdrew from the study after r and omization , leaving 10 teams with 241 players for analysis in both groups . Results There were 90 injured players ( 132 injuries ) in the intervention group , and 10 of these ( 11 % ) suffered 14 reinjuries during the season . In the control group , 23 of 79 injured players ( 29 % ) had 40 recurrences ( 134 injuries ) . A Cox regression analysis showed a 66 % reinjury risk reduction in the intervention group for all injury locations ( hazard ratio [ HR ] 0.34 , 95 % confidence interval [ CI ] 0.16 - 0.72 , P = .0047 ) and 75 % for lower limb injuries ( HR 0.25 , 95 % CI 0.11 - 0.57 , P < .001 ) . The preventive effect was greatest within the first week of return to play . Injured players in the intervention group complied with the intervention for 90 of 132 injuries ( 68 % ) . Conclusion The reinjury rate in amateur male soccer players was reduced after a controlled rehabilitation program implemented by coaches Sedentary individuals , particularly new military recruits , who start a physical training program have a substantial risk of developing an overuse injury of the lower limb . In this study we investigated the effect of neoprene insoles on the incidence of overuse injuries during 9 weeks of basic military training . The experimental group consisted of 237 r and omly selected new recruits , while 1151 recruits were the control group . Insoles were given to the experimental group and compliance was monitored . A panel of doctors documented and classi fied all injuries occurring during the 9 week period . A total of 54 ( 22.8 % ) and 237 ( 31.9 % ) injuries were reported in the experimental and control groups , re spectively . In both groups , the majority of injuries were overuse ( experimental group , 90.7 % ; control group , 86.4 % ) . The mean weekly incidence of total overuse injuries and tibial stress syndrome was significantly lower ( P < 0.05 ) in the experimental group . The mean incidence of stress fractures was lower in the experimental group but not significantly so ( 0.05 < P < 0.1 ) . This study shows that the incidence of total overuse injuries and tibial stress syndrome during 9 weeks of basic military training can be reduced by wearing insoles 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 In a prospect i ve study of stress fractures the hypothesis that training with custom made biomechanical shoe orthoses could lessen the incidence of stress fractures in infantry recruits was tested . Recruits were assigned r and omly to groups and given soft biomechanical orthoses or semirigid biomechanical orthoses and compared with a control group that did not train in biomechanical orthoses . All recruits wore infantry boots with soles design ed like those of basketball shoes . Recruits were examined biweekly during 14 weeks of basic training . The incidence of stress fractures was 15.7 % for the recruits with the semirigid biomechanical orthoses , 10.7 % for the recruits with the soft biomechanical orthoses , and 27 % for the control group . The soft biomechanical orthoses were tolerated better by the recruits than were the semirigid devices . Among trainees at high risk for stress fractures , prophylactic use of custom made biomechanical orthoses may be warranted Background Although running has positive effects on health and fitness , the incidence of a running-related injury ( RRI ) is high . Research on prevention of RRI is scarce ; to date , no studies have involved novice runners . Hypothesis A grade d training program for novice runners will lead to a decrease in the absolute number of RRIs compared with a st and ard training program . Study Design R and omized controlled trial ; Level of evidence , 1 . Methods GRONORUN ( Groningen Novice Running ) is a 2-armed r and omized controlled trial comparing a st and ard 8-week training program ( control group ) and an adapted , grade d , 13-week training program ( intervention group ) , on the risk of sustaining an RRI . Participants were novice runners ( N = 532 ) preparing for a recreational 4-mile ( 6.7-km ) running event . The grade d 13-week training program was based on the 10 % training rule . Both groups registered information on running characteristics and RRI using an Internet-based running log . The primary outcome measure was RRIs per 100 participants . An RRI was defined as any musculoskeletal complaint of the lower extremity or back causing a restriction of running for at least 1 week . Results The grade d training program was not preventive for sustaining an RRI ( χ 2 = 0.016 , df = 1 , P = .90 ) . The incidence of RRI was 20.8 % in the grade d training program group and 20.3 % in the st and ard training program group . Conclusions This r and omized controlled trial showed no effect of a grade d training program ( 13 weeks ) in novice runners , applying the 10 % rule , on the incidence of RRI compared with a st and ard 8-week training program Background : Ankle injuries are the most common injury in basketball players . However , no prospect i ve studies have been performed to determine if wearing lace-up ankle braces will reduce the incidence of ankle injuries in high school athletes . Purpose : This trial was undertaken to determine if lace-up ankle braces reduce the incidence and severity of acute first-time and recurrent ankle injuries sustained by high school basketball players . Design : R and omized controlled trial ; Level of evidence , 1 . Methods : A total of 1460 male and female basketball players from 46 high schools were r and omly assigned to a braced or control group . The braced group players wore lace-up ankle braces during the 2009 - 2010 basketball season . Athletic trainers recorded brace compliance , athlete exposures , and injuries . Cox proportional hazards models ( adjusted for demographic covariates ) , accounting for intracluster correlation , were utilized to compare time to first acute ankle injury between groups . Injury severity ( days lost ) was tested with the Wilcoxon rank-sum test . Results : The rate of acute ankle injury ( per 1000 exposures ) was 0.47 in the braced group and 1.41 in the control group ( Cox hazard ratio [ HR ] 0.32 ; 95 % confidence interval [ CI ] 0.20 , 0.52 ; P < .001 ) . The median severity of acute ankle injuries was similar ( P = .23 ) in the braced ( 6 days ) and control group ( 7 days ) . For players with a previous ankle injury , the incidence of acute ankle injury was 0.83 in the braced group and 1.79 in the control group ( Cox HR 0.39 ; 95 % CI 0.17 , 0.90 ; P = .028 ) . For players who did not report a previous ankle injury , the incidence of acute ankle injury was 0.40 in the braced group and 1.35 in the control group ( Cox HR 0.30 ; 95 % CI 0.17 , 0.52 , P < .001 ) . Conclusion : Use of lace-up ankle braces reduced the incidence but not the severity of acute ankle injuries in male and female high school basketball athletes both with and without a previous history of an ankle injury The objective was to study the effectiveness of a brochure and video at improving skiing and snowboarding knowledge . Sixty-nine Grade 7 students were r and omised to an educational intervention ( n = 35 ) or control ( n = 34 ) group . The intervention group viewed an injury prevention video aim ed at improving skiers and snowboarder 's knowledge , attitudes and behaviours about ski and snowboard safety and received a brochure . The control group participated in a teaching session and had a simple question and answer session about snow sports . Pre- and post-tests were administered and injuries during four trips were documented . Pre-test scores were similar between the two groups . Compared with the control group , there was a significantly greater improvement in post-test scores among the intervention group ( WMD : 2.1 ; 95 % CI : 0.19–4.01 ) . There was no significant difference in injury rates ( RR : 0.49 ; 95 % CI : 0.04 , 3.39 ) . All injuries were minor and did not require medical attention . The intervention aim ed at youth skiers and snowboarders appears to be effective at improving knowledge , attitudes and behaviours of skiing and snowboarding safety OBJECTIVES To assess the benefits , if any , of the use of shock absorbing insoles in reducing lower limb injury among Air Force recruits , and to assess the differences , if any , in the efficacy of two commonly available shock absorbing insoles . DESIGN R and omized controlled trial . SETTING RAF Halton , UK . Site of all basic training for RAF personnel . PARTICIPANTS 1205 recruits participating in basic training between 17 September 2003 and 7 April 2004 . INTERVENTIONS Participants were r and omized to receive either st and ard issue Saran non-shock absorbing insoles , or shock absorbing Sorbothane or Poron insoles , on a 1:1:1 basis . MAIN OUTCOME MEASURES The primary outcome measure was withdrawal from training for lower limb injury . The two primary comparisons were shock absorbing insole versus non-shock absorbing insole , and Sorbothane versus Poron ( comparison of different shock absorbing insoles ) . Secondary outcomes were medical withdrawals for reasons other than those qualifying for the primary outcome measure . RESULTS When comparing the non-shock absorbing insole to the shock absorbing insoles 72/401 participants ( 18.0 % ) allocated to Saran insoles were removed from training because of a qualifying lower limb injury , compared with 149/804 ( 18.5 % ) allocated to the shock absorbing insole ( Sorbothane or Poron ) , odds ratio 1.04 ( 95 % CI 0.75 to 1.44 ; P=0.87 ) . When comparing the two shock absorbing insole 73/421 participants ( 17.3 % ) r and omized to Sorbothane were removed from training because of a qualifying lower limb injury , compared with 76/383 for Poron ( 19.8 % ) , odds ratio 0.85 ( 95 % CI 0.58 to 1.23 ; P=0.37 ) . CONCLUSIONS Similar rates of lower limb injuries were observed for all insoles ( shock absorbing and non-shock absorbing ) in the trial . The trial provides no support for a change in policy to the use of shock absorbing insoles for military recruits Using a prospect i ve , r and omized experimental design , 622 college intramural basketball players were stratified by a previous history of ankle sprains to wear a new pair of either high-top , high-top with inflatable air cham bers , or low-top basketball shoes during all games for a complete season . Subjects were asked to complete a history question naire and were given a complete ankle examination . They were allowed to wear these shoes only during basketball competition . Followed over the course of a 2-month intramural season , 15 ankle injuries occurred during 39,302 minutes of player-time : 7 in high-top shoes , 4 in low-top shoes , and 4 in high-top shoes with inflatable air chambers . The injury rates ( injuries per player-minute ) were 4.80 × 10 - 4 in high-top shoes , 4.06 x 10 - 4 in low-top shoes , and 2.69 x 10 -4 in high-top shoes with inflatable air chambers . There was no significant difference among these 3 groups , leading to the conclusion that there is no strong rela tionship between shoe type and ankle sprains Objective : Head/orofacial ( H/O ) injuries are common in Australian rules football . Mouthguards are widely promoted to prevent these injuries , in spite of the lack of formal evidence for their effectiveness . Design : The Australian football injury prevention project was a cluster r and omized controlled trial to evaluate the effectiveness of mouthguards for preventing H/O injuries in these players . Setting and subjects : Twenty three teams ( 301 players ) were recruited from the largest community football league in Australia . Intervention : Teams were r and omly allocated to either the MG : custom made mouthguard or C : control ( usual mouthguard behaviours ) study arm . Main outcome measures : All injuries , participation in training and games , and mouthguard use were monitored over the 2001 playing season . Injury rates were calculated as the number of injuries per 1000 person hours of playing time . Adjusted incidence rate ratios were obtained from Poisson regression models . Results : Players in both study arms wore mouthguards , though it is unlikely that many controls wore custom made ones . Wearing rates were higher during games than training . The overall rate of H/O injury was 2.7 injuries per 1000 exposure hours . The rate of H/O injury was higher during games than training . The adjusted H/O injury incidence rate ratio was 0.56 ( 95 % CI 0.32 to 0.97 ) for MG versus C during games and training , combined . Conclusions : There was a significant protective effect of custom made mouthguards , relative to usual mouthguard use , during games . However , the control players still wore mouthguards throughout the majority of games and this could have diluted the effect Background : Although ankle injuries occur frequently in high school football players , no prospect i ve studies have been performed to determine if wearing lace-up ankle braces will reduce the incidence and severity of ankle and other lower extremity injuries in these athletes . Purpose : This study was conducted to determine if lace-up ankle braces reduce the incidence and severity of lower extremity injuries sustained by high school football players . Design : R and omized controlled trial ; Level of evidence , 1 . Methods : A total of 2081 players from 50 high schools were r and omly assigned to a braced or control group . Braced group players wore lace-up ankle braces during the 2010 football season . Athletic trainers recorded brace compliance , athlete-exposures , and injuries . Cox proportional hazards models were utilized to compare injury rates between groups . Injury severity ( days lost ) was tested with Wilcoxon rank sum . Results : The rate of acute ankle injury ( per 1000 exposures ) was 0.48 in the braced group compared with 1.12 in the control group ( Cox hazard ratio [ HR ] = 0.39 ; 95 % confidence interval [ CI ] , 0.24 - 0.65 ; P < .001 ) . The severity ( median days lost ) of acute ankle injuries was the same ( 5 days ) in both groups ( P = .985 ) . The rate of acute knee injury was 0.70 in the braced group compared with 0.69 in the control group ( HR = 0.92 ; 95 % CI , 0.57 - 1.47 ; P = .721 ) . There was no difference ( P = .242 ) in the severity of knee injuries between the groups ( controls = 11.5 days , braced = 17 days ) . The rate of other lower extremity injuries was 0.95 in the braced group and 1.32 in the control group ( HR = 0.72 ; 95 % CI , 0.48 - 1.09 ; P = .117 ) , while the severity was similar in both groups ( 6 days vs 7 days ; P = .295 ) . Conclusion : Players who used lace-up ankle braces had a lower incidence of acute ankle injuries but no difference in the incidence of acute knee or other lower extremity injuries . Braces did not reduce the severity of ankle , knee , or other lower extremity injuries Hamstring injuries are the most common injury sustained by Australian Football players . Eccentric training has been proposed as a potential preventative strategy . This pilot r and omised controlled trial ( RCT ) evaluated the effectiveness of a pre-season eccentric training program for preventing hamstring injuries at the community level of Australian Football . Seven amateur clubs ( n=220 players ) were recruited . Players were r and omised within clubs to the intervention ( eccentric exercise ) or control ( stretching ) groups and r and omisation was stratified according to previous history of hamstring injury . Five exercise sessions were completed over a 12-week period , three during the pre-season and two during the first 6 weeks of the season . Compliance was recorded and players were monitored for the season to collect injury and participation data . There was no difference between the control ( n=106 ) or intervention ( n=114 ) groups with respect to baseline characteristics . Only 46.8 % of all players completed at least two program sessions . Compliance was poorest for the intervention group . Intention-to-treat analysis suggested that players in the intervention group were not at reduced risk of hamstring injury ( RR 1.2 , 95 % CI : 0.5 , 2.8 ) . When only control and intervention group players who participated in at least the first two sessions were analysed , 4.0 % of intervention and 13.2 % of control group players sustained a hamstring injury ( RR 0.3 , 95 % CI : 0.1 , 1.4 ; p=0.098 ) . The findings suggest that a simple program of eccentric exercise could reduce the incidence of hamstring injuries in Australian Football but widespread implementation of this program is not likely because of poor compliance OBJECTIVE Indoor soccer is a sport that exposes the athletes to muscle and joint lesions . The effect of rhythmic stabilization ( RS ) technique to prevent these kinds of lesions in indoor soccer athletes is largely unknown and its use in athletes is controversial . Nevertheless , empiric evidence suggests that RS might be effective to prevent lesions in indoor soccer athletes . A controlled clinical trial of efficacy was performed to test this hypothesis . METHODS Athletes were r and omly divided into two groups : a RS group ( 7 athletes ) and passive stretching ( PS ) group ( 7 athletes ) . At the beginning and at the end of the experiment ( after four months ) all athletes were subjected to clinical evaluation . Assessment s were performed by subjective pain intensity , clinical evaluation and measurements of the range of maximal lower limb flexion movement . RESULTS Athletes of both groups had lower limb injuries during the four months . The athletes su bmi tted to RS technique had fewer injuries than those subjected to the PS technique although the difference was not significant . CONCLUSIONS Although no significant difference was found between RS and PS , a trend suggests RS may be more effective than PS to prevent muscular and ankle joint lesions in indoor soccer athletes , but more research is needed BACKGROUND Hamstring strains are the most common soft-tissue injury observed in recreational and athletic activities , yet no consensus exists regarding appropriate primary and secondary strategies to prevent these strains . Eccentric exercise has been reported to reduce the incidence of ham-string strains but its role has not been clearly defined . OBJECTIVE The objective of this systematic review was to determine the effectiveness of eccentric exercise in preventing hamstring strains . DATA SOURCES Online data bases , including MED-LINE , PubMed , CINAHL , PEDro , SPORTD iscus , EMBASE , Cochrane Data base of Systematic Review s , Cochrane Central Register of Controlled Trials , and Web of Science were search ed for relevant articles . Each data base was search ed from the earliest date to July 2007 . STUDY SELECTION Selection criteria included diagnosis of hamstring strain , otherwise healthy individuals , and at least one group receiving an eccentric exercise intervention . Seven articles { three r and omized controlled trials ( RCTs ) and four cohort studies } met the inclusion criteria . DATA EXTRACTION Data were extracted using a customized form . Method ological rigor of included studies was assessed using the PEDro scale and Oxford Centre for Evidence -based Medicine Levels of Evidence . DATA SYNTHESIS STUDIES WERE GROUPED BY ECCENTRIC EXERCISE INTERVENTION PROTOCOL : hamstring lowers , isokinetic strengthening , and other strengthening . A best- evidence synthesis of pooled data was qualitatively summarized . CONCLUSIONS Findings suggest that eccentric training is effective in primary and secondary prevention of hamstring strains . Study heterogeneity and poor method ological rigor limit the ability to provide clinical recommendations . Further RCTs are needed to support the use of eccentric training protocol s in the prevention of hamstring strains The effect of an early rehabilitation program , including postural training , on ankle joint function after an ankle ligament sprain was investigated prospect ively . Ninety-two subjects , matched for age , sex , and level of sports activity , were r and omized to a control or training group . All subject received the same st and ard information regarding early ankle mobilization . In addition , the training group participated in supervised physical therapy rehabilitation ( 1 h , twice weekly ) with emphasis on balance training . Postural sway , position sense and isometric ankle strength were measured 6 weeks and 4 months after the injury , and at 12 months re-injury data were obtained . In the training group , there was a significant difference between the injured and uninjured side for plantar flexion ( P < 0.01 ) , eversion ( P < 0.01 ) and inversion ( P < 0.05 ) , but not for dorsiflexion at 6 weeks . In the control group , there was a significant difference between the injured and uninjured side for plantar flexion ( P < 0.01 ) , eversion ( P < 0.01 ) , inversion ( P < 0.01 ) , and dorsiflexion ( P < 0.05 ) at 6 weeks . Postural sway , but not position sense , differed between the injured and uninjured side in both groups ( P < 0.01 ) at 6 weeks . The side-to-side percent differences were similar in both groups for all variables ( P > 0.05 ) at 6 weeks , and there were no side-to-side differences at 4 months in either group . In the control group , 11/38 ( 29 % ) suffered a re-injury , while this number was only 2/29 ( 7 % ) in the training group ( P < 0.05 ) . These data showed that an ankle injury result ed in reduced ankle strength and postural control at 6 weeks , but that these variables had normalized at 4 months , independent of the supervised rehabilitation . However , the findings also demonstrated that supervised rehabilitation may reduce the number of re-injuries , and therefore may play a role in injury prevention INTRODUCTION The prevention of injuries in all sports calls for a structured plan . The plan consists , as earlier described , of four steps . We have previously presented studies incorporating all four steps . The studies have shown that it is possible to prevent most injuries in young female players in European h and ball by applying a training programme combining the use of an ankle disc with functional strength training . In the previous studies we were not able to discriminate whether the preventive effect was due to the functional strength training or the training with the ankle disc . The aim of this study was to compare a programme with ankle disc and functional strength training with a programme with functional strength training only . METHODS Twenty h and ball teams were asked to participate , and 16 of 20 h and ball teams agreed to participate . The teams were cluster r and omised to either the programme with or without an ankle disc . RESULTS The group using the programme without the ankle disc had a significantly higher number of traumatic injuries ( 16 vs. 6 ) . The incidences of traumatic injuries in the ankle disc group were 2.4 ( 95 % CI 0.7 ; 6.2 ) injuries per 1000 h of match and 0.2 ( 95 % CI 0.02 ; 0.7 ) injuries per 1000 h of practice . In the group without ankle disc the incidences were 6.9 ( 95 % CI 3.3 ; 12.7 ) injuries per 1000 h of match and 0.6 ( 95 % CI 0.2 ; 1.3 ) injuries per 1000 h of practice . A significantly higher multivariate odds ratio ( 4.8 ) was found in the group not using the ankle disc . In addition the group using the ankle disc had significantly fewer moderate and major injuries . CONCLUSION By adding ankle disc training to a training programme with functional strength training , it is possible to reduce the number of injuries significantly , especially the number of moderate and major injuries 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 Objectives : To compare the effectiveness of the WIPSS mouth guard to other currently used mouth guards in the prevention of concussion injuries in athletes participating in varsity football and rugby . Design : Multicenter , cluster-r and omized , controlled trial comparing the WIPSS Brain-Pad mouth guard against the st and ard use mouth guard of choice . Teams were monitored by their respective athletic therapist , trainer , or sports physician for 1 playing season to diagnose and record incident concussion injuries and dental trauma . Concussion symptoms were also recorded at the time of injury . Setting : Five Ontario universities . Participants : University male football ( 394 ) and university male ( 129 ) and female ( 123 ) rugby athletes reporting to 2003 fall training camps . Main Outcome Measurements : The primary end point was the incidence of any diagnosed concussion events during the 2003 playing season as defined by the American Academy of Neurology Concussion Guidelines . Secondary endpoints included the incidence of dental trauma events and observed concussion symptoms . Results : There was no significant difference in the number of concussions observed between the intervention and control arms of this trial ( P = 0.79 ; odds ratio , 1.06 , in favor of controls ; 95 % CI , 0.51 , ≪1.61 ) . No dental trauma events occurred . The 5 most common symptoms experienced by concussed athletes were dizziness , general headache , nausea , loss of visual focus , and personality changes . Conclusions : In this study , concussion rates were not significantly different for varsity football and rugby players who wore the WIPSS Brain-Pad mouth guard compared with other types of mouth guards In a prospect i ve study of the effect of the appropriateness of foot-shoe fit and training shoe type on the incidence of overuse injuries among infantry recruits , it was found that three shoe widths for each shoe length size were necessary to adequately accommo date the recruit population 's foot anatomy . Recruits compensated for the lack of available shoe widths by choosing larger shoe sizes . However , this compensation did not result in an increase in the incidence of overuse injuries . Recruits who trained in basketball shoes had a lower incidence of overuse injuries of the feet than recruits who trained in infantry boots ( p = 0.0001 ) , but the overall incidence of overuse injuries was the same in both groups Background Soccer is a leading sport for participation and injury in youth . Objective To examine the effectiveness of a neuromuscular prevention strategy in reducing injury in youth soccer players . Design Cluster-r and omised controlled trial . Setting Calgary soccer clubs ( male or female , U13–U18 , tier 1–2 , indoor soccer ) . Participants Eighty-two soccer teams were approached for recruitment . Players from 60 teams completed the study ( 32 training ( n=380 ) , 28 control ( n=364 ) ) . Intervention The training programme was a soccer-specific neuromuscular training programme including dynamic stretching , eccentric strength , agility , jumping and balance ( including a home-based balance training programme using a wobble board ) . The control programme was a st and ardised warm-up ( static and dynamic stretching and aerobic components ) and a home-based stretching programme . Main outcome measures Previously vali date d injury surveillance included injury assessment by a study therapist . The injury definition was soccer injury result ing in medical attention and /or removal from a session and /or time loss . Results The injury rate in the training group was 2.08 injuries/1000 player-hours , and in the control group 3.35 injuries/1000 player-hours . Based on Poisson regression analysis , adjusted for clustering by team and covariates , the incidence rate ratios ( IRR ) for all injuries and acute onset injury were 0.62 ( 95 % CI 0.39 to 0.99 ) and 0.57 ( 95 % CI 0.35 to 0.91 ) . Point estimates also suggest protection of lower extremity , ankle and knee sprain injuries ( IRR=0.68 ( 95 % CI 0.42 to 1.11 ) , IRR=0.5 ( 95 % CI 0.24 to 1.04 ) and IRR=0.38 ( 95 % CI 0.08 to 1.75 ) ) . Conclusions A neuromuscular training programme is protective of all injuries and acute onset injury in youth soccer players The primary purpose of this study was to evaluate whether a preseason strength training programme for the hamstring muscle group - emphasising eccentric overloading - could affect the occurrence and severity of hamstring injuries during the subsequent competition season in elite male soccer players . Thirty players from two of the best premier-league division teams in Sweden were divided into two groups ; one group received additional specific hamstring training , whereas the other did not . The extra training was performed 1 - 2 times a week for 10 weeks by using a special device aim ing at specific eccentric overloading of the hamstrings . Isokinetic hamstring strength and maximal running speed were measured in both groups before and after the training period and all hamstring injuries were registered during the total observational period of 10 months . The results showed that the occurrence of hamstring strain injuries was clearly lower in the training group ( 3/15 ) than in the control group ( 10/15 ) . In addition , there were significant increases in strength and speed in the training group . However , there were no obvious coupling between performance parameters and injury occurrence . These results indicate that addition of specific preseason strength training for the hamstrings - including eccentric overloading - would be beneficial for elite soccer players , both from an injury prevention and from performance enhancement point of view 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 Background : Foot orthoses are widely prescribed both to treat existing pathological conditions and to prevent overuse injuries , but little is known about the effect of their material composition and fabrication technique on patient comfort and the incidence of overuse injuries . Material s and Methods : The acceptance rates and comfort scores of soft custom , soft prefabricated , semirigid biomechanical , and semirigid prefabricated orthoses and their effect on the incidence of stress fractures , ankle sprains , and foot problems were studied in a prospect i ve , r and omized , single-blinded clinical trial among 874 infantry recruits during basic training . Results : A statistically significantly lower number of recruits given soft prefabricated orthoses ( 53 % ) finished basic training in their assigned devices than in the soft custom group ( 72 % ) , in the semirigid biomechanical group ( 75 % ) , and in the semirigid prefabricated group ( 82 % ) ( p = .003 ) . For recruits who finished training in their assigned orthoses , the soft custom ( 3.54 ) and soft prefabricated ( 3.43 ) orthoses had significantly higher comfort scores than the semirigid biomechanical ( 3.23 ) and prefabricated ( 3.17 ) orthoses , ( p = .0001 ) . There was no statistically significant difference in the incidence of stress fractures , ankle sprains , or foot problems between recruits using the different types of orthoses . Conclusions : These findings suggest that if a foot orthosis is being dispensed as prophylaxis for overuse injuries in an active , healthy population , there is little justification for prescribing semirigid biomechanical orthoses . Their cost is high compared to other types of orthoses , without an advantage in comfort or a reduction in stress fractures , ankle sprains , and foot problems Background : Overuse lower limb injury is common in incidence and morbidity . Many risk factors , gait related and biomechanical , have been identified , although little conclusive evidence has been found in terms of injury prevention to date . Hypothesis : Orthoses , as produced by proprietary software interpretation of plantar pressures , are able to reduce injury rates in an “ at risk ” military population . Study Design : R and omized controlled trial ; Level of evidence , 1 . Methods : Four hundred military officer trainees were assessed by means of pressure plate recording of their contact foot pressures during walking . Participants were risk assessed and r and omized to receive or not receive customized orthoses using the D3D system . Both cohorts were followed up for injury through their basic training at the 7-week point . Results : The orthotic intervention group sustained 21 injuries in total ( 1 injury per 4666 hours of training ) , whereas the control group sustained 61 injuries in total ( 1 injury per 1600 hours of training ) ( P < .0001 ) , thereby demonstrating an absolute risk reduction of 0.49 from use of the orthoses ( P < .0001 , chi square ; confidence interval , 1.7 , 2.4 ) . Conclusion : In this military trainee population , orthoses were effective in the prevention of overuse lower limb injury . This is the first study to identify a positive preventive role of orthoses Background : Recently , structured training programs for sports injury prevention ( “ The 11 ” and “ The 11 + ” ) have been vali date d in soccer . The FIFA 11 + program has not been evaluated in basketball . Hypothesis : The FIFA 11 + program is effective in reducing the rates of injury in male basketball players . Study Design : R and omized controlled trial ; Level of evidence , 1 . Methods : The authors r and omized 11 teams of the same club . Seven teams were allocated to the intervention group ( 80 players ; mean [ SD ] age 13.5 [ 2.3 ] years ) , and 4 teams were allocated to the control group ( 41 players ; mean [ SD ] age 15.2 [ 4.6 ] years ) . The authors conducted an injury surveillance program during a 9-month season . The primary outcome was any injury to the athletes . The secondary outcome was any injury to the lower extremity ( foot , ankle , lower leg , knee , thigh , groin , and hip ) . They included an analysis of the type of exposure ( match or training ) , injury location in the body , and type of injury ( acute or overuse ) . Results : During the 9-month season , 23 ( 19 % ) of the 121 players included in the study sustained a total of 31 injuries ( 14 in the intervention group and 17 in the control group ) . In the intervention group , injury rates per 1000 athlete-exposures were lower than those in the control group , with statistical significance , for overall injuries ( 0.95 vs 2.16 ; P = .0004 ) , training injuries ( 0.14 vs 0.76 ; P = .007 ) , lower extremity injuries ( 0.68 vs 1.4 ; P = .022 ) , acute injuries ( 0.61 vs 1.91 ; P < .0001 ) , and severe injuries ( 0 vs 0.51 ; P = .004 ) . The intervention group also had statistically significant lower injury rates for trunk ( 0.07 vs 0.51 ; P = .013 ) , leg ( 0 vs 0.38 ; P = .007 ) , and hip and groin ( 0 vs 0.25 ; P = .023 ) compared with the control group . There was no statistically significant difference in match injuries , knee injuries , ankle injuries , and overuse injuries between 2 groups . The most frequent acute injury diagnoses were ligament sprains ( 0.41 and 0.38 in the intervention and control groups , respectively ; P < .006 ) and contractures ( 0.76 and 0.07 in the control and intervention groups , respectively ; P < .003 ) . Conclusion : The FIFA 11 + warm-up program is effective in reducing the rates of injuries in elite male basketball players INTRODUCTION Stress fractures ( SFx ) are one of the most common and debilitating overuse injuries seen in military recruits , and they are also problematic for nonmilitary athletic population s. The goal of this r and omized double-blind , placebo-controlled study was to determine whether a calcium and vitamin D intervention could reduce the incidence of SFx in female recruits during basic training . MATERIAL S AND METHODS We recruited 5201 female Navy recruit volunteers and r and omized them to 2000 mg calcium and 800 IU vitamin D/d or placebo . SFx were ascertained when recruits reported to the Great Lakes clinic with symptoms . All SFx were confirmed with radiography or technetium scan according to the usual Navy protocol . RESULTS A total of 309 subjects were diagnosed with a SFx result ing in an incidence of 5.9 % per 8 wk . Using intention-to-treat analysis by including all enrolled subjects , we found that the calcium and vitamin D group had a 20 % lower incidence of SFx than the control group ( 5.3 % versus 6.6 % , respectively , p = 0.0026 for Fisher 's exact test ) . The per protocol analysis , including only the 3700 recruits who completed the study , found a 21 % lower incidence of fractures in the supplemented versus the control group ( 6.8 % versus 8.6 % , respectively , p = 0.02 for Fisher 's exact test ) . CONCLUSIONS Generalizing the findings to the population of 14,416 women who entered basic training at the Great Lakes during the 24 mo of recruitment , calcium and vitamin D supplementation for the entire cohort would have prevented approximately 187 persons from fracturing . Such a decrease in SFx would be associated with a significant decrease in morbidity and financial costs |
12,316 | 15,198,745 | In particular , there is little evidence for the effectiveness of the prophylactic use of FFP . | Summary R and omized controlled trials of good quality are a recognized means to robustly assess the efficacy of interventions in clinical practice . | Early changes in coagulation were found in patients following a paracetamol overdose . Low levels of clotting factors II , V and VII were present within 24 hours of the overdose . As the levels of factor II correlated with plasma fibrinogen values at this time , it is possible that they were consumed in the process of intravascular coagulation , although this was not supported by the presence of raised titres of fibrin degradation products . The prothrombin time ratio was greater than 2 - 2 within 30 hours of ingestion of the overdose in all patients who eventually died , whereas it was less than this in those developing only moderate liver damage . The administration of fresh frozen plasma to patients did appear to reduce the maximum abnormality of the prothrombin time ratio , which was significantly less three days after the overdose in the group receiving fresh frozen plasma . However , the coagulation disturbance was of short duration , and the prothrombin time ratio had also returned to normal within one week of the overdose in the control patients , and the administration of fresh frozen plasma did not appear to reduce the morbidity or mortality in the treated patients A prospect i ve study to evaluate efficacy and safety of partial exchange blood transfusion ( PEBT ) with normal saline or plasma was conducted in 30 symptomatic polycythemic newborns . Babies were r and omly assigned to receive PEBT either with normal saline or plasma . Both groups were comparable in terms of birth weight , gestational age , preexchange hematocrit and viscosity . A significant fall in hematocrit and viscosity was noticed at 6 hours following PEBT which persisted even at 24 hours ( P < 0.001 ) . Hematocrit and viscosity were comparable in the two groups at 6 and 24 hours ( p > 0.05 for both ) . Majority of babies became asymptomatic after 24 hours of PEBT , but one baby in the saline group remained polycythemic and symptomatic requiring repeat PEBT . No complications related to the procedure were encountered in the two groups . Partial exchange with normal saline was as effective and safe as plasma in symptomatic polycythemic newborns Thrombotic thrombocytopenic purpura ( TTP ) is a potentially fatal disease that is treated with plasma exchange and typically with replacement with fresh frozen plasma ( FFP ) . This approach results in an approximate 50 % response rate following 1 week of therapy and 80 % survival . Cryoprecipitate poor plasma ( CPP ) is plasma from which the cryoprecipitate fraction is removed . CPP has been reported to be successful as salvage therapy in refractory TTP and has been suggested to be superior to FFP in retrospective studies . The present report compares initial therapy of TTP with exchange using replacement with either FFP or CPP in a multi-institutional prospect i ve r and omized study performed by the North American TTP Group ( NATG Group ) from 1993 to 1995 . Initial therapy also included corticosteroids . Antiplatelet drugs or vinca alkaloids were not employed . A severity score index , response score , and individual clinical parameters ( platelet count , LDH x upper limit of normal , hemoglobin level , and creatinine ) were compared at their nadir or peak values , baseline , and days + 6 and + 13 of therapy . Thirteen patients were r and omized to FFP exchange and 14 to CPP exchange . Results were equivalent for all parameters . Survival was equal with three deaths in each group . These data indicate that the efficacy of FFP and CPP are the same in the initial treatment of TTP in adults OBJECTIVES To assess the benefits of withdrawn autologous plasma , the objective of this study was to investigate whether withdrawal of acutely performed platelet-rich or platelet-poor plasmapheresis allays changes in the protein C-thrombomodulin and fibrinolytic systems after retransfusion secondary to cardiopulmonary bypass ( CPB ) . In addition , the study attempted to determine the influence of acute plasmapheresis ( APP ) on the protein C-thrombomodulin and fibrinolytic systems as well as on homologous blood consumption and perioperative blood loss in elective aortocoronary bypass patients . DESIGN The investigation was scheduled as a prospect i ve , r and omized , unblinded study . SETTING This single investigation was conducted in the Department of Anesthesiology and Intensive Care Medicine at a university in Germany . The study protocol was approved by the Ethics Committee of the hospital , and informed consent was obtained . PARTICIPANTS Sixty male patients scheduled for elective coronary artery bypass grafting with extracorporeal circulation were included in the study . INTERVENTIONS APP was performed between induction of anesthesia and incision , collecting either 10 mL/kg of autologous platelet-poor plasma ( PPP patients , group 1 ; n = 20 ) or the same amount of platelet-rich plasma ( PRP patients , group 2 ; n = 20 ) . Patients of group 3 ( n = 20 ) had no APP ( control group ) . All patients were maintained on their usual regimen of cardiac drugs until the morning of surgery . To preserve hemodynamic stability and restore the intravascular oncotic pressure , the separated plasma was replaced by infusion of an equal amount of hydroxyethyl starch solution ( HES ) ( 6 % HES , molecular weight 2 x 10(5 ) , substitution rate 0.5 % ) . In all operations , the same surgical procedure was chosen . For all patients , induction and maintenance of anesthesia were similar , consisting of weight-related doses of fentanyl ( 35 micrograms/kg ) , midazolam ( 0.65 mg/kg ) , and pancuronium bromide ( 0.15 mg/kg ) . The lungs of all patients were mechanically ventilated during the first 5 hours after the end of the operation . MEASUREMENTS AND MAIN RESULTS All patients had serial coagulation studies including antithrombin ( AT ) III-activity , prekallikrein , factor XII , and immunologic tests such as thrombin-antithrombin III ( TAT ) , fibrinopeptide A ( FPA ) , protein C and S ( PC and PS ) , thrombomodulin ( TM ) , tissue-plasminogen-activator ( t-PA ) , plasminogen-activator-inhibitor ( PAI 1 ) , fibrinopeptide B beta 15 - 42 ( FPB beta 15 - 42 ) , D-dimers , and hemoglobin and platelet counts determined intraoperatively and postoperatively . Chest tube drainage and transfusion requirements were recorded . APP had no negative effects on the quality of PPP and PRP plasma . The platelet count of the withdrawn plasma was 28 + /- 12 x 10(9)/L ( PPP group ) and 245 + /- 36 x 10(9)/L ( PRP group ) . At the end of the operation ( after retransfusion of autologous plasma ) and on the morning of the first postoperative day , platelet counts were significantly higher ( p > 0.05 ) in the PRP than in the PPP and control groups . Plasma concentrations of TAT and FPA increased ( ranging from + 185 % to + 340 % from baseline values ) and AT III-activity , PC , PS , and TM antigen decreased ( ranging from -8 % to -55 % from baseline values ) to a different extent for all three groups throughout CPB . t-PA-activity increased with a maximum at the end of CPB ( PPP group , 6.9 + /- 1.5 IU/mL : PRP group , 3.8 + /- 0.8 IU/mL ; control group , 10.9 + /- 2.8 IU/mL ) . Fibrin and fibrinogen degradation markers such as D-dimers and FPB beta 15 to 42 occurred in peak concentrations after neutralization of heparin by protamine . Only PRP patients showed baseline concentrations of coagulation parameters the next morning ( p < 0.05 ) . Total postoperative blood loss within the first 24 hours reached 482 + /- 273 mL ( PRP group ) , 775 + /- 256 mL ( PPP group ) , and 948 + /- 342 mL in the control group ( p < 0.05 ) . ( ABSTRACT TRUNCATED In thrombotic microangiopathies hemolytic uremic syndrome and thrombocytopenic purpura , plasma exchange ( PE ) therapy using fresh frozen plasma is st and ard . In almost 20 % of the patients , however , this approach is ineffective . This prospect i ve , r and omized study for the treatment of patients with thrombotic microangiopathies ( PRODROMI ) compares PE with fresh frozen plasma ( A ) and cryosupernatant ( B ) . The participating centers were the University Clinics of Freiburg , Hamburg , Düsseldorf , Essen , Göttingen , Mannheim , Ulm , Jena , Tübingen , Würzburg , Kreiskrankenhaus Offenburg , Städt Klinikum Karlsruhe , and Horst-Schmidt Kliniken in Wiesbaden , Germany . Patients ( 18 to 80 years ) were diagnosed by the individual centers based on clinical and laboratory findings ( thrombocyte/fragmentocyte count , hemoglobin , serum creatinine , haptoglobin and lactate dehydrogenase levels ; negative Coombs-test is obligatory ) . HIV infection , bone marrow , or solid organ transplantation were exclusion criteria . After written consent , patients were r and omized in the A or B group . All patients received 1.5 mg/kg methylprednisolone as a basic therapy . The first PE always was performed with fresh frozen plasma ( 50 ml/kg ) . A minimum of 5 and a maximum of 10 PEs were required . Thrombocyte count above 150,000/microl was considered to be a successful therapy . Treatment failure was defined as not responding to 10 PE with a thrombocyte count above 150,000/microl or a fall below this value within 30 days after stopping PE . Patients with clinical and laboratory signs of thrombotic microangiopathy occurring later than 30 days after having stopped PE were considered to have a relapse . Primary endpoints were survival , intensity of required PE sessions ( duration , volume , and number ) , and relapse rate . Follow-up of clinical outcome was 2 years ; von Willebr and Factor ( vWF ) , vWF-cleaving-protease activity , and Factor H were determined The use of partial plasma exchange transfusion in newborns with polycythemia and hyperviscosity was evaluated . Ninety-three infants with polycythemia and hyperviscosity were r and omly assigned to receive either partial plasma exchange transfusion or symptomatic treatment ; the infants were matched with control infants without polycythemia . Neonatal course and outcome at 1 and 2 years were evaluated for each of the three groups . Polycythemic infants had more fine motor and speech problems at 1 year of age than did control infants . At 2 years of age , polycythemic infants had more gross motor delays , neurologic diagnoses , fine motor abnormalities , and speech delays than did the control infants . There was no significant difference at 1 year between the polycythemic infants who had received partial plasma exchange transfusion and those given only symptomatic care . At 2 years , the group receiving partial plasma exchange transfusion had fewer neurologic diagnoses and fine motor abnormalities Seventy three preterm infants weighing less than 1500 g or less than 32 weeks ' gestation , or both , were allocated r and omly to treatment ( fresh frozen plasma 10 ml/kg on admission and at 24 hours of age ) or control groups . Fifteen ( 41 % ) out of 37 control patients sustained intraventricular haemorrhage compared with five ( 14 % ) of 36 patients receiving treatment ( X2 = 5.24 , P = 0.022 ) . No difference was found in coagulation factors measured at birth or at 48 hours of age in both groups . Fresh frozen plasma appears to have a beneficial effect in the prevention of intraventricular haemorrhage Colloid infusions are often given to treat hypotension in preterm infants . The aim of this work was to assess whether it was the amount of protein or the volume of the colloid infused which accounted for the observed increase in blood pressure . Sixty preterm infants were r and omised ( 20 in each group ) to receive 5 ml/kg 20 % albumin , 15 ml/kg fresh frozen plasma , or 15 ml/kg 4.5 % albumin . All infusions were given at a rate of 5 ml/kg/hour in addition to maintenance fluids . The infants were r and omised when hypotensive ( systolic blood pressure less than 40 mm Hg for two hours ) . There was no significant difference in the blood pressure of the three groups before or one hour after beginning the infusion . The mean increase in blood pressure one hour after completing the infusion , however , was significantly lower in infants receiving 20 % albumin : 9 % compared with 17 % in the group receiving 4.5 % albumin , and 19 % in the group receiving fresh frozen plasma . It is concluded that the volume infused rather than albumin load is important in producing a sustained increase in blood pressure The goals of this multicenter controlled trial were : ( 1 ) to study the short‐term effect of plasma exchange in the Guillain‐Barré syndrome when applied alone within 17 days of onset of the disease ; and ( 2 ) to compare two replacement fluids , diluted albumin and fresh frozen plasma ( FFP ) with regard to efficacy and morbidity . Two hundred twenty patients were included , 111 in the control group , 109 in the plasma exchange group , 57 of whom were assigned to receive albumin and 52 to receive fresh frozen plasma . Treatment consisted of four plasma exchanges of two plasma volumes each , initiated on the day of r and omization and repeated on alternate days . Significant short‐term benefits appeared in the group that received plasma exchange as demonstrated by the reduction in the proportion of patients who required assisted ventilation after r and omization , and the decrease in time before beginning weaning from ventilator , time to onset of motor recovery , and time to walk with and without assistance . No statistically significant difference was found between the group that received albumin and the group that received fresh frozen plasma . Incidents during exchanges and complications related to the plasma exchange were more frequent in patients who received fresh frozen plasma . Plasma exchange is beneficial in Guillain‐Barré syndrome when it is carried out early in the course of the disease . Given its risks and the lack of its clear superiority over albumin , however , we recommend that fresh frozen plasma be ab and oned in the treatment of Guillain‐Barré syndrome BACKGROUND Neonatal polycythemia remains a significant clinical problem in Thail and . Partial exchanges transfusion ( PET ) with fresh frozen plasma ( FFP ) has been the mainstay of management for this condition in Thail and . Since FFP is difficult to find in certain areas and can cause concerns of transfusion related diseases , this study was undertaken to investigate the possibility of using plasma substitute and normal saline ( NSS ) for PET in the newborn infant with polycythemia . OBJECTIVE 1 . To compare the rate and duration of decrease of venous hematocrit ( Hct ) before and after PET with FFP , Haemaccel and NSS . 2 . To compare any complications from using FFP , Haemaccel and NSS such as coagulation defect , electrolytes change , etc . in PET . METHODS AND SUBJECTS A r and omized prospect i ve trial was conducted in Neonatal Unit , Department of Pediatrics , Ramathibodi Hospital . The first phase of study : July 1 , 1993 to June 30 , 1994 : r and omized prospect i ve trial using FFP or Haemaccel for PET in 26 newborn infants with polycythemia . The second phase of study : July 1 , 1994 to June 30 , 1995 : consecutive enrollment trial using NSS for PET in 38 consecutive newborn infants with polycythemia . RESULTS There was significant decrease in Hct in both groups after PET but there was no statistically significant difference in the rate of decrease of Hct . There was no significant difference in biochemical profiles in both groups of infants 24 hours after PET . In the NSS group , there was significant decrease of Hct level after PET . There was no significant change of biochemical profiles and coagulation activity in these patients 24 hours after exchange transfusion . There were 2 patients with complications related to umbilical venous catheter and PET . CONCLUSION Haemaccel and NSS can be safely used for PET to treat neonatal polycythemia . However , the attending physician should be aware of possible complications related to umbilical venous catheterization and PET Fresh frozen plasma and intravenous immunoglobulin are used as prophylaxis against , and for the treatment of , neonatal infection . It is assumed that any beneficial effect is mediated through the humoral immune factors contained in each preparation . The effect of fresh frozen plasma and intravenous immunoglobulin on humoral immune markers ( immunoglobulins and IgG subclasses , complement components and activation products , and C reactive protein ) was investigated over a 24 hour period after their r and omised administration to 67 infants with suspected infection . Thirty infants without suspicion of infection were studied as controls . Compared with control infants , infants with suspected infection had increased concentrations of C reactive protein , reduced concentrations of fibronectin , and increased concentrations of the complement activation marker C3d , but similar concentrations of IgG , IgG subclasses , IgA , and IgM. After intravenous immunoglobulin treatment ( 500 mg/kg ) concentrations of total IgG and all IgG subclasses increased , as did IgA and complement component C4 . Concentrations of C reactive protein decreased after intravenous immunoglobulin treatment and were significantly lower than baseline after 24 hours . In contrast , no change in IgG or IgG subclass concentrations occurred after fresh frozen plasma administration . At 24 hours after fresh frozen plasma administration , concentrations of IgA , IgM , and C4 were significantly higher than baseline and serum IgA was significantly higher than in infants tested 24 hours after intravenous immunoglobulin treatment . These results confirm the rational basis for intravenous immunoglobulin treatment but question the value of fresh frozen plasma , particularly in the light of its attendant problems as an untreated blood product The results of a controlled trial to ascertain the usefulness of plasma infusion for the treatment of hemolytic-uremic syndrome ( HUS ) are reported . Criteria for admission were ( 1 ) observation within 8 days from first symptoms , ( 2 ) dialysis treatment required , and ( 3 ) no special treatments and no more than 25 ml blood/kg previously received . Children were subdivided according to age ( less than or more than 3 years ) and then r and omly assigned to treatment with plasma or symptomatic therapy . Thirty-two children ranging in age from 4 months to 6 years entered this study ; 17 received plasma ( P+ group ) and 15 only symptomatic therapy ( P- group ) . The mean follow-up period was 16 months in both groups . Surgical renal biopsy was performed 29 to 49 days after onset in 11 P+ and 11 P- children , and 33 histologic findings were semiquantitatively evaluated . No death occurred in either group . No differences were found in blood pressure , proteinuria , or hematuria at the end of the follow-up period ; in no case were severe arteriolar lesions found . There were no significant differences for the scores of the individual histologic measurements ; on electron microscopy , no vascular changes were observed in seven children of the P+ group , whereas in five of seven of the P- group , thickening of the lamina rara interna and arteriolar damage were present . The ability of plasma to stimulate prostacyclin ( PGI2 ) production , measured as its stable derivative 6-keto-PGF1 alpha , was within the normal range for all patients . In our patients with predominant glomerular involvement who were treated in a very early phase of HUS , infusions of plasma did not significantly influence the short- and medium-term clinical outcome and were not effective in severe HUS when given later in the course of the disease . A longer follow-up is needed to ascertain whether the presence of endothelial damage , demonstrated by electron microscopy in children who were not given plasma , is of clinical relevance Background Previous studies failed to demonstrate any benefit from prophylaxis with fresh frozen plasma ( FFP ) after cardiopulmonary bypass ( CPB ) . The results , however , were limited by either retrospective study design or use of FFP in subtherapeutic doses ( 2–3 units ) . The authors evaluated whether a therapeutic dose ( 15 ml/kg ) of FFP reduces blood loss and transfusion requirements in elective coronary artery bypass surgery . The risks of multiple allogeneic blood donor exposure were circumvented by using autologous plasma . Methods Sixty adult patients scheduled for elective primary coronary artery bypass grafting were r and omized to receive , after CPB , an intravenous infusion of 15 ml/kg of either autologous FFP ( 30 patients ) or 6 % hydroxyethyl starch 450/0.7 ( HES ; 30 patients ) . Autologous plasma was obtained by platelet-poor plasmapheresis several weeks before surgery . Perioperative blood transfusions were administered per protocol . Postoperative blood loss was defined as the chest tube drainage during the first 24 h after surgery . Results The data from 56 patients ( FFP group , 27 patients ; HES group , 29 patients ) who completed the study according to protocol were analyzed . Median postoperative blood loss was 630 ml ( range , 450–1,840 ml ) and 830 ml ( range , 340–1,980 ml ) in the FFP and HES groups , respectively ( P = 0.08 ) . Both postoperative ( 0–24 h ) and total perioperative erythrocyte transfusion requirements did not differ significantly between the groups ( P = 0.32 and 0.14 , respectively ) . Conclusion The prophylactic administration of a therapeutic dose ( 15 ml/kg ) of autologous FFP after CPB failed to reduce blood loss and transfusion requirements in patients undergoing uncomplicated , elective , primary coronary artery bypass surgery Exchange transfusion , as a form of therapy , was contrasted with the use of fresh frozen plasma or conventional supportive care alone in the management of 19 infants with birth weights of less than 1,000 gm , without severe respiratory distress , and in the management of 82 infants , birth weights less than 2,000 gm , with severe respiratory distress whose disease manifested itself within the first 24 hours of life . Survival for more than five days was similar , regardless of therapy , in infants weighing less than 1,000 gm without severe RDS . In contrast , the use of exchange transfusion significantly decreased the case fatality rate of infants with severe RDS . In the groups receiving exchange transfusion , the mortality rate was 41 % , whereas the groups receiving either plasma or supportive care alone the mortality was 80 % . Study of coagulation factors and red cell concentrations of fetal hemoglobin and of 2,3-DPG failed to demonstrate any relationship between either improvement in coagulation or oxygen unloading and the improved survival of infants receiving exchange transfusion . Following exchange transfusion there was a significant decrease in the ratio of FIO2 to PaO2 , suggesting that pulmonary perfusion and /or ventilation was improved by the procedure A common question in clinical consultations is : “ For this person , what are the likely effects of one treatment compared with another ? ” The central tenet of evidence based medicine is that this task is achieved by using the best evidence combined with consideration of that person 's individual needs.1 A further question then arises : “ What is the best evidence ? ” Two recent studies in the New Engl and Journal of Medicine have caused uproar in the research community by finding no difference in estimates of treatment effects between r and omised controlled trials and non-r and omised trials . The r and omised controlled trial and , especially , systematic review s of several of these trials are traditionally the gold st and ards for judging the benefits of treatments , mainly because it is conceptually easier to attribute any observed effect to the treatments being compared . The role of non-r and omised ( observational ) studies in evaluating treatments is contentious : deliberate choice of the treatment for each person implies that observed outcomes may be caused by differences among people being given the two treatments , rather than the treatments alone . Unrecognised confounding factors can always interfere with attempts to correct for identified differences between groups . These considerations have supported a hierarchy of evidence , with r and omised controlled trials and derivatives at the top , controlled Seventy-nine children with haemolytic uraemic syndrome ( mean age 28 months ) were r and omly assigned either to a group receiving plasma infusions ( plasma group , n=39 ) or to a group treated conservatively ( control group , n=40 ) . The duration of haemolysis , thrombocytopenia and anuria was similar in the two groups . Serum creatinine levels were similar in the two groups at the 1-month follow-up but were higher in the control group at 3 months ( plasma group 49±14 , control group 66±28 μmol/l;P<0.02 ) and at 6 months ( plasma group 48±13 , control group 63±21 μmol/l;P<0.005 ) . The prevalence of proteinuria was also higher in the control group at the 6-month follow-up ( plasma group 17 % , control group 46%;P<0.02 ) . However differences were no longer significant after 1 year . Renal tissue was examined in 54 cases ( plasma group , n=27 ; control group , n=27 ) . Diffuse cortical necrosis was present in 7 cases in the control group but was absent in the plasma group ( P<0.02 ) . Taking into consideration the higher serum creatinine levels , the higher prevalence of proteinuria during the first 6 months of follow-up in the control group and the presence of diffuse cortical necrosis in this group compared with the plasma group , we conclude that plasma infusions should be regarded as beneficial . Further study is needed to determine which plasma fraction is involved Studies on the use of fresh frozen plasma in Britain , where its administration has increased more than 10-fold in the past 15 years , and elsewhere have shown that it is often misused.'-3 Probably the main reasons for this are limited knowledge of its efficacy in specific situations , ignorance of its risks , and its increased availability . Guidelines on its use have recently been published by the British Committee for St and ards in Haematology4 ; they complement those included in ABC of Transfusion5 and the National Blood Transfusion Service 's H and book of Transfusion Medicine.6 Although fresh frozen plasma is widely advocated for patients with multiple coagulation defects associated with severe liver disease , disseminated intravascular coagulation , and massive blood transfusions , its effect is poorly defined . As a result , various ill supported practice s persist , such as the transfusion of 2 units of fresh frozen plasma before liver biopsy when the prothrombin time is prolonged by 2 - 3 seconds . Large prospect i ve controlled multicentre studies are needed to define the role of fresh frozen plasma in patients with acquired multiple coagulation defects , but the difficulties of undertaking such studies are formidable . What is clear is that if any benefit is to be obtained adequate quantities of fresh frozen plasma must be given of perhaps 4 - 6 donor units ( about 800 - 1200 ml ) over one or two hours- and then repeated . Fresh frozen plasma has no role as a volume exp and er ; synthetic colloids are more effective , safer and cheaper . Fresh frozen plasma has no place in " formula " replacement protocol s-for example , the administration of 1 unit of fresh frozen plasma after every 6 units of blood . Fresh frozen plasma should not be used to provide nutrition in patients with protein losing states . Its use as a source of immunoglobulins in the treatment of congenital immunodeficiency states has been superseded by use of intravenous immunoglobulin preparations . Several reasons exist for avoiding the inappropriate use of fresh frozen plasma . Risks associated with its transfusion , particularly those of infection , should not be underestimated . The current estimated risk of acquiring HIV infection by transfusion in Britain is one in 3000000 donations ; for hepatitis B it is one in 20 000 and for hepatitis C it is less than one in 13 000 ( M Contreras and J Barbara , North London Blood Transfusion Centre , personal communication ) . Other adverse effects include allergic reactions ; intravascular haemolysis of recipient red cells after infusion of ABO incompatible plasma ; fluid overload ; the formation of antibodies to donor granulocytes , leading to leucocyte aggregation in pulmonary vessels and acute lung injury , a syndrome known to be related to transfusion ; and possibly immune suppression . Two other factors merit consideration . Firstly , in the past few years in Britain , despite efforts to recruit new donors , rates of blood donation have remained static and in some places have fallen.3 Secondly , most regional transfusion centres charge between C22 and £ 28 for a unit of fresh frozen plasma , containing about 180 ml . Doctors should take careful account of these factors before treating patients with fresh frozen plasma ; inappropriate use of such a scarce re source is wasteful . Firm indications for the use of fresh frozen plasma are few . It is useful in the replacement of , usually congenital , single procoagulant factor deficiencies ( for example , factor V ) when a specific or combined factor concentrate is unavailable . It has been used as replacement treatment in patients with congenital deficiencies of the naturally occurring anticoagulants antithrombin III , protein C , and protein S. Antithrombin III concentrates are now widely available , and commercially made protein C concentrates have recently become available for clinical trial . Fresh frozen plasma has been used in patients with congenital deficiency ofC 1 esterase inhibitor who develop severe angio-oedema , but a C 1 esterase inhibitor concentrate is available . The role of specific factor concentrates in various acquired deficiency states ( such as antithrombin III concentrate in disseminated intravascular coagulation ) is being assessed ; if found to be effective they could obviate the use of fresh frozen plasma . Fresh frozen plasma may be used to reverse oral anticoagulation associated with serious bleeding if prothrombin complex and factor VII concentrates are not available ( about a litre is required for an adult).7 A similar regimen should be used to treat haemorrhagic disease of the newborn and bleeding associated with malabsorption of vitamin K. Used aggressively in large volumes ( at least 3 litres/day ) , usually with plasma exchange , fresh frozen plasma is the mainstay of treatment in patients with thrombotic thrombocytopenia purpura and related syndromes . It should be used to correct depletion of coagulation factors in bleeding associated with thrombolysis . Several steps could be taken to optimise the use of fresh frozen plasma . Firstly , the guidelines of the British Committee for St and ards in Haematology emphasise the importance of implementing educational programmes outlining the benefits and complications of treatment with blood components . Such programmes have been shown to reduce both the total amount of fresh frozen plasma transfused Rapid administration of intravascular volume exp and ers is often necessary during anesthesia . Significant controversy still exists on the relative values of different volume exp and ers . Fifteen hypoxemic patients ( Pa02 < 70 torr on room air ) were studied preoperatively . They were r and omized into three groups . One group received 1.5 ml/kg of 25 % salt-poor human albumin , a second group , 7 ml/kg of fresh frozen plasma ; a third group , 7 ml/kg of 0.9 % NaCI in water ( normal saline ) . The infusions were given intravenously and completed in 20 minutes . Changes in hemodynamic pressures and flows , blood chemistries , and oxygen uptake and transport variables were studied . It was concluded that fresh frozen plasma afforded the greatest increase in cardiac output and oxygen availability with the least increase in left ventricular stroke work . Colloid osmotic pressure was more significantly increased by fresh frozen plasma than by salt-poor human albumin . Normal saline caused both a decrease in oxygen availability and colloid osmotic pressure . Pulmonary venous admixture increased to some extent in all patients receiving fresh frozen plasma or normal saline . In three patients , this increase was very marked and accompanied by severe arterial hypoxemia Fresh frozen plasma ( FFP ) has been proposed as a specific therapy for acute pancreatitis . It may replenish important circulating proteins , particularly the naturally occurring anti-protease system . To investigate this potential therapy , 72 patients with predicted severe disease were selected from 301 admissions with acute pancreatitis using the modified Glasgow prognostic scoring system . They were r and omised within 6 h of diagnosis to receive FFP ( 8 units daily for 3 days ) or a similar volume of colloid control as part of their intravenous fluid therapy . Clinical progress was monitored and specific blood proteins were measured on days 1 , 3 and 7 . FFP therapy significantly increased the day 3 concentrations of some of the acute phase proteins ( C1-reactive protein P less than 0.02 , D-dimer P less than 0.05 and fibrinogen P less than 0.05 ) as well as some proteins which showed a fall in circulating concentration during the early stages of the disease ( alpha 2 macroglobulin P less than 0.001 , antithrombin III P less than 0.01 and fibronectin P less than 0.001 ) . However , there was no significant difference between the two groups in terms of clinical outcome . Mortality was 20 % in patients who received FFP and 18 % in the colloid control group . Despite the ability of FFP therapy to supplement circulating concentrations of several potentially useful proteins during acute pancreatitis , it does not appear to improve clinical outcome Objectives : Baxter 's methylene blue ( MB ) photoinactivation of fresh frozen plasma ( FFP ) is a method that effectively removes any intracellular potentially infectious agent , such as prions , by filtration combined with an improved photochemical virus inactivation on a single unit of FFP . The purpose of this study was to demonstrate clinical and biochemical tolerance of MB – treated plasma in healthy human volunteers . Methods : The design was a crossover r and omized trial . Twelve subjects received alternatively treated and nontreated autologous FFP . Coagulation parameters were tested as well as clinical and biochemical parameters . Results : No clinical or statistically significant difference was detected for any of the parameters . Conclusion : Transfusion of FFP treated for viral reduction by an improved MB photoinactivation method was shown to be safe and did not affect the normal function of coagulation proteins . We consider this method as a valuable alternative to other methods described as it combines the photoinactivation with a filtration step removing any intracellular infectious agents , such as prions The aim of the study was the comparison of the influence of fresh frozen plasma ( FFP ) ( Freiburg , Germany ) and Biseko , Biotest Pharma GmbH ( Dreieich , Germany ) , as a plasma substitute ( a st and ardized , virus inactivated human serum protein solution ) on the coagulation factors , inhibitors , proteins , and complement factors in the plasma of autoimmune disease patients following membrane plasma separation . Patients ( n = 24 ) with autoimmune disease were r and omized to receive either FFP or Biseko for membrane plasma separation therapy . During each plasma exchange , 100 % of the plasma volume was replaced by the respective substitute . Plasma exchange volume was performed once daily for 3 days . Target test parameters of the coagulation system were fibrinogen , fibrinopeptide A , factor VIII ( FVIIIC ) , von Willebr and factor antigen ( vWFAg ) , partial thromboplastin time ( PTT ) , thromboplastin time ( Quick value ) , and antithrombin ( AT III ) . The immunoglobulins were IgG , IgA , and IgM and C-reactive protein ( CRP ) . The thrombocytes were platelet factor 4 ( PF4 ) , and complement factors were C3 and C4 . Biseko was well tolerated with 1 mild adverse drug reaction ( ADR ) ( n = 1 ) while FFP gave rise to ADR on 7 occasions ( n = 4 ) . Statistically significant differences in the 2 groups were observed for fibrinogen , PTT , Quick value , and AT III . From the clinical point of view , all fluctuations and differences in parameter levels remained clinical ly silent . The differences had no clinical consequences . Reflecting on a potential decrease in the risk of infections in comparison to FFP therapy and the lower rate of adverse drug reactions , it is possible to postulate an advantage of Biseko for plasma exchange therapy Thirty-three neonates with disseminated intravascular coagulation were assigned r and omly to one of three treatment groups : ( 1 ) exchange transfusion , ( 2 ) administration of fresh-frozen plasma and platelets , and ( 3 ) control ( no therapy directed specifically at the coagulopathy ) . The three groups were comparable for degree of abnormality in initial coagulation studies and underlying pathologic processes . Shock was a common accompaniment of DIC and occurred in 85 % of all infants . In all cases , underlying disease states and shock were treated aggressively . Resolution of DIC and survival were not different in the three treatment groups . Outcome of DIC was dependent on the success of treatment of the underlying pathologic process and aggressive supportive care , including restoration of blood pressure , but was not altered by therapy specifically directed at the coagulopathy We assessed the effect of fresh frozen plasma ( FFP ) on extracellular volume ( ECV ) during the first few days of life in two groups of preterm infants , group 1 ( gestational age less than 30 weeks ) and group 2 ( gestational age 30 - 34 weeks ) . The infants were r and omly assigned to one of two treatment groups , one receiving FFP , the other not ; group 1 infants receiving no treatment ( n = 8) and group 1 infants receiving FFP ( n = 11 ) , and group 2 infants receiving no treatment ( n = 9 ) and group 2 receiving FFP ( n = 10 ) . FFP was given at a dose of 10 ml/kg daily during a two-hour period for the first three days of life . ECV was measured on day 1 before FFP was given and on day 4 by the distribution of bromide . There was a significant correlation between birth weight and initial ECV ( r = 0.85 , P less than 0.001 ) . In group 1 ECV was significantly higher than in group 2 ( P less than 0.02 ) . In group 1 receiving no treatment mean weight loss and mean decrease in ECV were equal ( 84 g/kg and 78 ml/kg , respectively ) , but no correlation between the two parameters could be found ( r = 0.68 , P = 0.06 ) . In the other study groups , mean weight loss was higher than mean decrease in ECV , with no correlation between weight loss and change in ECV . ( ABSTRACT TRUNCATED AT 250 WORDS Withdrawal of autologous plasma offers the possibility of improving patients ' hemostasis and of reducing homologous blood consumption in cardiac surgery . The influence of acute , preoperatively performed plasmapheresis ( APP ) on platelet function was investigated in elective aortocoronary bypass patients subjected to APP producing either platelet-poor plasma ( PPP ; group 1 ; n = 12 ) or platelet-rich plasma ( PRP ; group 2 ; n = 12 ) . APP-treated patients were r and omly compared to patients without APP ( control group ; n = 12 ) . Platelet aggregation induced by ADP ( concentration 0.25 , 0.5 , 1.0 , and 2.0 mumol/L ) , collagen ( 4 microL/mL ) , and epinephrine ( 25 mumol/L ) was determined by the turbidometric method before and after APP , as well as before and after cardiopulmonary bypass ( CPB ) until the morning of the 1st postoperative day . APP had no negative effects on the patients ' aggregation parameters ( maximum aggregation and maximum gradient of aggregation ) . The platelet counts in the withdrawn plasma were 25 + /- 10 x 10(9)/L ( PPP-group ) and 250 + /- 30 x 10(9)/L ( PRP-group ) . Platelet counts were highest in the PRP-group at the end of the operation ( after retransfusion of autologous plasma ) . After CPB , maximum aggregation and maximum gradient of aggregation were reduced in all groups ( ranging from -6 % to -25 % from baseline values ) . Retransfusion of autologous plasma improved platelet aggregability significantly only in the PRP-group . By the first postoperative day , maximum aggregation and maximum gradient of aggregation recovered in all groups ( including the control group ) or even exceeded baseline values ( ranging from + 8 % to + 42 % from baseline values . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Infants and children undergoing cardiopulmonary bypass become substantially hemodiluted secondary to the volume used to prime the oxygenator . Fresh-frozen plasma has been included in the prime to lessen dilution of clotting factors and correspondingly minimize blood loss and transfusions . METHODS We prospect ively r and omized 56 patients weighing 10 kg or less who required cardiopulmonary bypass to receive either one unit of fresh-frozen plasma or 200 mL of albumin 5 % in the prime . After protamine administration , sample s for prothrombin time , fibrinogen , platelet count , and thromboelastogram were obtained . Mediastinal chest tube drainage and transfusion requirements were documented . RESULTS There were no significant differences between groups regarding demographic or surgical characteristics . Blood loss during the first 24 hours was similar in both groups , but total transfusions were significantly greater in those who received fresh-frozen plasma instead of albumin 5 % in the prime ( 8.0 + /- 4.2 versus 6.1 + /- 4.5 U , respectively ; p = 0.035 ) . Post hoc analyses suggest that for cyanotic patients and patients undergoing complex operations , fresh-frozen plasma in the prime results in less blood loss than albumin 5 % . CONCLUSIONS Substitution of albumin 5 % for fresh-frozen plasma in the prime of acyanotic patients weighing 10 kg or less who undergo noncomplex operations requiring cardiopulmonary bypass significantly reduces perioperative transfusions without increasing blood loss . Further investigation is needed to determine whether increased blood loss is associated with increased transfusions when albumin 5 % is substituted for fresh-frozen plasma in the prime of infants and children who are cyanotic or undergoing complex operations OBJECTIVE Anticoagulation-treated patients presenting with intracranial hemorrhage , including subdural hematoma , epidural hematoma , subarachnoid hemorrhage , and intracerebral hemorrhage , require urgent correction of their coagulopathy to prevent worsening hemorrhage and to facilitate surgical intervention when necessary . In this study , we compared the use of fresh frozen plasma ( FFP ) with that of Factor IX complex concentrate ( FIXCC ) to achieve rapid correction of warfarin anticoagulation . METHODS Patients admitted to a tertiary care center with computed tomography-proven intracranial hemorrhage and a prothrombin time of more than 17 seconds were considered for inclusion in the study protocol . Complete data sets were obtained for eight patients r and omized to treatment with FFP and five patients r and omized to treatment with FFP supplemented with FIXCC . The prothrombin time and International Normalized Ratio were measured every 2 hours for 14 hours . Correction of anticoagulation was defined as an International Normalized Ratio of < or = 1.3 . RESULTS A difference in repeated International Normalized Ratio measurements during the first 6 hours of correction was observed between the FIXCC and FFP groups ( P < 0.03 ) . The rate of correction was greater ( P < 0.01 ) and the time to correction was shorter ( P < 0.01 ) for the FIXCC-treated group . No difference in neurological outcomes was detected between groups , but a higher complication rate was observed for the FFP-treated group . CONCLUSION The use of FIXCC accelerated correction of warfarin-related anticoagulation in the presence of intracranial hemorrhage BACKGROUND Transfusion-related acute lung injury ( TRALI ) and other posttransfusion reactions may be caused by granulocyte and /or HLA antibodies , which are often present in blood from multiparous donors . The purpose of this study was to compare the effects of plasma from multiparous donors with those of plasma from donors with no history of transfusion or pregnancy ( control plasma ) in a prospect i ve , r and omized , double-blind , crossover study . STUDY DESIGN AND METHODS Intensive care patients , judged to need at least 2 units of plasma , were r and omly assigned to receive a unit of control plasma and , 4 hours later , a plasma unit from a multiparous donor ( > or = 3 live births ) or to receive the plasma units in opposite order . The patients were closely monitored , and body temperature , blood pressure , and heart rate were recorded . Blood sample s for analysis of blood gases , TNFalpha , IL-1 receptor antagonist , soluble E selectin , and C3d complement factor were collected at least on four occasions ( before and after the transfusion of each unit ) . RESULTS Transfusion of plasma from multiparous donors was associated with significantly lower oxygen saturation and higher TNFalpha concentrations than transfusion of control plasma . The mean arterial pressure increased significantly after the transfusion of control plasma , whereas plasma from multiparous donors had no effect on it . Five posttransfusion reactions were observed in 100 patients , in four cases after the transfusion of plasma from multiparous donors . CONCLUSION Plasma from multiparous blood donors may impair pulmonary function in intensive care unit patients BACKGROUND Virus inactivation of pooled fresh-frozen plasma ( FFP ) by the solvent/detergent ( SD ) method results in a loss of approximately 20 percent of factor VIII . This study aim ed to assess the efficacy of SD-treated plasma in correcting the coagulopathy associated with liver disease and liver transplantation . STUDY DESIGN AND METHODS Forty-nine patients with coagulation deficits due to liver disease , who required FFP for invasive procedures or liver transplantation , were r and omly assigned to receive either FFP or SD-treated plasma . Patients were assessed for side effects , correction of coagulopathy over 24 hours , and seroconversion for viral markers 6 to 18 months after treatment . RESULTS In the liver disease group , equal correction of clotting factors and partial thromboplastin time was seen with FFP and SD-treated plasma , with a similar return to baseline values over 24 hours . There was greater correction of the International Normalised Ratio in patients receiving SD-treated plasma ( p = 0.037 ) , but this patient group had higher baseline values than recipients of FFP ( p = 0.024 ) . Liver transplant patients also showed equivalent correction of coagulopathy with the same dose of FFP and SD-treated plasma . The use of other blood components during transplantation was identical in the two treatment groups . No seroconversions were seen for HIV or hepatitis B or C virus . One patient who had received FFP seroconverted for human parvovirus B19 . Apparent seroconversion for hepatitis A virus seen at 9 to 13 months in four other patients was probably due to detection of passively transferred antibodies , as later testing of these patients gave negative results . Minor side effects were rare in both groups . CONCLUSION SD-treated plasma is an efficacious source of coagulation factors for patients with liver disease who are undergoing biopsy or transplantation . Assessment of seroconversion for viral markers in recipients of plasma-derived products and plasma components should include consideration of the possibility that passively transferred antibodies were detected Prior studies at Harborview Medical Center have suggested that dilutional thrombocytopenia is a major etiology of microvascular , nonmechanical bleeding ( MVB ) . We undertook a prospect i ve r and omized double-blind clinical study to compare the prophylactic effects of 6 units of platelet concentrates ( PLT ) versus 2 units of fresh frozen plasma ( FFP ) administered with every 12 units of modified whole blood in patients undergoing massive transfusion ( 12 or more units in 12 hours ) . After exclusions , three of 17 patients who received PLT and three of 16 patients who received FFP developed MVB , an incidence no different from our previous findings . Regression lines of platelet counts during transfusion were no different between groups , and both groups had higher platelet counts than predicted from a st and ard washout equation . Only one patient had evidence of dilutional thrombocytopenia as a cause for MVB . Prophylactic platelet administration is not warranted as a routine measure to prevent MVB Donor plasmapheresis that is carried out weeks before the operation has proven to be of benefit in elective orthopedic patients with regard to reducing homologous blood consumption and preserving coagulation . In this study acute preoperatively performed plasmapheresis ( APP ) was investigated in cardiac surgery patients . Forty-five patients scheduled for elective aortocoronary bypass surgery were r and omly divided into three groups of 15 patients each : 1 ) removal of platelet-poor plasma ( PPP ) , 2 ) removal of platelet-rich plasma ( PRP ) , and 3 ) no plasmapheresis ( control group ) . Plasma volume removed was 10 ml/kg in all APP patients , and plasma was replaced by the same amount of low-molecular weight hydroxyethylstarch solution ( 6 % HES 200/0.5 ) . Various laboratory data were investigated before , during , and after extracorporeal circulation ( ECC ) . Blood loss in control patients was more pronounced than in the two APP groups ; two of the control patients needed packed red cells . APP itself did not affect coagulation variables , free hemoglobin , or polymorphonuclear ( PMN ) elastase . At the end of the operation , 5 h after ECC , and at the first postoperative day the number of platelets was significantly lower in the control group ; PRP patients showed the highest values . Fibrinogen and AT-III levels were less compromised in APP patients than in the control group . Global coagulation parameters did not differ between the groups within the whole investigation period . PMN elastase increased significantly during ECC in all groups with the greatest increase in the control group ( 722 % ) and the smallest increase in PRP patients ( 280 % ) , possibly due to the removal of cellular elements in this group . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND AND OBJECTIVES Solvent/detergent-treated plasma ( SDP ) contains markedly lower protein S ( PS ) and plasmin inhibitor ( PI ) activity than st and ard fresh-frozen plasma ( FFP ) . It has also been reported that SDP contains no alpha(1)-antitrypsin . Despite the lack of clinical data , it is suspected that SDP may be less effective than FFP in the treatment of complex coagulopathies . We therefore conducted a prospect i ve trial to study the impact of SDP and FFP on haemostasis and fibrinolysis in complex coagulopathy after open-heart surgery . MATERIAL S AND METHODS Patients received either 600 ml of SDP ( n = 36 ) or 600 ml of FFP ( n = 31 ) at an infusion rate of 30 ml/min . The following parameters were measured before treatment and 60 min after termination of plasma infusion : prothrombin time ( PT ) , activated partial thromboplastin time ( APTT ) , fibrinogen , factor VIII , antithrombin , protein C ( PC ) , free PS and PS activity , prothrombin fragments F1 + 2 ( F1 + 2 ) , D-dimers ( DD ) , fibrinogen degradation products ( FDP ) , plasmin-plasmin inhibitor complexes ( PPI ) , plasminogen , PI and alpha(1)-antitrypsin . RESULTS The rise in fibrinogen , factor VIII , antithrombin , PC , free PS , alpha(1)-antitrypsin and plasminogen , and the decrease in PT and APTT , did not significantly differ between the two study arms . However , PS activity did not increase after SDP infusion but did show a significant elevation after infusion with FFP . PI declined significantly after SDP and remained uninfluenced by FFP . Neither SDP nor FFP had any significant influence on F1 + 2 , DD or FDP . However , a significant decrease in PPI levels caused by both types of plasma indicated a reduction in hyperfibrinolysis . Clinical haemostasis evaluation revealed no significant difference between the two treatment regimens . No adverse reactions were observed . CONCLUSION With the exception of PS and PI , SDP and FFP improved haemostasis and fibrinolysis to a similar degree . The clinical significance of these findings has to be determined in patients with severe acquired PS and PI deficiency requiring plasma transfusions Abstract 461 consecutive inborn babies , delivered during the period September 1993–March 1994 were subjected to a microhematocrit assessment at 6 hours of age to determine the incidence of polycythemia . 47 babies ( inborn and out born ) , admitted to the neonatal unit with confirmed polycythemia were studied for clinical and laboratory abnormalities . These 47 babies were then r and omly assigned to receive partial exchange transfusion with either normal saline or fresh plasma . The incidence of polycythemia was 27 of 461 ( 5.8 % ) . 23 of 27 ( 85.1 % ) were term babies and 15 of 27 ( 55.5 % ) were small for gestational age . 14 of 27 ( 51.1 % ) babies had mothers who had pregnancy induced hypertension . Feeding problems ( 16/47 ) and lethargy ( 25/47 ) were the commonest symptoms ( 34 % and 51 % respectively ) . 25 of 47 ( 51 % ) babies had hypoglycemia and 5 of 47 ( 10.6 % ) had hypocalcemia . Thrombocytopenia was seen in 13/47 ( 27.65 % ) of cases . 24 babies received normal saline and 23 received fresh plasma for partial exchange transfusion . The immediate post-exchange fall in hematocrit was significant in both groups and this was well sustained over the following 48 hours . However , improvement in clinical and laboratory parameters was more remarkable with fresh plasma . Polycythemia appears to be a real clinical entity in neonates in India and babies with known risk factors should be actively screened for this condition . Once diagnosis is established special attempts should be made to rule out hypoglycemia . For treatment of polycythemia fresh plasma is preferable for partial exchange transfusion but normal saline appears to be an adequate substitute To assess the place of passive immunotherapy in the treatment of AIDS , a r and omized study was conducted that evaluated the safety and short-term efficacy of serial transfusions of human immunodeficiency virus type 1 ( HIV-1 ) seropositive plasma in 18 patients . Heat-inactivated anti-HIV antibody-rich plasma was compared with seronegative fresh-frozen seronegative plasma given in addition to zidovudine and other conventional prophylactic treatments . Seven transfusions every 2 weeks of immune plasma significantly reduced ( 2 vs. 8 , P = .016 ) the number of opportunistic infections . Antigenemia became undetectable . When transfusions were stopped , positive p24 antigenemia returned at a level higher than before treatment and was correlated with a severe clinical deterioration , suggesting a rebound effect . This trial suggests that passive immunotherapy is promising in AIDS treatment . It confirms also that plasma donation does not affect donors ' CD4 cell count over a 1-year period . In patients with severe immunodeficiency , special attention should be paid to withdrawal of an effective therapy as virologic relapse may be explosive and poorly tolerated Patients undergoing cardiac operations constitute the majority of recipients of fresh frozen plasma . In most centers the reason for transfusing fresh frozen plasma is to replace clotting factors . However , the decrease of clotting factors during cardiopulmonary bypass is not sufficient in most patients to cause abnormal bleeding . One of the major causes of nonsurgical bleeding after cardiac operations is acquired platelet dysfunction , which can be corrected by transfusion of 1 unit of fresh whole blood . Because plasmatic factors in fresh whole blood may be responsible for this improvement , a study was design ated to evaluate the effect of transfusing fresh plasma on platelet function after cardiac operations . Forty patients undergoing cardiopulmonary bypass were r and omized to receive either fresh plasma or the fresh packed cell fraction . Administration of packed cells increased platelet number ( 118 + /- 8.5 to 154 + /- 7.6 x 10(9)/L , p less than 0.05 ) , shortened bleeding time ( 7.57 + /- 0.4 to 4.0 + /- 0.3 minutes , p less than 0.05 ) , and improved platelet aggregation in response to collagen and epinephrine ( 32 % + /- 4.7 % to 50 % + /- 5.6 % and 37 % + /- 5.8 % to 50 % + /- 5.8 % , respectively , p less than 0.05 ) . Fresh plasma , however , neither increased platelet number nor improved bleeding time or platelet aggregation . Each group later received the remainder of the blood unit , with similar results . The results suggest that improvement of platelet function in patients receiving fresh whole blood after cardiac operations is not related to plasmatic factors . Therefore the massive use of fresh frozen plasma in patients after cardiopulmonary bypass should be reconsidered A prospect i ve study was design ed to compare the administration of available fresh blood and component therapy in the treatment of gastrointestinal bleeding in patients with cirrhosis of the liver . Fifty bleeding cirrhotic patients were r and omly assigned to treatment : 17 patients recieved 51 percent fresh blood ( Group 1 ) , 16 patients received 22 percent fresh blood ( Group 2 ) , and 17 patients received 25 percent component therapy consisting of packed cells , fresh frozen plasma , and platelet concentrate ( Group 3 ) . The mortality rate was unaffected by the type of blood replacement . Neither the blood replacement requirement ( Group 1:51 plus or minus 0.9 units Group 2:5.5 plus or minus 0.8 units , Group 3:7.1 plus or minus 1.1 units ) nor the duration of bleeding ( Group 1:39 plus or minus 0.8 days , Group 2:6.3 plus or minus 2.4 days , Groups 3:5.8 plus or minus 1.0 days ) were significantly different . There was no correlation between the mean age of blood or plasma received and the units of blood replaced or the duration of bleeding . Patients with severe coagulation abnormalties had a significantly increased mortality . Component therapy was as effective as the fresh blood regimen in cirrhotic patients with acute gastrintestinal hemorrhage Fresh frozen plasma ( FFP ) has been proposed as a specific therapy for acute pancreatitis . Reduced mortality encountered in an uncontrolled clinical study and a controlled experimental study may be attributable to replenishment by FFP of the naturally occurring antiprotease system . To investigate this potential therapy further , 202 patients presenting with acute pancreatitis were r and omized to receive FFP ( 2 units daily for 3 days ) or a similar volume of colloid control as part of their intravenous fluid therapy . Clinical progress was monitored and the major serum antiproteases ( α1‐antiprotease and α2‐macroglobulin ) were measured on days 1 , 3 and 7 . There was no significant difference between the two groups in terms of clinical outcome . α1‐Antiprotease levels rose significantly from day 1 to day 3 in both groups ( P < 0·0001 ) and remained elevated at day 7 . α1‐Antiprotease is an acute phase protein in man and raised serum levels would be anticipated . FFP appears to have no effect on the magnitude of this rise . Serum α2‐macroglobulin levels were reduced in both groups on day 1 and continued to fall significantly from day 1 to day 3 in the colloid control group ( P<0·005 ) whilst remaining substantially unaltered in patients receiving FFP ( P = 0·6527 ) . α2‐Macroglobulin plays a central role in the elimination of proteases during acute pancreatitis and the ability of relatively low volumes of FFP to reduce the fall in serum α2‐macroglobulin levels seen during the early stages of this disease may have therapeutic implication Background : Reduced levels of protein S ( PS ) and α2-antiplasmin α2-AP ) in solvent/detergent virus-inactivated plasma ( S/D-VIP ) might induce an imbalance of plasma coagulation factors and inhibitors in patients transfused . We investigated 40 patients ( 23 fresh frozen plasma ( FFP ) , 17 S/D-VIP , r and om distribution by a list calculated by statisticians ) who suffered from dilution coagulopathy , liver disease , disseminated intravascular coagulation ( DIC ) , polytrauma or were connected to extracorporeal circulation . Study Design and Methods : The following markers of activated coagulation ( MAC ) were measured : Prothrombin fragment F1 + 2 ( F1 + 2 ) , fibrin monomers ( FM ) , D-dimers ( DD ) , thrombin-antithrombin ( TAT ) and plasmin-antiplasmin ( PAP ) complexes as well as fibrinogen degradation products ( FgDP ) , and additionally antithrombin III ( antithrombin ) , protein C ( PC ) , PS and α2-AP . Blood was taken only just before and 1 h after the first plasma replacement ( 2 units ) . No additional blood products were transfused before the second blood withdrawal . Pre- and posttransfusion ( pre/post ) values of all parameters measured were compared within the same group and between both groups . Statistical evaluation of the data was done by Wilcoxon ’s paired test for data in the same plasma group and by the test of Mann and Whitney for data comparison between both plasma groups . Results : Average pretransfusion values of all inhibitors for both plasma groups were in the same range and increased after transfusion , except for PS in both groups . Whereas the pre/post values did not differ significantly in the FFP group , antithrombin ( p = 0.02 ) , PC ( p = 0.0005 ) , and α2-AP ( p = 0.02 ) showed a significantly higher increase in the S/D-VIP group . Considering the pre/post differences between both plasma groups , there were no significant differences . The same was true for MAC measured pre- and posttransfusion . Conclusion : Data showed no significant difference between both plasma groups , indicating that S/D-VIP plasma behaves as FFP under the study conditions employed Twenty patients with burn injuries involving 45 % or more total body surface area were r and omly allocated to receive either fresh-frozen plasma ( plasma ) , 200 ml/m2/d ( 11 patients ) , or an approximately equal amount of plasma protein derivative ( Plasmanate ) ( nine patients ) during the first 45 days postburn . To study the potential effects of these two adjunctive therapies on host resistance to infection , measurements were made twice weekly of the antibacterial funciton of neutrophils , the opsonic index ( ability to opsonize alternative pathway dependent E. coli 075 ) , C3(B ) , IgG , properdin , factor B , total protein , and albumin . The average size of burn in the plasma group was 61.5 % total and 42 % 3 degrees compared with 61 % total and 46 % 3 degrees in the Plasmanate group . Ten and 18 episodes of bacteremia occurred in the plasma and Plasmanate groups , respectively . Analysis of the results indicates only slightly better support of host resistance when plasma is administered , but this is counterbalanced by the increased risk of viral hepatitis BACKGROUND To date , no clinical trials have characterized FFP infusion efficacy , and infusion still carries infectious risk . This single-blinded crossover study compared postinfusion kinetics of FVII in photochemically treated FFP to st and ard FFP . STUDY DESIGN AND METHODS Subjects donated plasma by apheresis . Half of the collected plasma was treated with the psoralen amotosalen hydrochloride ( S-59 ) and UVA light , and half were prepared as st and ard plasma . Subjects received warfarin over 4 days to lower FVII levels . On Day 4 , subjects received 1 L of either treated or st and ard FFP . After 2 weeks , subjects underwent a regimen identical to that with the other type of FFP . RESULTS After warfarin ingestion , the mean FVII concentration was 0.33 IU per mL. Both types of FFP exhibited comparable FVII kinetics , with a mean peak increment of 0.10 to 0.12 IU per mL occurring at the end of infusion . The effect disappeared after 8 hours . DISCUSSION Study data of warfarin-treated healthy volunteers demonstrate that psoralen plus UV-treated FFP provides an equivalent in vivo coagulation response to control plasma . A 1-L dose of FFP in adults may provide an initial increment of 0.10 IU per mL of FVII . In the absence of bleeding , FVII levels return to baseline after 8 hours OBJECTIVE To determine the efficacy and relative effectiveness of conjugated entrogens ( CE ) and fresh-frozen plasma ( FFP ) in normalizing prolonged preoperative bleeding times during renal transplantation . DESIGN Prospect i ve , r and omized trial . SETTING A university regional referral center for transplantation . PATIENTS Patients scheduled for renal transplantation with preoperative bleeding times greater than 10 minutes ( normal , < 7 minutes ) following informed consent were asked to participate in the r and omized protocol . Those with bleeding times of 8 to 9.5 minutes were asked , following informed consent , to be a control group receiving neither CE nor FFP . INTERVENTIONS Following induction of anesthesia and drawing of baseline laboratory tests , patients were administered r and omly , using a table of r and om numbers , either 50 mg of CE or 2 U of FFP . MAIN OUTCOME MEASURES Bleeding time measurements and other laboratory tests were repeated at the end of surgery as well as at 24 and 48 hours postoperatively . RESULTS Treatment with CE and FFP decreased the patients ' bleeding times from 16.68 + /- 0.8 ( SEM ) and 17.13 + /- 0.85 minutes to 7.67 + /- 0.79 ( P < .001 ) and 10.50 + /- 1.27 minutes ( P < .001 ) , respectively , by the end of surgery . At 24 and 48 hours postoperatively , the CE group had bleeding times of 9.77 + /- 0.99 and 9.81 + /- 1.24 minutes ( P < .001 for both ) , respectively , whereas the FFP group bleeding times were 12.76 + /- 1.57 ( P = .003 ) and 12.14 + /- 1.56 minutes ( P = .001 ) , respectively . There were no statistical differences for the control group compared with baseline either at the end of surgery or at 24 hours . CONCLUSIONS Although both CE and FFP significantly decreased prolonged preoperative bleeding times during renal transplantation , CE might be preferred because of lower risk and cost , as well as a longer duration of action We have compared the effect of therapy with immunosuppression alone to immunosuppression plus plasma exchange on the clinical course and rate of disappearance of antibody in 17 patients with anti-glomerular basement membrane ( anti-GBM ) antibody-induced renal disease . Patients receiving immunosuppression ( n = 9 ) and those receiving plasma exchange ( n = 8) were similar in terms of entry clinical characteristics , pulmonary manifestations and complications associated with therapy . Rate of disappearance of anti-GBM antibody as estimated from serial estimates of antibody binding was significantly more rapid in patients receiving plasma exchange , and mean serum creatinine in these patients at end of therapy was half that of the patients receiving immunosuppression alone . Analysis of clinical and pathologic values at study entry , however , indicated that the percent of crescents on initial renal biopsy and entry serum creatinine correlated better with outcome than did therapeutic modality . Thus , though plasma exchange may offer some advantage over immunosuppression alone in the treatment of this disease , degree of pathologic involvement appears to be the major factor affecting outcome . Patients with low cresents ( less than 30 % ) and well preserved function did well with either treatment , while patients with severe crescentic involvement and impaired glomerular filtration rate did poorly The effect on abnormal coagulation tests of infusions of fresh-frozen plasma ( F.F.P ) , prothrombin complex concentrates , and a combination of these treatments was compared in 30 patients with chronic liver disease undergoing needle biopsy . A single dose of F.F.P. ( 12 ml/kg body-weight ) was found to be the least effective therapeutic regimen . The concentrate containing factors II , IX , and X was also not adequate , but the additional administration of factor-VII concentrate corrected the prothrombin-time ( P.T. ) and " Normotest " ( N.T. ) in most patients . However , this regimen did not correct the prolonged kaolin activated partial thromboplastin-time ( K.P.T.T. ) . The results of tests for exploring both the extrinsic ( P.T. and N.T. ) and intrinsic ( K.P.T.T. ) coagulation systems only became normal after the combined administration of a lower dose of F.F.P. ( 8 ml/kg body-weight ) and of both concentrates ( 12 units/ml ) . There was no clinical or laboratory evidence of thrombotic complications . No patient developed acute hepatitis or hepatitis-B surface antigen in the twelve months after biopsy . These results indicate that prothrombin-complex concentrates in combination with F.F.P. may therefore be used to allow liver biopsy to be performed safely in patients presenting with severe coagulation defects Transfusions with incompatible blood products including plasma are a well-known problem . The present study was performed to test the effects of Uniplas , universal plasma that can be transfused regardless of a patient 's blood group , with respect to bleeding and hemostatic activity . The study comprised 84 adult patients scheduled for elective openheart surgery . A total of 55 patients received plasma transfusions , while 29 patients not requiring plasma served as controls . If plasma transfusion was indicated during operation or over the two following days , patients were r and omised 2:1 to receive Uniplas or Octaplas of blood group AB . Relevant clinical observations were recorded and blood tests taken repeatedly . The transfused patient groups were comparable , and no significant differences were observed with respect to activated clotting time ( ACT ) , activated partial thromboplastin time ( APTT ) or postoperative bleeding into chest drains . The median number of transfused units of Uniplas was 3 , with a range of 1 - 23 , while the median for Octaplas was 2 with a range of 1 - 11 . These differences were not significant . Thus , Uniplas has a similar effect as Octaplas in the treatment of bleeding in patients undergoing openheart surgery . Uniplas can therefore substitute for Octaplas and eliminate the risk of ABO-incompatible transfusions BACKGROUND The negative influence of cardiopulmonary bypass on hemostasis has been documented . Although abnormalities in platelet function are reported as the major cause of postoperative blood loss related to this hemostasis defect , fresh frozen plasma is often used in operations with cardiopulmonary bypass because it is thought to contribute to the reduction of postoperative bleeding complications . This study was design ed to evaluate the effect of the administration of fresh frozen plasma after cardiopulmonary bypass on blood loss , transfusion requirements , and a number of coagulation parameters . METHODS In a prospect i ve , r and omized , double-blind clinical trial 50 patients ( mean age 63 years ; 35 men/15 women ) undergoing elective operation with cardiopulmonary bypass were r and omly assigned to one of two groups : group I ( n = 24 ) received 3 units of fresh frozen plasma after operation and group II ( n = 26 ) received an equal amount of Gelofusine plasma substitute . At seven points before , during , and after operation hemoglobin concentration , hematocrit level , thrombocyte count , and coagulation parameters were analyzed . Study endpoints were the volume of blood loss and the transfusion requirement . RESULTS There were no significant differences between the two study groups in blood loss , transfusion requirement , coagulation parameters , or thrombocyte counts . CONCLUSION The routine use of fresh frozen plasma in operations with cardiopulmonary bypass can not be recommended Haemorrhage , including intracranial bleeding , is a common , potentially lethal complication of warfarin therapy and rapid and complete reversal of anticoagulation may be life-saving . Fresh frozen plasma ( FFP ) and vitamin K are most frequently administered . Because of the variable content of vitamin K-dependent clotting factors in FFP , and the effects of dilution , the efficacy of this approach is open to doubt . We have therefore compared the effects of FFP and clotting factor concentrates on the INRs and clotting factor levels of orally anticoagulated subjects requiring rapid correction of their haemostatic defect . In many , the pre-treatment INR was considered to be dangerously above the target therapeutic range . In the 12 patients given FFP , the INR did not completely correct ( range 1.6 - 3.8 , mean 2.3 ) indicating an ongoing anticoagulated state in all . In contrast , the INR in 29 subjects given clotting factor concentrates was completely corrected in 28 ( range 0.9 - 3.8 , mean 1.3 ) . Following treatment , marked differences were observed in clotting factor IX levels between the two groups . The median factor IX level was 19 u/dl ( range 10 - 63 ) following FFP infusion and 68.5 u/dl ( range 31 - 111 ) following concentrate . In FFP treated patients , poorer responses were also observed for each of the other vitamin K-dependent clotting factors but these were less marked than for factor IX , which was present in low concentrations in some batches of FFP . Thus , haemostatically effective levels of factor IX can not be achieved , in most instances , by the conventional use of FFP in patients requiring reversal of their anticoagulant therapy . Clotting factor concentrates are the only effective option where complete and immediate correction of the coagulation defect is indicated in orally anticoagulated patients with life or limb-threatening haemorrhage Coagulation change was studied in 16 adult female patients undergoing radical hysterectomy with BPLND surgery . None had preoperative alterations in coagulation or liver function and was receiving anticoagulant or antiplatelet medication . Sixteen ASA class I-II were divided into 2 groups r and omly with eight patients in each group . One group accepted autologous plasma transfusion near the end of surgery , the other group did not . Autologous plasma was retrieved by plasma saver post induction of anesthesia . Every patient received induced hypotensive anesthesia during the operation . Whole blood coagulation status was quantitated by using thromboelastography ( TEG ) . Blood sample s for TEG were obtained before induction of anesthesia , after closure of peritoneum , and 2 hours post autologous plasma transfusion or 2 hours post peritoneum closure . Most parameters measured by TEG showed improved coagulation status in autologous plasma transfusion group . We concluded that coagulation change was minimal during induced hypotension , and improved coagulation was obtained 2 hours post autologous plasma transfusion during radical hysterectomy with BPLND surgery We measured the influence of maturation and early freshly frozen plasma infusion ( FFP ) on renal function ( day 2 and day 5 ) in preterm infants in intensive care ; they were divided into two groups , those with gestational ages less than 30 weeks ( G less than 30 ) and those with gestational ages of 30 - 34 weeks ( G 30 - 34 ) . A total of 35 infants was studied . The infants were r and omly assigned to one of two treatment groups , one receiving FFP , the other not , yielding four study groups ; G less than 30 and no FFP ( 8 infants ) , G less than 30 and FFP ( 8 infants ) , G 30 - 34 and no FFP ( 9 infants ) and G 30 - 34 and FFP ( 10 infants ) . The infants in the two FFP groups received FFP 10 ml/kg on days 1 - 3 . FFP did not significantly influence creatinine clearance ( CCr ) or the urinary sodium excretion rate either in G less than 30 or G 30 - 34 . CCr was significantly lower ( p less than 0.001 ) and fractional urinary sodium excretion significantly higher ( p less than 0.002 ) in infants of G less than 30 than in infants of G 30 - 34 . Infants of G less than 30 had significantly higher plasma potassium concentrations ( p less than 0.01 ) than infants of G 30 - 34 . Despite the low CCr and the high urinary sodium excretion rate , infants of G less than 30 had stable fluid and electrolyte balance Objectives : To compare the laboratory and clinical outcome of patients who received solvent/detergent-treated plasma ( SDP ) and fresh-frozen plasma ( FFP ) . Methods : A r and omized , double-blinded study to assess the ability of SDP and FFP to reduce a prolonged prothrombin time ( PT ) to ≤15 s in patients with acquired coagulation deficits . Results : 45 patients ( 22 SDP vs. 23 FFP ) were treated with 71 infusions . There were no significant differences in mean dose of plasma infused ( 7.8 ml/kg for SDP vs. 8.0 ml/kg for FFP , p = 0.46 ) , percentage of patients who corrected their PT to ≤15 s ( 32 % for SDP vs. 26 % for FFP , p = 0.67 ) , or percentage of patients whose bleeding ceased ( 27 % for SDP vs. 22 % for FFP ) . Conclusion : No clinical or statistically significant differences were observed after infusion with SDP or FFP in patients with acquired coagulation deficits |
12,317 | 23,450,552 | There was a reduction in mortality that did not reach statistical significance on endothelin receptor antagonists ( OR 0.57 ; 95 % CI 0.26 to 1.24 ) , and limited data suggest that endothelin receptor antagonists improve the Borg dyspnoea score and cardiopulmonary haemodynamics in symptomatic patients .
Hepatic toxicity was not common , and endothelin receptor antagonists were well tolerated in this population .
Endothelin receptor antagonists can increase exercise capacity , improve WHO/NYHA functional class , prevent WHO/NYHA functional class deterioration , reduce dyspnoea and improve cardiopulmonary haemodynamic variables in patients with pulmonary arterial hypertension with WHO/NYHA functional class II and III .
However , there was only a trend towards endothelin receptor antagonists reducing mortality in patients with pulmonary arterial hypertension .
Efficacy data are strongest in those with idiopathic pulmonary hypertension .
The irreversible liver failure caused by sitaxsentan and its withdrawal from global markets emphasise the importance of hepatic monitoring in patients treated with endothelin receptor antagonists | BACKGROUND Pulmonary arterial hypertension is a devastating disease , which leads to right heart failure and premature death .
Recent evidence suggests that endothelin receptor antagonists may be promising drugs in the treatment of pulmonary arterial hypertension .
OBJECTIVES To evaluate the efficacy of endothelin receptor antagonists in pulmonary arterial hypertension .
However , several cases of irreversible liver failure caused by sitaxsentan have been reported that led to license holder for sitaxsentan to withdraw the product from all markets worldwide . | BACKGROUND Primary pulmonary hypertension is a progressive disease for which no treatment has been shown in a prospect i ve , r and omized trial to improve survival . METHODS We conducted a 12-week prospect i ve , r and omized , multicenter open trial comparing the effects of the continuous intravenous infusion of epoprostenol ( formerly called prostacyclin ) plus conventional therapy with those of conventional therapy alone in 81 patients with severe primary pulmonary hypertension ( New York Heart Association functional class III or IV ) . RESULTS Exercise capacity was improved in the 41 patients treated with epoprostenol ( median distance walked in six minutes , 362 m at 12 weeks vs. 315 m at base line ) , but it decreased in the 40 patients treated with conventional therapy alone ( 204 m at 12 weeks vs. 270 m at base line ; P < 0.002 for the comparison of the treatment groups ) . Indexes of the quality of life were improved only in the epoprostenol group ( P < 0.01 ) . Hemodynamics improved at 12 weeks in the epoprostenol-treated patients . The changes in mean pulmonary-artery pressure for the epoprostenol and control groups were -8 percent and + 3 percent , respectively ( difference in mean change , -6.7 mm Hg ; 95 percent confidence interval , -10.7 to -2.6 mm Hg ; P < 0.002 ) , and the mean changes in pulmonary vascular resistance for the epoprostenol and control groups were -21 percent and + 9 percent , respectively ( difference in mean change , -4.9 mm Hg/liter/min ; 95 percent confidence interval , -7.6 to -2.3 mm Hg/liter/min ; P < 0.001 ) . Eight patients died during the study , all of whom had been r and omly assigned to conventional therapy ( P = 0.003 ) . Serious complications included four episodes of catheter-related sepsis and one thrombotic event . CONCLUSIONS As compared with conventional therapy , the continuous intravenous infusion of epoprostenol produced symptomatic and hemodynamic improvement , as well as improved survival in patients with severe primary pulmonary hypertension Background — Eisenmenger syndrome is characterized by the development of pulmonary arterial hypertension with consequent intracardiac right-to-left shunt and hypoxemia in patients with preexisting congenital heart disease . Because Eisenmenger syndrome is associated with increased endothelin expression , patients may benefit from endothelin receptor antagonism . Theoretically , interventions that have some effect on the systemic vascular bed could worsen the shunt and increase hypoxemia . Methods and Results — The Bosentan R and omized Trial of Endothelin Antagonist Therapy-5 ( BREATHE-5 ) was a 16-week , multicenter , r and omized , double-blind , placebo-controlled study evaluating the effect of bosentan , a dual endothelin receptor antagonist , on systemic pulse oximetry ( primary safety end point ) and pulmonary vascular resistance ( primary efficacy end point ) in patients with World Health Organization functional class III Eisenmenger syndrome . Hemodynamics were assessed by right- and left-heart catheterization . Secondary end points included exercise capacity assessed by 6-minute walk distance , additional hemodynamic parameters , functional capacity , and safety . Fifty-four patients were r and omized 2:1 to bosentan ( n=37 ) or placebo ( n=17 ) for 16 weeks . The placebo-corrected effect on systemic pulse oximetry was 1.0 % ( 95 % confidence interval , −0.7 to 2.8 ) , demonstrating that bosentan did not worsen oxygen saturation . Compared with placebo , bosentan reduced pulmonary vascular resistance index ( −472.0 dyne · s · cm−5 ; P=0.0383 ) . The mean pulmonary arterial pressure decreased ( −5.5 mm Hg ; P=0.0363 ) , and the exercise capacity increased ( 53.1 m ; P=0.0079 ) . Four patients discontinued as a result of adverse events , 2 ( 5 % ) in the bosentan group and 2 ( 12 % ) in the placebo group . Conclusions — In this first placebo-controlled trial in patients with Eisenmenger syndrome , bosentan was well tolerated and improved exercise capacity and hemodynamics without compromising peripheral oxygen saturation Background — Pulmonary hypertension ( PH ) is associated with restricted physical capacity , limited quality of life , and a poor prognosis because of right heart failure . The present study is the first prospect i ve r and omized study to evaluate the effects of exercise and respiratory training in patients with severe symptomatic PH . Methods and Results — Thirty patients with PH ( 21 women ; mean age , 50±13 years ; mean pulmonary artery pressure , 50±15 mm Hg ; mean World Health Organization [ WHO ] class , 2.9±0.5 ; pulmonary arterial hypertension , n=23 ; chronic thromboembolic PH , n=7 ) on stable disease-targeted medication were r and omly assigned to a control ( n=15 ) and a primary training ( n=15 ) group . Medication remained unchanged during the study period . Primary end points were the changes from baseline to week 15 in the distance walked in 6 minutes and in scores of the Short Form Health Survey quality -of-life question naire . Changes in WHO functional class , Borg scale , and parameters of echocardiography and gas exchange also were assessed . At week 15 , patients in the primary and secondary training groups had an improved 6-minute walking distance ; the mean difference between the control and the primary training group was 111 m ( 95 % confidence interval , 65 to 139 m ; P<0.001 ) . Exercise training was well tolerated and improved scores of quality of life , WHO functional class , peak oxygen consumption , oxygen consumption at the anaerobic threshold , and achieved workload . Systolic pulmonary artery pressure values at rest did not change significantly after 15 weeks of exercise and respiratory training ( from 61±18 to 54±18 mm Hg ) within the training group . Conclusions — This study indicates that respiratory and physical training could be a promising adjunct to medical treatment in severe PH . The effects add to the beneficial results of modern medical treatment RATIONALE A previous trial of bosentan in idiopathic pulmonary fibrosis ( IPF ) showed a trend to delayed IPF worsening or death . Also , improvements in some measures of dyspnea and health-related quality of life were observed . OBJECTIVES To demonstrate that bosentan delays IPF worsening or death . METHODS Prospect i ve , r and omized ( 2:1 ) , double-blind , placebo-controlled , event-driven , parallel-group , morbidity-mortality trial of bosentan in adults with IPF of less than 3 years ' duration , confirmed by surgical lung biopsy , and without extensive honeycombing on high-resolution computed tomography . The primary endpoint was time to IPF worsening ( a confirmed decrease from baseline in FVC ≥ 10 % and diffusing capacity of the lung for carbon monoxide ≥ 15 % , or acute exacerbation of IPF ) or death up to End of Study . Effects of bosentan on health-related quality of life , dyspnea , and the safety and tolerability of bosentan were investigated . MEASUREMENTS AND MAIN RESULTS Six hundred sixteen patients were r and omized to bosentan ( n=407 ) or placebo ( = 209 ) . No significant difference between treatment groups was observed in the primary endpoint analysis ( hazard ratio , 0.85 ; 95 % confidence interval , 0.66 - 1.10 ; P=0.2110 ) . No treatment effects were observed on health-related quality of life or dyspnea . Some effects of bosentan treatment were observed in changes from baseline to 1 year in FVC and diffusing capacity of the lung for carbon monoxide . The safety profile for bosentan was similar to that observed in other trials . CONCLUSIONS The primary objective in the Bosentan Use in Interstitial Lung Disease-3 trial was not met . Bosentan was well tolerated . Clinical trial registered with www . clinical trials.gov ( NCT 00391443 ) OBJECTIVE Recurrent digital ulcers are a manifestation of vascular disease in patients with systemic sclerosis ( SSc ; scleroderma ) and lead to pain , impaired function , and tissue loss . We investigated whether treatment with the endothelin receptor antagonist , bosentan , decreased the development of new digital ulcers in patients with SSc . METHODS This was a r and omized , prospect i ve , placebo-controlled , double-blind study of 122 patients at 17 centers in Europe and North America , evaluating the effect of treatment on prevention of digital ulcers . The primary outcome variable was the number of new digital ulcers developing during the 16-week study period . Secondary assessment s included healing of existing digital ulcers and evaluation of h and function using the Scleroderma Health Assessment Question naire . RESULTS Patients receiving bosentan had a 48 % reduction in the mean number of new ulcers during the treatment period ( 1.4 versus 2.7 new ulcers ; P = 0.0083 ) . Patients who had digital ulcers at the time of entry in the study were at higher risk for the development of new ulcers ; in this subgroup the mean number of new ulcers was reduced from 3.6 to 1.8 ( P = 0.0075 ) . In patients receiving bosentan , a statistically significant improvement in h and function was observed . There was no difference between treatment groups in the healing of existing ulcers . Serum transaminase levels were elevated to > 3-fold the upper limit of normal in bosentan-treated patients ; this elevation is comparable with that observed in previous studies of this agent . Other side effects were similar in the 2 treatment groups . CONCLUSION Endothelins may play an important role in the pathogenesis of vascular disease in patients with SSc . Treatment with the endothelin receptor antagonist bosentan may be effective in preventing new digital ulcers and improving h and function in patients with SSc Background — The degree of pulmonary hypertension in healthy subjects exposed to acute hypobaric hypoxia at high altitude was found to be related to increased plasma endothelin (ET)-1 . The aim of the present study was to investigate the effects of ET-1 antagonism on pulmonary hypertension , renal water , and sodium balance under acute and prolonged exposure to high-altitude – associated hypoxia . Methods and Results — In a double-blind fashion , healthy volunteers were r and omly assigned to receive bosentan ( 62.5 mg for 1 day and 125 mg for the following 2 days ; n=10 ) or placebo ( n=10 ) at sea level and after rapid ascent to high altitude ( 4559 m ) . At sea level , bosentan did not induce any significant changes in hemodynamic or renal parameters . At altitude , bosentan induced a significant reduction of systolic pulmonary artery pressure ( 21±7 versus 31±7 mm Hg , P<0.03 ) and a mild increase in arterial oxygen saturation versus placebo after just 1 day of treatment . However , both urinary volume and free water clearance ( H2OCl/glomerular filtration rate ) were significantly reduced versus placebo after 2 days of ET-1 antagonism ( 1100±200 versus 1610±590 mL ; −6.7±3.5 versus −1.8±4.8 mL/min , P<0.05 versus placebo for both ) . Sodium clearance and segmental tubular function were not significantly affected by bosentan administration . Conclusions — The present results indicate that the early beneficial effect of ET-1 antagonism on pulmonary blood pressure is followed by an impairment in volume adaptation . These findings must be considered for the prevention and treatment of acute mountain sickness BACKGROUND Patients with precapillary pulmonary hypertension ( PH ) exhibit a poor exercise capacity due to an impaired vasodilatory response of their pulmonary arteries . By causing the pulmonary artery to dilate , inhaled nitric oxide ( NO ) may allow an increase in exercise capacity in patients with PH . METHODS AND RESULTS On 2 separate days , 3 days apart , 14 patients with precapillary PH ( 10 primary PH , 4 residual PH after correction of an intracardiac shunt ; age , 40+/-12 years ; mean pulmonary artery pressure , 60+/-23 mm Hg ) performed exercise , with and without inhalation of 20 ppm NO , on a cycle ergometer . The work rate was increased 15 W/min until their symptom-limited maximum , with breath-by-breath gas analysis . Patients were r and omly and blindly selected to inhale NO on either their first or second test . Peak exercise load and anaerobic threshold tended to increase , but not significantly . Peak oxygen consumption ( f1.gif " BORDER="0" > O(2 ) ) and Deltaf1.gif " BORDER="0" > O(2)/DeltaW ratio increased significantly , by 18 % and 22 % , respectively ( peak f1.gif " BORDER="0" > O(2 ) , 13.6+/-3.6 to 16.0+/-4 . 1 mL. kg(-1 ) . min(-1 ) ; Deltaf1.gif " BORDER="0" > O(2)/DeltaW ratio , 5 . 8+/-2.4 to 7.1+/-2.3 mL. kg(-1 ) . min(-1 ) . W(-1 ) ; both P<0.01 ) . Peak f1.gif " BORDER="0" > O(2 ) increased > 10 % in 12 of the 14 patients . However , respiratory quotient at peak exercise decreased from 1 . 22+/-0.15 to 1.09+/-0.15 ( P<0.01 ) . CONCLUSIONS Inhaled NO substantially increases oxygen consumption at the same workload during exercise . This finding supports the possibility of ambulatory NO inhalation therapy in patients with precapillary PH BACKGROUND Sildenafil inhibits phosphodiesterase type 5 , an enzyme that metabolizes cyclic guanosine monophosphate , thereby enhancing the cyclic guanosine monophosphate-mediated relaxation and growth inhibition of vascular smooth-muscle cells , including those in the lung . METHODS In this double-blind , placebo-controlled study , we r and omly assigned 278 patients with symptomatic pulmonary arterial hypertension ( either idiopathic or associated with connective-tissue disease or with repaired congenital systemic-to-pulmonary shunts ) to placebo or sildenafil ( 20 , 40 , or 80 mg ) orally three times daily for 12 weeks . The primary end point was the change from baseline to week 12 in the distance walked in six minutes . The change in mean pulmonary-artery pressure and World Health Organization ( WHO ) functional class and the incidence of clinical worsening were also assessed , but the study was not powered to assess mortality . Patients completing the 12-week r and omized study could enter a long-term extension study . RESULTS The distance walked in six minutes increased from baseline in all sildenafil groups ; the mean placebo-corrected treatment effects were 45 m ( + 13.0 percent ) , 46 m ( + 13.3 percent ) , and 50 m ( + 14.7 percent ) for 20 , 40 , and 80 mg of sildenafil , respectively ( P<0.001 for all comparisons ) . All sildenafil doses reduced the mean pulmonary-artery pressure ( P=0.04 , P=0.01 , and P<0.001 , respectively ) , improved the WHO functional class ( P=0.003 , P<0.001 , and P<0.001 , respectively ) , and were associated with side effects such as flushing , dyspepsia , and diarrhea . The incidence of clinical worsening did not differ significantly between the patients treated with sildenafil and those treated with placebo . Among the 222 patients completing one year of treatment with sildenafil monotherapy , the improvement from baseline at one year in the distance walked in six minutes was 51 m. CONCLUSIONS Sildenafil improves exercise capacity , WHO functional class , and hemodynamics in patients with symptomatic pulmonary arterial hypertension Heart failure is commonly associated with high plasma concentrations of endothelin-1 , a powerful vasoconstrictor produced by endothelium . The role of endogenously released endothelin-1 in the maintenance of vascular tone in chronic heart failure was assessed by acute administration of an endothelin receptor antagonist , bosentan . 24 patients with chronic heart failure received r and omly and double blind two intravenous infusions of either placebo or bosentan ( 100 mg followed after 60 min by 200 mg ) . Systemic haemodynamics and plasma endothelin-1 and big-endothelin-1 concentrations were determined before and repeatedly during the 120 min observation period . Baseline endothelin-1 and big-endothelin-1 concentrations , which were above the normal range in all patients , correlated directly with the extent of pulmonary hypertension , with left and right heart filling pressures , and with pulmonary vascular resistance and inversely with cardiac index . Compared with placebo , bosentan reduced mean arterial pressure by 7.7 % ( 95 % CI 7.1 - 9.7 ) , pulmonary artery pressure by 13.7 % ( 10.5 - 16.9 ) , right atrial pressure by 18.2 % ( 12.0 - 24.4 ) , and pulmonary artery wedged pressure by 8.6 % ( 5.3 - 12.0 ) ; it increased cardiac index by 13.6 % ( 9.1 - 18.2 ) , decreased systemic vascular resistance by 16.5 % ( 13.2 - 19.8 ) , and decreased pulmonary vascular resistance by 33.2 % ( 22.4 - 44.0 ) . Heart rate did not change . Plasma endothelin-1 concentrations rose more than twofold from baseline in bosentan recipients while big-endothelin-1 concentrations were unchanged . These findings indicate that , in patients with chronic heart failure who have high circulatory endothelin-1 concentrations , this peptide contributes to maintenance of vascular tone . The acute haemodynamic effects of bosentan suggest that chronic endothelin antagonism could be beneficial in such patients AIMS To evaluate the efficacy of combining the dual endothelin receptor antagonist , bosentan , and the phosfodiesterase-5-inhibitor , sildenafil , in patients with Eisenmenger syndrome . METHODS AND RESULTS The study was a r and omized , placebo-controlled , double-blinded , cross-over design . Patients with Eisenmenger syndrome ( n = 21 ) were treated open label with bosentan for 9 months . After 3 months , sildenafil/placebo was added for 3 months , and a cross-over was performed for the last 3 months . At baseline and after 3 , 6 , and 9 months , patients were examined with 6 min walk test , oxygen saturations , N-terminal pro-brain natriuretic peptide , New York Heart Association ( NYHA ) classification , cardiac catheterization , and magnetic resonance imaging . The primary endpoint was changed in 6 min walk distance ( MWD ) . Bosentan improved the 6 MWD ( 377 vs. 414 m , P = 0.001 ) , pulmonary vascular resistance ( PVR ) ( 28 vs. 22 wood , P = 0.01 ) , and pulmonary blood flow ( 2.6 vs. 3.5 L/min , P = 0.01 ) . Adding sildenafil to bosentan did not improve the 6 MWD significantly ( 21 vs. 8 m , P = 0.48 ) , but increased saturation at rest ( 2.9 vs. -1.8 % , P < 0.01 ) . CONCLUSION In Eisenmenger syndrome , treatment with bosentan significantly improved walking distance , pulmonary blood flow , and PVR . Adding sildenafil to bosentan did not significantly improve walking distance but did increase saturation at rest . http://www . Clinical Trial.gov : NCT00303004 Background — Treatment options for pulmonary arterial hypertension target the prostacyclin , endothelin , or nitric oxide pathways . Tadalafil , a phosphodiesterase type-5 inhibitor , increases cGMP , the final mediator in the nitric oxide pathway . Methods and Results — In this 16-week , double-blind , placebo-controlled study , 405 patients with pulmonary arterial hypertension ( idiopathic or associated ) , either treatment-naive or on background therapy with the endothelin receptor antagonist bosentan , were r and omized to placebo or tadalafil 2.5 , 10 , 20 , or 40 mg orally once daily . The primary end point was the change from baseline to week 16 in the distance walked in 6 minutes . Changes in World Health Organization functional class , clinical worsening , and health-related quality of life were also assessed . Patients completing the 16-week study could enter a long-term extension study . Tadalafil increased the distance walked in 6 minutes in a dose-dependent manner ; only the 40-mg dose met the prespecified level of statistical significance ( P<0.01 ) . Overall , the mean placebo-corrected treatment effect was 33 m ( 95 % confidence interval , 15 to 50 m ) . In the bosentan-naive group , the treatment effect was 44 m ( 95 % confidence interval , 20 to 69 m ) compared with 23 m ( 95 % confidence interval , −2 to 48 m ) in patients on background bosentan therapy . Tadalafil 40 mg improved the time to clinical worsening ( P=0.041 ) , incidence of clinical worsening ( 68 % relative risk reduction ; P=0.038 ) , and health-related quality of life . The changes in World Health Organization functional class were not statistically significant . The most common treatment-related adverse events reported with tadalafil were headache , myalgia , and flushing . Conclusions — In patients with pulmonary arterial hypertension , tadalafil 40 mg was well tolerated and improved exercise capacity and quality of life measures and reduced clinical worsening Background — Ambrisentan is a propanoic acid – based , A-selective endothelin receptor antagonist for the once-daily treatment of pulmonary arterial hypertension . Methods and Results — Ambrisentan in Pulmonary Arterial Hypertension , R and omized , Double-Blind , Placebo-Controlled , Multicenter , Efficacy Study 1 and 2 ( ARIES-1 and ARIES-2 ) were concurrent , double-blind , placebo-controlled studies that r and omized 202 and 192 patients with pulmonary arterial hypertension , respectively , to placebo or ambrisentan ( ARIES-1 , 5 or 10 mg ; ARIES-2 , 2.5 or 5 mg ) orally once daily for 12 weeks . The primary end point for each study was change in 6-minute walk distance from baseline to week 12 . Clinical worsening , World Health Organization functional class , Short Form-36 Health Survey score , Borg dyspnea score , and B-type natriuretic peptide plasma concentrations also were assessed . In addition , a long-term extension study was performed . The 6-minute walk distance increased in all ambrisentan groups ; mean placebo-corrected treatment effects were 31 m ( P=0.008 ) and 51 m ( P<0.001 ) in ARIES-1 for 5 and 10 mg ambrisentan , respectively , and 32 m ( P=0.022 ) and 59 m ( P<0.001 ) in ARIES-2 for 2.5 and 5 mg ambrisentan , respectively . Improvements in time to clinical worsening ( ARIES-2 ) , World Health Organization functional class ( ARIES-1 ) , Short Form-36 score ( ARIES-2 ) , Borg dyspnea score ( both studies ) , and B-type natriuretic peptide ( both studies ) were observed . No patient treated with ambrisentan developed aminotransferase concentrations > 3 times the upper limit of normal . In 280 patients completing 48 weeks of treatment with ambrisentan monotherapy , the improvement from baseline in 6-minute walk at 48 weeks was 39 m. Conclusions — Ambrisentan improves exercise capacity in patients with pulmonary arterial hypertension . Improvements were observed for several secondary end points in each of the studies , although statistical significance was more variable . Ambrisentan is well tolerated and is associated with a low risk of aminotransferase abnormalities OBJECTIVES We sought to determine the optimal dose of the selective endothelin A ( ET(A ) ) receptor antagonist sitaxsentan for the treatment of pulmonary arterial hypertension ( PAH ) ; for observation only , an open-label ( OL ) bosentan arm was included . BACKGROUND Endothelin is a mediator of PAH . In a preliminary PAH study , the selective ET(A ) receptor antagonist sitaxsentan improved six-min walk ( 6MW ) distance , World Health Organization ( WHO ) functional class ( FC ) , and hemodynamics . METHODS In this double-blind , placebo-controlled 18-week study , 247 PAH patients ( idiopathic , or associated with connective tissue disease or congenital heart disease ) were r and omized ; 245 patients were treated : placebo ( n = 62 ) , sitaxsentan 50 mg ( n = 62 ) or 100 mg ( n = 61 ) , or OL ( 6MW tests , Borg dyspnea scores , and WHO FC assessment s third-party blind ) bosentan ( n = 60 ) . The primary end point was change in 6MW distance from baseline to week 18 . Secondary end points included change in WHO FC , time to clinical worsening , and change in Borg dyspnea score . RESULTS At week 18 , patients treated with sitaxsentan 100 mg had an increased 6MW distance compared with the placebo group ( 31.4 m , p = 0.03 ) , and an improved WHO FC ( p = 0.04 ) . The placebo-subtracted treatment effect for sitaxsentan 50 mg was 24.2 m ( p = 0.07 ) and for OL bosentan , 29.5 m ( p = 0.05 ) . The incidence of elevated hepatic transaminases ( > 3x the upper limit of normal ) was 6 % for placebo , 5 % for sitaxsentan 50 mg , 3 % for sitaxsentan 100 mg , and 11 % for bosentan . CONCLUSIONS Treatment with the selective ET(A ) receptor antagonist sitaxsentan , orally once daily at a dose of 100 mg , improves exercise capacity and WHO FC in PAH patients , with a low incidence of hepatic toxicity AIMS This study evaluated the effects of sitaxentan on the pharmacodynamic [ systemic blood pressure ( BP ) ] and pharmacokinetic ( PK ) parameters of sildenafil in healthy volunteers . METHODS Healthy subjects ( 18–60 years , n= 24 ) were r and omized into two sequence groups . Group 1 received sitaxentan sodium 100 mg daily ( 7 days ) , followed by placebo ( 7 days ) . Group 2 received placebo ( 7 days ) , followed by sitaxentan sodium 100 mg ( 7 days ) . On day 7 of each treatment period , participants received sildenafil 100 mg . PK parameters and BP were analysed on day 7 in each treatment period . RESULTS Sildenafil exposure was slightly higher [ AUC∞ geometric mean ratio ( GMR ) , 128 % ] when co-administered with sitaxentan 100 mg vs. placebo , demonstrating a weak , but statistically significant interaction ( 90 % confidence interval 115.5 % , 141.2 % ) . The mean maximum positive ( Emax+ ) and maximum negative ( Emax– ) changes from baseline in both systolic and diastolic BP were comparable for sitaxentan and placebo ( range 4.8–7.3 mmHg ) with three of four geometric mean ratios falling within the equivalence window , suggesting that the drug interaction was not clinical ly significant . Adverse events were similar between sitaxentan 100 mg ( 39 % ) and placebo ( 30 % ) . No deaths or serious adverse events occurred during the study . CONCLUSION The dose of sildenafil does not need to be adjusted when co-administered with sitaxentan OBJECTIVE Endothelin is implicated as a participatory pathway in systemic sclerosis ( SSc ) . We tested this hypothesis in a 12-month trial of bosentan , a nonselective endothelin receptor antagonist , as a therapy for SSc-related interstitial lung disease ( ILD ) . METHOD Patients with SSc and significant ILD were recruited to this prospect i ve , double-blind , r and omized , placebo-controlled , parallel group study . The inclusion criteria were design ed to select a cohort enriched for patients with active and progressive disease . Exclusion factors included significant pulmonary hypertension . Patients with a diffusing capacity for carbon monoxide of < 80 % predicted and a 6-minute walk distance of 150 - 500 meters or a 6-minute walk distance of > or = 500 meters with a decrease in oxygen saturation received bosentan or placebo . The primary efficacy end point was a change in the 6-minute walk distance from baseline up to month 12 . Secondary end points included time to death or worsening results of pulmonary function tests ( PFTs ) . The safety and tolerability of bosentan were also assessed . RESULTS Among the 163 patients , 77 were r and omized to receive bosentan , and 86 were r and omized to receive placebo . No significant difference between treatment groups was observed for change in the 6-minute walk distance up to month 12 . No deaths occurred in this study group . Forced vital capacity and diffusing capacity for carbon monoxide remained stable in the majority of patients in both groups . Significant worsening of PFT results occurred in 25.6 % of patients receiving placebo and 22.5 % of those receiving bosentan ( P not significant ) . CONCLUSION No improvement in exercise capacity was observed in the bosentan-treated group compared with the placebo group , and no significant treatment effect was observed for the other end points . Although many outcome variables were stable , bosentan did not reduce the frequency of clinical ly important worsening . These data do not support the use of endothelin receptor antagonists as therapy for ILD secondary to SSc After the approval of bosentan for the treatment of pulmonary arterial hypertension ( PAH ) , European authorities required the introduction of a post-marketing surveillance system ( PMS ) to obtain further data on its safety profile . A novel , prospect i ve , internet-based PMS was design ed , which solicited reports on elevated aminotransferases , medical reasons for bosentan discontinuation and other serious adverse events requiring hospitalisation . Data captured included demographics , PAH aetiology , baseline functional status and concomitant PAH-specific medications . Safety signals captured included death , hospitalisation , serious adverse events , unexpected adverse events and elevated aminotransferases . Within 30 months , 4,994 patients were included , representing 79 % of patients receiving bosentan in Europe . In total , 4,623 patients were naïve to treatment ; of these , 352 had elevated aminotransferases , corresponding to a crude incidence of 7.6 % and an annual rate of 10.1 % . Bosentan was discontinued due to elevated aminotransferases in 150 ( 3.2 % ) bosentan-naïve patients . Safety results were consistent across subgroups and aetiologies . The novel post-marketing surveillance captured targeted safety data ( “ potential safety signals ” ) from the majority of patients and confirmed that the incidence and severity of elevated aminotransferase levels in clinical practice was similar to that reported in clinical trials . These data complement those from r and omised controlled clinical trials and provide important additional information on the safety profile of bosentan The efficacy and safety of combining bosentan , an orally active dual endothelin receptor antagonist and epoprostenol , a continuously infused prostagl and in , in the treatment of pulmonary arterial hypertension ( PAH ) was investigated . In this double-blind , placebo-controlled prospect i ve study , 33 patients with PAH started epoprostenol treatment ( 2 ng·kg−1min−1 starting dose , up to 14±2 ng·kg−1min−1 at week 16 ) and were r and omised for 16 weeks in a 2:1 ratio to bosentan ( 62.5 mg b.i.d for 4 weeks then 125 mg b.i.d ) or placebo . Haemodynamics , exercise capacity and functional class improved in both groups at week 16 . In the combination treatment group , there was a trend for a greater ( although nonsignificant ) improvement in all measured haemodynamic parameters . There were four withdrawals in the bosentan/epoprostenol group ( two deaths due to cardiopulmonary failure , one clinical worsening , and one adverse event ) and one withdrawal in the placebo/epoprostenol group ( adverse event ) . This study showed a trend but no statistical significance towards haemodynamics or clinical improvement due to the combination of bosentan and epoprostenol therapy in patients with pulmonary arterial hypertension . Several cases of early and late major complications were reported . Additional information is needed to evaluate the risk/benefit ratio of combined bosentan-epoprostenol therapy in pulmonary arterial hypertension Primary pulmonary hypertension ( PPH ) is a progressive disease with high mortality . Administration of i.v . epoprostenol has demonstrated improved exercise tolerance , haemodynamics , and survival . The orally active , dual endothelin receptor antagonist bosentan improves exercise endurance , haemodynamics , and functional class over the short term . To determine the effect of first-line bosentan therapy on survival , this study followed 169 patients with PPH treated with bosentan in two placebo-controlled trials and their extensions . Data on survival and alternative treatments were collected from September 1999 ( start of the first placebo-controlled study ) to December 31 , 2002 . Observed survival up to 36 months was reported as Kaplan-Meier estimates and compared with predicted survival as determined for each patient by the National Institutes of Health Registry formula . Kaplan-Meier survival estimates were 96 % at 12 months and 89 % at 24 months . In contrast , predicted survival was 69 % and 57 % , respectively . In addition , at the end of 12 and 24 months , 85 % and 70 % of patients , respectively , remained alive and on bosentan monotherapy . Factors that predicted a worse outcome included World Health Organization Functional Class IV and 6-min walk distance below the median ( 358 m ) at baseline . First-line bosentan therapy was found to improve survival in patients with advanced primary pulmonary hypertension Idiopathic pulmonary arterial hypertension ( IPAH ) is characterised by in situ thrombosis and increased thromboxane ( Tx ) A2 synthesis ; however , there are no studies of antiplatelet therapy in IPAH . The aim of the current study was to determine the biochemical effects of aspirin ( ASA ) and clopidogrel on platelet function and eicosanoid metabolism in patients with IPAH . A r and omised , double-blind , placebo-controlled crossover study of ASA 81 mg once daily and clopidogrel 75 mg once daily was performed . Plasma P-selectin levels and aggregometry were measured after exposure to adenosine diphosphate , arachidonic acid and collagen . Serum levels of TxB2 and urinary metabolites of TxA2 and prostagl and in I2 ( Tx-M and PGI-M , respectively ) were assessed . A total of 19 IPAH patients were enrolled , of whom nine were being treated with continuous intravenous epoprostenol . ASA and clopidogrel significantly reduced platelet aggregation to arachidonic acid and adenosine diphosphate , respectively . ASA significantly decreased serum TxB2 , urinary Tx-M levels and the Tx-M/PGI-M ratio , whereas clopidogrel had no effect on eicosanoid levels . Neither drug significantly lowered plasma P-selectin levels . Epoprostenol use did not affect the results . In conclusion , aspirin and clopidogrel inhibited platelet aggregation , and aspirin reduced thromboxane metabolite production without affecting prostagl and in I2 metabolite synthesis . Further clinical trials of aspirin in patients with idiopathic pulmonary arterial hypertension should be performed BACKGROUND Elevated plasma endothelin-1 ( ET-1 ) levels in patients with chronic heart failure correlate with pulmonary artery pressures and pulmonary vascular resistance . ET(A ) receptors on vascular smooth muscle cells mediate pulmonary vascular contraction and hypertrophy . We determined the acute hemodynamic effects of sitaxsentan , a selective ET(A ) receptor antagonist , in patients with chronic stable heart failure receiving conventional therapy . METHODS AND RESULTS This multicenter , double-blind , placebo-controlled trial enrolled 48 patients with chronic New York Heart Association functional class III or IV heart failure ( mean left ventricular ejection fraction 21+/-1 % ) treated with ACE inhibitors and diuretics . Patients with a baseline pulmonary capillary wedge pressure > /=15 mm Hg and a cardiac index < /=2.5 L. min(-1 ) . m(-2 ) were r and omized to 1 of 3 doses ( 1.5 , 3.0 , or 6.0 mg/kg ) of sitaxsentan or placebo as an intravenous infusion over 15 minutes . Hemodynamic responses were assessed by catheterization of the right side of the heart for 6 hours . Sitaxsentan decreased pulmonary artery systolic pressure , pulmonary vascular resistance , mean pulmonary artery pressure , and right atrial pressure ( P</=0.001 , 0.003 , 0.017 , and 0.031 , respectively ) but had no effect on heart rate , mean arterial pressure , pulmonary capillary wedge pressure , cardiac index , or systemic vascular resistance . Plasma ET-1 levels were elevated at baseline and decreased with sitaxsentan . CONCLUSIONS In patients with moderate to severe heart failure receiving conventional therapy , acute ET(A ) receptor blockade caused selective pulmonary vasodilation associated with a reduction in plasma ET-1 . Sitaxsentan may be of value in the treatment of patients with pulmonary hypertension secondary to chronic heart failure Pulmonary hypertension during exercise is common in severe chronic obstructive pulmonary disease ( COPD ) . It was hypothesised that the use of the endothelin-receptor antagonist bosentan can improve cardiopulmonary haemodynamics during exercise , thus increasing exercise tolerance in patients with severe COPD . In the present double-blind , placebo-controlled study , 30 patients with severe or very severe COPD were r and omly assigned in a 2:1 ratio to receive either bosentan or placebo for 12 weeks . The primary end-point was change in the 6-min walking distance . Secondary end-points included changes in health-related quality of life , lung function , cardiac haemodynamics , maximal oxygen uptake and pulmonary perfusion patterns . Compared with placebo , patients treated with bosentan during 12 weeks showed no significant improvement in exercise capacity as measured by the 6-min walking distance ( mean±sd 331±123 versus 329±94 m ) . There was no change in lung function , pulmonary arterial pressure , maximal oxygen uptake or regional pulmonary perfusion pattern . In contrast , arterial oxygen pressure dropped , the alveolar – arterial gradient increased and quality of life deteriorated significantly in patients assigned bosentan . The oral administration of the endothelin receptor antagonist bosentan not only failed to improve exercise capacity but also deteriorated hypoxaemia and functional status in severe chronic obstructive pulmonary disease patients without severe pulmonary hypertension at rest Addition of inhaled iloprost to bosentan may have beneficial effects in patients with idiopathic pulmonary arterial hypertension ( IPAH ) . A multicentre , open , r and omised , controlled trial was performed to assess the safety and efficacy of inhaled iloprost in patients with IPAH who had already been treated with bosentan . The trial was terminated early after a futility analysis predicted failure with respect to the predetermined sample size . At that time , 40 patients were r and omised to receive either bosentan alone ( control group ) or bosentan plus inhaled iloprost ( combination group ) for a 12-week period . The primary end-point , change in 6-min walking distance , was not met ( mean changes + 1 m and -9 m in the control and combination group , respectively ) . These results may have been skewed by three outliers in the iloprost group who presented with severe clinical worsening . None of the secondary end-points including functional class , peak oxygen uptake , and time to clinical worsening differed significantly between groups . The current study failed to show a positive effect of adding inhaled iloprost to bosentan in idiopathic pulmonary arterial hypertension patients . Further studies involving larger sample sizes and long-term follow-up are needed to determine the efficacy of adding inhaled iloprost to bosentan in patients with idiopathic pulmonary arterial hypertension Treprostinil diethanolamine is an oral prostacyclin analog currently being evaluated for the treatment of pulmonary arterial hypertension ( PAH ) . Treprostinil is metabolized primarily by cytochrome P450 ( CYP ) 2C8 with minor contribution from CYP2C9 . It is expected that oral treprostinil will be administered with bosentan , approved for the treatment of PAH and known to induce CYP2C9 and 3A4 . This study evaluated whether a drug interaction exists between oral treprostinil , bosentan , and its active metabolite Ro 48 - 5033 during co-administration . Twenty-four participants were r and omized in a 3-way crossover study to oral treprostinil 1 mg twice daily , bosentan 125 mg twice daily , and oral treprostinil 1 mg twice daily and bosentan 125 mg twice daily . Treprostinil geometric mean ratios ( GMRs ) ( 90 % confidence interval [ CIs ] ) for steady-state AUC(0 - 12 ) and C(max ) ( combination/treprostinil ) were 0.92 ( 0.83 , 1.03 ) and 0.96 ( 0.83 , 1.11 ) , respectively , whereas bosentan GMRs ( combination/bosentan ) were 1.02 ( 0.95 , 1.10 ) and 1.04 ( 0.94 , 1.15 ) , respectively , and Ro 48 - 5033 GMRs were 0.99 ( 0.93 , 1.06 ) and 1.03 ( 0.94 , 1.13 ) . In conclusion , because the GMR and 90 % CI are within the equivalence interval of 0.8 to 1.25 , co-administration of oral treprostinil and bosentan did not result in a pharmacokinetic interaction for either agent OBJECTIVES The purpose of this study was to investigate the effects of bosentan ( 125 or 250 mg twice daily ) on echocardiographic and Doppler variables in 85 patients with World Health Organization class III or IV pulmonary arterial hypertension ( PAH ) . BACKGROUND Bosentan , an orally active dual endothelin-receptor antagonist , improves symptoms , exercise capacity , and hemodynamics in patients with PAH . METHODS Patients had primary pulmonary hypertension ( 84 % ) or PAH associated with connective tissue disease . Of these , 29 patients received placebo and 56 received bosentan ( 1:2 r and omization ) . Six-minute walk tests and echocardiograms were performed at baseline and after 16 weeks of treatment . RESULTS Baseline characteristics were similar in the placebo and bosentan groups , and echocardiographic and Doppler findings were consistent with marked abnormalities of right ventricular ( RV ) and left ventricular ( LV ) structure and function that were due to PAH . The treatment effect on 6-min walking distance was 37 m in favor of bosentan ( p = 0.036 ) . Treatment effects of bosentan compared with placebo on other parameters were as follows : Doppler-derived cardiac index = + 0.4 l/min/m(2 ) ( p = 0.007 ) , LV early diastolic filling velocity = + 10.5 cm/s ( p = 0.003 ) , LV end-diastolic area = + 4.2 cm(2 ) ( p = 0.003 ) , LV systolic eccentricity index = -0.12 ( p = 0.047 ) , RV end-systolic area = -2.3 cm(2 ) ( p = 0.057 ) , RV : LV diastolic areas ratio = -0.64 ( p = 0.007 ) , Doppler RV index = -0.06 ( p = 0.03 ) , and percentage of patients with an improvement in pericardial effusion score = 17 % ( p = 0.05 ) . CONCLUSIONS Bosentan improves RV systolic function and LV early diastolic filling and leads to a decrease in RV dilation and an increase in LV size in patients with PAH BACKGROUND Bosentan , an oral ET(A)/ET(B ) receptor antagonist , is approved for the treatment of pulmonary arterial hypertension ( PAH ) . However , some patients discontinue bosentan because of hepatotoxicity or inadequate efficacy . Sitaxsentan , an oral , ET(A)-selective endothelin antagonist currently under investigation , may be an alternative treatment option . In this study we evaluate the safety and efficacy of sitaxsentan in patients discontinuing bosentan . METHODS Forty-eight patients with idiopathic PAH or PAH associated with connective-tissue disease or congenital heart disease were r and omized ( double-blind ) to a single daily dose of either 50 mg or 100 mg sitaxsentan . Thirty-five of the 48 patients discontinued bosentan because of inadequate efficacy , as judged by the investigator , and 13 discontinued bosentan for safety concerns . Study end-points included change in 6-minute walk distance ( 6MWD ) , change in World Health Organization ( WHO ) functional class , time to clinical worsening , and change in Borg dyspnea score ( Borg ) from baseline to Week 12 . RESULTS With 100 mg sitaxsentan , 5 of 15 patients ( 33 % ) who discontinued bosentan because inadequate efficacy improved , demonstrating a > 15 % increase in 6MWD , vs 2 of 20 patients ( 10 % ) treated with 50 mg sitaxsentan . Fifteen percent and 20 % of these patients had a > 15 % decrease in 6MWD in the 50- and 100-mg groups , respectively . Similar results were seen for the Borg and WHO functional class . Of the 12 patients discontinuing bosentan because of hepatotoxicity , 1 developed elevated liver enzymes at 13 weeks of sitaxsentan therapy . Overall , sitaxsentan was well tolerated . CONCLUSIONS Sitaxsentan may represent a safe and efficacious alternative endothelin receptor antagonist for patients discontinuing bosentan BACKGROUND Endothelin-1 is a potent vasoconstrictor and smooth-muscle mitogen . In a preliminary study , the orally administered dual endothelin-receptor antagonist bosentan improved exercise capacity and cardiopulmonary hemodynamics in patients with pulmonary arterial hypertension . The present trial investigated the effect of bosentan on exercise capacity in a larger number of patients and compared two doses . METHODS In this double-blind , placebo-controlled study , we r and omly assigned 213 patients with pulmonary arterial hypertension ( primary or associated with connective-tissue disease ) to receive placebo or to receive 62.5 mg of bosentan twice daily for 4 weeks followed by either of two doses of bosentan ( 125 or 250 mg twice daily ) for a minimum of 12 weeks . The primary end point was the degree of change in exercise capacity . Secondary end points included the change in the Borg dyspnea index , the change in the World Health Organization ( WHO ) functional class , and the time to clinical worsening . RESULTS At week 16 , patients treated with bosentan had an improved six-minute walking distance ; the mean difference between the placebo group and the combined bosentan groups was 44 m ( 95 percent confidence interval , 21 to 67 ; P<0.001 ) . Bosentan also improved the Borg dyspnea index and WHO functional class and increased the time to clinical worsening . CONCLUSIONS The endothelin-receptor antagonist bosentan is beneficial in patients with pulmonary arterial hypertension and is well tolerated at a dose of 125 mg twice daily . Endothelin-receptor antagonism with oral bosentan is an effective approach to therapy for pulmonary arterial hypertension PH ( pulmonary hypertension ) often complicates the disease course of patients with COPD ( chronic obstructive pulmonary disease ) and is an indication of a worse prognosis . In the present study , we assessed whether pravastatin administration was effective in improving PH and exercise capacity in COPD patients with PH , and whether the pulmonary protection was mediated by inhibiting ET-1 ( endothelin-1 ) production . In a double-blind parallel design , 53 COPD patients with PH were r and omly assigned to receive either placebo or pravastatin ( 40 mg/day ) over a period of 6 months at a medical centre . Baseline characteristics were similar in both groups . The exercise time remained stable throughout the study in the placebo group . After 6 months , the exercise time significantly increased 52 % from 660+/-352 to 1006+/-316 s ( P<0.0001 ) in pravastatin-treated patients . With pravastatin , echocardiographically derived systolic PAP ( pulmonary artery pressure ) decreased significantly from 47+/-8 to 40+/-6 mmHg . There was significant improvement in the Borg dyspnoea score after administering pravastatin . Despite unchanged plasma ET-1 levels throughout the study , urinary excretion of the peptide was decreased and significantly correlated with an improvement in exercise time in pravastatin-treated patients ( r=-0.47 , P=0.01 ) . In conclusion , pravastatin significantly improved exercise tolerance , and decreased PH and dyspnoea during exercise in COPD patients with PH , probably by inhibiting ET-1 synthesis OBJECTIVES We sought to determine the factors associated with long-term survival in patients with primary pulmonary hypertension ( PPH ) treated with continuous epoprostenol infusion . BACKGROUND Epoprostenol improves survival in patients with PPH in New York Heart Association ( NYHA ) functional class III or IV . However , some patients do not benefit from epoprostenol and must be considered for lung transplantation . The best timing for listing these patients on a lung transplantation program is currently unknown . METHODS Between December 1992 and January 2001 , 178 patients with PPH in NYHA functional class III or IV were treated with epoprostenol . The 6-min walk test ( WT ) and right-sided heart catheterization were performed at baseline , after three months on epoprostenol and thereafter once a year . RESULTS Overall survival rates at one , two , three , and five years were 85 % , 70 % , 63 % , and 55 % , respectively . On univariate analysis , the baseline variables associated with a poor outcome were a history of right-sided heart failure , NYHA functional class IV , 6-min WT < or=250 m ( median value ) , right atrial pressure > or=12 mm Hg , and mean pulmonary artery pressure < 65 mm Hg . On multivariate analysis , including both baseline variables and those measured after three months on epoprostenol , a history of right-sided heart failure , persistence of NYHA functional class III or IV at three months , and the absence of a fall in total pulmonary resistance of > 30 % , relative to baseline , were associated with poor survival . CONCLUSIONS Survival of patients with PPH treated with epoprostenol depends on the severity at baseline , as well as the three-month response to therapy . These findings suggest that lung transplantation should be considered in a subset of patients who remain in NYHA functional class III or IV or in those who can not achieve a significant hemodynamic improvement after three months of epoprostenol therapy , or both Objective The aim of this study was to systematic ally investigate the mutual pharmacokinetic interactions in healthy volunteers between sildenafil , a phosphodiesterase-5 inhibitor , and bosentan , a dual endothelin receptor antagonist , both approved for treating pulmonary arterial hypertension ( PAH ) . Methods A r and omised , double-blind , placebo-controlled , parallel-group study with three treatment arms ( sildenafil plus placebo , bosentan plus placebo and sildenafil plus bosentan ) was conducted in 55 healthy male volunteers ( 51 completers ) . Study duration was 18 days per treatment group . Sildenafil was administered three times daily on Days 1–6 and 11–16 ( 20 mg initially , increased to 80 mg after 3 days ) , and bosentan ( 125 mg ) was administered twice daily on Days 7–17 . Results On Day 16 , bosentan decreased the maximum plasma concentration of sildenafil © max ) by 55.4 % [ 90 % confidence interval ( CI ) 40.3–66.6 % ] and the area under the plasma concentration versus time curve over a dosing interval $ $ { \left ( { { \text{AUC}}_{\tau } } \right ) } $ $ by 62.6 % ( 90 % CI 56.8–67.7 % ) . Sildenafil increased bosentan Cmax by 42.0 % ( 90 % CI 15.4–74.8 % ) and $ $ { \left ( { { \text{AUC}}_{\tau } } \right ) } $ $ by 49.8 % ( 90 % CI 28.7–74.5 % ) . Bosentan and sildenafil in combination were well tolerated , with no serious adverse events reported . All adverse events were of mild or moderate intensity . Conclusions In healthy volunteers , there is a mutual pharmacokinetic interaction between bosentan and sildenafil that may influence the dosage of each drug in a combination treatment . The clinical implication s of combination therapy with bosentan and sildenafil are as yet unknown , and further trials in patients with PAH are needed Doppler‐defined pulmonary hypertension ( PH ) in sickle cell disease ( SCD ) is associated with 40 % mortality at 40 months . To assess the effect of bosentan in SCD‐PH , two r and omized , double‐blind , placebo‐controlled , 16‐week studies were initiated . Safety concerns are particularly relevant in SCD due to comorbid conditions . ASSET‐1 and ‐2 enrolled patients with pulmonary arterial hypertension ( PAH ) and pulmonary venous hypertension ( PH ) , respectively . Haemodynamics and 6‐min walk distance ( 6MWD ) were obtained at baseline and week 16 . The studies were terminated due to slow site initiation and patient enrolment ( n = 26 ) . Bosentan appeared to be well tolerated . Although sample sizes were limited , in ASSET‐1 at baseline , 6MWD correlated with cardiac output ( CO ; P = 0·006 ) with non‐significant inverse correlations between 6MWD and pulmonary vascular resistance ( PVR ; P = 0·07 ) and between 6MWD and right atrial pressure ( P = 0·08 ) . In ASSET‐2 at baseline , there was a non‐significant correlation between 6MWD and CO ( P = 0·06 ) . Due to limited sample sizes , efficacy endpoints were not analysed . However , in both studies , non‐significant increases in CO were observed with bosentan compared to placebo . Similarly , non‐significant decreases in PVR were observed with bosentan . Limited data in SCD‐PH suggest that a low 6MWD predicts a low CO . St and ard‐dose bosentan appears to be well tolerated . Further investigation is warranted . Clinical trials.gov registration numbers NCT00310830 , NCT00313196 , NCT00360087 Objective : Toevaluate the effects of bosentan on echo-derived hemodynamic measurements , and clinical variables in symptomatic heart failure ( HF ) patients . Method : Multi- center , double-blind , r and omized ( 2:1 ) , placebo-controlled study comparing bosentan ( 8–125 mg b.i.d . ) to placebo in patients with New York Heart Association class IIIb – IV HF , left ventricular ejection fraction < 35 % and systolic pulmonary artery pressure ( SPAP ) > 40 mm Hg . Primary and secondary endpoints were change from baseline to 20 weeks in SPAP and cardiac index , respectively . Safety endpoints were treatment emergent adverse events ( AEs ) , change in body weight , hemoglobin , hematocrit , systolic blood pressure and diuretic use . Results : Ninety-four patients enrolled : 60 to bosentan , 34 to placebo . There was no significant difference between the 2 arms in SPAP change ( 0.1 ± 11.5 mm Hg , 95 % confidence limit ( CL ) –5.4 to 5.2 , p = 0.97 ) , cardiac index shift ( 0.12 ± 0.45 , 95 % CL –0.09 to 0.33 , p = 0.24 ) or any of the other 22 echocardigraphic measurements obtained . Therapy- duration was longer in the placebo arm , while more patients in the bosentan arm experienced adverse and serious AEs . Conclusion : In HF patients with left ventricular dysfunction and secondary pulmonary hypertension , bosentan did not provide any measurable hemodynamic benefit , and was associated with more frequent AEs , requiring drug discontinuation Background : Endothelin-1 is considered to be a central pathogenic factor in connective tissue diseases ( CTDs ) such as systemic sclerosis ( SSc ) , leading to vasoconstriction , fibrosis , hypertrophy and inflammation . A frequent complication of CTD is pulmonary arterial hypertension ( PAH ) , which has a major effect on functioning and quality of life , and is associated with a particularly poor prognosis . Objective : To present a subgroup analysis that summarises experiences from the pivotal studies and their open-label extensions with the oral dual endothelin-1 receptor antagonist bosentan in patients with PAH and CTD , mostly SSc and lupus erythematosus . Methods : 66 patients with PAH secondary to CTD , in World Health Organization functional class III or IV , were r and omised to two double-blind , placebo-controlled studies and followed up for 12 and 16 weeks , respectively . The primary end point was change in exercise capacity , assessed using the 6-min walk test . In both studies and their extensions , survival was assessed from start of treatment to death or data cut-off and analysed as Kaplan – Meier estimates . Results : 44 patients with PAH secondary to CTD who were treated with bosentan were stable in 6-min walk distance at the end of the study ( + 19.5 m , 95 % confidence interval ( CI ) −3.2 to 42.2 ) , whereas patients treated with placebo deteriorated ( −2.6 m , 95 % CI −54.0 to 48.7 ) . 64 patients subsequently received bosentan in an open-label long-term extension study . Mean ( st and ard deviation ( SD ) ) exposure to bosentan was 1.6 ( 0.9 ) years , and duration of observation was 1.8 ( 0.8 ) years . 8 ( 16 % ) patients received epoprostenol as add-on treatment and 7 ( 14 % ) after discontinuation of bosentan . Survival in those receiving bosentan was 85.9 % after 1 year and 73.4 % after 2 years . Conclusion : Short-term bosentan treatment in a subgroup of patients with PAH secondary to CTD seems to have a favourable effect compared with placebo . The long-term follow-up of these patients suggests that first-line bosentan , with the subsequent addition of other PAH treatments if required , is safe for long-term treatment and may have a positive effect on outcome RATIONALE Phosphodiesterase type 5 ( PDE5 ) inhibition has been proposed for the treatment for pulmonary arterial hypertension ( PAH ) . OBJECTIVE This study compared adding sildenafil , a PDE5 inhibitor , to conventional treatment with the current practice of adding bosentan , an endothelin receptor antagonist . METHODS Twenty-six patients with PAH , idiopathic or associated with connective tissue disease , World Health Organization ( WHO ) functional class III , were r and omized in a double-blind fashion to receive sildenafil ( 50 mg twice daily for 4 weeks , then 50 mg three times daily ) or bosentan ( 62.5 mg twice daily for 4 weeks , then 125 mg twice daily ) over 16 weeks . MEASUREMENTS Changes in right ventricular ( RV ) mass ( using cardiovascular magnetic resonance ) , 6-minute walk distance , cardiac function , brain natriuretic peptide , and Borg dyspnea index . MAIN RESULTS When analyzed by intention to treat , there were no significant differences between the two treatment groups . One patient on sildenafil died suddenly . Patients on sildenafil who completed the protocol showed significant changes from baseline , namely , reductions in RV mass ( -8.8 g ; 95 % confidence interval [ CI ] , -2 , -16 ; n = 13 , p = 0.015 ) and plasma brain natriuretic peptide levels ( -19.4 fmol x ml(-1 ) ; 95 % CI , -5 , -34 ; p = 0.014 ) and improvements in 6-minute walk distance ( 114 m ; 95 % CI , 67 , 160 ; p = 0.0002 ) , cardiac index ( 0.3 L x min(-1 ) x m(-2 ) ; 95 % CI , 0.1 , 0.4 ; p = 0.008 ) , and systolic left ventricular eccentricity index ( -0.2 ; 95 % CI , -0.02 , -0.37 ; p = 0.031 ) . Bosentan improved 6-minute walk distance ( 59 m ; 95 % CI , 29 , 89 ; n = 12 , p = 0.001 ) and cardiac index ( 0.3 ; 95 % CI , 0.1 , 0.4 ; p = 0.008 ) . CONCLUSIONS Sildenafil added to conventional treatment reduces RV mass and improves cardiac function and exercise capacity in patients with PAH , WHO functional class III . Safety monitoring is important until more experience is obtained Altitude exposure is associated with decreased exercise capacity and increased pulmonary vascular resistance ( PVR ) . Echocardiographic measurements of pulmonary haemodynamics and a cardiopulmonary exercise test were performed in 13 healthy subjects at sea level , in normoxia and during acute hypoxic breathing ( 1 h , 12 % oxygen in nitrogen ) , and in 22 healthy subjects after acclimatisation to an altitude of 5,050 m. The measurements were obtained after r and omisation , double-blinded to the intake of placebo or the endothelin A receptor blocker sitaxsentan ( 100 mg·day−1 for 7 days ) . Blood and urine were sample d for renal function measurements . Normobaric as well as hypobaric hypoxia increased PVR and decreased maximum workload and oxygen uptake ( V′O2,max ) . Sitaxsentan decreased PVR in acute and chronic hypoxia ( both p<0.001 ) , and partly restored V′O2,max , by 30 % in acute hypoxia ( p<0.001 ) and 10 % in chronic hypoxia ( p<0.05 ) . Sitaxsentan-induced changes in PVR and V′O2,max were correlated ( p = 0.01 ) . Hypoxia decreased glomerular filtration rate and free water clearance , and increased fractional sodium excretion . These indices of renal function were unaffected by sitaxsentan intake . Selective endothelin A receptor blockade with sitaxsentan improves mild pulmonary hypertension and restores exercise capacity without adverse effects on renal function in hypoxic normal subjects BACKGROUND Altitude exposure is associated with mild pulmonary hypertension and decreased exercise capacity . We tested the hypothesis that pulmonary vascular resistance ( PVR ) contributes to decreased exercise capacity in hypoxic healthy subjects . METHODS An incremental cycle ergometer cardiopulmonary exercise test and echocardiographic estimation of pulmonary artery pressure ( Ppa ) and cardiac output to calculate total PVR were performed in 11 healthy volunteers in normoxia and after 1 h of hypoxic breathing ( 12 % O(2 ) ) . The measurements were performed in a r and om order at 1-week intervals after the receiving either a placebo or bosentan , following a double-blind r and omized crossover design . Bosentan was administered twice a day for 3 days , 62.5 mg on the first day and 125 mg on the next 2 days . RESULTS Hypoxic breathing decreased the mean ( + /- SE ) pulse oximetric saturation ( Spo(2 ) ) from 99 + /- 1 % to 3 + /- 1 % and increased the mean PVR from 5.6 + /- 0.3 to 7.2 + /- 0.5 mm Hg/L/min/m(2 ) , together with a decrease in mean maximum O(2 ) uptake ( Vo(2)max ) from 47 + /- 2 to 35 + /- 2 mL/kg/min . Bosentan had no effect on normoxic measurements and did not affect hypoxic Spo(2 ) , but decreased PVR to 5.6 + /- 0.3 mm Hg/L/min/m(2 ) ( p < 0.01 ) and increased Vo(2)max to 39 + /- 2 mL/kg/min ( p < 0.01 ) in hypoxia . Bosentan therapy , on average , restored 30 % of the hypoxia-induced decrease in Vo(2)max . Bosentan-induced changes in Ppa and Vo(2)max were correlated ( p = 0.01 ) . CONCLUSIONS We conclude that hypoxic pulmonary hypertension partially limits exercise capacity in healthy subjects , and that bosentan therapy can prevent it BACKGROUND Primary pulmonary hypertension is a progressive , fatal disease of unknown cause . Vasodilator drugs have been used as a treatment , but their efficacy is uncertain . METHODS We treated 64 patients with primary pulmonary hypertension with high doses of calcium-channel blockers . Patients who responded to treatment ( defined as those whose pulmonary-artery pressure and pulmonary vascular resistance immediately fell by more than 20 percent after challenge ) were treated for up to five years . Their survival was compared with that of the patients who did not respond and with patients enrolled in the National Institutes of Health ( NIH ) Registry on Primary Pulmonary Hypertension . Warfarin was given to 55 percent of the patients as concurrent therapy , on the basis of a lung scan showing nonuniformity of pulmonary blood flow ( 47 percent of patients who responded and 57 percent of those who did not respond ) . RESULTS Seventeen patients ( 26 percent ) responded to treatment , as indicated by a 39 percent fall in pulmonary-artery pressure and a 53 percent fall in the pulmonary-vascular-resistance index ( P less than 0.001 ) . Nifedipine ( mean [ + /- SD ] daily dose , 172 + /- 41 mg ) was given to 13 patients , and diltiazem ( mean daily dose , 720 + /- 208 mg ) was given to 4 patients . After five years , 94 percent of the patients who responded ( 16 of 17 ) were alive , as compared with 55 percent of the patients who did not respond ( 26 of 47 , P = 0.003 ) . The survival of the patients who responded was also significantly better than that of the NIH registry cohort ( P = 0.002 ) and patients from the NIH registry who were treated at the University of Illinois ( P = 0.001 ) . The use of warfarin was associated with improved survival ( P = 0.025 ) , particularly in the patients who did not respond . CONCLUSIONS This study suggests that high doses of calcium-channel blockers in patients with primary pulmonary hypertension who respond with reductions in pulmonary-artery pressure and pulmonary vascular resistance may improve survival over a five-year period Pulmonary hypertension is characterized by progressive elevation of pulmonary artery pressure and vascular resistance , often leading to right ventricular failure and death ( 1 - 3 ) . Continuous intravenous infusion of epoprostenol improves prognosis and symptoms in patients with primary ( idiopathic ) pulmonary hypertension ( 4 - 8 ) . R and omized , controlled clinical trials of epoprostenol for secondary pulmonary hypertension have not been conducted . Pulmonary hypertension frequently complicates the scleroderma spectrum of disease , which includes diffuse scleroderma , limited scleroderma ( the CREST syndrome [ calcinosis cutis , the Raynaud phenomenon , esophageal dysfunction , sclerodactyly , and telangectasia ] ) , and the overlap syndrome . These multisystem diseases are characterized by connective tissue and vascular abnormalities ; vascular lesions are prominent in all affected tissues ( 9 ) . Pulmonary hypertension occurs in up to 33 % of patients with diffuse scleroderma and 10 % to 50 % of those with the CREST syndrome ( 10 , 11 ) , in which it is one of the leading causes of death ( 12 , 13 ) . Pulmonary hypertension in the scleroderma spectrum of disease may be associated with interstitial pulmonary fibrosis or may consist of a direct involvement of small and medium-sized pulmonary arteries and arterioles with smooth-muscle hyperplasia , medial hypertrophy , and intimal proliferation ( 10 , 13 , 14 ) . Principal involvement of the pulmonary vasculature is more common in the CREST syndrome , whereas patients with pulmonary hypertension and diffuse scleroderma more often have interstitial lung disease ( 13 ) . No therapies have been proven effective for pulmonary hypertension secondary to the scleroderma spectrum of disease . Small numbers of patients have responded to captopril ( 15 ) , nifedipine ( 16 - 20 ) , and prazosin . In a short-term study of intravenous epoprostenol in seven patients with scleroderma ( two with diffuse scleroderma and five with limited scleroderma ) , six had a decrease in mean pulmonary artery pressure and pulmonary vascular resistance ( 21 ) . In a small study of pulmonary hypertension secondary to connective tissue disease , long-term infusion therapy with a prostacyclin analogue , iloprost , result ed in improvement in New York Heart Association ( NYHA ) functional class and quality of life but a variable hemodynamic response ( 22 ) . Results from a single-center , uncontrolled study suggest that long-term , continuously infused epoprostenol therapy can produce hemodynamic and symptomatic responses in patients with connective tissue disease who have severe pulmonary hypertension that is refractory to conventional medical therapy ( 23 ) . The rationale for using continuous epoprostenol infusion to treat pulmonary hypertension secondary to the scleroderma spectrum of disease was based on the efficacy of this therapy for primary pulmonary hypertension ( 4 - 8 ) and recognition that scleroderma is a disease characterized by vasospasm and structural changes in the walls of blood vessels . Prostacyclin is a naturally occurring substance produced by vascular endothelium that has vasodilating , antiplatelet aggregation , and cytoprotective effects ( 24 - 33 ) . Endogenous production of prostacyclin is decreased in an animal model of neonatal pulmonary hypertension ( 34 ) and in adult humans with pulmonary hypertension ( 35 ) . Continuous infusion of prostacyclin normalizes plasma markers of endothelial cell injury and platelet aggregation in patients with primary pulmonary hypertension ( 36 ) . Endothelial dysfunction also plays an important role in the vascular manifestations of the scleroderma spectrum of disease ( 37 , 38 ) , including the Raynaud phenomenon and digital ischemia , which cause considerable morbidity . Calcium-channel blockers ( 39 - 45 ) , enalapril ( 46 ) , and intermittent intravenous infusions of prostacyclin ( 47 - 49 ) and iloprost ( 50 - 54 ) improve the Raynaud phenomenon in some patients . Mixed results have been obtained with oral prostacyclin analogues ( 55 , 56 ) , and a recent multicenter trial of oral iloprost showed no benefit ( 57 ) . The effect of long-term , continuously infused epoprostenol on the severity of the Raynaud phenomenon and on digital ulcer counts has not been previously evaluated . Our 12-week multicenter , open-label , r and omized study was design ed to determine whether the beneficial effect of epoprostenol seen in patients with primary pulmonary hypertension could be extended to patients with pulmonary hypertension secondary to the scleroderma spectrum of disease . Our objective was to evaluate the effects of continuous infusion of epoprostenol on exercise capacity in patients with pulmonary hypertension secondary to the scleroderma spectrum of disease . A secondary objective was assessment of the effects of long-term continuous epoprostenol infusion on cardiopulmonary hemodynamics , Borg Dyspnea Score , Dyspnea-Fatigue Rating , NYHA functional class , survival , and safety . Vasospastic manifestations , such as the Raynaud phenomenon and digital ulcerations , were also followed . Methods Patient Selection Eligible patients had pulmonary hypertension secondary to the scleroderma spectrum of disease in accordance with the inclusion and exclusion criteria summarized in Table 1 . For the purpose s of this study , the scleroderma spectrum of disease was defined as systemic sclerosis with diffuse or limited scleroderma ( 58 ) ; systemic sclerosis that overlapped with another connective tissue disease ; or the presence of definite features of systemic sclerosis , including the Raynaud phenomenon and positive test result for antinuclear antibody , plus positive test results for anticentromere antibody , anti-Scl 70 antibody , or nailfold capillary abnormalities . Systemic sclerosis with limited cutaneous involvement ( the CREST syndrome ) was defined as the presence of any three of the following conditions : subcutaneous calcinosis , the Raynaud phenomenon , esophageal dysfunction ( defined clinical ly ) , sclerodactyly , or telangectasia . Patients with interstitial lung disease of a more than mild degree were not included in the study because such patients were thought to be less likely to show benefit . Table 1 . Key Inclusion and Exclusion Criteria On the basis of a previous 12-week study of the effects of epoprostenol infusion in patients with severe primary pulmonary hypertension ( 6 ) and using the 6-minute walk test as the primary outcome measure , we calculated that 50 patients per treatment group would provide 80 % power to detect a difference of 50 meters in the average change from baseline , at an level of 0.05 ( two-tailed t-test ) . R and omization and Treatment The protocol was approved by the institutional review boards of the 17 participating centers . After giving informed consent , 111 eligible patients were r and omly assigned ( 1:1 ) to receive continuous epoprostenol infusion ( Flolan , Glaxo Wellcome , Inc. , Research Triangle Park , North Carolina ) plus conventional therapy or to receive conventional therapy alone . Investigators contacted a central r and omization center to obtain treatment assignment , which was based on a stratified r and omized block design . Assignments were stratified on the basis of vasodilator use at baseline ( yes or no ) and exercise capacity at baseline ( 50 to<200 m or 200 m ) and were r and omized within blocks . Fifty-six patients were assigned to receive epoprostenol plus conventional therapy , and 55 patients were assigned to receive conventional therapy alone . Investigators were not blinded to treatment group assignment ; however , independent blinded observers assessed the primary efficacy measure , exercise capacity . Patients taking calcium-channel blockers at study entry continued to take them during the study period . Adjustments in concomitant medications were allowed during the study on the basis of clinical judgment . Patients in both groups were to receive oral anticoagulants during the study ; 94 of the 111 enrolled patients took warfarin . Venous access for epoprostenol infusion ( in the epoprostenol group only ) was obtained by insertion of a permanent indwelling central venous catheter . Epoprostenol was infused continuously by a portable infusion pump ( CADD-1 Model 5100 HF , SIMS Deltec , St. Paul , Minnesota ) . Patients were instructed in sterile technique , catheter care , and drug preparation and administration . Epoprostenol therapy was initiated at a low dose ( usually 2 ng/kg of body weight per minute ) . During the 12-week study , doses were adjusted on the basis of signs or symptoms consistent with persistent pulmonary hypertension in the absence of intolerable adverse effects ( Figure 1 ) . Figure 1 . Epoprostenol dosing . Outcome Measures The primary measure of efficacy was exercise capacity , as defined by the distance a patient could walk in 6 minutes . Trained observers at each site who were not otherwise involved in patient care administered the 6-minute walk test . All patients wore an ambulatory infusion pump and a hospital gown over their clothes to mask the presence or absence of a long-term indwelling catheter , thereby blinding testers to the patients ' treatment groups . Each patient performed one practice walk test . A st and ardized , unencouraged 6-minute walk test was performed as described elsewhere ( 59 ) at baseline and at 1 , 6 , and 12 weeks . The 6-minute walk test has been shown to provide meaningful outcome data in assessing potential therapy for patients with pulmonary hypertension ( 6 ) . Secondary measures of efficacy were cardiopulmonary hemodynamics measured by performing right-heart catheterization using st and ard techniques at baseline and week 12 ; the Borg Dyspnea Score ( 60 ) , obtained immediately after completion of the 6-minute walk test at baseline and 1 , 6 , and 12 weeks ( 6 , 59 ) ; the Dyspnea-Fatigue Rating , obtained before the 6-minute walk test at baseline and weeks 1 , 6 , and 12 ( 61 ) ; NYHA functional class ( 62 ) , measured at baseline and weeks 1 , 6 , and 12 ; digital ulcer counts , done at baseline and weeks 6 and 12 ; and the severity of the Raynaud phenomenon , RATIONALE Small , open-label studies suggest that combinations of existing therapies may be effective for pulmonary arterial hypertension ( PAH ) . OBJECTIVE To evaluate the safety and efficacy of adding inhaled iloprost , a prostacyclin analog , to the endothelin receptor antagonist bosentan in patients with PAH . METHODS In a r and omized , multicenter , double-blind trial , inhaled iloprost ( 5 mug ) or placebo was added to stable monotherapy with bosentan for 12 wk . Efficacy endpoints included change from baseline in 6-min-walk distance ( 6-MWD ) , modified New York Heart Association ( NYHA ) functional class , hemodynamic parameters , and time to clinical worsening . MEASUREMENTS AND MAIN RESULTS A total of 67 patients with PAH ( 55 % idiopathic PAH , 45 % associated PAH , 94 % NYHA class III , and mean baseline 6-MWD of 335 m ) were r and omized . At Week 12 , patients receiving iloprost had a mean increase in 6-MWD of 30 m ( p = 0.001 ) ; placebo patients had a mean 6-MWD increase of 4 m ( p = 0.69 ) , with a placebo-adjusted difference of + 26 m ( p = 0.051 ) . NYHA status improved by one class in 34 % of iloprost versus 6 % of placebo patients ( p = 0.002 ) . Iloprost delayed the time to clinical worsening ( p = 0.0219 ) . Improvements were noted in postinhalation placebo-adjusted change in mean pulmonary artery pressure (-8 mm Hg ; p < 0.001 ) and pulmonary vascular resistance ( -254 dyn x s x cm(-5 ) ; p < 0.001 ) . Combination therapy was well tolerated . CONCLUSIONS Within the limitations of a relatively small sample size , results of this study demonstrate that the addition of inhaled iloprost in patients with PAH with reduced exercise capacity on bosentan monotherapy is safe and efficacious OBJECTIVES In proximal chronic thromboembolic pulmonary hypertension , pulmonary endarterectomy is the treatment of first choice . In general , medical treatment before pulmonary endarterectomy is not indicated . However , selected " high-risk " patients might benefit by optimization of pulmonary hemodynamics . Moreover , in patients whose surgery is delayed owing to limited medical re sources , pretreatment may prevent clinical deterioration . The primary objective of this study was to determine whether the dual endothelin-1 antagonist bosentan improves pulmonary hemodynamics and functional capacity in patients with proximal chronic thromboembolic pulmonary hypertension waiting for pulmonary endarterectomy . METHODS We used an investigator-initiated , r and omized , controlled single-blind study . Patients were r and omized to receive bosentan ( n = 13 ) or no bosentan ( n = 12 ) for 16 weeks , next to " best st and ard of care . " The primary end point was change in total pulmonary resistance . Secondary end points included changes in 6-minute walk distance , mean pulmonary artery pressure , and cardiac index . RESULTS After 16 weeks , the mean differences in change from baseline between the groups were as follows : total pulmonary resistance 299 dynes x s x cm(-5 ) ( P = .004 ) , 6-minute walk distance 33 m ( P = .014 ) , mean pulmonary artery pressure 11 mm Hg ( P = .005 ) , and cardiac index 0.3 L x min(-1 ) x m(-2 ) ( P = .08 ) . Treatment with bosentan was safe . After pulmonary endarterectomy , 4 patients died ( no-bosentan group : n = 3 ) ; the short-term in-hospital postoperative clinical course was similar in both groups of patients . CONCLUSIONS Patients with proximal chronic thromboembolic pulmonary hypertension may benefit hemodynamically and clinical ly from treatment with bosentan before pulmonary endarterectomy . Individual factors predictive of a beneficial response and whether this influences either morbidity or mortality associated with pulmonary endarterectomy remain to be established Sitaxsentan may benefit patients with pulmonary arterial hypertension by blocking the vasoconstrictor effects of endothelin-A while maintaining the vasodilator/clearance functions of endothelin-B receptors . Patients with pulmonary arterial hypertension that was idiopathic , related to connective tissue disease or congenital heart disease , were r and omized to receive placebo ( n = 60 ) , sitaxsentan 100 mg ( n = 55 ) , or sitaxsentan 300 mg ( n = 63 ) orally once daily for 12 weeks . The primary endpoint was change in peak VO(2 ) at Week 12 . Secondary endpoints included 6-minute walk , New York Heart Association class , VO(2 ) at anaerobic threshold , VE per carbon dioxide production at anaerobic threshold , hemodynamics , quality of life , and time to clinical worsening . Although the 300-mg group increased peak VO(2 ) compared with placebo ( + 3.1 % , p < 0.01 ) , none of the other endpoints derived from cardiopulmonary exercise testing were met . However , both the 100-mg dose and the 300-mg dose , compared with placebo , increased 6-minute walk distance ( 100 mg : + 35 m , p < 0.01 ; 300 mg : + 33 m , p < 0.01 ) ; functional class , cardiac index , and pulmonary vascular resistance also improved ( p < 0.02 for each parameter at both doses ) . The incidence of elevated aminotransferase values ( > three times normal ) was 3 % for the placebo group , 0 % for the 100-mg group , and 10 % for the 300-mg group OBJECTIVES The purpose of this study was to examine the efficacy and safety of four doses of ambrisentan , an oral endothelin type A receptor-selective antagonist , in patients with pulmonary arterial hypertension ( PAH ) . BACKGROUND Pulmonary arterial hypertension is a life-threatening and progressive disease with limited treatment options . Endothelin is a vasoconstrictor and smooth muscle cell mitogen that plays a critical role in the pathogenesis and progression of PAH . METHODS In this double-blind , dose-ranging study , 64 patients with idiopathic PAH or PAH associated with collagen vascular disease , anorexigen use , or human immunodeficiency virus infection were r and omized to receive 1 , 2.5 , 5 , or 10 mg of ambrisentan once daily for 12 weeks followed by 12 weeks of open-label ambrisentan . The primary end point was an improvement from baseline in 6-min walk distance ( 6MWD ) ; secondary end points included Borg dyspnea index , World Health Organization ( WHO ) functional class , a subject global assessment , and cardiopulmonary hemodynamics . RESULTS At 12 weeks , ambrisentan increased 6MWD ( + 36.1 m , p < 0.0001 ) with similar and statistically significant increases for each dose group ( range , + 33.9 to + 38.1 m ) . Improvements were also observed in Borg dyspnea index , WHO functional class , subject global assessment , mean pulmonary arterial pressure ( -5.2 mm Hg , p < 0.0001 ) , and cardiac index ( + 0.33 l/min/m2 , p < 0.0008 ) . Adverse events were mild and unrelated to dose , including the incidence of elevated serum aminotransferase concentrations > 3 times the upper limit of normal ( 3.1 % ) . CONCLUSIONS Ambrisentan appears to improve exercise capacity , symptoms , and hemodynamics in patients with PAH . The incidence and severity of liver enzyme abnormalities appear to be low BACKGROUND Treatments for pulmonary arterial hypertension have been mainly studied in patients with advanced disease ( WHO functional class [ FC ] III and IV ) . This study was design ed to assess the effect of the dual endothelin receptor antagonist bosentan in patients with WHO FC II pulmonary arterial hypertension . METHODS Patients with WHO FC II pulmonary arterial hypertension aged 12 years or over with 6-min walk distance of less than 80 % of the normal predicted value or less than 500 m associated with a Borg dyspnoea index of 2 or greater were enrolled in this double-blind , placebo-controlled , multicentre trial . 185 patients were r and omly assigned to receive bosentan ( n=93 ) or placebo ( n=92 ) for the 6-month double-blind treatment period via a central ised integrated voice recognition system . Primary endpoints were pulmonary vascular resistance at month 6 expressed as percentage of baseline and change from baseline to month 6 in 6-min walk distance . Analyses of the primary endpoints were done with all r and omised patients who had a valid baseline assessment and an assessment or an imputed value for month 6 . This trial was registered with Clinical Trials.gov , number NCT00091715 . FINDINGS Analyses were done with 168 patients ( 80 in the bosentan group , 88 in the placebo group ) for pulmonary vascular resistance and with 177 ( 86 and 91 ) for 6-min walking distance . At month 6 , geometric mean pulmonary vascular resistance was 83.2 % ( 95 % CI 73.8 - 93.7 ) of the baseline value in the bosentan group and 107.5 % ( 97.6 - 118.4 ) of the baseline value in the placebo group ( treatment effect -22.6 % , 95 % CI -33.5 to -10.0 ; p<0.0001 ) . Mean 6-min walk distance increased from baseline in the bosentan group ( 11.2 m , 95 % CI -4.6 to 27.0 ) and decreased in the placebo group ( -7.9 m , -24.3 to 8.5 ) , with a mean treatment effect of 19.1 m ( 95 % CI 3.6 - 41.8 ; p=0.0758 ) . 12 ( 13 % ) patients in the bosentan group and eight ( 9 % ) in the placebo group reported serious adverse events , the most common of which were syncope in the bosentan group and right ventricular failure in the placebo group . INTERPRETATION Bosentan treatment could be beneficial for patients with WHO FC II pulmonary arterial hypertension The last two decades have seen major advances in the treatment of chronic heart failure , primarily as a result of therapeutic manipulation of activated neurohormonal systems . Despite this progress , many patients still suffer significant morbidity and premature death . Antagonism of the biological effects of endothelin , a potent vasoconstrictor , represents a further potential target . To date , positive results from animal models of heart failure have not been translated into clinical practice , perhaps as a consequence of the high doses of drug used . The ENABLE ( Endothelin Antagonist Bosentan for Lowering Cardiac Events in Heart Failure ) study evaluated the effects of low dose bosentan , a non-selective endothelin receptor antagonist , in patients with severe heart failure ( left ventricular ejection fraction < 35 % , New York Heart Association class IIIb-IV ) . A total of 1,613 patients were r and omized to receive either bosentan ( 125 mg twice a day ) or placebo . The preliminary results were presented at the 51st Annual Scientific Session of the American College of Cardiology ( 17 - 20 March 2002 , Atlanta , GA , USA ) . The primary endpoint of all-cause mortality or hospitalization for heart failure was reached in 321/808 patients on placebo and 312/805 receiving bosentan . Treatment with bosentan appeared to confer an early risk of worsening heart failure necessitating hospitalization , as a consequence of fluid retention . It has been suggested that further studies using even lower doses of bosentan or more aggressive concomitant diuretic therapy may avoid this adverse effect . The results from the ENABLE study have , however , thrown further doubt on the potential benefits of non-specific endothelin receptor blockade in heart failure Intravenous epoprostenol is currently FDA approved for management of primary pulmonary hypertension , but it requires intravenous infusion and is associated with adverse effects . The objective of this study was to evaluate the effects of an epoprostenol analog , treprostinil , for management of pulmonary hypertension . Ten tertiary care academic institutions with pulmonary hypertension programs participated in these pilot trials . In the first trial , intravenous epoprostenol and intravenous treprostinil were compared . In the second trial , intravenous treprostinil and subcutaneous treprostinil were compared . In the third trial , subcutaneous treprostinil was compared with placebo infusion during an 8-week period . Intravenous epoprostenol and intravenous treprostinil result ed in a similar reduction in pulmonary vascular resistance acutely ( 22 % and 20 % , respectively ) . Intravenous treprostinil and subcutaneous treprostinil also demonstrated comparable short-term decrease in pulmonary vascular resistance ( 23 % and 28 % , respectively ) . The placebo-controlled 8-week trial demonstrated a mean improvement of 37 ± 17 m as measured by the 6-minute walk distance in patients receiving treprostinil compared with a 6 ± 28 m reduction in those receiving placebo . There were trends toward an improvement in cardiac index and pulmonary vascular resistance index in the treprostinil group . Subcutaneous treprostinil has favorable hemodynamic effects when given acutely and in the short term . Treprostinil can be given safely to an ambulatory patient with a novel subcutaneous delivery pump system Tadalafil , an oral phosphodiesterase 5 ( PDE5 ) inhibitor , is being investigated as a treatment for pulmonary arterial hypertension . Bosentan is an oral endothelin receptor antagonist widely used in the treatment of pulmonary arterial hypertension . Tadalafil is mainly metabolized by cytochrome P450 ( CYP ) 3A4 , and as bosentan induces CYP2C9 and CYP3A4 , a pharmacokinetic interaction is possible between these agents . This open-label , r and omized study investigated whether any pharmacokinetic interaction exists between tadalafil and bosentan . Healthy adult men ( n = 15 ; 19 - 52 years of age ) received 10 consecutive days of tadalafil 40 mg once daily , bosentan 125 mg twice daily , and a combination of both in a 3-period , crossover design . Following 10 days of multiple-dose coadministration of bosentan and tadalafil , compared with tadalafil alone , tadalafil geometric mean ratios ( 90 % confidence interval [ CI ] ) for AUCtau and Cmax were 0.59 ( 0.55 , 0.62 ) and 0.73 ( 0.68 , 0.79 ) , respectively , with no observed change in tmax . Following coadministration of bosentan with tadalafil , bosentan ratios ( 90 % CI ) for AUCtau and Cmax were 1.13 ( 1.02 , 1.24 ) and 1.20 ( 1.05 , 1.36 ) , respectively . Tadalafil alone and combined with bosentan was generally well tolerated . In conclusion , after 10 days of coadministration , bosentan decreased tadalafil exposure by 41.5 % with minimal and clinical ly irrelevant differences ( < 20 % ) in bosentan exposure BACKGROUND Endothelin 1 , a powerful endogenous vasoconstrictor and mitogen , might be a cause of pulmonary hypertension . We describe the efficacy and safety of bosentan , a dual endothelin-receptor antagonist that can be taken orally , in patients with severe pulmonary hypertension . METHODS In this double-blind , placebo-controlled study , 32 patients with pulmonary hypertension ( primary or associated with scleroderma ) were r and omly assigned to bosentan ( 62.5 mg taken twice daily for 4 weeks then 125 mg twice daily ) or placebo for a minimum of 12 weeks . The primary endpoint was change in exercise capacity . Secondary endpoints included changes in cardiopulmonary haemodynamics , Borg dyspnoea index , WHO functional class , and withdrawal due to clinical worsening . Analysis was by intention to treat . FINDINGS In patients given bosentan , the distance walked in 6 min improved by 70 m at 12 weeks compared with baseline , whereas it worsened by 6 m in those on placebo ( difference 76 m [ 95 % CI 12 - 139 ] , p=0.021 ) . The improvement was maintained for at least 20 weeks . The cardiac index was 1.0 L min(-1 ) m(-2 ) ( 95 % CI 0.6 - 1.4 , p<0.0001 ) greater in patients given bosentan than in those given placebo . Pulmonary vascular resistance decreased by 223 dyn s cm(-)(5 ) with bosentan , but increased by 191 dyn s cm(-5 ) with placebo ( difference -415 [ -608 to -221 ] , p=0.0002 ) . Patients given bosentan had a reduced Borg dyspnoea index and an improved WHO functional class . All three withdrawals from clinical worsening were in the placebo group ( p=0.033 ) . The number and nature of adverse events did not differ between the two groups . INTERPRETATION Bosentan increases exercise capacity and improves haemodynamics in patients with pulmonary hypertension , suggesting that endothelin has an important role in pulmonary hypertension BACKGROUND Tadalafil 40 mg orally once daily , was shown to be well-tolerated and efficacious for pulmonary arterial hypertension in a 16-week , double-blind , placebo (PBO)-controlled trial . Inclusion criteria included the option for background bosentan . Analyses of tadalafil in treatment-naive patients and as add-on to bosentan were pre-specified . Objectives were to provide safety and efficacy data for both groups . METHODS Groups analyzed included : treatment-naive + PBO ; treatment-naive + tadalafil ; background bosentan + PBO ; and background bosentan + tadalafil . Patients r and omized to tadalafil or PBO ( N = 405 ) were analyzed by bosentan use ( yes = 216 , no = 189 ) . Treatment differences in 6-minute walk distance ( 6MWD , PBO-adjusted ) , functional class ( FC ) , clinical worsening ( CW ) and adverse events were assessed . Hazard ratios ( HRs ) with 95 % confidence intervals ( CIs ) are presented for FC and CW . RESULTS At Week 16 , PBO-adjusted 6MWD increases were 44 m ( CI : 20 to 69 m ; n = 37 ) for tadalafil 40 mg in treatment-naive patients and 23 m ( CI : -2 to 48 m ; n = 42 ) for tadalafil 40 mg add-on to bosentan . The 6MWD for treatment-naive and background bosentan PBO patients decreased by 3 m and increased by 19 m , respectively , at Week 16 compared with baseline . Two ( 5 % ) treatment-naive patients had CW with tadalafil 40 mg vs 8 ( 22 % ) with PBO ( HR = 3.3 , CI : 1.1 to 10.0 ) . Two ( 5 % ) background bosentan patients had CW with tadalafil 40 mg add-on vs 5 ( 11 % ) for PBO add-on ( HR = 1.9 , CI : 0.4 to 10.2 ) . Adverse events for tadalafil monotherapy and as add-on were similar . CONCLUSION Tadalafil 40 mg was well-tolerated and provided clinical benefit in patients as monotherapy . It was also well-tolerated when added to background bosentan , but data are insufficient to conclude additional benefit OBJECTIVES Our goal was to investigate the effect of treatment with the oral dual endothelin receptor antagonist bosentan on the hemodynamics and exercise capacity of patients with chronic thromboembolic pulmonary hypertension ( CTEPH ) . BACKGROUND CTEPH is characterized by vascular obstruction and remodeling , leading to increased pulmonary vascular resistance ( PVR ) . Although pulmonary endarterectomy ( PEA ) is potentially curative , medical therapy is needed in patients with inoperable disease or persistent/recurrent pulmonary hypertension after PEA . METHODS The BENEFiT ( Bosentan Effects in iNopErable Forms of chronIc Thromboembolic pulmonary hypertension ) study was a double-blind , r and omized , placebo-controlled study in CTEPH including patients with either inoperable CTEPH or persistent/recurrent pulmonary hypertension after PEA ( > 6 months after PEA ) . Independent co primary end points were change in PVR as a percentage of baseline and change from baseline in 6-min walk distance after 16 weeks of treatment with bosentan or placebo . Secondary end points included change from baseline in World Health Organization functional class and other hemodynamic parameters . RESULTS One hundred fifty-seven patients were enrolled and r and omized : 80 to placebo , 77 to bosentan . A statistically significant treatment effect ( TE ) of bosentan over placebo on PVR was demonstrated : -24.1 % of baseline ( 95 % confidence interval [ CI ] : -31.5 % to -16.0 % ; p < 0.0001 ) . Total pulmonary resistance ( TE : -193 dynxsxcm(-5 ) ; 95 % CI : -283 to -104 dyn.s.cm(-5 ) ; p < 0.0001 ) and cardiac index ( TE : 0.3 lxmin(-1)xm(-2 ) ; 95 % CI : 0.14 to 0.46 lxmin(-1)xm(-2 ) ; p = 0.0007 ) improved . Mean TE on 6-min walk distance was + 2.2 m ( 95 % CI : -22.5 to 26.8 m ; p = 0.5449 ) . Bosentan treatment was well tolerated . CONCLUSIONS This study demonstrated a positive TE of bosentan on hemodynamics in this patient population . No improvement was observed in exercise capacity . Further trials are needed to define the role of medical therapy in patients with CTEPH ( Bosentan Effects in Inoperable Forms of Chronic Thromboembolic Pulmonary Hypertension ; NCT00313222 ) OBJECTIVES This study evaluated the safety and efficacy of ambrisentan for a period of 2 years in patients with pulmonary arterial hypertension ( PAH ) . BACKGROUND Ambrisentan is an oral , once-daily endothelin receptor antagonist that is selective for the endothelin type A receptor . The ARIES-1 ( Ambrisentan in Pulmonary Arterial Hypertension , R and omized , Double-Blind , Placebo-Controlled , Multicenter , Efficacy Studies ) and ARIES-2 trials were the pivotal 12-week , placebo-controlled studies that led to the regulatory approval of ambrisentan ( 5 and 10 mg ) for the treatment of PAH . METHODS In the ARIES-1 and -2 studies , and the subsequent long-term extension protocol , the ARIES-E study , 383 patients received ambrisentan ( 2.5 , 5 , or 10 mg ) . Efficacy and safety assessment s are presented from the time of the first dose of ambrisentan for all patients with post-baseline data . RESULTS After 2 years of ambrisentan exposure , the mean change from baseline in 6-min walk distance was improved for the 5-mg ( + 23 m ; 95 % confidence interval : 9 to 38 m ) and 10-mg ( + 28 m ; 95 % confidence interval : 11 to 45 m ) groups . Estimates of survival and freedom from clinical worsening for the combined dose group were 94 % and 83 % , respectively , at 1 year and 88 % and 72 % , respectively , at 2 years . The annualized risk of aminotransferase abnormalities > 3x the upper limit of normal was approximately 2 % per year ; most of these events were mild and did not lead to discontinuation of drug . CONCLUSIONS Two years of ambrisentan treatment was associated with sustained improvements in exercise capacity and a low risk of clinical worsening and death in patients with PAH . Ambrisentan was generally well tolerated and had a low risk of aminotransferase abnormalities over the 2-year study period . ( A Long Term Study of Ambrisentan in Pulmonary Arterial Hypertension Subjects Having Completed AMB-320 or AMB-321 ; NCT00578786 ) OBJECTIVES This study assessed the efficacy and safety of inhaled treprostinil in pulmonary arterial hypertension ( PAH ) patients receiving therapy with either bosentan or sildenafil . BACKGROUND There is no cure for PAH , despite effective treatments , and outcomes remain suboptimal . The addition of inhaled treprostinil , a long-acting prostacyclin analog , might be a safe and effective treatment addition to other PAH-specific oral therapies . METHODS Two hundred thirty-five PAH patients with New York Heart Association ( NYHA ) functional class III ( 98 % ) or IV symptoms and a 6-min walk distance ( 6MWD ) of 200 to 450 m while treated with bosentan ( 70 % ) or sildenafil were r and omized to inhaled treprostinil ( up to 54 mug ) or inhaled placebo 4 times daily . The primary end point was peak 6MWD at 12 weeks . Secondary end points included time to clinical worsening , Borg Dyspnea Score , NYHA functional class , 12-week trough 6MWD , 6-week peak 6MWD , quality of life , and PAH signs and symptoms . The biomarker N-terminal pro-brain natriuretic peptide ( NT-proBNP ) was assessed . RESULTS Twenty-three patients withdrew from the study prematurely ( 13 treprostinil , 10 placebo ) . The Hodges-Lehmann between-treatment median difference in change from baseline in peak 6MWD was 19 m at week 6 ( p = 0.0001 ) and 20 m at week 12 ( p = 0.0004 ) . Hodges-Lehmann between-treatment median difference in change from baseline in trough 6MWD at week 12 was 14 m ( p = 0.0066 ) . Quality of life measures and NT-proBNP improved on active therapy . There were no improvements in other secondary end points , including time to clinical worsening , Borg Dyspnea Score , NYHA functional class , and PAH signs and symptoms . Inhaled treprostinil was safe and well-tolerated . CONCLUSIONS This trial demonstrates that , among PAH patients who remain symptomatic on bosentan or sildenafil , inhaled treprostinil improves exercise capacity and quality of life and is safe and well-tolerated . ( TRIUMPH I : Double Blind Placebo Controlled Clinical Investigation Into the Efficacy and Tolerability of Inhaled Treprostinil Sodium in Patients With Severe Pulmonary Arterial Hypertension ; NCT00147199 ) Hypoxic pulmonary vasoconstriction in response to high altitude ascent may contribute to decreased exercise capacity . Endothelin receptor antagonists reduce pulmonary artery pressure and improve exercise capacity in patients with pulmonary arterial hypertension , but their effects on exercise capacity at altitude are unknown . We studied the efficacy of bosentan started 5 days prior to ascent on exercise capacity and pulmonary artery systolic pressure ( PASP ) at 3800 m altitude . Eight healthy subjects completed a double-blinded , r and omized , placebo-controlled , crossover study . The end-points were time to complete a cycle ergometer time trial , PASP , and hemoglobin oxygen saturation ( SpO2 ) . The time to complete the time trial at altitude in subjects on placebo and bosentan was 527+/-159 and 525+/-156 s respectively ( P=0.90 ) . PASP was not different on bosentan compared with placebo . Mean SpO2 during the altitude time trial was lower in subjects taking bosentan compared to placebo ( 78+/-6 vs. 85+/-8 % respectively , P=0.03 ) . Bosentan initiated 5 days prior to ascent to high altitude did not improve exercise capacity or reduce PASP , and worsened SpO2 during high intensity exercise at altitude |
12,318 | 22,472,280 | In a systematic review to estimate the optimal dietary fat to carbohydrate ratio , it was found that obese subjects with hyperinsulinemia ( or insulin resistance ) lost more weight on a mild low-carbohydrate ( LC ) ( or low-glycemic load diet ; 40 % carbohydrate , 30 - 35 % fat ) than on a low-fat ( LF ) diet ( 55 - 60 % carbohydrate , 20 % fat ) , whereas those without hyperinsulinemia showed the opposite .
In non-obese primarily insulin-sensitive subjects , decreasing fat rather than carbohydrate intake is generally more effective to prevent obesity .
Physiological and molecular evidence supports this conclusion .
Increased carbohydrate intake , especially in high-glycemic food , leads to postpr and ial hyperglycemia and hyperinsulinemia , which are exaggerated in obese insulin-resistant subjects .
Even in an insulin-resistant state , insulin is able to stimulate fatty acid synthesis in liver , activate lipoprotein lipase , and prevent lipolysis in adipose tissues , which all facilitate adipose tissue enlargement . | The prevention of obesity , which leads to diabetes and other diseases , is a major concern for public health .
There might be an optimal dietary fat to carbohydrate ratio for prevention and treatment of obesity .
According to the Japanese Dietary Reference Intakes ( RDA ) for 2010 , the optimal fat intake is 20 - 30 % of energy for ages 1 - 29 y and 20 - 25 % for ages 30 y and over .
Upper boundary values of this recommendation were the median of the percentage of energy from dietary fat in Japanese . | Background Low-fat ( LF ) and high-fat ( HF ) weight loss diets improve brachial artery flow-mediated dilation ( FMD ) in obese individuals , although results are conflicting . Moreover , the role that adipose tissue plays in mediating these diet-related effects are unknown . Objective This study examined how modulations in FMD by HF and LF diets relate to changes in adipocyte parameters . Design Obese subjects ( n = 17 ) were r and omized to a HF diet ( 60 % kcal as fat ) or a LF diet ( 25 % kcal as fat ) for 6 weeks . Both groups were restricted by 25 % of energy needs . Results Body weight decreased ( P < 0.05 ) in both groups ( HF : -6.6 ± 0.5 kg , LF : -4.7 ± 0.6 kg ) . Fat mass and waist circumference were reduced ( P < 0.05 ) in the LF group only ( -4.4 ± 0.3 kg ; -3.6 ± 0.8 cm , respectively ) . FMD improved ( P < 0.05 ) in the LF group ( 7.4 ± 0.8 % to 9.8 ± 0.8 ; 32 % increase ) and was impaired in the HF group ( 8.5 ± 0.6 % to 6.9 ± 0.7 ; 19 % reduction ) . Increases in plasma adiponectin ( P < 0.05 , 16 ± 5 % ) , and decreases in resistin ( P < 0.05 , -26 ± 11 % ) , were shown by the LF diet only . Greater decreases in leptin were observed with LF ( -48 ± 9 % ) versus HF ( -28 ± 12 % ) ( P < 0.05 , diet × time ) . Increased FMD by the LF diet was associated with increased adiponectin , and decreased fat mass , waist circumference , leptin , and resistin . Conclusion Beneficial modulations in vascular health by LF diets may be mediated by improvements in adipocyte parameters CONTEXT Obesity in the United States has increased dramatically during the past several decades . There is debate about optimum calorie balance for prevention of weight gain , and proponents of some low-carbohydrate diet regimens have suggested that the increasing obesity may be attributed , in part , to low-fat , high-carbohydrate diets . OBJECTIVES To report data on body weight in a long-term , low-fat diet trial for which the primary end points were breast and colorectal cancer and to examine the relationships between weight changes and changes in dietary components . DESIGN , SETTING , AND PARTICIPANTS R and omized intervention trial of 48,835 postmenopausal women in the United States who were of diverse background s and ethnicities and participated in the Women 's Health Initiative Dietary Modification Trial ; 40 % ( 19,541 ) were r and omized to the intervention and 60 % ( 29,294 ) to a control group . Study enrollment was between 1993 and 1998 , and this analysis includes a mean follow-up of 7.5 years ( through August 31 , 2004 ) . INTERVENTIONS The intervention included group and individual sessions to promote a decrease in fat intake and increases in vegetable , fruit , and grain consumption and did not include weight loss or caloric restriction goals . The control group received diet-related education material s. MAIN OUTCOME MEASURE Change in body weight from baseline to follow-up . RESULTS Women in the intervention group lost weight in the first year ( mean of 2.2 kg , P<.001 ) and maintained lower weight than control women during an average 7.5 years of follow-up ( difference , 1.9 kg , P<.001 at 1 year and 0.4 kg , P = .01 at 7.5 years ) . No tendency toward weight gain was observed in intervention group women overall or when stratified by age , ethnicity , or body mass index . Weight loss was greatest among women in either group who decreased their percentage of energy from fat . A similar but lesser trend was observed with increases in vegetable and fruit servings , and a nonsignificant trend toward weight loss occurred with increasing intake of fiber . CONCLUSION A low-fat eating pattern does not result in weight gain in postmenopausal women . Clinical Trial Registration Clinical Trials.gov , NCT00000611 Dietary glycemic load , the mathematical product of the glycemic index ( GI ) of a food and its carbohydrate content , has been proposed as an indicator of the glucose response and insulin dem and induced by a serving of food . To vali date this concept in vivo , we tested the hypotheses that 1 ) . portions of different foods with the same glycemic load produce similar glycemic responses ; and 2 ) . stepwise increases in glycemic load for a range of foods produce proportional increases in glycemia and insulinemia . In the first study , 10 healthy subjects consumed 10 different foods in r and om order in amounts calculated to have the same glycemic load as one slice of white bread . Capillary blood sample s were taken at regular intervals over the next 2 h. The glycemic response as determined by area under the curve was not different from that of white bread for nine foods . However , lentils produced lower than predicted responses ( P < 0.05 ) . In the second study , another group of subjects was tested to determine the effects of increasing glycemic load using a balanced 5 x 5 Greco-Latin square design balanced for four variables : subject , dose , food and order . Two sets of five foods were consumed at five different glycemic loads ( doses ) equivalent to one , two , three , four and six slices of bread . Stepwise increases in glycemic load produced significant and predictable increases in both glycemia ( P < 0.001 ) and insulinemia ( P < 0.001 ) . These findings support the concept of dietary glycemic load as a measure of overall glycemic response and insulin dem and BACKGROUND The role of glycemic index ( GI ) in appetite and body-weight regulation is still not clear . OBJECTIVE The objective of the study was to investigate the long-term effects of a low-fat , high-carbohydrate diet with either low glycemic index ( LGI ) or high glycemic index ( HGI ) on ad libitum energy intake , body weight , and composition , as well as on risk factors for type 2 diabetes and ischemic heart disease in overweight healthy subjects . DESIGN The study was a 10-wk parallel , r and omized , intervention trial with 2 matched groups . The LGI or HGI test foods , given as replacements for the subjects ' usual carbohydrate-rich foods , were equal in total energy , energy density , dietary fiber , and macronutrient composition . Subjects were 45 ( LGI diet : n = 23 ; HGI diet : n = 22 ) healthy overweight [ body mass index ( in kg/m(2 ) ) : 27.6 + /- 0.2 ] women aged 20 - 40 y. RESULTS Energy intake , mean ( + /- SEM ) body weight ( LGI diet : -1.9 + /- 0.5 kg ; HGI diet : -1.3 + /- 0.3 kg ) , and fat mass ( LGI diet : -1.0 + /- 0.4 kg ; HGI diet : -0.4 + /- 0.3 kg ) decreased over time , but the differences between groups were not significant . No significant differences were observed between groups in fasting serum insulin , homeostasis model assessment for relative insulin resistance , homeostasis model assessment for beta cell function , triacylglycerol , nonesterified fatty acids , or HDL cholesterol . However , a 10 % decrease in LDL cholesterol ( P < 0.05 ) and a tendency to a larger decrease in total cholesterol ( P = 0.06 ) were observed with consumption of the LGI diet as compared with the HGI diet . CONCLUSIONS This study does not support the contention that low-fat LGI diets are more beneficial than HGI diets with regard to appetite or body-weight regulation as evaluated over 10 wk . However , it confirms previous findings of a beneficial effect of LGI diets on risk factors for ischemic heart disease The National Weight Control Registry ( NWCR ) is , to the best of our knowledge , the largest study of individuals successful at long-term maintenance of weight loss . Despite extensive histories of overweight , the 629 women and 155 men in the registry lost an average of 30 kg and maintained a required minimum weight loss of 13.6 kg for 5 y. A little over one-half of the sample lost weight through formal programs ; the remainder lost weight on their own . Both groups reported having used both diet and exercise to lose weight and nearly 77 % of the sample reported that a triggering event had preceded their successful weight loss . Mean ( + /-SD ) current consumption reported by registry members was 5778 + /- 2200 kJ/d , with 24 + /- 9 % of energy from fat , Members also appear to be highly active : they reported expending approximately 11830 kJ/wk through physical activity . Surprisingly , 42 % of the sample reported that maintaining their weight loss was less difficult than losing weight . Nearly all registry members indicated that weight loss led to improvements in their level of energy , physical mobility , general mood , self-confidence , and physical health . In summary , the NWCR identified a large sample of individuals who were highly successful at maintaining weight loss . Future prospect i ve studies will determine variables that predict continued maintenance of weight loss BACKGROUND The optimal nutritional approach for the prevention of cardiovascular disease among obese persons remains a topic of intense controversy . Available approaches range from conventional low-fat to very-low-carbohydrate diets . OBJECTIVE The aim of this pilot study was to evaluate the efficacy of an ad libitum low-glycemic load diet , without strict limitation on carbohydrate intake , as an alternative to a conventional low-fat diet . DESIGN A r and omized controlled trial compared 2 dietary treatments in obese young adults ( n = 23 ) over 12 mo . The experimental treatment emphasized ad libitum consumption of low-glycemic-index foods , with 45 - 50 % of energy from carbohydrates and 30 - 35 % from fat . The conventional treatment was restricted in energy ( 250 - 500 kcal/d deficit ) and fat ( < 30 % of energy ) , with 55 - 60 % of energy from carbohydrate . We compared changes in study outcomes by repeated- measures analysis of log-transformed data and expressed the results as mean percentage change . RESULTS Body weight decreased significantly over a 6-mo intensive intervention in both the experimental and conventional diet groups ( -8.4 % and -7.8 % , respectively ) and remained below baseline at 12 mo ( -7.8 % and -6.1 % , respectively ) . The experimental diet group showed a significantly greater mean decline in plasma triacylglycerols than did the conventional diet group ( -37.2 % and -19.1 % , respectively ; P = 0.005 ) . Mean plasminogen activator inhibitor 1 concentrations decreased ( -39.0 % ) in the experimental diet group but increased ( 33.1 % ) in the conventional diet group ( P = 0.004 ) . Changes in cholesterol concentrations , blood pressure , and insulin sensitivity did not differ significantly between the groups . CONCLUSION An ad libitum low-glycemic load diet may be more efficacious than a conventional , energy-restricted , low-fat diet in reducing cardiovascular disease risk The effects of macronutrient composition on fasting and postpr and ial activities of adipose tissue lipoprotein lipase ( ATLPL ) and skeletal muscle LPL ( SMLPL ) and on insulin sensitivity ( S(I ) ) were studied in 25 normal-weight subjects . Each subject was fed a high-carbohydrate ( HC ) diet for 16 d and a high-fat ( HF ) diet for 16 d , in r and omized order . On day 15 of each diet , biopsies for ATLPL and SMLPL were done in the fasted state and 6 h postpr and ially . On day 16 of each diet , a euglycemic clamp was used to measure S(I ) . There was no effect of diet composition on fasting ATLPL or SMLPL . With both diets and in both tissues , LPL increased significantly from fasting to 6 h postpr and ially . In adipose tissue only there was a significant difference between the 2 diets in LPL meal response ( HC > HF , P = 0.024 ) . There was no effect of diet composition on S(I ) . After the HC diet only , there were significant correlations between fasting SMLPL and S(I ) , but not ATLPL . After the HF diet , associations between insulin action and LPL were evident only in the postpr and ial state . In summary , 16 d of HC compared with HF feeding in normal-weight subjects increased the responsiveness of ATLPL to an HC compared with an HF meal . However , the same diets had no effect on fasting ATLPL or SMLPL , the responsiveness of SMLPL to a meal , or S(I ) . These data suggest that in normal-weight subjects habitual dietary carbohydrate intake may have a stronger effect on subcutaneous fat storage than does dietary fat intake OBJECTIVE To determine whether macronutrient composition of a hypocaloric diet can enhance its effectiveness and whether insulin sensitivity ( Si ) affects the response to hypocaloric diets . RESEARCH METHODS AND PROCEDURES Obese nondiabetic insulin-sensitive ( fasting insulin < 10 microU/mL ; n = 12 ) and obese nondiabetic insulin-resistant ( fasting insulin > 15 microU/mL ; n = 9 ) women ( 23 to 53 years old ) were r and omized to either a high carbohydrate ( CHO ) (HC)/low fat ( LF ) ( 60 % CHO , 20 % fat ) or low CHO (LC)/high fat ( HF ) ( 40 % CHO , 40 % fat ) hypocaloric diet . Primary outcome measures after a 16-week dietary intervention were : changes in body weight ( BW ) , Si , resting metabolic rate , and fasting lipids . RESULTS Insulin-sensitive women on the HC/LF diet lost 13.5 + /- 1.2 % ( p < 0.001 ) of their initial BW , whereas those on the LC/HF diet lost 6.8 + /- 1.2 % ( p < 0.001 ; p < 0.002 between the groups ) . In contrast , among the insulin-resistant women , those on the LC/HF diet lost 13.4 + /- 1.3 % ( p < 0.001 ) of their initial BW as compared with 8.5 + /- 1.4 % ( p < 0.001 ) lost by those on the HC/LF diet ( p < 0.04 between two groups ) . These differences could not be explained by changes in resting metabolic rate , activity , or intake . Overall , changes in Si were associated with the degree of weight loss ( r = -0.57 , p < 0.05 ) . DISCUSSION The state of Si determines the effectiveness of macronutrient composition of hypocaloric diets in obese women . For maximal benefit , the macronutrient composition of a hypocaloric diet may need to be adjusted to correspond to the state of Si OBJECTIVE Low-fat hypocaloric diets reduce insulin resistance and prevent type 2 diabetes in those at risk . Low-carbohydrate , high-fat diets are advocated as an alternative , but reciprocal increases in dietary fat may have detrimental effects on insulin resistance and offset the benefits of weight reduction . RESEARCH DESIGN AND METHODS We investigated a low-fat ( 20 % fat , 60 % carbohydrate ) versus a low-carbohydrate ( 60 % fat , 20 % carbohydrate ) weight reduction diet in 24 overweight/obese subjects ( [ mean ± SD ] BMI 33.6 ± 3.7 kg/m2 , aged 39 ± 10 years ) in an 8-week r and omized controlled trial . All food was weighed and distributed , and intake was calculated to produce a 500 kcal/day energy deficit . Insulin action was assessed by the euglycemic clamp and insulin secretion by meal tolerance test . Body composition , adipokine levels , and vascular compliance by pulse-wave analysis were also measured . RESULTS Significant weight loss occurred in both groups ( P < 0.01 ) , with no difference between groups ( P = 0.40 ) . Peripheral glucose uptake increased , but there was no difference between groups ( P = 0.28 ) , and suppression of endogenous glucose production was also similar between groups . Meal tolerance – related insulin secretion decreased with weight loss with no difference between groups ( P = 0.71 ) . The change in overall systemic arterial stiffness was , however , significantly different between diets ( P = 0.04 ) ; this reflected a significant decrease in augmentation index following the low-fat diet , compared with a nonsignificant increase within the low-carbohydrate group . CONCLUSIONS This study demonstrates comparable effects on insulin resistance of low-fat and low-carbohydrate diets independent of macronutrient content . The difference in augmentation index may imply a negative effect of low-carbohydrate diets on vascular risk CONTEXT The results of clinical trials involving diet in the treatment of obesity have been inconsistent , possibly due to inherent physiological differences among study participants . OBJECTIVE To determine whether insulin secretion affects weight loss with 2 popular diets . DESIGN , SETTING , AND PARTICIPANTS R and omized trial of obese young adults ( aged 18 - 35 years ; n = 73 ) conducted from September 2004 to December 2006 in Boston , Mass , and consisting of a 6-month intensive intervention period and a 12-month follow-up period . Serum insulin concentration at 30 minutes after a 75-g dose of oral glucose was determined at baseline as a measure of insulin secretion . Outcomes were assessed at 6 , 12 , and 18 months . Missing data were imputed conservatively . INTERVENTIONS A low-glycemic load ( 40 % carbohydrate and 35 % fat ) vs low-fat ( 55 % carbohydrate and 20 % fat ) diet . MAIN OUTCOME MEASURES Body weight , body fat percentage determined by dual-energy x-ray absorptiometry , and cardiovascular disease risk factors . RESULTS Change in body weight and body fat percentage did not differ between the diet groups overall . However , insulin concentration at 30 minutes after a dose of oral glucose was an effect modifier ( group x time x insulin concentration at 30 minutes : P = .02 for body weight and P = .01 for body fat percentage ) . For those with insulin concentration at 30 minutes above the median ( 57.5 microIU/mL ; n = 28 ) , the low-glycemic load diet produced a greater decrease in weight ( -5.8 vs -1.2 kg ; P = .004 ) and body fat percentage ( -2.6 % vs -0.9 % ; P = .03 ) than the low-fat diet at 18 months . There were no significant differences in these end points between diet groups for those with insulin concentration at 30 minutes below the median level ( n = 28 ) . Insulin concentration at 30 minutes after a dose of oral glucose was not a significant effect modifier for cardiovascular disease risk factors . In the full cohort , plasma high-density lipoprotein cholesterol and triglyceride concentrations improved more on the low-glycemic load diet , whereas low-density lipoprotein cholesterol concentration improved more on the low-fat diet . CONCLUSIONS Variability in dietary weight loss trials may be partially attributable to differences in hormonal response . Reducing glycemic load may be especially important to achieve weight loss among individuals with high insulin secretion . Regardless of insulin secretion , a low-glycemic load diet has beneficial effects on high-density lipoprotein cholesterol and triglyceride concentrations but not on low-density lipoprotein cholesterol concentration . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00130299 Context Low-carbohydrate weight reduction diets are popular despite a dearth of data on long-term efficacy and adverse effects . Contribution Community-dwelling hyperlipidemic persons were r and omly assigned to either a low-carbohydrate , ketogenic diet or a low-fat , low-cholesterol , reduced-calorie diet for 24 weeks . Compared to the low-fat group , patients in the low-carbohydrate group lost more weight , had a greater decrease in triglyceride levels , and had higher high-density lipoprotein cholesterol levels . Levels of low-density lipoprotein cholesterol remained stable in both groups . Side effects were more common in the low-cholesterol group but were generally mild . Caution s While the study suggests the efficacy and relative safety of the low-cholesterol diet , the high dropout rate , self-directed adherence to the diet , and relatively short observation period challenge the generalizability of the findings . The Editors As the prevalence of obesity has increased over the past 20 years ( 1 ) , the difficulties faced by overweight patients and their health care practitioners have become apparent . Fewer than 25 % of Americans who attempt to lose weight actually reduce caloric intake and increase exercise as currently recommended ( 2 ) . Persons who successfully lose weight have difficulty maintaining their weight loss ( 3 ) . Therefore , it is not surprising that consumers spend $ 33 billion yearly on weight loss products and services in search of effective therapies ( 2 ) . Because many weight loss interventions are unproven and untested , practitioners often lack information with which to recommend a certain therapy or to monitor a patient once a therapy is chosen . One approach to weight loss that has gained recognition in the face of modest supportive scientific evidence is the low-carbohydrate diet . A popular version of this diet recommends extreme restriction of carbohydrate intake to less than 20 g/d initially ( 4 ) . This level of carbohydrate restriction can induce serum and urinary ketones and weight loss ( 5 , 6 ) . However , until recently , available data on low-carbohydrate diets came from small studies of short duration , most of which were uncontrolled ( 5 , 7 - 10 ) . We examined body weight , body composition , serum lipid levels , and adverse effects over 24 weeks in hyperlipidemic persons who were r and omly assigned to follow a low-carbohydrate , ketogenic diet or a low-fat , low-cholesterol , reduced-calorie diet commonly used to induce weight loss and decrease serum lipid levels . Methods Participants Generally healthy persons were recruited from the community . Inclusion criteria were age 18 to 65 years , body mass index of 30 to 60 kg/m2 , desire to lose weight , elevated lipid levels ( total cholesterol level > 5.17 mmol/L [ > 200 mg/dL ] , low-density lipoprotein [ LDL ] cholesterol level > 3.36 mmol/L [ > 130 mg/dL ] , or triglyceride level > 2.26 mmol/L [ 200 mg/dL ] ) , and no serious medical condition . Exclusion criteria were use of any prescription medication in the previous 2 months ( except for oral contraceptives , estrogen therapy , and stable thyroid medication ) , pregnancy or breastfeeding , use of any weight loss diet or diet pills in the previous 6 months , and baseline ketonuria . All participants provided written informed consent , and the institutional review board of Duke University Health System approved the study . Participants received no monetary incentive . Interventions By using a computer-generated simple r and omization list , participants were allocated to receive the low-carbohydrate diet or low-fat diet . The intervention for both groups included group meetings , diet instruction , and an exercise recommendation . Group meetings took place at an outpatient research clinic twice monthly for 3 months , then monthly for 3 months . These meetings typically lasted 1 hour and consisted of diet instruction , supportive counseling , question naires , and biomedical measurements . During the study , participants selected their own menus and prepared or bought their own meals according to the guidelines presented to them . Participants were encouraged to exercise for 30 minutes at least 3 times weekly , but no formal exercise program or incentives were provided . Low-Carbohydrate Diet Using a popular diet book published by a lay press and additional h and outs , trained research staff instructed participants to restrict intake of carbohydrates to less than 20 g/d ( 4 ) . Participants were permitted unlimited amounts of animal foods ( meat , fowl , fish , and shellfish ) , unlimited eggs , 4 oz of hard cheese , 2 cups of salad vegetables ( such as lettuce , spinach , or celery ) , and 1 cup of low-carbohydrate vegetables ( such as broccoli , cauliflower , or squash ) daily . Participants were encouraged to drink 6 to 8 glasses of water daily . When participants were halfway to their goal body weight ( determined at the week 10 visit with assistance from research personnel ) , they were advised to add approximately 5 g of carbohydrates to their daily intake each week until they reached a level at which body weight was maintained . To simulate the practice of the study sponsor , the low-carbohydrate diet group also received daily nutritional supplements ( multivitamin , essential oils , diet formulation , and chromium picolinate ; for a list of the composition of these supplements , see the Appendix ) ( 6 ) . Low-Fat Diet Using a commonly available booklet and additional h and outs , a registered dietitian instructed participants in a diet consisting of less than 30 % of daily energy intake from fat , less than 10 % of daily energy intake from saturated fat , and less than 300 mg of cholesterol daily ( 11 , 12 ) . The recommended energy intake was 2.1 to 4.2 MJ ( 500 to 1000 kcal ) less than the participant 's calculated energy intake for weight maintenance ( body weight in pounds 10 ) ( 13 ) . Primary Outcome Measure Body weight and body mass index were the primary outcome measures . At each visit , participants were weighed on the same calibrated scale while wearing lightweight clothing and no shoes . Body mass index was calculated as body weight in kilograms divided by height in meters squared . Secondary Outcome Measures Adherence Adherence to the diet was measured by self-report , food records , and , for the low-carbohydrate diet group , urinary ketone assessment . Diet Composition All participants completed a 24-hour recall of food intake at baseline and take-home food records ( 5 consecutive days , including a weekend ) that were collected at each meeting during the study . Participants were instructed on how to document food intake and were given h and outs with examples of how to complete the records . A sample of participants ( 13 in the low-carbohydrate diet group and 7 in the low-fat diet group ) who completed the study was selected for food record analysis by the research staff on the basis of adequacy of detail in their records . A registered dietitian analyzed the food records by using a nutrition software program ( Nutritionist Five , version 1.6 [ First Data Bank , Inc. , San Bruno , California ] ) . Ketonuria Restriction of dietary intake of carbohydrates to less than 40 g/d typically results in ketonuria that is detectable by dipstick analysis , which can be used to monitor adherence to the low-carbohydrate diet ( 14 , 15 ) . At each return visit , participants provided a fresh urine specimen for analysis . The following semi-quantitative scale was used to categorize ketone content : none , trace ( up to 0.9 mmol/L [ 5 mg/dL ] ) , small ( 0.9 to 6.9 mmol/L [ 5 to 40 mg/dL ] ) , moderate ( 6.9 to 13.8 mmol/L [ 40 to 80 mg/dL ] ) , large80 ( 13.8 to 27.5 mmol/L [ 80 to 160 mg/dL ] ) , and large160 ( > 27.5 mmol/L [ > 160 mg/dL ] ) . Body Composition Body composition was estimated by using bioelectric impedance ( model TBF-300A [ Tanita Corp. , Arlington Heights , Illinois ] ) at approximately the same time of day ( afternoon or evening ) at each return visit . In a subset of 33 participants , the percentage of body fat as measured by bioelectric impedance had excellent correlation with the percentage as measured by dual-energy x-ray absorptiometry ( r = 0.93 [ 95 % CI , 0.87 to 0.97 ] ) . Vital Signs Blood pressure and pulse rate were measured in the nondominant arm by using an automated digital cuff ( model HEM-725C [ Omron Corp. , Vernon Hills , Illinois ] ) after the participant had been sitting for 3 minutes . Two measurements were taken at each visit and averaged for the analysis . Serum Lipids and Lipoproteins Serum specimens for lipid measurement were obtained in the morning after at least 8 hours of fasting at the screening visit and at 8 , 16 , and 24 weeks . Other Metabolic Effects Serum tests for sodium , potassium , chloride , urea nitrogen , creatinine , calcium , phosphorus , total protein , albumin , uric acid , total bilirubin , alanine aminotransferase , aspartate aminotransferase , alkaline phosphatase , thyroid-stimulating hormone , iron , hemoglobin , leukocyte count , and platelet count were obtained at the screening visit and at 8 , 16 , and 24 weeks . The glomerular filtration rate was estimated by using an equation that included age ; sex ; race ; and serum levels of albumin , creatinine , and urea nitrogen ( Modification of Diet in Renal Disease Study equation ) ( 16 ) . Adverse Effects At all return visits , participants completed an open-ended question naire on side effects . At the 20- and 24-week visits , participants completed a checklist of the side effects that were most often mentioned during the study . Statistical Analysis Analyses were performed by using S-PLUS software , version 6.1 ( Insightful Corp. , Seattle , Washington ) , or SAS software , version 8.02 ( SAS Institute , Inc. , Cary , North Carolina ) . For categorical outcomes , groups were compared by using the chi-square test or Fisher exact test , as appropriate . For all primary and secondary continuous outcomes , linear mixed-effects models ( PROC MIXED procedure in SAS software ) that included fixed and r and om effects were used to determine expected mean values at each time point and to test hypotheses of group differences . In most body weight and BACKGROUND Despite the popularity of the low-carbohydrate , high-protein , high-fat ( Atkins ) diet , no r and omized , controlled trials have evaluated its efficacy . METHODS We conducted a one-year , multicenter , controlled trial involving 63 obese men and women who were r and omly assigned to either a low-carbohydrate , high-protein , high-fat diet or a low-calorie , high-carbohydrate , low-fat ( conventional ) diet . Professional contact was minimal to replicate the approach used by most dieters . RESULTS Subjects on the low-carbohydrate diet had lost more weight than subjects on the conventional diet at 3 months ( mean [ + /-SD ] , -6.8+/-5.0 vs. -2.7+/-3.7 percent of body weight ; P=0.001 ) and 6 months ( -7.0+/-6.5 vs. -3.2+/-5.6 percent of body weight , P=0.02 ) , but the difference at 12 months was not significant ( -4.4+/-6.7 vs. -2.5+/-6.3 percent of body weight , P=0.26 ) . After three months , no significant differences were found between the groups in total or low-density lipoprotein cholesterol concentrations . The increase in high-density lipoprotein cholesterol concentrations and the decrease in triglyceride concentrations were greater among subjects on the low-carbohydrate diet than among those on the conventional diet throughout most of the study . Both diets significantly decreased diastolic blood pressure and the insulin response to an oral glucose load . CONCLUSIONS The low-carbohydrate diet produced a greater weight loss ( absolute difference , approximately 4 percent ) than did the conventional diet for the first six months , but the differences were not significant at one year . The low-carbohydrate diet was associated with a greater improvement in some risk factors for coronary heart disease . Adherence was poor and attrition was high in both groups . Longer and larger studies are required to determine the long-term safety and efficacy of low-carbohydrate , high-protein , high-fat diets BACKGROUND : We have previously reported that a fat-reduced high-protein diet had more favourable effects on body weight loss over 6 months than a medium-protein diet . OBJECTIVE : To extend this observation by a further 6–12 months less stringent intervention and a 24 months follow-up . DESIGN : A r and omised 6 months strictly controlled dietary intervention followed by 6–12 months dietary counselling period , and a subsequent 24 months follow-up , comparing an ad libitum , fat-reduced diet ( 30 % of energy ) either high in protein ( 25 % of energy , HP ) or medium in protein ( 12 % of energy , MP).SUBJECTS : A total of 50 overweight and obese subjects ( age : 19–55 y ; BMI : 26–34 kg/m2 ) . MEASUREMENTS : Change in body weight , body composition and blood parameters . RESULTS : After 6 months , the HP group ( n=23 ) achieved a greater weight loss than the MP group ( n=23 ) ( 9.4 vs 5.9 kg ) ( P<0.01 ) . After 12 months , 8 % had dropped out in the HP vs 28 % in the MP group ( P<0.07 ) . After 12 months , the weight loss was not significantly greater among the subjects in the HP group ( 6.2 and 4.3 kg ) , but they had a 10 % greater reduction in intra-abdominal adipose tissue and more in the HP group ( 17 % ) lost > 10 kg than in the MP ( P<0.09 ) . At 24 months , both groups tended to maintain their 12 months weight loss , but more than 50 % were lost to follow-up . CONCLUSION : A fat-reduced diet high in protein seems to enhance weight loss and provide a better long-term maintenance of reduced intra-abdominal fat stores Untested alternative weight loss diets , such as very low carbohydrate diets , have unsubstantiated efficacy and the potential to adversely affect cardiovascular risk factors . Therefore , we design ed a r and omized , controlled trial to determine the effects of a very low carbohydrate diet on body composition and cardiovascular risk factors . Subjects were r and omized to 6 months of either an ad libitum very low carbohydrate diet or a calorie-restricted diet with 30 % of the calories as fat . Anthropometric and metabolic measures were assessed at baseline , 3 months , and 6 months . Fifty-three healthy , obese female volunteers ( mean body mass index , 33.6 + /- 0.3 kg/m(2 ) ) were r and omized ; 42 ( 79 % ) completed the trial . Women on both diets reduced calorie consumption by comparable amounts at 3 and 6 months . The very low carbohydrate diet group lost more weight ( 8.5 + /- 1.0 vs. 3.9 + /- 1.0 kg ; P < 0.001 ) and more body fat ( 4.8 + /- 0.67 vs. 2.0 + /- 0.75 kg ; P < 0.01 ) than the low fat diet group . Mean levels of blood pressure , lipids , fasting glucose , and insulin were within normal ranges in both groups at baseline . Although all of these parameters improved over the course of the study , there were no differences observed between the two diet groups at 3 or 6 months . beta- Hydroxybutyrate increased significantly in the very low carbohydrate group at 3 months ( P = 0.001 ) . Based on these data , a very low carbohydrate diet is more effective than a low fat diet for short-term weight loss and , over 6 months , is not associated with deleterious effects on important cardiovascular risk factors in healthy women Abstract Objective To compare the effectiveness of four commercial weight loss diets available to adults in the United Kingdom . Design Six month multicentre r and omised unblinded controlled trial . Setting Community based sample of otherwise healthy overweight and obese adults . Interventions Dr Atkins ' new diet revolution , Slim-Fast plan , Weight Watchers pure points programme , and Rosemary Conley 's eat yourself slim diet and fitness plan . Main outcome measures Weight and body fat changes over six months . Results All diets result ed in significant loss of body fat and weight over six months . Groups did not differ significantly but loss of body fat and weight was greater in all groups compared with the control group . In an intention to treat analysis , average weight loss was 5.9 kg and average fat loss was 4.4 kg over six months . The Atkins diet result ed in significantly higher weight loss during the first four weeks , but by the end was no more or less effective than the other diets . Conclusions Clinical ly useful weight loss and fat loss can be achieved in adults who are motivated to follow commercial diets for a substantial period . Given the limited re sources for weight management in the NHS , healthcare practitioners should discuss with their patients programmes known to be effective . Trial registration Clinical trials NCT00327821 [ Clinical Trials.gov ] BACKGROUND Despite the popularity of low-glycemic index ( GI ) and high-protein diets , to our knowledge no r and omized , controlled trials have systematic ally compared their relative effects on weight loss and cardiovascular risk . METHODS A total of 129 overweight or obese young adults ( body mass index , > or = 25 [ calculated as weight in kilograms divided by the square of height in meters ] ) were assigned to 1 of 4 reduced-fat , high-fiber diets for 12 weeks . Diets 1 and 2 were high carbohydrate ( 55 % of total energy intake ) , with high and low GIs , respectively ; diets 3 and 4 were high protein ( 25 % of total energy intake ) , with high and low GIs , respectively . The glycemic load was highest in diet 1 and lowest in diet 4 . Changes in weight , body composition , and blood chemistry profile were studied . RESULTS While all groups lost a similar mean + /- SE percentage of weight ( diet 1 , -4.2 % + /- 0.6 % ; diet 2 , -5.5 % + /- 0.5 % ; diet 3 , -6.2 % + /- 0.4 % ; and diet 4 , -4.8 % + /- 0.7 % ; P = .09 ) , the proportion of subjects in each group who lost 5 % or more of body weight varied significantly by diet ( diet 1 , 31 % ; diet 2 , 56 % ; diet 3 , 66 % ; and diet 4 , 33 % ; P = .01 ) . Women on diets 2 and 3 lost approximately 80 % more fat mass ( -4.5 + /- 0.5 [ mean + /- SE ] kg and -4.6 + /- 0.5 kg ) than those on diet 1 ( -2.5 + /- 0.5 kg ; P = .007 ) . Mean + /- SE low-density-lipoprotein cholesterol levels declined significantly in the diet 2 group ( -6.6 + /- 3.9 mg/dL [ -0.17 + /- 0.10 mmol/L ] ) but increased in the diet 3 group ( + 10.0 + /- 3.9 mg/dL [ + 0.26 + /- 0.10 mmol/L ] ; P = .02 ) . Goals for energy distribution were not achieved exactly : both carbohydrate groups ate less fat , and the diet 2 group ate more fiber . CONCLUSION Both high-protein and low-GI regimens increase body fat loss , but cardiovascular risk reduction is optimized by a high-carbohydrate , low-GI diet OBJECTIVE To evaluate whether a 5-week low-glycemic index ( LGI ) diet versus a high-glycemic index ( HGI ) diet can modify glucose and lipid metabolism as well as total fat mass in nondiabetic men . RESEARCH DESIGN AND METHODS In this study , 11 healthy men were r and omly allocated to 5 weeks of an LGI or HGI diet separated by a 5-week washout interval in a crossover design . RESULTS The LGI diet result ed in lower postpr and ial plasma glucose and insulin profiles and areas under the curve ( AUCs ) than the HGI diet . A 5-week period of the LGI diet lowered plasma triacylglycerol excursion after lunch ( AUC , P < 0.05 LGI vs. HGI ) . These modifications were associated with a decrease in the total fat mass by approximately 700 g ( P < 0.05 ) and a tendency to increase lean body mass ( P < 0.07 ) without any change in body weight . This decrease in fat mass was accompanied by a decrease in leptin , lipoprotein lipase , and hormone-sensitive lipase RNAm quantities in the subcutaneous abdominal adipose tissue ( P < 0.05 ) . CONCLUSIONS We concluded that 5 weeks of an LGI diet ameliorates some plasma lipid parameters , decreases total fat mass , and tends to increase lean body mass without changing body weight . These changes were accompanied by a decrease in the expression of some genes implicated in lipid metabolism . Such a diet could be of benefit to healthy , slightly overweight subjects and might play a role in the prevention of metabolic diseases and their cardiovascular complications This prospect i ve study was undertaken to eluci date the relationship between progressive log increments in plasma free insulin concentration and the result ant changes in the concentrations of plasma glucose , potassium , ketones , and free fatty acids in man . We attempted to define both the maximal and minimal threshold for substrate response relative to circulating concentrations of plasma insulin . Hyperglycemia and hyperketonemia were experimentally induced with dexamethasone in six diabetic subjects . Circulating plasma insulin concentration was acutely elevated by the continuous iv infusion of insulin in order to attain ten-fold increments in circulating plasma insulin concentration . Specifically , following a progressive elevation above basal concentration , maximal increments in circulating plasma insulin of 7 μU/ml , 90μU/ml , and 1 , 621 μU/ml were obtained . The differential effects of these acute alterations in plasma insulin concentration on plasma substrate concentrations were compared to a controlsaline Lifestyle changes , in particular reducing energy intake , are the cornerstone of current approaches to weight loss and prevention of type 2 diabetes . However , there is currently no consensus that one dietary regimen is more effective than another for weight loss ( 1 ) or whether particular diets work better for identifiable groups of individuals . There is evidence , however , to suggest that both insulin resistance and insulin secretion play a role in body weight regulation ( 2–12 ) . Therefore , dietary factors such as the dietary glycemic load ( glycemic load = glycemic index [ GI ] × available carbohydrate amount ) that influence these parameters may theoretically interact with subject-specific characteristics of glucose-insulin dynamics to influence the effect of different hypocaloric diets on weight loss or maintenance ( 13,14 ) . Weight loss studies using the concept of the dietary glycemic index or glycemic load have shown conflicting results for heterogeneous groups of individuals ( 15–21 ) . In a 6-month controlled feeding trial in healthy overweight adults with normal glucose tolerance , we tested the hypothesis that individuals with higher insulin secretion lose more weight when r and omized to a low – glycemic load diet compared with a high – glycemic load diet . This study was performed as part of the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy ( CALERIE ) trial at the Human Nutrition Research Center on Aging at Tufts University with approval from the Tufts-New Engl and Medical Center Human Investigation Review Committee . Written informed consent was obtained from all participants . Healthy women and men aged 24–42 BACKGROUND The incidence of type 2 diabetes increases markedly for obese children after puberty . However , the effect of dietary composition on body weight and diabetes risk factors has not been studied in adolescents . OBJECTIVE To compare the effects of an ad libitum , reduced-glycemic load ( GL ) diet with those of an energy-restricted , reduced-fat diet in obese adolescents . DESIGN R and omized control trial consisting of a 6-month intervention and a 6-month follow-up . MAIN OUTCOME MEASURES Body composition ( body mass index [ BMI ; calculated as weight in kilograms divided by the square of height in meters ] and fat mass ) and insulin resistance ( homeostasis model assessment ) were measured at 0 , 6 , and 12 months . Seven-day food diaries were used as a process measure . SUBJECTS Sixteen obese adolescents aged 13 to 21 years . Intervention Experimental ( reduced-GL ) treatment emphasized selection of foods characterized by a low to moderate glycemic index , with 45 % to 50 % of energy from carbohydrates and 30 % to 35 % from fat . In contrast , conventional ( reduced-fat ) treatment emphasized selection of low-fat products , with 55 % to 60 % of energy from carbohydrates and 25 % to 30 % from fat . RESULTS Fourteen subjects completed the study ( 7 per group ) . The GL decreased significantly in the experimental group , and dietary fat decreased significantly in the conventional group ( P<.05 for both ) . At 12 months , mean + /- SEM BMI ( -1.3 + /- 0.7 vs 0.7 + /- 0.5 ; P = .02 ) and fat mass ( -3.0 + /- 1.6 vs 1.8 + /- 1.0 kg ; P = .01 ) had decreased more in the experimental compared with the conventional group , differences that were material ly unchanged in an intention-to-treat model ( n = 16 ) ( BMI , P = .02 ; fat mass , P = .01 ) . Insulin resistance as measured by means of homeostasis model assessment increased less in the experimental group during the intervention period ( -0.4 + /- 0.9 vs 2.6 + /- 1.2 ; P = .02 ) . In post hoc analyses , GL was a significant predictor of treatment response among both groups ( R2 = 0.51 ; P = .006 ) , whereas dietary fat was not ( R2 = 0.14 ; P = .22 ) . CONCLUSIONS An ad libitum reduced-GL diet appears to be a promising alternative to a conventional diet in obese adolescents . Large-scale r and omized controlled trials are needed to further evaluate the effectiveness of reduced-GL and -glycemic index diets in the treatment of obesity and prevention of type 2 diabetes OBJECTIVE To compare the effects of an energy reduced very low carbohydrate , high saturated fat diet ( LC ) and an isocaloric high carbohydrate , low fat diet ( LF ) on endothelial function after 12 months . DESIGN AND SUBJECTS Forty-nine overweight or obese patients ( age 50.0 + /- 1.1 years , BMI 33.7 + /- 0.6 kg m(-2 ) ) were r and omized to either an energy restricted ( approximately 6 - 7 MJ ) , planned isocaloric LC or LF for 52 weeks . Body weight , endothelium-derived factors , flow-mediated dilatation ( FMD ) , adiponectin , augmentation index ( AIx ) and pulse wave velocity ( PWV ) were assessed . All data are mean + /- SEM . RESULTS Weight loss was similar in both groups ( LC -14.9 + /- 2.1 kg , LF -11.5 + /- 1.5 kg ; P = 0.20 ) . There was a significant time x diet effect for FMD ( P = 0.045 ) ; FMD decreased in LC ( 5.7 + /- 0.7 % to 3.7 + /- 0.5 % ) but remained unchanged in LF ( 5.9 + /- 0.5 % to 5.5 + /- 0.7 % ) . PWV improved in both groups ( LC -1.4 + /- 0.6 m s(-1 ) , LF -1.5 + /- 0.6 m s(-1 ) ; P = 0.001 for time ) with no diet effect ( P = 0.80 ) . AIx and VCAM-1 did not change in either group . Adiponectin , eSelectin , tPA and PAI-1 improved similarly in both groups ( P < 0.01 for time ) . CONCLUSION Both LC and LF hypoenergetic diets achieved similar reductions in body weight and were associated with improvements in PWV and a number of endothelium-derived factors . However , the LC diet impaired FMD suggesting chronic consumption of a LC diet may have detrimental effects on endothelial function |
12,319 | 29,914,039 | CONCLUSION Current evidence indicates that antihypertensives and statins might reduce the incidence of dementia and AD . | BACKGROUND Epidemiological evidence has associated Alzheimer 's disease ( AD ) with vascular risk factors ( VRFs ) , but whether treatment of VRFs reduces the incidence of dementia and AD is uncertain .
OBJECTIVE To conduct a systematic review and meta- analysis to summarize available data on the impact of treatment of VRFs on dementia and AD incidence . | Objectives Possible association between diabetes mellitus ( DM ) and Alzheimer ’s disease ( AD ) has been controversial . This study used a nationwide population -based data set to investigate the relationship between DM and subsequent AD incidence . Methods Data were collected from Taiwan ’s National Health Insurance Research Data base , which released a cohort data set of 1,000,000 r and omly sample d people and confirmed it to be representative of the Taiwanese population . We identified 71,433 patients newly diagnosed with diabetes ( age 58.74±14.02 years ) since January 1997 . Using propensity score , we matched them with 71,311 non-diabetic subjects by time of enrollment , age , gender , hypertension , hyperlipidemia , and previous stroke history . All the patients were followed up to December 31 , 2007 . The endpoint of the study was occurrence of AD . Results Over a maximum 11 years of follow-up , diabetic patients experienced a higher incidence of AD than non-diabetic subjects ( 0.48 % vs. 0.37 % , p<0.001 ) . After Cox proportional hazard regression model analysis , DM ( hazard ratio [ HR ] , 1.76 ; 95 % confidence interval [ CI ] , 1.50–2.07 , p<0.001 ) , age ( HR , 1.11 ; 95 % CI , 1.10–1.12 , p<0.001 ) , female gender ( HR , 1.24 ; 95 % CI , 1.06–1.46 , p = 0.008 ) , hypertension ( HR , 1.30 ; 95 % CI , 1.07–1.59 , p = 0.01 ) , previous stroke history ( HR , 1.79 ; 95 % CI , 1.28–2.50 , p<0.001 ) , and urbanization status ( metropolis , HR , 1.32 ; 95 % CI , 1.07–1.63 , p = 0.009 ) were independently associated with the increased risk of AD . Neither monotherapy nor combination therapy with oral antidiabetic medications were associated with the risk of AD after adjusting for underlying risk factors and the duration of DM since diagnosis . However , combination therapy with insulin was found to be associated with greater risk of AD ( HR , 2.17 ; 95 % CI , 1.04–4.52 , p = 0.039 ) . Conclusion Newly diagnosed DM was associated with increased risk of AD . Use of hypoglycemic agents did not ameliorate the risk Background : Several lines of evidence have linked cholesterol to dementia . Objective : To investigate lipid-lowering drug use and dementia development in a Finnish population . Methods : FINRISK is a large population -based survey of cardiovascular risk factors carried out since 1972 every 5 years using independent , r and om and representative population sample s from different parts of Finl and . Several cohorts were part of the WHO-MONICA study . Data from cohorts 1972–2002 were linked to the Hospital Discharge Registry and Drug Reimbursement Registry ( 1995–2007 ) to ascertain dementia diagnoses and lipid-lowering treatment . Selection criteria for the study were : ( 1 ) alive and without dementia in 1995 ; ( 2 ) age ≧60 years ( in 1995 for earlier cohorts and in 1997 or 2002 for later cohorts ; ( 3 ) treatment prescribed at least 1 year before dementia diagnosis . Results : 17,597 persons were included in the study . Lipid-lowering treatment was related to decreased dementia risk . In Cox proportional hazards model , hazard ratio ( 95 % CI ) was 0.42 ( 0.37–0.49 ; controlled for age , sex , education , survey region , survey year , baseline cholesterol , body mass index and systolic blood pressure ) . Conclusion : Preliminary results from the FINRISK study indicate that lipid-lowering drugs may have a beneficial effect in dementia prevention . Further data linkage is ongoing in order to investigate the roles of different types of lipid-lowering drugs The aim of this prospect i ve cohort study was to evaluate the effects of lipid lowering agent ( LLA ) intake on cognitive function in 6,830 community-dwelling elderly persons . Cognitive performance ( global cognitive functioning , visual memory , verbal fluency , psychomotor speed , and executive function ) , clinical diagnosis of dementia , and fibrate and statin use , were evaluated at baseline , and 2 , 4 , and 7 year follow-up . Multivariate Cox models were stratified by gender and adjusted for sociodemographic characteristics , mental and physical health including vascular risk factors , and genetic vulnerability ( apolipoprotein E and cholesteryl ester transfer protein ) . For women but not men , fibrate use was specifically associated with an increased risk over 7 years of decline in visual memory only ( HR = 1.29 , 95 % CI = 1.09 - 1.54 , p = 0.004 ) , and did not increase risk for incident dementia . This association was independent of genetic vulnerability related to apolipoprotein E and cholesteryl exchange transfer protein polymorphisms and occurred only in women with higher low density lipoprotein (LDL)-cholesterol levels and treated with fibrate ( HR = 1.39 , 95 % CI = 1.08 - 1.79 , p = 0.01 ) and not in those with lower LDL-cholesterol levels irrespective of fibrate treatment . For both genders , no significant associations were found between statins ( irrespective of their lipophilicity ) and either cognitive decline or dementia incidence . This prospect i ve study , adjusting for multiple confounders , found no evidence that LLA given in late life reduced the risk of cognitive decline and dementia , but did raise the possibility that women with treatment-resistant high LDL-cholesterol may be at increased risk of decline in visual memory Background : Previously reported associations between statin use and incident dementia or cognitive decline have been inconsistent . We report the results from a 3-year prospect i ve study on the association of statin use on cognitive decline and incident dementia in elderly African Americans . Methods : A community-based cohort of 1,146 African Americans aged 70 and older living in Indianapolis , Indiana , was evaluated in 2001 and 2004 . The instrument used for cognitive assessment was the Community Screening Interview for Dementia ( CSI-D ) . Cognitive decline was defined as CSI-D scores measured at 2001 minus scores at 2004 . Measurements of low-density lipoprotein cholesterol ( LDL-C ) and C-reactive protein ( CRP ) were obtained from baseline blood sample s. Results : Adjusting for age at baseline , gender , education , and the possession of ApoE ε4 allele , baseline statin use was associated with less cognitive decline ( p = 0.0177 ) . There were no significant interactions of statin use when LDL-C and CRP were included . Logistic regression with the four independent variables showed that statin use may be associated with a reduction in incident dementia ( OR = 0.32 ; p = 0.0673 ) . Association with cognitive decline was less clear when investigating statin use over time . Significance remained only for those who discontinued prior to follow-up compared to continuous users or users who started after baseline . Conclusions : The relationship between statin use and cognitive decline is complex and subjected to unknown confounders . This effect may not be associated with the cholesterol lowering or anti-inflammatory action of statins . GLOSSARY : AD = Alzheimer disease ; ANCOVA = analysis of covariance ; BMI = body mass index ; CAMDEX = Cambridge Examination for Mental Disorders of the Elderly informant interview ; CERAD = Consortium to Establish a Registry for Alzheimer ’s Disease ; CHIF = Clinician Home-based Interview to assess Function ; CRP = C-reactive protein ; CSI-D = Community Screening Instrument for Dementia ; HDL = high-density lipoprotein ; HMG-CoA = 3-hydroxy-3-methylglutaryl-coenzyme A ; LDL-C = low-density lipoprotein cholesterol ; LLAs = lipid-lowering agents ; NSAIDs = nonsteroidal anti-inflammatory drugs BACKGROUND Prior reports suggest reduced occurrence of dementia and Alzheimer disease ( AD ) in statin users , but , to our knowledge , no prospect i ve studies relate statin use and dementia incidence . OBJECTIVE To examine the association of statin use with both prevalence and incidence of dementia and AD . DESIGN Cross-sectional studies of prevalence and incidence and a prospect i ve study of incidence of dementia and AD among 5092 elderly residents ( aged 65 years or older ) of a single county . Participants were assessed at home in 1995 - 1997 and again in 1998 - 2000 . A detailed visual inventory of medicines , including statins and other lipid-lowering agents , was collected at both assessment s. MAIN OUTCOME MEASURES Diagnosis of dementia and of AD . RESULTS From 4895 participants with data sufficient to determine cognitive status , we identified 355 cases of prevalent dementia ( 200 with AD ) at initial assessment . Statin use was inversely associated with prevalence of dementia ( adjusted odds ratio , 0.44 ; 95 % confidence interval , 0.17 - 0.94 ) . Three years later , we identified 185 cases of incident dementia ( 104 with AD ) among 3308 survivors at risk . Statin use at baseline did not predict incidence of dementia or AD ( adjusted hazard ratio for dementia , 1.19 ; 95 % confidence interval , 0.53 - 2.34 ; adjusted hazard ratio for AD , 1.19 ; 95 % confidence interval , 0.35 - 2.96 ) , nor did statin use at follow-up ( adjusted odds ratio for dementia , 1.04 ; 95 % confidence interval , 0.56 - 1.81 ; adjusted odds ratio for AD , 0.85 ; 95 % confidence interval , 0.32 - 1.88 ) . CONCLUSIONS Although statin use might be less frequent in those with prevalent dementia , we found no association between statin use and subsequent onset of dementia or AD . Further research is warranted before costly dementia prevention trials with statins are undertaken We investigated whether angiotensin II receptor blockers ( ARBs ) and angiotensin converting enzyme inhibitors ( ACE-Is ) are more strongly associated with Alzheimer 's disease ( AD ) , vascular dementia ( VaD ) , and other dementias , than other anti-hypertensive drugs . We conducted a nested case-control analysis within the UK general practice research data base , with prospect ively recorded anti-hypertensive prescribing data . We sample d cases aged ≥60 years and diagnosed between 1997 - 2008 ( 5,797 with AD , 2,186 with VaD , 1,214 with unspecified/other dementia ) which were matched to up to four controls by age , general practice and gender . We computed odds-ratios and dose response effects for AD , vascular and unspecified/other dementia , comparing those prescribed ARBs or ACE-Is for at least six months with patients prescribed other anti-hypertensives . We controlled for matching factors , co-morbidities , smoking status , an area measure of socioeconomic status , consultation rate and blood pressure and accounted for reverse causality by introducing time-lags of up to eight years prior to diagnosis/index date . Patients diagnosed with AD , vascular and unspecified/other dementia had fewer prescriptions for ARBs and ACE-Is . Inverse associations with AD were strongest for ARBs ( odds-ratio ; 0.47 , 95%CI , 0.37 - 0.58 ) compared with ACE-Is ( odds-ratio ; 0.76 , 95%CI , 0.69 - 0.84 ) ( p(difference ) < 0.001 ) . Associations of ARBs with AD were stronger than for vascular dementia ( p(difference ) = 0.01 ) and unspecified/other dementia ( p(difference ) = 0.23 ) . There were inverse dose-response relationships between ARBs and ACE-Is with AD ( both p(trend ) < 0.01 ) . The inverse association of ACE-Is with AD diminished when using longer time lags but the ARB-AD association persisted . Patients with AD were around half as likely to be prescribed ARBs . Further r and omized controlled trial evidence is required to rigorously test these findings BACKGROUND Dementia affects an estimated 10 % of the population older than 65 years . Because vascular and lipid-related mechanisms are thought to have a role in the pathogenesis of Alzheimer 's disease and vascular dementia , we did an epidemiological study of the potential effect of HMGCoA ( 3 hydroxy-3methylglutaryl-coenzyme A ) reductase inhibitors ( statins ) and other lipid-lowering agents on dementia . METHODS We used a nested case-control design with information derived from 368 practice s which contribute to the UK-based General Practice Research Data base . The base study population included three groups of patients age 50 years and older : all individuals who had received lipid-lowering agents ( LLAs ) ; all individuals with a clinical diagnosis of untreated hyperlipidaemia ; and a r and omly selected group of other individuals . From this base population , all cases with a computer-recorded clinical diagnosis of dementia were identified . Each case was matched with up to four controls derived from the base population on age , sex , practice , and index date of case . FINDINGS The study encompassed 284 cases with dementia and 1080 controls . Among controls 13 % had untreated hyperlipidaemia , 11 % were prescribed statins , 7 % other LLAs , and 69 % had no hyperlipidaemia or LLA exposure . The relative risk estimates of dementia adjusted for age , sex , history of coronary-artery disease , hypertension , coronary-bypass surgery and cerebral ischaemia , smoking and body mass index for individuals with untreated hyperlipidaemia ( odds ratio 0.72 [ 95 % CI 0.45 - 1.14 ] ) , or treated with nonstatin LLAs ( 0.96 [ 0.47 - 1.97 ] , was close to 1.0 and not significant compared with people who had no diagnosis of hyperlipidaemia or exposure to other lipid-lowering drugs . The adjusted relative risk for those prescribed statins was 0.29 ( 0.13 - 0.63 ; p=0.002 ) . INTERPRETATION Individuals of 50 years and older who were prescribed statins had a substantially lowered risk of developing dementia , independent of the presence or absence of untreated hyperlipidaemia , or exposure to nonstatin LLAs . The available data do not distinguish between Alzheimer 's disease and other forms of dementia Background : Cross-sectional reports suggest that statin users are less likely to have Alzheimer disease ( AD ) . Prospect i ve studies have provided inconsistent evidence . Moreover , it is unclear whether the association differs for lipohilic statins , those that could more easily pass the blood – brain barrier and hydrophilic statins . Objectives : To prospect ively evaluate whether use of statins is associated with the risk of AD , and to determine whether associations differ for lipophilic and hydrophilic statins . Method : 6992 participants of the prospect i ve , population -based Rotterdam Study were followed , from baseline ( 1990–1993 ) until January 2005 for incident AD . Data on all filled prescriptions came from pharmacy records . For each date on which each event occurred , cholesterol-lowering drug use for the person who experienced the event and all remaining persons in the cohort was categorised as “ any ” or “ never ” use . A distinction was made between statin , lipophilic and hydrophilic statins , and non-statin cholesterol-lowering drugs . Data were analysed with the Cox regression analysis , adjusting for sex , age and potential confounders . Results : During follow-up ( mean 9 years ) , 582 persons developed AD . Compared with never use of cholesterol-lowering drugs , statin use was associated with a decreased risk of AD ( HR 0.57 ; 95 % CI 0.37 to 0.90 ) , but non-statin cholesterol-lowering drug use was not ( HR 1.05 ; 95 % CI 0.45 to 2.44 ) . HRs were equal for lipophilic ( HR 0.54 ; 95 % CI 0.32 to 0.89 ) and hydrophilic statins ( HR 0.54 ; 95 % CI 0.26 to 1.11 ) . Conclusion : In the general population , the use of statins , but not of non-statin cholesterol-lowering drugs , was associated with a lower risk of AD compared with never use of cholesterol-lowering drugs . The protective effect was independent of the lipophilicity of statins OBJECTIVES The objective of this study was to examine the association between the use of statins and the risk of newly diagnosed dementia in an elderly population . DESIGN , SETTING AND PARTICIPANTS R and om sample s of 1,000,000 individuals covered by the National Health Insurance in Taiwan were included in the analysis . All participants were 65 years or older without dementia and either did or did not start treatment with statins from 1 August 1997 to 31 December 2010 . Patients with established dementia before the start of treatment were excluded . Baseline characteristics were matched ( by propensity score ) in those who did and did not receive statins . RESULTS A total of 57,669 subjects were included in the analysis with approximately 12 years of follow-up . Propensity score matching identified 2003 patients who received statins and another 2003 patients who did not with comparable baseline characteristics . Adjusted hazard ratios ( HRs ) for dementia were significantly inversely associated with total or daily equivalent statin dosage ( total accumulated dose : HRs 0.829 , 0.720 and 0.385 from T1 to T3 vs. control , P < 0.001 for trend ; mean daily dose : HRs 0.667 , 0.798 and 0.503 from T1 to T3 vs. control , P < 0.001 ) . The results remained robust after propensity adjustment . CONCLUSION Independent of traditional risk factors , there was a decrease in newly diagnosed cases of dementia in elderly patients who had received a high total or daily dose of statins . The more potent statins ( e.g. atorvastatin and rosuvastatin ) seemed to be particularly effective in the prevention of dementia AIMS To assess the effect of statins on a range of health outcomes . METHODS We undertook a population -based cohort study to assess the effect of statins on a range of health outcomes using a propensity score-based method to control for differences between people prescribed and not prescribed statins . We vali date d our design by comparing our results for vascular outcomes with the effects established in large r and omized trials . The study was based on the United Kingdom Health Improvement Network data base that includes the computerized medical records of over four and a half million patients . RESULTS People who initiated treatment with a statin ( n = 129,288 ) were compared with a matched sample of 600,241 people who did not initiate treatment , with a median follow-up period of 4.4 years . Statin use was not associated with an effect on a wide range of outcomes , including infections , fractures , venous thromboembolism , gastrointestinal haemorrhage , or on specific eye , neurological or autoimmune diseases . A protective effect against dementia was observed ( hazard ratio 0.80 , 99 % confidence interval 0.68 , 0.95 ) . There was no effect on the risk of cancer even after > or = 8 years of follow-up . The effect sizes for statins on vascular end-points and mortality were comparable to those observed in large r and omized trials , suggesting bias and confounding had been well controlled for . CONCLUSIONS We found little evidence to support wide-ranging effects of statins on health outcomes beyond their established beneficial effect on vascular disease Objective To quantify the unintended effects of statins according to type , dose , and duration of use . Design Prospect i ve open cohort study using routinely collected data . Setting 368 general practice s in Engl and and Wales supplying data to the Q Research data base . Participants 2 004 692 patients aged 30 - 84 years of whom 225 922 ( 10.7 % ) were new users of statins : 159 790 ( 70.7 % ) were prescribed simvastatin , 50 328 ( 22.3 % ) atorvastatin , 8103 ( 3.6 % ) pravastatin , 4497 ( 1.9 % ) rosuvastatin , and 3204 ( 1.4 % ) fluvastatin . Methods Cox proportional hazards models were used to estimate effects of statin type , dose , and duration of use . The number needed to treat ( NNT ) or number needed to harm ( NNH ) was calculated and numbers of additional or fewer cases estimated for 10 000 treated patients . Main outcome measure First recorded occurrence of cardiovascular disease , moderate or serious myopathic events , moderate or serious liver dysfunction , acute renal failure , venous thromboembolism , Parkinson ’s disease , dementia , rheumatoid arthritis , cataract , osteoporotic fracture , gastric cancer , oesophageal cancer , colon cancer , lung cancer , melanoma , renal cancer , breast cancer , or prostate cancer . Results Individual statins were not significantly associated with risk of Parkinson ’s disease , rheumatoid arthritis , venous thromboembolism , dementia , osteoporotic fracture , gastric cancer , colon cancer , lung cancer , melanoma , renal cancer , breast cancer , or prostate cancer . Statin use was associated with decreased risks of oesophageal cancer but increased risks of moderate or serious liver dysfunction , acute renal failure , moderate or serious myopathy , and cataract . Adverse effects were similar across statin types for each outcome except liver dysfunction where risks were highest for fluvastatin . A dose-response effect was apparent for acute renal failure and liver dysfunction . All increased risks persisted during treatment and were highest in the first year . After stopping treatment the risk of cataract returned to normal within a year in men and women . Risk of oesophageal cancer returned to normal within a year in women and within 1 - 3 years in men . Risk of acute renal failure returned to normal within 1 - 3 years in men and women , and liver dysfunction within 1 - 3 years in women and from three years in men . Based on the 20 % threshold for cardiovascular risk , for women the NNT with any statin to prevent one case of cardiovascular disease over five years was 37 ( 95 % confidence interval 27 to 64 ) and for oesophageal cancer was 1266 ( 850 to 3460 ) and for men the respective values were 33 ( 24 to 57 ) and 1082 ( 711 to 2807 ) . In women the NNH for an additional case of acute renal failure over five years was 434 ( 284 to 783 ) , of moderate or severe myopathy was 259 ( 186 to 375 ) , of moderate or severe liver dysfunction was 136 ( 109 to 175 ) , and of cataract was 33 ( 28 to 38 ) . Overall , the NNHs and NNTs for men were similar to those for women , except for myopathy where the NNH was 91 ( 74 to 112 ) . Conclusions Cl aims of unintended benefits of statins , except for oesophageal cancer , remain unsubstantiated , although potential adverse effects at population level were confirmed and quantified . Further studies are needed to develop utilities to individualise the risks so that patients at highest risk of adverse events can be monitored closely A prospect i ve analysis of risk factors for Alzheimer 's disease was a major objective of the Canadian Study of Health and Aging , a nationwide , population -based study . Of 6,434 eligible subjects aged 65 years or older in 1991 , 4,615 were alive in 1996 and participated in the follow-up study . All participants were cognitively normal in 1991 when they completed a risk factor question naire . Their cognitive status was reassessed 5 years later by using a similar two-phase procedure , including a screening interview , followed by a clinical examination when indicated . The analysis included 194 Alzheimer 's disease cases and 3,894 cognitively normal controls . Increasing age , fewer years of education , and the apolipoprotein E epsilon4 allele were significantly associated with increased risk of Alzheimer 's disease . Use of nonsteroidal anti-inflammatory drugs , wine consumption , coffee consumption , and regular physical activity were associated with a reduced risk of Alzheimer 's disease . No statistically significant association was found for family history of dementia , sex , history of depression , estrogen replacement therapy , head trauma , antiperspirant or antacid use , smoking , high blood pressure , heart disease , or stroke . The protective associations warrant further study . In particular , regular physical activity could be an important component of a preventive strategy against Alzheimer 's disease and many other conditions BACKGROUND It is uncertain whether high blood pressure increases the risk of developing Alzheimer disease ( AD ) . OBJECTIVE To examine the association between incident AD and blood pressure measured up to 13 years before diagnosis . DESIGN Longitudinal cohort study conducted from 1982 to 1988 , with blood pressure measured every 3 years in home interviews , and in 1973 for a portion ( 60 % ) of the sample . SETTING Community of East Boston , Mass. PARTICIPANTS Six hundred thirty-four subjects 65 years or older and without AD were selected as a stratified r and om sample of participants of the East Boston Established Population s for Epidemiologic Studies of the Elderly . MAIN OUTCOME MEASURE Alzheimer disease was diagnosed by a neurologist using a structured clinical evaluation . RESULTS High blood pressure was not associated with an increased risk of AD in logistic regression models adjusted for age , sex , and level of education . There was no association with systolic pressure measured 13 years before diagnosis ( odds ratio = 1.03/10 mm Hg ; 95 % confidence interval , 0.80 - 1.32 ) and an inverse association with systolic pressure measured 4 years before diagnosis ( odds ratio = 0.82/10 mm Hg ; 95 % confidence interval , 0.72 - 0.95 ) . Associations for diastolic pressure were in the same direction as those for systolic pressure except with wider confidence intervals . The odds ratios were not material ly different with further adjustment for cardiovascular risk factors and diseases . CONCLUSION In this large community study , high blood pressure was not associated with an increased risk of AD BACKGROUND Observational epidemiological studies have shown a positive association between hypertension and risk of incident dementia ; however , the effects of antihypertensive therapy on cognitive function in controlled trials have been conflicting , and meta-analyses of the trials have not provided clear evidence of whether antihypertensive treatment reduces dementia incidence . The Hypertension in the Very Elderly trial ( HYVET ) was design ed to assess the risks and benefits of treatment of hypertension in elderly patients and included an assessment of cognitive function . METHODS Patients with hypertension ( systolic pressure 160 - 200 mm Hg ; diastolic pressure < 110 mm Hg ) who were aged 80 years or older were enrolled in this double-blind , placebo-controlled trial . Participants were r and omly assigned to receive 1.5 mg slow release indapamide , with the option of 2 - 4 mg perindopril , or placebo . The target systolic blood pressure was 150 mm Hg ; the target diastolic blood pressure was 80 mm Hg . Participants had no clinical diagnosis of dementia at baseline , and cognitive function was assessed at baseline and annually with the mini-mental state examination ( MMSE ) . Possible cases of incident dementia ( a fall in the MMSE score to < 24 points or a drop of three points in 1 year ) were assessed by st and ard diagnostic criteria and expert review . The trial was stopped in 2007 at the second interim analysis after treatment result ed in a reduction in stroke and total mortality . Analysis was by intention to treat . The trial is registered with Clinical Trials.gov , number NCT00122811 . FINDINGS 3336 HYVET participants had at least one follow-up assessment ( mean 2.2 years ) and were included : 1687 participants were r and omly assigned to the treatment group and 1649 to the placebo group . Only five reports of adverse effects were attributed to the medication : three in the placebo group and two in the treatment group . The mean decrease in systolic blood pressure between the treatment and placebo groups at 2 years was systolic -15 mm Hg , p<0.0001 ; and diastolic -5.9 mm Hg , p<0.0001 . There were 263 incident cases of dementia . The rates of incident dementia were 38 per 1000 patient-years in the placebo group and 33 per 1000 patient-years in the treatment group . There was no significant difference between treatment and placebo groups ( hazard ratio [ HR ] 0.86 , 95 % CI 0.67 - 1.09 ) ; however , when these data were combined in a meta- analysis with other placebo-controlled trials of antihypertensive treatment , the combined risk ratio favoured treatment ( HR 0.87 , 0.76 - 1.00 , p=0.045 ) . INTERPRETATION Antihypertensive treatment in elderly patients does not statistically reduce incidence of dementia . This negative finding might have been due to the short follow-up , owing to the early termination of the trial , or the modest effect of treatment . Nevertheless , the HYVET findings , when included in a meta- analysis , might support antihypertensive treatment to reduce incident dementia BACKGROUND Lipid-lowering medications ( LLMs ) and especially statin drugs can delay cognitive decline and dementia onset in individuals with and without mild cognitive impairment ( MCI ) at baseline . METHODS A longitudinal , observational study was conducted of 3069 cognitively healthy elderly patients ( ≥75 years of age ) who were enrolled in the Ginkgo Evaluation of Memory Study . The primary outcome measure was the time to adjudicated all-cause dementia and Alzheimer dementia ( AD ) . The secondary outcome measure was the change in global cognitive function over time measured by scores from the Modified Mini-Mental State Exam ( 3MSE ) and the cognitive subscale of the AD Assessment Scale ( ADAS-Cog ) . RESULTS Among participants without MCI at baseline , the current use of statins was consistently associated with a reduced risk of all-cause dementia ( hazard ratio [ HR ] , 0.79 ; 95 % confidence interval [ 95 % CI ] , 0.65 - 0.96 ; P = .021 ) and AD ( HR , 0.57 ; 95 % CI , 0.39 - 0.85 ; P = .005 ) . In participants who initiated statin therapy , lipophilic statins tended to reduce dementia risk more than nonlipophilic agents . In contrast , there was no significant association between LLM use ( including statins ) , dementia onset , or cognitive decline in individuals with baseline MCI . However , in individuals without MCI at baseline , there was a trend for a neuroprotective effect of statins on cognitive decline . CONCLUSIONS Statins may slow the rate of cognitive decline and delay the onset of AD and all-cause dementia in cognitively healthy elderly individuals , whereas individuals with MCI may not have comparable cognitive protection from these agents . However , the results from this observational study need to be interpreted with caution and will require confirmation by r and omized clinical trials stratifying treatment groups based on MCI status at baseline BACKGROUND Hypertension ( HTN ) is a risk factor for dementia , and animal studies suggest that central ly active angiotensin-converting enzyme ( ACE ) inhibitors ( those that cross the blood-brain barrier ) may protect against dementia beyond HTN control . METHODS Participants in the Cardiovascular Health Study Cognition Sub study with treated HTN and no diagnosis of congestive heart failure ( n = 1054 ; mean age , 75 years ) were followed up for a median of 6 years to determine whether cumulative exposure to ACE inhibitors ( as a class and by central activity ) , compared with other anti-HTN agents , was associated with a lower risk of incident dementia , cognitive decline ( by Modified Mini-Mental State Examination [ 3MSE ] ) , or incident disability in instrumental activities of daily living ( IADLs ) . RESULTS Among 414 participants who were exposed to ACE inhibitors and 640 who were not , there were 158 cases of incident dementia . Compared with other anti-HTN drugs , there was no association between exposure to all ACE inhibitors and risk of dementia ( hazard ratio [ HR ] , 1.01 ; 95 % confidence interval [ CI ] , 0.88 - 1.15 ) , difference in 3MSE scores ( -0.32 points per year ; P = .15 ) , or odds of disability in IADLs ( odds ratio [ OR ] , 1.06 ; 95 % CI , 0.99 - 1.14 ) . Adjusted results were similar . However , central ly active ACE inhibitors were associated with 65 % less decline in 3MSE scores per year of exposure ( P = .01 ) , and non central ly active ACE inhibitors were associated with a greater risk of incident dementia ( adjusted HR , 1.20 ; 95 % CI , 1.00 - 1.43 per year of exposure ) and greater odds of disability in IADLs ( adjusted OR , 1.16 ; 95 % CI , 1.03 - 1.30 per year of exposure ) compared with other anti-HTN drugs . CONCLUSIONS While ACE inhibitors as a class do not appear to be independently associated with dementia risk or cognitive decline in older hypertensive adults , there may be within-class differences in regard to these outcomes . These results should be confirmed with a r and omized clinical trial of a central ly active ACE inhibitor in the prevention of cognitive decline and dementia BACKGROUND After the double-blind , placebo-controlled Systolic Hypertension in Europe ( Syst-Eur ) trial ended in February 1997 , r and omized patients were offered active study medication for a further period of observation . OBJECTIVE To refine the estimates of the long-term effects of antihypertensive therapy on the incidence of dementia . METHODS Eligible patients had no dementia and were at least 60 years old . Their systolic blood pressure at entry was 160 to 219 mm Hg , with diastolic blood pressure below 95 mm Hg . Antihypertensive therapy was started immediately after r and omization in the active treatment group , but only after termination of the double-blind trial in the control patients . Treatment consisted of nitrendipine ( 10 - 40 mg/d ) , with the possible addition of enalapril maleate ( 5 - 20 mg/d ) , hydrochlorothiazide ( 12.5 - 25 mg/d ) , or both add-on drugs . RESULTS Median follow-up increased from 2.0 years in the double-blind trial to 3.9 years overall . The incidence of dementia doubled from 32 to 64 cases , 41 of whom had Alzheimer disease . Throughout follow-up , systolic/diastolic blood pressure was 7.0/3.2 mm Hg higher in the 1417 control patients than in the 1485 subjects r and omized to active treatment . At the last examination , the blood pressure difference was still 4.2/2.9 mm Hg ; 48.1 % , 26.4 % , and 11.4 % of the control patients were taking nitrendipine , enalapril , and /or hydrochlorothiazide , whereas in the active treatment group these proportions were 70.2 % , 35.4 % , and 18.4 % , respectively . Compared with the controls , long-term antihypertensive therapy reduced the risk of dementia by 55 % , from 7.4 to 3.3 cases per 1000 patient-years ( 43 vs 21 cases , P<.001 ) . After adjustment for sex , age , education , and entry blood pressure , the relative hazard rate associated with the use of nitrendipine was 0.38 ( 95 % confidence interval , 0.23 - 0.64 ; P<.001 ) . Treatment of 1000 patients for 5 years can prevent 20 cases of dementia ( 95 % confidence interval , 7 - 33 ) . CONCLUSION The extended follow-up of Syst-Eur patients reinforces the evidence that blood pressure-lowering therapy initiated with a long-acting dihydropyridine protects against dementia in older patients with systolic hypertension Background The prognostic benefits of blood pressure lowering treatment in elderly hypertensive patients were established more than a decade ago , but are less clear in those with mildly to moderately elevated blood pressure . Objective To assess whether c and esartan-based antihypertensive treatment in elderly patients with mildly to moderately elevated blood pressure confers a reduction in cardiovascular events , cognitive decline and dementia . Design Prospect i ve , double-blind , r and omized , parallel-group study conducted in 1997–2002 . Setting and participants The study was of 4964 patients aged 70–89 years , with systolic blood pressure 160–179 mmHg , and /or diastolic blood pressure 90–99 mmHg , and a Mini Mental State Examination ( MMSE ) test score ⩾ 24 . A total of 527 centres in 15 countries participated in the study . Intervention Patients were assigned r and omly to receive the angiotensin receptor blocker c and esartan or placebo , with open-label active antihypertensive therapy added as needed . As a consequence , active antihypertensive therapy was extensively used in the control group ( 84 % of patients ) . Mean follow-up was 3.7 years . Main outcome measures The primary outcome measure was major cardiovascular events , a composite of cardiovascular death , non-fatal stroke and non-fatal myocardial infa rct ion . Secondary outcome measures included cardiovascular death , non-fatal and fatal stroke and myocardial infa rct ion , cognitive function measured by the MMSE and dementia . Results Blood pressure fell by 21.7/10.8 mmHg in the c and esartan group and by 18.5/9.2 mmHg in the control group . A first major cardiovascular event occurred in 242 c and esartan patients and in 268 control patients ; risk reduction with c and esartan was 10.9 % [ 95 % confidence interval ( CI ) , −6.0 to 25.1 , P = 0.19 ] . C and esartan-based treatment reduced non-fatal stroke by 27.8 % ( 95 % CI , 1.3 to 47.2 , P = 0.04 ) , and all stroke by 23.6 % ( 95 % CI , −0.7 to 42.1 , P = 0.056 ) . There were no significant differences in myocardial infa rct ion and cardiovascular mortality . Mean MMSE score fell from 28.5 to 28.0 in the c and esartan group and from 28.5 to 27.9 in the control group ( P = 0.20 ) . The proportions of patients who had a significant cognitive decline or developed dementia were not different in the two treatment groups . Conclusions In elderly hypertensive patients , a slightly more effective blood pressure reduction during c and esartan-based therapy , compared with control therapy , was associated with a modest , statistically non-significant , reduction in major cardiovascular events and with a marked reduction in non-fatal stroke . Cognitive function was well maintained in both treatment groups in the presence of substantial blood pressure reductions . Both treatment regimens were generally well tolerated Objective : To determine the influence of type 2 diabetes mellitus on the risk of dementia and AD . Background : Both dementia and diabetes are frequent disorders in elderly people . Methods : Prospect i ve population -based cohort study among 6,370 elderly subjects . At baseline study participants were examined for presence of diabetes mellitus . Nondemented participants were followed up , on average , for 2.1 years . Incident dementia was diagnosed using a three-step screening and comprehensive diagnostic workup . To complete the follow-up , medical files were studied of persons who could not be reexamined . We estimated relative risks with proportional hazard regression , adjusting for age , sex , and possible confounders . Results : During the follow-up , 126 patients became demented , of whom 89 had AD . Diabetes mellitus almost doubled the risk of dementia ( relative risk [ RR ] 1.9 [ 1.3 to 2.8 ] ) and AD ( RR 1.9 [ 1.2 to 3.1 ] ) . Patients treated with insulin were at highest risk of dementia ( RR 4.3 [ 1.7 to 10.5 ] ) . Conclusion : The diabetes attributable risk for dementia of 8.8 % suggests that diabetes may have contributed to the clinical syndrome in a substantial proportion of all dementia patients BACKGROUND Some disagreements surround the effects of calcium-channel blockers ( CCBs ) on the risk of dementia . The purpose of this study was to investigate the protective effects of CCBs on dementia among elderly hypertensive Koreans . Methods and Results : We conducted a large population -based cohort study using the senior cohort data base of the Korean National Health Insurance Service ( 2002 - 2013 ) . Subjects were elderly hypertensive Koreans older than 60 years of age . A total of 18,423 patients ( CCB user group : 13,692 patients ; non-CCB antihypertensive user group : 4,731 patients ) were statistically analyzed using the Cox proportional hazard regression model to estimate the adjusted hazard ratio ( aHR ) and confidence intervals ( CIs ) of dementia associated with CCB use . There were 2,881 cases ( 21.0 % ) of dementia in the CCB user group and 1,124 cases ( 23.8 % ) in the non-user group . CCB use significantly reduced the risk of total dementia ( aHR 0.81 , 95 % CI 0.75 - 0.87 , P<0.0001 ) , Alzheimer 's dementia ( aHR 0.80 , 95 % CI 0.72 - 0.88 , P<0.0001 ) , and vascular dementia ( aHR 0.81 , 95 % CI 0.70 - 0.94 , P=0.0067 ) . CONCLUSIONS CCB use had a protective effect on the risk of dementia among elderly hypertensive Koreans . ( Circ J 2016 ; 80 : 2336 - 2342 ) BACKGROUND High blood pressure and stroke are associated with increased risks of dementia and cognitive impairment . This study aim ed to determine whether blood pressure lowering would reduce the risks of dementia and cognitive decline among individuals with cerebrovascular disease . METHODS The Perindopril Protection Against Recurrent Stroke Study ( PROGRESS ) was a r and omized , double-blind , placebo-controlled trial conducted among 6105 people with prior stroke or transient ischemic attack . Participants were assigned to either active treatment ( perindopril for all participants and indapamide for those with neither an indication for nor a contraindication to a diuretic ) or matching placebo(s ) . The primary outcomes for these analyses were dementia ( using DSM-IV criteria ) and cognitive decline ( a decline of 3 or more points in the Mini-Mental State Examination score ) . RESULTS During a mean follow-up of 3.9 years , dementia was documented in 193 ( 6.3 % ) of the 3051 r and omized participants in the actively treated group and 217 ( 7.1 % ) of the 3054 r and omized participants in the placebo group ( relative risk reduction , 12 % [ 95 % confidence interval , -8 % to 28 % ] ; P = .2 ) . Cognitive decline occurred in 9.1 % of the actively treated group and 11.0 % of the placebo group ( risk reduction , 19 % [ 95 % confidence interval , 4 % to 32 % ] ; P = .01 ) . The risks of the composite outcomes of dementia with recurrent stroke and of cognitive decline with recurrent stroke were reduced by 34 % ( 95 % confidence interval , 3 % to 55 % ) ( P = .03 ) and 45 % ( 95 % confidence interval , 21 % to 61 % ) ( P<.001 ) , respectively , with no clear effect on either dementia or cognitive decline in the absence of recurrent stroke . CONCLUSIONS Active treatment was associated with reduced risks of dementia and cognitive decline associated with recurrent stroke . These findings further support the recommendation that blood pressure lowering with perindopril and indapamide therapy be considered for all patients with cerebrovascular disease OBJECTIVE To assess the ability of antihypertensive drug treatment to reduce the risk of nonfatal and fatal ( total ) stroke in isolated systolic hypertension . DESIGN Multicenter , r and omized , double-blind , placebo-controlled . SETTING Community-based ambulatory population in tertiary care centers . PARTICIPANTS 4736 persons ( 1.06 % ) from 447,921 screenees aged 60 years and above were r and omized ( 2365 to active treatment , 2371 to placebo ) . Systolic blood pressure ranged from 160 to 219 mm Hg and diastolic blood pressure was less than 90 mm Hg . Of the participants , 3161 were not receiving antihypertensive medication at initial contact , and 1575 were . The average systolic blood pressure was 170 mm Hg ; average diastolic blood pressure , 77 mm Hg . The mean age was 72 years , 57 % were women , and 14 % were black . INTERVENTIONS -- Participants were stratified by clinical center and by antihypertensive medication status at initial contact . For step 1 of the trial , dose 1 was chlorthalidone , 12.5 mg/d , or matching placebo ; dose 2 was 25 mg/d . For step 2 , dose 1 was atenolol , 25 mg/d , or matching placebo ; dose 2 was 50 mg/d . MAIN OUTCOME MEASURES Primary . Nonfatal and fatal ( total ) stroke . Secondary . Cardiovascular and coronary morbidity and mortality , all-cause mortality , and quality of life measures . RESULTS Average follow-up was 4.5 years . The 5-year average systolic blood pressure was 155 mm Hg for the placebo group and 143 mm Hg for the active treatment group , and the 5-year average diastolic blood pressure was 72 and 68 mm Hg , respectively . The 5-year incidence of total stroke was 5.2 per 100 participants for active treatment and 8.2 per 100 for placebo . The relative risk by proportional hazards regression analysis was 0.64 ( P = .0003 ) . For the secondary end point of clinical nonfatal myocardial infa rct ion plus coronary death , the relative risk was 0.73 . Major cardiovascular events were reduced ( relative risk , 0.68 ) . For deaths from all causes , the relative risk was 0.87 . CONCLUSION In persons aged 60 years and over with isolated systolic hypertension , antihypertensive stepped-care drug treatment with low-dose chlorthalidone as step 1 medication reduced the incidence of total stroke by 36 % , with 5-year absolute benefit of 30 events per 1000 participants . Major cardiovascular events were reduced , with 5-year absolute benefit of 55 events per 1000 BACKGROUND Dementia is a major public health problem because of its high prevalence in elderly individuals , particularly in the growing category of subjects aged 80 years or more . There is accumulating evidence that cholesterol may be implicated in the pathogenesis of dementia , and this has led us to assess the relationship between time spent with statins available and the risk of hospitalization for dementia . METHODS A population -based , nested case-control study was carried out by including the cohort of 152,729 patients from Lombardy ( Italy ) aged 40 years or older who were newly treated with statins between 2003 and 2004 . Cases were the 1380 patients who experienced hospitalization for dementia disease from initial prescription until 2010 . Up to twenty controls were r and omly selected for each case . Logistic regression was used to model the risk of dementia associated with the cumulative time during which statins were available . Monte-Carlo and rule-out sensitivity analyses were performed to account for unmeasured confounders . RESULTS Compared with patients who had very short statins coverage ( less than 6 months ) , those on 7 - 24 , 25 - 48 , and > 48 months of coverage respectively had risk reductions of 15 % ( OR : 0.85 ; 95 % CI : 0.74 to 0.98 ) , 28 % ( OR : 0.72 ; 95 % CI : 0.61 to 0.85 ) , and 25 % ( OR : 0.75 ; 95 % CI : 0.61 to 0.94 ) . Simvastatin and atorvastatin were both associated with a reduced risk of dementia , while no similar evidence was observed for fluvastatin and pravastatin . CONCLUSIONS Long-term use of statins seems effective for the prevention of dementia Statins have been reported to reduce the risk and be of benefit in the treatment of Alzheimer 's disease ( AD ) . Individuals enrolling in the r and omized controlled trial testing two anti-inflammatory agents for primary prevention of AD ( Alzheimer 's Disease Anti-inflammatory Prevention Trial ; ADAPT ) were allowed the elective use of statins . Our objective was to assess whether statin use is associated with reduced risk of incident AD among ADAPT participants . In primary ADAPT study , participants were assessed annually for cholesterol levels and cognitive status . If impairment in cognition was noted , a dementia evaluation was performed . Onset of mild cognitive impairment ( MCI ) or AD was taken as the date of this evaluation . Time-to-onset was analyzed in six-month intervals following enrollment . Without knowledge of primary treatment assignment in ADAPT , participants were grouped by their self-reported use of lipid-lowering agents ( LLA ) . In the current ancillary ADAPT study we found that elective statin use was associated with significantly reduced risk of incident AD after adjustment for age , gender , education and Apolipoprotein E ( ApoE ) genotype . The findings were similar when comparing all LLA use ( statin and non-statin LLA ) to non-LLA use . Cholesterol levels were lower among statin users compared with non-LLA users , but the MMSE scores were equivalent . The data suggest that statin therapy may be of benefit in reducing the risk of AD Objective : To determine the association between discrete antihypertensive drug classes and incident dementia controlling for blood pressure variability ( BPV ) in the preceding 4 years . Methods : A total of 6,537 participants ( mean age 79 years , 62 % women ) in a prospect i ve population -based cohort were followed up for incident dementia . A 4-year time lag period was created to classify drug exposure and measure blood pressure . BPV ( percent coefficient of variation [ CV ] ) was regressed against 9 antihypertensive drug classes ( BPVreg ) . Cox regression models were employed to determine hazard ratios ( HRs ) for incident dementia thereafter according to drug class , adjusted for mean blood pressure , covariates , and BPV or BPVreg . Results : Over a median 8.4 years follow-up ( interquartile range 6.7–9.0 ) , lower dementia risk was associated with nondihydropyridine calcium channel blocker ( HR 0.56 ; 95 % confidence interval [ CI ] 0.31–1.00 , p = 0.05 ) and loop diuretics ( HR 0.45 ; 95 % CI 0.22–0.93 , p = 0.03 ) after adjusting for CV-BPV . Similar findings were obtained in analyses restricted to antihypertensive drug users for nondihydropyridine calcium channel blocker ( HR 0.52 ; 95 % CI 0.28–0.95 , p = 0.03 ) and loop diuretics ( HR 0.40 ; 95 % CI 0.19–0.83 , p = 0.01 ) . All systolic BPV × antihypertensive drug interaction terms were not different from p < 0.05 . Conclusions : Nondihydropyridine calcium channel blocker and loop diuretics were associated with a reduced dementia risk independent of CV-BPV in the preceding 4 years . Systolic BPV was not the primary mechanism through which antihypertensive drug classes lower dementia risk Although the use of antihypertensive medications has been associated with reduced risk of Alzheimer 's disease ( AD ) , it remains unclear which class provides the most benefit . The Cache County Study of Memory Health and Aging is a prospect i ve longitudinal cohort study of dementing illnesses among the elderly population of Cache County , Utah . Using waves I to IV data of the Cache County Study , 3417 participants had a mean of 7.1 years of follow-up . Time-varying use of antihypertensive medications including different class of diuretics , angiotensin converting enzyme inhibitors , β-blockers , and calcium channel blockers was used to predict the incidence of AD using Cox proportional hazards analyses . During follow-up , 325 AD cases were ascertained with a total of 23,590 person-years . Use of any antihypertensive medication was associated with lower incidence of AD ( adjusted hazard ratio [ aHR ] , 0.77 ; 95 % confidence interval [ CI ] , 0.61 - 0.97 ) . Among different classes of antihypertensive medications , thiazide ( aHR , 0.7 ; 95 % CI , 0.53 - 0.93 ) , and potassium-sparing diuretics ( aHR , 0.69 ; 95 % CI , 0.48 - 0.99 ) were associated with the greatest reduction of AD risk . Thiazide and potassium-sparing diuretics were associated with decreased risk of AD . The inverse association of potassium-sparing diuretics confirms an earlier finding in this cohort , now with longer follow-up , and merits further investigation BACKGROUND The relation between plasma lipid levels and Alzheimer disease ( AD ) and vascular dementia ( VaD ) , and the impact of drugs to lower lipid levels remains unclear . OBJECTIVE To investigate the relation between plasma lipid levels and the risk of AD and VaD and the impact of drugs to lower lipid levels on this relationship . DESIGN AND SETTING Cross-sectional and prospect i ve community-based cohort studies . PARTICIPANTS R and om sample of 4316 Medicare recipients , 65 years and older , residing in northern Manhattan , NY . MAIN OUTCOME MEASURES Vascular dementia and AD according to st and ard criteria . RESULTS Elevated levels of non-high-density lipoprotein ( HDL-C ) and low-density lipoprotein cholesterol ( LDL-C ) and decreased levels of HDL-C were weak risk factors for VaD in either cross-sectional or prospect i ve analyses . Higher levels of total cholesterol were associated with a decreased risk of incident AD after adjustment for demographics , apolipoprotein E genotype , and cardiovascular risk factors . Treatment with drugs to lower lipid levels did not change the disease risk of either disorder . CONCLUSIONS We found a weak relation between non-HDL-C , LDL-C , and HDL-C levels and the risk of VaD. Lipid levels and the use of agents to lower them do not seem to be associated with the risk of AD OBJECTIVE To investigate the association between use of calcium channel blockers ( CCB ) , dihydropyridine ( DHP ) or nondihydropyridine ( nonDHP ) type CCB and risk of developing Alzheimer 's Disease ( AD ) or mortality . There is evidence suggesting that calcium plays a key role in changes in the brain leading to AD . Previous reports suggest a possible role for CCB in the treatment of AD . However , there are some indications that CCB increase mortality in patients with cardiac disease . METHODS Subjects were 1092 participants in the Baltimore Longitudinal Study of Aging ( BLSA ) older than 60 years of age . Data on CCB use was collected prospect ively for up to 19 years . Cox proportional hazards regression was used to estimate relative risks ( RR ) and confidence intervals ( CI ) of AD and mortality associated with use of CCB or use of only DHP or nonDHP-CCB . Analyses were adjusted for gender , education , smoking , blood pressure and history of heart problems . RESULTS Use of DHP-CCB was not associated with a significantly reduced risk of AD compared to non-users , although the estimate of the RR was low with DHP-CCB ( RR = 0.30 , 95 % CI = 0.07 - 1.25 , P = 0.10 ) . Use of nonDHP-CCB was not associated with reduced risk of AD and the estimate of the RR risk was close to one ( RR = 0.82 , 95 % CI = 0.37 - 1.83 , P = 0.63 ) . In addition , there was no increase in mortality among users of DHP-CCB ( RR = 0.64 , 95 % CI = 0.32 - 1.29 , P = 0.21 ) or nonDHP-CCB ( RR = 1.10 , 95 % CI = 0.65 - 1.87 , P = 0.72 ) . CONCLUSION Users of DHP-CCB and nonDHP-CCB in this study did not have a significantly reduced risk of AD Objective : To assess the association between statin therapy and risk of Alzheimer disease ( AD ) in a prospect i ve cohort study with documented statin exposure and incident dementia . Methods : This is a prospect i ve , cohort study of statin use and incident dementia and probable AD . A cohort of 2,356 cognitively intact persons , aged 65 and older , were r and omly selected from a health maintenance organization ( HMO ) , and were assessed biennially for dementia . Statin use was identified using the HMO pharmacy data base . A proportional hazards model with statin use as a time-dependent covariate was used to assess the statin – dementia/AD association . Results : Among 312 participants with incident dementia , 168 had probable AD . The unadjusted hazard ratios ( HRs ) with statin use were 1.33 ( 95 % CI 0.95 to 1.85 ) for all-cause dementia and 0.90 ( CI 0.54 to 1.51 ) for probable AD . Adjusted corresponding HRs were 1.19 ( CI 0.82 to 1.75 ) and 0.82 ( CI 0.46 to 1.46 ) . A subgroup analysis of participants with at least one APOE-ε4 allele who entered the study before age 80 produced an adjusted HR of 0.33 ( CI 0.10 to 1.04 ) . Conclusion : Employing time-dependent proportional hazards modeling , the authors found no significant association between statin use and incident dementia or probable AD . In contrast , when the data were analyzed , inappropriately , as a case-control study , the authors found an OR of 0.55 for probable AD , falsely indicating a protective effect of statins . Study design and analytic methods may explain the discrepancy between the current null findings and earlier findings |
12,320 | 29,741,208 | However , operative vaginal birth was more common in the inductions at < 41 weeks ' gestation subgroup compared with inductions at later gestational ages .
A policy of labour induction at or beyond term compared with expectant management is associated with fewer perinatal deaths and fewer caesarean sections ; but more operative vaginal births .
NICU admissions were lower and fewer babies had low Apgar scores with induction . | BACKGROUND Beyond term , the risks of stillbirth or neonatal death increase .
It is unclear whether a policy of labour induction can reduce these risks .
This Cochrane review is an up date of a review that was originally published in 2006 and subsequently up date d in 2012 OBJECTIVES : To assess the effects of a policy of labour induction at or beyond term compared with a policy of awaiting spontaneous labour or until an indication for birth induction of labour is identified ) on pregnancy outcomes for infant and mother . | OBJECTIVE : To compare induction of labor at gestational age 41 weeks with expectant management in regard to neonatal morbidity . Secondary aims were to assess the effect of these managements on mode of delivery and maternal complications . METHODS : Between September 2002 and July 2004 , postterm women with singleton cephalic presentation and no prelabor rupture of membranes were r and omly assigned to induction of labor at 289 days or antenatal fetal surveillance every third day until spontaneous labor . Main outcome measures were neonatal morbidity , operative delivery rates , and maternal complications . RESULTS : Five hundred eight women were r and omly assigned , 254 in each group . No differences of clinical importance were observed in women in whom labor was induced compared with women who were expectantly managed with regard to the following outcomes : neonates whose 5-minute Apgar score was less than 7 ( three neonates in the induction group compared with four in the monitoring group , P=.72 ) ; neonates whose umbilical cord pH was less than 7 ( three compared with two , P=.69 ) ; prevalence of cesarean delivery ( 28 compared with 33 , P=.50 ) ; or prevalence of operative vaginal delivery ( 32 compared with 27 , P=.49 ) . In the induction group more women had precipitate labors ( 33 compared with 12 , P<.01 ; number needed to treat was 13 ) , and the duration of second stage of labor was more often less than 15 minutes ( 94 compared with 56 , P<.01 ; number needed to treat was 7 ) . CONCLUSION : No differences were found between the induced and monitored groups regarding neonatal morbidity or mode of delivery , and the outcomes were generally good . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00385229 LEVEL OF EVIDENCE : OBJECTIVE To clarify the safety of elective induction of labor at 39 weeks of gestation . STUDY DESIGN Prospect i ve r and omized study . SUBJECTS AND METHODS Uncomplicated nulliparas ( N = 194 ) were r and omly assigned at 36 weeks of gestation . Labor was electively induced in 63 women at 39 weeks of gestation in the active management group ( I group , N = 98 ) . Spontaneous labor onset was expected with semi-weekly nonstress test ( NST ) and amniotic fluid index ( AFI ) by 42 weeks of gestation in the expectant group ( E group , N = 96 ) . Perinatal events were compared between the 2 groups . RESULTS A significantly higher incidence of meconium-stained amnios ( 19.4 % vs 3.2 % ) and fetal resuscitation ( 16.7 % vs 4.8 % ) was found in the E group than in the I group . Also , although a significantly higher incidence of epidural analgesia was noted in the I group ( 89 % ) than in the E group ( 54 % ) ( labor onset > or = 39 weeks , N = 72 ) , the duration of the 1st stage was shorter in I group and the duration of the 2nd stage was not significantly different . No other significant difference was noted between the 2 groups in terms of the rate of C-section , blood loss , incidence of pathological FHR , birth weight , Apgar score , umbilical arterial pH , or admission to NICU . CONCLUSION Active management of labor at 39 weeks could be made as safely as expectant management with modified biophysical profile monitoring OBJECTIVE Management of the uncomplicated pregnancy prolonged beyond the estimated date of confinement is controversial , particularly when the cervix is unfavorable for induction . The benefit of reducing potential fetal risk with induction of labor must be balanced against the morbidity associated with this procedure . The objective of this study was to compare two strategies for managing postterm pregnancy ( i.e. , immediate induction and expectant management ) . STUDY DESIGN Four hundred forty patients with uncomplicated pregnancies at 41 weeks ' gestation were r and omized to either immediate induction of labor ( n = 265 ) or expectant management ( n = 175 ) . Patients with expectant management underwent nonstress testing and amniotic fluid volume assessment twice per week . Patients in the induction group underwent induction within 24 hours of r and omization . To evaluate the efficacy of intracervical prostagl and in E2 gel , patients in the induction group were r and omized in a 2:1 scheme to receive either 0.5 mg prostagl and in E2 gel or placebo gel intracervically 12 hours before induction of labor with oxytocin . RESULTS The incidence of adverse perinatal outcome ( neonatal seizures , intracranial hemorrhage , the need for mechanical ventilation , or nerve injury ) was 1.5 % in the induction group and 1 % in the expectant management group ( p > 0.05 ) . There were no fetal deaths in either group . There were no differences in mean birth weight or the frequency of macrosomia ( birth weight > or = 4000 gm ) between the two groups ( p > 0.05 ) . Regardless of parity , prostagl and in E2 intracervical gel was not more effective than placebo in ripening the cervix . The cesarean delivery rate was not significantly different in the expectant ( 18 % ) , prostagl and in E2 gel ( 23 % ) , or placebo gel ( 18 % ) groups . CONCLUSIONS Adverse perinatal outcome in otherwise uncomplicated pregnancies of > or = 41 weeks is very low with either of the management schemes described . Thus from the perspective of perinatal morbidity or mortality either management scheme is acceptable In 345 women with a favorable cervical score at due date , labor was either induced by means of intravaginal application of tablets containing 3 mg of prostagl and in E2 or spontaneous onset of labor was awaited until the 42nd week of pregnancy . Eighty percent of the nulliparae and 96.3 % of the multiparae of the induction group gave birth within 24 h of the administration of the first tablet . All pertinent delivery intervals were significantly shorter in this group compared to those women where spontaneous onset of labor was awaited . The rate of operative deliveries was lower in the induction group . With the exception of 1 fetal death 3 days after due date , fetal outcome was excellent in both groups . Elective induction was at least equivalent to awaiting the onset of spontaneous labor and was not associated with higher complication rates due to the method of induction Labor characteristics after intracervical application of 0.5 mg prostagl and in ( PG ) E2 gel ( n = 83 ) versus intravenous administration of oxytocin ( n = 82 ) for labor induction were investigated in uncomplicated prolonged pregnancies with unripe cervix . The induction to delivery time as well as the total oxytocin dose were significantly reduced in the PGE2 group ( p < 0.001 ) . Cesarean sections , instrumental deliveries and fetal distress had the same frequency , but the failures of trial were significantly higher in the oxytocin group than in the PGE2 group ( 20.7 vs. 6 % , p < 0.01 ) . Twenty-four percent of women needed a second PGE2 dose , and almost half of the women in the PGE2 group experienced ' spontaneous ' labor . More neonates in the oxytocin group had 5-min Apgar scores < 7 ( p < 0.05 ) . Intracervical PGE2 gel application is superior to intravenous oxytocin in terms of shortening the induction-delivery interval and increasing the frequency of successful vaginal delivery . In addition , it is safe for mother and fetus Two hundred consecutive women with uncomplicated pregnancies , at or within 4 days of their expected date of confinement , were prospect ively r and omized into 2 groups . One group had expectant management , with twice weekly surveillance tests , while the other group had 3 mg of vaginal prostagl and in E2 as outpatient treatment . There were 104 women in the expectant group and 70 in the induction group ( 26 women allocated to induction preferred no treatment ) . The average number of days to delivery was 1.6 in the induction group and 5.2 in the expectant group ( p < 0.001 ) . While meconium was much less frequent in the induction group ( p < 0.002 ) , all other outcome measures , including cesarean section rates , incidence of macrosomia , and Apgar scores , were similar in the two groups A prospect i ve r and omized controlled trial design ed to investigate selective planned delivery is reported : 264 obstetrically normal women in the 38th week of pregnancy were admitted to this trial and 184 completed it . The infants of mothers in the planned delivery group had higher serum bilirubin levels on the fifth day post partum than control infants but no baby required treatment for hyperbilirubinaemia . Mothers in the planned delivery group required significantly greater amounts of pethidine while control mothers had a significantly higher incidence of meconium staining of the amniotic fluid . However , the infants in the two groups had similar Apgar scores at birth . There was one stillbirth in the control group ; this was due to unrecognized fetal hypoxia during labour induced at 42 weeks for postmaturity In a prospect i ve r and omized study , pregnancies with unfavorable cervix and well established gestational age of at least 42 weeks were selected for management by either antepartum fetal testing or prostagl and in gel induction of labor . Of the 108 pregnancies studied , 57 ( 53 % ) had labor induced and 51 ( 47 % ) continued without intervention . Comparison of the two groups showed no difference in meconium staining , fetal distress , length of first stage of labor , the need for intervention , or the mode of delivery . In terms of Apgar score the neonatal outcome was not significantly different but a greater proportion of the babies ( 7.8 % versus 1.8 % ) in the noninduced group required intubation . Our data show that there is no particular advantage in letting the pregnancy go beyond 42 completed weeks of gestation especially if prostagl and in is available for induction of labor OBJECTIVE To study the cesarean rate between expectant management and immediate induction in the otherwise uncomplicated postterm pregnancy with favorable cervix . STUDY DESIGN A total of 249 women with uncomplicated pregnancies at 41 weeks plus 3 days ( 290 days ) with favorable cervix ( Bishop score > or = 6 ) were r and omized to either expectant management ( n=125 ) or immediate induction of labor ( n=124 ) . The women in the induction group were sent to labor ward for induction by artificial rupture of membranes ( ARM ) and /or oxytocin infusion . The women with expectant management had nonstress test ( NST ) and amniotic fluid index ( AFI ) performed once a week and twice a week after 43 weeks of gestation until spontaneous labor . RESULTS The cesarean rate was not different between expectant management and immediate induction ( 21.6 % versus 26.6 % ; P=0.36 ) . Ninety-five percent of the expectant group delivered within 1 week after enrollment , and all of them delivered within 9 days after r and omization . Maternal and fetal complications in both groups were not different . There was also no difference in the mean birth weight ( P=0.24 ) and the frequency of macrosomia ( birth weight > or = 4000 g ) between the two groups ( P=0.23 ) . CONCLUSION Cesarean section rate between expectant management and immediate induction in the otherwise uncomplicated postterm pregnancy with favorable cervix was not different . Due to the very low adverse perinatal outcome , both expectant management and immediate induction are acceptable Objecfive To determine the proper management of pregnancy in uncomplicated cases going beyond 42 weeks Objective To assess the efficacy of sweeping of membranes beyond 40 weeks of gestation in reducing the incidence of induction of labour , when induction was planned at 42 weeks Background British women are increasingly delaying childbirth . The proportion giving birth over the age of 35 rose from 12 % in 1996 to 20 % in 2006 . Women over this age are at a higher risk of perinatal death , and antepartum stillbirth accounts for 61 % of all such deaths . Women over 40 years old have a similar stillbirth risk at 39 weeks as women who are between 25 and 29 years old have at 41 weeks . Many obstetricians respond to this by suggesting labour induction at term to forestall some of the risk . In a national survey of obstetricians 37 % already induce women aged 40–44 years . A substantial minority of parents support such a policy , but others do not on the grounds that it might increase the risk of Caesarean section . However trials of induction in other high-risk scenarios have not shown any increase in Caesarean sections , rather the reverse . If induction for women over 35 did not increase Caesareans , or even reduced them , it would plausibly improve perinatal outcome and be an acceptable intervention . We therefore plan to perform a trial to test the effect of such an induction policy on Caesarean section rates . This trial is funded by the NHS Research for Patient Benefit ( RfPB ) Programme . Design The 35/39 trial is a multi-centre , prospect i ve , r and omised controlled trial . It is being run in twenty UK centres and we aim to recruit 630 nulliparous women ( 315 per group ) aged over 35 years of age , over two years . Women will be r and omly allocated to one of two groups : Induction of labour between 390/7 and 396/7weeks gestation . Expectant management i.e. awaiting spontaneous onset of labour unless a situation develops necessitating either induction of labour or Caesarean Section . The primary purpose of this trial is to establish what effect a policy of induction of labour at 39 weeks for nulliparous women of advanced maternal age has on the rate of Caesarean section deliveries . The secondary aim is to act as a pilot study for a trial to answer the question , does induction of labour in this group of women improve perinatal outcomes ? R and omisation will occur at 360/7 – 396/7 weeks gestation via a computerised r and omisation programme at the Clinical Trials Unit , University of Nottingham . There will be no blinding to treatment allocation . Discussion The 35/39 trial is powered to detect an effect of induction of labour on the risk of caesarean section , it is underpowered to determine whether it improves perinatal outcome . The current study will also act as a pilot for a larger study to address this question .Trial registration IS RCT CONTEXT Despite wide use of castor oil to initiate labor , the obstetric literature contains few references to this botanical laxative . Derived from the castor plant Ricinus communis , castor oil may possess properties that are useful in post-term pregnancies . OBJECTIVE To evaluate the relationship between the use of castor oil and the onset of labor . DESIGN Prospect i ve evaluation . SETTING A community hospital in Brooklyn , NY . PATIENTS A total of 103 singleton pregnancies with intact membranes at 40 to 42 weeks referred for antepartum testing . Inclusion criteria included cervical examination , Bishop score of 4 or less , and no evidence of regular uterine contractions . INTERVENTION Patients were alternately assigned to 1 of 2 study groups : a single oral dose of castor oil ( 60 mL ) or no treatment . MAIN OUTCOME MEASURES Castor oil was considered successful if labor began within 24 hours after dosing . Groups were compared for onset of labor in 24 hours , method of delivery , presence of meconium-stained amniotic fluid , Apgar score , and birth weight . RESULTS Fifty-two women received castor oil and 48 were assigned no treatment . Following administration of castor oil , 30 of 52 women ( 57.7 % ) began active labor compared to 2 of 48 ( 4.2 % ) receiving no treatment . When castor oil was successful , 83.3 % ( 25/30 ) of the women delivered vaginally . CONCLUSIONS Women who receive castor oil have an increased likelihood of initiation of labor within 24 hours compared to women who receive no treatment . Castor oil use in pregnancy is underreported worldwide . This small series represents the first attempt to evaluate the medication Abstract . In a prospect i ve r and omized study spontaneous and oxytocin induced labor “ for convenience ” have been compared with respect to uterine activity , duration of labor , the condition of the fetus and the newborn infant . The study consists of 84 normal patients , of whom 43 were induced at full term by amniotomy and oxytocin infusion using the Cardiff Infusion System Mark II ; 41 patients served as controls . No difference in maternal age , number of previous pregnancies and pelvic score one week before the day of delivery were found between the groups . The following parameters were calculated : duration of labor , uterine activity , amount of bleeding in the third stage of labor , number of early and late decelerations as well as number of episodes of bradycardia in the CTG‐recordings , birth weight , Apgar score one and five minutes post‐delivery and blood gases in mother and child 60 seconds after delivery . No significant differences between the two groups were found . It is concluded that there are no increased risks to mother or fetus compared to normal labor provided that there is cephalic presentation and normal pregnancy , careful selection with respect to the length of pregnancy and the condition of the cervix and that the Cardiff infusion system is used with intrauterine pressure recording and continuous fetal heart monitoring BACKGROUND Several r and omized , controlled trials compared the policies of induction of labor and expectant management for women who reach 41 weeks ' gestation , and although they suggest a better outcome for mothers and infants with such a policy in place , controversy continues as to which is the better form of care . The Canadian Multicenter Postterm Pregnancy Trial ( CMPPT ) enrolled 3407 women , of whom 1701 were r and omized to a policy of induction of labor ( induced group ) and 1706 were r and omized to a policy of expectant management ( expectant group ) . Secondary analyses of data from the CMPPT were undertaken to explore a number of controversial issues . METHODS We used data from the CMPPT to explore further the timing of delivery for women enrolled between 41 0/7 and 41 6/7 weeks ' gestation , the potential impact of more liberal use of prostagl and ins on cesarean section rates , and the relative merits of induced versus spontaneous labor in the two groups . RESULTS Most women in the CMPPT ( 89 % ) were enrolled at 41 0/7 to 41 6/7 weeks ' gestation , of whom 86.2 percent in the induced group and 63.6 percent in the expectant group gave birth before 42 weeks ' gestation . Assuming that administration of prostagl and ins would reduce the likelihood of cesarean section by 12 to 15 percent , cesarean section rates were reduced in the induction group from 21.2 percent to 20.8 to 20.9 percent , and in the expectant group from 24.5 percent 23.3 to 24.2 percent . If labor was induced as part of a policy of expectant management , the cesarean section rate was much higher ( 33.5 % ) than if labor was either spontaneous or induced as part of a policy of induction ( 18.5 % , 22.4 % ) . CONCLUSIONS Women should be informed of the benefits and risks associated with the policies of induction of labor and expectant management , and their preferences regarding these policies should be respected CONTEXT Misoprostol , a synthetic E1 methyl analog prostagl and in , is at present receiving attention as a cervical modifier and labor induction agent . However , there is still a need for better determination of its safety and effectiveness . OBJECTIVE To compare intravaginal misoprostol versus intravenous oxytocin for cervical ripening and labor induction in pregnant women with unripe cervices . DESIGN R and omized controlled trial . SETTING The study was performed at the Leonor Mendes de Barros Maternity Hospital between November 1998 and December 2000 . PARTICIPANTS 210 pregnant women with intact membranes and indication for labor induction were selected . PROCEDURES The women r and omly received 25 g of vaginal misoprostol every 4 hours , not exceeding 8 doses ( 105 women ) , or oxytocin in a continuous infusion ( 105 women ) . MAIN MEASUREMENTS The main parameters measured were : latent period , time from induction to vaginal delivery , delivery route , occurrence of vaginal delivery with time , occurrence of uterine tonus alterations , hypoxia and neonatal morbidity . To verify the statistical significance of the differences between the groups , the chi-squared , Student t and log-rank tests were used . RESULTS There were no significant differences between the groups concerning conditions for labor induction , age , parity , race , marital status , family income , initial Bishop Index and number of prenatal visits . The cesarean section rate , latent period and period from induction to vaginal delivery were significantly lower for the misoprostol group . With regard to uterine tonus alterations , tachysystole was significantly more common in the misoprostol group . However , there was no difference in hypoxia and neonatal morbidity between the groups . CONCLUSION 25 g of misoprostol used vaginally every 4 hours is safer and more efficient for cervical ripening and labor induction than oxytocin Traditionally pregnancy has been considered ‘ post-term ’ at 42 completed weeks of gestation . At this gestation , if the cervix is unfavourable , debate over best practice has been between routine induction of labour and expectant management with some form of serial fetal monitoring . Popular wisdom seems to be that meta- analysis of the available r and omised controlled trials has settled the question in favour of routine induction . The largest included trial , containing over half the cases ( n 1⁄4 3407 ) , was carried out in Canada and published in 1992 . The results of the meta- analysis led the Society of Obstetricians and Gynaecologists of Canada ( SOGC ) to issue Clinical Practice Guidelines in 1997 . The guidelines recommended that : 1 . after 41 completed weeks of gestation , if the date s are certain , women should be offered elective delivery ; 2 . if the cervix is unfavourable , ripening should be undertaken ; and 3 . if expectant management is chosen , assessment of fetal health should be initiated . It is presumed that r and omised controlled trials or , even better , meta-analyses of r and omised trials , provide the best evidence to determine appropriate care . However , once information has been declared ‘ the best available evidence ’ , particularly if that assertion is used to justify clinical practice guidelines or ‘ consensus ’ , further inquiry may be inhibited . Since it is implied that ‘ the answers are all in ’ , mutation from clinical practice guideline to st and ard of care is prompt and uncomplicated , particularly if the labels ‘ consensus ’ or ‘ policy statement ’ are used between the two as conceptual mutagens . The st and ard of care in Canada now is assumed to be routine induction at 41 weeks . This commentary is intended to give pause to those who have accepted and adopted this st and ard OBJECTIVE Within the obstetric community , several studies suggest that cervical ripening and labor induction after 40 weeks ' gestation leads to improved maternal and neonatal outcomes . The most effective drug regimen to safely promote labor has not been determined . METHOD Forty-nine subjects followed in an outpatient obstetrical clinic with pregnancies of at least 40 weeks ' gestation , and an unfavorable Bishop score were assigned r and omly to receive oral misoprostol 50 or 25 microg every 3 days for a maximum of three doses . RESULTS Twenty-three subjects received misoprostol 25 microg and 26 received 50 microg . The mean interval ( + /-st and ard deviation ) from start of cervical ripening to delivery was 2.4 days + /-0.3 vs. 3.9 days + /-0.7 for the 50 and 25 microg groups ( P<0.05 ) . No adverse events were noted . However , due to small sample size , less frequent adverse events may be missed . Type II errors can not be excluded . CONCLUSION In the prevention of post date pregnancy , out patients use of oral misoprostol 50 microg appears to result in earlier delivery , as compared to 25 microg The effect of induction of labor on the neonatal bilirubin levels was investigated in a prospect i ve r and omized study . Forty‐three infants born after elective induction with oxytocin using the Cardiff infusion system and 38 infants born after spontaneous delivery were studied . Several factors other than oxytocin administration which could influence the bilirubin levels such as gestational age , placental transfusion and feeding routines did not differ between the two groups . There were no differences with regard to pH in umbilical vein , Apgar scores , haemoglobin and erythrocyte volume fractions or bilirubin levels neonatally . Thus there was no evidence of an association between induction of labor with oxytocin and jaundice during the neonatal period BACKGROUND The two methods of management of prolonged pregnancy , induction of labour and expectant management with foetal surveillance , have pros and cons . Therefore , we compared the induction of labour with serial antenatal foetal monitoring in the management of post-term pregnancy . METHODS Seventy-four women with uncomplicated pregnancy at 41 weeks ( 287 days ) of gestation were r and omly assigned to undergo either induction of labour or serial antenatal foetal monitoring . Labour was induced in the latter group whenever there was evidence of foetal compromise . Antenatal monitoring consisted of the foetal kick count , non-stress test and biophysical profile . RESULTS Fifty-seven per cent of women went into spontaneous labour by 41 weeks and 4 days ( 291 days ) of gestation and only 14 % developed foetal compromise before that . However , when the gestational age was more than 41 weeks and 4 days ( 291 days ) , the incidence of meconium staining of amniotic fluid and evidence of uteroplacental insufficiency increased significantly . The rate of caesarean section , instrumental delivery , foetal distress and duration of labour did not differ significantly between the two groups . CONCLUSION The policy of inducing labour at 41 weeks and 4 days ( 291 days of gestation ) in uncomplicated pregnancies is justified in our population . However , foetal monitoring should begin at 41 weeks of gestation Abstract Our purpose was to examine the hypothesis that corticosteroids , when administered intramuscularly , can enhance the labor process and reduce the time interval between the induction and the active phase . A r and omized , controlled study was conducted on 66 women with gestational age of 41 weeks and over and favorable cervix ( bishop score ≥ 7 ) . The study group ( n = 32 ) received 10 mg of dexamethasone phosphate intramuscularly in two doses at an interval of 12 hours , and the day after the enrolling administration intravenous oxytocin was given . The control group ( n = 33 ) received only intravenous oxytocin 24 hours after enrolling . The number of patients to enter the active phase of labor was significantly higher in the study group than in the control group ( n = 33 [ 100 % ] vs n = 29 [ 87.9 % ] , p < 0.039 ) . The mean time interval between induction of labor and the active phase was significantly shorter in the study group than in the control group ( 1.7±1.5 hours vs 4±1.7 , P < 0.0001 ) , and the mean of oxytocin dose was significantly lower in the study group ( 1.15±1.5u vs 4.16±2.5u , P < 0.0001 ) . Induction of labor with the use of intramuscularly injected dexamethasone phosphate reduced the time interval between the induction of labor and the active phase A double-blind , placebo-controlled , prospect i ve investigation was undertaken to determine whether the outpatient administration of prostagl and in E2 gel was helpful for ripening the cervix in post date pregnancies . One hundred eighteen women with an uncomplicated pregnancy at or beyond 42 weeks ' gestation with an unripe cervix ( Bishop score less than or equal to 5 ) were r and omly administered a single dose of gel containing either 2.5 mg prostagl and in E2 ( n = 55 ) or a placebo ( n = 63 ) before induction of labor with Pitocin . No side effects were detected in these healthy mothers and fetuses . A distinct change in Bishop score after 12 hours occurred more often in the prostagl and in E2 than in the placebo group ( 42 % versus 6 % , p less than 0.0001 ) . Forty-four women ( 80 % ) who had received prostagl and in E2 were admitted in early labor ; they required little or no oxytocin for augmentation . The duration of labor and maximum dose of oxytocin infused were significantly decreased in the prostagl and in E2 group , and forceps delivery or primary cesarean sections were performed less often when prostagl and in E2 was used ( 24 % versus 44 % , p less than 0.05 ) . The outpatient administration of a single dose of prostagl and in E2 gel is safe in the uncomplicated post date pregnancy and was found to significantly change the unripe cervix , enhance the onset of labor , minimize the need for oxytocin administration , and encourage a spontaneous vaginal delivery OBJECTIVE To compare the obstetric outcome of induction of labor at 41 weeks and of follow-up until 42 weeks and induction if the patient has still not given birth at 42 weeks . STUDY DESIGN Six hundred women at 287+/-1 days of gestation with definitely unfavorable cervical scores were r and omized to labor induction ( N=300 ) or spontaneous follow-up ( N=300 ) with twice-weekly nonstress testing and amniotic fluid measurement and once-weekly biophysical scoring . The treatments used in the induction group were ( 1 ) vaginal administration of 50 microg misoprostol ( n=100 ) , ( 2 ) oxytocin induction ( n=100 ) , and ( 3 ) transcervical insertion of a Foley balloon ( n=100 ) . The primary outcome measures were the cesarean delivery rate , whether or not the normal hospital stay had to be extended , and the neonatal outcomes . Secondary outcome measure included number of emergency cesarean deliveries performed for abnormalities of the fetal heart rate ( FHR ) . RESULTS The abdominal delivery rate was 19.3 % in the induction group and 22 % in the follow-up group ( p=0.4 ) . The mean length of hospital stay in the two main groups was 1.4+/-0.8 days and 1.3+/-1 days , respectively ( p=0.1 ) . Significantly higher rates of macrosomia and shoulder dystocia were seen in the follow-up group ( 24.6 and 2.3 % ) than in the induction group ( 7.6 % , p<0.001 ; 0.3 % , p=0.03 ) . Meconium-stained amniotic fluid and meconium aspiration syndrome were observed significantly less frequently in the induction group ( 9.3 and 1.3 % ) than in the follow-up group ( 20.3 % , p<0.001 ; 4 % , p=0.03 ) . Rates of emergency abdominal delivery in response to worrying FHR traces , neonatal intensive care unit admission , and low umblical artery pH were similar in the two groups . There was one intrauterine fetal death in the follow-up group . CONCLUSION Induction of labor at 41 weeks of gestation does not increase the cesarean delivery rate or cause a longer stay in hospital than follow-up until 42 weeks , and neonatal morbidity is also lower after induction Recent experience has suggested that porcine ovarian relaxin may promote cervical changes . We have performed two double-blind r and omized studies : ( 1 ) comparing cervical changes with relaxin versus placebo during oxytocic labor induction and ( 2 ) as out patients in post date s pregnancies . In the induction study , cervical changes were speeded up by both 2 and 4 mg doses of relaxin , and times to delivery were decreased . In the outpatient study , 2 mg doses of relaxin produced greater cervical changes than did control or 4 mg doses . We conclude that relaxin may have benefit in ripening of the cervix . Since relaxin works directly on the cervix and not through uterine contractions , relaxin may have advantages in cervical ripening of pregnancies in which stress to the fetus is an issue OBJECTIVE Our purpose was to determine the optimal management of pregnancies beyond 41 weeks ' gestation with a cervix unfavorable for induction . STUDY DESIGN All uncomplicated pregnancies that reached 41 weeks ' gestation with a Bishop score of < or = 4 were r and omly assigned to one of three groups : ( 1 ) daily cervical examinations , ( 2 ) daily membrane stripping , or ( 3 ) daily placement of prostagl and in gel until 42 weeks . RESULTS In 105 pregnancies the Bishop score on admission to labor and delivery was significantly greater in the groups receiving prostagl and in or stripping of the membranes versus the control group , whereas the converse was time of gestational age at delivery ( p = 0.0001 ) . Fewer patients required induction in the two treatment groups ( 20 % , 17 % ) versus the control ( 69 % ) patients ( p < 0.0001 ) . CONCLUSIONS Daily membrane stripping or daily placement of prostagl and in gel is successful in reducing the number of inductions at 42 weeks for postdatism The effects of oestriol sulphate on myometrial activity in a group of young primigravidae , who were at 41 or more weeks ' gestation , are compared with those of a placebo in a double-blind trial . Both compounds were administered over a period of six hours directly into the uterine cavity following artificial rupture of membranes . Intra-amniotic pressure recordings demonstrated a peak in the mean intensity in uterine contractions in the oestriol-treated and placebo-treated groups at six and four hours , respectively . The length of labour tended to be shorter in those patients having greater uterine activity Objective : To shorten post- date pregnancies in a safe , effective manner by outpatient acceleration of cervical ripening . Methods : Eighty patients with uncomplicated pregnancies at or beyond 41 weeks ' gestation and a cervical Bishop score less than 9 were r and omized to daily self-administered , 2-mg intravaginal prostagl and in E2 ( PGE2 ) or placebo suppositories . Each followed a st and ard post- date antepartum surveillance protocol . Patients were admitted for spontaneous labor or for induction if the Bishop score reached 9 , antepartum testing was nonreassuring , exclusion criteria were fulfilled , or if the gestational age reached 44 weeks . Results : Fewer suppositories were used in the PGE2 group ( four versus seven ; P=.006 ) , result ing in earlier gestational age on admission ( 295 versus 297 days ; P=.021 ) and lower antepartum testing charges ( $ 476.97 versus $ 647.29 ; P=.001 ) . Labor and delivery time was significantly decreased in nulliparas ( 10.7 ± 5.1 versus 15.3 ± 7.6 hours ; P=.035 ) . Conclusions : Daily low-dose , patient-administered PGE2 vaginal suppositories can decrease the gestational length and cost of uncomplicated post- date pregnancies by reducing the time to achieve a favorable cervix , the need for antepartum testing , and , potentially , post- date -related complications In a prospect i ve , r and omised trial , 111 obstetrically normal pregnant women , who had elective induction of labour performed between 39 and 40 weeks , were compared with 117 controls who were managed expectantly until 41 weeks . Compared with the controls , the patients who had elective induction of labour had significantly less meconium staining in labour and a smaller blood-loss after delivery . The mean length of labour , the amount of pethidine used , and the Apgar scores at 1 minute were similar in the two groups . In the electively induced group , the caesarean-section rate was lower and the use of epidural analgesia more common than in the controls , but the differences were mot statistically signficant . The hour of delivery was similar in the two groups , suggesting that convenience to medical and nursing staff would not be greatly changed by elective induction of labour . There was no evidence that the hazards to mother and child were increased by elective induction , and its use might improve perinatal mortality by reducing the number of unexplained mature stillbirths OBJECTIVE To evaluate the efficacy of mifepristone in inducing labor in women with an unripe cervix , its effect on the cervix and on the status of the newborn . METHODS In a prospect i ve double-blind study , 36 post-term pregnant women with a Bishop score of 5 or less received either 400 mg mifepristone ( n=24 ) or placebo ( n=12 ) . If , 48 hours after the treatment was started , labor had not begun or the Bishop score was 5 or less , the women were given 0.5 mg prostagl and in E2 intracervically , a treatment which was repeated 12 hours later , if necessary . RESULTS During the first 48 hours following treatment , 19 ( 79.2 % ) of the women treated with mifepristone and two of the women ( 16.7 % ) treated with placebo went into labor . In addition , one and three women , respectively , had a ripe cervix at the end of the 48h period . The overall success rate was thus 83.3 % for mifepristone and 41.7 % for placebo ( p=0.008 ; OR 14.8 ; 95 % CI 2.1 - 107.6 ) . The median time from the start of treatment to delivery was also shorter ( mifepristone 36h23 ' and placebo 53h17 ' ) . Treatment with intracervical PGE2 was needed more often after the placebo . The duration of labor , however , tended to be shorter after placebo than after mifepristone in the women who delivered vaginally . The frequencies of instrumental delivery were similar in both treatment groups . The median Apgar score was slightly lower at 1 minute ( p<0.05 ) following mifepristone treatment , but did not differ at 5 and 10 minutes . There was no difference between the two treatment groups in the umbilical pH at delivery . CONCLUSION The results of the present study show that mifepristone is a simple and effective treatment for inducing labor in post-term women with an unripe cervix OBJECTIVE The purpose of this study was to compare birth outcomes that result from the active management of risk in pregnancy at term ( AMOR-IPAT ) to those outcomes that result from st and ard management . STUDY DESIGN This was a r and omized clinical trial with 270 women of mixed parity . AMOR-IPAT used preventive labor induction to ensure delivery before the end of an estimated optimal time of delivery . Rates of 4 adverse obstetric events and 2 composite measures were used to evaluate birth outcomes . RESULTS The AMOR-IPAT-exposed group had a similar cesarean delivery rate ( 10.3 % vs 14.9 % ; P = .25 ) , but a lower neonatal intensive care unit admission rate ( 1.5 % vs 6.7 % ; P = .03 ) , a higher uncomplicated vaginal birth rate ( 73.5 % vs 62.8 % ; P = .046 ) , and a lower mean Adverse Outcome Index score ( 1.4 vs 8.6 ; P = .03 ) . CONCLUSION AMOR-IPAT exposure improved the pattern of birth outcomes . Larger r and omized clinical trials are needed to explore further the impact of AMOR-IPAT on birth outcomes and to determine the best methods of preventive labor induction OBJECTIVE To compare the clinical effectiveness and safety of outpatient administration of intracervical prostagl and in ( PG ) E2 gel with expectant treatment for women desiring vaginal births after cesareans . METHODS This was a r and omized , multicenter investigation involving term pregnant women who each had one previous low-transverse cesarean and an unfavorable cervix ( Bishop score no more than 6 ) , and who was a c and i date for vaginal delivery . They were assigned to receive 0.5 mg of PGE2 , ( Prepidil ; Pharmacia-Upjohn , Kalamazoo , MI ) intracervically at 39 weeks ' gestation , repeated at weekly office visits for up to three doses , or expectant treatment . The main outcome variable was vaginal birth . RESULTS Of 294 cases , 143 received gel and 151 were treated expectantly . No differences between groups were found for maternal age , race , or Bishop score . Compared with the expectant treatment group , the PGE2 gel group was not more likely to deliver sooner or vaginally ( 57 % versus 55 % , P = .68 ) . The onset of labor , duration of labor among those delivering vaginally , and 1- and 5-minute Apgar scores were not different between groups . No uterine ruptures occurred , and adverse effects were equally likely in both groups . CONCLUSION Although its safety was confirmed for outpatient use , weekly doses of intracervical PGE2 did not improve the likelihood of vaginal births after cesareans OBJECTIVE To examine the misoprostol efficacy and safety in induction of labor of women with severe preeclampsia at or near term when the cervix is unfavorable . METHODS A prospect i ve comparative study was conducted in Al-Thawara General Hospital Sana'a , Yemen , from June 2009 to June 2010 . One hundred and thirteen women met the inclusion criteria . They were divided into 2 groups . The study group ( n = 56 ) and the control group ( n = 57 ) . The study group were given 50 μg of Misoprostol intravaginally every 4 hours to a maximum of 6 doses . Maternal age , gestational age , parity , initial cervical status , the rate of cesarean section , and neonatal outcomes were analyzed and compared to the control group . RESULTS The vaginal delivery was achieved in 69.6 % in the study group versus 15.8 % in the control group ( p < 0.0001 ) . The overall cesarean section was performed in 30.3 % of the study group versus 84.2 % ( p < 0.0001 ) . The mean time from insertion to delivery was 12.12 + /- 2.1 hours and the mean dosing was 2.77+/-1.3 . There were no significant differences between the 2 groups in the frequency of abnormal fetal heart rate , Apgar score and admission to the neonatal intensive care unit . CONCLUSION Misoprostol when given intravaginally in 50 mcg 4-hourly dosing regimen is an effective agent for ripening the cervix in this group of women Background . Clinical guidelines for post‐term management differ , and studies on women 's attitudes are lacking . We aim ed to assess the experiences and attitudes among women managed with serial antenatal monitoring or induction of labor , and the effects of post‐term pregnancy on self‐reports of quality of life . Methods . Women were r and omized at 41weeks to immediate induction of labor or antenatal fetal surveillance every third day . At inclusion women answered a question naire about their attitudes towards post‐term pregnancy and health‐related quality of life . This was repeated in a follow‐up phone interview 6months later , including questions about their experiences of labor and perspective on future deliveries . Results . A total of 508women entered the study . At 41weeks 74 % of all women preferred to be induced . Women reported good general and mental health , but physical health and vitality scores were low . In the induction group , 74 % of women said they would prefer the same management in future pregnancies ; only 38 % of women who had serial antenatal monitoring would prefer this option again ( p<0.001 ) . In the induction group , contractions were reported as more intense ( n = 157 versus n = 118 , p<0.01 ) and frequent ( n = 116 versus n = 87 , p<0.01 ) compared to the monitored group . The majority ( 84 % ) reported a positive labor induction experience . Conclusion . Women preferred induction of labor to serial antenatal monitoring beyond 41weeks . Labors were shorter and contractions were reported to be more frequent and intense in the induction group compared with the monitored group . However , their experience with labor induction was positive OBJECTIVES To compare expectant management with early induction of labour in pregnant patients with prelabour rupture of membranes at term and unfavourable cervix . STUDY DESIGN A prospect i ve , r and omised study of 154 women with prelabour rupture of membranes at term of whom 80 had been managed expectantly , and 74 had undergone oxytocin induction at a rate of 2.5 mU/min . Digital examination was not performed before oxytocin infusion , and the first was delayed until 4 h ( nulliparae ) , or 2 h ( multiparae ) of regular uterine contractions . RESULTS The mean period from rupture of membranes to delivery was significantly shorter in the induction group . The mean duration of labour was significantly shorter in the expectant group . Operative vaginal deliveries were more common in the induction group , and fetal distress was the most common cause of operative vaginal deliveries . The caesarean rates were low and similar in both groups . Maternal and neonatal infectious morbidity was similar and no difference was found in the length of hospitalisation . CONCLUSIONS Expectant management in patients with ruptured membranes at term is safe and reduces the frequency of operative vaginal deliveries OBJECTIVE To determine maternal and perinatal morbidity and the spontaneous labor rate beyond 41 weeks of gestation . METHOD Patients with uncomplicated pregnancy were recruited at 41 weeks and screened for fetal or maternal well-being . Following observation between 41 and 42 weeks , patients were r and omized to either serial monitoring by cardiotocography and measurement of amniotic fluid index , or to immediate induction . Comparisons were made using the chi(2 ) test . Results after 42 weeks were analyzed according to intention at r and omization . RESULTS Morbidity was not increased before 42 weeks . After 42 weeks , the cesarean section rate and incidence of meconium below the vocal cords were increased in monitored patients . The median gestational age in patients who were monitored was 298.5 ( 294 - 321 ) days . In patients observed from 41 weeks , 91.6 % labored spontaneously . CONCLUSION It is reasonable to observe uncomplicated pregnancy until 42 weeks with adequate monitoring . After 42 weeks , induction of labor is preferred Objective . To determine if elective induction ( IND ) increases the risk of cesarean delivery compared to expectant management ( EM ) . Methods . A r and omized clinical trial involving women ⩾39 weeks ' gestation , according to strict dating criteria , with a Bishop score of 5 or more in nulliparous patients and 4 or more in multiparous patients . The control group was expectantly managed and delivered for obstetric indications , but not later than 42 weeks ' gestation . The study had 80 % power to detect a three-fold increase in cesarean delivery . Results . One-hundred- and -sixteen patients ( 45 nulliparous ) were r and omized to IND and 110 ( 58 nulliparous ) to EM . Demographic characteristics were no different between the groups . The cesarean delivery rate in the IND group was 6.9 % ( 8/116 ) compared to 7.3 % ( 8/110 ) in the EM group ( p = NS ) . Rates of cesarean delivery for nulliparous patients r and omized to IND compared to EM were also not significantly different : 13.3 % ( 6/45 ) versus 10.3 % ( 6/58 ) respectively ( p = NS ) . Neonates delivered of IND patients weighed less than those of the EM group ( 3459 ± 347 versus 3604 ± 438 , p = 0.006 ) . Conclusion . In women with favorable Bishop scores , elective induction of labor result ed in no increase in cesarean delivery compared to expectant management A r and omized blinded investigation was undertaken to determine the efficacy and safety of sequentially applied intravaginal prostagl and in E2 ( PGE2 ) gel for accelerating cervical ripening in an outpatient setting in low-risk prolonged pregnancies . Fifty women with uncomplicated pregnancies at or beyond 41 weeks ' gestation and Bishop scores below 9 received twice-weekly outpatient administration of gel containing 2.0 mg of PGE2 or placebo . Thirty nulliparas and 20 multiparas were enrolled . The PGE2 gel failed to improve cervical ripening over placebo , as judged by Bishop scores . There was no difference between the groups in gestational age on admission to the labor and delivery suite , number of gel applications , requirement for oxytocin , incidence of cesarean delivery , or neonatal outcome . Only two patients ( 4 % ) experienced regular uterine contractions after gel insertion ; these subsided spontaneously in both . None of the subjects experienced labor , tetanic contractions , evidence of fetal distress , or any other side effects related to gel insertion . We conclude that PGE2 gel in this dosage may be used safely in an outpatient setting , but more frequent application or earlier initiation may be required to produce a clinical Objective To compare the effect of mifepristone with placebo on cervical ripening before labor induction in prolonged pregnancies . Methods One hundred eighty women with pregnancies beyond 41 weeks and undilated , uneffaced cervices were assigned r and omly to receive mifepristone 200 mg or placebo and observed for 24 hours . We then gave intravaginal misoprostol 25 μg every 4 hours or intravenous oxytocin . We expected 60 % of placebo-treated and 80 % of mifepristone-treated women to deliver vaginally within 48 hours . Results Among 180 subjects , 97 received mifepristone and 83 received placebo . The mean interval ( ± st and ard deviation [ SD ] ) from start of induction to delivery was 2209 ± 698 minutes for mifepristone-treated subjects and 2671 ± 884 minutes for placebo-treated subjects ( P < .001 , log-transformed data ) . Twelve ( 13.6 % ) mifepristone-treated women and seven ( 10.8 % ) placebo-treated women delivered vaginally on day 1 ( P = .60 ) . After 24 hours , the median Bishop score for both groups was 3 ( 0–11 ) ( P = .51 ) . One hundred thirty-one subjects required misoprostol , 65 ( 67.0 % ) were mifepristone-treated women , and 66 ( 79.5 % ) placebo-treated women ( P = .06 ) . The median ( range ) oxytocin dose was 871.5 ( 0–22,174 ) mU for mifepristone-treated women and 2021.0 ( 0–24,750 ) mU for placebo-treated women ( P = .02 ) . Seventy-seven ( 87.5 % ) mifepristone-treated women and 46 ( 70.8 % ) placebo-treated women delivered vaginally 48 hours after the start of treatment ( P = .01 ) . There were nine cesareans in the mifepristone group and 18 in the placebo group ( P = .02 ) . More nonreassuring fetal heart rate patterns and uterine contractile abnormalities occurred in mifepristone-treated subjects . There were no statistically significant differences in neonatal outcomes between groups . Conclusion Mifepristone had a modest effect on cervical ripening when given 24 hours before labor induction , appearing to reduce the need for misoprostol and oxytocin compared with placebo A r and omized prospect i ve clinical trial of induction of labor at 42 completed weeks gestation versus expectant management in post date s pregnancies was performed . The primary screening test was the 24-hr urinary estriol creatinine ratio . The cesarean section rate was high in both groups and did not differ statistically . Intervention by delivery at 42 weeks decreased the development of small for gestational age infants , but costs slightly more . Twenty-four-hour urinary estriol creatinine ratio determinations predicted fetal distress in labor , but could not predict postmaturity syndrome or infants who were small for gestational age . As expectant management did not differ from induction of labor at 42 weeks from the st and point of maternal outcome , and as the cost difference was small , induction of labor at 42 weeks may be the preferred management as it improves infant outcome The influence of nipple stimulation ( NS ) at term on the duration of pregnancy was investigated among low-risk gravidas in a r and omized prospect i ve study . A significant inverse relationship was found between the duration of pregnancy and both gestational age at recruitment and cervical ( Bishop ) score , although the influence of cervical score was quantitatively small . Nipple stimulation did not influence either the duration of pregnancy or the probability of having a cesarean section or an instrumental delivery . Patient compliance was , however , poor , which may in part account for these findings , as there was an inverse trend between the daily average duration of NS and the duration of pregnancy OBJECTIVE : To determine the best method of cervical ripening to prevent post date inductions in women with an unfavorable cervix at 41 weeks ’ gestation . STUDY DESIGN : Women presenting at 41 weeks ’ gestation with a Bishop score of ≤4 received daily dinoprostone ( Cervidil ) vaginal inserts ( group I ) or daily membrane sweeping ( group II ) . RESULTS : One-hundred and eighty-two women were prospect ively r and omized with 91 women in each arm . The women in group II , membrane sweeping , had Bishop scores significantly greater on admission for delivery ( p < 0.001 ) , had less time elapsed from admission to delivery ( p = 0.018 ) , and had fewer labor inductions at 42 weeks ( p = 0.04 ) than the women in group I , the dinoprostone group . In addition , a greater number of women in group II were admitted in spontaneous labor ( p = 0.006 ) than in group I. Total antenatal costs for the membrane sweeping group was $ 15,120 versus $ 59,540 for the dinoprostone group . CONCLUSION : Daily membrane sweeping was more effective than dinoprostone administration with fewer post date inductions at one-fourth the cost Objective 1 . To evaluate the effectiveness of sweeping of the membranes to reduce the need for a formal induction of labour ; 2 . to evaluate the side effects of this intervention Objective : The appropriate date of delivery in twin pregnancies is supposed to be earlier than that in singleton pregnancy . The aim of this study was to compare two strategies for managing twin pregnancies ( i.e. , immediate induction and expectant management ) . Methods : Seventeen patients underwent immediately induced labor by administration of oral prostagl and in E2 at 37 weeks , while 19 patients underwent expectant management . Results : The average gestational age at delivery in the induction group was 37.5 ± 0.4 weeks , significantly earlier than that in the expectant management group ( 39.0 ± 1.1 weeks ) . However , there were no significant differences in the average birth weight between the two groups ( 2,700 ± 330 g in the induction group vs. 2,672 ± 392 g in the expectant management group ) . The cesarean delivery rate in the induction group was 18 % , not significantly different from that in the expectant management group ( 32 % ) . The most common indication for cesarean section in the expectant management group was maternal infection , while there was no maternal infection in the induction group ( p = 0.08 ) . Conclusion : It may be acceptable do intervene in twin pregnancies earlier than in singleton pregnancies during term Objective To determine the efficacy and safety of mifepristone for cervical ripening in post-term pregnancies . Methods Women with post-term pregnancies and Bishop scores less than 6 were assigned r and omly to mifepristone ( 41 patients ) or placebo ( 42 patients ) . Mifepristone was given orally in a dose of 400 mg . Efficacy was assessed by change in the Bishop score within 48 hours after treatment ; a score of 6 or greater was considered a “ strict ” success . An “ extended ” success rate was defined , including all patients with scores of at least 6 or those who delivered within 48 hours of treatment . Antenatal safety was assessed by fetal heart rate testing before and throughout labor . Neonatal safety was assessed by Apgar score , arterial or venous pH of cord blood , and blood glucose level during the first 48 hours . Analysis used Student t test for continuous variables , Kruskal-Wallis test for ordinal data , and χ2 for categoric variables . Results Strict success was achieved in 10 of 18 mifepristone patients ( 55 % ) evaluated for Bishop score on day 2 versus 8 of 29 placebo patients ( 27.5 % ) ( P = .004 ) . Extended success was achieved in 33 mifepristone patients ( 80.5 % ) and 21 placebo patients ( 50.0 % ) ( P = .004 ) . There were no statistical differences with regard to number of cesareans or fetal and neonatal safety . Conclusion Mifepristone proved effective for cervical ripening and reduced the time to delivery compared with placebo , but it did not improve the rate of cesarean . Our study did not include enough pregnancies to reach conclusions about fetal or neonatal safety Prolonged pregnancy was rigorously defined in 180 gravid women without other complications . Patients were r and omly assigned to be serially followed , either by amniocenteses or by oxytocin challenge tests ( OCT 's ) . Induction of labor , based upon only ( 1 ) a finding of meconium in the amniocentesis group or ( 2 ) a positive test in the OCT group , was nearly three times more frequent in the amniocentesis group . The incidence of meconium , which overall was 22 % initially and 44 % at delivery , as well as the frequencies of obstetric and perinatal complications , were similar in both management groups . Although meconium was significantly associated with abnormal labor progression , intrapartum fetal distress , and low 1 and 5 minute Apgar scores , induction of labor after discovery of meconium , when compared to nonintervention , did not improve perinatal outcome . It is concluded that a search for meconium is of little value in the management of prolonged pregnancy This study was carried out to evaluate the efficacy and safety of membrane stripping at term in reducing the incidence of post-term ( 41 weeks or greater ) pregnancies . One hundred and thirty-seven pregnant women at 38 weeks gestation were r and omised to receive either membrane stripping ( 69 ) or gentle cervical examination ( 68 ) . Women who received stripping had earlier delivery ( 4·8 vs. 12·1 days ; P < 0·001 ) and less incidence of delivery at 41 weeks or greater ( 3 % vs. 16 % ; P = 0·009 ) . No statistically significant difference was noted in incidence of premature rupture of membranes , clinical evidence of chorioamnionitis , intrapartum characteristics and perinatal outcome . We conclude that membrane stripping is a safe method to reduce the incidence of post-term pregnancy Three hundred two low-risk obstetric patients with an unfavorable cervical examination and well-established gestational age of at least 287 days were r and omly selected for management by either antepartum fetal testing or prostagl and in gel cervical ripening followed by aggressive induction of labor and delivery . The patients managed by induction of labor had a lower incidence of meconium-stained amniotic fluid , meconium aspiration , low Apgar scores , postmaturity syndrome , fetal distress , and cesarean delivery than did patients managed with antepartum fetal testing . Our data suggest that prostagl and in gel cervical ripening and induction of labor and delivery by 42 weeks ' gestation may be the most appropriate management for patients with well-established gestational age and an unfavorable cervical examination In a prospect i ve r and omized study spontaneous and oxytocin induced labor have been compared with respect to duration of labor and the condition of the fetus and the newborn infant . The study consists of 166 normal patients at full term . No significant differences between the two groups were found , and the results of the study showed that induction of labor between the 40th and 41st week of pregnancy was safe for the fetus . It is concluded that there seems to be no increased risks to mother or fetus from induction of labor compared to normal labor provided that there is cephalic presentation and a normal pregnancy A non-aggressive approach to the management of post- date pregnancies was tested in a clinical trial involving 156 patients who had reached 294 days of amenorrhea and had a pelvic score of 4 or less . Date s had been established with certainty in each case . In half of the patients ( the study group ) no time limit was imposed on the pregnancy , but the women were checked at frequent intervals for any increase in pelvic score and for changes in any of the following : fetal movement count recorded daily by the mother , an oxytocin challenge test , and amnioscopy . The pregnancy ended either through spontaneous contractions or through surgical induction carried out because of a change in any one of the parameters or an increase above 4 in the pelvic score . In the 78 control patients labor was induced surgically on day 294 , even if the pelvic score was low . In the study group , labor started spontaneously in 52 patients ; labor was induced in 17 women after they showed an elevated pelvic score , in 7 because of a pathologic parameter and in one because a mild pre-eclampsia developed . There were 7 cesarean sections in the study group compared with 16 in the control group ( P less than 0.05 ) . The average duration of labor was 6.7 h in the study group , compared with 9.4 h in the control ( P less than 0.01 ) . There was no significant difference between the two groups with regard to meconium staining during labor , pathologic fetal heart rate , or the 5 min Apgar score . In the study group there was one neonatal death as a result of severe congenital heart disease , and in the control group one infant died due to asphyxia . It is concluded that conservative management of prolonged pregnancies , with close supervision , gives better results than routine induction of labor at 42 wk . The importance of the pelvic score as an indication for induction is stressed . A protocol has been developed which can be used in cases of uncertain date s as well The study evaluates breast stimulation and oxytocin infusion as methods for cervical ripening in patients where an obstetric indication for induction of labour exists . Forty patients with a Bishop score of 5 or 6 were r and omly selected for either breast stimulation or oxytocin infusion . In a similar group of 20 cases , no method was employed . The Bishop score improved in 41.2 % of cases where breast stimulation was used as compared to 75 % where an oxytocin infusion was given . Three foetal deaths in the breast stimulation group brought the study to a stop after 17 cases . Cervical ripening with an oxytocin infusion drip appears to be a better method since infusion dosage can be precisely controlled making the technique more predictable and reliable . Though breast stimulation is effective in ripening the cervix , it may be used only in cases of intrauterine foetal death as it may otherwise adversely affect foetal outcome Vaginal application of tablets containing prostagl and in at term in pregnant women with a favorable cervical score is a very efficacious method of induction of labour . Due to the motility of the women they consider this method of induction as almost natural . We , therefore , aim ed at discussing the optimal procedure in low-risk pregnancies at due date , by means of a prospect i ve r and omised trial . In 345 women with a favourable cervical score , labour was either induced by means of intravaginal application of tablets containing PGE2 according to a precise plan , or spontaneous onset of labour was awaited while CTG-controls were performed on an outpatient basis every second day until the 42nd week of pregnancy was completed . 80 per cent of the nulliparas and 96.3 per cent of the multiparas of the induction group delivered within 24 hours of the first tablet application . All pertinent delivery intervals were significantly shorter in this group compared to those women where spontaneous onset of labour was awaited . The incidence of prolonged labour was low in both groups and not significantly different . Only 4.2 per cent of the women in the group where spontaneous labour was awaited , reached the completed 42nd week of pregnancy . Only one woman had to be induced because of a suspicious CTG . The rate of operative deliveries was lower in the induction group ( 1.1 % versus 3.8 % Caesarean sections ) . With the exception of one foetal death due to a cord complication three days after the due date the foetal outcome was excellent in both groups . The acceptance of the procedure was tested by means of a question naire during the post partum period . ( ABSTRACT TRUNCATED AT 250 WORDS The purpose of the study was to determine the safety and efficacy of outpatient intravaginal prostagl and in E2 ( PGE2 ) and membrane stripping in promoting labor in the uncomplicated post date pregnancy . In a double-blind placebo-controlled study , 150 enrollees were r and omized to one of four treatment groups ; group I , no membrane stripping and placebo gel ; group II , no membrane stripping and PGE2 gel ; group III , membrane stripping and placebo gel ; and group IV , membrane stripping and PGE2 gel . The treatments were administered at 287 days ( 41 weeks ) and 294 days ( 42 weeks ) of gestation , then every 3 - 4 days until 307 days ( 43 completed weeks ) of gestation . The patients in group IV had the shortest interval to delivery with a median of 1 day , P = .001 , and the fewest antenatal surveillance visits with only 21 % requiring more than one visit , P = .02 . Group I patients in comparison , had a 7-day median to delivery , and 61 % required more than one visit . The time spent in labor and delivery and the need for oxytocin augmentation was not significantly reduced in groups II , III , and IV . No adverse side effects to either mother or neonate could be directly attributed to this outpatient treatment combination . We conclude that intravaginal PGE2 gel combined with membrane stripping reduces postterm pregnancies and antenatal visits in our patients OBJECTIVE This study was undertaken to estimate the risk of fetal and maternal complications associated with postterm delivery in Denmark . STUDY DESIGN A cross-sectional study that used records from the Danish Medical Birth Registry from 1978 to 1993 was performed . All women with registered prolonged pregnancy ( n = 78022 ) and a 5 % r and om sample of all women who gave birth ( n = 47021 ) were linked to the Danish National Discharge Register . We established a postterm group of 77956 singleton deliveries and a term group of 34140 singleton spontaneous deliveries . Logistic regression models were used to analyze data . RESULTS The risk of perinatal and obstetric complications was high in postterm delivery compared with term delivery ( adjusted odds ratios between 1.2 and 3.1 ) . The risk of perinatal death was 1.33 ( 1.05 - 1.68 ) . CONCLUSION Postterm delivery was associated with significantly increased risks of perinatal and maternal complications in Denmark in the period from 1978 to 1993 BACKGROUND We compare trends and current levels of cesarean section delivery by indication in some industrialized countries to help us underst and factors underlying national differences in obstetric delivery practice and identify pathways to lower cesarean rates . STUDY DESIGN In this report we describe the schemes employed at our Department for the management of low-risk at term and postterm pregnancies and list the most important motivations for increased cesarean section rate and remedies suggested to reduce high cesarean section rate . Moreover a r and omized trial to assess the role of labor induction with PGE2 gel vs i.v . Oxytocin+Amniotomy in the management of prolonged pregnancy is being evaluated presently at our center . METHODS To date , 75 postterm pregnancies have been followed . Patients are enrolled at > or = 287 days ( 41 weeks ) . Intracervical PGE2 gel ( 0.5 mg ) is used for cervical ripening . Induction of labor is r and omly performed using intravaginal PGE2 gel ( 2 mg ) or i.v . Oxytocin+Amniotomy . RESULTS Overall rates of 75 % for spontaneous delivery , and 25 % for cesarean section have been observed in our study group of prolonged pregnancies . CONCLUSIONS The accurate labelling of low- and high-risk pregnancy and the appropriate management of term and postterm pregnancy are two important steps for the reduction of a high rate of cesarean section Abstract Aim : Pharmacological labor induction is obtained through intracervical/vaginal prostagl and ins and /or oxytocin infusion ; however , the use of these agents produces fetal and maternal side effects . Traditional Chinese medicine advocates the use of acupuncture to soften the cervix and induce uterine contractions . The aim of the present study is to investigate the effect of acupuncture to induce labor . Acupuncture was applied in post- date pregnancies one week before a planned induction ; the primary outcome was the rate of women su bmi tted to labor induction for prolonged pregnancy at week 41 + 5 . Methods : After informed consent , 221 undelivered women ranging between 40 + 2/40 + 6 gestational age were considered eligible for the study and 202 were r and omized to receive acupuncture or observation . Sessions of acupuncture were planned every odd day from the r and omization till 41a week plus 4 days . At 41 + 5 week a pharmacological induction of labor was planned . Results : The total rate of labor induction did not significantly differ between observation and acupuncture group ( 20 % versus 17 % ) . Moreover no differences were found as far as the indications to induce labor , in particular “ prolonged pregnancy ” was similar between groups ( 8/96 versus 5/99 ) . To investigate between-group differences in time elapsed between inclusion and delivery , survival analysis was performed excluding women requiring labor induction : women receiving acupuncture showed a trend to deliver earlier than women in the observation group ( p < 0.09 ) . Conclusion : The present study demonstrated that acupuncture applied every odd day for one week seems ineffective in reducing the rate of labor induction performed for prolonged pregnancy at 41 + 5 weeks . Previous reports reached similar conclusions , independently of the different timing , duration and mode of stimuli application Abstract . The effect of induction of labour on the foetus and the newborn was investigated in a prospect i ve r and omized study . 41 neonates were studied after induction at full term by amniotomy and intravenous oxytocin infusion . The infusion rate was regulated by the intraamniotic pressure using the Cardiff infusion pump system . 39 neonates served as controls where the labour started spontaneously followed by amniotomy . In both groups foetal heart rate monitoring and intraamniotic pressure recordings were performed . There were no differences in Apgar score and pH in cord blood between the groups . The newborns were evaluated the first and the fifth day of life with the Brazelton Neonatal Behavioral Assessment Scale and with a modified Prechtl neurological examination . There were no differences in behaviour and neurological state between the two groups . However , within the groups there were significant differences between the first and the fifth day concerning both neonatal behaviour and neurological state Objective : To assess the safety of vaginal recombinant human relaxin in pregnant women treated before the induction of labor and to collect preliminary data on the efficacy of recombinant human relaxin in promoting cervical ripening . Methods : In a multi-center , r and omized , double-blind placebo-controlled trial , 40 women were studied before induction of labor because of post- date s. The women were r and omized to receive either 1.5 mg recombinant human relaxin in 3 % methylcellulose gel or gel only , placed into the posterior vaginal fornix after a cervical assessment on the evening before scheduled induction . If a subject did not go into spontaneous labor overnight , another cervical assessment was performed 15 hours following treatment , immediately before the st and ard induction regimen of the hospital . Results : No important maternal or fetal-neonatal complications could be attributed to the drug . The differences between the recombinant human relaxin group and the placebo group for all the outcome measures of efficacy did not achieve statistical significance . Placebo patients were more likely to report moderate or strong uterine contractions in the first 4 hours following treatment than were the recombinant human relaxin-treated patients . Conclusions : The use of recombinant human relaxin at a dose of 1.5 mg was not associated with any significant maternal or fetal-neonatal complications . The relatively small number of subjects in this study was chosen deliberately because this was the first use of the drug in pregnant subjects . Assessment of efficacy will require studies that include more patients and a range of relaxin doses OBJECTIVE Our purpose was to evaluate whether inserting prostagl and in E2 gel at the time of scheduled nonstress tests in patients with post date pregnancies can decrease rates of intervention . STUDY DESIGN A multicenter pilot study enrolled women with post date pregnancies with Bishop score < or = 6 who were undergoing antepartum fetal heart rate testing . Patients were r and omized in a double-blind fashion to receive either a prostagl and in E2 intracervical gel ( Prepidil ) or a placebo gel after each of their scheduled nonstress tests . RESULTS There were no significant differences in the number of antepartum tests , labor inductions , or cesarean sections , the maximum oxytocin dosage , or the interval from admission to delivery in the prostagl and in E2 gel and placebo gel groups ( n = 90 ) . In the subset of patients with a Bishop score between 3 and 6 ( 63 patients ) , there were fewer inductions in the prostagl and in E2 group ( 30 % vs 55 % , P < .05 ) . CONCLUSION Application of prostagl and in E2 gel at the time of scheduled antepartum testing in patients with post date pregnancies with unfavorable cervices decreased the induction rate only among patients with intermediate Bishop scores OBJECTIVE To determine the cost-effectiveness of induction of labour versus serial fetal monitoring while awaiting spontaneous labour in postterm pregnancies . DESIGN Cost-effectiveness and cost-minimization analyses conducted as part of a Canadian multicentre r and omized clinical trial . SETTING Twenty-two Canadian hospitals , of which 19 were teaching hospitals and 3 were community hospitals . PATIENTS Women with uncomplicated pregnancies of 41 or more weeks ' gestation were r and omly assigned to induction of labour or serial antenatal monitoring . Of the 3418 women enrolled , no data were received on 11 . Therefore , results were based on data from 1701 women in the induction arm of the study and 1706 women in the monitoring arm . MAIN OUTCOME MEASURES Perinatal mortality and neonatal morbidity , rates of cesarean section and health care costs . Hospital costing models were developed specifically for the study . Data on use of major re sources ( e.g. , length of hospital stay , surgical procedures , major diagnostic tests and procedures , and medications ) for all trial participants were collected and combined with data on minor tests and procedures ( e.g. , laboratory tests ) abstract ed from a detailed review of medical records of a sample of patients . RESULTS Because the results of the clinical trial showed a nonsignificant difference in perinatal mortality and neonatal morbidity between the induction and monitoring arms , the authors conducted a cost-minimization rather than a cost-effectiveness analysis . The mean cost per patient with a postterm pregnancy managed through monitoring was $ 3132 ( 95 % confidence interval [ CI ] $ 3090 to $ 3174 ) and per patient who underwent induction of labour was $ 2939 ( 95 % CI $ 2898 to $ 2981 ) , for a difference of $ 193 . The significantly higher ( p < 0.0001 ) mean cost per patient in the monitoring arm was due mainly to the costs of additional monitoring and the significantly higher rates of cesarean section among these patients . Estimated conservatively , the savings result ing from a universal policy of managing postterm pregnancies by induction of labour in Canada may be as high as $ 8 million a year . CONCLUSIONS A policy of managing postterm pregnancy through induction of labour not only results in more favourable outcomes than a monitoring strategy but does so at a lower cost For the induction of labour prostagl and in ( PG ) E2 has been recommended either as intracervical gel ( 0.5 mg ) or as vaginal tablet ( 3 mg ) depending on the Bishop score of the cervix . A prospect i ve trial was conducted in 79 , mainly postterm , pregnancies ( 59 with a Bishop score < 5 ) , in whom either PG-E2 tablet or gel was given r and omly without respect to the cervical score . In addition , 51 inductions in primiparous women ( 44 with a Bishop score < 5 ) were analysed retrospectively . In pregnancies with a Bishop score < 5 the rate of successful inductions , duration of labour or incidence of neonatal acidosis was not different in both groups . Similar results were obtained in the prospect i ve trial for inductions with a cervical score > 4 . These data suggest the lack of superiority of the intracervical over the vaginal route of PG-E2 administration for the induction of labour Post date pregnancy is estimated to occur in 3 % to 12 % of all gestations . Morbidity and mortality rates associated with this common obstetric problem are higher than those with term gestation . The incidence of fetal distress , birth injury , meconium aspiration , congenital malformations , macrosomia , and oligohydramnios is also greater in post date pregnancy . We prospect ively evaluated breast self-stimulation to determine its effect on the incidence of post date pregnancy . Two hundred low-risk patients at 39 weeks ' gestation were r and omly assigned to either a control group or a breast-stimulation group . Results showed that breast stimulation reduced the number of pregnancies managed as post date s from 17 per 100 ( 17 % ) to five per 100 ( 5 % ) ( p less than 0.01 ) , a 70 % reduction . It is concluded that breast stimulation in post date s pregnancies can decrease significantly the number of patients that must be monitored by biochemical or biophysical means In a prospect i ve r and omised study of mothers referred for prolonged pregnancy ( around the 42nd week ) 214 ( group 1 ) were su bmi tted to attempted induction of labour and 195 ( group 2 ) assigned to continue for a further week without intervention . Strict selection criteria were used for the certainty of term . Mothers in group 2 were given regular non-stress tests to ensure fetal wellbeing , as were those in group 1 in whom induction failed . In group 1 , 48 ( 23 % ) out of 210 first attempted inductions failed . In group 2 , 135 ( 69 % ) of the births started spontaneously as compared with 38 ( 18 % ) in group 1 . The mean duration of labour was 7.5 hours in each group . There was no significant difference in incidence of operative delivery , use of analgesics , or signs of perinatal asphyxia . Significantly more children in group 1 needed phototherapy for hyperbilirubinaemia . There was a clustering of births in the late afternoon and evening , which was most pronounced in group 1 . A policy of vigilant non-intervention up to the 44th completed week of pregnancy does not appear to jeopardize mother or fetus A prospect i ve trial was conducted to compare the effects of conservative management of prolonged pregnancy ( conservative group ) with routine induction of labour at 42 weeks ' gestation ( active group ) in otherwise uncomplicated pregnancies . Of the 402 pregnancies studied , 207 ( 51 % ) were allocated to conservative management and 195 ( 49 % ) were allocated to have labour induced . The groups were well matched for age , parity , and smoking habits . One hundred and sixty six ( 80 % ) of the patients in the conservative group went into spontaneous labour . Of the remainder , two underwent elective caesarean section , 19 had labour induced because of clinical concern , and the remaining 20 had labour induced at the patient 's own request . One hundred and twenty five ( 64 % ) of the patients in the planned active group underwent induction of labour . Of the remaining 70 , 49 went into spontaneous labour and 21 ( 11 % ) asked that they should not have labour induced . Comparison of the two groups showed no difference in the length of the first stage of labour but a trend towards an increased need for intervention for fetal distress ( p less than 0.06 ) in the active group . There were no differences in the length of the second stage , the need for intervention , or the mode of delivery . In terms of Apgar scores the neonatal outcome was not significantly different between the two groups , but a greater proportion of the babies ( 15 % v 8 % ) in the active group required intubation . Umbilical cord venous pH estimated in the last 183 consecutive deliveries in the study showed a significantly lower mean value in the active group ( p less than 0.05 ) . There was no difference in birth weight between the two groups . Two deaths occurred in the study . There was a stillbirth in the conservative group at 292 days after massive abruption , and one neonatal death in the active group owing to multiple congenital abnormalities . The outcome for mother and baby in patients from both groups who went into spontaneous labour was generally good . The outcome for patients for whom conservative management was planned but induction became necessary was no different from that of patients who underwent planned induction at term . Thus from our results we can find no evidence to support the view that women with normal prolonged pregnancy should undergo routine induction of labour at 42 weeks ' gestation OBJECTIVES To compare the effectiveness of 25 microg vs. 50 microg of intravaginal misoprostol for cervical ripening and labor induction beyond 41 weeks ' gestation . METHODS The study population consisted of 120 women not in active labor with a gestational age > 41 weeks , singleton pregnancy with vertex presentation , reactive fetal heart rate tracing , amniotic fluid index > /=5 , and Bishop score < 5 . Women were r and omized to receive either 25 microg ( n=60 ) or 50 microg ( n=60 ) of intravaginal misoprostol . The dose was repeated every 4 h ( maximum number of doses limited to six ) until the patient exhibited three contractions in 10 min . The main outcome measure was the induction-vaginal delivery interval . RESULTS There was no significant difference between the two groups with regard to the induction-vaginal delivery interval ( 685+/-201 min in the 25 microg group vs. 627+/-177 min in the 50 microg group , P=0.09 ) . The proportion of women delivering vaginally with one dose of vaginal misoprostol was significantly greater in the 50 microg group ( 0/49 vs. 41/47 , P<0.001 ) . There were no differences in the rates of cesarean and operative vaginal delivery rates , or in the incidences of tachysystole and hyperstimulation syndrome in the two treatment groups . Neonatal outcomes were also similar . CONCLUSIONS Intravaginal administration of 25 microg of misoprostol appears to be as effective as 50 microg for cervical ripening and labor induction beyond 41 weeks ' gestation Objective To evaluate weekly stripping of membranes at term to determine its safety and effectiveness in reducing the incidence of prolonged and postterm pregnancies . Methods One hundred forty-two pregnant women with certain gestational date s were r and omly selected to receive , starting at 38 weeks , either weekly stripping of membranes ( 73 patients ) or weekly gentle cervical examinations ( 69 patients ) . Results Women who received stripping had earlier delivery ( 8.2 versus 12.2 days ; P < .005 ) and less incidence of delivery at 41 weeks or greater ( three versus 13 patients ; P < .01 ) . The reduction remained consistent for favorable and unfavorable Bishop scores , and for nulliparas and multiparas . Only three subjects in the study delivered at 42 weeks or greater . No woman reported rupture of membranes after stripping . Conclusion Stripping of membranes is a safe method to reduce the incidence of prolonged pregnancies and the length of term gestations . Larger trials on population s with a higher incidence of postterm pregnancies are needed to evaluate its efficacy in reducing the incidence of postterm pregnancies OBJECTIVES To compare the effect of misoprostol vs. oxytocin on blood flow in uteroplacental circulation during labor induction . METHODS Ninety-one women with indications for induction of labor were assigned to receive either misoprostol 50 microg per vagina every 4 h as needed or intravenous oxytocin by means of a r and omization table generated by computer . Doppler velocimetry of umbilical , uterine and arcuate arteries was performed immediately before and 2 - 3 h after administration of misoprostol or oxytocin . Pulsatility index ( PI ) , resistance index ( RI ) and systolic/diastolic ( S/D ) ratios were measured for these arteries . The SAS system was used to perform statistical analysis . RESULTS There were no significant changes of PI , RI and S/D ratios in umbilical arteries during misoprostol and oxytocin inductions . Vaginal application of misoprostol significantly increased PI , RI and S/D ratios in arcuate arteries and S/D ratio in uterine arteries . CONCLUSIONS Our results indicate that intravaginal misoprostol administration increases uteroplacental resistance but probably does not substantially affect placental perfusion The ideal regimen for induction of labor with oxytocin with respect to the magnitude and frequency of dosage changes has not been defined . In spite of few data regarding labor induction with an unfavorable cervix , the initial dose recommended by the American College of Obstetricians and Gynecologists is lower than that of other commonly used protocol s. Eighty patients with unfavorable cervices and unruptured membranes , without evidence of labor , were r and omized to one of two protocol s and met criteria for data analysis . Patients in both protocol s were given an initial dose of oxytocin of 2 mU/min . Patients in protocol A ( n = 32 ) then received incremental increases of oxytocin of 1 mU/min at 30-minute intervals , while those in protocol B ( n = 48 ) received incremental increases of 2 mU/min at 15-minute intervals . Induction failures were higher among patients on protocol A ( 31 % vs 8 % , p less than 0.05 ) . Patients on protocol B had shorter times to delivery ( mean = 10 hours 57 minutes vs 8 hours 3 minutes ; p less than 0.05 ) . The number of operative deliveries were similar regardless of protocol . There were no significant differences ( p = NS ) among groups and protocol s in maternal and fetal complications , cesarean section rate , and uterine hyperstimulation . In this population a more aggressive protocol may lead to fewer induction failures and shorter induction-to-delivery intervals The effectiveness of transcutaneous electrical stimulation at acupuncture points for increasing uterine contractions in 20 post- date s pregnant women was assessed in a controlled study . Subjects were r and omly assigned to either a treatment condition , consisting of the application via surface electrodes of a 30-Hz current to the points " spleen 6 " ( lower leg ) and " liver 3 " ( foot ) , or a placebo condition , in which the equipment was attached but not activated . The frequency and strength of uterine contractions were monitored for 1 hour prior to stimulation and then for the final 2 hours of a 4-hour test period . A significant increase in frequency and strength of uterine contractions was found in the electrically stimulated women compared with the placebo-group women . The possible physiologic mechanisms underlying this effect , and its implication for labor induction , are discussed |
12,321 | 28,639,262 | Compared to multidisciplinary audio conferencing , multidisciplinary video conferencing may reduce the average length of treatment and may reduce the number of multidisciplinary conferences needed per patient and the patient length of stay .
Given that the certainty of evidence from the included studies was judged to be low to very low , there is not sufficient evidence to draw clear conclusions on the effects of IPC interventions . | BACKGROUND Poor interprofessional collaboration ( IPC ) can adversely affect the delivery of health services and patient care .
Interventions that address IPC problems have the potential to improve professional practice and healthcare outcomes .
OBJECTIVES To assess the impact of practice -based interventions design ed to improve interprofessional collaboration ( IPC ) amongst health and social care professionals , compared to usual care or to an alternative intervention , on at least one of the following primary outcomes : patient health outcomes , clinical process or efficiency outcomes or secondary outcomes ( collaborative behaviour ) . | BACKGROUND Sharing information with the team is critical in developing a shared mental model in an emergency , and fundamental to effective teamwork . We developed a structured call-out tool , encapsulated in the acronym ' SNAPPI ' : Stop ; Notify ; Assessment ; Plan ; Priorities ; Invite ideas . We explored whether a video-based intervention could improve structured call-outs during simulated crises and if this would improve information sharing and medical management . METHODS In a simulation-based r and omized , blinded study , we evaluated the effect of the video-intervention teaching SNAPPI on scores for SNAPPI , information sharing , and medical management using baseline and follow-up crisis simulations . We assessed information sharing using a probe technique where nurses and technicians received unique , clinical ly relevant information probes before the simulation . Shared knowledge of probes was measured in a written , post-simulation test . We also scored sharing of diagnostic options with the team and medical management . RESULTS Anaesthetists ' scores for SNAPPI were significantly improved , as was the number of diagnostic options they shared . We found a non-significant trend to improve information-probe sharing and medical management in the intervention group , and across all simulations , a significant correlation between SNAPPI and information-probe sharing . Of note , only 27 % of the clinical ly relevant information about the patient provided to the nurse and technician in the pre-simulation information probes was subsequently learnt by the anaesthetist . CONCLUSIONS We developed a structured communication tool , SNAPPI , to improve information sharing between anaesthetists and their team , taught it using a video-based intervention , and provide initial evidence to support its value for improving communication in a crisis It is important to underst and the effects of a new care model on health professionals ' satisfaction , which may help inform organizations ' decisions regarding the adoption of the model . This study evaluates the effect of the Guided Care model of primary care on physicians ' , Guided Care Nurses ' and practice staff satisfaction with processes of care for chronically ill older patients . In Guided Care , a specially educated registered nurse works with 2 - 5 primary care physicians , performing 8 clinical activities for 50 - 60 chronically ill older patients . This model was tested in a 3-year matched-pair cluster-r and omized controlled trial with 14 pods ( teams of physicians and staff ) r and omly assigned , within pairs , to provide Guided Care or usual care . Physicians and Guided Care Nurses were surveyed at baseline and annually for 3 years . Staff were surveyed at baseline and 2 years later . Physicians ' satisfaction with chronic care processes , knowledge of patients , and care coordination were measured , as well as Guided Care Nurses ' satisfaction with chronic care processes and staff perceptions of quality of care . Findings suggest that Guided Care improved physician satisfaction with patient/family communication and management of chronic care , and it may bolster staff beliefs that care is patient oriented . Differences in other aspects of care were not statistically significant BACKGROUND Previous research has shown that communication between members of multidisciplinary teams ( MDTs ) is often suboptimal and communication about trials between MDTs and their patients is difficult . Educational interventions can help dyadic exchanges with different aspects of trial recruitment but less work has focussed on team interventions . METHODS 22 multidisciplinary cancer teams in the UK participated in an RCT of a novel Teams Talking Trials ( TTT ) Workshop aim ed at improving the following : awareness , involvement , communication and recruitment to cancer trials . MDTs were r and omised following either 6 or 12 months of audits , which were repeated after the intervention . Audits included numbers approached about trials , team members ' attitudes , involvement and awareness of their teams ' trial portfolios . RESULTS There was no significant difference in the rate of approaching patients about trials post workshop ( estimated improvement 22 % higher regression coefficient of 0.2 , exp . (0.2)=1.22 ) . There was improvement in team members ' involvement in trials in 4 areas ( p≤0.04 ) : the pressure to enter patients into RCTs , the likelihood of a start-up meeting to discuss a newly accepted trial , the informational role played by individuals and recognition of this HCP 's role by other team members . Also , confidence in communication about RCTS increased and awareness of different aspects of trial management improved on all 14 aspects ( p=0.001 ) . CONCLUSION Attendance by teams at focussed workshops design ed to enhance communication and trial recruitment improved several aspects of team functioning , but a significant impact on the number of patients approached could not be demonstrated Background Crew re source management ( CRM ) has the potential to enhance patient safety in intensive care units ( ICU ) by improving the use of non-technical skills . However , CRM evaluation studies in health care are inconclusive with regard to the effect of this training on behaviour and organizational outcomes , due to weak study design s and the scarce use of direct observations . Therefore , the aim of this study is to determine the effectiveness and cost-effectiveness of CRM training on attitude , behaviour and organization after one year , using a multi- method approach and matched control units . The purpose of the present article is to describe the study protocol and the underlying choices of this evaluation study of CRM in the ICU in detail . Methods / Design Six ICUs participated in a paired controlled trial , with one pre-test and two post test measurements ( respectively three months and one year after the training ) . Three ICUs were trained and compared to matched control ICUs . The 2-day classroom-based training was delivered to multidisciplinary groups . Typical CRM topics on the individual , team and organizational level were discussed , such as situational awareness , leadership and communication . All levels of Kirkpatrick 's evaluation framework ( reaction , learning , behaviour and organisation ) were assessed using question naires , direct observations , interviews and routine ICU administration data . Discussion It is expected that the CRM training acts as a generic intervention that stimulates specific interventions . Besides effectiveness and cost-effectiveness , the assessment of the barriers and facilitators will provide insight in the implementation process of CRM.Trial registration Netherl and s Trial Register ( NTR ) : Promotoras from the communities in which interventions are implemented can be effective contributors to validity and fidelity efforts . This article describes a 48-week r and omized controlled trial Madres para la Salud ( Mothers for Health ) and illustrates the use of promotoras as collaborative members of the research team to contribute to attaining integrative validity and treatment fidelity . Madres para la Salud implements a culturally tailored physical activity program to effect changes in body fat , systemic and fat tissue inflammation , and depression symptoms . The significance of Madres para la Salud treatment validity and fidelity processes includes cultural tailoring of a social support intervention , and a promotora model to incorporate initial and ongoing fidelity monitoring OBJECTIVE The aim of the study was to evaluate the interprofessional SDM training program " Fit for SDM " in medical rehabilitation , which was implemented in two steps : ( 1 ) university staff trained providers in executive positions as trainers and ( 2 ) the providers trained their staff . METHODS For the evaluation of the first step a question naire for shared decision-making ( SDM ) skills and satisfaction with the training was completed by the providers in executive positions . A staff survey was used in a cluster-r and omized controlled study to determine the overall impact of the train-the-trainer program on internal and external participation in the team . RESULTS The providers in the six clinics evaluated their SDM competences and satisfaction very positively after training ( step 1 ) . External participation was enhanced by application of the training content , with significant changes recorded for females and nurses in particular . However , it had no direct influence on internal participation . CONCLUSIONS This is the first interprofessional SDM train-the-trainer program in Germany to bridge interprofessionalism ( internal participation ) and SDM ( external participation ) ; it was implemented successfully and evaluated positively . PRACTICE IMPLICATION S Establishing interprofessional SDM training programs should be encouraged for all health care professionals . Implementation in the interprofessional setting should consider interprofessional team factors There is evidence for a team-based approach in the management of chronic disease in primary health care . However , the st and ard of care is variable , probably reflecting the limited organisational capacity of health services to provide the necessary structured and organised care for this group of patients . This study aim ed to evaluate the impact of a structured intervention involving non-GP staff in GP practice s on the quality of care for patients with diabetes or cardiovascular disease . A cluster r and omised trial was undertaken across 60 GP practice s. The intervention was implemented in 30 practice s with staff and patients interviewed at baseline and at 12 - 15 months follow up . The change in team roles was evaluated using a question naire completed by practice staff . The quality of care was evaluated using the Patient Assessment of Chronic Illness Care question naire . We found that although the team roles of staff improved in the intervention practice s and there were significant differences between practice s , there was no significant difference between those in the intervention and control groups in patient-assessed quality of care after adjusting for baseline-level score and covariates at the 12-month follow up . Practice team roles were not significantly associated with change in Patient Assessment of Chronic Illness Care scores . Patients with multiple conditions were more likely to assess their quality of care to be better . Thus , although previous research has shown a cross-sectional association between team work and quality of care , we were unable to replicate these findings in the present study . These results may be indicative of insufficient time for organisational change to result in improved patient-assessed quality of care , or because non-GP staff roles were not sufficiently focussed on the aspects of care assessed . The findings provide important information for research ers when design ing similar studies IMPORTANCE Hospital readmissions are common and costly , and no single intervention or bundle of interventions has reliably reduced readmissions . Virtual wards , which use elements of hospital care in the community , have the potential to reduce readmissions , but have not yet been rigorously evaluated . OBJECTIVE To determine whether a virtual ward-a model of care that uses some of the systems of a hospital ward to provide interprofessional care for community-dwelling patients -can reduce the risk of readmission in patients at high risk of readmission or death when being discharged from hospital . DESIGN , SETTING , AND PATIENTS High-risk adult hospital discharge patients in Toronto were r and omly assigned to either the virtual ward or usual care . A total of 1923 patients were r and omized during the course of the study : 960 to the usual care group and 963 to the virtual ward group . The first patient was enrolled on June 29 , 2010 , and follow-up was completed on June 2 , 2014 . INTERVENTIONS Patients assigned to the virtual ward received care coordination plus direct care provision ( via a combination of telephone , home visits , or clinic visits ) from an interprofessional team for several weeks after hospital discharge . The interprofessional team met daily at a central site to design and implement individualized management plans . Patients assigned to usual care typically received a typed , structured discharge summary , prescription for new medications if indicated , counseling from the resident physician , arrangements for home care as needed , and recommendations , appointments , or both for follow-up care with physicians as indicated . MAIN OUTCOMES AND MEASURES The primary outcome was a composite of hospital readmission or death within 30 days of discharge . Secondary outcomes included nursing home admission and emergency department visits , each of the components of the primary outcome at 30 days , as well as each of the outcomes ( including the composite primary outcome ) at 90 days , 6 months , and 1 year . RESULTS There were no statistically significant between-group differences in the primary or secondary outcomes at 30 or 90 days , 6 months , or 1 year . The primary outcome occurred in 203 of 959 ( 21.2 % ) of the virtual ward patients and 235 of 956 ( 24.6 % ) of the usual care patients ( absolute difference , 3.4 % ; 95 % CI , -0.3 % to 7.2 % ; P = .09 ) . There were no statistically significant interactions to indicate that the virtual ward model of care was more or less effective in any of the prespecified subgroups . CONCLUSIONS AND RELEVANCE In a diverse group of high-risk patients being discharged from the hospital , we found no statistically significant effect of a virtual ward model of care on readmissions or death at either 30 days or 90 days , 6 months , or 1 year after hospital discharge . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01108172 A project based at the Alfred Emergency and Trauma Centre in Melbourne , Australia aim ed to st and ardise trauma resuscitation , documentation and interventions by developing best practice algorithms . The primary study objective was to demonstrate a reduction in management errors using a real-time computer based algorithm ( the study group ) compared to the control group in an open r and omised controlled interventional study . A baseline control group was also used for comparison with usual ( current ) practice . In order to examine the existing evidence and algorithms in trauma care , nine teams of emergency nurses and doctors were formed . Specific literature search es performed by each team revealed a paucity of evidence supporting clinical practice in the trauma setting for procedures . Subsequently , the multidisciplinary teams worked together and developed algorithms based on best practice . The process revealed three main areas of challenges in the development of algorithms : ( i ) clinical , ( ii ) research and ( iii ) nursing challenges . The completion of the project demonstrated benefits in the real-time computer based algorithm with a reduction in the error rate per patient from the baseline control group to the intervention study group ( 2.30 vs. 2.13 , p=0.04 ) and error-free resuscitations increasing from 16 % to 21.8 % ( p=.049 ) . This project supported the implementation of a real-time computer based algorithm system with improved protocol compliance and reduced errors and morbidity Background There are many avoidable deaths in hospitals because the care team is not well attuned . Training in emergency situations is generally followed on an individual basis . In practice , however , hospital patients are treated by a team composed of various disciplines . To prevent communication errors , it is important to focus the training on the team as a whole , rather than on the individual . Team training appears to be important in contributing toward preventing these errors . Obstetrics lends itself to multidisciplinary team training . It is a field in which nurses , midwives , obstetricians and paediatricians work together and where decisions must be made and actions must be carried out under extreme time pressure . It is attractive to belief that multidisciplinary team training will reduce the number of errors in obstetrics . The other side of the medal is that many hospitals are buying expensive patient simulators without proper evaluation of the training method . In the Netherl and s many hospitals have 1,000 or less annual deliveries . In our small country it might therefore be more cost-effective to train obstetric teams in medical simulation centres with well trained personnel , high fidelity patient simulators , and well defined training programmes . Methods / design The aim of the present study is to evaluate the cost-effectiveness of multidisciplinary team training in a medical simulation centre in the Netherl and s to reduce the number of medical errors in obstetric emergency situations . We plan a multicentre r and omised study with the centre as unit of analysis . Obstetric departments will be r and omly assigned to receive multidisciplinary team training in a medical simulation centre or to a control arm without any team training . The composite measure of poor perinatal and maternal outcome in the non training group was thought to be 15 % , on the basis of data obtained from the National Dutch Perinatal Registry and the guidelines of the Dutch Society of Obstetrics and Gynaecology ( NVOG ) . We anticipated that multidisciplinary team training would reduce this risk to 5 % . A sample size of 24 centres with a cluster size of each at least 200 deliveries , each 12 centres per group , was needed for 80 % power and a 5 % type 1 error probability ( two-sided ) . We assumed an Intraclass Correlation Coefficient ( ICC ) value of maximum 0.08.The analysis will be performed according to the intention-to-treat principle and stratified for teaching or non-teaching hospitals . Primary outcome is the number of obstetric complications throughout the first year period after the intervention . If multidisciplinary team training appears to be effective a cost-effective analysis will be performed . Discussion If multidisciplinary team training appears to be cost-effective , this training should be implemented in extra training for gynaecologists . Trial Registration The protocol is registered in the clinical trial register number IMPORTANCE Resuscitation training programs use simulation and debriefing as an educational modality with limited st and ardization of debriefing format and content . Our study attempted to address this issue by using a debriefing script to st and ardize debriefings . OBJECTIVE To determine whether use of a scripted debriefing by novice instructors and /or simulator physical realism affects knowledge and performance in simulated cardiopulmonary arrests . DESIGN Prospect i ve , r and omized , factorial study design . SETTING The study was conducted from 2008 to 2011 at 14 Examining Pediatric Resuscitation Education Using Simulation and Scripted Debriefing ( EXPRESS ) network simulation programs . Interprofessional health care teams participated in 2 simulated cardiopulmonary arrests , before and after debriefing . PARTICIPANTS We r and omized 97 participants ( 23 teams ) to nonscripted low-realism ; 93 participants ( 22 teams ) to scripted low-realism ; 103 participants ( 23 teams ) to nonscripted high-realism ; and 94 participants ( 22 teams ) to scripted high-realism groups . INTERVENTION Participants were r and omized to 1 of 4 arms : permutations of scripted vs nonscripted debriefing and high-realism vs low-realism simulators . MAIN OUTCOMES AND MEASURES Percentage difference ( 0%-100 % ) in multiple choice question ( MCQ ) test ( individual scores ) , Behavioral Assessment Tool ( BAT ) ( team leader performance ) , and the Clinical Performance Tool ( CPT ) ( team performance ) scores postintervention vs preintervention comparison ( PPC ) . RESULTS There was no significant difference at baseline in nonscripted vs scripted groups for MCQ ( P = .87 ) , BAT ( P = .99 ) , and CPT ( P = .95 ) scores . Scripted debriefing showed greater improvement in knowledge ( mean [ 95 % CI ] MCQ-PPC , 5.3 % [ 4.1%-6.5 % ] vs 3.6 % [ 2.3%-4.7 % ] ; P = .04 ) and team leader behavioral performance ( median [ interquartile range ( IQR ) ] BAT-PPC , 16 % [ 7.4%-28.5 % ] vs 8 % [ 0.2%-31.6 % ] ; P = .03 ) . Their improvement in clinical performance during simulated cardiopulmonary arrests was not significantly different ( median [ IQR ] CPT-PPC , 7.9 % [ 4.8%-15.1 % ] vs 6.7 % [ 2.8%-12.7 % ] , P = .18 ) . Level of physical realism of the simulator had no independent effect on these outcomes . CONCLUSIONS AND RELEVANCE The use of a st and ardized script by novice instructors to facilitate team debriefings improves acquisition of knowledge and team leader behavioral performance during subsequent simulated cardiopulmonary arrests . Implementation of debriefing scripts in resuscitation courses may help to improve learning outcomes and st and ardize delivery of debriefing , particularly for novice instructors IMPORTANCE Heart failure ( HF ) has a major effect on patients ' health status , including their symptom burden , functional status , and health-related quality of life . OBJECTIVE To determine the effectiveness of a collaborative care patient-centered disease management ( PCDM ) intervention to improve the health status of patients with HF . DESIGN , SETTING , AND PARTICIPANTS The Patient-Centered Disease Management ( PCDM ) trial was a multisite r and omized clinical trial comparing a collaborative care PCDM intervention with usual care in patients with HF . A population -based sample of 392 patients with an HF diagnosis from 4 Veterans Affairs centers who had a Kansas City Cardiomyopathy Question naire ( KCCQ ) overall summary score of less than 60 ( heavy symptom burden and impaired functional status and quality of life ) were enrolled between May 2009 and June 2011 . INTERVENTIONS The PCDM intervention included collaborative care by a multidisciplinary care team consisting of a nurse coordinator , cardiologist , psychiatrist , and primary care physician ; home telemonitoring and patient self-management support ; and screening and treatment for comorbid depression . MAIN OUTCOMES AND MEASURES The primary outcome was change in the KCCQ overall summary score at 1 year ( a 5-point change is clinical ly significant ) . Mortality , hospitalization , and depressive symptoms ( Patient Health Question naire 9 ) were secondary outcomes . RESULTS There were no significant differences in baseline characteristics between patients r and omized to the PCDM intervention ( n=187 ) vs usual care ( n=197 ) ; baseline mean KCCQ overall summary scores were 37.9 vs 36.9 ( P=.48 ) . There was significant improvement in the KCCQ overall summary scores in both groups after 1 year ( mean change , 13.5 points in each group ) , with no significant difference between groups ( P=.97 ) . The intervention was not associated with greater improvement in the KCCQ overall summary scores when the effect over time was estimated using 3-month , 6-month , and 12-month data ( P=.74 ) . Among secondary outcomes , there were significantly fewer deaths at 1 year in the intervention arm ( 8 of 187 [ 4.3 % ] ) than in the usual care arm ( 19 of 197 [ 9.6 % ] ) ( P = .04 ) . Among those who screened positive for depression , there was a greater improvement in the Patient Health Question naire 9 scores after 1 year in the intervention arm than in the usual care arm ( 2.1 points lower , P=.01 ) . There was no significant difference in 1-year hospitalization rates between the intervention arm and the usual care arm ( 29.4 % vs 29.9 % , P=.87 ) . CONCLUSIONS AND RELEVANCE This multisite r and omized trial of a multifaceted HF PCDM intervention did not demonstrate improved patient health status compared with usual care . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00461513 Recent advances in technology provide support for multisite , Web-based data -entry systems and the storage of data in a central ized location , result ing in immediate access to data for investigators , reduced participant burden and human entry error , and improved integrity of clinical trial data . The purpose of this article was to describe the development of a comprehensive , Web-based data management system for a multisite r and omized behavioral intervention trial . Strategies used to create this study -specific data management system included interdisciplinary collaboration , design mapping , feasibility assessment s , and input from an advisory board of former patients with characteristics similar to the targeted population . The result ing data management system and development strategies provide a template for other behavioral intervention studies Objective To determine the extent to which computerised decision support can improve concordance of multidisciplinary teams with therapeutic decisions recommended by guidelines . Design Multicentre cluster r and omised trial . Participants Multidisciplinary cardiac rehabilitation teams in Dutch centres and their cardiac rehabilitation patients . Interventions Teams received an electronic patient record system with or without additional guideline based decision support . Main outcome measures Concordance with guideline recommendations assessed for two st and ard rehabilitation treatments — exercise and education therapy— and for two new but evidence based rehabilitation treatments — relaxation and lifestyle change therapy ; generalised estimating equations were used to account for intra-cluster correlation and were adjusted for patient ’s age , sex , and indication for cardiac rehabilitation and for type and volume of centre . Results Data from 21 centres , including 2787 patients , were analysed . Computerised decision support increased concordance with guideline recommended therapeutic decisions for exercise therapy by 7.9 % ( control 84.7 % ; adjusted difference 3.5 % , 95 % confidence 0.1 % to 5.2 % ) , for education therapy by 25.7 % ( control 63.9 % ; adjusted difference 23.7 % , 15.5 % to 29.4 % ) , and for relaxation therapy by 25.5 % ( control 34.1 % ; adjusted difference 41.6 % , 25.2 % to 51.3 % ) . The concordance for lifestyle change therapy increased by 3.2 % ( control 54.1 % ; adjusted difference 7.1 % , −2.9 % to 18.3 % ) . Computerised decision support reduced cases of both overtreatment and undertreatment . Conclusions In a multidisciplinary team motivated to adopt a computerised decision support aid that assists in formulating guideline based care plans , computerised decision support can be effective in improving the team ’s concordance with guidelines . Therefore , computerised decision support may also be considered to improve implementation of guidelines in such setting s. Trial registration Current Controlled Trials IS RCT N36656997 Objective : To compare the effectiveness of an interprofessional within-team debriefing with that of an instructor-led debriefing on team performance during a simulated crisis . Background : Although instructor-led simulation debriefing is considered the “ gold st and ard ” in team-based simulation education , cost and logistics are limiting factors for its implementation . Within-team debriefing , led by the individuals of the team itself rather than an external instructor , has the potential to address these limitations . Methods : One hundred twenty subjects were grouped into 40 operating room teams consisting of 1 anesthesia trainee , 1 surgical trainee , and 1 staff circulating operating room nurse . All teams managed a simulated crisis scenario ( pretest ) . Teams were then r and omized to either a within-team debriefing group or an instructor-led debriefing group . In the within-team debriefing group , the teams review ed the video of their scenario by themselves . The teams in the instructor-led debriefing group review ed their scenario guided by a trained instructor . Immediately after debriefing , all teams managed a different intraoperative crisis scenario ( posttest ) . All sessions were videotaped . Blinded expert examiners used the vali date d Team Emergency Assessment Measure scale to assess crisis re source management performance of all teams in r and om order . Result : Team performance significantly improved from pretest to posttest ( P = 0.008 ) regardless of the type of debriefing . There was no significant difference in the degree of improvement between within-team debriefing and instructor-led debriefing ( P = 0.52 ) . Conclusions : Within-team debriefing results in measurable improvements in team performance in simulated crisis scenarios . This form of debriefing may be as effective as instructor-led team debriefing , which could improve re source utilization and feasibility of team-based simulation ( NCT01067378 ) Introduction : In this study design ed with adequate statistical power to detect relevant training effects , investigators evaluated Crisis Re source Management ( CRM ) training during a simulated patient crisis . This study is guided by the Team Effectiveness Conceptual Model by Kozlowski and Ilgen . Methods : An experimental pretest/posttest design was used . Four-member , interdisciplinary teams , each composed of nursing and medical students , were r and omly assigned to experimental or control conditions : Basic Life Support plus CRM training or Basic Life Support only , respectively . Team process ( task management , teamworking , situation awareness , and interprofessional attitude ) and team effectiveness ( team error rate and response times ) were the outcomes of interest . Results : Experimental teams demonstrated significant improvement in team process measures compared with control teams . CRM training predicted 13 % of the variance in task management ( P = 0.05 ) , 15 % of the variance in teamworking ( P = 0.04 ) , and 18 % of the variance in situation awareness ( P = 0.03 ) . CRM training and task management predicted 22 % of the variance ( P = 0.04 ) in team error rate ; CRM training and teamworking predicted 35 % of the variance ( P = 0.01 ) , while CRM training and situation awareness predicted 20 % of the variance ( P = 0.04 ) in response time to chest compressions . Both experimental and control teams demonstrated significant improvement in team effectiveness measures . Conclusions : CRM team training and team practice in an environment of high-fidelity simulation and facilitated debriefing have significant effects on team process and team effectiveness . The conceptual framework is potentially adaptable to additional setting s and population s for team-related research and education Please cite this paper as : Fransen A , van de Ven J , Merién A , de Wit‐Zuurendonk L , Houterman S , Mol B , Oei S. Effect of obstetric team training on team performance and medical technical skills : a r and omised controlled trial . BJOG 2012;119:1387–1393 Background The measurement of safety culture in healthcare is generally regarded as a first step towards improvement . Based on a self- assessment of safety culture , the Frankfurt Patient Safety Matrix ( FraTrix ) aims to enable healthcare teams to improve safety culture in their organisations . In this study we assessed the effects of FraTrix on safety culture in general practice . Methods We conducted an open r and omised controlled trial in 60 general practice s. FraTrix was applied over a period of 9 months during three facilitated team sessions in intervention practice s. At baseline and after 12 months , scores were allocated for safety culture as expressed in practice structure and processes ( indicators ) , in safety climate and in patient safety incident reporting . The primary outcome was the indicator error management . Results During the team sessions , practice teams reflected on their safety culture and decided on about 10 actions per practice to improve it . After 12 months , no significant differences were found between intervention and control groups in terms of error management ( competing probability=0.48 , 95 % CI 0.34 to 0.63 , p=0.823 ) , 11 further patient safety culture indicators and safety climate scales . Intervention practice s showed better reporting of patient safety incidents , reflected in a higher number of incident reports ( mean ( SD ) 4.85 ( 4.94 ) vs 3.10 ( 5.42 ) , p=0.045 ) and incident reports of higher quality ( scoring 2.27 ( 1.93 ) vs 1.49 ( 1.67 ) , p=0.038 ) than control practice s. Conclusions Applied as a team-based instrument to assess safety culture , FraTrix did not lead to measurable improvements in error management . Comparable studies with more positive results had less robust study design s. In future research , vali date d combined methods to measure safety culture will be required . In addition , more attention should be paid to evaluation of process parameters . Implemented actions and incident reporting may be more appropriate target endpoints . Trial registration German Clinical Trials Register ( Deutsches Register Klinischer Studien , DRKS ) No. The objectives of this study were to compare indices of 24-hour blood pressure ( BP ) following a physician-pharmacist collaborative intervention and to describe the associated changes in antihypertensive medications . This was a secondary analysis of a prospect i ve , cluster-r and omized clinical trial conducted in 6 family medicine clinics r and omized to co-managed ( n=3 clinics , 176 patients ) or control ( n=3 clinics , 198 patients ) groups . Mean ambulatory systolic BP ( SBP ) was significantly lower in the co-managed vs the control group : daytime BP 122.8 mm Hg vs 134.4 mm Hg ( P<.001 ) ; nighttime SBP 114.8 mm Hg vs 123.7 mm Hg ( P<.001 ) ; and 24-hour SBP 120.4 mm Hg vs 131.8 mm Hg ( P<.001 ) , respectively . Significantly more drug changes were made in the co-managed than in the control group ( 2.7 vs 1.1 changes per patient , P<.001 ) , and there was greater diuretic use in co-managed patients ( 79.6 % vs 62.6 % , P<.001 ) . Ambulatory BPs were significantly lower for the patients who had a diuretic added during the first month compared with those who never had a diuretic added ( P<.01 ) . Physician-pharmacist co-management significantly improved ambulatory BP compared with the control group . Antihypertensive drug therapy was intensified much more for patients in the co-managed group Objective : Evaluation of the effect of the train-the-trainer programme ‘ Fit for Shared Decision-Making ’ on internal ( team ) and external ( patient ) participation in medical rehabilitation from a patient and staff perspective . Design : A multicentre , cluster-r and omized controlled study . Setting : Eleven medical rehabilitation clinics , divided into intervention and control groups . Subjects : A staff and a patient survey were conducted pre- and post-intervention , plus a further patient survey six months later . Intervention : Train-the-trainer programme ‘ Fit for Shared Decision-Making ’ for interprofessional setting s. Main measures : Each survey measured internal participation with a self-compiled six-item scale ( Internal Participation Scale , IPS ) , and external participation by means of a nine-item Shared Decision-Making Question naire ( SDM-Q-9 ) for the patients and for healthcare professionals . Results : Patient sample s numbered 402 for the pre- , 463 for the post-intervention data collection period and 461 six months after the intervention . Patients ’ appraisal of external participation ( Fperiod x group ( 2 ) = 0.256 , p=0.774 , η2=0.000 ) showed no change , whereas internal participation ( Fperiod x group ( 2 ) = 3.785 , p=0.023 , η2=0.007 ) showed a significant increase . A total of 195 healthcare professionals participated in the pre- and 168 in the post-intervention staff survey . Here external participation was significantly enhanced in the intervention group ( Fperiod x group ( 1 ) = 4.893 , p=0.028 , η2=0.014 ) . Conclusions : The train-the-trainer approach can be recommended for implementing internal and external participation in interprofessional setting s such as medical rehabilitation clinics . However , there is a need for more intensive staff training for internal participation and an additional intervention for patients to achieve success in all aspects Objectives To identify teamwork behaviors associated with improving efficiency and quality of simulated resuscitation training . Methods Secondary analysis of a r and omized controlled trial of trainees undergoing neonatal resuscitation training was performed . Trainees at a large academic center ( n = 100 ) were r and omized to receive st and ard curriculum ( n = 36 ) versus supplemental team training curriculum ( n = 62 ) . A 2-hour team training session focused on communication skills , and team behaviors served as the intervention . Outcomes of interest included resuscitation duration , time required to complete a simulated newborn resuscitation , and performance score , determined by evaluation of each of the team ’s steps during simulated resuscitation scenarios . Results The teamwork behaviors assertion and sharing information were associated with shorter resuscitation duration and higher performance scores . Each additional use of assertion ( per minute ) was associated with a duration reduction of 41 s ( 95 % confidence interval [ CI ] , −71.5 to −10.2 ) and an increase in performance score of 1.6 % ( 95 % CI , 0.4–2.7 ) . Each additional use of sharing information ( per minute ) was associated with a 14-second reduction in duration ( 95 % CI , −30.4 to 2.9 ) and a 0.8 % increase in performance score ( 95 % CI , 0.05–1.5 ) . Conclusions Teamwork behaviors of assertion and sharing information are 2 important mediators of efficiency and quality of resuscitations OBJECTIVE To test whether a team training intervention in stroke rehabilitation is associated with improved patient outcomes . DESIGN A cluster r and omized trial of 31 rehabilitation units comparing stroke outcomes between intervention and control groups . SETTING Thirty-one Veterans Affairs medical centers . PARTICIPANTS A total of 237 clinical staff on 16 control teams and 227 staff on 15 intervention teams . Stroke patients ( N=487 ) treated by these teams before and after the intervention . INTERVENTION The intervention consisted of a multiphase , staff training program delivered over 6 months , including : an off-site workshop emphasizing team dynamics , problem solving , and the use of performance feedback data ; and action plans for process improvement ; and telephone and videoconference consultations . Control and intervention teams received site-specific team performance profiles with recommendations to use this information to modify team process . MAIN OUTCOME MEASURES Three patient outcomes : functional improvement as measured by the change in motor items of the FIM instrument , community discharge , and length of stay ( LOS ) . RESULTS For both the primary ( stroke only ) and secondary analyses ( all patients ) , there was a significant difference in improvement of functional outcome between the 2 groups , with the percentage of stroke patients gaining more than a median FIM gain of 23 points increasing significantly more in the intervention group ( difference in increase , 13.6 % ; P=.032 ) . There was no significant difference in LOS or rates of community discharge . CONCLUSIONS Stroke patients treated by staff who participated in a team training program were more likely to make functional gains than those treated by staff receiving information only . Team based clinicians are encouraged to examine their own team . ( Clinical Trials.gov identifier NCT00237757 ) Multidisciplinary case conferencing using a video-link was compared with multidisciplinary case conferencing by telephone . One hundred patients were r and omized to either videoconferencing ( intervention group , 50 patients ) or audioconferencing ( control group , 50 patients ) . The effectiveness of the intervention compared with the control was evaluated in terms of : the number of conferences per patient , average length of conference , length of treatment , number of occasions of service , degree of multidisciplinary team involvement , recorded level of communication , quality of the management plan ( in terms of the number of points contained in it ) and staff satisfaction . The intervention and control groups showed significant differences on only two of the outcome measures : the mean number of case conferences per patient was less for the intervention group , and the intervention group had a shorter length of treatment ( 6 days ) than the control group ( 10 days ) . The study did not demonstrate any significant differences in occasions of service or time commitment , which might have result ed in lower costs . However , the introduction of case conferencing by video-link was accompanied by a high level of satisfaction on the part of the 14 team members who were interviewed This 24-month exploratory study evaluated whether a 6-month programme supported by a trained external facilitator was feasible , acceptable and led to the adoption of a multidisciplinary approach to audit by secondary care staff . Undertaken in five acute hospital sites in the East Midl and s UK , 22 multidisciplinary teams were r and omised to either an intervention or control arm . Employing mixed methods , a range of outcomes , including collaborative behaviour , was measured . The intervention was feasible and acceptable to staff . Involvement in the facilitated programme had a positive impact on self-reported knowledge ( P=0.000 post-intervention and at 4-months follow-up ) , skills ( P=0.000 post-intervention and P=0.02 at 4-months follow-up ) and attitudes ( P<0.01 post-intervention ) , appeared to have some influence on improving self-reported ( P<0.05 post-intervention ) and observed collaborative behaviour ( P=0.01 ) and led to better quality audit result ing in measurable improvements to care . Improved collaborative behaviour may have result ed from an increase in assertive behaviour by nurses . Research to test approaches to support teams to work effectively together is currently hampered by a lack of suitable research instruments and needs addressing before main ( phase 111 ) trials are undertaken Background : Effective interprofessional teamwork is an essential component for the delivery of high- quality patient care in an increasingly complex medical environment . The objective is to evaluate whether the implementation of care pathways ( CPs ) improves teamwork in an acute hospital setting . Design and Measures : A posttest-only cluster r and omized controlled trial was performed in Belgian acute hospitals . Teams caring for patients hospitalized with a proximal femur fracture and those hospitalized with an exacerbation of chronic obstructive pulmonary disease , were r and omized into intervention and control groups . The intervention group implemented a CP . The control group provided usual care . A set of team input , process , and output indicators were used as effect measures . To analyze the results , we performed multilevel statistical analysis . Results : Thirty teams and a total of 581 individual team members participated . The intervention teams scored significantly better in conflict management [ & bgr;=0.30 ( 0.11 ) ; 95 % confidence interval ( CI ) , 0.08 to 0.53 ] ; team climate for innovation [ & bgr;=0.29 ( 0.10 ) ; 95 % CI , 0.09 to 0.49 ] ; and level of organized care [ & bgr;=5.56 ( 2.05 ) ; 95 % CI , 1.35 to 9.76 ] . They also showed lower risk of burnout as they scored significantly lower in emotional exhaustion [ & bgr;=−0.57 ( 0.21 ) ; 95 % CI , −1.00 to −0.14 ] and higher in the level of competence ( & bgr;=0.39 ; 95 % CI , 0.15 to 0.64 ) . No significant effect was found on relational coordination . Conclusions : CPs are effective interventions for improving teamwork , increasing the organizational level of care processes , and decreasing risk of burnout for health care teams in an acute hospital setting . Through this , high-performance teams can be built Objectives The authors conducted a r and omised controlled trial of four pedagogical methods commonly used to deliver teamwork training and measured the effects of each method on the acquisition of student teamwork knowledge , skills , and attitudes . Methods The authors recruited 203 senior nursing students and 235 fourth-year medical students ( total N=438 ) from two major universities for a 1-day interdisciplinary teamwork training course . All participants received a didactic lecture and then were r and omly assigned to one of four educational methods : didactic ( control ) , audience response didactic , role play and human patient simulation . Student performance was assessed for teamwork attitudes , knowledge and skills using : ( a ) a 36-item teamwork attitudes instrument ( CHIRP ) , ( b ) a 12-item teamwork knowledge test , ( c ) a 10-item st and ardised patient ( SP ) evaluation of student teamwork skills performance and ( d ) a 20-item modification of items from the Mayo High Performance Teamwork Scale ( MHPTS ) . Results All four cohorts demonstrated an improvement in attitudes ( F1,370=48.7 , p=0.001 ) and knowledge ( F1,353=87.3 , p=0.001 ) pre- to post-test . No educational modality appeared superior for attitude ( F3,370=0.325 , p=0.808 ) or knowledge ( F3,353=0.382 , p=0.766 ) acquisition . No modality demonstrated a significant change in teamwork skills ( F3,18=2.12 , p=0.134 ) . Conclusions Each of the four modalities demonstrated significantly improved teamwork knowledge and attitudes , but no modality was demonstrated to be superior . Institutions should feel free to utilise educational modalities , which are best supported by their re sources to deliver interdisciplinary teamwork training PURPOSE AND BACKGROUND Emergency medical services ( EMSs ) vary considerably . While some are physician staffed , most systems are run by paramedics . The objective of this r and omized , controlled simulation study was to compare the emergency care between physician staffed EMS teams ( control group ) and paramedic teams that were supported telemedically by an EMS physician ( telemedicine group ) . METHODS Overall 16 teams ( 1 EMS physician , 2 paramedics ) were r and omized to the control group or the telemedicine group . Telemedical functionalities included two-way audio communication , transmission of vital data ( numerical values and curves ) and video streaming from the scenario room to the remotely located EMS physician . After a run-in scenario all teams completed four st and ardized scenarios , in which no highly invasive procedures ( e.g. thoracic drain ) were required , two using high-fidelity simulation ( burn trauma , intoxication ) and two using st and ardized patients ( renal colic , barotrauma ) . All scenarios were videotaped and analyzed by two investigators using predefined scoring items . RESULTS Non case-specific items ( 31 vs. 31 scenarios ) : obtaining of ' symptoms ' , ' past medical history ' and ' events ' were carried out comparably , but in the telemedicine group ' allergies ' ( 17 vs. 28 , OR 7.69 , CI 2.1 - 27.9 , p=0.002 ) and ' medications ' ( 17 vs. 27 , OR 5.55 , CI 1.7 - 18.0 , p=0.004 ) were inquired more frequently . No significant differences were found regarding the case-specific items and in both groups no potentially dangerous mistreatments were observed . CONCLUSION Telemedically assisted paramedic care was feasible and at least not inferior compared to st and ard EMS teams with a physician on-scene in these scenarios AIM The TELEMAM trial aim ed to assess the clinical effectiveness and costs of telemedicine in conducting breast cancer multi-disciplinary meetings ( MDTs ) . METHODS Over 12 months 473 MDT patient discussion s in two district general hospitals ( DGHs ) were cluster r and omised ( 2:1 ) to the intervention of telemedicine linkage to breast specialists in a cancer centre or to the control group of ' in-person ' meetings . Primary endpoints were clinical effectiveness and costs . Economic analysis was based on a cost-minimisation approach . RESULTS Levels of agreement of MDT members on a scale from 1 to 5 were high and similar in both the telemedicine and st and ard meetings for decision sharing ( 4.04 versus 4.17 ) , consensus ( 4.06 versus 4.20 ) and confidence in the decision ( 4.16 versus 4.07 ) . The threshold at which the telemedicine meetings became cheaper than st and ard MDTs was approximately 40 meetings per year . CONCLUSION Telemedicine delivered breast cancer multi-disciplinary meetings have similar clinical effectiveness to st and ard ' in-person ' meetings 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 The intensive care unit ( ICU ) , where death is common and even survivors of an ICU stay face the risk of long-term morbidity and re-admissions to the ICU , represents an important setting for improving communication about palliative and end-of-life care . Communication about the goals of care in this setting should be a high priority since studies suggest that the current quality of ICU communication is often poor and is associated with psychological distress among family members of critically ill patients . This paper describes the development and evaluation of an intervention design ed to improve the quality of care in the ICU by improving communication among the ICU team and with family members of critically ill patients . We developed a multi-faceted , interprofessional intervention based on self-efficacy theory . The intervention involves a " communication facilitator " - a nurse or social worker - trained to facilitate communication among the interprofessional ICU team and with the critically ill patient 's family . The facilitators are trained using three specific content areas : a ) evidence -based approaches to improving clinician-family communication in the ICU , b ) attachment theory allowing clinicians to adapt communication to meet individual family member 's communication needs , and c ) mediation to facilitate identification and resolution of conflict including clinician-family , clinician-clinician , and intra-family conflict . The outcomes assessed in this r and omized trial focus on psychological distress among family members including anxiety , depression , and post-traumatic stress disorder at 3 and 6 months after the ICU stay . This manuscript also reports some of the lessons that we have learned early in this study UNLABELLED Interdisciplinary rounds ( IRs ) have been proposed to improve staff communication and reduce LOS . There have been no studies of IRs on an inpatient telemetry ward . Patients on a telemetry unit of a community hospital were r and omly assigned to either an IR intervention or st and ard care . Charts were review ed to determine LOS , patient characteristics , and indirect indices of quality of care . INTERVENTION Daily work rounds , in which resident physicians , nurses , and ancillary staff meet to discuss patients on the team . RESULTS 84 patients were enrolled , 42 r and omized to the intervention and 42 to st and ard care . There was no significant difference in LOS . Indirect measures of quality of care ( dietician , pharmacist , or physical therapist visit ) did not differ . In a multiple linear regression model , only abnormal laboratory data , the presence of dementia , and the presence of a home health aid significantly predicted LOS . CONCLUSION IRs did not decrease LOS in a telemetry ward . Whereas a potential benefit of IRs in other setting s can not be ruled out , this study emphasizes the importance of rigorous testing of strategies to enhance the quality or reduce the costs of inpatient care Procedural checklists may be useful for increasing the reliability of safety-critical processes because of their potential capacity to improve teamwork , situation awareness , and error catching . To test the hypothesized utility and adaptability of checklists to surgical teams , we performed a r and omized controlled trial of procedural checklists to determine their capacity to increase the frequency of safety-critical behaviors during 47 laparoscopic cholecystectomies . Ten attending surgeons at an academic tertiary care center were r and omized into two equal groups - half of these surgeons received basic team training and used a preprocedural checklist whereas the other half performed st and ard laparoscopic cholecystectomies . All procedures were videotaped and scored by trained review ers for the presence of safety-critical behaviors . There were no differences detected in patient outcomes , case times , or technical proficiency between groups . Cases performed by surgeons in the intervention ( checklist ) group were significantly more likely to involve positive safety-related team behaviors such as case presentations , explicit discussion s of roles and responsibilities , contingency planning , equipment checks , and postcase debriefings . Overall , situational awareness did not significantly differ between the intervention and control groups . Participants in the intervention ( checklist ) group consistently rated their cases as involving less satisfactory subjective levels of comfort , team efficiency , and communication compared with those performed by surgeons in the control group . Surgical procedural safety checklists have the capacity to increase the frequency of positive team behaviors in the operating room during laparoscopic surgery . Adapting to the use of a procedural checklist may be initially uncomfortable for participants Background To evaluate the effectiveness of a multifaceted implementation strategy on physicians ’ referral rate to and knowledge on the community occupational therapy in dementia program ( COTiD program ) . Methods A cluster r and omized controlled trial with 28 experimental and 17 control clusters was conducted . Cluster included a minimum of one physician , one manager , and two occupational therapists . In the control group physicians and managers received no interventions and occupational therapists received a postgraduate course . In the experimental group physicians and managers had access to a website , received newsletters , and were approached by telephone . In addition , physicians were offered one outreach visit . In the experimental group occupational therapists received the postgraduate course , training days , outreach visits , regional meetings , and access to a reporting system . Main outcome measure was the number of COTiD referrals received by each cluster which was assessed at 6 and 12 months after the start of the intervention . Referrals were included from both participating physicians ( enrolled in the study and received either the control or experimental intervention ) and non-participating physicians ( not enrolled but of whom referrals were received by participating occupational therapists ) . Mixed model analyses were used to analyze the data . All analyses were based on the principle of intention-to-treat . Results At 12 months experimental clusters received significantly more referrals with an average of 5,24 referrals ( SD 5,75 ) to the COTiD program compared to 2,07 referrals in the control group ( SD 5,14 ) . The effect size at 12 months was 0.58 . Although no difference in referral rate was found for the physicians participating in the study , the number of referrals from non-participating physicians ( t −2,55 / 43 / 0,02 ) differed significantly at 12 months . Conclusion Passive dissemination strategies are less likely to result in changes in professional behavior . The amount of physicians exposed to active strategies was limited . In spite of this we found a significant difference in the number of referrals which was accounted for by more referrals of non-participating physicians in the experimental clusters . We hypothesize that the increase in referrals was caused by an increase in occupational therapists ’ efforts to promote their services within their network . Trial registration |
12,322 | 27,113,258 | The results indicate that there is very low quality evidence that back schools are no more effective than a placebo ( or sham or attention control ) or another treatment ( physical therapies , myofascial therapy , joint manipulations , advice ) on pain , disability , work status and adverse events at short-term , intermediate-term and long-term follow-up .
There is very low quality evidence that shows a statistically significant difference between back schools and a placebo ( or sham or attention control ) for return to work at short-term follow-up in favour of back school .
Very low quality evidence suggests that back school added to a back care programme is more effective than a back care programme alone for disability at short-term follow-up .
Very low quality evidence also indicates that there is no difference in terms of adverse events between back school and myofascial therapy , joint manipulation and combined myofascial therapy and joint manipulation .
AUTHORS ' CONCLUSIONS It is uncertain if back schools are effective for acute and subacute non-specific LBP as there is only very low quality evidence available . | BACKGROUND Since the introduction of the Swedish back school in 1969 , back schools have frequently been used for treating people with low-back pain ( LBP ) .
However , the content of back schools has changed and appears to vary widely today .
In this review we defined back school as a therapeutic programme given to groups of people , which includes both education and exercise .
This is an up date of a Cochrane review first published in 1999 , and up date d in 2004 .
For this review up date , we split the review into two distinct review s which separated acute from chronic LBP .
OBJECTIVES To assess the effectiveness of back schools on pain and disability for people with acute or subacute non-specific LBP .
We also examined the effect on work status and adverse events . | 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 OBJECTIVES To evaluate the effectiveness of a back school program in pain , functional status , quality of life , and in anxiety and depression in patients with non-specific low back pain . METHODS Sixty patients with low back pain were r and omized to an intervention and control group . The intervention group underwent a five-weekly back school program . The control group was seen in weekly medical visits , without educative approaches . Both groups took acetaminophen as analgesic medication . All subjects were evaluated by a blind physiotherapist after r and omization , 30 , 60 and 120 days . Roll and -Morris , SF-36 , STAI and Beck question naires , pain visual analogical scale and Schober 's test were applied . Non-steroidal anti-inflammatory drugs ( NSAID ) consumption was considered co-intervention . The statistical analyses were performed using Pearson 's Chi-Square analysis and Student 's t-test to compare the baseline characteristics of the groups and the analysis of variance ( ANOVA ) with repeated measures to assess changes inter/intra groups . RESULTS There were no significant differences in the baseline characteristics between the two groups . Fifty-five patients completed the study . The intervention group showed a significant improvement in the general health domain , assessed by SF-36 , and also in the reduction of acetaminophen and NSAID intake . There was no significant difference between the groups in pain , functional status , anxiety or depression . CONCLUSION The back school program was more effective than any educational intervention in general health status and in decreasing acetaminophen and NSAID intake . It was ineffective in the other quality of life domains , in pain , functional status , anxiety and depression In a prospect i ve trial , 222 adults with low-back pain of at least 2 weeks ' duration in a Health Maintenance Organization ( HMO ) were r and omly assigned to usual care ( UC ) , a 4-hour back school psychoeducational session ( LBS ) , or the same back school plus a 1-year “ compliance package ” program design ed to encourage appropriate self-management for back pain ( CP ) . Sixty-four percent of LBS and CP subjects attended their back school sessions . Follow-up measurement of pain level ( using the Visual Analogue Scale ) , functional status ( using the Sickness Impact Profile ) , and various other indicators of health status showed no measurable effect of either treatment condition ( LBS or CP ) compared with UC at 3 , 6 , 12 , and 18 months after entry into the study . Initial disability resolved by 3 months in most patients , and a minority of subjects ( 10–15 % ) showed residual or recurrent functional Impairment 1 year after entry . Health care utilization tended to be slightly higher after intervention In the CP group . With or without follow-up encouragement , back school instructions given in a single 4-hour session had no measurable impact on the comfort or functional status of the majority of patients with new onset back pain in this HMO Background Different interventions can reduce the burden of the chronic low back pain . One example is the use of a ' Back School Programme ' . This is a brief therapy that uses a health education method to empower participants through a procedure of assessment , education and skill development . This study aim ed to evaluate to what extent the programme could improve quality of life in those who suffer from the condition . Methods This was a r and omized controlled trial . One-hundred and two female patients with low back pain ( n = 102 ) were r and omly allocated into two groups , matched in terms of age , weight , education , socioeconomic status , occupation and some aspects of risk behavior . Group 1 ( back school group , n = 50 ) but not group 2 ( clinic group , n = 52 ) received the ' Back School Programme ' . Then quality of life using the Short Form Health Survey ( SF-36 ) was assessed at two time points : at baseline and at three months follow-up . The findings were compared both within and between two groups . Results The ' Back School Programme ' was effective in improving patients ' quality of life ; significant differences were found on all eight subscales of the SF-36 for group 1 . In the clinic group ( group 2 ) , improvement was observed on three scales ( bodily pain , vitality and mental health ) but these improvements were less than in group 1 . The mean improvement over all eight subscales of the SF-36 was significantly better for the ' Back School Programme ' group . Conclusion The ' Back School Programme ' is an effective intervention and might improve the quality of life over a period of 3 months in patients who experience chronic low back pain The purpose of this study was to assess the effects of two different treatment modalities on the rehabilitation process of chronic sacroiliac joint patients . The treatment modalities included spinal manipulative therapy given by a chiropractor and a program of back school therapy given by a physiotherapist . The rehabilitation process was assessed using clinical and biomechanical measures . It was found that back school therapy was a better treatment modality than the spinal manipulative therapy , according to the clinical measures of rehabilitation . Precisely the opposite result was found for the biomechanical measures The aim of this trial was to determine whether social interaction between patients with long-lasting nonspecific back pain reduces subjective or objective disability . The participants were selected from persons visiting an occupational health care unit because of back pain . After a clinical examination in a university clinic , subjects without a specific diagnosis and having no disabilities preventing active rehabilitation were selected for study . The subjects ( n = 108 ) were r and omized into treatment ( n = 54 ) and control groups ( n = 54 ) . Altogether 18 study groups , 9 treatment groups and 9 groups for controls , were formed . Before starting the back schools altogether 15 subjects dropped out . Both the treatment groups ( n = 47 ) and the controls ( n = 46 ) attended a back school consisting of 10 lessons and demonstrations supervised by a physiotherapist . The participants in treatment groups , but not the controls , had physical exercise and social intercourse with other members within the group . The clinical examination was repeated after 6 and 12 months . Both the treatment groups and the controls showed improvement in perceived functional capacity ( assessed with Oswestry disability question naire ) and in perceived life quality ( assessed with 15D score ) . At the 6-month follow-up life quality had improved statistically significantly more among the participants in treatment groups than among the controls , and at the 12-month follow-up the Oswestry index showed corresponding improvement . Among subjects suffering from nonspecific back pain , social support improves the results of active rehabilitation A clinical trial , aim ed at secondary prevention of low-back pain , was performed in 142 hospital employees reporting at least three annual episodes of this condition . Participants were r and omly assigned to one of three groups : a calisthenics program ( CAL ) for 3 months with biweekly sessions of flexion exercises , a back school program ( 5 sessions ) , and a control group . The effectiveness of the two intervention programs was evaluated over a 1-year period . Baseline preintervention data and evaluation at the end of 3 months of intervention and after an additional 6 months were collected . A monthly surveillance for the whole year showed a mean of 4.5 “ painful months ” in the CAL group versus 7.3 and 7.4 months in the back school and control groups , respectively ( P < 0.0001 ) . The superiority of the CAL group was achieved partly because of the significant increase in trunk forward flexion and to initial increment in abdominal muscle strength . The increased trunk flexion was associated with the rate of participation in the CAL sessions . Further research is needed to answer the question of “ intensity versus type of exercise ” by comparing different intervention programs , with similar intensity Study Design . R and omized controlled trial . Objectives . To compare high- and low-intensity back schools with usual care in occupational health care . Summary of Background Data . The content and intensity of back schools vary widely and the method ologic quality of r and omized controlled trials is generally weak . Until now , no back school has proven to be superior for workers sick-listed because of subacute nonspecific low back pain . Methods . Workers ( n = 299 ) sick-listed for a period of 3 to 6 weeks because of nonspecific low back pain were recruited by the occupational physician and r and omly assigned to a high-intensity back school , a low-intensity back school , or care as usual . Outcome measures were days until return to work , total days of sick-leave , pain , functional status , kinesiophobia , and perceived recovery and were assessed at baseline and at 3 and 6 months of follow-up . Principal analyses were performed according to the intention-to-treat principle . Results . We r and omly allocated 299 workers . Workers in the low-intensity back school returned to work faster compared with usual care and the high-intensity back school , with hazard ratios of 1.4 ( P = 0.06 ) and 1.3 ( P = 0.09 ) , respectively . The comparison between high-intensity back school and usual care result ed in a hazard ratio of 1.0 ( P = 0.83 ) . The median number of sick-leave days was 68 , 75 , and 85 in the low-intensity back school , usual care , and high-intensity back school , respectively . Beneficial effects on functional status and kinesiophobia were found at 3 months in favor of the low-intensity back school . No substantial differences on pain and perceived recovery were found between groups . Conclusions . The low-intensity back school was most effective in reducing work absence , functional disability , and kinesiophobia , and more workers in this group scored a higher perceived recovery during the 6-month follow-up Low back injury is the leading cause of compensable injury . A National Health Objective for the year 2000 is to increase to at least 50 % the number of worksites offering back injury protection programs . The 6 week Back School intervention included exercise and education . A portion of the sample of 74 back injured municipal employees also was assigned r and omly to a counseling intervention . Pre-intervention and post-intervention testing revealed significant posttest increases in back strength and flexibility . Significant improvements also were noted in psychological well being , depression , anxiety , and perceptions of pain . No significant differences were found , on any of the measures , between employees who did and who did not receive the counseling intervention . Method ological concerns relate to the possibility of sampling bias and instrumentation . Future research with control groups is needed , as well as the testing of interventions that may be both effective and require less work release time Inpatient and outpatient treatments were compared with a control intervention in 288 men and 168 women , aged 35 - 54 , who were at work , but suffered from chronic or recurrent low back pain . Physical measurements and back pain assessment s were carried out before the intervention and at a 3-month follow-up . Physical fitness improved most in the in patients , but the out patients did not differ from the controls . Correlations between back pain and physical measurements indicated that increase of lumbar and hip mobility was more important than increase of trunk strength for subjective progress in these patients . Increased trunk extension strength correlated significantly with subjective progress in women , who also had higher correlations between improved physical fitness and progress than men Ninety-two chronic low back pain patients were r and omly allocated to two groups to evaluate the effectiveness of a back school compared with an exercise-only regimen according to specified outcome variables . The data from 78 patients with 7 years mean duration of symptoms was analyzed . Three assessment s were made : before treatment and 6 and 16 weeks after treatment . Changes in patients ' levels of pain , functional disability , and other related variables were compared in the two groups . Almost all variables showed an improvement at 6 weeks . At 16 weeks , functional disability and pain levels showed a significant difference . Back school patients continued to make an improvement . This method of managing low back pain makes maximal use of limited re sources and appears to be effective , especially in the longer term OBJECTIVE To assess the efficacy of a back school program for patients with a first episode of acute work-related low back pain requiring compensation . DESIGN A r and omized single-blind controlled trial . SETTING A private physiatrics outpatient clinic . PATIENTS The mean duration of low back pain was 15 days . INTERVENTION Eligible patients were r and omized to a st and ard treatment program that included daily physiotherapy ( n = 86 ) or the same program with the addition of back school ( n = 82 ) . The back school program consisted of three 90-minute sessions given by a single trained instructor at 0 , 1 , and 8 weeks . MAIN OUTCOME MEASURES The primary outcomes were the time off work for the presenting episode of back pain and the number and duration of recurrences in the year following the study onset . Secondary outcomes included the level of pain , spinal mobility , active straight-leg raising , and functional disability assessed by the Oswestry and Rol and -Morris scales . RESULTS Those r and omized to the back school group gained significantly more knowledge , based on the multiple choice examination ( p = .0001 ) and performed the exercise program significantly better ( p = .0001 ) than the st and ard care group . There were no differences between the two treatment groups for either of the primary outcomes . The median time to return to work from r and omization was 33 days for both the back school and the st and ard care groups ( p = .48 ) . The number of compensated recurrences of low back pain over 1 year was similar ( back school = 14 , st and ard care = 10 , p = .16 ) , as was the median duration of these episodes ( back school = 25 days , st and ard care = 70 days , p = .21 ) . There were no significant differences favoring the back school group for any of the secondary outcomes at the posttreatment , 6-month , or 12-month assessment s. CONCLUSION A back school intervention in addition to st and ard care result ed in no reduction in the time to return to work or the number or duration of recurrences of low back pain requiring compensation over a period of one year The long-term outcome results of inpatient and outpatient treatment of low back pain ( LBP ) were studied in 476 subjects ( aged 35 - 54 , 63 % men ) r and omly assigned to three study groups : in patients ( n = 157 ) , out patients ( n = 159 ) , and controls ( n = 160 ) . The study included changes in the severity of low back pain , grade and disability , compliance with self-care , data on disability pensions , and days of sickness allowance during a 2.5-year follow-up period . These variables were used as outcome criteria . Pain and disability had decreased significantly in the two treated groups up to the 3-month follow-up . LBP was still a little slighter in the in patients at the 1.5-year and 22-month follow-ups , but there were no significant differences between the groups in disability caused by LBP . The refresher programme carried out 1.5 years after the first one did not bring about as clear short-term improvement in pain and disability as the first treatment . During the whole 2.5-year follow-up compliance with self-care was better in the two treated groups , especially in the in patients . Days of sickness allowance had increased somewhat more in the controls than in the in patients during the follow-up . No differences between the groups were found in the number of disability pensions granted 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 & NA ; The current investigation studied the effectiveness of a secondary prevention program for nurses with back pain who were deemed at risk for developing a chronic problem . A 2 × 3 repeated measures design was employed with 2 groups and 3 assessment periods . The treatment group received an intervention design ed to reduce current problems , but above all to prevent reinjury and minor pains from becoming chronic medical problems , and it included a physical and behavioral therapy package . The control group was placed on a waiting‐list . Results indicated that the treatment group had significantly greater improvements than the control group for pain intensity , anxiety , sleep quality and fatigue ratings , observed pain behavior , activities , mood , and helplessness . These differences were generally maintained at the 6 month follow‐up . In addition , the treatment group broke a trend for increasing amounts of pain‐related absenteeism , while the control group did not . Taken as a whole , the results suggest that a secondary prevention program aim ed at altering life style factors may represent an effective method for dealing with musculoskeletal pain problems Outcome of inpatient and outpatient treatment of low back pain was studied in 459 patients ( aged 35 - 54 years , 63 % men ) ; 156 in patients , 150 out patients and 153 controls . Changes in low back pain and in disability caused by it , and adherence and accomplishment of back exercises were used as short-term outcome criteria . The overall results showed a significant decrease in pain and disability and better compliance in the two treated groups when compared to the controls . There was also a significant difference in treatment gains between the in patients and out patients ; i.e. the decrease in pain was greater and the frequency of back exercises higher in the in patients . The in patients also estimated their treatment benefits more positively than the out patients Study Design . A controlled clinical trial . Objectives . To examine the long‐term effect of an informative approach to low back pain . Summary of Background Data . In management and prevention of low back pain , back school based on an ergonomic approach have played an important role . The effect of such informative interventions is not clear . Methods . A 5‐year follow‐up study was done on patients included in a previous study . The outcome was measured by return to work or still on sick leave . The patients were allocated to an intervention group ( n = 245 ) and a control group ( n = 244 ) . Only the intervention group was called in for examination and intervention and answered a battery of tests for psychological and health factors . The intervention apart from the clinical examination consisted of education in a " mini back school . " The program was based on a new medical model for low back pain . Results . Forty‐seven ( 19 % ) of the patients in the intervention group , compared with 84 patients ( 34 % ) in the control group , were still on sick leave after 5 years ( P < 0.001 ) . There were fewer recurrences of sick leave ( P < 0.03 ) in the intervention group than in the control group . Based on Internal Health Locus of Control , number of children , and income , 75 % were correctly classified as nonreturners in the intervention group . Conclusions . This study indicates that subchronic low back pain may be managed successfully with an approach that includes clinical examination combined with information for patients about the nature of the problem , provided in a manner design ed to reduce fear and give them reason to resume light activity The purpose of the present study was to investigate the long-term effect of the Active Back School programme on minimizing recurrences of episodes of low back pain . Forty-three subjects were r and omly allocated to the Active Back School group and 38 to the control group . There were no significant differences between the groups with regard to baseline characteristics . The Active Back School programme comprised 20 lessons each divided into a 20-min theoretical and a 40-min exercise part during a 13-week period . Nine participants ( 11 % ) dropped out during the study period . Recurrence of new low back pain episodes was significantly less ( p = 0.04 ) , and the time from inclusion to the first new low back pain episode was significantly on the side of the Active Back School group ( p < 0.01 ) . The duration of sick leave was found to be significantly shorter ( p < 0.01 ) in the Active Back School group compared to the control group . The Active Back School reduced the recurrence and severity of new low back pain episodes at 36 months ' follow-up Study Design This study involved a post‐test only , control group design . Objectives To analyze the learning effects of back education programs ( video and classroom learning ) . Summary of Background Data Previous research has examined lost work time and workers ' compensation costs but has not addressed the learning effects of back schools . This study used the American Back School as the education intervention . The American Back School teaches students to maintain the lumbar lordosis while lifting . Methods The subjects ( n = 205 ) were assigned to three groups through modified r and omization . Three employees who previously sustained low back injury were placed in the back school group . The back school group , Group I , ( n = 74 ) attended a back school program that included cognitive learning strategies and practice in correct lifting . A video group , Group II , ( n = 64 ) viewed a similar program that consisted of spinal anatomy and biomechanics and instruction in correct lifting technique . A control group , Group III , ( n = 67 ) received no back education . One week after the education intervention , 145 of the subjects from the three groups had the lumbar lordosis measured with a flexible ruler while assuming a lifting position . The ruler was placed over the lumbar spinous processes , and the lordotic angle was calculated . A 12‐item multiple choice test and a 10‐item Likert scale were administered to 199 of the subjects in the three groups to determine the cognitive learning effect and the perceived relevance of the program , respectively . Results Multivariate analysis of variance was used and demonstrated significant differences between the back school group and the control group on the cognitive , psychomotor , and affective measures at the 0.001 level . No significant differences were found between the video and control groups on the measures with additional univariate testing . Conclusions The results indicate that the back school is an effective tool for influencing lifting posture and conveying information regarding spinal mechanics and lifting technique . In addition , the back school videos may not be an effective means of preventing low back injury AIMS The purpose of the study was to measure the effectiveness of a spine training programme ( Back School ) in nurses who have been living with chronic low back pain . It was hypothesised that active therapy , ergonomics and education called Back School will significantly decrease the pain intensity levels and improve the body posture of the study participants . BACKGROUND A chronic low back pain is a significant work-related health problem among healthcare workers around the world . Proper body posture is essential for decreasing pain in healthcare workers who have history of chronic low back pain . By teaching proper body posture and with the creation of occupational setting s that are ' spine-friendly ' hospitals and other healthcare setting s can significantly lower the suffering of their nursing staff . DESIGN Single-blinded r and omised controlled trial was utilised with six- and 12-months follow-up . METHODS The study was carried out at the University of Pecs , Faculty of Health Sciences from 2007 to 2008 involving 124 nurses with low back pain . Participants were r and omly assigned to the study group ( who have received ergonomics training and education called Back School ) with an intervention conducted once a week for a six-week period . The control group received passive physiotherapy once a week for a six-week period . Further follow-up measurements were conducted at six and 12 months , respectively . The study variables and outcome measures were pain intensity and body posture ( angle of thoracic kyphosis and lumbar lordosis ) . The pain intensity was investigated with the Visual Analogue Scale . Body posture was recorded and analysed with the Zebris biomechanical motion analysis system . RESULTS The statistical analysis of repeated measures indicated a significant decrease in back pain intensity after the therapy in both groups , compared with measurements before the therapy ; however , the BS group showed significantly better results during the six-month and one-year follow-up period . The biomechanical analysis of postures after the therapy in the BS group showed significant improvements over the control group ; during the follow-up , the difference was still significant , yet slightly reduced . CONCLUSIONS This study has shown that a significant reduction in the pain intensity and improvement in body posture can be achieved by the usage of the active physical therapy methods ( Back School ) in nurses who are experiencing chronic lower back pain . RELEVANCE TO CLINICAL PRACTICE The Back School programme when compared with the passive physical therapies ( such as massage , ultrasound treatment , etc . ) shows significant improvement in reduction in pain and greatly improves the posture of healthcare workers . The adoption of the Back School programme for the treatment of the healthcare workers with chronic low back problems should be a treatment of choice and st and ard that should be adopted when design ing occupational healthcare policies and procedures Objective . This r and omized clinical trial was design ed to determine the effect of treating low back pain as a benign , self limiting condition by light normal activity . Methods . Patients on sickness leave from work for more than 8 weeks were r and omized into two groups : intervention ( n = 463 ) and control ( n = 512 ) . Those in the intervention group were examined , provided information , and given instruction . Outcome was measured by return or failure to return to work ( still on sickness leave ) . Results . Survival analysis showed a highly significant ( P = 0.000 ) reduction in sickness leave in the intervention group as compared with the control group . At 200 days 60 % were still on sickness leave in the control group vs. 30 % in the intervention group . A multivariate analysis with age , sex , and treatment as cofactors showed that sex had no effect on length of sickness leave and that treatment retained its effect when adjusting for differences in age composition . Conclusion . This study indicates that low back pain treated as a benign , self limiting condition recommended to light mobilization gives superior results as compared to treatment within a conventional medical system The use of an education program for patients with chronic low back pain ( Back School ) has been investigated . The effect evaluation is based on a pretest-post-test-control group design , including a follow-up after 8 weeks . The Maastricht Back School is based on the theory that pain is also maintained by emotional , cognitive and environmental factors . Information and training are given on these and physical factors . The purpose of the course is to teach patients to manage their own pain problem . The results suggest that the Back School program for patients with chronic low back pain can have a positive effect Summary of Background Data . Back schools may be effective in treating back problems , but there is conflicting evidence of the effect on prevention . Objectives . To investigate if passive prone extensions of the back can prevent back problems . Study Design . Prospect i ve , r and omized controlled intervention trial . Methods . In total , 314 male conscripts were r and omized into two groups . After r and omization , 65 conscripts dropped out for administrative reasons , leaving 249 conscripts to participate fully in the study . Data were collected through question naires at the start of military duty and after 10 months . All conscripts in the intervention group had one 40-minute theoretical lesson on back problems and ergonomics and had to perform passive prone extensions of the back daily during the rest of their military duty . The control group had no intervention . Outcome variables were as follows : 1 ) number of persons with self-reported back problems during the last 3 weeks ; 2 ) number of persons with self-reported back problems during the last year ; and 3 ) number of persons who reported having consulted the regiment medical physician with back problems during their military service . Results . In an intention-to-treat analysis , significantly fewer persons in the intervention group versus those in the control group reported back problems during the last year ( 33%versus 51 % ) , and the number needed to prevent was 6 . Significantly fewer persons in the intervention group versus those in the control group consulted the regiment infirmary ( 9%versus 25 % ) , and the number needed to prevent was 6 . Conclusion . It may be possible to reduce the prevalence rate of back problems and the use of health care services during military service , at a low cost , using passive prone extensions of the back motivated by a back school approach , including the theory of the disc as a pain generator and ergonomic instructions Study Design . A r and omized , assessor-blinded clinical trial was conducted . Objective . To investigate the relative effectiveness of three manual treatments and back school for patients with subacute low back pain . Summary of Background Data . Literature comparing the relative effectiveness of specific therapies for low back pain is limited . Methods . Among the 5925 inquiries , 206 patients met the specific admission criteria , and 200 patients r and omly received one of four treatments for 3 weeks : back school , joint manipulation , myofascial therapy , and combined joint manipulation and myofascial therapy . These patients received assessment s at baseline , after 3 weeks of therapy , and 6 months after the completion of therapy . The primary outcomes were evaluated using visual analog pain scales and Rol and –Morris activity scales . Results . All four groups showed significant improvement in pain and activity scores after 3 weeks of care , but did not show further significant improvement at the 6-month follow-up assessment . No statistically significant between-group differences were found either at the 3-week or 6-month re assessment s. Conclusions . For subacute low back pain , combined joint manipulation and myofascial therapy was as effective as joint manipulation or myofascial therapy alone . Additionally , back school was as effective as three manual treatments STUDY DESIGN A r and omized , controlled , single-center trial with a stratified group design . OBJECTIVE To investigate the secondary prophylactic effect of the Active Back School program on minimizing recurrences of low back pain episodes . SUMMARY OF BACKGROUND DATA The results of back school interventions are controversial . Previous work often used short intervention periods and low doses of practical training . However , studies with the highest method ologic scores have shown the best results , especially when conducted in occupational setting s and coupled with a comprehensive rehabilitation program . METHODS By block r and omization , 19 men and 24 women were allocated to Active Back School , with 18 men and 20 women as control subjects . The Slumps test and number of low back pain episodes during the previous 36 months were used as stratification factors . There were no significant differences between the groups with regard to demographic factors and initially observed variables . Active Back School consisted of 20 lessons over a 13-week period . Each lesson was divided into a 20-minute theoretical part and a 40-minute exercise part . All participants were examined on enrollment , then 5 and 12 months after initiation of the program . Outcome measures were recurrence of low back pain episodes and number of days of sick leave . RESULTS The recurrence of new low back pain episodes was significantly lower ( P < 0.05 ) and the time from inclusion to the first new episode significantly longer ( P < 0.01 ) in the Active Back School group than in the control group . In the Active Back School group , seven participants took sick leave because of low back pain episodes during the first 12 months of follow-up compared with 11 among the control subjects . The number of sick leave days was significantly lower ( P < 0.05 ) in the Active Back School group than in the control group . CONCLUSION Active Back School reduced the recurrence and severity of new low back pain episodes according to results of follow-up examinations performed 5 and 12 months after enrollment Medical rehabilitation in Germany is still lacking in patient education programmes that meet certain quality requirements such as the use of manuals , patient-oriented didactics , and evaluations of effectiveness . For patients with chronic low back pain , no st and ardized and evaluated back school programme has so far been available for routine use . In this paper , we demonstrate the development of a quality -assured back school based on a health-education programme of the German statutory pension insurance scheme . Both topics and didactics incorporate treatment evidence , practice guidelines , quality criteria for patient education and theories of health and illness behaviour . First , formative evaluation was conducted to assess patient acceptance and practicability of the manual . Second , effects of the back school programme were assessed on a short-term ( at the end of rehabilitation ) , medium-term ( 6-month follow-up ) and long-term ( 12-month follow-up ) basis in a r and omized controlled study of patients with low back pain ( n=360 ) . Results show a significant medium treatment effect in patients ' knowledge about chronic back pain and its treatment at the end of rehabilitation ( p<0.001 ; eta (2)=0.080 ) . Furthermore , small to medium effects were also observed among some secondary outcomes , such as motivation to physical activity , pain beliefs and pain intensity . After the programme 's medium- and long-term effects have been demonstrated , it will be recommended for implementation in medical rehabilitation . The manual meets the requirements that allow for a successful transfer into clinical practice |
12,323 | 27,025,289 | It appears that the participants did not have previous complications such as bleeding or perforation .
We found no studies that provide the relative benefits and harms of medical versus surgical treatment for recurrent or refractory peptic ulcers . | BACKGROUND Refractory peptic ulcers are ulcers in the stomach or duodenum that do not heal after eight to 12 weeks of medical treatment or those that are associated with complications despite medical treatment .
Recurrent peptic ulcers are peptic ulcers that recur after healing of the ulcer .
Given the number of deaths due to peptic ulcer-related complications and the long-term complications of medical treatment ( increased incidence of fracture ) , it is unclear whether medical or surgical intervention is the better treatment option in people with recurrent or refractory peptic ulcers .
OBJECTIVES To assess the benefits and harms of medical versus surgical treatment for people with recurrent or refractory peptic ulcer . | Background Few studies have evaluated the prevention of upper gastrointestinal complications ( UGIC ; bleeding or perforation ) in patients with uncomplicated peptic ulcer ( PU ) . We assessed the effect of proton pump inhibitors ( PPI ) in a non-r and omized setting . To maximize exchangeability of exposed and unexposed groups we restricted the study to patients with a new diagnosis of PU , i.e. , a clear indication . To minimize selection bias we mimicked an intention to treat approach by assessing the effect of PPI prescription after PU diagnosis . Methods Within a population of subjects aged 40–84 years from The Health Improvement Network data base , 1997–2006 , we identified 3,850 patients with incident PU . Among them , we confirmed 74 first UGIC episodes during a mean follow-up of 4 years . Exposure was prescription coverage during the month following PU diagnosis . We performed a nested case – control analysis and compared UGIC cases with 400 controls matched for age , sex , year and duration of follow-up . Relative risks ( RR ) and 95 % confidence intervals ( CI ) were estimated . Results The overall incidence of UGIC was 4.6 cases/1,000 person-years ; it was highest during the months after PU diagnosis , increased with age , and it was higher in men and subjects with Helicobacter pylori infection , anemia , and alcohol use at PU diagnosis . The RR for UGIC associated with PPI prescriptions during the month after PU diagnosis was 0.56 ( 95 % CI 0.31–1.0 ) . The RR for NSAIDs with and without a PPI was 1.72 ( 0.68–4.45 ) and 3.27 ( 0.85–12.67 ) , respectively . Conclusions Findings suggest that prescription of PPIs after a PU diagnosis is associated with a reduced risk of UGIC Background Emergency surgery or transarterial embolization ( TAE ) are options for the treatment of recurrent or refractory nonvariceal upper gastrointestinal bleeding . Surgery has the disadvantage of high rates of postoperative morbidity and mortality . Embolization has become more available and has the advantage of avoiding laparotomy in this often unfit and elderly population . Objective To carry out a systematic review and meta- analysis of all studies that have directly compared TAE with emergency surgery in the treatment of major upper gastrointestinal bleeding that has failed therapeutic upper gastrointestinal endoscopy . Methods A literature search of Ovid MEDLINE , Embase , and Google Scholar was performed . The primary outcomes were all-cause mortality and rates of rebleeding . The secondary outcomes were length of stay and postoperative complications . Results A total of nine studies with 711 patients ( 347 who had embolization and 364 who had surgery ) were analyzed . Patients in the TAE group were more likely to have ischemic heart disease ( odds ratio [ OR ] = 1.99 ; 95 % confidence interval [ CI ] : 1.33 , 2.98 ; P=0.0008 ; I2=67 % [ r and om effects model ] ) and be coagulopathic ( pooled OR = 2.23 ; 95 % CI : 1.29 , 3.87 ; P=0.004 ; I2=33 % [ fixed effects model ] ) . Compared with TAE , surgery was associated with a lower risk of rebleeding ( OR = 0.41 ; 95 % CI : 0.22 , 0.77 ; P<0.0001 ; I2=55 % [ r and om effects ] ) . There was no difference in mortality ( OR = 0.70 ; 95 % CI : 0.48 , 1.02 ; P=0.06 ; I2=44 % [ fixed effects ] ) between TAE and surgery . Conclusion When compared with surgery , TAE had a significant increased risk of rebleeding rates after TAE ; however , there were no differences in mortality rates . These findings are subject to multiple sources of bias due to poor quality studies . These findings support the need for a well- design ed clinical trial to ascertain which technique is superior This is one of a series of statements discussing the use of GI endoscopy in common clinical situations . The St and ards of Practice Committee of the American Society for Gastrointestinal Endoscopy ( ASGE ) prepared this text . In preparing this guideline , a search of the medical literature was performed by using PubMed . Additional references were obtained from the bibliographies of the identified articles and from recommendations of expert consultants . When few or no data exist from well- design ed prospect i ve trials , emphasis is placed on results from large series and reports from recognized experts . Guidelines for appropriate use of endoscopy are based on a critical review of the available data and expert consensus at the time the guidelines are drafted . Further controlled clinical studies may be needed to clarify aspects of this guideline . This guideline may be revised as necessary to account for changes in technology , new data , or other aspects of clinical practice . The recommendations are based on review ed studies and are grade d on the quality of the supporting evidence ( Table 1 ) . The strength of individual recommendations is based on both the aggregate evidence quality and an assessment of the anticipated benefits and harms . Weaker recommendations are indicated by phrases such as ‘ ‘ we suggest , ’ ’ whereas stronger recommendations are typically stated as ‘ ‘ we recommend . ’ ’ This guideline is intended to be an educational device to provide information that may assist endoscopists in providing care to patients . This guideline is not a rule and should not be construed as establishing a legal st and ard of care or as encouraging , advocating , requiring , or discouraging any particular treatment . Clinical decisions in any particular case involve a complex analysis of the patient ’s condition and available courses of action . Therefore , clinical considerations may lead an endoscopist to take a course of action that varies from this guideline . Upper GI endoscopy has largely replaced upper GI barium x-ray series for the evaluation of upper GI tract disease or symptoms because it allows direct visualization , tissue acquisition , and therapeutic interventions . This guideline is an up date of a previous ASGE document and defines the role of upper GI endoscopy in the OBJECTIVES Primary : to assess the necessity of a second endoscopy with a pathology study to confirm the healing of all gastric ulcers previously diagnosed through endoscopy in a population at intermediate risk for gastric cancer . Secondary : to assess correlation between endoscopic findings and pathology diagnosis . PATIENTS AND METHODS a prospect i ve analysis of patients diagnosed with gastric ulcer through endoscopy at Hospital General de Ciudad Real ( Spain ) over three years . We collected demographic , clinical , endoscopic , and pathological data for the first and subsequent endoscopies . We collected at least six biopsies obtained from ulcer margins , and assessed H. pylori infection . RESULTS Three hundred and two patients were included in this study . H. pylori infection was diagnosed in 173 ( 57 % ) , and 113 ( 37 % ) patients had used NSAIDs . The positive and negative predictive value for malignancy of endoscopic diagnosis regarding ulcer fold , base , and margins were 34 and 97 % , respectively . Only one patient was diagnosed with a tumor during the second endoscopy . At the end of follow-up , the etiology of the ulcer was considered as peptic in 276 patients ; Crohn s disease-related in one , and neoplastic in 25 patients ( 21 adenocarcinomas , 4 lymphomas ) . CONCLUSIONS in an intermediate-risk population for gastric cancer a second endoscopy is not justified for gastric ulcer patients when endoscopy and biopsy results do not suggest malignancy Methods for combining data from several studies exist and appear to be quite useful . None satisfactorily addresses the question of what studies should be combined . This issue is the most serious method ological limitation . Even studies with statistically significant interaction might still be combined if the effect were in the same direction . Thus , substantial scientific input is required as to what criteria must be met by each potential study . Much can be learned from combining or pooling data but it must be done cautiously . Pooling exercises do not replace well design ed prospect i ve clinical trials . Efforts for establishing basic design criteria to allow for multicentre and multicountry trials to be more easily combined might be useful . Abstract Objective . Morbidity and mortality following perforated peptic ulcer ( PPU ) remain substantial . In the recently published PULP trial , 30-day mortality in patients surgically treated for PPU decreased from 27 % to 17 % following the implementation of a perioperative care protocol based on The Surviving Sepsis Guidelines . The objective of the present study was to evaluate long-term mortality in the PULP trial intervention and control cohort . Material and methods . Design : nationwide follow-up study of a multicenter , non-r and omized , clinical trial with external controls . Setting : Danish patients surgically treated for PPU between 1 January 2008 and 31 December 2009 . Patients : 117 patients in the intervention group and 512 in the control group . Intervention : a perioperative care protocol based on The Surviving Sepsis Guidelines . Outcome measures : 60-day , 90-day , 180-day , 1-year , and 2-year mortality rates . Statistical analysis : survival statistics . Results . Baseline characteristics , clinical , and perioperative data were in general , similar in the intervention and control group . Sixty days postoperatively , the originally observed difference in 30-day mortality had diminished ( 25 % vs. 30 % , p = 0.268 ) . After 180 days , the mortality difference was reduced additionally ( 31 % vs. 33 % , p = 0.645 ) , and one year postoperatively , a mortality difference was no longer present ( 36 % in both groups , p = 0.993 ) . Two years postoperatively , the mortality rate in the intervention group was 44 % , as compared to 40 % in the control group ( p = 0.472 ) . Conclusions . The survival benefit associated with a perioperative care protocol in patients treated for PPU decreases progressively after 30 days and is no longer present after one year . Registration number : NCT00624169 ( http://www . clinical trials.gov ) BACKGROUND AND AIM This prospect i ve cohort observational study , set in a district hospital , presents our experience ( 1976 - 1993 ) of duodenal ulcer refractory to histamine H2 receptor antagonists ( defined as not healed after 3 months ' treatment ) and comments on onset , outcome and spontaneous decline . METHODS Patients were treated mainly with cimetidine , the dose being titrated ( up to 3.2 g daily ) according to response , and followed by serial check endoscopy and clinical assessment . RESULTS A total of 782 of the 4032 duodenal ulcer patients seen ( 19 % ) were refractory ; the incidence declined over time : 1976 - 1978 : 124/379 ( 33 % ) ; 1979 - 1983 : 390/1240 ( 31 % ) ; 1984 - 1988 : 190/1295 ( 15 % ) ; 1989 - 1993 : 78/1118 ( 7 % ) . A total of 344 were refractory for the first time on their first healing course and 174 on their second . Healing was achieved in two-thirds after a mean of 7 months ' treatment with cimetidine 1 g ; treatment for 12 - 18 months with higher doses was needed in the remainder . Relapse occurred in up to three-quarters of patients despite maintenance cimetidine up to 3 g daily . Eventually 47 patients were operated upon but good results ( i.e. , no ulcer , no symptoms ) were achieved in only 11 . CONCLUSION Refractoriness was common until recently . Its incidence has declined dramatically , the fall preceding the newer more powerful treatment with proton pump inhibitors and with Helicobacter pylori eradication . We suggest this phenomenon is a modern example of a spontaneous change in the natural history of the disease In a prospect i ve controlled trial 86 duodenal ulcer patients with symptoms severe enough to indicate surgery were r and omized to a full-dose cimetidine course followed by maintenance therapy for 1 year or parietal cell vagotomy ( PCV ) . The average follow-up period was 57 months . In the group assigned to medical therapy 62 % of the patients were free of symptoms during maintenance therapy , and 12 % remained well during the follow-up period . Operation was later performed in 35 % , whereas 53 % had symptomatic recurrence dem and ing medical treatment regularly . After PCV no patient died , and there were no serious sequelae . The overall recurrence rate was 17 % ; after treatment of failures 9 % continued to have dyspepsia . Since nearly 3/4 of the patients were free of symptoms after PCV , operation seems to be the method of choice in patients with a severe history and fast recurrence after medical therapy . However , the aged and those at high risk of surgery may benefit from cimetidine maintenance therapy |
12,324 | 25,212,554 | Preuss HG , Knapka JJ , MacArthy P , Yousufi AK , Sabnis SG , Antonovych TT .
High sucrose diets increase blood pressure of both salt-sensitive and salt-resistant rats .
Rebello T , Hodges RE , Smith JL .
Short-term effects of various sugars on antinatriuresis and blood pressure changes in normotensive young men .
BunagRD , Tomita T , Sasaki S.Chronic sucrose ingestion induces mild hypertension and tachycardia in rats .
Fructose-induced leptin resistance exacerbates weight gain in response to subsequent high-fat feeding .
Lana A , Rodriguez-Artalejo F , Lopez-Garcia E. Consumption of sugar-sweetened beverages is positively related to insulin resistance and higher plasma leptin concentrations inmen and nonoverweight women .
Ekinci EI , Clarke S , Thomas MC , Moran JL , Cheong K , MacIsaac RJ , Jerums G. Dietary salt intake and mortality in patients with type 2 diabetes .
Paterna S , Gaspare P , Fasullo S , Sarullo FM , Di Pasquale P. Normal-sodium diet compared with low-sodium diet in compensated congestive heart failure : is sodium an old enemy or a new friend ?
Garg R , Williams GH , Hurwitz S , Brown NJ , Hopkins PN , Adler GK .
Low-salt diet increases insulin resistance in healthy subjects .
Graudal NA , Hubeck-Graudal T , Jurgens G. Effects of low sodium diet versus high sodium diet on blood pressure , renin , aldosterone , catecholamines , cholesterol , and triglyceride . | Salt intake , sugarsweetened soft drink consumption , and blood pressure .
Vital signs : food categories contributing the most to sodium consumption — United States , 2007 - 2008 .
Graudal NA , Galloe AM , Garred P. Effects of sodium restriction on blood pressure , renin , aldosterone , catecholamines , cholesterols , and triglyceride : a meta- analysis .
Preuss MB , Preuss HG .
The effects of sucrose and sodium on blood pressures in various substrains of Wistar rats .
L and sberg L. Insulin and the sympathetic nervous system in the pathophysiology of hypertension .
Young JB , L and sberg L. Stimulation of the sympathetic nervous system during sucrose feeding .
Haynes WG , Morgan DA , Djalali A , Sivitz WI , Mark AL .
Interactions between the melanocortin system and leptin in control of sympathetic nerve traffic .
A leptin-sympathetic-leptin feedback loop : potential implication s for regulation of arterial pressure and body fat .
Wang X , Jia X , Chang T , Desai K , Wu L. Attenuation of hypertension development by scavenging methylglyoxal in fructose-treated rats .
Wang H , MengQH , Chang T , Wu L. Fructoseinduced peroxynitrite production is mediated by methylglyoxal in vascular smooth muscle cells .
Chang T , Wang R , Wu L. Methylglyoxalinduced nitric oxide and peroxynitrite production in vascular smooth muscle cells .
Licata G , Di Pasquale P , Parrinello G , Cardinale A , Sc and urra A , Follone G , Argano C , Tuttolomondo A , Paterna S. Effects of high-dose furosemide and smallvolume hypertonic saline solution infusion in comparison with a high dose of furosemide as bolus in refractory congestive heart failure : long-term effects .
Paterna S , Di Pasquale P , Parrinello G , Fornaciari E , Di Gaudio F , Fasullo S , Giammanco M , Sarullo FM , Licata G. Changes in brain natriuretic peptide levels and bioelectrical impedance measurements after treatment with high-dose furosemide and hypertonic saline solution versus high-dose furosemide alone in refractory congestive heart failure : a double-blind study . | The aim of the present study was to evaluate the effects of a normal-sodium ( 120 mmol sodium ) diet compared with a low-sodium diet ( 80 mmol sodium ) on readmissions for CHF ( congestive heart failure ) during 180 days of follow-up in compensated patients with CHF . A total of 232 compensated CHF patients ( 88 female and 144 male ; New York Heart Association class II-IV ; 55 - 83 years of age , ejection fraction < 35 % and serum creatinine < 2 mg/dl ) were r and omized into two groups : group 1 contained 118 patients ( 45 females and 73 males ) receiving a normal-sodium diet plus oral furosemide [ 250 - 500 mg , b.i.d . ( twice a day ) ] ; and group 2 contained 114 patients ( 43 females and 71 males ) receiving a low-sodium diet plus oral furosemide ( 250 - 500 mg , b.i.d . ) . The treatment was given at 30 days after discharge and for 180 days , in association with a fluid intake of 1000 ml per day . Signs of CHF , body weight , blood pressure , heart rate , laboratory parameters , ECG , echocardiogram , levels of BNP ( brain natriuretic peptide ) and aldosterone levels , and PRA ( plasma renin activity ) were examined at baseline ( 30 days after discharge ) and after 180 days . The normal-sodium group had a significant reduction ( P<0.05 ) in readmissions . BNP values were lower in the normal-sodium group compared with the low sodium group ( 685+/-255 compared with 425+/-125 pg/ml respectively ; P<0.0001 ) . Significant ( P<0.0001 ) increases in aldosterone and PRA were observed in the low-sodium group during follow-up , whereas the normal-sodium group had a small significant reduction ( P=0.039 ) in aldosterone levels and no significant difference in PRA . After 180 days of follow-up , aldosterone levels and PRA were significantly ( P<0.0001 ) higher in the low-sodium group . The normal-sodium group had a lower incidence of rehospitalization during follow-up and a significant decrease in plasma BNP and aldosterone levels , and PRA . The results of the present study show that a normal-sodium diet improves outcome , and sodium depletion has detrimental renal and neurohormonal effects with worse clinical outcome in compensated CHF patients . Further studies are required to determine if this is due to a high dose of diuretic or the low-sodium diet Low-salt ( LS ) diet activates the renin-angiotensin-aldosterone and sympathetic nervous systems , both of which can increase insulin resistance ( IR ) . We investigated the hypothesis that LS diet is associated with an increase in IR in healthy subjects . Healthy individuals were studied after 7 days of LS diet ( urine sodium < 20 mmol/d ) and 7 days of high-salt ( HS ) diet ( urine sodium > 150 mmol/d ) in a r and om order . Insulin resistance was measured after each diet and compared statistically , unadjusted and adjusted for important covariates . One hundred fifty-two healthy men and women , aged 39.1 ± 12.5 years ( range , 18 - 65 ) and with body mass index of 25.3 ± 4.0 kg/m(2 ) , were included in this study . Mean ( SD ) homeostasis model assessment index was significantly higher on LS compared with HS diet ( 2.8 ± 1.6 vs 2.4 ± 1.7 , P < .01 ) . Serum aldosterone ( 21.0 ± 14.3 vs 3.4 ± 1.5 ng/dL , P < .001 ) , 24-hour urine aldosterone ( 63.0 ± 34.0 vs 9.5 ± 6.5 μg/d , P < .001 ) , and 24-hour urine norepinephrine excretion ( 78.0 ± 36.7 vs 67.9 ± 39.8 μg/d , P < .05 ) were higher on LS diet compared with HS diet . Low-salt diet was significantly associated with higher homeostasis model assessment index independent of age , sex , blood pressure , body mass index , serum sodium and potassium , serum angiotensin II , plasma renin activity , serum and urine aldosterone , and urine epinephrine and norepinephrine . Low-salt diet is associated with an increase in IR . The impact of our findings on the pathogenesis of diabetes and cardiovascular disease needs further investigation This is a report of the effects of sugars on salt metabolism and on blood pressure . Twenty young men , none of whom had a personal or family history of hypertension , were orally hydrated after an overnight fast and required to lie recumbent for 6 h except for urinary voiding and blood pressure measurements which were performed at 1/2 h intervals . Venous blood sample s were drawn at hourly intervals . The volunteers were kept constantly hydrated by giving them water to drink equivalent to the volumes of urine voided . Two hours from the start of the experiment each subject was given one of the following sugars : glucose , fructose , sucrose , galactose , lactose , or water alone . After oral hydration the subjects appeared to develop natriuresis and kaliuresis . This was quickly abolished by ingestion of either glucose , fructose , sucrose , or lactose , but not by galactose or water alone . Fructose was the most potent antinatriuretic agent . Both glucose and sucrose significantly elevated systolic blood pressure . This lasted for 2 h after glucose ingestion and 1 h after sucrose ingestion Introduction : Hypertonic saline solution ( HSS ) and a moderate Na restriction plus high furosemide dose showed beneficial effects in compensated heart failure ( HF ) , in short and long terms . The study was aim ed to verify the effects of this combination on hospitalization time , readmissions and mortality in patients in New York Heart Association ( NYHA ) class III . Method : Chronic ischemic or nonischemic cardiomyopathy uncompensated patients with HF in NYHA III functional class with ejection fraction < 40 % , serum creatinine < 2.5 mg/dL , blood urea nitrogen < 60 mg/dL and reduced urinary volume were single-blind r and omized in 2 groups : the first group received a 30-minute intravenous infusion of furosemide ( 250 mg ) plus HSS ( 150 mL ) twice daily and a moderate Na restriction ( 120 mmol ) ; the second group received furosemide intravenous bolus ( 250 mg ) twice a day , without HSS and a low Na diet ( 80 mmol ) ; both groups received a fluid intake of 1000 mL/d . After discharge , the HSS group continued with 120 mmol Na/d ; the second group continued with 80 mmol Na/d . Results : A total of 1771 patients ( 881 HSS group and 890 without HSS group ) met inclusion criteria : the first group ( 881 patients ) , compared with the second ( 890 patients ) , showed an increase in diuresis and serum Na levels , a reduction in hospitalization time ( 3.5 + 1 versus 5.5 + 1 days , P < 0.0001 ) and , during follow-up ( 57 + 15 months ) , a lower rate in readmissions ( 18.5 % versus 34.2 % , P < 0.0001 ) and mortality ( 12.9 % versus 23.8 % , P < 0.0001 ) ; the second group also showed a significant increase in blood urea nitrogen and serum creatinine . Conclusion : This study suggests that in-hospital HSS administration , combined with moderate Na restriction , reduces hospitalization time and that a moderate sodium diet restriction determines long-term benefit in patients with NYHA class III HF OBJECTIVES The aim of this study was to evaluate the effect of a new treatment for refractory congestive heart failure ( CHF ) on brain natriuretic peptide ( BNP ) plasma levels and hydration station . BACKGROUND The study was aim ed at evaluating the effects of the combination of high-dose furosemide and small-volume hypertonic saline solution ( HSS ) in refractory CHF patients . METHODS A total of 94 patients ( 34 women/60 men ) with refractory CHF ( age 55 to 80 years ) were enrolled . They had to have an ejection fraction < 35 % , serum creatinine < 2 mg/dl , blood urea nitrogen < 60 mg/dl , a reduced urinary volume , and a low natriuresis ( < 500 ml/24 h and < 60 mEq/24 h , respectively ) . Patients were divided ( double-blind ) into two groups : group 1 ( 18 women/30 men ) received an intravenous furosemide ( 500 to 1,000 mg ) plus HSS twice a day in 30 min . Group 2 ( 16 women/30 men ) received an intravenous bolus of furosemide ( 500 to 1,000 mg/twice a day ) alone , for four to six days . At entry , body weight , blood pressure , heart rate , and laboratory parameters were checked during hospitalization ; BNP levels were measured on admission , 6 and 30 days after discharge , while on admission and 6 days after , impedance plethysmography was performed . The HSS group received 120 mmol of Na intake versus 80 mmol in non-HSS group . Fluid intake of 1,000 was given to both groups . RESULTS The groups were similar for clinical characteristics . A significant increase in daily diuresis and natriuresis was observed in HSS group , p < 0.05 . The BNP values showed significant intragroup and intergroup differences , 6 and 30 days after treatment . The patients from the HSS group reached a better hydration state than the non-HSS group after six days . In addition , the HSS group showed a significant reduction in hospitalization time and readmission rate . CONCLUSIONS Our data show that the HSS group reached dry weight more rapidly , a significantly faster reduction in BNP levels , shorter hospitalization stay , and lower incidence in readmissions in the 30-day study period BACKGROUND Diuretics have been accepted as first-line treatment in refractory congestive heart failure ( CHF ) , but a lack of response to them is a frequent event . A r and omized , single-blind study was performed to evaluate the effects of the combination of high-dose furosemide and small-volume hypertonic saline solution ( HSS ) infusion in the treatment of refractory New York Heart Association ( NYHA ) class IV CHF and a normosodic diet during follow-up . Material s and Methods One hundred seven patients ( 39 women and 68 men , age range 65 - 90 years ) with refractory CHF ( NYHA class IV ) of different etiologies , who were unresponsive to high oral doses of furosemide , angiotensin-converting enzyme inhibitors , digitalis , and nitrates , were enrolled . Inclusion criteria included an ejection fraction ( EF ) < 35 % , serum creatinine level < 2 mg/dL , blood urea nitrogen level < or = 60 mg/dL , reduced urinary volume , and low natriuresis . The patients were r and omized in 2 groups ( single-blind ) . Patients in group 1 ( 20 women and 33 men ) received an intravenous ( IV ) infusion of furosemide ( 500 - 1000 mg ) plus HSS ( 150 mL of 1.4%-4.6 % NACl ) twice a day in 30 minutes . Patients in group 2 ( 19 women and 35 men ) received an IV bolus of furosemide ( 500 - 1000 mg ) twice a day , without HSS , during a period lasting 6 to 12 days . Both groups received IV KCl ( 20 - 40 mEq ) to prevent hypokalemia . At study entry , all patients underwent a physical examination and measurement of body weight ( BW ) , blood pressure ( BP ) , and heart rate ( HR ) , an evaluation of signs of CHF , and measurement of control levels of serum Na , K , Cl , bicarbonate , albumin , uric acid , creatinine , urea , and glycemia daily during hospitalization , and measurements of the daily output of urine for Na , K , and Cl . A chest radiograph , electrocardiogram , and echocardiogram were obtained at study entry , during hospitalization , and at the time of discharge from the hospital . During the treatment and after discharge , the daily dietary Na intake was 120 mmol in group 1 versus 80 mmol in group 2 , with a fluid intake of 1000 mL daily in both groups . An assessment of BW and 24-hour urinary volume , serum , and urinary laboratory parameters were performed daily until patients reached a compensated state , when IV furosemide was replaced with oral administration ( 250 - 500 mg/d ) . After discharge from the hospital , patients were observed as out patients weekly for the first 3 months and , subsequently , once a month . RESULTS The groups were similar in age , sex , EF , risk factors , treatment , and etiology of CHF . All patients showed a clinical improvement . Ten patients in both groups had hyponatremia at entry . A significant increase in daily diuresis and natriuresis was observed in both groups , but it was more significant in the group receiving HSS ( P < .05 ) . The serum Na level increased in group 1 and decreased in group 2 ( P < .05 ) . The serum K level was decreased in both groups ( P < .05 ) . BW was reduced in both groups ( P < .05 ) . Group 2 had an increase in serum creatinine level . Serum uric acid levels increased in both groups . BP values decreased and HR was corrected to normal values in both groups . In the follow-up period ( 31 + /- 14 months ) , 25 patients from group 1 were readmitted to the hospital for heart failure . In group 2 , 43 patients were readmitted to the hospital at a higher class than at discharge . Twenty-four patients in group 1 died during follow-up , versus 47 patients in group 2 ( P < .001 ) . CONCLUSION This treatment is effective and well tolerated , improves the quality of life through the relief of signs and symptoms of congestion , and may delay more aggressive treatments . The effects were also beneficial in a long period for mortality reduction ( 55 % vs 13 % survival rate ) and for clinical improvement |
12,325 | 20,158,996 | In couples treated with IUI , the clinical validity of SCSA is higher than that of sperm morphology alone , but not enough to introduce SCSA as a test in male infertility work-up | null | null |
12,326 | 31,906,979 | However , there was no definitely effective intervention with coherence and reproducibility . | Background Although medical requirements are urgent , no effective intervention has been proven for chronic fatigue syndrome/myalgic encephalomyelitis ( CFS/ME ) .
To facilitate the development of new therapeutics , we systematic ally review ed the r and omized controlled trials ( RCTs ) for CFS/ME to date . | Objective To evaluate the effectiveness of home delivered pragmatic rehabilitation — a programme of gradually increasing activity design ed collaboratively by the patient and the therapist— and supportive listening — an approach based on non-directive counselling — for patients in primary care with chronic fatigue syndrome/myalgic encephalomyelitis or encephalitis ( CFS/ME ) . Design Single blind , r and omised , controlled trial . Setting 186 general practice s across the north west of Engl and between February 2005 and May 2007 . Participants 296 patients aged 18 or over with CFS/ME ( median illness duration seven years ) diagnosed using the Oxford criteria . Interventions Participants were r and omly allocated to pragmatic rehabilitation , supportive listening , or general practitioner treatment as usual . Both therapies were delivered at home in 10 sessions over 18 weeks by one of three adult specialty general nurses who had received four months ’ training , including supervised practice , in each of the interventions . GP treatment as usual was unconstrained except that patients were not to be referred for systematic psychological therapies during the treatment period . Main outcome measures The primary clinical outcomes were fatigue and physical functioning at the end of treatment ( 20 weeks ) and 70 weeks from recruitment compared with GP treatment as usual . Lower fatigue scores and higher physical functioning scores denote better outcomes . Results A total of 257 ( 87 % ) of the 296 patients who entered the trial were assessed at 70 weeks , the primary outcome point . Analysis was on an intention to treat basis , with robust treatment effects estimated after adjustment for missing data using probability weights . Immediately after treatment ( at 20 weeks ) , patients allocated to pragmatic rehabilitation ( n=95 ) had significantly improved fatigue ( effect estimate -1.18 , 95 % confidence interval -2.18 to -0.18 ; P=0.021 ) but not physical functioning ( -0.18 , 95 % CI -5.88 to + 5.52 ; P=0.950 ) compared with patients allocated to treatment as usual ( n=100 ) . At one year after finishing treatment ( 70 weeks ) , there were no statistically significant differences in fatigue or physical functioning between patients allocated to pragmatic rehabilitation and those on treatment as usual ( -1.00 , 95 % CI -2.10 to + 0.11 ; P=0.076 and + 2.57 , 95 % CI 3.90 to + 9.03 ; P=0.435 ) . At 20 weeks , patients allocated to supportive listening ( n=101 ) had poorer physical functioning than those allocated to treatment as usual ( -7.54 , 95 % CI -12.76 to -2.33 ; P=0.005 ) and no difference in fatigue . At 70 weeks , patients allocated to supportive listening did not differ significantly from those allocated to treatment as usual on either primary outcome . Conclusions For patients with CFS/ME in primary care , pragmatic rehabilitation delivered by trained nurse therapists improves fatigue in the short term compared with unconstrained GP treatment as usual , but the effect is small and not statistically significant at one year follow-up . Supportive listening delivered by trained nurse therapists is not an effective treatment for CFS/ME . Trial registration International St and ard R and omised Controlled Trial Number I RCT N74156610 BACKGROUND Reports of mild hypocortisolism in chronic fatigue syndrome led us to postulate that low-dose hydrocortisone therapy may be an effective treatment . METHODS In a r and omised crossover trial , we screened 218 patients with chronic fatigue . 32 patients met our strict criteria for chronic fatigue syndrome without co-morbid psychiatric disorder . The eligible patients received consecutive treatment with low-dose hydrocortisone ( 5 mg or 10 mg daily ) for 1 month and placebo for 1 month ; the order of treatment was r and omly assigned . Analysis was by intention to treat . FINDINGS None of the patients dropped out . Compared with the baseline self-reported fatigue scores ( mean 25.1 points ) , the score fell by 7.2 points for patients on hydrocortisone and by 3.3 points for those on placebo ( paired difference in mean scores 4.5 points [ 95 % CI 1.2 - 7.7 ] , p=0.009 ) . In nine ( 28 % ) of the 32 patients on hydrocortisone , fatigue scores reached a predefined cut-off value similar to the normal population score , compared with three ( 9 % ) of the 32 on placebo ( Fisher 's exact test p=0.05 ) . The degree of disability was reduced with hydrocortisone treatment , but not with placebo . Insulin stress tests showed that endogenous adrenal function was not suppressed by hydrocortisone . Minor side-effects were reported by three patients after hydrocortisone treatment and by one patient after placebo . INTERPRETATION In some patients with chronic fatigue syndrome , low-dose hydrocortisone reduces fatigue levels in the short term . Treatment for a longer time and follow-up studies are needed to find out whether this effect could be clinical ly useful Background Chronic fatigue is common in the general population . Complementary therapies are often used by patients with chronic fatigue or chronic fatigue syndrome to manage their symptoms . Purpose This study aim ed to assess the effect of a 4-month qigong intervention program among patients with chronic fatigue or chronic fatigue syndrome . Methods Sixty-four participants were r and omly assigned to either an intervention group or a wait list control group . Outcome measures included fatigue symptoms , physical functioning , mental functioning , and telomerase activity . Results Fatigue symptoms and mental functioning were significantly improved in the qigong group compared to controls . Telomerase activity increased in the qigong group from 0.102 to 0.178 arbitrary units ( p < 0.05 ) . The change was statistically significant when compared to the control group ( p < 0.05 ) . Conclusion Qigong exercise may be used as an alternative and complementary therapy or rehabilitative program for chronic fatigue and chronic fatigue syndrome Abstract Objective : To assess the efficacy of an educational intervention explaining symptoms to encourage grade d exercise in patients with chronic fatigue syndrome . Design : R and omised controlled trial . Setting : Chronic fatigue clinic and infectious diseases outpatient clinic . Subjects : 148 consecutively referred patients fulfilling Oxford criteria for chronic fatigue syndrome . Interventions : Patients r and omised to the control group received st and ardised medical care . Patients r and omised to intervention received two individual treatment sessions and two telephone follow up calls , supported by a comprehensive educational pack , describing the role of disrupted physiological regulation in fatigue symptoms and encouraging home based grade d exercise . The minimum intervention group had no further treatment , but the telephone intervention group received an additional seven follow up calls and the maximum intervention group an additional seven face to face sessions over four months . Main outcome measure : A score of 25 or an increase of 10 on the SF-36 physical functioning subscale ( range 10 to 30 ) 12 months after r and omisation . Results : 21 patients dropped out , mainly from the intervention groups . Intention to treat analysis showed 79 ( 69 % ) of patients in the intervention groups achieved a satisfactory outcome in physical functioning compared with two ( 6 % ) of controls , who received st and ardised medical care ( P<0.0001 ) . Similar improvements were observed in fatigue , sleep , disability , and mood . No significant differences were found between the three intervention groups . Conclusions : Treatment incorporating evidence based physiological explanations for symptoms was effective in encouraging self managed grade d exercise . This result ed in substantial improvement compared with st and ardised medical care Background The causes of chronic fatigue syndrome ( CFS ) and idiopathic chronic fatigue ( ICF ) are not clearly known , and there are no definitive treatments for them . Therefore , patients with CFS and ICF are interested in Oriental medicine or complementary and alternative medicine . For this reason , the effectiveness of complementary and alternative treatments should be verified . We investigated the effectiveness of two forms of acupuncture added to usual care for CFS and ICF compared to usual care alone . Methods A three-arm parallel , non-blinded , r and omized controlled trial was performed in four hospitals . We divided 150 participants into treatment and control groups at the same ratio . The treatment groups ( Group A , body acupuncture ; Group B , Sa-am acupuncture ) received 10 sessions for 4 weeks . The control group ( Group C ) continued usual care alone . The primary outcome was the Fatigue Severity Scale ( FSS ) at 5 weeks after r and omization . Secondary outcomes were the FSS at 13 weeks and a short form of the Stress Response Inventory ( SRI ) , the Beck Depression Inventory ( BDI ) , the Numeric Rating Scale ( NRS ) , and the EuroQol-5 Dimension ( EQ-5D ) at 5 and 13 weeks . Results Group A showed significantly lower FSS scores than Group C at 5 weeks ( P = 0.023 ) . SRI scores were significantly lower in the treatment groups than in the control group at 5 ( Group A , P = 0.032 ; B , P < 0.001 ) and 13 weeks ( Group A , P = 0.037 ; B , P < 0.001 ) . Group B showed significantly lower BDI scores than Group C at 13 weeks ( P = 0.007 ) . NRS scores from the treatment groups were significantly reduced compared to control at 5 ( Group A and B , P < 0.001 ) and 13 weeks ( Group A , P = 0.011 ; B , P = 0.002 ) . Conclusions Body acupuncture for 4 weeks in addition to usual care may help improve fatigue in CFS and ICF patients .Trial registration Clinical Research Information Service ( CRIS ) KCT0000508 ; Registered on 12 August 2012 CONTEXT Given that the etiology of chronic fatigue syndrome ( CFS ) is believed to be multidimensional , interventions generally have been nonspecific and typically produce only mild to moderate effects . In medical practice , treatment for CFS remains largely symptomatic . Preliminary evidence of the efficacy of acupuncture for CFS is available , but the field has lacked high- quality trials . OBJECTIVE The research team conducted the study to determine the efficacy of acupuncture for CFS . DESIGN A two-arm , r and omized , controlled , singleblinded design was adopted . SETTING The study took place in a teaching laboratory at the School of Chinese Medicine at the University of Hong Kong , Hong Kong , China . PARTICIPANTS Recruited through press publicity in Hong Kong , 127 individuals--40 men and 87 women -- participated in the study . Intervention Through careful implementation of sham acupuncture in the control group ( CG ) , the study blinded all participants with regard to their experimental or control status . The treatment regime was 2 sessions/wk for 4 consecutive wk . OUTCOME MEASURES Measures of fatigue ( Chalder 's Fatigue Scale ) , health-related quality of life ( SF-12 ) , and general mental health ( GH Q-12 ) were taken at baseline and upon completion of treatment . RESULTS Ninety-nine participants completed the interventions , with 50 and 49 participants in the experimental group ( EG ) and CG respectively . Repeated measures ANOVA revealed a significant decrease in physical ( F(1,93 ) = 4.327 ; P = .040 ) and mental fatigue ( F(1,96 ) = 10.451 ; P = .002 ) and improvement in the physical component score of SF-12 ( F(1,93 ) = 4.774 ; P = .031 ) . Considerable effects with Cohen 's d were observed in the sham-control group : 0.92 , 0.78 , and 0.38 for the three scores , respectively . These positive effects could have included some therapeutic effects due to pressure on the acupuncture points from the sham needles in addition to normal placebo effects . The EG showed moderate net effect sizes with Cohen 's d : 0.52 , 0.63 , and 0.54 for the three outcome measures , respectively . CONCLUSION Despite considerable positive effects for the CG , the EG demonstrated significant net-effect sizes at a moderate magnitude in physical and mental fatigue and in the physical component of health-related quality of life . The impacts on general mental health outcomes appeared to be smaller OBJECTIVE Cognitive behavior therapy for chronic fatigue syndrome was compared with relaxation in a r and omized controlled trial . METHODS Sixty patients with chronic fatigue syndrome were r and omly assigned to 13 sessions of either cognitive behavior therapy ( grade d activity and cognitive restructuring ) or relaxation . Outcome was evaluated by using measures of functional impairment , fatigue , mood , and global improvement . RESULTS Treatment was completed by 53 patients . Functional impairment and fatigue improved more in the group that received cognitive behavior therapy . At final follow-up , 70 % of the completers in the cognitive behavior therapy group achieved good outcomes ( substantial improvement in physical functioning ) compared with 19 % of those in the relaxation group who completed treatment . CONCLUSIONS Cognitive behavior therapy was more effective than a relaxation control in the management of patients with chronic fatigue syndrome . Improvements were sustained over 6 months of follow-up CONTEXT Chronic fatigue syndrome ( CFS ) is associated with a dysregulated hypothalamic-pituitary adrenal axis and hypocortisolemia . OBJECTIVE To evaluate the efficacy and safety of low-dose oral hydrocortisone as a treatment for CFS . DESIGN A r and omized , placebo-controlled , double-blind therapeutic trial , conducted between 1992 and 1996 . SETTING A single-center study in a tertiary care research institution . PATIENTS A total of 56 women and 14 men aged 18 to 55 years who met the 1988 Centers for Disease Control and Prevention case criteria for CFS and who withheld concomitant treatment with other medications . INTERVENTION Oral hydrocortisone , 13 mg/m2 of body surface area every morning and 3 mg/m2 every afternoon , or placebo , for approximately 12 weeks . MAIN OUTCOME MEASURES A global Wellness scale and other self-rating instruments were completed repeatedly before and during treatment . Resting and cosyntropin-stimulated cortisol levels were obtained before and at the end of treatment . Patients recorded adverse effects on a checklist . RESULTS The number of patients showing improvement on the Wellness scale was 19 ( 54.3 % ) of 35 placebo recipients vs 20 ( 66.7 % ) of 30 hydrocortisone recipients ( P = .31 ) . Hydrocortisone recipients had a greater improvement in mean Wellness score ( 6.3 vs 1.7 points ; P=.06 ) , a greater percentage ( 53 % vs 29 % ; P=.04 ) recording an improvement of 5 or more points in Wellness score , and a higher average improvement in Wellness score on more days than did placebo recipients ( P<.001 ) . Statistical evidence of improvement was not seen with other self-rating scales . Although adverse symptoms reported by patients taking hydrocortisone were mild , suppression of adrenal glucocorticoid responsiveness was documented in 12 patients who received it vs none in the placebo group ( P<.001 ) . CONCLUSIONS Although hydrocortisone treatment was associated with some improvement in symptoms of CFS , the degree of adrenal suppression precludes its practical use for CFS Background : Distant healing , a form of spiritual healing , is widely used for many conditions but little is known about its effectiveness . Methods : In order to evaluate distant healing in patients with a stable chronic condition , we r and omised 409 patients with chronic fatigue syndrome ( CFS ) from 14 private practice s for environmental medicine in Germany and Austria in a two by two factorial design to immediate versus deferred ( waiting for 6 months ) distant healing . Half the patients were blinded and half knew their treatment allocation . Patients were treated for 6 months and allocated to groups of 3 healers from a pool of 462 healers in 21 European countries with different healing traditions . Change in Mental Health Component Summary ( MHCS ) score ( SF-36 ) was the primary outcome and Physical Health Component Summary score ( PHCS ) the secondary outcome . Results : This trial population had very low quality of life and symptom scores at entry . There were no differences over 6 months in post-treatment MHCS scores between the treated and untreated groups . There was a non-significant outcome ( p = 0.11 ) for healing with PHCS ( 1.11 ; 95 % CI –0.255 to 2.473 at 6 months ) and a significant effect ( p = 0.027 ) for blinding ; patients who were unblinded became worse during the trial ( –1.544 ; 95 % CI –2.913 to –0.176 ) . We found no relevant interaction for blinding among treated patients in MHCS and PHCS . Expectation of treatment and duration of CFS added significantly to the model . Conclusions : In patients with CFS , distant healing appears to have no statistically significant effect on mental and physical health but the expectation of improvement did improve outcome BACKGROUND Accumulating data support the involvement of the serotonin ( 5-hydroxytryptamine [ 5-HT ] ) system in the pathophysiology of chronic fatigue syndrome . Neuropharmacologic studies point to a hyperactive 5-HT system , and open-label treatment studies with 5-HT(3 ) receptor antagonists have shown promising results . In this r and omized controlled clinical trial , the effect of ondansetron , a 5-HT(3 ) receptor antagonist , was assessed on fatigue severity and functional impairment in adult patients with chronic fatigue syndrome . METHOD A r and omized , placebo-controlled , double-blind clinical trial was conducted at Radboud University Nijmegen Medical Centre , The Netherl and s. Sixty-seven adult patients who fulfilled the US Centers for Disease Control and Prevention ( CDC ) criteria for chronic fatigue syndrome and who were free from current psychiatric comorbidity participated in the clinical trial . Participants received either ondansetron 16 mg per day or placebo for 10 weeks . The primary outcome variables were fatigue severity ( Checklist Individual Strength fatigue severity subscale [ CIS-fatigue ] ) and functional impairment ( Sickness Impact Profile-8 [ SIP-8 ] ) . The effect of ondansetron was assessed by analysis of covariance . Data were analyzed on an intention-to-treat basis . All patients were recruited between June 2003 and March 2006 . RESULTS Thirty-three patients were allocated to the ondansetron condition , 34 to the placebo condition . The 2 groups were well matched in terms of age , sex , fatigue severity , functional impairment , and CDC symptoms . Analysis of covariance showed no significant differences between the ondansetron- and placebo-treated groups during the 10-week treatment period in fatigue severity and functional impairment . CONCLUSIONS This clinical trial demonstrates no benefit of ondansetron compared to placebo in the treatment of chronic fatigue syndrome . TRIAL REGISTRATION www.trialregister.nl : IS RCT N02536681 OBJECTIVE To assess the efficacy and safety of duloxetine in patients with chronic fatigue syndrome . METHODS A 12-week , r and omized , double-blind study was design ed to compare duloxetine 60 - 120 mg/d ( n = 30 ) with placebo ( n = 30 ) for efficacy and safety in the treatment of patients with chronic fatigue syndrome . The primary outcome measure was the Multidimensional Fatigue Inventory general fatigue subscale ( range : 4 - 20 , with higher scores indicating greater fatigue ) . Secondary measures were the remaining Multidimensional Fatigue Inventory subscales , Brief Pain Inventory , Medical Outcomes Study Short Form-36 , Hospital Anxiety and Depression Scale , Centers for Disease Control and Prevention Symptom Inventory , Patient Global Impression of Improvement , and Clinical Global Impression of Severity . The primary analysis of efficacy for continuous variables was a longitudinal analysis of the intent-to-treat sample , with treatment-by-time interaction as the measure of effect . RESULTS The improvement in the Multidimensional Fatigue Inventory general fatigue scores for the duloxetine group was not significantly greater than for the placebo group ( P = 0.23 ; estimated difference between groups at week 12 = -1.0 [ 95 % CI : -2.8 , 0.7 ] ) . The duloxetine group was significantly superior to the placebo group on the Multidimensional Fatigue Inventory mental fatigue score , Brief Pain Inventory average pain severity and interference scores , Short Form-36 bodily pain domain , and Clinical Global Impression of Severity score . Duloxetine was generally well tolerated . CONCLUSION The primary efficacy measure of general fatigue did not significantly improve with duloxetine when compared with placebo . Significant improvement in secondary measures of mental fatigue , pain , and global measure of severity suggests that duloxetine may be efficacious for some chronic fatigue syndrome symptom domains , but larger controlled trials are needed to confirm these results PURPOSE To evaluate the potential benefit of immunologic therapy with dialyzable leukocyte extract and psychologic treatment in the form of cognitive-behavioral therapy ( CBT ) in patients with chronic fatigue syndrome ( CFS ) . PATIENTS AND METHODS Immunologic and psychologic treatments were administered to 90 adult patients who fulfilled diagnostic criteria for CFS in a double-blind , r and omized , and placebo-controlled study . A four-cell trial design allowed the assessment of benefit from immunologic and psychologic treatment individually or in combination . Outcome was evaluated by measurement of global well-being ( visual analogue scales ) , physical capacity ( st and ardized diaries of daily activities ) , functional status ( Karnofsky performance scale ) , and psychologic morbidity ( Profile of Mood States question naire ) , and cell-mediated immunity was evaluated by peripheral blood T-cell subset analysis and delayed-type hypersensitivity skin testing . RESULTS Neither dialyzable leukocyte extract nor CBT ( alone or in combination ) provided greater benefit than the nonspecific treatment regimens . CONCLUSIONS In this study , patients with CFS did not demonstrate a specific response to immunologic and /or psychologic therapy . The improvement recorded in the group as a whole may reflect both nonspecific treatment effects and a propensity to remission in the natural history of this disorder BACKGROUND Chronic fatigue syndrome ( CFS ) is a disorder of unknown etiology , consisting of prolonged , debilitating fatigue , and a multitude of symptoms including neurocognitive dysfunction , flu-like symptoms , myalgia , weakness , arthralgia , low- grade fever , sore throat , headache , sleep disturbances , and swelling and tenderness of lymph nodes . No effective treatment for CFS is known . OBJECTIVE The purpose of the study was to evaluate the efficacy of the reduced form of nicotinamide adenine dinucleotide ( NADH ) i.e. , ENADA the stabilized oral absorbable form , in a r and omized , double-blind , placebo-controlled crossover study in patients with CFS . Nicotinamide adenine dinucleotide is known to trigger energy production through ATP generation which may form the basis of its potential effects . METHODS Twenty-six eligible patients who fulfilled the Center for Disease Control and Prevention criteria for CFS completed the study . Medical history , physical examination , laboratory studies , and question naire were obtained at baseline , 4 , 8 , and 12 weeks . Subjects were r and omly assigned to receive either 10 mg of NADH or placebo for a 4-week period . Following a 4-week washout period , subjects were crossed to the alternate regimen for a final 4-week period . RESULTS No severe adverse effects were observed related to the study drug . Within this cohort of 26 patients , 8 of 26 ( 31 % ) responded favorably to NADH in contrast to 2 of 26 ( 8 % ) to placebo . Based upon these encouraging results we have decided to conduct an open-label study in a larger cohort of patients . CONCLUSION Collectively , the results of this pilot study indicate that NADH may be a valuable adjunctive therapy in the management of the chronic fatigue syndrome and suggest that further clinical trials be performed to establish its efficacy in this clinical ly perplexing disorder Abstract Objective : To evaluate the acceptability and efficacy of adding cognitive behaviour therapy to the medical care of patients presenting with the chronic fatigue syndrome . Design : R and omised controlled trial with final assessment at 12 months . Setting : An infectious diseases outpatient clinic . Subjects : 60 consecutively referred patients meeting consensus criteria for the chronic fatigue syndrome . Interventions : Medical care comprised assessment , advice , and follow up in general practice . Patients who received cognitive behaviour therapy were offered 16 individual weekly sessions in addition to their medical care . Main outcome measures : The proportions of patients ( a ) who achieved normal daily functioning ( Karnofsky score 80 or more ) and ( b ) who achieved a clinical ly significant improvement in functioning ( change in Karnofsky score 10 points or more ) by 12 months after r and omisation . Results : Only two eligible patients refused to participate . All r and omised patients completed treatment . An intention to treat analysis showed that 73 % ( 22/30 ) of recipients of cognitive behaviour therapy achieved a satisfactory outcome as compared with 27 % ( 8/30 ) of patients who were given only medical care ( difference 47 percentage points ; 95 % confidence interval 24 to 69 ) . Similar differences were observed in subsidiary outcome measures . The improvement in disability among patients given cognitive behaviour therapy continued after completion of therapy . Illness beliefs and coping behaviour previously associated with a poor outcome changed more with cognitive behaviour therapy than with medical care alone . Conclusion : Adding cognitive behaviour therapy to the medical care of patients with the chronic fatigue syndrome is acceptable to patients and leads to a sustained reduction in functional impairment . Key messages Key messages There is no generally accepted form of treatment New findings show that patients referred to hospital for the chronic fatigue syndrome have a better outcome if they are given a course of cognitive behaviour therapy than if they receive only basic medical care Clinical improvement with cognitive behaviour therapy may be slow but often continues after treatment has ended Cognitive behaviour therapy should be considered as an option for patients presenting with the chronic fatigue Objectives : It is unclear whether insulin-like growth factor ( IGF ) function is involved in the pathophysiology of chronic fatigue syndrome ( CFS ) . Unpublished data and reports in patient organization newsletters suggest that Acclydine , a food supplement , could be effective in the treatment of CFS by increasing biologically active IGF1 levels . Here we aim ed to measure the IGF1 and IGF binding protein ( IGFBP ) 3 status of CFS patients compared to age- and gender-matched neighborhood controls , and to assess the effect of Acclydine on fatigue severity , functional impairment , and biologically active IGF1 level ( IGFBP3/IGF1 ratio ) . Design : A r and omized , placebo-controlled , double-blind clinical trial . Setting : Radboud University Nijmegen Medical Centre , The Netherl and s. Participants : Fifty-seven adult patients who fulfilled the US Centers for Disease Control and Prevention criteria for CFS . IGF status of 22 CFS patients was compared to that of 22 healthy age- and gender-matched neighborhood control individuals . Intervention : Acclydine or placebo for 14 wk . Outcome measures : Outcomes were fatigue severity ( Checklist Individual Strength , subscale fatigue severity [ CIS-fatigue ] ) , functional impairment ( Sickness Impact Profile-8 [ SIP-8 ] ) , and biologically active IGF1 serum concentrations . Analyses were on an intention-to-treat basis . Results : There was no difference in IGF status in 22 CFS patients compared to healthy age- and gender-matched control individuals . Treatment with Acclydine did not result in significant differences compared with the placebo group on any of the outcome measures : CIS-fatigue + 1.1 ( 95 % CI −4.4 to + 6.5 , p = 0.70 ) , SIP-8 + 59.1 ( 95 % CI −201.7 to + 319.8 , p = 0.65 ) , and IGFBP3/IGF1 ratio −0.5 ( 95 % CI −2.8 to + 1.7 , p = 0.63 ) . Conclusion : We found no differences in IGF1 status in CFS patients compared to healthy matched neighborhood controls . In addition , the results of this clinical trial do not demonstrate any benefit of Acclydine over placebo in the treatment of CFS BACKGROUND No somatic treatment has been found to be effective for chronic fatigue syndrome ( CFS ) . Antidepressant therapy is commonly used . Fluoxetine is recommended in preference to tricyclic agents because it has fewer sedative and autonomic nervous system effects . However , there have been no r and omised , placebo-controlled , double-blind studies showing the effectiveness of antidepressant therapy in CFS . We have carried out such a study to assess the effect of fluoxetine in depressed and non-depressed CFS patients . METHODS In this r and omised , double-blind study , we recruited 44 patients to the depressed CFS group , and 52 to the non-depressed CFS group . In each group participants were r and omly assigned to receive either fluoxetine ( 20 mg once daily ) or placebo for 8 weeks . The effect of fluoxetine was assessed by question naires , self-observation lists , st and ard neuropsychological tests , and a motion-sensing device ( Actometer ) , which were applied on the day treatment started and on the last day . FINDINGS The two groups were well matched in terms of age , sex distribution , employment and marital status , and duration of CFS . There were no significant differences between the placebo and fluoxetine-treated groups in the change during the 8-week treatment period for any dimension of CFS . There was no change in subjective assessment s of fatigue , severity of depression , functional impairment , sleep disturbances , neuropsychological function , cognitions , or physical activity in the depressed or the non-depressed subgroup . INTERPRETATION Fluoxetine in a 20 mg daily dose does not have a beneficial effect on any characteristic of CFS . The lack of effect of fluoxetine on depressive symptoms in CFS suggests that processes underlying the presentation of depressive symptoms in CFS may differ from those in patients with major depressive disorder CONTEXT There is no established pharmacological treatment for the core symptoms of chronic fatigue syndrome ( CFS ) . Galantamine hydrobromide , an acetyl cholesterone inhibitor , has pharmacological properties that might benefit patients with CFS . OBJECTIVE To compare the efficacy and tolerability of galantamine hydrobromide in patients with CFS . DESIGN , SETTING , AND PATIENTS R and omized , double-blind trial conducted June 1997 through July 1999 at 35 outpatient centers in the United Kingdom ( n = 17 ) , United States ( n = 14 ) , the Netherl and s ( n = 2 ) , Sweden ( n = 1 ) , and Belgium ( n = 1 ) involving 434 patients with a clinical diagnosis of CFS ( modified US Centers for Disease Control and Prevention criteria ) . INTERVENTIONS A total of 89 patients were r and omly assigned to receive 2.5 mg of galantamine hydrobromide ; 86 patients , 5.0 mg ; 91 patients , 7.5 mg ; and 86 patients , 10 mg ( these patients received medicine in the tablet form 3 times per day ) ; a total of 82 patients received matching placebo tablets 3 times per day . MAIN OUTCOME MEASURES The primary efficacy variable was the global change on the Clinician Global Impression Scale after 4 , 8 , 12 , and 16 weeks of treatment . Secondary outcomes were changes in core symptoms of CFS on the Chalder Fatigue Rating Scale , the Fibromyalgia Impact Question naire , and the Pittsburgh Sleep Quality Index ; changes in quality of life on the Nottingham Health Profile ; and assessment of plasma-free cortisol levels and cognitive performance on a computer-based battery of tests . RESULTS After 16 weeks , there were no statistically significant differences between any of the galantamine or placebo groups in clinical condition on the Clinician Global Impression Scale , or for any of the secondary end points . Exploratory regression analysis failed to detect any consistent prognostic factor that might have influenced the primary or any secondary outcome measures . CONCLUSION This trial did not demonstrate any benefit of galantamine over placebo in the treatment of patients with CFS A double blind r and omized controlled trial was conducted in 71 adolescents aged 11 - 18 years . Inclusion in the trial required fulfilment of the diagnostic criteria , ( Fukuda et al. , 1994 ) . Three infusions of 1 gm/kg ( max 1 litre of 6 gm/100 ml in 10 % w/v maltose solution ) were given one month apart . The dummy solution was a 10 % w/v maltose solution with 1 % albumin of equivalent volume for weight . Efficacy was assessed by difference in a mean functional score including school attendance , school work , social activity and physical activity , between baseline , three months and six months after the final infusion . There was a significant mean functional improvement at the six month follow-up of 70 adolescents with Chronic Fatigue Syndrome of average duration 18 months . There was also a significant improvement for both groups from the beginning of the trial to the six month post infusion follow-up . Adverse effects were common with both solutions but not predictive of response . Neither solution could be identified by recipients BACKGROUND Face-to-face cognitive-behavioural therapy ( CBT ) leads to a reduction of fatigue in chronic fatigue syndrome ( CFS ) . Aims To test the efficacy of internet-based CBT ( iCBT ) for adults with CFS . METHOD A total of 240 patients with CFS were r and omised to either iCBT with protocol -driven therapist feedback or with therapist feedback on dem and , or a waiting list . Primary outcome was fatigue severity assessed with the Checklist Individual Strength ( Netherl and s Trial Register : NTR4013 ) . RESULTS Compared with a waiting list , intention-to-treat ( ITT ) analysis showed a significant reduction of fatigue for both iCBT conditions ( protocol -driven feedback : B = -8.3 , 97.5 % CI -12.7 to -3.9 , P < 0.0001 ; feedback on dem and : B = -7.2 , 97.5 % CI -11.3 to -3.1 , P < 0.0001 ) . No significant differences were found between both iCBT conditions on all outcome measures ( P = 0.3 - 0.9 ) . An exploratory analysis revealed that feedback-on-dem and iCBT required less therapist time ( mean 4 h 37 min ) than iCBT with protocol -driven feedback ( mean 6 h 9 min , P < 0.001 ) and also less than face-to-face CBT as reported in the literature . CONCLUSIONS Both iCBT conditions are efficacious and time efficient . Declaration of interest None OBJECTIVE To provide a preliminary assessment of the efficacy and safety of fludrocortisone acetate treatment of chronic fatigue syndrome . DESIGN A placebo-controlled , double-blind , r and om-allocation crossover trial of 6 weeks of fludrocortisone . SETTING An outpatient clinical trials unit . PATIENTS Twenty-five participants with chronic fatigue syndrome ( mean age , 40 years ; 19 [ 76 % ] women ; mean duration of illness , 7.0 years ) were recruited from a research and clinic registry . Five patients withdrew from the trial . INTERVENTIONS All participants were scheduled to receive fludrocortisone acetate ( 0.1 - 0.2 mg ) or a placebo for 6 weeks in each treatment . MAIN OUTCOME MEASURES Self-administered question naires were completed at the beginning and end of each treatment arm that asked patients to rate the severity of their symptoms on a visual analogue scale . The Medical Outcomes Study 36-Item Short-Form Health Survey , a reaction time test , and a treadmill exercise test were used to assess functional status . Blood pressure , heart rate , and plasma norepinephrine levels were obtained at baseline . Blood pressure and heart rate were recorded at the end of the exercise test and monitored at all subsequent visits . RESULTS At baseline , the study participants reported symptom severity greater than 5 for most symptoms , and all had evidence of marked functional impairments . No improvement was observed in the severity of any symptom or in any test of function for the 20 participants who completed both arms of the trial . Blood pressure and heart rate readings were unaffected by treatment , and plasma norepinephrine levels did not differ from those of a healthy control group . The incidence of adverse experiences was similar in the fludrocortisone and placebo arms of the trial . CONCLUSION Low-dose fludrocortisone does not provide sufficient benefit to be evident in a preliminary blinded trial of unselected patients with chronic fatigue syndrome Background Myalgic Encephalopathy/Chronic Fatigue Syndrome ( ME/CFS ) is a disease of unknown etiology . We previously reported a pilot case series followed by a small , r and omized , placebo-controlled phase II study , suggesting that B-cell depletion using the monoclonal anti-CD20 antibody rituximab can yield clinical benefit in ME/CFS . Methods In this single-center , open-label , one-armed phase II study ( NCT01156909 ) , 29 patients were included for treatment with rituximab ( 500 mg/m2 ) two infusions two weeks apart , followed by maintenance rituximab infusions after 3 , 6 , 10 and 15 months , and with follow-up for 36 months . Findings Major or moderate responses , predefined as lasting improvements in self-reported Fatigue score , were detected in 18 out of 29 patients ( intention to treat ) . Clinical ly significant responses were seen in 18 out of 28 patients ( 64 % ) receiving rituximab maintenance treatment . For these 18 patients , the mean response duration s within the 156 weeks study period were 105 weeks in 14 major responders , and 69 weeks in four moderate responders . At end of follow-up ( 36 months ) , 11 out of 18 responding patients were still in ongoing clinical remission . For major responders , the mean lag time from first rituximab infusion until start of clinical response was 23 weeks ( range 8–66 ) . Among the nine patients from the placebo group in the previous r and omized study with no significant improvement during 12 months follow-up after saline infusions , six achieved a clinical response before 12 months after rituximab maintenance infusions in the present study . Two patients had an allergic reaction to rituximab and two had an episode of uncomplicated late-onset neutropenia . Eight patients experienced one or more transient symptom flares after rituximab infusions . There was no unexpected toxicity . Conclusion In a subgroup of ME/CFS patients , prolonged B-cell depletion with rituximab maintenance infusions was associated with sustained clinical responses . The observed patterns of delayed responses and relapse after B-cell depletion and regeneration , a three times higher disease prevalence in women than in men , and a previously demonstrated increase in B-cell lymphoma risk for elderly ME/CFS patients , suggest that ME/CFS may be a variant of an autoimmune disease . Trial registration Clinical Trials.gov Few studies have examined therapist effects and therapeutic alliance ( TA ) in treatments for chronic fatigue syndrome ( CFS ) . Therapist effects are the differences in outcomes achieved by different therapists . TA is the quality of the bond and level of agreement regarding the goals and tasks of therapy . Prior research suffers the method ological problem that the allocation of therapist was not r and omized , meaning therapist effects may be confounded with selection effects . We used data from a r and omized controlled treatment trial of 296 people with CFS . The trial compared pragmatic rehabilitation ( PR ) , a nurse led , home based self-help treatment , a counselling-based treatment called supportive listening ( SL ) , with general practitioner treatment as usual . Therapist allocation was r and omized . Primary outcome measures , fatigue and physical functioning were assessed blind to treatment allocation . TA was measured in the PR and SL arms . Regression models allowing for interactions were used to examine relationships between ( i ) therapist and therapeutic alliance , and ( ii ) therapist and average treatment effect ( the difference in mean outcomes between different treatment conditions ) . We found no therapist effects . We found no relationship between TA and the average treatment effect of a therapist . One therapist formed stronger alliances when delivering PR compared to when delivering SL ( effect size 0.76 , SE 0.33 , 95 % CI 0.11 to 1.41 ) . In these therapies for CFS , TA does not influence symptomatic outcome . The lack of significant therapist effects on outcome may result from the trial ’s rigorous quality control , or r and om therapist allocation , eliminating selection effects . Further research is needed . Trial Registration : IS RCT IMPORTANCE Chronic fatigue syndrome ( CFS ) is a disabling condition with unknown disease mechanisms and few treatment options . OBJECTIVE To explore the pathophysiology of CFS and assess clonidine hydrochloride pharmacotherapy in adolescents with CFS by using a hypothesis that patients with CFS have enhanced sympathetic activity and that sympatho-inhibition by clonidine would improve symptoms and function . DESIGN , SETTING , AND PARTICIPANTS Participants were enrolled from a single referral center recruiting nationwide in Norway . A referred sample of 176 adolescents with CFS was assessed for eligibility ; 120 were included ( 34 males and 86 females ; mean age , 15.4 years ) . A volunteer sample of 68 healthy adolescents serving as controls was included ( 22 males and 46 females ; mean age , 15.1 years ) . The CSF patients and healthy controls were assessed cross-sectionally at baseline . Thereafter , patients with CFS were r and omized 1:1 to treatment with low-dose clonidine or placebo for 9 weeks and monitored for 30 weeks ; double-blinding was provided . Data were collected from March 2010 until October 2012 as part of the Norwegian Study of Chronic Fatigue Syndrome in Adolescents : Pathophysiology and Intervention Trial . INTERVENTIONS Clonidine hydrochloride capsules ( 25 µg or 50 µg twice daily for body weight < 35 kg or > 35 kg , respectively ) vs placebo capsules for 9 weeks . MAIN OUTCOMES AND MEASURES Number of steps per day . RESULTS At baseline , patients with CFS had a lower number of steps per day ( P < .001 ) , digit span backward score ( P = .002 ) , and urinary cortisol to creatinine ratio ( P = .001 ) , and a higher fatigue score ( P < .001 ) , heart rate responsiveness ( P = .02 ) , plasma norepinephrine level ( P < .001 ) , and serum C-reactive protein concentration ( P = .04 ) compared with healthy controls . There were no significant differences regarding blood microbiology evaluation . During intervention , the clonidine group had a lower number of steps per day ( mean difference , -637 steps ; P = .07 ) , lower plasma norepinephrine level ( mean difference , -42 pg/mL ; P = .01 ) , and lower serum C-reactive protein concentration ( mean ratio , 0.69 ; P = .02 ) compared with the CFS placebo group . CONCLUSIONS AND RELEVANCE Adolescent CFS is associated with enhanced sympathetic nervous activity , low- grade systemic inflammation , attenuated hypothalamus-pituitary-adrenal axis function , cognitive impairment , and large activity reduction , but not with common microorganisms . Low-dose clonidine attenuates sympathetic outflow and systemic inflammation in CFS but has a concomitant negative effect on physical activity ; thus , sympathetic and inflammatory enhancement may be compensatory mechanisms . Low-dose clonidine is not clinical ly useful in CFS . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01040429 OBJECTIVE There is no management regime for chronic fatigue syndrome ( CFS ) that has been found to be universally beneficial and no treatment can be considered a " cure " . Patients with CFS may use complementary and alternative medicine ( CAM ) . Our aim was to evaluate homeopathic treatment in reducing subjective symptoms of CFS . METHOD Using a triple-blind design ( patient and homeopath blind to group assignment and data analyst blind to group until after initial analyses to reduce the possibility of bias due to data analyst ) , we r and omly assigned patients to homeopathic medicine or identical placebo . One hundred and three patients meeting the Oxford criteria for CFS were recruited from two specialist hospital out patient departments . Patients had monthly consultations with a professional homeopath for 6 months . Main outcome measures were scores on the subscales of the Multidimensional Fatigue Inventory ( MFI ) and proportions of each group attaining clinical ly significant improvements on each subscale . Secondary outcome measures were the Fatigue Impact Scale ( FIS ) and the Functional Limitations Profile ( FLP ) . Ninety-two patients completed treatment in the trial ( 47 homeopathic treatment , 45 placebo ) . Eighty-six patients returned fully or partially completed posttreatment outcome measures ( 41 homeopathic treatment group who completed treatment , 2 homeopathic treatment group who did not complete treatment , 38 placebo group who completed treatment , and 5 placebo group who did not complete treatment ) . RESULTS Seventeen of 103 patients withdrew from treatment or were lost to follow-up . Patients in the homeopathic medicine group showed significantly more improvement on the MFI general fatigue subscale ( one of the primary outcome measures ) and the FLP physical subscale but not on other subscales . Although group differences were not statistically significant on four out of the five MFI subscales ( the primary outcome measures ) , more people in the homeopathic medicine group showed clinical ly significant improvement . More people in the homeopathic medicine group showed clinical improvement on all primary outcomes ( relative risk=2.75 , P=.09 ) . CONCLUSIONS There is weak but equivocal evidence that the effects of homeopathic medicine are superior to placebo . Results also suggest that there may be nonspecific benefits from the homeopathic consultation . Further studies are needed to determine whether these differences hold in larger sample BACKGROUND Previous research has suggested that natural killer ( NK ) cell activity may be reduced in patients with chronic fatigue syndrome ( CFS ) . AIM To evaluate the effectiveness of a putative NK cell stimulant , BioBran MGN-3 , in reducing fatigue in CFS patients . DESIGN R and omized , double-blind , placebo-controlled trial . METHODS We recruited 71 patients with CFS ( according to the Centers for Disease Control 1994 criteria ) attending an out-patient specialist CFS service . Participants were given oral BioBran MGN-3 for 8 weeks ( 2 g three times per day ) or placebo equivalent . The primary outcome measure was the Chalder physical fatigue score . Self-reported fatigue measures , self- assessment of improvement , change in key symptoms , quality of life , anxiety and depression measures were also included . RESULTS Data were complete in 64/71 patients . Both groups showed marked improvement over the study duration , but without significant differences . Mean improvement in the Chalder fatigue score ( physical scale ) was 0.3 ( 95%CI -2.6 to 3.2 ) lower in the BioBran group . DISCUSSION The findings do not support a specific therapeutic effect for BioBran in CFS . The improvement showed by both groups over time highlights the importance of placebo controls when evaluating interventions in CFS Summary Background Grade d exercise therapy is an effective and safe treatment for chronic fatigue syndrome , but it is therapist intensive and availability is limited . We aim ed to test the efficacy and safety of grade d exercise delivered as guided self-help . Methods In this pragmatic r and omised controlled trial , we recruited adult patients ( 18 years and older ) who met the UK National Institute for Health and Care Excellence criteria for chronic fatigue syndrome from two secondary -care clinics in the UK . Patients were r and omly assigned to receive specialist medical care ( SMC ) alone ( control group ) or SMC with additional guided grade d exercise self-help ( GES ) . Block r and omisation ( r and omly varying block sizes ) was done at the level of the individual with a computer-generated sequence and was stratified by centre , depression score , and severity of physical disability . Patients and physiotherapists were necessarily unmasked from intervention assignment ; the statistician was masked from intervention assignment . SMC was delivered by specialist doctors but was not st and ardised ; GES consisted of a self-help booklet describing a six-step grade d exercise programme that would take roughly 12 weeks to complete , and up to four guidance sessions with a physiotherapist over 8 weeks ( maximum 90 min in total ) . Primary outcomes were fatigue ( measured by the Chalder Fatigue Question naire ) and physical function ( assessed by the Short Form-36 physical function subscale ) ; both were self-rated by patients at 12 weeks after r and omisation and analysed in all r and omised patients with outcome data at follow-up ( ie , by modified intention to treat ) . We recorded adverse events , including serious adverse reactions to trial interventions . We used multiple linear regression analysis to compare SMC with GES , adjusting for baseline and stratification factors . This trial is registered at IS RCT N , number IS RCT N22975026 . Findings Between May 15 , 2012 , and Dec 24 , 2014 , we recruited 211 eligible patients , of whom 107 were assigned to the GES group and 104 to the control group . At 12 weeks , compared with the control group , mean fatigue score was 19·1 ( SD 7·6 ) in the GES group and 22·9 ( 6·9 ) in the control group ( adjusted difference −4·2 points , 95 % CI −6·1 to −2·3 , p<0·0001 ; effect size 0·53 ) and mean physical function score was 55·7 ( 23·3 ) in the GES group and 50·8 ( 25·3 ) in the control group ( adjusted difference 6·3 points , 1·8 to 10·8 , p=0·006 ; 0·20 ) . No serious adverse reactions were recorded and other safety measures did not differ between the groups , after allowing for missing data . Interpretation GES is a safe intervention that might reduce fatigue and , to a lesser extent , physical disability for patients with chronic fatigue syndrome . These findings need confirmation and extension to other health-care setting s. Funding UK National Institute for Health Research Research for Patient Benefit Programme and the Sue Estermann Fund We have previously conducted a small treatment study on staphylococcus toxoid in fibromyalgia ( FM ) and chronic fatigue syndrome ( CFS ) . The aim of the present study was to further assess the efficacy of the staphylococcus toxoid preparation Staphypan Berna ( SB ) during 6 months in FM/CFS patients . One hundred consecutively referred patients fulfilling the ACR criteria for FM and the 1994 CDC criteria for CFS were r and omised to receive active drug or placebo . Treatment included weekly injections containing 0.1 ml , 0.2 ml , 0.3 ml , 0.4 ml , 0.6 ml , 0.8 ml , 0.9 ml , and 1.0 ml SB or coloured sterile water , followed by booster doses given 4‐weekly until endpoint . Main outcome measures were the proportion of responders according to global ratings and the proportion of patients with a symptom reduction of ≥50 % on a 15‐item subscale derived from the comprehensive psychopathological rating scale ( CPRS ) . The treatment was well tolerated . Intention‐to‐treat analysis showed 32/49 ( 65 % ) responders in the SB group compared to 9/49 ( 18 % ) in the placebo group ( P<0.001 ) . Sixteen patients ( 33 % ) in the SB group reduced their CPRS scores by at least 50 % compared to five patients ( 10 % ) in the placebo group ( P<0.01 ) . Mean change score on the CPRS ( 95 % confidence interval ) was 10.0 ( 6.7–13.3 ) in the SB group and 3.9 ( 1.1–6.6 ) in the placebo group ( P<0.01 ) . An increase in CPRS symptoms at withdrawal was noted in the SB group . In conclusion , treatment with staphylococcus toxoid injections over 6 months led to significant improvement in patients with FM and CFS . Maintenance treatment is required to prevent relapse A minimal intervention , based on cognitive-behavioural therapy for chronic fatigue syndrome and consisting of self-instructions combined with email contact , was tested in a r and omised controlled trial ( IS RCT N27293439 ) . A total of 171 patients participated in the trial : 85 were allocated to the intervention condition and 86 to the waiting-list condition . All patients met the Centers for Disease Control and Prevention criteria for chronic fatigue syndrome . An intention-to-treat analysis showed a significant decrease in fatigue and disability after self-instruction . The level of disability was negatively correlated with treatment outcome . Guided self-instructions are an effective treatment for patients with relatively less severe chronic fatigue syndrome PURPOSE Chronic fatigue syndrome has been associated with decreased function of the hypothalamic-pituitary-adrenal axis . Although neurally mediated hypotension occurs more frequently in patients with chronic fatigue syndrome than in controls , attempts to alleviate symptoms by administration of hydrocortisone or fludrocortisone have not been successful . The purpose of this study was to investigate the effect of combination therapy ( 5 mg/d of hydrocortisone and 50 microg/d of 9-alfa-fludrocortisone ) on fatigue and well-being in chronic fatigue syndrome . METHODS We performed a 6-month , r and omized , placebo-controlled , double-blind , crossover study in 100 patients who fulfilled the 1994 Centers for Disease Control and Prevention criteria for chronic fatigue syndrome . Between-group differences ( placebo minus treatment ) were calculated on a 10-point visual analog scale . RESULTS Eighty patients completed the 3 months of placebo and 3 months of active treatment in a double-blind fashion . There were no differences between treatment and placebo in patient-reported fatigue ( mean difference , 0.1 ; 95 % confidence interval [ CI ] : -0.3 to 0.6 ) or well-being ( mean difference , -0.4 ; 95 % CI : -1.0 to 0.1 ) . There were also no between-group differences in fatigue measured with the Abbreviated Fatigue Question naire , the Short Form-36 Mental or Physical Factor scores , or in the Hospital Anxiety and Depression Scale . CONCLUSION Low-dose combination therapy of hydrocortisone and fludrocortisone was not effective in patients with chronic fatigue syndrome OBJECTIVE The monoaminergic stabiliser (-)-OSU6162 has in previous studies shown promising effects on mental fatigue after stroke and traumatic brain injury . This study investigated the safety and effectiveness of (-)-OSU6162 in patients with myalgic encephalomyelitis/chronic fatigue syndrome . METHODS A total of 62 patients were r and omly assigned to placebo or (-)-OSU6162 . Primary outcomes were assessment on the mental fatigue scale ( MFS ) and the clinical global impression of change ( CGI-C ) scale . Secondary outcomes were results on the FibroFatigue scale ( FF ) , the Beck Depression Inventory ( BDI ) , the pain visual analogue scale and neuropsychological tests . Assessment s were performed at baseline , after 1 and 2 weeks of treatment and at follow-up after 6 weeks . RESULTS MFS and CGI-C showed significant improvements for both treatment groups after treatment but not at follow-up ; a similar pattern was seen for FF and BDI . However , significant differences between groups could not be demonstrated . On the other h and , correlation analyses showed a significant correlation between (-)-OSU6162 concentration and change in MFS , FF , and BDI score within the concentration interval 0.1 - 0.7 µM. Exploratory subgroup analyses showed a larger treatment effect with (-)-OSU6162 in improving MFS and FF symptoms in patients on antidepressant therapy compared to those without antidepressant treatment . CONCLUSION (-)-OSU6162 was found to be safe and well tolerated . When analysing the entire material (-)-OSU6162 was not found to differ significantly from placebo in alleviating fatigue in ME patients but was superior to placebo in counteracting fatigue in a subgroup of ME patients who received concomitant pharmacological treatment for depression Chronic fatigue syndrome ( CFS ) produces physical and neurocognitive disability that significantly affects health-related quality of life ( HRQL ) . Multidisciplinary treatment combining grade d exercise therapy ( GET ) cognitive behavioural therapy ( CBT ) and pharmacological treatment has shown only short-term improvements . To compare the effects on HRQL of ( 1 ) multidisciplinary treatment combining CBT , GET , and pharmacological treatment , and ( 2 ) usual treatment ( exercise counselling and pharmacological treatment ) at 12 months of follow-up . Prospect i ve , r and omized controlled trial with a follow-up of 12 months after the end of treatment . Patients consecutively diagnosed with CFS ( Fukuda criteria ) were r and omly assigned to intervention ( n = 60 ) or usual treatment ( n = 60 ) groups . HRQL was assessed at baseline and 12 months by the Medical Outcomes Study Short-Form question naire ( SF-36 ) . Secondary outcomes included functional capacity for activities of daily living measured by the Stanford Health Assessment Question naire ( HAQ ) and comorbidities . At baseline , the two groups were similar , except for lower SF-36 emotional role scores in the intervention group . At 12 months , the intervention did not improve HRQL scores , with worse SF-36 physical function and bodily pain scores in the intervention group . Multidisciplinary treatment was not superior to usual treatment at 12 months in terms of HRQL . The possible benefits of GET as part of multidisciplinary treatment for CFS should be assessed on an individual patient basis BACKGROUND Only one previous r and omized controlled trial ( RCT ) has examined the efficacy of cognitive behaviour therapy ( CBT ) for chronic fatigue syndrome ( CFS ) in children . The aim of this study was to compare family-focused CBT with psycho-education for CFS in adolescents . METHOD Sixty-three 11- to 18-year-olds ( 43 girls , 20 boys ) with CFS were r and omly assigned to either family-focused CBT or psycho-education delivered over 6 months . School attendance was the main outcome , which was assessed at the end of treatment and at 3 , 6 and 12 months follow-up . RESULTS At the main outcome point ( the 6-month follow-up ) both groups had improved similarly . However , although those who received family-focused CBT were attending school for longer than those who received psycho-education , at discharge from treatment and at 3 months follow-up , they improved less quickly across the follow-up period . CONCLUSIONS Adolescents with CFS get back to school more quickly after family-focused CBT . This is important as they are at a crucial stage of their development . However , the finding that psycho-education was as effective as family-focused CBT at 6 and 12 months follow-up has important implication s for health service delivery OBJECTIVE In this r and omized noninferiority study , the effectiveness and efficiency of stepped care for chronic fatigue syndrome ( CFS ) was compared to care as usual . Stepped care was formed by guided self-instruction , followed by cognitive behavior therapy ( CBT ) if the patient desired it . Care as usual encompassed CBT after a waiting period . METHOD A total of 171 CFS patients were r and omly allocated to stepped care or care as usual . Patients in both conditions were assessed 3 times : at baseline , after guided self-instruction or the waiting period , and after CBT . The primary outcome variables were fatigue severity ( Checklist Individual Strength ) and disabilities ( Sickness Impact Profile and Medical Outcomes Survey Short Form-36 ) . RESULTS An intention to treat analysis showed that stepped care ( N = 84 ) for CFS is noninferior to care as usual ( N = 85 ) . Both conditions were equivalent in reducing fatigue severity , reducing disabilities , and increasing physical functioning . The treatment results of both conditions were in accordance with those of previous r and omized controlled trials testing the effectiveness of CBT for CFS . The total therapist time needed to treat a patient was significantly less in the stepped care condition . CONCLUSIONS Stepped care is as effective as CBT and is more time efficient for the therapist OBJECTIVE Chronic fatigue syndrome is a profoundly disabling condition characterized by severe , unrelenting fatigue and a number of other physical and cognitive symptoms . Currently , there is no cure or widely accepted treatment for chronic fatigue syndrome , and few rehabilitation programs exist to address quality of life issues in chronic fatigue syndrome . In the present r and omized clinical trial , the effects of an integrative , consumer-driven rehabilitation program on quality of life and symptom severity for individuals with chronic fatigue syndrome were examined . METHOD Forty-seven participants were r and omly assigned to either an immediate program group ( n = 23 ) or a delayed program control group ( n = 24 ) and assessed with the Chronic Fatigue Syndrome Symptom Rating Scale and the Quality of Life Index before the program , after program participants completed the group phase , and after program participants completed the one-on-one phase . It was hypothesized that the program would lead to improvements in quality of life and an overall reduction in symptom severity . RESULTS Linear growth models were estimated comparing program and control conditions over time using r and om-effects regression analyses . Significant condition by time interactions were observed for the main outcomes of symptom severity and overall quality of life . Effect sizes for these interactions involving symptom severity ( Cohen 's d = 0.71 ) and overall quality of life ( Cohen 's d = .66 ) were moderate . CONCLUSIONS Findings indicate that consumer driven programs such as this one can have a positive impact on symptom severity and quality of life over time for individuals with chronic fatigue syndrome Chronic fatigue syndrome ( CFS ) is a physically debilitating illness associated with immunologic abnormalities , viral reactivation , and impairment of cognition . In a r and omized , multicenter , placebo-controlled , double-blind study of 92 patients meeting the CFS case definition of the Centers for Disease Control and Prevention , the response of several laboratory and clinical variables to an antiviral and immunomodulatory drug , poly(I).poly(C12U ) , was determined . Measures of clinical response included Karnofsky performance score , a cognition scale derived from a self-administered instrument assessing symptomatology ( SCL-90-R ) , an activities of daily living scale , and exercise treadmill performance . After 24 weeks , patients receiving poly(I).poly(C12U ) had higher scores for both global performance and perceived cognition than did patients receiving placebo . In particular , patients given poly(I).poly(C12U ) had increased Karnofsky performance scores ( P < .03 ) , exhibited a greater ability to do work during exercise treadmill testing ( P = .01 ) , displayed an enhanced capacity to perform the activities of daily living ( P < .04 ) , had a reduced cognitive deficit ( P = .05 ) , and required less use of other medications ( P < .05 ) OBJECTIVE To test the efficacy of a grade d aerobic exercise programme in the chronic fatigue syndrome . DESIGN R and omised controlled trial with control treatment crossover after the first follow up examination . SETTING Chronic fatigue clinic in a general hospital department of psychiatry . SUBJECTS 66 patients with the chronic fatigue syndrome who had neither a psychiatric disorder nor appreciable sleep disturbance . INTERVENTIONS R and om allocation to 12 weeks of either grade d aerobic exercise or flexibility exercises and relaxation therapy . Patients who completed the flexibility programme were invited to cross over to the exercise programme afterwards . MAIN OUTCOME MEASURE The self rated clinical global impression change score , " very much better " or " much better " being considered as clinical ly important . RESULTS Four patients receiving exercise and three receiving flexibility treatment dropped out before completion . 15 of 29 patients rated themselves as better after completing exercise treatment compared with eight of 30 patients who completed flexibility treatment . Analysis by intention to treat gave similar results ( 17/33 v 9/33 patients better ) . Fatigue , functional capacity , and fitness were significantly better after exercise than after flexibility treatment . 12 of 22 patients who crossed over to exercise after flexibility treatment rated themselves as better after completing exercise treatment 32 of 47 patients rated themselves as better three months after completing supervised exercise treatment 35 of 47 patients rated themselves as better one year after completing supervised exercise treatment . CONCLUSION These findings support the use of appropriately prescribed grade d aerobic exercise in the management of patients with the chronic fatigue syndrome The aim of this study was to investigate the potential mechanisms underlying the efficacy of grade d exercise therapy for chronic fatigue syndrome ( CFS ) . Forty-nine CFS patients were r and omized to a 12-week grade d exercise programme or to st and ard medical care . At the end of treatment the exercise group rated themselves as significantly more improved and less fatigued than the control group . A decrease in symptom focusing rather than an increase in fitness mediated the treatment effect . Grade d exercise appears to be an effective treatment for CFS and it operates in part by reducing the degree to which patients focus on their symptoms BACKGROUND The efficacy of dietary supplements in chronic fatigue syndrome ( CFS ) is uncertain , with conflicting evidence . AIM To assess the effect of a polynutrient supplement on fatigue and physical activity of patients with CFS . DESIGN Prospect i ve r and omized placebo-controlled , double-blind trial . METHODS Fifty-three patients ( 16 males , 37 females ) fulfilling the CDC criteria of CFS . The entry criteria were a score on the Checklist Individual Strength subscale fatigue severity ( CIS fatigue ) > or=40 and a weighted sum score of > or=750 for the eight subscales of the Sickness Impact Profile ( SIP8 ) and no use of nutritional supplements in the 4 weeks prior to entry . The exclusion criteria were pregnancy and lactose intolerance . The intervention-a polynutrient supplement containing several vitamins , minerals and (co)enzymes , or placebo , twice daily for 10 weeks-was preceded by 2 weeks of baseline measurements . Outcome measurements took place in week 9 and 10 of the intervention . Five participants dropped out ( 4 supplement , 1 placebo ) . The main outcome measures were CIS fatigue score , number of CDC symptoms and SIP8 score . Efficacy analyses were performed on an intention-to-treat basis . RESULTS No significant differences were found between the placebo and the treated group on any of the outcome measures : CIS fatigue + 2.16 ( 95%CI -4.3 to + 4.39 , p=0.984 ) ; CDC symptoms + 0.42 ( 95%CI -0.61 to + 1.46 , p=0.417 ) ; SIP8 + 182 ( 95%CI -165 to + 529 , p=0.297 ) . No patient reported full recovery . DISCUSSION The findings do not support the use of a broad-spectrum nutritional supplement in treating CFS-related symptoms OBJECTIVES To test the hypothesis that group cognitive behavioural therapy ( CBT ) will produce an effective and cost-effective management strategy for patients in primary care with chronic fatigue syndrome/myalgic encephalopathy ( CFS/ME ) . DESIGN A double-blind , r and omised controlled trial was adopted with three arms . Outcomes were assessed at baseline and 6 and 12 months after first assessment and results were analysed on an intention-to-treat basis . SETTING A health psychology department for the management of chronic illness in a general hospital in Bristol , UK . PARTICIPANTS Adults with a diagnosis of CFS/ME referred by their GP . INTERVENTIONS The three interventions were group CBT incorporating grade d activity scheduling , education and support group ( EAS ) and st and ard medical care ( SMC ) . OUTCOME MEASURES The primary outcome measure was the Short Form with 36 Items ( SF-36 ) physical and mental health summary scales . Other outcome measures included the Chalder fatigue scale , Hospital Anxiety and Depression Scale , General Health Question naire , physical function ( shuttles walked , walking speed and perceived fatigue ) , health utilities index and cognitive function ( mood , recall and reaction times ) . RESULTS A total of 153 patients were recruited to the trial and 52 were r and omised to receive CBT , 50 to EAS and 51 to SMC . Twelve patients failed to attend for the 12-month follow-up and 19 patients attended one follow-up , but not both . The sample was found to be representative of the patient group and the characteristics of the three groups were similar at baseline . Three outcome measures , SF-36 mental health score , Chalder fatigue scale and walking speed , showed statistically significant differences between the groups . Patients in the CBT group had significantly higher mental health scores [ difference + 4.35 , 95 % confidence interval ( CI ) + 0.72 to + 7.97 , p = 0.019 ] , less fatigue ( difference -2.61 , 95 % CI -4.92 to -0.30 , p = 0.027 ) and were able to walk faster ( difference + 2.83 shuttles , 95 % CI + 1.12 to + 5.53 , p = 0.0013 ) than patients in the SMC group . CBT patients also walked faster and were less fatigued than those r and omised to EAS ( walking speed : difference + 1.77 , 95 % CI + 0.025 to + 3.51 , p = 0.047 ; fatigue : difference -3.16 , 95 % CI -5.59 to -0.74 , p = 0.011 ) . Overall , no other statistically significant difference across the groups was found , although for many measures a trend towards an improved outcome with CBT was seen . Except for walking speed , which , on average , increased by + 0.87 shuttles ( 95 % CI + 0.09 to + 1.65 , p = 0.029 ) between the 6- and 12-month follow-ups , the scores were similar at 6 and 12 months . At baseline , 30 % of patients had an SF-36 physical score within the normal range and 52 % had an SF-36 mental health score in the normal range . At 12 months , the physical score was in the normal range for 46 % of the CBT group , 26 % of the EAS group and 44 % of SMC patients . For mental health score the percentages were CBT 74 % , EAS 67 % and SMC 70 % . Of the CBT group , 32 % showed at least a 15 % increase in physical function and 64 % achieved a similar improvement in their mental health . For the EAS and SMC groups , this improvement in physical and mental health was achieved for 40 and 60 % ( EAS ) and 49 and 53 % ( SMC ) , respectively . The cost-effectiveness of the intervention proved very difficult to assess and did not yield reliable conclusions . CONCLUSIONS Group CBT did not achieve the expected change in the primary outcome measure as a significant number did not achieve scores within the normal range post-intervention . The treatment did not return a significant number of subjects to within the normal range on this domain ; however , significant improvements were evident in some areas . Group CBT was effective in treating symptoms of fatigue , mood and physical fitness in CFS/ME . It was found to be as effective as trials using individual therapy in these domains . However , it did not bring about improvement in cognitive function or quality of life . There was also evidence of improvement in the EAS group , which indicates that there is limited value in the non-specific effects of therapy . Further research is needed to develop better outcome measures , assessment s of the broader costs of the illness and a clearer picture of the characteristics best fitted to this type of intervention Background : Meta-analyses have been inconclusive about the efficacy of cognitive behaviour therapies ( CBTs ) delivered in groups of patients with chronic fatigue syndrome ( CFS ) due to a lack of adequate studies . Methods : We conducted a pragmatic r and omised controlled trial with 204 adult CFS patients from our routine clinical practice who were willing to receive group therapy . Patients were equally allocated to therapy groups of 8 patients and 2 therapists , 4 patients and 1 therapist or a waiting list control condition . Primary analysis was based on the intention-to-treat principle and compared the intervention group ( n = 136 ) with the waiting list condition ( n = 68 ) . The study was open label . Results : Thirty-four ( 17 % ) patients were lost to follow-up during the course of the trial . Missing data were imputed using mean proportions of improvement based on the outcome scores of similar patients with a second assessment . Large and significant improvement in favour of the intervention group was found on fatigue severity ( effect size = 1.1 ) and overall impairment ( effect size = 0.9 ) at the second assessment . Physical functioning and psychological distress improved moderately ( effect size = 0.5 ) . Treatment effects remained significant in sensitivity and per- protocol analyses . Subgroup analysis revealed that the effects of the intervention also remained significant when both group sizes ( i.e. 4 and 8 patients ) were compared separately with the waiting list condition . Conclusions : CBT can be effectively delivered in groups of CFS patients . Group size does not seem to affect the general efficacy of the intervention which is of importance for setting s in which large treatment groups are not feasible due to limited referral BACKGROUND Anecdotal reports and books have been published linking an over growth of C and ida Albicans with chronic fatigue syndrome ( CFS ) , suggesting dietary change as a treatment option . Little scientific data has been published to vali date this controversial theory . This study aims to determine the efficacy of dietary intervention on level of fatigue and quality of life ( QoL ) in individuals with CFS . METHODS A 24-week r and omized intervention study was conducted with 52 individuals diagnosed with CFS . Patients were r and omized to either a low sugar low yeast ( LSLY ) or healthy eating ( HE ) dietary interventions . Primary outcome measures were fatigue as measured by the Chalder Fatigue Score and QoL measured by Medical Outcomes Survey Short Form-36 . RESULTS A high drop out rate occurred with 13 participants not completing the final evaluation ( 7HE/6LSLY ) . Intention to treat analysis showed no statistically significant differences on primary outcome measurements . CONCLUSION In this r and omized control trial , a LSLY diet appeared to be no more efficacious on levels of fatigue or QoL compared to HE . Given the difficulty with dietary compliance experienced by participants , especially in the LSLY group , it would appear HE guidance is a more pragmatic approach than advocating a complicated dietary regime |
12,327 | 24,864,275 | RESULTS Behavioral interventions generally improve children 's pedestrian safety , both immediately after training and at follow-up several months later .
Available evidence suggested interventions targeting dash-out prevention , crossing at parked cars , and selecting safe routes across intersections were effective .
Individualized/small-group training for children was the most effective training strategy based on available evidence .
Behaviorally based interventions improve children 's pedestrian safety . | OBJECTIVE Pedestrian injuries represent a pediatric public health challenge .
This systematic review /meta- analysis evaluated behavioral interventions to teach children pedestrian safety . | Sixty percent to 70 % of pedestrian injuries in children under the age of 10 years are the result of the child either improperly crossing intersections or dashing out in the street between intersections . The purpose of this injury prevention research study was to evaluate a desktop virtual reality ( VR ) program that was design ed to educate and train children to safely cross intersections . Specifically , the objectives were to determine whether children can learn pedestrian safety skills while working in a virtual environment and whether pedestrian safety learning in VR transfers to real world behavior . Following focus groups with a number of key experts , a virtual city with eight interactive intersections was developed . Ninety-five children participated in a community trial from two schools ( urban and suburban ) . Approximately half were assigned to a control group who received an unrelated VR program , and half received the pedestrian safety VR intervention . Children were identified by group and grade by colored tags on their backpacks , and actual street crossing behavior of all children was observed 1 week before and 1 week after the interventions . There was a significant change in performance after three trials with the VR intervention . Children learned safe street crossing within the virtual environment . Learning , identified as improved street-crossing behavior , transferred to real world behavior in the suburban school children but not in the urban school . The results are discussed in relation to possibilities for future VR interventions for injury prevention Objective : to evaluate the effectiveness of a school-based injury prevention program . Design : Cluster r and omised controlled trial . Setting : 20 primary schools in Nottingham , UK . Participants : 459 children aged 7 to 10 years . Intervention : The “ Risk Watch ” program delivered by teachers , aim ed at improving bike and pedestrian , falls , poisoning and fire and burns safety . Main outcome measures : Safety knowledge , observed safety skills and self-reported safety behaviour . Results : At follow-up , intervention group children correctly answered more fire and burn prevention knowledge questions than control group children ( difference between means 7.0 % ( 95 % CI 1.5 % to12.6 % ) ) . Children in intervention group schools were more likely to know the correct actions to take if clothes catch fire and the correct way to wear a cycle helmet ( difference between school means 35.3 % ( 95 % CI 22.7 % to 47.9 % ) and 6.3 % ( 95 % CI 1.4 % to 11.1 % ) respectively ) . They were also more likely to know the correct actions to take in a house fire and on finding tablets ( OR 2.80 ( 95 % CI 1.08 to 7.22 ) and OR 3.50 ( 95 % CI 1.18 to 10.38 ) respectively ) and correctly demonstrated more safety skills than control group children ( difference between means 11.9 % ( 95 % CI 1.4 % to 22.5 % ) ) . There was little evidence to suggest the first year of the program impacted on self-reported safety behaviours . Conclusions : The Risk Watch program delivered by teachers in primary schools increased some aspects of children ’s safety knowledge and skills and primary schools should consider delivering this program . Longer term , larger scale evaluations are required to examine retention of knowledge and skills and impact on safety behaviours and child injury rates It was hypothesized that practical training is effective in improving children 's pedestrian skills because adult scaffolding and peer discussion during training specifically promote E3 level representation ( linguistically-encoded , experientially-grounded , generalizable knowledge ) , as defined by Karmiloff-Smith 's ( 1992 ) representational redescription ( RR ) model . Two studies were conducted to examine in detail the impact of this social input in the context of simulation-based training in roadside search skills . A group of 5 - 8-year-olds were pre-tested on ability to detect relevant road-crossing features . They then participated in four training sessions design ed to promote attunement to these , under peer discussion versus adult guidance conditions ( Study 1 ) , and adult-child versus adult-group conditions ( Study 2 ) . Performance at post-test was compared with that of controls who underwent no training . Study 1 found that children in the adult guidance condition improved significantly more than those in the peer discussion or control conditions , and this improvement was directly attributable to appropriation of E3 level representations from adult dialogue . Study 2 found that progress was greater still when adult scaffolding was supplemented by peer discussion , with E3 level representation attributable to the children 's exploration of conflicting ideas . The implication s of these findings for the RR model and for practical road safety education are discussed OBJECTIVE Child pedestrian injury is a global public health challenge . This r and omized , controlled trial considered comparative efficacy of individualized streetside training , training in a virtual pedestrian environment , training using videos and Web sites , plus no-training control , to improve children 's street-crossing ability . METHODS Pedestrian safety was evaluated among 231 7- and 8-year-olds using both streetside ( field ) and laboratory-based ( virtual environment ) trials before intervention group assignment , immediately posttraining , and 6 months posttraining . All training groups received 6 30-min sessions . Four outcomes assessed pedestrian safety : start delay ( temporal lag before initiating crossing ) , hits/close calls ( collisions/near-misses with vehicles in simulated crossings ) , attention to traffic ( looks left and right , controlled for time ) , and missed opportunities ( safe crossing opportunities that were missed ) . RESULTS Results showed training in the virtual pedestrian environment and especially individualized streetside training result ed in safer pedestrian behavior postintervention and at follow-up . As examples , children trained streetside entered safe traffic gaps more quickly posttraining than control group children and children trained streetside or in the virtual environment had somewhat fewer hits/close calls in postintervention VR trials . Children showed minimal change in attention to traffic posttraining . Children trained with videos/websites showed minimal learning . CONCLUSION Both individualized streetside training and training within virtual pedestrian environments may improve 7- and 8-year-olds ' street-crossing safety . Individualized training has limitations of adult time and labor . Virtual environment training has limitations of accessibility and cost . Given the public health burden of child pedestrian injuries , future research should explore innovative strategies for effective training that can be broadly disseminated Using a simulation game design ed to teach children to obey certain traffic safety rules , an experimental study was conducted with 136 five-year-old children in four Quebec schools . Within each classroom , subjects were r and omly divided into four groups : three intervention groups and one control group . Each of the experimental groups was subjected to a different intervention with outcome measured using three instruments related to attitudes , behavior , and transfer of learning of pedestrian traffic safety . Results suggest that simulation games including role-playing/group dynamics and modeling/training can change attitudes and modify behavior in the area of pedestrian traffic safety in children of this age Pedestrian injuries contribute greatly to child morbidity and mortality . Recent evidence suggests that training within virtual pedestrian environments may improve children ’s street crossing skills , but may not convey knowledge about safety in street environments . We hypothesized that ( a ) children will gain pedestrian safety knowledge via videos/software/internet websites , but not when trained by virtual pedestrian environment or other strategies ; ( b ) pedestrian safety knowledge will be associated with safe pedestrian behavior both before and after training ; and ( c ) increases in knowledge will be associated with increases in safe behavior among children trained individually at streetside locations , but not those trained by means of other strategies . We analyzed data from a r and omized controlled trial evaluating pedestrian safety training . We r and omly assigned 240 children ages 7–8 to one of four training conditions : videos/software/internet , virtual reality ( VR ) , individualized streetside instruction , or a no-contact control . Both virtual and field simulations of street crossing at 2-lane bi-directional mid-block locations assessed pedestrian behavior at baseline , post-training , and 6-month follow-up . Pedestrian knowledge was assessed orally on all three occasions . Children trained by videos/software/internet , and those trained individually , showed increased knowledge following training relative to children in the other groups ( ps < 0.01 ) . Correlations between pedestrian safety knowledge and pedestrian behavior were mostly non-significant . Correlations between change in knowledge and change in behavior from pre- to post-intervention also were non-significant , both for the full sample and within conditions . Children trained using videos/software/internet gained knowledge but did not change their behavior . Children trained individually gained in both knowledge and safer behavior . Children trained virtually gained in safer behavior but not knowledge . If VR is used for training , tools like videos/internet might effectively supplement training . We discovered few associations between knowledge and behavior , and none between changes in knowledge and behavior . Pedestrian safety knowledge and safe pedestrian behavior may be orthogonal constructs that should be considered independently for research and training purpose BACKGROUND Programmes design ed to teach children about road safety have often failed to assess their effectiveness in terms of either an increase in children 's knowledge or an improvement in children 's behaviour . AIM The two studies reported here sought to address both issues , by focusing on the abilities of Primary 1 children ( 5 years old ) . SAMPLE A total of 120 Primary 1 children within the age range 4 - 5 years old participated in this study , drawn from three different primary schools within an educational district of Scotl and . METHODS In the first study the effects of three different road safety interventions were tested , all of which employed commercially marketed products : 1 ) a three-dimensional model of the traffic environment ; 2 ) a road safety board game ; and 3 ) illustrated posters and flip-chart material s. In the second study the transfer of knowledge to children 's behaviour in a real-life traffic environment was tested , using a sub sample of 47 children who had taken part in the first study . RESULTS Results from the first study showed , surprisingly , that all three interventions were effective in increasing children 's knowledge about safe and dangerous locations at which to cross the street , and that this knowledge was retained for a period of six months . Study 2 , however , showed that increased knowledge did not result in improved traffic behaviour . Children who had received training performed no better than children in a control group . CONCLUSION These findings highlight the need to distinguish between children 's road safety knowledge and their behaviour , particularly for teachers and parents , who may mistakenly believe that children who know more will be safer on the road Background Pedestrian injuries are among the leading causes of morbidity and mortality in middle childhood . One limitation to existing pedestrian safety interventions is that they do not provide children with repeated practice needed to develop the complex perceptual and cognitive skills required for safe street crossing . Virtual reality offers training through repeated unsupervised practice without risk , automated feedback on success of crossings , adjustment of traffic to match children 's skill and a fun , appealing environment for training . Objective To test the efficacy of virtual reality to train child pedestrians in safe street crossing . Setting Birmingham , Alabama , USA . Methods A r and omised controlled trial is underway with an expected sample of four groups of 60 children aged 7–8 years ( total N=240 ) . One group receives training in an interactive , immersive virtual pedestrian environment . A second receives pedestrian safety training via widely used video and computer strategies . The third group receives what is judged to be the most efficacious treatment currently available , individualised behavioural training at streetside locations . The fourth group serves as a no-contact control group . All participants are exposed to a range of field and laboratory-based measures of pedestrian skill during baseline and post-intervention visits , as well as during a 6-month follow-up assessment . Outcome Measures Primary analyses will be conducted through linear mixed models testing change over time in the four intervention groups . Three pedestrian safety measures will serve as primary outcomes : temporal gap before initiating crossing , temporal gap remaining after crossing and attention to traffic while waiting to cross . Clinical Trial Registration This study is registered at the US government website , www . clinical trials.gov , under the title ‘ Using virtual reality to train children in pedestrian safety ’ , registration number NCT00850759 BACKGROUND Young children in the 5 - 9 age range are particularly vulnerable to road accidents as pedestrians and previous research has identified a range of motivational and cognitive skill factors which may play a part in this . AIMS The present study aim ed to examine the extent to which the development of pedestrian skills in young children was related to individual differences in visual search strategies . SAMPLE A sample of 180 children aged 4/5 , 7/8 and 10/11 years was presented with tasks intended to assess their pedestrian skills . From this analysis a subset of 60 children was selected who had particularly high or low levels of pedestrian skills , together with a r and om sample of 10 adults , for more detailed analysis of their visual search strategies when confronted with the problem of crossing a road safely . METHOD The children 's pedestrian skills were assessed using three tasks based on slide and video presentations of real roadside situations ; these tasks assessed the ability to identify safe places to cross the road , and to decide when it was safe to cross based on the ability to detect dangerous traffic and to co-ordinate information from different directions . Visual search strategies were assessed using a ' spot the difference ' test and by analysing the head and eye movements of children and adults while they were carrying out the video task requiring them to co-ordinate information from different directions . This task was also used to make an assessment of individuals ' processing speeds by measuring the time it took to make decisions that it was safe to cross the road . RESULTS Significant differences emerged in strategic approaches between children in different age groups , and those who had high and low levels of pedestrians skills . A significant strategic shift appeared to be occurring around the age of 7/8 years . CONCLUSIONS The results indicate that the explicit training of visual search strategies might well be beneficial , but that these can not simply be the strategies of the adult pedestrian . Children may need to master simpler strategies which their slower processing speeds allow them to manage before they proceed on to the more sophisticated strategic approaches , typically involving predictions , used by older children and adults OBJECTIVE This r and omized controlled trial examined one aspect of child pedestrian behavior , route selection across intersections , to evaluate whether a combination of widely-available videos and websites effectively train children in safe pedestrian route selection compared to active pedestrian safety control training and a no-contact control group . METHODS A sample of 231 seven- and eight-year-olds were r and omly assigned to one of four groups : training with videos and internet websites , active control groups of individualized streetside training or training within a virtual pedestrian environment , or a no-contact control group . All training groups received six 30-minute training sessions . Pedestrian route selection was assessed using two strategies , vignettes accompanied by illustrations and tabletop models of intersections , on three occasions : prior to intervention group assignment , immediately post-training , and six months after training . RESULTS Although there were differences in route selection over time , no time by condition interaction effects were significant ( ps > .05 ) , suggesting children in the video/internet training group did not learn pedestrian route selection skills at a rate different from those in the other training groups or those in the no-contact control group . CONCLUSION Safe route selection is a critical component of pedestrian safety . Our results suggest children may not learn route selection from widely-available videos or websites . Explanations for the null finding and implication s for both research and future practice are discussed |
12,328 | 26,053,953 | Ibuprofen 200 mg with caffeine 100 mg or 200 mg had a reasonable analgesic effect with fewer side effects .
It was found in this systematic review Ibuprofen 400 mg combined with oxycodone HCL 5 mg has superior analgesic efficacy when compared to the other analgesic combinations included in this study | OBJECTIVES To run a systematic review and meta- analysis of r and omized clinical trials aim ing to answer the clinical question " which analgesic combination and dosage is potentially the most effective and safe for acute post-operative pain control after third molar surgery ? " . | BACKGROUND Combination therapy has been widely used for the clinical management of acute pain . By combining 2 drugs with different mechanisms of action , such therapy provides additive analgesic effects while reducing the risk for adverse effects . OBJECTIVE This study compared the efficacy and tolerability of oxycodone 5 mg/ibuprofen 400 mg with those of oxycodone 5 mg/acetaminophen 325 mg , hydrocodone 7.5 mg/acetaminophen 500 mg , and placebo in a dental pain model . METHODS This was a multicenter , r and omized , double-blind , placebo- and active-controlled , parallel-group , single-dose study in patients experiencing moderate to severe pain after surgical removal of > or = 2 ipsilateral impacted third molars . Patients were r and omly assigned to receive oxycodone 5 mg/ibuprofen 400 mg , oxycodone 5 mg/acetaminophen 325 mg , hydrocodone 7.5 mg/acetaminophen 500 mg , or placebo . The primary outcome measures were total pain relief through 6 hours after dosing ( TOTPAR6 ) , sum of pain intensity differences through 6 hours ( SPID6 ) , and adverse events . Secondary efficacy measures included SPID3 and TOTPAR3 , peak pain relief , peak pain intensity difference , time to onset of pain relief , time to use of rescue medication , proportion of patients reporting pain half gone , and the patient 's global evaluation . RESULTS Two hundred forty-nine patients ( 43.5 % male ; 87.5 % white ; mean age , 19.1 years ; mean body weight , 153.6 pounds ) were r and omized to treatment as follows : 62 to oxycodone 5 mg/ibuprofen 400 mg , 61 to oxycodone 5 mg/acetaminophen 325 mg , 63 to hydrocodone 7.5 mg/acetaminophen 500 mg , and 63 to placebo . Oxycodone 5 mg/ibuprofen 400 mg provided significantly greater analgesia compared with oxycodone 5 mg/acetaminophen 325 mg , hydrocodone 7.5 mg/acetaminophen 500 mg , and placebo ( mean [ SD ] TOTPAR6 , 14.98 [ 5.37 ] , 9.53 [ 6.77 ] , 8.36 [ 6.68 ] , and 5.05 [ 6.49 ] , respectively ; P < 0.001 , oxycodone 5 mg/ibuprofen 400 mg vs all other treatments ) . SPID6 values also differed significantly for oxycodone 5 mg/ibuprofen 400 mg compared with all other treatments ( mean : 7.78 [ 4.11 ] , 3.58 [ 4.64 ] , 3.32 [ 4.73 ] , and 0.69 [ 4.85 ] ; P < 0.001 ) . Oxycodone 5 mg/ibuprofen 400 mg was significantly more effective compared with the other treatments on all secondary end points ( P < 0.001 , all variables except peak PID vs oxycodone 5 mg/acetaminophen 325 mg [ P = 0.006 ] ) , with the exception of the time to onset of analgesia . The lowest frequency of nausea and vomiting occurred in the groups that received oxycodone 5 mg/ibuprofen 400 mg ( 6.5 % and 3.2 % , respectively ) and placebo ( 3.2 % and 1.6 % ) . Rates of nausea and vomiting were significantly lower with oxycodone 5 mg/ibuprofen 400 mg compared with oxycodone 5 mg/acetaminophen 325 mg ( P = 0.011 and P = 0.009 , respectively ) but not with hydrocodone 7.5 mg/acetaminophen 500 mg . CONCLUSIONS In this study in patients with moderate to severe pain after surgery to remove impacted third molars , oxycodone 5 mg/ibuprofen 400 mg provided significantly better analgesia throughout the 6-hour study compared with the other opioid/nonopioid combinations tested , and was associated with fewer adverse events BACKGROUND The aim of this study was to evaluate the comparative efficacy of three commonly used analgesics ( Panadeine , Diflunisal and Etodolac ) in the control of pain after third molar surgery under local anaesthesia . METHODS A r and omized control study . Outcome of primary efficacy was judged by overall assessment of the area under the curve of graphs for pain intensity , measured from serial visual analogue scales over a 24-hour period . Other measures of efficacy included the number ( per cent ) of patients who took ' additional ' analgesics and the incidence of adverse effects occurring in each treatment group over the study period . RESULTS The three drugs were effective in the control of post-operative pain ( p<0.01 ) . Variations in pain intensity and the use of additional medication between the treatment groups were observed over the study period . The Diflunisal group experienced less pain than the Panadeine or Etodolac group ( p<0.01 ) . Furthermore , a lesser number of those in the Diflunisal group used additional medication compared to the other two groups ( p<0.01 ) . The incidence of side effects from all three drugs was low . CONCLUSION Diflunisal is superior in the control of pain following third molar surgery under local anaesthesia than either Panadeine or Etodolac , and has few side effects BACKGROUND Butorphanol tartrate , a mixed synthetic agonistantagonist opioid analgesic has been used for management of postoperative pain in minor and major surgical procedures .(14,20 ) Tramadol hydrochloride is a central ly acting opioid which is effectively used in postoperative pain in various minor and major surgeries . MATERIAL S AND METHODS Twenty subjects selected r and omly received butorphanol tartrate 1 mg intramuscular and 20 subjects received tramadol hydrochloride 50 mg intramuscular after the removal of m and ibular third molars . Time of injection , amount of anesthetic injected , duration of surgery , adverse effects were recorded.(21 ) RESULTS The mean amount of LA administered in butorphanol group was 2.6450 ml and in tramadol group was 2.640 ml respectively , the mean duration for surgery was 56.75 and 53.5 minutes for butorphanol and tramadol groups respectively which was statistically not significant . Pain assessment was done with VAS which showed mean of 19.2 and 15.5 mm ( p = 0.001 ) which was significant for butorphanol and tramadol respectively after 12 hours . The mean time for rescue medication requirement was 5.9 hours ( for tramadol ) and 8.4 hours ( for butorphanol ) . Effective analgesic activity was seen by butorphanol 1 mg intramuscular then tramadol 50 mg . CONCLUSION Butorphanol 1 mg was more effective than tramadol 50 mg in respect to postoperative analgesia We conducted a r and omised double-blind placebo-controlled single-centre study to compare the effect of preoperative ibuprofen 600 mg , diclofenac 100 mg , paracetamol 1 g with codeine 60 mg or placebo ( Vitamin C 50 mg ) tablets for relief of postoperative pain in 119 patients who had day case operations under general anaesthesia for removal of impacted third molars . Patients were given the tablets 1 h before operation . Pain was assessed using visual analogue scales and verbal rating scales preoperatively at 15 and 30 min and 1 and 3 h postoperatively . After they had gone home , patients were contacted by telephone at 6 and 24 h postoperatively to find out whether they had any adverse effects from the analgesics . There was no significant difference in the extent of postoperative pain among the four groups , but the placebo group had significantly shorter times before their first request for postoperative analgesics ( median 17 min , range 14 - 90 ) than the diclofenac group ( median 32 , range 15 - 150 ) . Preoperative analgesics at the stated doses are effective in providing immediate postoperative pain control after operations on third molars . There were , however , some side-effects including nausea , vomiting , headaches , and gastrointestinal discomfort , but there were no significant differences among the active analgesic groups with respect to adverse events either shortly after operation or at 6 or 24 Tramadol hydrochloride is a novel , central ly acting analgesic with two complementary mechanisms of action : opioid and aminergic . Relative to codeine , tramadol has similar analgesic properties but may have fewer constipating , euphoric , and respiratory depressant effects . A two-center r and omized double-blind controlled clinical trial was performed to assess the analgesic efficacy and reported side effects of tramadol 100 mg , tramadol 50 mg , codeine 60 mg , aspirin ( ASA ) 650 mg with codeine 60 mg , and placebo . Using a third molar extraction pain model , 200 healthy subjects were enrolled in a 6-hour evaluation after a single dose of drug . Of the 200 patients enrolled , seven provided incomplete efficacy data or discontinued prematurely and one was lost to follow-up . Using st and ard measures of analgesia , including total pain relief score ( TOTPAR ) , maximum pain relief score ( MaxPAR ) , sum of pain intensity difference scores ( SPID ) , peak pain intensity difference ( Peak PID ) , remedication , and global evaluations , all active treatments were found to be numerically superior to placebo . ASA/codeine was found to be statistically superior to placebo for all measures of efficacy . Tramadol 100 mg was statistically superior to placebo for TOTPAR , SPID , and time of remedication , whereas tramadol 50 mg was statistically superior to placebo onlyfor remedication time . Codeine was not found to be statistically superior to placebo for any efficacy measure . A greater TOTPAR response compared with all other active measures was seen for ASA/codeine during the first 3 hours of study . The 6-hour TOTPAR scores for the tramadol groups and ASA/ codeine group were not significantly different . Gastrointestinal side effects ( nausea , dysphagia , vomiting ) were reported more frequently with tramadol 100 mg , ASA/ codeine , and codeine 60 mg than with placebo BACKGROUND Aspirin is a widely used NSAID that has been extensively studied in numerous conditions . Nonprescription analgesics , such as aspirin , are frequently used for a wide variety of common ailments , including conditions such as dental pain and tension-type headache . OBJECTIVE We sought to compare the efficacy and safety profiles of aspirin , acetaminophen with codeine , and placebo in the treatment of post-operative dental pain and tension-type headache . METHODS These were 2 r and omized , double-blind , placebo-controlled , single-dose clinical trials that assigned participants ( 2:2:1 ) to receive either aspirin ( 1000 mg ) , acetaminophen ( 300 mg ) with codeine ( 30 mg ) , or placebo . The primary efficacy end point was the sum of pain intensity differences from baseline ( SPID ) over 6 hours for the dental pain study and over 4 hours for the tension-type headache study . Other common analgesic measures , in addition to safety , were also evaluated . RESULTS The results of the dental pain study for aspirin and acetaminophen with codeine suggest statistically significant efficacy for all measures compared with placebo at all time points . Aspirin provided statistically significant efficacy compared with acetaminophen with codeine for SPID(0 - 4 ) ( P = 0.028 ) . In the tension-type headache study , aspirin and acetaminophen with codeine provided statistically significant efficacy compared with placebo for SPID(0 - 4 ) and SPID(0 - 6 ) ( P < 0.001 ) and for total pain relief ( P < 0.001 ) . There were no significant differences between aspirin and acetaminophen with codeine at any evaluation of SPID ( P ≥ 0.070 ) , complete relief ( P ≥ 0.179 ) , or time to meaningful relief ( P ≥ 0.245 ) . Regarding safety , there were no statistically significant differences between treatment groups in the incidence of adverse events in the dental pain and tension-type headache studies . CONCLUSIONS These 2 r and omized , double-blind , placebo-controlled studies demonstrate that treatment with aspirin ( 1000 mg ) provides statistically significant analgesic efficacy compared with placebo use and comparable efficacy with acetaminophen ( 300 mg ) with codeine ( 30 mg ) therapy after impacted third molar extraction and in tension- type headache Three hundred fifty out patients with postoperative pain after the surgical removal of impacted third molars were r and omly assigned , on a double-blind basis , to receive a single oral dose of aspirin 650 or 1000 mg , caffeine 65 mg , a combination of aspirin 650 mg with caffeine 65 mg , or placebo . Using a self-rating record , subjects rated their pain and its relief hourly for 6 hours after medicating . Estimates of summed pain intensity difference , peak pain intensity difference , total relief , peak relief , and hours of 50 % relief were derived from these subjective reports . All active treatments except caffeine were significantly superior to placebo . Pairwise comparisons indicated the aspirin-caffeine combination was statistically superior to aspirin 650 mg alone for hours of 50 % relief among patients who had severe baseline pain . Adverse effects were transitory and none were serious BACKGROUND Improved clinical outcomes have been documented with combinations of oral analgesic agents , particularly those with complementary activities . However , because not all combinations or dose ratios lead to enhanced analgesia or reduced adverse events ( AEs ) , each combination and dose ratio must be evaluated individually in carefully design ed pre clinical and clinical trials . OBJECTIVE The goal of the study was to compare the efficacy and safety of 37.5 mg tramadol/325 mg acetaminophen tablets ( T/APAP ) , 10 mg hydrocodone bitartrate/650 mg acetaminophen tablets ( HC/APAP ) , and placebo in the treatment of postoperative dental pain . METHODS This was a single-center , double-blind , parallel-group , placebo- and active-controlled study in adults with at least moderate pain ( score > or = 50 on a 100-mm pain visual analog scale ) after extraction of > or = 2 impacted third molars . Patients were r and omized to receive 1 or 2 T/APAP tablets , 1 HC/APAP tablet , or placebo . Scores for hourly pain relief ( PAR ) , pain intensity difference ( PID ) , and combined PAR and PID ( PRID ) were based on reported pain at 30 minutes and each successive hour for 8 hours . Primary efficacy measures were summary pain intensity and pain relief scores ( total pain relief [ TOTPAR ] , sum of pain intensity differences [ SPID ] , and sum of pain relief and pain intensity differences [ SPRIDI ) for 0 to 4 hours , 4 to 8 hours , and 0 to 8 hours . Secondary efficacy measures were hourly PAR , PID , and PRID scores ; onset and duration of pain relief ; time to remedication with a supplemental analgesic agent ; and patients ' overall assessment of medication . RESULTS Two hundred adults took part in the study ( 50 per treatment group ) and were included in the efficacy and safety analyses . T/APAP 75/650 mg and HC/APAP were statistically superior to placebo on the primary efficacy measures of TOTPAR , SPID , and SPRID ( P < or = 0.024 ) , as well as on hourly PAR , PID , and PRID over 6 hours ( P < or = 0.045 ) . All active treatments were statistically superior to placebo in terms of onset of pain relief ( P < or = 0.001 ) , duration of pain relief ( P < or = 0.024 ) , time to remedication ( P < 0.001 ) , and patients ' overall assessment of medication ( P < 0.001 ) . A statistically significant dose response with T/APAP ( 2 tablets > 1 tablet > placebo ) was seen for TOTPAR , SPID , and SPRID ( all , P < or = 0.018 ) . The median time to onset of pain relief was approximately 34.0 minutes with 2 T/APAP tablets and 25.4 minutes with HC/APAP . Although the median time to onset of pain relief was shorter with HC/APAP , two T/APAP tablets had comparable efficacy to HC/APAP . The median time to remedication with a supplemental analgesic agent was 169.0 minutes in the T/APAP 75/650 mg group and 204.0 minutes in the HC/APAP group . However , the duration of pain relief , as defined by time to remedication , was not significantly different between these 2 groups . The overall incidence of AEs was lower with T/APAP ( 0 % treatment-related AEs ) than with HC/APAP ( 4 % ) or placebo ( 10 % ) . The incidence of nausea ( 18 % T/APAP , 36 % HC/APAP ) and vomiting ( 12 % T/APAP , 30 % HC/APAP ) was approximately 50 % lower with 2 T/APAP tablets than with HC/APAP ( P < 0.05 ) . CONCLUSIONS T/APAP tablets provided effective , rapid ( < or = 34 minutes ) , dose-dependent analgesia for the treatment of postoperative dental pain . Two T/APAP tablets provided analgesia comparable to that provided by HC/APAP with better tolerability A double-blind r and omized analgesic trial was carried out on 180 patients undergoing surgical removal of an impacted lower wisdom tooth . The patients took their first dose of either 1000 mg paracetamol plus 60 mg codeine or 650 mg paracetamol plus 65 mg dextropropoxyphene when pain appeared after the decline of the local anaesthesia . If needed , another two doses were available during the observation period ( ≤10 h ) . The analgesic efficacy of paracetamol/codeine was overall superior to paracetamol/dextropropoxyphene in all variables . Sufficient pain relief was obtained in most patients . The pain reduction after the first dose was 64 % in the group receiving paracetamol/codeine compared with 53 % in the group receiving paracetamol/dextropropoxyphene and the mean duration s of effect of the first dose were 6.6 and 5.8 h , respectively . Side-effects appeared in all patient groups but were most frequent in women taking paracetamol/codeine Pattern of analgesic consumption after unilateral m and ibular third-molar surgery was investigated in an open study in 201 patients . All patients were supplied with six analgesic tablets containing 500 mg paracetamol and 30 mg codeine . Instructions for use were given . A mean consumption of 4.9 tablets over the 1st week and 3.6 tablets the day of operation was found . Eight ( 4 % ) patients indicated inadequate or no effect of the medication . The remaining patients were able to control pain , to a level of one-third of maximum pain , by using from one to five tablets . One hundred and thirty-two ( 68 % ) patients followed instructions with regard to start of medication . No difference in mean tablet consumption was found between compliant patients and those who delayed the intake of the first analgesic dose by more than 1 h. Predictor analysis showed the most powerful predictors to be preoperative depth of the third molar and moderate or heavy smoking . Thirteen per cent explanatory power of all predictors together was found Objective This study was conducted to evaluate the dose range of etoricoxib in acute pain using the postoperative dental pain model further . Methods This double-blind , r and omized controlled study evaluated etoricoxib ( 90 and 120 mg ) , ibuprofen ( 600 mg ) , and acetaminophen ( 600 mg/codeine ) ( 60 mg , ( A/C ) ) in patients aged ≥18 years with moderate or severe pain after surgical extraction of ≥2 third molars ( ≥1 impacted ) . The patients reported pain intensity and pain relief over 24 hours . The primary efficacy endpoint was total pain relief over 6 hours ( TOPAR6 ) . Adverse events were evaluated throughout the study . Results There were 588 patients r and omized to placebo ( n=46 ) , etoricoxib ( 90 mg ( n=191 ) ) , etoricoxib ( 120 mg ( n=97 ) ) , ibuprofen ( 2400 mg ( n=192 ) ) , and A/C ( n=62 ) . The overall analgesic effect ( TOPAR6 ) of etoricoxib ( 90 , 120 mg ) was significantly greater than that of placebo ( P⩽0.001 ) , and not inferior to that of ibuprofen ; no discernible difference was observed between etoricoxib 90 and 120 mg . Both etoricoxib doses were superior to A/C ( P⩽0.001 ) . Etoricoxib ( 90 and 120 mg ) and ibuprofen ( 2400 mg ) were generally well tolerated and had a similar incidence of adverse events ( AEs ) . A/C was associated with significantly more AEs that led to discontinuation ( ie , nausea and vomiting ) . Conclusions Etoricoxib ( 90 and 120 mg ) showed similar efficacy in the postoperative dental pain model , which was noninferior to ibuprofen and superior to A/C. A higher number of tooth extraction s or a higher mean impaction score may have led to a greater separation in efficacy between the 2 etoricoxib doses & NA ; There is uncertainty over whether the patient group in which acute pain studies are conducted ( pain model ) has any influence on the estimate of analgesic efficacy . Data from four recently up date d systematic review s of aspirin 600/650 mg , paracetamol 600/650 mg , paracetamol 1000 mg and ibuprofen 400 mg were used to investigate the influence of pain model . Area under the pain relief versus time curve equivalent to at least 50 % maximum pain relief over 6 h was used as the outcome measure . Event rates with treatment and placebo , and relative benefit ( RB ) and number needed to treat ( NNT ) were used as outputs from the meta‐analyses . The event rate with placebo was systematic ally statistically lower for dental than postsurgical pain for all four treatments . Event rates with analgesics , RB and NNT were infrequently different between the pain models . Systematic difference in the estimate of analgesic efficacy between dental and postsurgical pain models remains unproven , and , on balance , no major difference is likely In a double-blind , single dose study of analgesic efficacy , 165 patients who were expected to develop moderate to severe pain following the removal of an impacted m and ibular third molar tooth were allocated to receive aspirin , placebo , or an increasing dose of a fixed ratio ibuprofen/codeine combination . The degree of pain experienced prior to medication was noted and the patients were asked to record the degree of pain and of pain relief hourly for the following 5 hours . The study produced clear evidence of the superior efficacy of the combinations when compared to placebo and aspirin . In addition , the high dose combination appeared to be superior with respect to pain relief and the need for additional analgesia compared to the low dose treatment . There were few side effects and only one severe reaction was reported by a patient in the high dose group . To avoid side effects it is suggested that the medium-dose combination , ibuprofen 400 mg/codeine 30 mg , is optimal Third molar extraction is a common procedure frequently accompanied by moderate or severe pain , and involves sufficient numbers of patients to make studies relatively easy to perform . The aim of the present study was to determine the efficacy and safety of the therapeutic combination of 10 mg piroxicam , 1 mg dexamethasone , 35 mg orphenadrine citrate , and 2.5 mg cyanocobalamin ( Rheumazin ) when compared with 20 mg piroxicam alone ( Feldene ) in m and ibular third molar surgery . Eighty patients scheduled for removal of the third molar were included in this r and omized and double-blind study . They received ( vo ) Rheumazin or Feldene 30 min after tooth extraction and once daily for 4 consecutive days . Pain was determined by a visual analogue scale and by the need for escape analgesia ( paracetamol ) . Facial swelling was evaluated with a measuring tape and adverse effects and patient satisfaction were recorded . There was no statistically significant difference in facial swelling between Rheumazin and Feldene ( control group ) . Both drugs were equally effective in the control of pain , with Rheumazin displaying less adverse effects than Feldene . Therefore , Rheumazin appears to provide a better risk/benefit ratio in the m and ibular molar surgery . Since the side effects result ing from nonsteroidal anti-inflammatory drug administration are a severe limitation to the routine use of these drugs in clinical practice , our results suggest that Rheumazin can be a good choice for third molar removal treatment To determine the effect of pretreatment and multiple doses on postsurgical pain , a study of the relative analgesic efficacy of placebo , acetaminophen 650 mg , and propoxyphene napsylate 100 mg alone and in combination was conducted . Forty-five patients undergoing surgical removal of impacted third molar teeth under local anesthesia were r and omly allocated to the four treatment regimens under double-blind conditions . The first oral dose was administered one hour preoperatively and the second dose when the pain became moderate or severe , following the dissipation of the local anesthesia . Pain intensity and pain relief were assessed using st and ard verbal descriptor scales at 30 minutes and hourly for four hours after the postoperative dose . Measures of total effect , peak effect and duration of their effect were derived from these descriptors . Acetaminophen was no better than placebo . For peak and total effects , propoxyphene alone and the propoxyphene-acetaminophen combination were substantially superior to both placebo and acetaminophen alone . Duration of analgesia was also significantly longer with both propoxyphene-containing treatments . No side effects were reported . The results suggest that pretreatment with a narcotic agonist markedly improves postoperative analgesia OBJECTIVE The aim of this study was to compare preemptive analgesia of oral ketorolac plus submucous local placebo with oral ketorolac plus submucous local tramadol after impacted m and ibular third molar surgery . STUDY DESIGN A double-blind , r and omized , placebo-controlled clinical trial was conducted . Patients were r and omized into two treatment groups ( n = 15 per group ) : group A , oral ketorolac 10 mg , 30 minutes before surgery plus submucous local placebo ( 1 mL saline solution ) ; group B , oral ketorolac 10 mg , 30 minutes before surgery plus submucous local tramadol ( 50 mg diluted in 1 mL saline solution ) . We evaluated the intensity of pain , time for the first analgesic rescue medication , and total analgesic consumption . RESULTS Pain intensity , number of patients requiring analgesic rescue medication , number of patients in each group not requiring analgesic rescue medication , and total analgesic consumption showed statistical significance . CONCLUSIONS Preemptive use of oral ketorolac plus submucous local tramadol is an alternative treatment for acute pain after surgical removal of an impacted m and ibular third molar A double blind trial to study the effects of analgetics was carried out in patients suffering from pain after third molar osteotomy . 204 patients were evaluated after r and om allocation to treatment with paracetamol 500 mg and paracetamol 500 mg plus codeine 30 mg . Statistical evaluation revealed a tendency for better analgesia using the combination of paracetamol and codeine . For further studies an exact stratification for sex and age is necessary . Sample sizes of 150 patients are necessary for each parameter In a double-blind , placebo-controlled study , 207 patients with moderate pain after surgical removal of impacted third molars were r and omly assigned to receive a single oral dose of 10 mg of ketorolac tromethamine , 10 mg of hydrocodone plus 1000 mg of acetaminophen , or placebo . Analgesic effect as assessed by summed pain intensity difference at 3 and 6 hours was significantly ( P < or = 0.01 ) greater after ketorolac than after hydrocodone/acetaminophen . Total pain relief at 3 and 6 hours was significantly ( P < 0.026 ) greater after ketorolac than after hydrocodone/acetaminophen or placebo . Patients taking hydrocodone/acetaminophen remedicated significantly ( P = 0.027 ) sooner than those taking ketorolac . In this single-dose study , adverse events were reported more frequently by patients taking hydrocodone/acetaminophen than with ketorolac or placebo . It is concluded that , in this pain model , 10 mg of ketorolac affords better pain relief with fewer side effects than hydrocodone/acetaminophen Four common oral analgesics were tested in a single-blind trial to determine their relative efficacy in the management of postsurgical pain in 103 patients who had their impacted third molars surgically removed under general anesthesia . The analgesics tested were acetylsalicylic acid ( 26 patients ) , ibuprofen ( 26 patients ) , a paracetamol/codeine/caffeine combination ( Solpadeine ) ( 25 patients ) , and dihydrocodeine ( 26 patients ) . The paracetamol/codeine/caffeine combination , ibuprofen , and acetylsalicylic acid preparations produced equally effective analgesia . Dihydrocodeine was found to be a poor analgesic in this pain model . There were no adverse reactions to any of the preparations Non-steroidal anti-inflammatory analgesics are commonly prescribed to out- patients who have undergone oral surgical procedures , since they are said to provide excellent pain relief for mild to moderate pain , allied with minimal side-effects . One hundred patients were entered into a r and omised clinical trial to compare the efficacy of a simple non-steroidal analgesic with that of a combination analgesic compound following the removal of lower third molars under local anaesthesia . Pain scores were measured for patients post-operatively by means of a verbal rating scale for 3 days and data were analysed using the Mann-Whitney U-test . Results suggest that this combination product offers no advantages ( but shows definite disadvantages ) when compared to an effective non-steroidal anti-inflammatory In a r and omised , double‐blind , double‐dummy , multiple dose , crossover study in 30 patients we compared an ibuprofen/codeine combination ( 400 mg ibuprofen/25.6 mg codeine phosphate ) with a paracetamol/codeine/caffeine combination ( 1 g paracetamol/ 16 mg codeine phosphate/60 mg caffeine ) for pain relief over 6 days after two‐stage bilateral lower third molar removal . The ibuprofen combination produced significantly greater analgesia than the paracetamol combination , both on single‐dose analysis of the first and second days and on multiple‐dose measures for days 1 , 2 , 3 and 4 . The mean incidence of adverse effects over the 6 days was 20 % for both combinations . This trial design ( crossover with multiple dosing in out patients ) is a sensitive way of testing for analgesia , and is potentially more predictive of adverse effect problems than single‐dose studies . It confirms that multiple dosing may show increased efficacy BACKGROUND The authors conducted two studies to compare the analgesic efficacy and safety of the cyclooxygenase , or COX , -2-specific inhibitor , valdecoxib , with oxycodone/ acetaminophen in patients who have undergone oral surgery . METHODS In total , 205 eligible subjects in Study A and 201 in Study B were r and omized to receive a single oral dose of valdecoxib ( 20 or 40 milligrams ) , a combination of oxycodone 10 mg/acetaminophen 1,000 mg or placebo . Eligible subjects experienced moderate-to-severe pain within six hours of surgery during which two or more impacted third molars were extracted . Analgesic efficacy was assessed over 24 hours or until the patient required rescue analgesia . RESULTS In both studies , subjects receiving either dose of valdecoxib experienced a rapid onset of analgesia and ( among those who received valdecoxib 40 mg ) a level of pain relief comparable with that of those who received oxycodone/ acetaminophen . Both valdecoxib doses had a significantly longer duration of analgesic effect than did oxycodone/acetaminophen . Pooled safety data demonstrated that each valdecoxib dose had a tolerability profile superior to that of oxycodone/ acetaminophen and similar to that of placebo . CONCLUSIONS Orally administered valdecoxib is as rapidly acting and effective as oxycodone/acetaminophen , and it has a superior duration of analgesic effect in patients after oral surgery . Valdecoxib has a tolerability profile superior to that of oxycodone/acetaminophen . CLINICAL IMPLICATION S The current st and ard of care for alleviating acute pain after oral surgery has rested largely on conventional nonsteroidal anti-inflammatory drugs or opioid/analgesic combination products . The studies reported here suggest that the COX-2-specific inhibitor valdecoxib offers an efficacious and safe alternative to other analgesics used to treat pain after oral surgery We studied 90 adults undergoing surgical removal of at least both lower third molar teeth as day cases under st and ardized general anaesthesia . Patients were allocated r and omly ( with stratification for surgeon ) to receive tenoxicam 40 mg , tenoxicam 20 mg or placebo i.v . at induction of anaesthesia and orally ( effervescent tablets ) with food on each of the subsequent 2 days . Panadeine ( paracetamol 500 mg-codeine 8 mg ) was given before operation and was available as needed for pain thereafter , to a limit of two tablets every 4 h. Nefopam i.v . was also available . Efficacy variables and adverse reactions were assessed over 6 days . Over the 6-day period , patients who received tenoxicam reported less pain on rest ( area under the curve ; P < 0.05 ) and less disturbance in sleep ( P < 0.01 ) even though they used fewer Panadeine tablets ( P < 0.05 ) . Differences between tenoxicam 40 mg and 20 mg were not significant . There was no significant difference in nefopam requirements or side effects , and no adverse event attributable to the study medication A double blind r and omized analgesic trial was carried out in patients suffering from pain after removal of an impacted lower wisdom tooth . In a repeated dose regimen , 120 patients received one of three different analgesics : phenazone , phenazone plus dextropropoxyphene , or paracetamol . The assessment s of pain were made hourly on a visual analogue scale and the evaluation was carried out according to a method which considers repeated dose intake . The analgesic efficacy of 500 mg phenazone was similar to 500 mg of paracetamol . The pain reduction seemed adequate in most patients and no statistical differences were obtained between the treatment drugs . All analgesics were taken when needed , and the time interval from end of operation to first tablet intake , as well as the pain score at first tablet intake , were factors which significantly influenced the efficacy of the drugs . Therefore , these factors may be of significant importance in the evaluation of analgesics in small sample studies BACKGROUND The combination of tramadol and acetaminophen has demonstrated good efficacy in various clinical pain models . However , there is a need for comparisons of the onset of analgesia and other measures of analgesic efficacy with this combination and other strong combination analgesics for the management of acute pain . OBJECTIVE The goal of this study was to compare the time to onset of analgesia and other measures of analgesic efficacy with tramadol/acetaminophen 75/650 mg ( Tr/Ac ) and codeine/acetaminophen/ibuprofen 20/500/400 mg ( Co/Ac/Ib ) in the management of acute pain after oral surgery . METHODS This was a single-center , single-dose , r and omized , active-controlled , parallel-group study in healthy subjects who had undergone surgical extraction of > or = 1 impacted third molar requiring bone removal . When patients reported at least moderate pain after dental surgery ( score > or = 5 on a 10-point scale ) , they were r and omized to 1 of 2 treatment groups . The time to onset of analgesia was measured using a 2-stopwatch technique . The time to the onset of perceptible and meaningful pain relief , pain intensity , pain relief , patient 's overall assessment , and adverse events were recorded for 6 hours after dosing . RESULTS One hundred twenty-eight subjects participated in the study , 64 in each treatment group . The 2 groups were similar in terms of baseline pain severity and demographic characteristics ( mean age , 23.7 and 23.4 years in the Tr/Ac and Co/Ac/Ib groups , respectively ; mean body weight , 58.5 and 60.3 kg ) . The median times to the onset of perceptible pain relief were a respective 21.0 and 24.4 minutes , and the median times to the onset of meaningful pain relief were 56.4 and 57.3 minutes . Mean total pain relief and the sum of pain intensity difference were also similar in the early period after dosing ( 0 - 4 hours ) . However , between 4 and 6 hours , Co/Ac/Ib was associated with significant differences in both variables compared with Tr/Ac ( P < 0.05 ) . Although similar through the 4-hour assessment , mean pain intensity difference was significantly greater with Co/Ac/Ib at 5 to 6 hours . The proportion of patients assessing their assigned treatment as good or better was significantly greater with Co/Ac/Ib compared with Tr/Ac ( P < 0.05 ) . The safety profile of Tr/Ac was comparable to that of Co/Ac/Ib . CONCLUSIONS In this small and selected group of subjects , the onset of analgesia and analgesic efficacy of Tr/Ac was comparable to that of Co/Ac/Ib . Tr/Ac provided rapid and effective analgesia for acute postoperative dental pain in this population Summary A double-blind , multicentre analgesic trial was carried out in patients suffering from pain after removal of an impacted lower wisdom tooth . 266 patients were evaluated after r and om allocation to treatment with paracetamol 500 mg , paracetamol 500 mg plus codeine 20 mg , paracetamol 500 mg plus codeine 30 mg , or paracetamol 500 mg plus codeine 40 mg . On the day of surgery the patients assessed their own pain intensity hourly on a visual analogue scale . The analysis of the results was carried out according to a method which considered repeated dose intake . A statistically significant dose-response relationship was obtained between the supplementary doses of codeine and analgesic efficacy . In the comparison of side effects , their frequency increased with increasing amounts of codeine . In clinical practice codeine 30 mg appeared to be the optimal supplement for paracetamol 500 mg BACKGROUND Although acetaminophen is one of the oldest and most widely used of all analgesic drugs , the incremental benefit of the 1000-mg dose compared with the 650-mg dose has been question ed . OBJECTIVE The aim of this study was to assess the relative efficacy of acetaminophen 1000 mg versus acetaminophen 650 mg over a 6-hour period in patients experiencing at least moderate postsurgical dental pain . METHODS This single-center , r and omized , double-blind , placebo-controlled , single-dose study enrolled patients aged 16 to 50 years who experienced at least moderate pain after surgical removal of impacted third molars . Each patient received either acetaminophen 1000 mg ( n = 239 ) , acetaminophen 650 mg ( n = 241 ) , or placebo ( n = 60 ) when they had at least moderate pain and a score ≥50 on the 100-mm Visual Analog Scale ( VAS ) postsurgically . Pain intensity and pain relief were measured over 6 hours ( VAS 0 - 100 mm ) . RESULTS All 540 patients ( 52 % female ; age range , 16 - 30 years ; 95 % white ) were included in the efficacy analysis . For the primary efficacy endpoint ( weighted sum of the pain intensity difference from baseline [ PID ] and pain relief [ PAR ] scores over 6 hours [ SPRID6 ] ) , acetaminophen 1000 mg demonstrated a 24 % improvement compared with acetaminophen 650 mg ( 529.4 vs 427.3 ; P = 0.001 ) . In addition , acetaminophen 650 mg was significantly superior compared with placebo ( P < 0.001 ) . The weighted sum of PID over 6 hours ( SPID6 ) , the weighted total pain relief over 6 hours ( TOTPAR6 ) , and the percentage of patients with > 50 % of the maximum possible TOTPAR6 score were significantly greater for patients treated with acetaminophen 1000 mg compared with those receiving acetaminophen 650 mg ( P ≤ 0.006 ) or placebo ( P < 0.001 ) and for patients treated with acetaminophen 650 mg compared with placebo ( P < 0.001 ) . Time to rescue , rescue rates through 4 and 6 hours , and patient global assessment demonstrated similar findings . Patients treated with acetaminophen 1000 mg or 650 mg had a significantly different distribution in times to confirmed perceptible and meaningful pain relief compared with those receiving placebo ( P < 0.001 ) . Adverse events were reported by 18.5 % of patients , with no clinical ly important difference between active treatment groups and placebo . CONCLUSIONS Acetaminophen 1000 mg provided clinical ly meaningful and statistically significantly greater efficacy in treating postsurgical dental pain compared with acetaminophen 650 mg and placebo . The outcomes of this study are limited to the single-dose design of this study . Clinical Trials.gov identifier : NCT01115673 & NA ; A combination of 20 mg codeine base and ibuprofen 400 mg was compared with ibuprofen 400 mg in a r and omised double‐blind cross‐over study of multiple doses in 25 patients after 2‐stage bilateral third molar removal . The combination produced significantly greater pain relief and doubled the hours of minimum pain intensity and maximal relief on the day of surgery . The patients rated the combination significantly better than ibuprofen alone , and the combination was preferred by 16 of the 22 patients expressing a preference . There was no significant increase in side‐effect incidence with the combination . The 30 % increase in analgesic effect may be of clinical benefit , and this trial design , cross‐over with multiple dosing in out‐ patients , may be a sensitive test for analgesics , potentially more predictive of side‐effect problems than single‐dose studies 155 patients undergoing surgical removal of lower third molars took part in a parallel group , r and omised double-blind study to assess the analgesic effect of single pre-operative doses of ibuprofen ( 400 mg ) , codeine phosphate ( 30 mg ) , a combination of ibuprofen/codeine ( 400 mg/30 mg ) , placebo and post-operative single doses of the same combination or diflunisal ( 250 mg ) . Patients receiving the combination or ibuprofen pre-operatively took significantly longer between surgery completion and needing the post-operative study treatment than patients receiving codeine phosphate or placebo . At 1 1/2 - 2 h after post-operative administration , patients receiving the combination post-operatively reported significantly greater decreases in pain severity than those receiving diflunisal . Patients taking the combination post-operatively experienced significantly better pain relief than patients taking diflunisal at 1 and 2 h , but the reverse was true at 5 h. Side-effects reported were mild with no significant differences between the different treatment groups A double-blind r and omized crossover analgesic trial was carried out on 70 patients undergoing surgical removal of one lower third molar at each visit . The analgesic efficacy of a two-dose regimen of the combination ibuprofen-codeine , 400 to 60 mg , was compared with ibuprofen , 400 mg . Each of the two doses was taken when the patient needed pain relief and the pain intensity was measured on a visual analog scale during the 10-hour period after the first medication . Because of carryover effects between periods 1 and 2 , the analysis was carried out only for period 1 according to a parallel group design . Of the 60 patients who were evaluated for analgesic effect , the mean pain reduction of dose 1 was 63 % for the 29 patients given ibuprofen-codeine and 50 % for the 31 patients given ibuprofen ; the mean duration of effect was 7.5 and 6.3 hours , respectively . The difference in pain reduction index ( pain reduction X duration of effect ) between the two treatments was significant in favor of the combination , whereas the separate variables of pain reduction and duration of effect were not significantly different . The mean pain reduction was 67 % after doses 1 and 2 for patients on ibuprofen-codeine and 52 % for those on ibuprofen ; the mean duration of effect was 9.4 and 9.2 hours , respectively . For doses 1 and 2 , the difference in pain reduction index per dose between the two treatments was significant but not the difference for the separate variables , pain reduction , and duration of effect . ( ABSTRACT TRUNCATED AT 250 WORDS Two analgesics commonly used in oral surgery , ibuprofen ( Ibumetin ) and a paracetamol/codeine combination ( Citodon ) have been compared in a single-blind multi-centre trial after third molar surgery . The study comprised 120 patients , 60 in each treatment group . The profiles of postoperative pain in the two groups were similar from the first postoperative day , but Ibumetin was better pain reliever on the day of surgery . The profiles of postoperative swelling and trismus had the same general course , but patients taking Ibumetin reported lower scores for these variables during the whole postoperative period . Citodon induced significantly more side-effects than Ibumetin Objectives : To compare the relative merits of single doses of ibuprofen and ibuprofen plus caffeine in the treatment of pain after third molar removal . Design : R and omised , double‐blind , placebo‐controlled , single‐dose parallel‐group comparison of placebo , ibuprofen 200 and 400 mg with ibuprofen 200 mg plus 50 , 100 or 200 mg of caffeine . Subjects : 161 patients undergoing lower third molar removal . Results : All active treatments produced significant analgesia and mood elevation compared with placebo . There was no significant difference in the effects of 200 and 400 mg of ibuprofen . Adding caffeine to 200 mg ibuprofen produced significantly more analgesic effect at 45 and 60 min than ibuprofen 200 mg alone . Ten patients reported 11 adverse effects , none in the highest caffeine dose group . Conclusions : Caffeine increased the analgesic effect of ibuprofen 200 mg , through an earlier onset of analgesic effect . This was achieved in this single dose context without problematic adverse effects Acetaminophen ( APAP ) 1000 mg , APAP 2000 mg , the combination of APAP 1000 mg plus codeine phosphate 60 mg ( APAPCOD ) , and placebo ( PBO ) were compared in a 6-hour , r and omized , single-dose , double-blind , parallel-group analgesic trial . All active treatments were statistically superior ( p less than 0.05 ) to placebo for 4 hours after medication with respect to pain intensity ( PI ) and pain intensity difference ( PID ) , and up to 3 hours regarding pain relief ( PAR ) . The combination scored better than all other treatments on the summary analgesic efficacy measures sum PI ( SUMPI ) , sum PID ( SPID ) , and total PAR ( TOTPAR ) . The combination was statistically superior to APAP 1000 mg on SUMPI , TOTPAR and maximum PAR ( MAXPAR ) . Acetaminophen 2000 mg showed marginal numerical superiority over 1000 mg for SUMPI , but was not statistically superior for any summary efficacy measure . The 2000-mg dose was numerically inferior to APAPCOD for every summary efficacy measure and statistically inferior regarding SPID and MAXPAR . We concluded that codeine 60 mg added to acetaminophen 1000 mg offers analgesic advantages , and acetaminophen reaches an analgesic ceiling effect at 1000 mg using the dental pain model Summary A double-blind , r and omised analgesic trial was carried out in 165 patients undergoing surgical removal of one impacted lower wisdom tooth . In a two-dose regimen , the analgesic efficacy of the combination ibuprofen-codeine 200 mg : 30 mg was compared with that of acetylsalicylic acid-codeine 500 mg : 30 mg and codeine 30 mg . Each dose was taken when the patient needed pain relief . The intensity of the pain was measured on a visual analogue scale during the 10-h period after the first dose . The mean pain reduction by Dose 1 in patients on ibuprofen-codeine , acetylsalicylic acid-codeine and codeine was 64 % , 45 % and 26 % , respectively , and the mean duration of effect was 8.3 , 6.3 and 5.6 h. According to the pain reduction , duration of effect and pain reduction index after Doses 1 and 1 + 2 . there was a significant difference between ibuprofen-codeine and the other two drugs . The maximum pain reduction within 4 hours was 84 % with ibuprofen-codeine . This was significantly different from the reduction achieved both with acetylsalicylic acid-codeine ( 64 % ) and codeine ( 35 % ) . Seventeen patients reported adverse events : 5 on ibuprofen-codeine , 4 on acetylsalicylic acid-codeine and 8 on codeine . The most common events were tiredness and vertigo . It is concluded that the combination ibuprofen-codeine 200 mg : 30 mg had greater analgesic efficacy compared to the combination acetylsalicylic acid-codeine 500 mg : 30 or codeine 30 mg in patients with pain after removal of the lower third molars A comparison of the efficacy of Myprodol , a combination analgesic ( Ibuprofen , Paracetamol and Codeine phosphate ) and Ponstan ( Mefenamic acid ) was undertaken in a r and omised double blind trial of 52 patients who underwent surgical removal of impacted or unerupted teeth . Pain scores were measured for patients pre- and post operatively by means of a visual analogue scale and data was analysed using the BMPD package on the ISM main frame computer at the Medical Research Council . The results indicated that although Myprodol and Ponstan were equally adequate and well tolerated in the control of post operative dental pain , Myprodol exceeded Ponstan in duration of analgesia and in the degree of pain intensity control experienced by the patient Our objective was to determine the value of caffeine in combination with acetaminophen in the relief of pain from uterine cramping , episiotomy , and third molar extraction . In the dental study , 173 patients received two or four tablets of 500 mg acetaminophen or the combination of 500 mg acetaminophen and 65 mg caffeine . In the three postpartum studies , 1345 patients received one , two , or three tablets of acetaminophen , the combination , or a placebo . The mean scores for the summary variable percent sum of the pain intensity differences ( % SPID ) were higher in all for the combination than for acetaminophen alone , and in two studies the null hypothesis of no differences was rejected . The relative potency estimates for % SPID were 1.9 , 1.8 , and 1.3 for the three studies in which bioassays could be performed and the pooled relative potency was 1.7 with a 95 % confidence interval of 1.1 to 3.1 . The results were essentially the same among pain models and among patient groups with similar habitual caffeine consumption . Onset of analgesia was also faster with the combination . We conclude that caffeine enhances the analgesic efficacy of acetaminophen A double-blind clinical study of analgesic drugs was conducted involving 47 healthy adults requiring removal of 90 bony impacted m and ibular third molars . The analgesic effect of paracetamol plus codeine ( P + C ) 350 + 20 mg was compared to that of acetylsalicylic acid ( ASA ) 500 mg and placebo . A st and ardized surgical procedure under local anesthesia was used . Insufficient analgesic effect was noted in 16 % of the ASA group and in 69 % of the placebo group but in none in the P+C group . On the first postoperative day , patients given P+C suffered less pain compared with those given ASA ( P less than 0.01 ) . No relationship could be demonstrated between the type of impaction and intensity of pain . Trismus , however , was found to be associated with difficulty of extirpation . Drowsiness and an increased sleeping tendency were the main side effects found in the P+C group . The incidence of secondary hemorrhage was high in the ASA group , compared with the P+C group a significance of 0.01 less than P less than 0.05 was found on various postoperative days . Registration of swelling revealed less postoperative edema in the P+C group than in the ASA group ( 0.01less thanPless than0.05 ) . The main conclusion from this study is that the analgesic effect of P+C orally administered after a specific oral surgical procedure is superior to ASA and placebo . P+C also appears to have a more marked antiphologistic effect than ASA This study analyzes the combination of oral ketorolac 10 mg with varying amounts of codeine phosphate , and the postoperative pain relief that developed from these combinations . Five groups of patients were administered the codeine/ketorolac combinations . Variations of the combinations were analyzed to ascertain if an optimal analgesic ratio existed . All controllable variables involved with the surgical procedure were held constant to allow for better evaluation of postoperative pain . Results obtained from 67 patients indicated that the best pain relief was achieved with a combination of 10 mg ketorolac and 15 mg codeine phosphate . Codeine alone provided adequate analgesia , but the addition of ketorolac reduced the patients ' perceived side effects . The presence of codeine in the analgesic combination was also shown to reduce the number of days that the patient required the medication postoperatively . Reducing the duration of medication use postoperatively may also minimize the possible side effects of ketorolac and codeine , which could develop with extended periods of use Summary A double-blind r and omized analgesic trial was carried out in 180 patients undergoing surgical removal of an impacted lower wisdom tooth . The patients received the first dose of either paracetamol 1000 mg plus codeine 60 mg , paracetamol 500 mg plus codeine 30 mg or placebo immediately after surgery during the effect of the local anaesthetic . The mean pain intensity , the duration of effect and the number of patients needing additional analgesics were all significantly dose related . In the evaluation procedure a pain intensity index was defined which took into account both the efficacy and the duration of effect . In addition , the analgesic efficacy was calculated over a 12 hour period after first medication and thereby including the efficacy of a second dose , if taken . Paracetamol 1000 mg plus codeine 60 mg followed by paracetamol 500 mg plus codeine 30 mg after around 5 hours was a very effective treatment and over 40 % of these patients did not need any further pain relief during the evaluation period . In conclusion , an effective analgesic taken immediately after oral surgery reduces the total pain and diminishes the need of analgesics A study is presented which was design ed to compare Solpadeine ( paracetamol 500 mg , codeine phosphate 8 mg and caffeine 30 mg ) and soluble DNP ( dextropropoxyphene napsylate , equivalent to 32·5 mg hydrochloride and paracetamol 325 mg ) in the control of pain following wisdom teeth extraction . A higher percentage of patients found Solpadeine more effective and significantly more Solpadeine patients considered their treatment easier to take PURPOSE The analgesic efficacy of 50 and 100 mg flurbiprofen was compared with acetaminophen 650 mg , acetaminophen 650 mg plus codeine 60 mg , and placebo . PATIENTS AND METHODS Subjects undergoing the surgical removal of impacted third molars were r and omly administered one of the five treatments after the onset of moderate to severe postoperative pain . Pain intensity , pain relief , and side effects were evaluated for 6 hours after drug administration . RESULTS Both doses of flurbiprofen result ed in significant analgesia in comparison with placebo , acetaminophen , and acetaminophen plus codeine as measured by pain intensity difference , pain relief , and global evaluation . The greatest incidence of side effects occurred in the group receiving acetaminophen plus codeine , and the fewest side effects were reported by subjects administered flurbiprofen . CONCLUSION The results of this study indicate that flurbiprofen is more effective and causes fewer effects than acetaminophen and codeine when used for post-operative dental pain , in ambulatory patients INTRODUCTION Acute postoperative pain is a common experience in oral surgery practice . Non-steroidal anti-inflammatory drugs ( NSAIDs ) are quite effective against mild to moderate pain and they are generally better suited in ambulatory out patients than narcotic analgesics . The analgesic activity of piroxicam , a well known NSAID has been documented in many pain states . Piroxicam can be administered once daily because of its long half-life , but its absorption in the gastrointestinal tract is slow as it is its onset of action . Piroxicam-beta-cyclodextrin ( PBCD ) is a new formulation of piroxicam which is the product of supermolecular encapsulation of piroxicam with the cyclic oligosaccharide beta-cyclodextrin . PBCD is absorbed much faster than st and ard piroxicam , and its action as an analgesic is consequently more rapid . The purpose of this study was to assess the efficacy and the rapidity of action of piroxicam-beta-cyclodextrin in comparison with st and ard piroxicam , paracetamol and placebo following surgical extraction of impacted third molars . MATERIAL S AND METHODS The study population was composed of 32 patients of both sexes and in good health . To be included into the study , patients must have had third molar removal result ing in acute post-surgical pain of at least moderate intensity . The patients were then r and omly assigned to one of four treatment groups . PBCD 20 mg tablets ; piroxicam 20 mg capsules ; paracetamol 500 mg tablets , or placebo . The study was conducted according to a double-blind , double-dummy design . Pain intensity and pain relief were recorded at 0.5 , 1 , 1.5 , 2 , 3 , 4 hours after a single dose of the study drugs , by means of a Keele-type rating scale . Rescue analgesics were not allowed before one and a half hour after taking the study drugs . A global evaluation of study drugs was expressed by patients at the end of the observation period . RESULTS Treatment groups were homogeneous for demographic characteristics of the patients and for pain intensity at the time of medication with study drugs . All patients who received placebo requested supplemental analgesics , while none of the patients treated with the active drugs needed rescue analgesics . PBCD and paracetamol were comparable for their analgesic effect , while the time lag before a significant reduction of pain intensity with piroxicam was longer . Piroxicam and PBCD were superior to paracetamol because they showed a substantial analgesic effect through the 4-hour study duration , while paracetamol did not induce a complete relief from pain . DISCUSSION One of the most commonly utilized model for the evaluation of analgesics is the third molar extraction pain . Our study clearly differentiated between active drugs and placebo . Furthermore , while PBCD and paracetamol showed a rapid effect , piroxicam was slow in inducing pain relief . The analgesic and anti-inflammatory activity of PBCD and piroxicam brought about the resolution of pain and inflammation consequent to the dental extraction . Paracetamol , a pure analgesic , was not equally active and pain persisted , even if at a low grade , throughout the observation period ; probably this was due to local inflammation and edema . The results of our study appear to confirm the pharmacokinetic data on PBCD , which showed that therapeutic blood levels are reached faster with PBCD than with the st and ard piroxicam formulation . This results should be confirmed in studies with an adequate number of patients In a r and omized double‐blind study , 120 patients with moderate to strong pain after surgical removal of wisdom teeth were given the following in single oral doses : 100‐mg enteric‐coated diclofenac tablets ; 1 g acetaminophen ( INN , paracetamol ) ; 1 g acetaminophen plus 60 mg codeine ; 100‐mg enteric‐coated diclofenac tablets plus 1 g acetaminophen ; or 100‐mg enteric‐coated diclofenac tablets plus 1 g acetaminophen plus 60 mg codeine . Patients recorded pain intensity and pain relief for 8 hours . Upside assay sensitivity was confirmed because acetaminophen plus codeine was superior to acetaminophen . Diclofenac plus acetaminophen with and without codeine had superior analgesic effect compared with diclofenac , acetaminophen , or acetaminophen plus codeine . Addition of 60 mg codeine increased the degree of side effects . These results support the clinical practice of combining diclofenac with acetaminophen for acute pain . Of clinical importance are superior and prolonged analgesia and fewer side effects after enteric‐coated diclofenac tablets plus acetaminophen compared with acetaminophen plus codeine BACKGROUND Codeine is frequently added to paracetamol to treat post-operative dento-alveolar pain ; studies have shown effectiveness in relief of post-operative pain at high doses but at the expense of central nervous and gastrointestinal side effects . There has been no trial to compare the efficacy and safety of paracetamol 1000 mg with paracetamol 1000 mg combined with codeine 30 mg . METHOD A r and omized , single centre , double-blind prospect i ve parallel group trial was performed to compare paracetamol 1000 mg with paracetamol 1000 mg with codeine 30 mg for the relief of pain following surgical removal of impacted third molars , and analysed on an intention-to-treat ( ITT ) basis . Eighty-two patients were assigned r and omly to receive either drug for a maximum of three doses . Patients recorded their pain intensity one hour after surgery and hourly thereafter for 12 hours . RESULTS The average increase in pain intensity over 12 hours was significantly less in patients receiving paracetamol plus codeine than in those receiving paracetamol alone ( p=0.03 ) -1.81 cm/h compared with 0.45 cm/h - a difference of 1.13 cm/h ( 95 per cent CI : 0.18 to 2.08 ) . Of the patients who received the paracetamol codeine combination , 62 per cent used escape medication compared with 75 per cent of those on paracetamol alone ( p=0.20 ) . There was no significant difference between the two groups in the proportion of patients experiencing adverse events ( p=0.5 ) . CONCLUSION A combination of 1000 mg paracetamol and 30 mg codeine was significantly more effective in controlling pain for 12 hours following third molar removal , with no significant difference of side effects during the 12 hour period studied The analgesic efficacy of a hydrocodone-acetaminophen combination , a codeine-acetaminophen combination , a codeine-APC ( aspirin , phenacetin , and caffeine ) combination , and a placebo was evaluated in out patients who had moderate or severe pain after the surgical removal of impacted third molars . Each of the active medications had a significant effect on essentially all measures of total and peak analgesia ; they did not differ significantly on any measure of analgesia . Adverse effects were transitory and , in general , appear to have been related to the central ly acting component of each combination analgesic PURPOSE The purpose of this double-blind , r and omized study was to compare the efficacy and safety of a single dose of the following medications : 2 tablets of Vicoprofen ( ibuprofen 200 mg/hydrocodone 7.5 mg ; Knoll Pharmaceutical Co , Mount Olive , NJ ) , 2 tablets ofp6 acetaminophen with codeine phosphate ( acetaminophen 300 mg/codeine 30 mg ) , and 2 tablets of placebo in the management of moderate to severe postoperative dental pain after surgical extraction of at least one impacted m and ibular third molar . PATIENTS AND METHODS One hundred twenty-five patients ( 75 women , 50 men ) participated in the study . The time of first perceptible pain relief and meaningful pain relief were measured using a stopwatch technique . Pain intensity and pain relief scores were recorded using st and ard verbal descriptors at 0.5 , 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 7 , and 8 hours after dosing . At the conclusion of the study , patients completed a global evaluation for the effectiveness of the study medication . RESULTS Both active treatments were superior to placebo for all analgesic measures . Pain relief scores were significantly better for Vicoprofen than placebo throughout the study and significantly better than for acetaminophen with codeine from 2 through 8 hours after dosing . The duration of analgesia ( time to remedication ) was significantly longer for Vicoprofen ( median , 5.50 hours ) compared with acetaminophen with codeine ( median , 3.03 hours ) and placebo ( median , 1.00 hours ) . Mean global evaluation for Vicoprofen was significantly better than for placebo and acetaminophen with codeine . Overall , there were no significant differences in the adverse event profile among the 3 treatment groups . CONCLUSIONS Vicoprofen was found to be an effective postoperative analgesic medication in the management of acute postoperative dental pain . Its total analgesic effect , duration of analgesia , and global evaluation were superior to acetaminophen with codeine and placebo in this study model STUDY OBJECTIVE To determine the relative analgesic potency and adverse effect liability of hydrocodone bitartrate 7.5 mg with acetaminophen 500 mg , codeine phosphate 30 mg with acetaminophen 300 mg , and placebo in the treatment of pain following oral surgery . DESIGN R and omized , double-blind , single-dose , placebo-controlled , parallel-group study with self-ratings at 30 minutes and then at hourly intervals from hour 1 to hour 6 . SETTING Private , oral surgery practice sites . PATIENTS Three hundred twenty-four out patients with moderate or severe pain after the surgical removal of impacted third molars were selected . One was lost to follow-up and 32 did not need an analgesic ; 232 patients had valid efficacy data . INTERVENTIONS Patients were treated with a single oral dose of hydrocodone bitartrate 7.5 mg with acetaminophen 500 mg , codeine phosphate 30 mg with acetaminophen 300 mg , or placebo when they experienced steady , moderate or severe pain that , in their opinion , required an analgesic . Using a self-rating record , subjects rated their pain and its relief for 6 hours after medicating ; estimates of peak and total analgesia were derived from these subjective reports . MEASUREMENTS AND MAIN RESULTS This study was a valid analgesic assay . Both active treatments were significantly superior to placebo for all measures of analgesic efficacy . The hydrocodone-acetaminophen combination was significantly superior to the codeine-acetaminophen combination for total pain relief and the number of evaluations with 50 % relief . Both active treatments manifested an analgesic effect within 30 minutes ; the effect persisted for 5 hours for the codeine combination and 6 hours for the hydrocodone combination . Adverse effects were transient , consistent with the pharmacologic profiles of opioids , and none required treatment . CONCLUSIONS A slight advantage in analgesic efficacy was demonstrated in this single-dose study for the hydrocodone-acetaminophen combination . Repeat-dose studies , however , should be conducted to determine the clinical significance of the difference in analgesic effect of these opioid combinations OBJECTIVE To determine analgesic efficacy of a single oral dose of rofecoxib 50 mg compared with acetaminophen/codeine 600/60 mg , we conducted a double-blind , r and omized , placebo- and active-comparator-controlled , parallel-group study . STUDY DESIGN Patients ( N = 390 ) experiencing moderate or severe pain post extraction of 2 or more third molars , with at least 1 m and ibular impaction , were r and omized to placebo ( n = 30 ) , rofecoxib ( n = 180 ) , or codeine/acetaminophen 60/600 mg ( n = 180 ) . Time to confirmed perceptible pain relief , and patient evaluations of pain intensity , pain relief , and global assessment s were recorded . RESULTS For total pain relief over 6 hours ( primary end point ) , rofecoxib was superior to codeine/acetaminophen ( 15.5 vs 10.7 ; P < .001 ) . Rofecoxib was statistically significantly superior to codeine/acetaminophen with respect to TOPAR4 , patient global assessment , peak pain relief , and duration of analgesic effect . Median onset of analgesia was similar for both drugs . The codeine/acetaminophen group had more patients with 1 or more adverse events . CONCLUSION Rofecoxib provided superior analgesic efficacy compared with codeine/acetaminophen with fewer gastrointestinal and nervous system adverse events One-hundred twenty-eight out patients with postoperative pain after the surgical removal of impacted third molars were r and omly assigned , on a double-blind basis , to receive oral doses of ketorolac tromethamine 10 mg , aspirin 650 mg , a combination of acetaminophen 600 mg plus codeine 60 mg , or placebo . Using a self-rating record , subjects rated their pain and its relief hourly for 6 hours after medicating . All active medications were significantly superior to placebo . The acetaminophen-codeine combination was significantly superior to aspirin for peak analgesia . Ketorolac was significantly superior to aspirin for every measure of total and peak analgesia , and significantly superior to acetaminophen-codeine for measures of total effect . The analgesic effect of ketorolac was significant by hour 1 and persisted for 6 hours . Repeat-dose data also suggested that ketorolac 10 mg was superior to aspirin 650 mg and acetaminophen-codeine on the day of surgery . Differences among the active medications were trivial for the postoperative days 1 - 6 analyses . The frequency of adverse effects was over 4 times greater for acetaminophen-codeine than for ketorolac or aspirin In a prospect i ve , double blind , and r and omized study , we compared methylprednisolone and ketoprofen after anesthesia for multiple third molar extraction . In addition to paracetamol , 90 patients were allocated to receive intravenously either ketoprofen 100 mg or methylprednisolone 1 mg/kg . Severity of pain was measured with visual analogue scale ( VAS ) in recovery room . Sixty-three percent of patients receiving methylprednisolone had a VAS score < 30 mm compared with 42 % of those receiving ketoprofen ( P = 0.04 ) , with no difference in the consumption of morphine . We observed only marginal difference between methylprednisolone and ketoprofen to relieve pain after this surgery A single-dose , r and omized , double-blind , parallel-treatment study was performed in 200 out patients with acute pain caused by the surgical removal of impacted third molars . Meclofenamate 100 mg plus codeine 60 mg , meclofenamate 50 mg plus codeine 30 mg , meclofenamate 100 mg , codeine 60 mg , and placebo treatment groups were compared for sum of pain intensity differences , peak pain intensity difference , sum of pain relief scores , peak pain relief , number of observations at which pain was half relieved , overall evaluation of effectiveness , and time to remedication with a backup analgesic . Meclofenamate 100 mg plus codeine 60 mg was significantly more effective ( P less than .005 ) than codeine 60 mg for all variables except number of observations at which pain was half relieved . Both meclofenamate-codeine combinations and meclofenamate 100 mg alone were significantly more effective ( P less than .005 ) than placebo for all variables . Eleven adverse experiences were reported in 7 patients ( 3.5 % ) ; the most common was somnolence in 1 patient receiving meclofenamate 100 mg plus codeine 60 mg , in 2 treated with meclofenamate 50 mg plus codeine 30 mg , and in 1 treated with codeine 60 mg BACKGROUND Ibuprofen liquigel is a solubilized potassium ibuprofen 200-mg gelatin capsule formulation that was approved for over-the-counter use in 1995 . OBJECTIVE This study compared the analgesic efficacy and tolerability of ibuprofen liquigel 200 mg , ibuprofen liquigel 400 mg , acetaminophen caplets 1000 mg , and placebo in patients experiencing moderate or severe pain after surgical removal of impacted third molars . METHODS This r and omized , double-blind , parallel-group , 6-hour study was conducted in 210 patients experiencing moderate or severe postoperative pain . Ratings of pain intensity and pain relief were recorded every 15 minutes for the first hour , at 90 and 120 minutes , and then hourly through hour 6 . The onsets of first perceptible relief and meaningful relief were recorded using 2 stopwatches . An analysis of variance model was employed to test for significant differences ( P < or = 0.05 ) between treatment groups with respect to pain relief , pain intensity difference , total pain relief ( TOTPAR ) , and summed pain intensity difference ( SPID ) . Stopwatch measures were analyzed using the Cox proportional hazards model . Drug tolerability was assessed by monitoring the occurrence of adverse events . RESULTS During the first 2 hours of the study ( TOTPAR 2 and SPID 2 ) , all active treatments were significantly more efficacious than placebo ( P < 0.001 ) , with ibuprofen liquigel 200 and 400 mg significantly more efficacious than acetaminophen 1000 mg ( P < 0.05 and P < 0.01 , respectively ) . For the entire duration of the study ( TOTPAR 6 and SPID 6 ) , only the 2 doses of ibuprofen liquigel were significantly more efficacious than placebo ( P < 0.001 ) . Ibuprofen liquigel 200 and 400 mg were also significantly more efficacious than acetaminophen 1000 mg on the summary measures TOTPAR 6 and SPID 6 ( P < 0.01 and P < 0.001 , respectively ) . Analysis of the stopwatch data revealed that all active treatments displayed significantly more rapid onsets to confirmed first perceptible relief ( P < 0.001 to < 0.05 ) and meaningful relief ( P < 0.001 to < 0.01 ) than did placebo , with ibuprofen liquigel 400 mg displaying a significantly more rapid onset to meaningful relief than acetaminophen 1000 mg ( P < 0.05 ) and a significantly more rapid onset to confirmed first perceptible relief than acetaminophen 1000 mg ( P < 0.001 ) and ibuprofen liquigel 200 mg ( P < 0.01 ) . All adverse events were considered mild or moderate , with an overall incidence of 11.5 % in the ibuprofen liquigel 200-mg group , 6.8 % in the ibuprofen liquigel 400-mg group , 19.0 % in the acetaminophen 1000-mg group , and 25.9 % in the placebo group . CONCLUSIONS Ibuprofen liquigel provided greater peak and overall analgesic effects and a more rapid onset to analgesia than did acetaminophen 1000 mg In a multicenter , double blind clinical trial a combination of acetylsalicylic acid 500 mg + codeine phosphate 30 mg has been compared with acetylsalicylic acid 500 mg as postoperative analgesics in patients with pain after surgical removal of impacted m and ibular third molars . Evaluation of the results from 129 patients showed that the combination of acetylsalicylic acid and codeine provided better pain relief and also the number of tablets used was smaller and the time intervals between repeated doses were longer than with acetylsalicylic acid only . Adverse effects were few and similar for both drugs . It may be concluded that the combination of 500 mg acetylsalicylic acid and 30 mg codeine phosphate provides a useful analgesic for more severe pain conditions in oral surgery A clinical trial comparing ibuprofen , 400 , 600 , and 800 mg , with aluminum ibuprofen , 400 mg , and placebo was conducted in patients with moderate or severe pain subsequent to third molar extraction . Pain intensity ratings and ibuprofen serum levels were obtained at baseline , 30 minutes , 1 hour , and hourly thereafter for 3 hours . Pain intensity ratings were also obtained at hours 4 , 5 , and 6 . Serum levels at 1 , 2 , and 3 hours correlated significantly with the log dose of ibuprofen ( r = 0.35 , 0.49 , and 0.48 , respectively ) and with global analgesic response as measured by the percentage of the sum of the pain intensity scores ( r = 0.28 , 0.34 , and 0.26 , respectively ) . However , possibly because of differences in drug formulation , the percentage of the sum of the pain intensity scores did not correlate significantly with log dose . The highest correlations were found between contemporaneous serum levels and pain intensity difference values , particularly at hour 1 ( r = 0.54 ) . Our results support the proposition that increased ibuprofen serum levels lead to increased analgesia The efficacy of an aspirin-caffeine-codeine-butalbital combination was compared to an acetaminophen-codeine combination and placebo in out patients who had moderate or severe pain after the surgical removal of impacted third molars . Using a self-rating record , patients rated their pain , relief , anxiety and relaxation hourly for up to 6 hours after medicating . Each active medication was significantly superior to placebo for measures of analgesia and relaxation . Although the butalbital-containing combination provided consistently greater analgesia , the differences between active medications were not statistically significant . The acetaminophen-codeine combination significantly reduced anxiety ; however , the butalbital containing combination did not . The results of this study suggest that female patients may have greater efficacy than male patients . All adverse effects were transitory and consistent with the known pharmacologic profiles of the study medications or the backup analgesic OBJECTIVE This study compared the efficacy and safety of a single dose of oxycodone 5 mg/ibuprofen 400 mg versus its individual components and placebo in a third-molar extraction model . METHODS In this multicenter , double-blind , double-dummy , parallel-group investigation , subjects with moderate to severe pain within 5 hours after extraction of > or = 2 ipsilateral bony impacted third molars were r and omized to single doses of oxycodone 5 mg/ibuprofen 400 mg , ibuprofen 400 mg , oxycodone 5 mg , or placebo . Primary efficacy variables were the sum of pain intensity difference over 6 hours ( SP1D6 ) and total pain relief through 6 hours ( TOTPAR6 ) . The pharmacokinetics of oxycodone and ibuprofen , alone and in combination , were also determined in a subset of patients . RESULTS A total of 498 subjects were r and omized to treatment ( 187 to oxycodone 5 mg/ibuprofen 400 mg , 186 to ibuprofen 400 mg , 63 to oxycodone 5 mg , and 62 to placebo ) . Baseline demographics were generally similar among treatment groups , despite differences in sex ( P = 0.041 ) and race ( P = 0.023 ) . Combination therapy was associated with greater analgesia than ibuprofen alone , oxycodone alone , or placebo ( mean [ SE ] TOTPAR6 : 13.3 [ 0.52 ] , 12.2 [ 0.52 ] , 4.3 [ 0.82 ] , and 4.2 [ 0.83 ] , respectively [ P < 0.001 vs oxycodone or placebo , P = 0.012 vs ibuprofen ] ; mean [ SE ] SP1D6 : 6.54 [ 0.42 ] , 5.41 [ 0.44 ] , 0.14 [ 0.60 ] , and 0.32 [ 0.59 ] , respectively [ P < 0.001 vs oxycodone or placebo , P = 0.002 vs ibuprofen ] ) . Combination therapy was well tolerated . Pharmacokinetic results implied no interaction between oxycodone and ibuprofen . CONCLUSIONS In this study , a single dose of oxycodone 5 mg/ibuprofen 400 mg was fast-acting , effective , and well tolerated in subjects with moderate to severe pain after dental surgery . Oxycodone 5 mg alone did not provide an efficacy benefit over placebo in this study Renewed interest in analgesic models has been stimulated by the development of several new nonsteroidal anti-inflammatory drugs . Many of these new analgesic agents appear to have higher peak effects and longer duration s of action than acetylsalicylic acid . Sensitive models are necessary to determine the dose-effect relationships and relative analgesic efficacies of these new agents . The basic principles of clinical methods --double-blinding , identical appearance of study medications , and r and om allocation of treatments to subjects -- must be adhered to . However , additional pre caution s must also be taken . The choice of pain models and further subdivision of subjects within a pain model are critical for assay sensitivity . The dental pain model has become popular because the surgical procedures can be easily categorized , and each sub population is relatively homogeneous . There now is a body of data that substantiates the assay sensitivity of the dental pain model , and its usefulness in predicting the general analgesic efficacy of nonsteroidal anti-inflammatory drugs . Other pain models , including general postsurgical , orthopedic postsurgical , and postpartum pain , also have demonstrated adequate assay sensitivity to determine the relative efficacy of new nonsteroidal anti-inflammatory drugs BACKGROUND Opiates , acetaminophen , nonselective nonsteroidal anti-inflammatory drugs ( NSAIDs ) , and cyclooxygenase-2-selective inhibitors such as rofecoxib are used in the treatment of acute pain because of their anti-inflammatory and /or analgesic properties . Rofecoxib has demonstrated an improved gastrointestinal safety profile compared with nonselective NSAIDs . OBJECTIVE The aim of this study was to compare the analgesic efficacy and tolerability profile of rofecoxib 50 mg with those of the central ly acting , nonsalicylate , opiate/nonopiate analgesic combination oxycodone/acetominophen 5/325 in patients with pain after dental surgery . METHODS In this r and omized , double-blind , placebo- and active comparator-controlled study , patients experiencing moderate to severe postoperative pain after extraction of > or = 2 third molars ( including > or = 1 m and ibular impaction ) received a single oral dose of rofecoxib 50 mg , oxycodone/acetaminophen 5/325 mg , or placebo . End points included total pain relief over 6 hours ( TOPAR6 , the primary end point ) and 4 hours ( TOPAR4 ) , patient 's global assessment of treatment at 6 hours ( GLOBAL6 ) and 24 hours ( GLOBAL24 ) , summed pain intensity difference over 6 hours ( SPID6 ) , onset of analgesic effect ( time to perceptible/meaningful pain relief , using a 2-stopwatch method ) , peak pain relief ( PEAKPR ) , peak pain intensity difference ( PEAKPID ) , and duration of analgesic effect ( time to use of rescue analgesia ) . RESULTS Two hundred twelve patients ( 63 % female , 37 % male ; 76 % white , 24 % other ; mean [ SD ] age , 20.9 [ 4.4 ] years ; age range , 16 - 41 years ) were enrolled in the study and received a single oral dose of rofecoxib 50 mg ( n = 90 ) , oxycodone/acetaminophen 5/325 mg ( n = 91 ) , or placebo ( n = 31 ) . The analgesic effect of rofecoxib was significantly greater than that of oxycodone/acetaminophen at P < 0.001 for TOPAR6 , TOPAR4 , GLOBAL6 , GLOBAL24 , and SPID6 ; at P < 0.010 for PEAKPR and PEAKPID ; and at P < 0.001 for median time to use of rescue analgesia . Significantly fewer patients in the rofecoxib group ( 72.2 % ) took rescue analgesia within 24 hours postdose compared with the oxycodone/acetaminophen group ( 94.5 % ; P < 0.001 ) and the placebo group ( 96.8 % ; P < 0.02 ) . Both active treatments were similar with respect to onset of analgesic effect . Both were generally well tolerated ; the overall incidence of adverse experiences in the rofecoxib , oxycodone/acetaminophen , and placebo groups was 51.1 % , 64.8 % , and 48.4 % , respectively . Rofecoxib was associated with a significantly lower incidence of nausea ( 18.9 % vs 39.6 % ; P < 0.001 ) and vomiting ( 6.7 % vs 23.1 % ; P < 0.001 ) compared with oxycodone/acetaminophen . CONCLUSIONS In study patients with moderate to severe pain after dental surgery , rofecoxib 50 mg had a greater analgesic effect than oxycodone/acetaminophen 5/325 mg and was associated with less nausea and vomiting A special model design ed for evaluating the analgesic effect of oral analgesics was based on a short-time registration period of immediate postoperative pain . One-hour intervals in pain registration and a minimum of 2 h between the tablet intake allowed a good estimation of changes in pain levels . The patient material consisted of 112 patients and from each patient a lower impacted wisdom tooth was removed . The test model was used to compare two analgesic drugs with placebo . The two pharmacologically active preparations were Doleron ( dextropropoxyphene , acetylsalicylic acid , phenazone , caffeine and Transergan ) and Astra 2167 ( dextropropoxyphene and acetylsalicylic acid ) . The trial was double blind and the tablets were administered according to a crossover design . There was no statistically significant difference in analgesic effect between Astra 2167 and Doleron , and both drugs were superior to placebo . Finally , the trial showed that a reduction of the number of components of a compound analgesic to some degree reduced the pain relieving effect on this particular postoperative pain . This observed reduction was however , not statistically significant PURPOSE This double-blind r and omized crossover study compared the analgesic efficacy of pre- and postoperative administration of oral pregabalin 75 mg using a postsurgical dental pain model . MATERIAL S AND METHODS Patients requiring third molar surgery in 2 separate stages under local anesthesia were recruited . They were given pregabalin 75 mg either 1 hour before or after their first surgical extraction . They then received the same dose of pregabalin at their second surgical extraction , but those who received it before surgery received it postsurgery , and vice versa . Postoperative analgesic effects were assessed at postoperative hours 2 , 4 , 8 , 12 , 24 , 48 , and 72 . Time to first analgesic , analgesic consumption and adverse events were also evaluated . RESULTS Forty patients were recruited , and 34 completed the study . The area under curves for numerical rating scale pain scores 1 to 24 hours were significantly lower at rest but not during mouth opening for patients receiving postoperative pregabalin ( P < .048 ) . Pain relief was similar for the period of 24 to 72 hours . No significant difference was found in time to first analgesic , total analgesic consumption , and side effects between preoperative and postoperative groups . No difference in the incidence of adverse events was noticed in relation to the timing of pregabalin administration . CONCLUSIONS Postoperative administration of oral pregabalin 75 mg appears to offer better analgesic efficacy than preoperative administration after third molar surgery under local anesthesia In a r and omised double‐blind trial in postoperative ambulant day case dental patients suprofen 200 mg ( 29 patients ) was compared with dextropropoxyphene hydrochloride 65 mg and paracetamol 650 mg ( Cosalgesic , 28 patients ) both available four times daily for 3 days . Suprofen was better than cosalgesic in the patients ' opinion of initial ( p = 0.01 ) and overall pain relief ( p = 0.08 ) compared to Cosalgesic and the second night 's sleep was better ( p = 0.01 ) . Side effects were reported in six suprofen patients and 10 cosalgesic patients ( two suffering from vomiting withdrew ) . Suprofen , a non‐steroidal anti‐inflammatory drug is as good as , or better than , a widely used opioiparacetamol mixture for ambulant patients with postoperative dental pain The analgesic efficacy of a single 50-mg preoperative dose of flurbiprofen was compared with ACC-30 ( aspirin 375 mg , codeine 30 mg , caffeine 30 mg ) and a placebo . Forty patients scheduled for the surgical removal of impacted maxillary third molars were enrolled in a double-blind , r and omized study . Using a within-subject design we compared the analgesic efficacy of ( 1 ) preoperative flurbiprofen 50 mg with placebo in 20 patients , and ( 2 ) preoperative ACC-30 with placebo in 20 other patients . Using a between-group design , we then compared the analgesic efficacy of ( 3 ) each drug given preoperatively and postoperatively , and ( 4 ) each drug given postoperatively only . Patients rated 2 pain dimensions , intensity and unpleasantness , hourly for 8 hours after the presurgical dose . The results of this study indicate that better analgesia was obtained when flurbiprofen was given preoperatively compared to only after surgery . Conversely , preoperative administration of ACC-30 did not demonstrate any significant influence on postsurgical analgesia . When comparing the 2 drugs , flurbiprofen proved to be superior in providing pain relief only when it was given prior to surgery . There was no difference between them when given only after surgery . Side effects were moderate and not significantly different between patients receiving flurbiprofen and those receiving ACC-30 Eighty-eight out patients with postoperative pain after the surgical removal of impacted third molars were r and omly assigned , on a double-blind basis , to receive a single , oral dose of flurbiprofen 100 mg , acetaminophen 600 mg , a combination of acetaminophen 600 mg with codeine 60 mg , or placebo . Using a self-rating record , subjects rated their pain and its relief hourly for 12 hours after medicating . Estimates of sum of pain intensity differences , peak pain intensity differences , total relief , peak relief , and hours of 50 % relief were derived from these subjective reports . Flurbiprofen and the acetaminophen-codeine combination were significantly superior to placebo for every measure of total and peak analgesia and significantly superior to acetaminophen alone for most measures of efficacy . Based on the 12-hour data , acetaminophen alone did not differ significantly from placebo ; however , it was superior to placebo for measures of total effect based on the 4-hour data . Flurbiprofen was significantly superior to the acetaminophen codeine combination with respect to the number of hours until remedication . All medications had manifested an effect by hour 1 ; analgesia persisted for 12 hours for flurbiprofen , 6 hours for acetaminophen-codeine , and 3 hours for acetaminophen alone . The frequency of adverse effects was similar for the active medications The relative analgesic efficacy and safety of single oral doses of 50 and 100 mg of flurbiprofen ( Ansaid , Upjohn ) were compared with 100 mg of zomepirac sodium , 650 mg of acetaminophen plus 60 mg of codeine , 650 mg of acetaminophen alone , and placebo in a r and omized , double-blind , parallel-group study . A total of 182 patients entered the study with moderate pain from a third molar extraction and were evaluated for six hours . For many efficacy variables , all active treatments were significantly ( p less than or equal to 0.05 ) more effective than placebo . The two doses of flurbiprofen gave approximately similar results , suggesting a plateau effect above 50 mg . With the exception of relief at one hour , there were no significant differences between zomepirac and either dose of flurbiprofen . However , the mean response with zomepirac was greater than with either 50 or 100 mg of flurbiprofen during the first four hours and lower during the last two hours . The analgesic effects of acetaminophen alone were not significantly different from acetaminophen in combination with codeine . At the first hour , acetaminophen plus codeine led to significantly better pain relief than did 100 mg of flurbiprofen . After the first hour , flurbiprofen result ed in greater mean scores than acetaminophen alone or acetaminophen plus codeine , and these differences were significant at the fifth and sixth hours . Five patients had adverse reactions while receiving acetaminophen , acetaminophen plus codeine , or placebo . There were no adverse effects with flurbiprofen or zomepirac A model was developed to evaluate mild analgesics in an oral surgery outpatient clinic population . On a reportform , patients recorded starting pain and then pain intensities , relief responses , and side effects hourly for 3 hr after drug administration . The treatments were r and omly allocated to patients on a single‐dose‐only basis , and the double‐blind technique was used . The first of two studies compared codeine 30 mg , aspirin 650 mg , codeine 30 mg with aspirin 650 mg , and placebo in 128 subjects . The second study compared codeine 60 mg , acetaminophen 600 mg , and codeine 60 mg with acetaminophen 600 mg and placebo in 160 subjects . Time‐effect curves were generated for both pain reliel and pain intensity difference ( PID ) . First‐hour scores , peak scores , and total scores were statistically analyzed by parametric and nonparametric factorial analysis . Both aspirin 650 mg and acetaminophen 600 mg proved superior to placebo ( p < 0.01 ) for all measures of effect with both parametric or nonparametric analyses , while codeine 30 mg was not significantly superior to placebo in any analysis . Codeine 60 mg proved significantly superior to placebo for certain measures of effect when analyzed with the nonparametric model . There was no significant interaction between either aspirin or acetaminophen and codeine Objective : To evaluate the analgesic effects of etoricoxib and comparator agents on the second and third days after oral surgery . Methods : There were 588 patients initially r and omized to placebo ( n=46 ) , etoricoxib 120 mg once daily ( n=97 ) , etoricoxib 90 mg once daily ( n=191 ) , ibuprofen 600 mg every 6 hours ( n=192 ) , and acetaminophen 600 mg/codeine 60 mg ( A/C ) every 6 hours ( n=62 ) after third-molar extraction ( ≥2 , ≥1 impacted ) in a double-blind controlled trial . Patients were allowed flexible dosing on days 2 and 3 ; 46 , 96 , 190 , 192 , and 56 patients on placebo , etoricoxib 120 mg , etoricoxib 90 mg , ibuprofen , and A/C , respectively , continued to Day 2 of the study . Outcomes included Average and Worst Recall Pain Assessment s ( 0 to 10 scale ) and Global Assessment s of Study Medication ( 0 to 4 scale ) . Rescue medication ( acetaminophen 325 mg up to 4 times daily ) usage was evaluated . Adverse experiences were collected and evaluated . Results : Average Pain Recall scores were lower than placebo for all active treatments on Day 2 but only for etoricoxib 120 and 90 mg on Day 3 . Worst Pain Recall scores were lower than placebo for only etoricoxib 120 and 90 mg on Day 2 ; all treatment groups were similar on day 3 . Rescue medicine was used on day 2 in 57 % of placebo patients , whereas use in active treatments ranged from 18 % to 23 % ; for Day 3 , rescue was used in 22 % of placebo patients , whereas use in active treatments ranged from 14 % to 20 % . Differences in mean Patient ’s Global Assessment of Study Medication scores were significant for etoricoxib versus placebo ( P<0.001 ) and for etoricoxib versus A/C ( P<0.010 ) . Nausea and vomiting were among the most common adverse events with higher frequency in the A/C group . Conclusions : Pain control was most favorable for the etoricoxib doses and ibuprofen . Global Assessment s of Study Medication continued to differentiate the treatments and demonstrated greater efficacy for etoricoxib on Days 2 and 3 compared with placebo and A/C ( NCT00694369 ) & NA ; Combination analgesia is often recommended for the relief of severe pain . This was a double‐blind , 5‐arm , parallel‐group , placebo‐controlled , r and omised , single‐dose study design ed to compare the efficacy and tolerability of a novel single‐tablet combination of ibuprofen and paracetamol with that of an ibuprofen/codeine combination , and a paracetamol/codeine combination , using the dental impaction pain model . Subjects with at least 3 impacted third molars and experiencing moderate to severe postoperative pain were r and omised to receive : 1 or 2 tablets of a single‐tablet combination of ibuprofen 200 mg/paracetamol 500 mg ; 2 tablets of ibuprofen 200 mg/codeine 12.8 mg ; 2 tablets of paracetamol 500 mg/codeine 15 mg ; or placebo . Results for the primary endpoint , the sum of the mean scores of pain relief combined with pain intensity differences over 12 hours , demonstrated that 1 and 2 tablets of the single‐tablet combination of ibuprofen/paracetamol were statistically significantly more efficacious than 2 tablets of placebo ( P < 0.0001 ) and paracetamol/codeine ( P ⩽ 0.0001 ) ; furthermore , 2 tablets offered significantly superior pain relief to ibuprofen/codeine ( P = 0.0001 ) , and 1 tablet was found noninferior to this combination . Adverse events were uncommon during this study and treatment emergent adverse events were statistically significantly less frequent in the groups taking the ibuprofen/paracetamol combination compared with codeine combinations . In conclusion , 1 or 2 tablets of a single‐tablet combination of ibuprofen 200 mg/paracetamol 500 mg provided highly effective analgesia that was comparable with , or superior to , other combination analgesics currently indicated for strong pain . A single‐tablet combination of ibuprofen 200 mg/paracetamol 500 mg provides highly effective analgesia , comparable or superior to other combination analgesics indicated for strong pain |
12,329 | 29,391,784 | Conclusion In the first systematic review of the area , current evidence demonstrates that continued supervised maintenance exercise compared to usual care following pulmonary rehabilitation reduces health care use in COPD . | Introduction The clinical benefit of continued supervised maintenance exercise programs following pulmonary rehabilitation in COPD remains unclear .
This systematic review aim ed to synthesize the available evidence on the efficacy of supervised maintenance exercise programs compared to usual care following pulmonary rehabilitation completion on health care use and mortality . | BACKGROUND Pulmonary rehabilitation programmes improve the health of patients disabled by lung disease but their cost effectiveness is unproved . We undertook a cost/utility analysis in conjunction with a r and omised controlled clinical trial of pulmonary rehabilitation versus st and ard care . METHODS Two hundred patients , mainly with chronic obstructive pulmonary disease , were r and omly assigned to either an 18 visit , 6 week rehabilitation programme or st and ard medical management . The difference between the mean cost of 12 months of care for patients in the rehabilitation and control groups ( incremental cost ) and the difference between the two groups in quality adjusted life years ( QALYs ) gained ( incremental utility ) were determined . The ratio between incremental cost and utility ( incremental cost/utility ratio ) was calculated . RESULTS Each rehabilitation programme for up to 20 patients cost £ 12 120 . The mean incremental cost of adding rehabilitation to st and ard care was £ –152 ( 95 % CI –881 to 577 ) per patient , p = NS . The incremental utility of adding rehabilitation was 0.030 ( 95 % CI 0.002 to 0.058 ) QALYs per patient , p=0.03 . The point estimate of the incremental cost/utility ratio was therefore negative . The bootstrapping technique was used to model the distribution of cost/utility estimates possible from the data . A high likelihood of generating QALYs at negative or relatively low cost was indicated . The probability of the cost per QALY generated being below £ 0 was 0.64 . CONCLUSIONS This outpatient pulmonary rehabilitation programme produces cost per QALY ratios within bounds considered to be cost effective and is likely to result in financial benefits to the health service Pulmonary rehabilitation is beneficial for patients with chronic lung disease . However , long-term maintenance has been difficult to achieve after short-term treatment . We evaluated a telephone-based maintenance program after pulmonary rehabilitation in 172 patients with chronic lung disease recruited from pulmonary rehabilitation graduates . Subjects were r and omly assigned to a 12-month maintenance intervention with weekly telephone contacts and monthly supervised reinforcement sessions ( n = 87 ) or st and ard care ( n = 85 ) and followed for 24 months . Except for a slight imbalance between sexes , experimental and control groups were equivalent at baseline and showed similar improvements after rehabilitation . During the 12-month intervention , exercise tolerance ( maximum treadmill workload and 6-minute walk distance ) and overall health status ratings were better maintained in the experimental group together with a reduction in hospital days . There were no group differences for other measures of pulmonary function , dyspnea , self-efficacy , generic and disease-specific quality of life , and health care use . By 24 months , there were no significant group differences . Patients returned to levels close to but above prerehabilitation measures . We conclude that a maintenance program of weekly telephone calls and monthly supervised sessions produced only modest improvements in the maintenance of benefits after pulmonary rehabilitation Objective To determine the feasibility and efficacy of a six-month , cell phone-based exercise persistence intervention for patients with chronic obstructive pulmonary disease ( COPD ) following pulmonary rehabilitation . Methods Participants who completed a two-week run-in were r and omly assigned to either MOBILE-Coached ( n = 9 ) or MOBILE-Self-Monitored ( n = 8) . All participants met with a nurse to develop an individualized exercise plan , were issued a pedometer and exercise booklet , and instructed to continue to log their daily exercise and symptoms . MOBILE-Coached also received weekly reinforcement text messages on their cell phones ; reports of worsening symptoms were automatically flagged for follow-up . Usability and satisfaction were assessed . Participants completed incremental cycle and six minute walk ( 6MW ) tests , wore an activity monitor for 14 days , and reported their health-related quality of life ( HRQL ) at baseline , three , and six months . Results The sample had a mean age of 68 ±11 and forced expiratory volume in one second 18 % predicted . Participants reported that logging their exercise and symptoms ( FEV1 ) of 40 ± was easy and that keeping track of their exercise helped them remain active . There were no differences between groups over time in maximal workload , 6MW distance , or HRQL ( p > 0.05 ) ; however , MOBILE-Self-Monitored increased total steps/day whereas MOBILE-Coached logged fewer steps over six months ( p = 0.04 ) . Conclusions We showed that it is feasible to deliver a cell phone-based exercise persistence intervention to patients with COPD post-rehabilitation and that the addition of coaching appeared to be no better than self-monitoring . The latter finding needs to be interpreted with caution since this was a purely exploratory study . Trial registration Clinical Trials.gov ( NCT00373932 ) Objectives Pulmonary rehabilitation ( PR ) provides benefit for patients with chronic obstructive pulmonary disease ( COPD ) in terms of quality of life ( QoL ) and exercise capacity ; however , the effects diminish over time . Our aim was to evaluate a maintenance programme for patients who had completed PR . Setting Primary and secondary care PR programmes in Norfolk . Participants 148 patients with COPD who had completed at least 60 % of a st and ard PR programme were r and omised and data are available for 110 patients . Patients had greater than 20 pack year smoking history and less than 80 % predicted forced expiratory volume in 1 s but no other significant disease or recent respiratory tract infection . Interventions Patients were r and omised to receive a maintenance programme or st and ard care . The maintenance programme consisted of 2 h ( 1 h individually tailored exercise training and 1 h education programme ) every 3 months for 1 year . Primary and secondary outcome measures The Chronic Respiratory Question naire ( CRQ ) ( primary outcome ) , endurance shuttle walk test ( ESWT ) , EuroQol ( EQ5D ) , hospital anxiety and depression score ( HADS ) , body mass index ( BMI ) , body fat , activity levels ( overall score and activity diary ) and exacerbations were assessed before and after 12 months . Results There was no statistically significant difference between the groups for the change in CRQ dyspnoea score ( primary end point ) at 12 months which amounted to 0.19 ( −0.26 to 0.64 ) units or other domains of the CRQ . There was no difference in the ESWT duration ( −10.06 ( −191.16 to 171.03 ) seconds ) , BMI , body fat , EQ5D , MET-minutes , activity rating , HADS , exacerbations or admissions . Conclusions A maintenance programme of three monthly 2 h sessions does not improve outcomes in patients with COPD after 12 months . We do not recommend that our maintenance programme is adopted . Other methods of sustaining the benefits of PR are required . Trial registration number NCT00925171 Background Chronic obstructive pulmonary disease ( COPD ) and chronic heart failure ( CHF ) frequently coexist , significantly reducing patients ’ quality of life and increasing morbidity and mortality . For either single disease , a multidisciplinary disease-management approach supported by telecommunication technologies offers the best outcome in terms of prolonged survival and reduced hospital readmissions . However , no data exist in patients with combined COPD /CHF.We planned a r and omized controlled trial to investigate the feasibility and efficacy of an integrated , home-based , medical/nursing intervention plus a rehabilitation program versus conventional care in patients with coexisting COPD /CHF . The purpose of the paper is to describe the rationale and design of the trial . Methods / design s Patients , after inpatient rehabilitation , were r and omly assigned to the intervention or control group , followed for 4 months at home , then assessed at 4 and 6 months . The intervention group followed a telesurveillance ( telephone contacts by nurse and remote monitoring of cardiorespiratory parameters ) and home-based rehabilitation program ( at least three sessions/week of mini-ergometer exercises , callisthenic exercises and twice weekly pedometer-driven walking , plus telephone contacts by a physiotherapist ) . Telephone follow-up served to verify compliance to therapy , maintain exercise motivation , educate for early recognition of signs/symptoms , and verify the skills acquired . At baseline and 4 and 6 months , the 6-min Walk Test , dyspnea and fatigue at rest , oxygenation ( PaO2/FiO2 ) , physical activity profile ( PASE question naire ) , and QoL ( Minnesota and CAT question naires ) were assessed . During the study , serious clinical events ( hospitalizations or deaths ) were recorded . Discussion Currently , no studies have assessed the impact of a telehealth program in patients with combined COPD and CHF . Our study will show whether this approach is effective in the management of such complex , frail patients who are at very high risk of exacerbations . Trial registration Network per la prevenzione e la sanità pubblica , CCM , Ministero della Salute “ Modelli innovativi di gestione integrata telegestita ospedale-territorio del malato cronico a fenotipo complesso : studio di implementazione , validazione e impatto , ” registered on 14 January 2014 . Clinical Trials.gov Identifier : NCT02269618 , registered on 17 October 2014 Background Pulmonary Rehabilitation for moderate Chronic Obstructive Pulmonary Disease in primary care could improve patients ’ quality of life . Methods This study aim ed to assess the efficacy of a 3-month Pulmonary Rehabilitation ( PR ) program with a further 9 months of maintenance ( RHBM group ) compared with both PR for 3 months without further maintenance ( RHB group ) and usual care in improving the quality of life of patients with moderate COPD .We conducted a parallel-group , r and omized clinical trial in Majorca primary health care in which 97 patients with moderate COPD were assigned to the 3 groups . Health outcomes were quality of life , exercise capacity , pulmonary function and exacerbations . Results We found statistically and clinical ly significant differences in the three groups at 3 months in the emotion dimension ( 0.53 ; 95%CI0.06 - 1.01 ) in the usual care group , ( 0.72 ; 95%CI0.26 - 1.18 ) the RHB group ( 0.87 ; 95%CI 0.44 - 1.30 ) and the RHBM group as well as in fatigue ( 0.47 ; 95%CI 0.17 - 0.78 ) in the RHBM group . After 1 year , these differences favored the long-term rehabilitation group in the domains of fatigue ( 0.56 ; 95%CI 0.22 - 0.91 ) , mastery ( 0.79 ; 95%CI 0.03 - 1.55 ) and emotion ( 0.75 ; 95%CI 0.17 - 1.33 ) . Between-group analysis only showed statistically and clinical ly significant differences between the RHB group and control group in the dyspnea dimension ( 0.79 95%CI 0.05 - 1.52 ) . No differences were found for exacerbations , pulmonary function or exercise capacity . Conclusions We found that patients with moderate COPD and low level of impairment did not show meaningful changes in QoL , exercise tolerance , pulmonary function or exacerbation after a one-year , community based rehabilitation program . However , long-term improvements in the emotional , fatigue and mastery dimensions ( within intervention groups ) were identified . Trial registration IS RCT Background Interventions for preventing falls in older people often involve several components , multidisciplinary teams , and implementation in a variety of setting s. We have developed a classification system ( taxonomy ) to describe interventions used to prevent falls in older people , with the aim of improving the design and reporting of clinical trials of fall-prevention interventions , and synthesis of evidence from these trials . Methods Thirty three international experts in falls prevention and health services research participated in a series of meetings to develop consensus . Robust techniques were used including literature review s , expert presentations , and structured consensus workshops moderated by experienced facilitators . The taxonomy was refined using an international test panel of five health care practitioners . We assessed the chance corrected agreement of the final version by comparing taxonomy completion for 10 r and omly selected published papers describing a variety of fall-prevention interventions . Results The taxonomy consists of four domains , summarized as the " Approach " , " Base " , " Components " and " Descriptors " of an intervention . Sub-domains include ; where participants are identified ; the theoretical approach of the intervention ; clinical targeting criteria ; details on assessment s ; descriptions of the nature and intensity of interventions . Chance corrected agreement of the final version of the taxonomy was good to excellent for all items . Further independent evaluation of the taxonomy is required . Conclusions The taxonomy is a useful instrument for characterizing a broad range of interventions used in falls prevention . Investigators are encouraged to use the taxonomy to report their interventions BACKGROUND Persons with chronic obstructive pulmonary disease ( COPD ) have reduced exercise capacity and levels of physical activity . Supervised , facility-based pulmonary rehabilitation programs improve exercise capacity and reduce dyspnea , but novel long-term strategies are needed to maintain the benefits gained . Mind-body modalities such as Tai Chi which combine aerobic activity , coordination of breathing , and cognitive techniques that alleviate the physical inactivity , dyspnea , and anxiety and depression that are the hallmarks of COPD are promising strategies . METHODS / DESIGN We have design ed a r and omized controlled study to examine whether Tai Chi will maintain exercise capacity in persons with COPD who have recently completed a supervised pulmonary rehabilitation program , compared to st and ard care . The primary outcome is 6-min walk test distance at 6 months . Secondary outcomes include health-related quality of life , dyspnea , mood , occurrence of acute exacerbations , engagement in physical activity , exercise self-efficacy , and exercise adherence . Simultaneously , we are conducting a pilot study of group walking . We will enroll 90 persons who will be r and omized to one of three arms in a 2:2:1 ratio : Tai Chi , st and ard care , or group-based walking . DISCUSSION The Long-term Exercise After Pulmonary Rehabilitation ( LEAP ) study is a novel and clinical ly relevant trial . We will enroll a well-characterized cohort of persons with COPD and will comprehensively assess physiological and psychosocial outcomes . Results of this study will provide the evidence base for persons with COPD to engage in Tai Chi as a low-cost , long-term modality to sustain physical activity in persons who have completed a st and ard short-term pulmonary rehabilitation program . TRIAL REGISTRATION This trial is registered in Clinical Trials.gov , with the ID number of NCT01998724 The aim of this study was to determine if weekly , supervised , outpatient-based exercise plus unsupervised home exercise following an 8-week pulmonary rehabilitation programme would maintain functional exercise capacity and quality of life at 12 months better than st and ard care of unsupervised home exercise training . Chronic obstructive pulmonary disease ( COPD ) subjects completed an 8-week pulmonary rehabilitation programme , were r and omised to an intervention group ( IG ) of weekly , supervised , exercise plus home exercise or to a control group ( CG ) of unsupervised home exercise and followed for 12 months . Outcome measurements at baseline ( after pulmonary rehabilitation ) , and 3 , 6 and 12 months included the 6-min walk test and St George 's Respiratory Question naire ( SGRQ ) . 59 subjects with moderate COPD ( Global Initiative for Chronic Obstructive Lung Disease stage II ) were recruited and 48 subjects completed the study . 12-month mean difference showed no significant change from baseline in 6-min walk distance ( IG -11 m , 95 % CI -21–10 m ; CG -6 m , 95 % CI -34–11 m ) or total SGRQ score ( IG 3 , 95 % CI -0.8–7 ; CG -3 , 95 % CI -7–3 ) . 12 months following pulmonary rehabilitation both weekly , supervised , outpatient-based exercise plus unsupervised home exercise and st and ard care of unsupervised home exercise successfully maintained 6-min walk distance and quality of life in subjects with moderate COPD Introduction Although pulmonary rehabilitation ( PR ) is associated with significant clinical benefits in chronic obstructive pulmonary disease ( COPD ) and has been recommended by guidelines , PR with conventional exercise training has not been widely applied in the clinic because of its inherent limitations . Alternative exercise such as Tai Chi has been investigated and the results are promising . However , the strengths and weaknesses of the exercise modality of Tai Chi , conventional PR and a combination of Tai Chi and conventional PR and the possible mechanisms underlying Tai Chi exercise remain unclear . This study aims to address the above research gaps in a well- design ed clinical trial . Methods and analysis This study is a single-blind , r and omised controlled trial . Participants with stable COPD will be recruited and r and omly assigned to one of four groups receiving Tai Chi exercise , conventional PR using a total body recumbent stepper ( TBRS ) , combined Tai Chi and TBRS , or usual care ( control ) in a 1:1:1:1 ratio . Participants will perform 30 min of supervised exercise three times a week for 8 weeks ; they will receive sequential follow-ups until 12 months after recruitment . The primary outcome will be health-related quality of life as measured by the St George 's Respiratory Question naire . Secondary outcomes will include 6 min walking distance , pulmonary function , the modified Medical Research Council Dyspnoea Scale , the COPD Assessment Test , the Hospital Anxiety and Depression Scale , the Berg Balance Scale , exacerbation frequency during the study period , and systemic inflammatory and immune markers . Ethics and dissemination Ethics approval has been granted by the Clinical Trial and Biomedical Ethics Committee of West China Hospital of Sichuan University ( No TCM-2015 - 82 ) . Written informed consent will be obtained from each participant before any procedures are performed . The study findings will be published in peer- review ed journals and presented at national and international conferences . Trial registration number ChiCTR-IOR-15006874 ; Pre- results Background : The effectiveness of pulmonary rehabilitation in advanced COPD is well established , but few data are available in less advanced disease . Methods : In a 2 year r and omised controlled trial , 199 patients with an average moderate airflow obstruction but impaired exercise capacity ( mean ( SD ) forced expiratory volume in 1 s ( FEV1 ) 60 (16)% , peak work load ( Wmax ) < 70 % ) were r and omised to the INTERdisciplinary COMmunity-based COPD management programme ( INTERCOM ) or usual care . Intervention consisted of 4 months multidisciplinary rehabilitation followed by a 20-month maintenance phase . Outcomes ( 4 , 12 , 24 months ) : health-related quality of life ( St George ’s Respiratory Question naire ( SGRQ ) ) , exacerbation frequency , MRC dyspnoea score , cycle endurance time ( CET ) , 6-minute walking distance ( 6MWD ) , skeletal muscle strength and patients ’ and caregivers ’ perceived effectiveness . Results : Between-group comparison after 4 months revealed the following mean ( SE ) significant differences in favour of INTERCOM : SGRQ total score 4.06 ( 1.39 ) , p = 0.004 ; activity and impact subscores , p<0.01 ; MRC score 0.33 ( 0.13 ) , p = 0.01 ; Wmax 6.0 ( 2.3 ) Watt , p = 0.02 ; CET 221 ( 104 ) s , p = 0.04 ; 6MWD 13 ( 6 ) m , p = 0.02 ; h and grip force 4.3 ( 1.5 ) lb , p<0.01 ; and fat-free mass index 0.34 ( 0.13 ) kg/m2 , p = 0.01 . Between-group differences over 2 years were as follows : SGRQ 2.60 ( 1.3 ) , p = 0.04 ; MRC score 0.21 ( 0.10 ) , p = 0.048 ; CET 253 ( 104 ) s , p = 0.0156 ; 6MWD 18 ( 8) m , p = 0.0155 . Exacerbation frequency was not different ( RR 1.29 ( 95 % CI 0.89 to 1.87 ) ) . Patients ’ and caregivers ’ perceived effectiveness significantly favoured the INTERCOM programme ( p<0.01 ) . Conclusions : This study shows that a multidisciplinary community-based disease management programme is also effective in patients with COPD with exercise impairment but less advanced airflow obstruction . Trial registration number : The purpose of this study was to examine the effects of two postrehabilitation programmes on functional exercise tolerance and health-related quality of life in patients with chronic obstructive pulmonary disease ( COPD ) . Subjects with COPD ( n=109 ) were r and omised to receive either enhanced follow-up ( EF ) or conventional follow-up ( CF ) . Subjects in the EF group attended a monthly support group and received a telephone call from a staff member at the midpoint ( 2 weeks ) between their visits . Both groups had scheduled appointments with a physical therapist and physician at 3‐monthly intervals after discharge . Longitudinal data were recorded in 85 subjects ( 37 EF and 48 CF ) . Over the course of the study , there was no difference in distance walked in 6 min between the two groups but a significant difference for time and a group-time interaction . There was no difference in total chronic respiratory disease question naire score between groups at baseline or at any time interval despite a significant difference with time . There was a clear deterioration in functional exercise capacity and health-related quality of life after completion of respiratory rehabilitation but no difference between the groups Background Pulmonary rehabilitation programs have been shown to increase functional exercise capacity and quality of life in COPD patients . However , following the completion of pulmonary rehabilitation the benefits begin to decline unless the program is of longer duration or ongoing maintenance exercise is followed . Therefore , the aim of this study is to determine if supervised , weekly , hospital-based exercise compared to home exercise will maintain the benefits gained from an eight-week pulmonary rehabilitation program in COPD subjects to twelve months . Methods Following completion of an eight-week pulmonary rehabilitation program , COPD subjects will be recruited and r and omised ( using concealed allocation in numbered envelopes ) into either the maintenance exercise group ( supervised , weekly , hospital-based exercise ) or the control group ( unsupervised home exercise ) and followed for twelve months . Measurements will be taken at baseline ( post an eight-week pulmonary rehabilitation program ) , three , six and twelve months . The exercise measurements will include two six-minute walk tests , two incremental shuttle walk tests , and two endurance shuttle walk tests . Oxygen saturation , heart rate and dyspnoea will be monitored during all these tests . Quality of life will be measured using the St George 's Respiratory Question naire and the Hospital Anxiety and Depression Scale . Participants will be excluded if they require supplemental oxygen or have neurological or musculoskeletal co-morbidities that will prevent them from exercising independently . Discussion Pulmonary rehabilitation plays an important part in the management of COPD and the results from this study will help determine if supervised , weekly , hospital-based exercise can successfully maintain functional exercise capacity and quality of life following an eight-week pulmonary rehabilitation program in COPD subjects in Australia Background : Chronic obstructive pulmonary disease ( COPD ) is a leading cause of death across the world and will become increasingly common with an aging population . Pulmonary rehabilitation ( PR ) is an evidence -based , nonpharmacological intervention for individuals with COPD , targeting the secondary impairments of the disease . Although the benefits of participation in PR are well established , improvements in exercise tolerance and health status typically deteriorate following discharge . Challenges with long-term adherence to recommended exercise regimens are thought to explain much of this decline . Therefore , we developed a community-based exercise maintenance program for patients with COPD following discharge from PR . Objectives This manuscript ( 1 ) outlines the intervention , ( 2 ) describes how its effectiveness is being evaluated in a pragmatic r and omized controlled trial , and ( 3 ) summarizes the embedded process evaluation aim ing to underst and key barriers and facilitators for implementation in new environments . Methods Participating centers refer eligible individuals with COPD following discharge from their local PR program . Consenting patients are assigned to a year-long community exercise program or usual care using block r and omization and stratifying for supplemental oxygen use . Patients in the intervention arm are asked to attend an exercise session at least twice per week at their local community facility where their progress is supervised by a case manager . Each exercise session includes a component of aerobic exercise , and activities design ed to optimize balance , flexibility , and strength . All study participants will have access to routine follow-up appointments with their respiratory physician , and additional health care providers as part of their usual care . Assessment s will be completed at baseline ( post-PR ) , 6 , and 12 months , and include measures of functional exercise capacity , quality of life , self-efficacy , and health care usage . Intervention effectiveness will be assessed by comparing functional exercise capacity between intervention and control groups . A mixed- methods process evaluation will be conducted to better underst and intervention implementation , guided by Normalization Process Theory and the Consoli date d Framework for Implementation Research . Results Based on results from our pilot work , we anticipate a maintenance of exercise capacity and improved health-related quality of life in the intervention group , compared with a decline in exercise capacity in the usual care group . Discussion Findings from this study will improve our underst and ing of the effectiveness of community-based exercise programs for maintaining benefits following PR in patients with COPD and provide information on how best to implement them . If effective , the intervention represents an opportunity to transition patients from institutionally-based rehabilitative management to community-based care . The results of the process evaluation will contribute to the science of translating evidence -based programs into regular practice OBJECTIVES To assess the efficacy of a pulmonary rehabilitation programme lasting 24 months and carried out at primary care health centres in improving the quality of life of patients with moderate COPD , compared with a programme of 12 weeks pulmonary rehabilitation with the usual care . Secondary aims include the assessment of the effects of the programme on dyspnoea , exercise capacity , reduction of crises , hospital admissions and length of time in hospital . DESIGN R and omised clinical trial , with 3 groups in parallel and with blind evaluation . The control group will continue with the customary care . SUBJECT Patients attended at primary health care centres with a diagnosis , based on GOLD criteria , of moderate COPD . Patients will be recruited from 5 health centres . 56 patients per group are needed ( allowing for 20 % drop-outs ) to detect the minimum clinical ly meaningful differences between treatments , with an alpha error of 0.005 and statistical power of 80 % . INTERVENTION All eligible patients with signed informed consent will be r and omised into the following groups : a ) pulmonary rehabilitation for 12 weeks and programme maintenance for 24 months ; b ) pulmonary rehabilitation for 12 weeks without maintenance programme ; c ) control group continuing with customary care . Pulmonary rehabilitation will include educational sessions , respiratory physiotherapy and low-intensity physical exercise . Follow-ups will be at the end of the rehabilitation programme , and at one and 2 years . MEASUREMENTS Quality of life with the Chronic Respiratory Question naire , 6-minute walking test , Borg Dyspnoea Scale , Medical Research Council Dyspnoea Score , Lung Function Tests , and intervention group Background Chronic obstructive pulmonary disease ( COPD ) affects approximately 3 million people in the UK . An 8-week pulmonary rehabilitation ( PR ) course is recommended under current guidelines . However , studies show that initial benefits diminish over time . Objective We present here an economic evaluation conducted alongside a r and omised controlled trial ( RCT ) of a low-intensity maintenance programme over a time horizon of 1 year delivered in UK primary and secondary care setting s. Methods Patients with COPD who completed at least 60 % of a st and ard 8-week PR programme were r and omised to a 2-h maintenance session at 3 , 6 and 9 months ( n = 73 ) or treatment as usual ( n = 75 ) . Outcomes were change in Chronic Respiratory Question naire ( CRQ ) score , EQ-5D-based QALYs , cost ( price year 2014 ) to the UK NHS and social services over the 12 months following initial PR , and incremental cost-effectiveness ratios ( ICERs ) . Results At 12 months , incremental cost to the NHS and social services was −£204.04 ( 95 % CI −£1522 to £ 1114 ) . Incremental CRQ and QALY gains were −0.007 ( −0.461 to 0.447 ) and + 0.015 ( −0.050 to 0.079 ) , respectively . Based on point estimates , PR maintenance therefore dominates treatment as usual from the perspective of the NHS and social services in terms of cost per QALY gained . Whether it is cost effective in terms of CRQ depends on whether the £ 204 per patient could be reinvested elsewhere to a CRQ gain of greater than 0.007 . However , there is much decision uncertainty : 95 % CIs around increments did not exclude zero , and there is a 72.9 % ( 72.5 % ) probability that the ICER is below £ 20,000 ( £ 30,000 ) per QALY . Conclusion Future research should explore whether more intensive maintenance regimens offer benefit to patients at reasonable cost BACKGROUND Even after a rehabilitation program , levels of physical activity in COPD progressively decrease unless strategies to encourage activity are implemented . We analyzed the effects of the implementation of urban walking circuits on levels of physical activity and exercise capacity of patients with severe and very severe COPD after a rehabilitation program . METHOD A total of 83 patients were r and omized to either urban circuits group ( UCG ) or usual care in the non-circuit group ( NCG ) , after completing a 2-week rehabilitation program . Results were evaluated 9 months after completion of the rehabilitation program and were compared with a control group of 54 patients not enrolled in the rehabilitation program . RESULTS At the end of follow-up , UCG patients increased their physical activity by a mean of 32.4 ( SE = 5.9 ) min per day and 1.09 ( SE = 0.22 ) days walked per week ; 33.9 ( SE = 5.6 ) min per day and 1.12 ( SE = 0.24 ) days per week more compared to the NCG ( p < 0.001 ) . There was a significant positive correlation between the results of the 6-min walking test and minutes walked per day in the UCG ( r(2 ) = 0.52 , p < 0.05 ) but not in the NCG ( r(2 ) = 0.094 , p > 0.05 ) . Controls showed a significant decrease in exercise capacity and physical activity over the follow-up . CONCLUSIONS Urban circuits are an easy , inexpensive strategy , which demonstrated to be useful to stimulate physical activity in our population of severe and very severe COPD patients and result ed in increased exercise capacity even 9 months after completion of a rehabilitation program OBJECTIVE To examine the short- and long-term effects of an outpatient pulmonary rehabilitation program for COPD patients on dyspnea , exercise , health-related quality of life , and hospitalization rate . SETTING Secondary -care respiratory clinic in Barcelona . METHODS We conducted a r and omized controlled trial with blinding of outcome assessment and follow-up at 3 , 6 , 9 , 12 , 18 , and 24 months . Sixty patients with moderate to severe COPD ( age 65 + /- 7 years ; FEV(1 ) 35 + /- 14 % ) were recruited . Thirty patients r and omized to rehabilitation received 3 months of outpatient breathing retraining and chest physiotherapy , 3 months of daily supervised exercise , and 6 months of weekly supervised breathing exercises . Thirty patients r and omized to the control group received st and ard care . RESULTS We found significant differences between groups in perception of dyspnea ( p < 0.0001 ) , in 6-min walking test distance ( p < 0.0001 ) , and in day-to-day dyspnea , fatigue , and emotional function measured by the Chronic Respiratory Question naire ( p < 0 . 01 ) . The improvements were evident at the third month and continued with somewhat diminished magnitude in the second year of follow-up . The PR group experienced a significant ( p < 0.0001 ) reduction in exacerbations , but not the number of hospitalizations . The number of patients needed to treat to achieve significant benefit in health-related quality of life for a 2-year period was approximately three . CONCLUSION Outpatient rehabilitation programs can achieve worthwhile benefits that persist for a period of 2 years The short- and long-term outcome of exercise reconditioning on exercise tolerance and breathlessness scores were evaluated in a group of patients with severe chronic obstructive pulmonary disease ( COPD ) . After a combined initial program of eight weeks , the patients were r and omized into two groups : group A followed a supervised training program for another 12 weeks ; group B was discharged after this initial program and received written instructions to continue exercise training at home . The patients were evaluated at the start , after the initial eight weeks ' training , after six months , and after one year . For the total group , exercise tolerance , assessed by 12-minute walking distance , increased significantly from 784 m to 848 m ( p less than .05 ) after the initial program . Neither breathlessness scores nor spirometric data changed significantly . In group A , the increase in exercise tolerance persisted not only at the end of the continued training program but even at the end of the one-year follow-up . In group B , there was a progressive and significant decline of exercise tolerance during the one-year follow-up . Our data confirm that even in severe COPD patients , exercise tolerance can increase significantly without any change in spirometric data and without an increased tolerance for the sensation of dyspnea . A supervised training program must be continued to stabilize the obtained effects because even when an initial improvement is experienced , patients may lack motivation to continue an unsupervised training program Background : Pulmonary rehabilitation is successful in improving exercise capacity and quality of life in patients with chronic obstructive pulmonary disease ( COPD ) . However , training effects diminish over time . Objectives : We evaluated the effects of simple , daily , structured , self-monitored , home-based exercise training for patients with moderate COPD after a 3-week outpatient rehabilitation . Methods : We conducted a r and omized , controlled , observer-blind trial . Twenty patients were recruited . Ten patients performed home-based exercise training ( mean age 67 years , 95 % confidence interval [ CI ] 63–72 ; FEV1 58.6 % , 95 % CI 53.8–63.4 ) , and 10 patients served as controls ( mean age 72 years , 95 % CI 69–77 ; FEV1 62.5 % , 95 % CI 57.7–67.3 ) . At baseline , and after 3 and 6 months , we assessed exercise capacity ( 6-min walk test , 6MWT , primary endpoint ) , health-related quality of life ( Chronic Respiratory Question naire , CRQ ) and lung function . An intention-to-treat analysis was performed using two-way ANOVA models for comparison of time trends between r and om groups . Results : The training group had better results than the control group in 6MWT ( p = 0.033 ) , in CRQ total ( p = 0.027 ) , CRQ dyspnea ( p = 0.014 ) and CRQ fatigue ( p = 0.016 ) . Improvement in FEV1 was also better in the intervention group than in the control group ( p = 0.007 ) . Conclusions : We demonstrated that training effects obtained from an outpatient rehabilitation program can be maintained by home-based exercise training in patients with moderate COPD Objective : To assess whether a maintenance integrated health care programme is effective in improving functional and emotional dimensions of quality of life in patients with chronic obstructive pulmonary disease ( COPD ) after a first pulmonary rehabilitation . Design : Prospect i ve controlled trial . Setting : Three rehabilitation centres and three patient self-help associations within a health care network in France . Subjects : Forty patients with moderate to severe COPD . Interventions : After a first four-week inpatient pulmonary rehabilitation programme , patients took part in a maintenance integrated health care programme or usual care for 12 months . Main measures : The primary outcomes were the change in functional and emotional dimensions of quality of life measured by the St George ’s Respiratory Question naire ( SGRQ ) , the brief World Health Organization Quality of Life question naire ( Brief-WHOQOL ) and six specific questions using a 10-cm visual analogue scale . Secondary outcomes were change in exercise tolerance measured by six-minute walking test and cycle exercise . Results : At one year , the maintenance intervention ( n = 11 ) produced improvements in functional and emotional dimensions scores of quality of life and exercise tolerance . Patients in the usual aftercare group ( n = 16 ) exhibited maintenance of functional dimension scores of quality of life , but a clinical ly relevant decline in emotional scores of quality of life and in six-minute walking distance one year after the pulmonary rehabilitation . Conclusion : Patient self-help association seems to be an innovative and efficient organizational structure to support patients with COPD after pulmonary rehabilitation in real-life setting s. A distinction between emotional and functional dimensions of quality of life may improve the design and evaluation of integrated health care programmes in patients with COPD PURPOSE To evaluate the differences in the long-term outcomes of dyspnea , exercise performance , health-related quality of life , and health re source utilization following a dyspnea self-management program with 3 different " doses " of supervised exercise . PATIENTS AND METHODS In a prospect i ve , r and omized , single-blind , 1-year trial , patients with stable chronic obstructive pulmonary disease ( N = 103 ; age 66 + /- 8 , females 57 ; FEV1 44.8 % + /- 14 % predicted ) were r and omly assigned to either : ( 1 ) Dyspnea self-management program ( DM ) ; ( 2 ) DM plus 4 supervised exercise sessions ( DM-exposure ) ; or ( 3 ) DM plus 24 supervised exercise sessions ( DM-training ) . The dyspnea self-management program included individualized education and demonstration of dyspnea self-management strategies , an individualized home walking prescription , and biweekly nurse telephone calls . Outcomes were measured at baseline and every 2 months for 1 year . RESULTS The DM-training group had significantly greater improvements in dyspnea during incremental treadmill test and in exercise performance on the incremental and endurance treadmill tests at 6 and 12 months compared with the other 2 groups . Dyspnea with activities of daily living and self-reported physical functioning significantly improved for all groups over time . The dose-response relationship between supervised exercise and improvement in dyspnea present at 2 months was not sustained over the year . CONCLUSION Consistent with previous findings from evaluation studies of pulmonary rehabilitation programs , the greater number of supervised exercise training sessions improved laboratory dyspnea and performance more than the other two doses of exercise . In the long term , the improvement in dyspnea with activities of daily living and physical functioning was similar for all 3 groups The aim of this study was to investigate the impact of a physical activity (PA)-focused behavioural intervention during and after pulmonary rehabilitation ( PR ) on PA levels ( primary aim ) , health-related outcomes and self-efficacy ( secondary aims ) of patients with COPD . Thirty-two patients were r and omly assigned to an experimental group ( EG ) or control group ( CG ) . The EG received a PA-focused behavioural intervention during PR ( 3 months ) and follow-up support ( 3 months ) . The CG received PR ( 3 months ) . Daily PA was collected : number of steps ; time spent in moderate-to-vigorous PA ( MVPA ) , total PA and sedentary activities ( SA ) . Secondary outcomes comprised exercise capacity , muscle strength , health-related quality of life ( HRQOL ) and self-efficacy . Measures were collected at baseline , 3 and 6 months . Compared with the CG , the EG improved the number of steps ( p = 0.006 ) and time spent in MVPA ( p = 0.007 ) , total PA ( p = 0.014 ) and SA ( p = 0.018 ) at 3 months . Differences were maintained after follow-up support ( 0.025 ≤ p ≤ 0.040 ) , except for SA ( p = 0.781 ) . Exercise capacity , muscle strength and HRQOL were increased at 3 and 6 months ( p ≤ 0.002 ) with no between-group differences ( 0.148 ≤ p ≤ 0.987 ) . No changes were observed in self-efficacy ( p = 0.899 ) . A PA-focused behavioural intervention during and after PR may improve patients ' PA levels . Further research is warranted to assess the sustainability of the findings |
12,330 | 27,707,850 | Of the currently used imaging techniques , leukocyte scintigraphy has satisfactory accuracy in confirming or excluding periprosthetic hip infection .
Although not significantly different , combined leukocyte and bone marrow scintigraphy was the most specific imaging technique .
FDG PET has an appropriate accuracy in confirming or excluding periprosthetic hip infection , but may not yet be the preferred imaging modality because of limited availability and relatively higher cost . | BACKGROUND Various imaging techniques are used for excluding or confirming periprosthetic hip infection , but there is no consensus regarding the most accurate technique .
The objective of this study was to determine the accuracy of current imaging modalities in diagnosing periprosthetic hip infection . | Aim To assess the extent to which bone marrow scintigraphy ( BMS ) makes the interpretation of leucocyte scintigraphy ( LS ) easier and improves its diagnostic value . Methods Seventy-three 111In LSs , 99mTc hydroxymethylene diphosphonate bone scintigraphies ( BSs ) and 99mTc sulfur colloid BMSs were performed in 60 patients with suspected infection related to a hip prosthesis or knee prosthesis , either in situ ( + group , n=43 ) or after removal for septic loosening ( −group , n=30 ) . Bacteriological sample s were obtained from all patients . LS was interpreted together with BS ( LS-BS ) or with BMS ( LS-BMS ) by three independent readers . Results The concordance among readers , estimated by the kappa test , was average with LS-BS ( κ/κm coefficients=0.58 , 0.58 and 0.46 , respectively , for the three pairs of readers ) and excellent with LS-BMS ( κ/κm coefficients=1.00 for the three pairs of readers ) . With LS-BS , 64/219 interpretations were equivocal whereas only one was equivocal with LS-BMS . Sensitivity , specificity and accuracy of LS-BMS were , respectively , 80 % , 94 % and 91 % in the+group , and 33 % , 100 % and 93 % in the−group . Conclusion We conclude that ( 1 ) the interpretation of the results for LS-BMS is very easy , in contrast to LS-BS ; ( 2 ) the diagnostic value of LS-BMS for detecting infected joint prostheses is good ; and ( 3 ) additional data are needed to assess the accuracy of LS-BMS when the prosthesis has been removed Purpose This study aims to assess and compare the value of FDG PET with combined 111In-labeled leukocyte/99mTc-sulfur colloid bone marrow ( WBC/BM ) imaging for diagnosing infection in hip and knee prostheses . Methods In this prospect i ve study , patients with painful hip or knee arthroplasty , who were scheduled to undergo clinical and diagnostic evaluation for prosthesis revision , were included . They have been studied by using FDG PET and WBC/BM scan . This study was institutional review board approved and Health Insurance Portability and Accountability Act compliant . All patients provided written informed consent . Results A total of 134 hip and 87 knee prostheses , suspected of being either infected or noninfectious loosening , were evaluated . All 221 prostheses underwent FDG PET , whereas both WBC/BM imaging and FDG PET were performed in 88 prostheses . The initial analysis of data from the WBC/BM images demonstrated somewhat suboptimal results compared with those of FDG PET scans on 88 patients . In addition , some patients were not willing to undergo both procedures and therefore participate in this study . Therefore , a decision was made to eliminate WBC/BM imaging from the procedures for the remainder of this research study . This decision was reached partly because of the significant radiation dose delivered from labeled WBC and safety issues related to preparing these labeled cells . Final diagnosis was based on microbiological examinations of the surgical specimens in 125 prostheses and joint aspirations combined with the clinical follow-up of 6 months or more in 86 prostheses . The sensitivity , specificity , positive predictive value , and negative predictive value of FDG PET in hip prostheses were 81.8 % , 93.1 % , 79.4 % , and 94.0 % , respectively , and in knee prostheses were 94.7 % , 88.2 % , 69.2 % , and 98.4 % , respectively . The sensitivity , specificity , positive predictive value , and negative predictive value of WBC/BM imaging in hip prostheses were 38.5 % , 95.7 % , 71.4 % , and 84.6 % , respectively , and in knee prostheses were 33.3 % , 88.5 % , 25.0 % , and 92.0 % , respectively . In those cases that underwent both FDG PET and WBC/BM imaging , there was a trend ( P = 0.0625 ) toward a higher sensitivity for FDG PET in hip prostheses , whereas other comparisons did not show any significant differences between the 2 imaging modalities . Conclusions Based on this study , the diagnostic performance of FDG PET scan in detecting infection in painful hip and knee prostheses is optimal for routine clinical application . Considering the complexity and costs of WBC/BM imaging and related safety issues associated with this preparation , FDG PET seems to be an appropriate alternative for assessing these patients PURPOSE To prospect ively determine the accuracy of computed tomography ( CT ) in the detection of painful infection at the site of hip prosthesis before surgery . MATERIAL S AND METHODS Helical CT examinations of hip prostheses were prospect ively performed before surgery after a st and ard clinical and radiologic examination of 65 patients . CT scans and conventional radiographs were review ed for periprosthetic bone abnormalities , and CT scans were review ed for periprosthetic soft-tissue abnormalities ( joint distention , fluid-filled bursae , and fluid collection in muscles and perimuscular fat ) . Patients subsequently underwent revision arthroplasty within 1 month , and infection was diagnosed in 12 ( 19 % ) patients . RESULTS Infection was detected clinical ly in 25 % of patients . Periprosthetic bone abnormalities did not allow differentiation of infection from complications not related to sepsis , except for periostitis , with 100 % specificity but only 16 % sensitivity . Soft-tissue findings were accurate for detection of infection , with 100 % sensitivity and 87 % specificity . Fluid collection in muscles and perimuscular fat had a 100 % positive predictive value , and absence of joint distention had a 96 % negative predictive value . CONCLUSION CT is accurate in the diagnosis of painful infection at the site of a hip prosthesis on the basis of soft-tissue findings , whereas periprosthetic bone abnormalities are not useful Aim To analyse the role played by bone scintigraphy in the diagnosis of infected joint prostheses . Methods The study included 77 patients , aged 32–77 years , in whom infection of a joint prosthesis ( 48 hip , 29 knee ) was suspected . In all patients the following examinations were performed consecutively : a two-phase 99mTc methylene diphosphonate ( 99mTc-MDP ) bone scan , a 99mTc hexamethylproplyene amine oxime ( 99mTc-HMPAO ) labelled white blood cell ( WBC ) scan , and a 99mTc microcolloid bone marrow ( BM ) scan . The minimum interval between examinations was 48 h. The diagnoses were based on data obtained from bacteriological cultures . Results The bone scan was positive in all patients and 28 of them had an infection ( sensitivity 100 % , specificity 0 % ) . The WBC scan was positive in 61 patients but only 27 had an infection . The WBC scan was negative in 16 patients , and the possibility of infection was discarded in 15 of these cases ( sensitivity 96 % , specificity 30 % ) . The results of the bone marrow scan were not compatible with those of the WBC scan ( suggestive of infection ) in 27 patients : 26 of them had prosthesis infection . The results of both examinations were compatible in the other 34 patients and the possibility of infection was discarded in 33 of these patients ( sensitivity 92.8 % , specificity 98 % ) . The addition of a BM scan to a WBC scan decreased the sensitivity from 96 % to 92.8 % but increased specificity from 30 % to 98 % . The addition of a bone scan to this dual combination did not alter the results . Conclusions When infection of a prosthesis is suspected the diagnostic procedure should start with a WBC scan followed , if positive , by a BM scan . This procedure reduces the cost , the time required for a diagnosis , and the dose of radiation received by the patient Ten per cent of patients with hip replacement will eventually complain of significant pain after surgery , often requiring a revision arthroplasty . The majority of these patients experience aseptic loosening rather than infection . Despite significant advances made in diagnostic imaging , distinguishing infection from aseptic loosening remains a significant challenge . Imaging using fluorodeoxyglucose ( FDG ) positron emission tomography ( PET ) has been reported to have excellent sensitivity in detecting infections associated with hip prostheses . However , in some studies , a high rate of false positive results has been reported , especially when increased tracer uptake adjacent to the prosthesis ( which is not surrounded by bone ) is used as the sole criterion for diagnosing infection . The objective of this investigation was to determine the optimal criteria for diagnosing periprosthetic infection , thereby avoiding false positive results in this setting . A total of 41 total hip arthroplasties from 32 patients and for whom complete clinical follow-up was available were included in this analysis . The location and intensity of FDG uptake were determined for each scan . Final diagnosis was made by microbiology , histopathology , surgical findings and clinical follow-up . Patients who did not undergo surgery were followed up to at least 9 months . Twelve patients were proven eventually to have periprosthetic infection . Images from 11 of these patients displayed increased tracer uptake along the interface between bone and prosthesis . The intensity of the increased tracer uptake varied from mild to moderate , with st and ardized uptake values less than 2 . In contrast , images from uninfected , loose hip prostheses revealed very intense uptake around the head or neck of the prosthesis with st and ardized uptake values as high as 7 . It is concluded that the intensity of increased FDG uptake is less important than the location of increased FDG uptake when FDG PET is used to diagnose periprosthetic infection in patients with hip arthroplasty . Using increased uptake as the sole criterion for diagnosing infection will result in false positive results in this setting To determine the value of immunoscintigraphy ( IS ) with antigranulocyte monoclonal antibodies ( Mab ) in the diagnosis of subacute or chronic infection of hip prostheses , we prospect ively studied 57 patients ( 23 women and 34 men ; age 29–92 years , mean 72.7 years ) sent to our institution in the past 6 years for clinical suspicion of septic loosening of a hip prosthesis . Nineteen patients had bilateral prostheses and one of them was studied twice . A total of 78 prostheses were examined . All patients had three-phase bone scans followed by IS with technetium-99 m antigranulocyte Mab BW 250/183 . Intervals between bone scans and IS varied from 2 days to 4 weeks . Final diagnosis was assessed by culture in 48 cases ( articular puncture or intraoperative sampling ) and by clinical follow-up of at least 8 months in 30 cases . Twelve prostheses were considered septic and 66 non-septic . The overall sensitivity and specificity were 92 % and 64 % respectively for bone scans , 67 % and 75 % for IS and 67 % and 84 % for both modalities together . In three cases , IS was doubtful and the final clinical diagnosis was negative for infection . False-positive results were observed in the presence of massive loosening of the prosthesis or in association with metaplastic peri-articular bone formation . In three of the four false-negative results , infection was proven only after enrichment of the culture , and the bacterium wasStaphylococcus epidermidis . In 12/33 ( 36 % ) positive bone scans IS allowed the diagnosis of infection to be excluded . Overall accuracy of both modalities together was 81 % and the negative predictive value was 93 % , which compares favourably with the results reported for other non-invasive methods We compared the accuracy of fluorine-18 labelled 2-fluoro-2-deoxy-d-glucose positron emission tomography ( 18FDG PET ) with that of technetium-99 m hexamethylpropylene amine oxime leucocyte scintigraphy ( LS ) in the detection of infected hip prosthesis . Seventeen patients with a hip prosthesis suspected for infection were prospect ively included and underwent 99mTc-methylene diphosphonate bone scintigraphy ( BS ) , LS and an 18FDG-PET scan within a 2-week period . Seven volunteers with ten asymptomatic hip prostheses were used as a control group and underwent BS and an 18FDG-PET scan . Bacteriology of sample s obtained by surgery or by needle aspiration and /or clinical follow-up for up to 6 months were used as the gold st and ard . Planar images of BS and LS ( 4 and 24 h p.i . ) were acquired , followed by single-photon emission tomography ( SPET ) LS images ( after 4 h ) . These images were scored as positive or negative by two experienced readers . The 18FDG-PET scans of the patients were compared with the tracer distribution pattern in the asymptomatic control group and with BS . A phantom study was performed in order to identify artefacts . For this purpose , three different attenuation correction methods were tested . The combined analysis of the planar BS and LS result ed in a 75 % sensitivity and a 78 % specificity . The SPET LS images showed a better lesion contrast , result ing in an 88 % sensitivity and a 100 % specificity , while 24-h planar images were of no additional value . The analysis of PET images alone result ed in an 88 % sensitivity and a 78 % specificity . The combination of 18FDG-PET and BS images result ed in an 88 % sensitivity and a 67 % specificity . Given the presence of small errors near the edge of the metal , which can induce significant artefacts in the corrected emission image , we decided to use the data without attenuation correction . In this preliminary study , 18FDG-PET scans alone showed the same sensitivity as combined BS and LS , although the specificity was slightly lower The purpose of this study was to compare the utility of 99mTc labelled ciprofloxacin ( Infecton ) imaging with the 99mTc white blood cell and three-phase bone imaging procedures for identifying hip prosthesis infection . We studied 30 symptomatic patients in whom infection was confirmed in eight and excluded in 22 cases based on clinical and microbiological findings . 99mTc ciprofloxacin images were obtained at 1 , 4 and 24 h after the injection of the tracer , and the data were compared to those obtained from 99mTc leukocyte and three-phase bone imaging . The 99mTc ciprofloxacin imaging correctly identified all true infections . In 13 ( 59 % ) of the non-infected patients , non-specific uptake of 99mTc ciprofloxacin was found in the 1-h and 4-h images , which disappeared , however , in the 24-h images . When the early and late 99mTc ciprofloxacin images were compared , the specificity was found to improve from 41 % to 95 % , positive predictive value from 38 % to 89 % , and the diagnostic accuracy from 57 % to 97 % . The accuracy of the conventional 99mTc leukocyte imaging was 90 % . Dynamic bone imaging also yielded abnormal findings in all the infected patients although also in 23 % of the non-infected patients . Current data indicate that 99mTc ciprofloxacin is a useful method for confirming hip prosthesis infection . The diagnostic efficiency of this method is improved when the imaging time is extended to 24 h post-injection of the tracer UNLABELLED The objectives of this study were to investigate (18)F-FDG imaging , using a coincidence detection system , for diagnosing prosthetic joint infection and to compare it with combined (111)In-labeled leukocyte/(99m)Tc-sulfur colloid marrow imaging in patients with failed lower extremity joint replacements . METHODS Fifty-nine patients --with painful , failed , lower extremity joint prostheses , 40 hip and 19 knee -- who underwent (18)F-FDG , labeled leukocyte , and bone marrow imaging , and had histopathologic and microbiologic confirmation of the final diagnosis , formed the basis of this investigation . (18)F-FDG images were interpreted as positive for infection using 4 different criteria : criterion 1 : any periprosthetic activity , regardless of location or intensity ; criterion 2 : periprosthetic activity on the (18)F-FDG image , without corresponding activity on the marrow image ; criterion 3 : only bone-prosthesis interface activity , regardless of intensity ; criterion 4 : semiquantitative analysis --a lesion-to- background ratio was generated , and the cutoff value yielding the highest accuracy for determining the presence of infection was determined . Labeled leukocyte/marrow images were interpreted as positive for infection when periprosthetic activity was present on the labeled leukocyte image without corresponding activity on the marrow image . RESULTS Twenty-five ( 42 % ) prostheses , 14 hip and 11 knee , were infected . The sensitivity , specificity , and accuracy of (18)F-FDG , by criterion , were as follows : criterion 1 : 100 % , 9 % , 47 % ; criterion 2 : 96 % , 35 % , 61 % ; criterion 3 : 52 % , 44 % , 47 % ; criterion 4 : 36 % , 97 % , 71 % . The sensitivity , specificity , and accuracy of labeled leukocyte/marrow imaging were 100 % , 91 % , and 95 % , respectively . WBC/marrow imaging , which was more accurate than any of the (18)F-FDG criteria for all prostheses , as well as for hips and knees separately , was significantly more sensitive than criterion 3 ( P < 0.001 ) and criterion 4 ( P < 0.001 ) and was significantly more specific than criterion 1 ( P < 0.001 ) , criterion 2 ( P < 0.001 ) , and criterion 3 ( P < 0.001 ) . CONCLUSION Regardless of how the images are interpreted , coincidence detection-based (18)F-FDG imaging is less accurate than , and can not replace , labeled leukocyte/marrow imaging for diagnosing infection of the failed prosthetic joint Pain is a common unspecific symptom in orthopaedic prosthetics . The accurate differentiation between synovitis , loosening or infection is often difficult with conventional X-rays , arthrography or bone scintigraphy . Because of the high glucose uptake of inflammatory cells , [18F]fluorodeoxyglucose ( 18F-FDG ) is an appropriate tracer for the evaluation of suspected inflammation or infection . In this preliminary study we describe 18F-FDG PET findings in patients referred for evaluation of painful hip or knee prostheses . We studied 23 patients with 28 prostheses , 14 hip and 14 knee prostheses , who had a complete operative or clinical follow-up . 18F-FDG PET scans were obtained with an ECAT EXACT HR+ PET scanner . High glucose uptake in the bone prostheses interface was considered as positive for infection , an intermediate uptake as suspect for loosening , and uptake only in the synovia was considered as synovitis . The imaging results were compared with operative findings or clinical outcome . PET correctly identified three hip and one knee prostheses as infected , two hip and two knee prostheses as loosening , four hip and nine knee prostheses as synovitis , and two hip and one knee prostheses as unsuspected for loosening or infection . In three patients covered with an exp and er after explantation of an infected prosthesis PET revealed no further evidence of infection in concordance with the clinical follow-up . PET was false negative for loosening in one case . Our preliminary results suggest that FDG PET could be a useful tool for differentiating between infected and loose orthopaedic prostheses as well as for detecting only inflammatory tissue such as synovitis Abstract . Hip arthroplasty is a common surgical procedure , but the diagnosis of infection associated with hip arthroplasty remains challenging . Fluorine-18 fluoro-2-deoxy-D-glucose positron emission tomography ( FDG-PET ) has been shown to be a promising imaging modality in setting s where infection is suspected . However , inflammatory reaction to surgery can result in increased FDG uptake at various anatomic locations , which may erroneously be interpreted as sites of infection . The purpose of this study was to assess the patterns and time course of FDG accumulation following total hip replacement over an extended period of time . Firstly , in a prospect i ve study nine patients with total hip replacement were investigated to determine the patterns of FDG uptake over time . Three FDG-PET scans were performed in each patient at about 3 , 6 and 12 months post arthroplasty . Secondly , in a retrospective analysis , the medical and surgical history and FDG-PET imaging results of 710 patients who had undergone whole-body scans for the evaluation of possible malignant disorders were review ed . The history of arthroplasty and FDG-PET findings in the hip region were review ed for this study . Patients with symptomatic arthroplasties or related complaints during FDG-PET scanning were excluded from the analysis . During the entire study period , all nine patients enrolled in the prospect i ve study were demonstrated to have increased FDG uptake around the femoral head or neck portion of the prosthesis that extended to the soft tissues surrounding the femur . Among the patients review ed in the retrospective study , 18 patients with a history of 21 hip arthroplasties who were asymptomatic at the time of FDG-PET scan met the criteria for inclusion . The time interval between the hip arthroplasty and the FDG-PET study ranged from 3 months to 288 months ( mean±SD : 80.4±86.2 months ) . In 81 % ( 17 of 21 ) of these prostheses , increased FDG uptake could be noted around the femoral head or neck portion of the prosthesis . The average time interval between arthroplasty and FDG-PET scan in these patients was 71.3 months . In only four prostheses ( 19 % , 4 of 21 ) was no abnormally increased FDG uptake seen around the prostheses or adjacent sites . The average time interval in these patients was 114.8 months . It is concluded that following hip arthroplasty , non-specifically increased FDG uptake around the head or neck of the prosthesis persists for many years , even in patients without any complications . Therefore , to minimize the number of false-positive results for infection with PET studies obtained to evaluate a painful hip prosthesis , caution should be exercised when interpreting FDG uptake around the head or neck portion of the prosthesis AIM To evaluate the usefulness of (99m)Tc-Sulphur colloid when combined with leukocyte scintigraphy in suspected prosthetic hip infection , comparing the results with information from (99m)Tc-HMPAO-leukocyte scintigraphy alone . MATERIAL S AND METHODS Seventy patients ( 42 women , 28 men ; mean age 68 + /- 13 years ) with painful hip prostheses and suspicion of infection were evaluated prospect ively . All patients had bone scintigraphy , (99m)Tc-HMPAO-labelled white blood cell scintigraphy and (99m)Tc-Sulphur colloid bone marrow scintigraphy . ESR and CRP levels were measured in all patients . The final diagnosis was made with microbiological findings or by clinical follow up of at least 12 months . RESULTS Infections were diagnosed in 12 of the 70 patients ( 3 coagulase-negative Staphylococcus , 2 Staphylococcus aureus , 2 Staphylococcus epidermidis , 2 enterococcus and 3 polymicrobial agents ) . ESR and CRP values were higher in patients with infection than in patients without infection ( 51.8 + /- 29.4 vs. 25.4 + /- 16.4 and 2.8 + /- 2.2 vs. 1.1 + /- 1.3 , respectively ; p < 0.05 ) . Bone scintigraphy did not show a characteristic pattern to differentiate infection from aseptic loosening . The pool phase of the bone scintigraphy was positive in only 3/12 patients with infection ( 25 % ) . Sensitivity and specificity of the leukocyte scintigraphy was 83 % and 57 % , respectively . When the results of the bone marrow scintigraphy were added , these values increased to 92 % and 98 % , respectively . CONCLUSION Performing bone marrow scintigraphy significantly improves results when compared with leukocyte scintigraphy alone in the diagnosis of infected hip prostheses . Bone scintigraphy did not help to differentiate aseptic loosening from infection in this series Infection following hip arthroplasties can present a diagnostic challenge . No test is 100 % sensitive and 100 % specific ; this prospect i ve study was undertaken to evaluate the utility of FDG-PET imaging for diagnosing infected joint replacements . 24 hip joint replacements were studied prospect ively and we have complete diagnoses with clinical signs and symptoms , laboratory test , radiography , joint aspiration , radionuclide imaging including FDG-PET , and histopathologic examination . 11 of 24 prostheses were infected . The sensitivity and specificity of PET for detecting infection associated with prostheses were 64,3 % and 64,7 % respectively , in our h and s. FDG imaging is not useful in patients with suspected prosthetic infection like a screening test Abstract A battery of diagnostic tests is often required to differentiate aseptic loosening from periprosthetic infection since the gold st and ard remains elusive . We design ed a prospect i ve study to determine the accuracy of fluorodeoxyglucose positron emission tomography ( FDG-PET ) imaging in diagnosing periprosthetic infection in a large multicenter setting . One hundred and thirteen patients with 127 painful hip prostheses were evaluated by FDG-PET . Images were considered positive for infection if PET demonstrated increased FDG activity at the bone-prosthesis interface of the femoral component . A combination of preoperative tests , intraoperative findings , histopathology , and clinical followup constituted the gold st and ard for diagnosing infection . Among the 35 positive PET scans , 28 hips were confirmed infected according to our criteria for diagnosing periprosthetic infection . Of the 92 hip prostheses with negative FDG-PET findings , 87 were considered aseptic . The sensitivity , specificity , positive and negative predictive values for FDG-PET were 0.85 ( 28 of 33 ) , 0.93 ( 87 of 94 ) , 0.80 ( 28 of 35 ) , and 0.95 ( 87 of 92 ) , respectively . The overall accuracy of this novel noninvasive imaging modality reached 0.91 ( 115 of 127 ) . Based on our results , FDG-PET appears a promising and accurate diagnostic tool for distinguishing septic from aseptic painful hip prostheses . Level of Evidence : Level II , diagnostic study . See Guidelines for Authors for a complete description of levels of evidence Although the diagnosis of hip prosthesis infection is clinical ly important , X-ray studies , blood chemistry and synovial fluid aspiration may be unreliable for this purpose . The aim of this study was to evaluate whether extending the time for technetium-99 m labelled leucocyte imaging to 24 h post injection improves the accuracy of diagnosis of hip replacement infections . We studied 64 symptomatic patients with hip prostheses . The presence of infections was verified by intraoperative bacterial cultures , and infection was excluded either by negative operative findings or by follow-up for at least 1 year . Leucocyte imaging was done with 99mTc-hexamethylpropylene amine oxime (HMPAO)-labelled leucocytes at 2–4 h ( routine images ) and at 24 h ( late images ) after the injection of the leucocytes . In addition , bone imaging was carried out with 99mTc-hydroxydiphosphonate ( HDP ) at the arterial , soft tissue and metabolic phases . A st and ardised method was used to compare leucocyte images with bone metabolic images . In this material , there were six confirmed infections . All the bone imaging methods had a sensitivity of 100 % in detecting prosthesis infections whereas the specificity varied from only 2 % to 82 % . Routine leucocyte imaging was less sensitive ( 50 % vs 83 % ) and less specific ( 90 % vs 100 % ) than late leucocyte imaging . All tests had a high negative predictive value for excluding infection ( 95%–100 % ) . However , both bone ( 10%–38 % ) and routine leucocyte imaging ( 33 % ) showed a poor positive predictive value ( PPV ) , whereas late leucocyte imaging had a PPV of 100 % and a diagnostic accuracy of 98 % . We conclude that late leucocyte imaging improves the specificity of diagnosis of infected hip prostheses . This type of imaging procedure should be combined with three-phase bone scintigraphy in studies of patients with painful joint replacement AIM Hip prosthesis implantation has witnessed a significant increase in recent years . Despite the advantages of this surgical procedure , it has some complications , the most serious of which is prosthetic infection . This study was conducted to investigate the feasibility of 99mTc-UBI scintigraphy in detection of infectious foci in painful hip prosthesis . UBI ( Ubiquicidin 29 - 41 ) is an antimicrobial peptide fragment with the ability to target the bacterial colony directly . PATIENTS , METHODS 34 patients , aged 20 - 79 years , with painful hip prosthesis were included . 99mTc-UBI scan and three phase bone scan were performed and two nuclear medicine specialists interpreted the UBI scans with and without bone scan results at h and . Both qualitative and semi-quantitative methods were used to interpret the 30 minute post injection images . The patients were actively followed up . According to the surgical findings , microbiological culture and active follow up , final diagnosis was made . RESULTS 24 negative and 10 positive UBI scans were recorded . The sensitivity , specificity , negative and positive predictive values and accuracy of the study were all 100 % . Bone scan did not have any influence on UBI interpretation . We were able to achieve excellent differentiation between infected and non-infected prostheses with a cut off value of 1.8 for target to non target ( T/NT ) ratio . No adverse effects were noticed following UBI scan . CONCLUSION Based on the findings , the authors believe that 99mTc-UBI scintigraphy , with its high sensitivity and specificity , provides the physician with an excellent tool for differentiating infection from aseptic loosening of hip prostheses . Using this radiopharmaceutical , it is possible to obtain highly accurate results only 30 minutes after the beginning of the study We aim ed to compare the accuracy of fluorodeoxyglucose positron emission tomography ( FDG-PET ) with technetium-99 m sulfur colloid (111)indium-labeled white blood cell scintigraphy ( TcSC-Ind BM/WBC ) in diagnosis of periprosthetic infection . Eighty-nine patients with 92 painful hip prostheses were recruited prospect ively and given the option of undergoing either combined FDG-PET and TcSC-Ind BM/WBC or FDG-PET only . FDG-PET correctly diagnosed 20 of the 21 infected cases ( sensitivity , 95.2 % ) and ruled out infection in 66 of the 71 aseptic hips ( specificity , 93 % ) corresponding to a positive predictive value of 80 % ( 20/25 ) and a negative predictive value of 98.5 % ( 66/67 ) . TcSC-Ind BM/WBC correctly identified 5 of the 10 infected cases ( sensitivity , 50 % ) and 39 of 41 aseptic cases ( specificity , 95.1 % ) corresponding to a positive and negative predictive values of 41.7 % ( 5/12 cases ) and 88.6 % ( 39/44 cases ) , respectively . Based on these preliminary results , FDG-PET appears to be a promising diagnostic tool for distinguishing septic from aseptic painful hip prostheses |
12,331 | 20,398,361 | The main findings based on this evidence were : ( 1 ) school-based interventions generally lead to short term improvement in physical activity levels , but there were large differences between interventions with regard to effect sizes ; ( 2 ) a multi-component approach ( including environmental components ) generally result ed in larger effect sizes , thereby providing evidence for the assumption that a multi-component approach should produce synergistic results ; and ( 3 ) if an intervention aim ed to affect more health behaviours besides physical activity , then the intervention appeared to be less effective in favour of physical activity | This commentary adds effect sizes to the recently published systematic review by De Meester and colleagues and provides a more detailed insight into the effectiveness of interventions to promote physical activity among European teenagers . | A r and omised control trial evaluated the effectiveness of a theory-based persuasive leaflet design ed to encourage students to undertake at least one additional physical exercise session a week . Participants were 503 secondary school students attending a school in South-East Engl and . The leaflet was written to target potentially modifiable cognitive antecedents of exercise specified by the Theory of Planned Behaviour . It was separately augmented with two cognitive change techniques , result ing in three intervention conditions , leaflet alone ; leaflet plus motivational quiz , and leaflet plus implementation intention prompt , as well as a no-leaflet control condition . Cognitions and behaviour were measured immediately before and 3 weeks after intervention . The results showed that all three-leaflet interventions significantly increased reported exercise , intention to exercise and related cognitions , compared to the control condition , but did not differ in their impact . Mediation analysis showed that intervention effects on exercise were partially mediated by intentions and perceived behavioural control OBJECTIVES ICAPS ( Intervention Centred on Adolescents ' Physical activity and Sedentary behaviour ) is aim ed at preventing excessive weight gain and cardiovascular risk in adolescents by promoting physical activity ( PA ) with an emphasis on recreational and daily-life PA , with a lifelong perspective . DESIGN R and omized study design ed to last for four years . Study cohort constituted of 954 first-level students ( 91 % of eligible pupils ) , aged 11.7 + /- 0.6 y ( mean + /- SD ) from four pairs of schools r and omly selected in eastern France , after sociogeographical stratification . In each pair , intervention status was r and omised at school-level . The program , not limited to school setting s , involves multiple partners with three objectives : 1 ) changing attitudes through debates and access to attractive activities during breaks and after-school hours , 2 ) encouraging social support , 3 ) providing environmental conditions that enable PA . Adapted times and places , open participation , emphasis on fun , meeting with others and absence of competitive aspects are used to reduce usual barriers to PA . Accessibility and safety are permanent concerns . RESULTS Prevalence of overweight was 23.7 % . High participation rates were attained ( 50 % participated in at least one weekly activity ) . At six-month , the proportion of intervention adolescents not performing supervised PA out of academic PA was reduced by half ( 36 % to 17 % vs 42 % to 42 % in controls P < 10 - 4 ) ; the proportion of those spending > 3 h/day in sedentary occupations decreased ( 34 % to 28 % vs 27 % to 36 % ; P < 10 - 4 ) . CONCLUSION These data demonstrate the feasibility of implementing a multilevel PA intervention program in adolescents . Six-month results document increased PA and decreased sedentary behaviour Abstract Objectives : To evaluate the effectiveness of inviting teenagers to general practice consultations to discuss health behaviour concerns and appropriate follow up care . Design : R and omised controlled trial , with participants r and omised to a consultation ( intervention ) or usual care ( control ) . Question naires completed at baseline , 3 months , and 12 months . Setting : Eight general practice s in Hertfordshire , Engl and . Participants : 1516 teenagers aged 14 - 15 years . Intervention : Consultations with practice nurses to discuss health concerns and develop plans for healthier lifestyles . Main outcome measures : Mental and physical health , “ stage of change ” for health related behaviour , and use of health services . Results : At baseline 970 teenagers completed question naires ; 23 % smoked , 35 % had been drunk in the previous three months , 64 % considered they ate unhealthily , 39 % took little exercise , and 36 % had possible depression . 41 % ( 304 ) of teenagers invited attended for a consultation ; over one third ( 112 ) were offered follow up care . More intervention group teenagers reported positive movement in stage of change for diet and exercise and in at least one of four behaviours ( diet , exercise , smoking , drinking alcohol ) at 3 months ( 41 % v 31 % , P<0.01 ) , but this did not persist at 12 months . There was marginally more positive change in actual behaviour by intervention teenagers at 3 months ( 16 % v 12 % , P=0.06 ) . Recognition of possible depression result ed in improved mental health outcomes at 3 and 12 months . 97 % of attenders said they would recommend the intervention to a friend . Conclusions : Change in behaviour was slight but encouraging , and the intervention was well received and relatively cheap Interventions to promote physical activity are important in preventing children from becoming overweight . Many projects have been developed but only a few showed ( moderate ) effects . JUMP-in is a systematic ally developed primary -school-based intervention that focuses on the use of theory , environmental changes , parental influences and cooperation with multi-level parties in intervention development . The effects of JUMP-in were evaluated with a quasi-experimental pre-test/post-test research design . In total , 510 children from Grade s 4 , 5 and 6 of four intervention schools and two control schools in Amsterdam were followed for an intervention period of one school year . Changes in physical activity as well as in the social cognitive determinants were assessed using self-reports . In addition , a process evaluation has been executed . The results show that JUMP-in was effective in influencing physical activity , especially among children from Grade 6 . Children in the control group decreased their level of physical activity considerably , while activity levels in intervention children from Grade 6 remained stable . The intervention effects could not be explained by changes in the measured social cognitive determinants . In contrast , process information illuminated differences in intervention effects between the participating schools . The results from the JUMP-in study show the importance of intervention design s that focus on a theory-based mix of relevant environmental and social cognitive factors Physical activity levels in young adults are low . Research supports the use of the Transtheoretical Model of behaviour change ( TM ) in design ing physical activity interventions . This study used a pre-post r and omized control design to investigate the effectiveness of a self-instructional intervention for helping sedentary young adults to initiate physical activity . Post-intervention , significantly more of the experimental group ( 80 % ) , in comparison to the control group ( 68 % ) , improved their exercise stage of change ( SOC ) from baseline ( P < 0.05 ) . Discriminant analyses revealed that discrimination between stage improvement/non-improvement was possible using the processes of change data . Stage improvers scored significantly higher on all of the behavioral and four out of five of the cognitive processes of change . For stage improvers , the processes of self-re-evaluation and self-liberation were most frequently used , whilst social liberation was used significantly more by the experimental than the control group . This inexpensive , self-instructional intervention , based on the TM and the ' active living message ' , is an effective method of assisting sedentary young adults to progress through the exercise SOC Low levels of physical activity coupled with high levels of television viewing have been linked with obesity in children . The objective of this study was to assess the efficacy of ' Switch Off-Get Active ' , a 16-week controlled health education intervention , in increasing physical activity and reducing screen time and BMI in primary school children . A secondary objective was to compare children with high and low screen time . Participants were 312 children aged 10.2+/-0.7 years , attending nine schools in areas of social disadvantage . The 10-lesson , teacher-led intervention , conducted in spring 2003 , emphasised self-monitoring , budgeting of time and selective viewing . Differences , adjusted for baseline values by ANCOVA , existed between intervention and control children at follow-up for self-reported physical activity ( intervention + 0.84 30 min blocks/day , 95%CI 0.11 - 1.57 , p<0.05 ) and self-efficacy for physical activity ( p<0.05 ) but not self-reported screen time ( intervention--0.41 blocks/day , 95%CI--0.93 - 0.12 , p=0.13 ) or BMI ( p=0.63 ) . Cross-sectional comparisons at baseline indicated lower physical activity , self-efficacy for physical activity and aerobic fitness and a higher BMI in children with high screen time . In conclusion , health education interventions can increase physical activity in primary school children but follow-ups of longer duration may be needed to demonstrate intervention effects on BMI Background Aim ing at an active lifestyle , healthy food habits and non-smoking among Swedish children , the Swedish Heart Lung Foundation initiated the health educational programme ‘ An adventure with Pelle Pump ' . A study kit , including theoretical and practical material on heart-lung function and healthy behaviour , was offered to all fourth grade rs in Sweden . The impact of the programme was examined by study ing health behaviours and health knowledge among programme participants using non- participants as a control population . Methods A question naire on health behaviour and health knowledge was answered by a r and om sample of 1369 children from different social classes and living conditions . Children subjected to the programme formed the programme group ( n = 523 ) and those without exposure served as a control group ( n = 846 ) . Results Children in the programme group had a significantly higher level of knowledge ( P < 0.001 ) on questions relating to health behaviour and bodily functions . The actual health behaviour was , however , not affected by the programme . Conclusion Children exposed to a health education programme had , compared with a control population , 2 years after completing the programme , an increased level of knowledge ; however , no difference was found in health behaviour PURPOSE To evaluate the effects of a middle school physical activity intervention , new in combining an environmental and computer tailored component ; and to evaluate the effects of parental involvement . METHODS A clustered r and omized controlled design was used . A r and om sample of 15 schools with 7th and 8th grade rs was r and omly assigned to one of three conditions : ( a ) intervention with parental support , ( b ) intervention alone , and ( c ) control group . The intervention was new in combining environmental strategies with computer-tailored feedback to increase levels of moderate to vigorous physical activity . The intervention was implemented by the school staff . Physical activity was measured through a question naire in the total sample and with accelerometers in a sub sample of adolescents . RESULTS The intervention with parental support led to an increase in self-reported school-related physical activity of , on average , 6.4 minutes per day ( p < or = .05 , d = .40 ) . Physical activity of light intensity measured with accelerometers decreased with , on average , 36 minutes per day as a result of the intervention with parental support ( p < or = .05 , d = .54 ) . Physical activity of moderate to vigorous intensity measured with accelerometers significantly increased with on average 4 minutes per day in the intervention group with parental support , while it decreased with almost 7 minutes per day in the control group ( p < or = .05 , d = .46 ) . CONCLUSIONS The physical activity intervention , implemented by the school staff , result ed in enhanced physical activity behaviors in both middle school boys and girls . The combination of environmental approaches with computer-tailored interventions seemed promising OBJECTIVE To evaluate acceptability , feasibility and effectiveness of computer-tailored physical activity education among adolescents . METHODS Two classes of 7th grade rs from 10 r and omly selected schools were assigned to the intervention ( computer-tailored intervention , n=139 ) or control ( no-intervention , n=142 ) condition . Question naires were completed 1 week before and 3 months after the intervention . The computer-tailored intervention was completed during classes . RESULTS Students had few problems with the diagnostic questions and with the use of a computer . About half of the students evaluated the advice as interesting and easy to underst and and about 40 % as personally relevant , easy to use and credible . Half of students evaluated the advice as too long and only 33 % reported to have used the advice . The computer-tailored intervention was effective for increasing school related physical activity levels with on average 25 min per week ( F=3.4 , P < or = .05 ) , but not for increasing total physical activity or leisure time physical activity . CONCLUSIONS A 1-h computer-tailored intervention offered during class-time has the potential to increase school related physical activity . PRACTICE IMPLICATION S Although favourable effects of large scale implementation may be expected , some adaptations that might increase effectiveness should be investigated in the future PURPOSE To investigate the effect of a six-month teacher-led osteogenic physical activity program , vs. a self-led activity program , on ultrasound measurements of bone in inactive teenage girls . METHODS Ninety sedentary girls [ mean ( SD ) age 16.3 ( .6 ) years ] were identified from 300 assessed for physical activity across five schools in southeast Irel and . Schools were matched and r and omly assigned to a teacher-led physical activity ( TLPA ) program , a self-led physical activity ( SLPA ) program , or a control group . Broadb and ultrasound attenuation ( BUA ) , speed of sound ( SOS ) , and os calcis stiffness index ( OCSI ) were measured using a portable ultrasound machine . Anthropometry , aerobic fitness , calcium intake , and physical activity were assessed , and focus groups held one month after program completion . Descriptive statistics , paired t-tests , and analysis of variance were used to analyze the data . RESULTS Both intervention groups demonstrated significant improvements ( p < .05 ) in BUA , SOS , OCSI and aerobic fitness , i.e. , TLPA : + 14.9 % , + 21.9 % , + 15.9 % , and + 8.5 % , respectively , and SLPA : + 10.6 % , + 30.3 % , + 15.6 % , and + 5.1 % , respectively , with no change in controls . Differences between intervention groups and controls were significant for BUA and OCSI ( p < .05 ) . TLPA and SLPA groups engaged in an average of 4.5 and 3.4 hours/week of physical activity , respectively , over the intervention period . The SLPA group continued to exercise after the intervention had ceased , whereas the TLPA group did not . CONCLUSIONS Previously inactive teenage girls can adhere to an osteogenic activity program whether supervised or directing their own activity . Longer-term , sustainable initiatives with this age group are needed and might focus on developing personal skills for physical activity BACKGROUND This study examines whether the adolescents ' current levels of physical activity are increased by their physicians ' advice provided in the office , in accordance with the American Medical Association recommendation . METHODS The first adolescent ( 12 - 21 years old ) of whichever age and gender , passing through six family physicians ' offices during a 6-month period was assigned to the intervention group , and the second adolescent of the same age and gender was assigned to the control group . Each patient was classified as active , partially active , and inactive , according to how they answered the questions about their physical activity levels , and patients in the intervention group were then provided with reinforcement , increase , or initiation counseling , respectively . Identical procedures were repeated at the 6- and 12-month office visits . Changes in prevalence of activity , as well as , duration , frequency , and intensity of exercise and /or sports were verified at each visit . RESULTS Of the 87.5 % of the original sample that completed the survey , 6- and 12-month data were available for 70.1 % . Among the 392 adolescents that finished the study , those provided with counseling had 41.5 % more active adolescents , as well as 26.8 % , 38.0 % and 26.2 % higher duration , frequency and intensity , respectively , than the control group . CONCLUSIONS The proportion of active adolescents , as well as , the duration , frequency and intensity of leisure time exercise and /or sports are increased by physician advice BACKGROUND During recess , children can be active on a daily basis , making it an important school environmental factor for the promotion of health-related physical activity . The aim of the present study was to investigate the effects of providing game equipment on children 's physical activity levels during morning recess and lunch break in elementary schools . METHODS Seven elementary schools were r and omly assigned to the intervention group ( four schools ) , including 122 children ( 75 boys , 47 girls , mean age : 10.8 + /- 0.6 years ) , and to the control group ( three schools ) , including 113 children ( 46 boys , 67 girls , mean age : 10.9 + /- 0.7 years ) . Children 's activity levels were measured before and three months after providing game equipment , using MTI accelerometers . RESULTS During lunch break , children 's moderate and vigorous physical activity significantly increased in the intervention group ( moderate : from 38 to 50 % , vigorous : from 10 to 11 % ) , while it decreased in the control group ( moderate : from 44 to 39 % , vigorous : from 11 to 5 % ) . At morning recess , providing game equipment was effective in increasing children 's moderate physical activity ( from 41 to 45 % ) , while it decreased in the control group ( from 41 to 34 % ) . CONCLUSION Providing game equipment during recess periods was found to be effective in increasing children 's physical activity levels . This finding suggests that promoting physical activity through game equipment provision during recess periods can contribute to reach the daily activity levels recommended for good health |
12,332 | 15,846,647 | Skills based programs appear to be effective in deterring early-stage drug use . | BACKGROUND Drug addiction is a chronic , relapsing disease .
Primary interventions should be aim ed to reduce first use , or prevent the transition from experimental use to addiction .
School is the appropriate setting for preventive interventions .
OBJECTIVES To evaluate the effectiveness of school-based interventions in improving knowledge , developing skills , promoting change , and preventing or reducing drug use versus usual curricular activities or a different school-based intervention . | AIMS Despite widespread prevention efforts to decrease adolescent risk-taking , substance use and driving after drinking ( DD ) are prevalent in the United States . The current study compared the efficacy of an abbreviated version of Drug Abuse and Resistance Education ( DARE-A ) to a new Risk Skills Training Program ( RSTP ) . DESIGN Adolescent participation in drinking , drug use , DD and riding with a drunk driver was examined longitudinally . After baseline assessment s , adolescents were r and omly assigned to the RSTP . DARE-A or a no intervention control group and then completed 2-month post-test and 6-month follow-up assessment s. SETTING Adolescents attended a mid-sized suburban high school . PARTICIPANTS The sample ( N = 300 ) was comprised of 58 % females and the age range was 14 - 19 years . INTERVENTION The RSTP was developed to target several risk behaviors and to examine the feasibility of conducting a brief personalized prevention program in a group setting . DARE-A focused on increasing knowledge and underst and ing the deleterious effects of substance use . MEASUREMENTS Risk-taking behavior , perception of peer risk-taking and positive and negative alcohol expectancies were assessed . FINDINGS RSTP participants decreased participation in several risk behaviors at post-test , but reductions were not maintained at 6-month follow-up . The control and DARE-A groups increased their positive and decreased their negative alcohol expectancies . The control group increased their alcohol consumption . CONCLUSIONS Results suggest that a brief , personalized , group prevention program is a feasible approach to reducing adolescent risk-taking . Strategies must be developed to solidify these positive changes so that they are longer-lasting OBJECTIVE To evaluate the effect of the middle and junior high school Drug Abuse Resistance Education ( D.A.R.E. ) and D.A.R.E. Plus programs on drug use and violence . DESIGN R and omized controlled trial of 24 schools , with 3 conditions : D.A.R.E. only , D.A.R.E. Plus , and delayed program control . SETTING Schools and neighborhoods , primarily in Minneapolis-St Paul . PARTICIPANTS All seventh- grade students in 24 schools in the academic year 1999 - 2000 ( N = 6237 at baseline , 67.3 % were white , and there was 84.0 % retention at final follow-up ) . INTERVENTIONS The middle and junior high school D.A.R.E. curriculum in the 16 schools that received D.A.R.E. only and D.A.R.E. Plus . In the 8 schoolts that received D.A.R.E. Plus , additional components included a peer-led parental involvement classroom program called " On the VERGE , " youth-led extracurricular activities , community adult action teams , and postcard mailings to parents . The interventions were implemented during 2 school years , when the cohort was in the seventh and eighth grade s. MAIN OUTCOME MEASURES Self-reported tobacco , alcohol , and marijuana use ; multidrug use ; violence ; and victimization , assessed at the beginning and end of seventh grade and at the end of eighth grade . Growth curve analytic methods were used to assess changes over time by condition . RESULTS There were no significant differences between D.A.R.E. only and the controls ; significant differences among boys between D.A.R.E. Plus and controls for tobacco , alcohol , and multidrug use and victimization ; significant differences among boys between D.A.R.E. Plus and D.A.R.E. only in tobacco use and violence ; and no significant behavioral differences among girls . CONCLUSION D.A.R.E. Plus significantly enhanced the effectiveness of the D.A.R.E. curriculum among boys and was more effective than the delayed program controls , underscoring the potential for multiyear , multicomponent prevention programs and demonstrating sex differences in response to intervention programs Outcome research has shown that drug prevention programs based on theories of social influence often prevent the onset of adolescent drug use . However , little is known empirically about the processes through which they have their effects . The purpose of the present study was to evaluate intervening mechanism theories of two program models for preventing the onset of adolescent drug use . Analyses based on a total of 3077 fifth grade rs participating in the Adolescent Alcohol Prevention Trial revealed that both normative education and resistance training activated the causal processes they targeted . While beliefs about prevalence and acceptability significantly mediated the effects of normative education on subsequent adolescent drug use , resistance skills did not significantly predict subsequent drug use . More impressively , this pattern of results was virtually the same across sex , ethnicity , context ( public versus private school students ) , drugs ( alcohol , cigarettes , and marijuana ) and levels of risk and was durable across time . These findings strongly suggest that successful social influence-based prevention programs may be driven primarily by their ability to foster social norms that reduce an adolescent 's social motivation to begin using alcohol , cigarettes , and marijuana 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 The central aim of this study was to evaluate Project PRIDE , a school-based affective education program offered in select schools since 1970 and throughout the entire Philadelphia Public School System since 1981 . The primary purpose of the program is to increase youth 's resistance to drug use and abuse through weekly small group counseling sessions . The 12 weekly student sessions focused on developing self-awareness , life skills , knowledge , and appropriate attitudes about drugs . Project PRIDE also developed training modules for teachers and parents . Evaluation was by means of a true experimental pretest-posttest design , with r and om assignment to treatment and control groups . Measures of attitudes , self-reported drug use , and behavioral intentions were administered to students , teachers , and parents ; process evaluation measures of the student component were collected throughout the treatment period as well . Data analyses indicate that , while a few of the broad aims of the prevention program were not met , there were reliable changes in the intended direction in many of the students ' attitudes and intentions . Student attitudes toward drug use and knowledge about drugs both improved . Project PRIDE participation was associated with a relative decrease in willingness to experiment with drugs , even though all groups showed strongly negative attitudes toward drug use . Treatment interacted with sex of student and /or SES on a number of items . Generally , effects were more pronounced for girls and for low SES students . All groups of participants felt they gained significant knowledge and skills from the program . Other effects for parents and teachers were infrequent and inconsistent A grade five through eight substance abuse prevention program , later incorporated into the Michigan Model for Comprehensive School Health Education , was developed , implemented , and evaluated . Results focus on students who received seven lessons on alcohol in grade six , and eight lessons on tobacco , alcohol , marijuana , and cocaine in grade seven taught by their regular classroom teachers ( after a 6-hour training in the social pressures resistance skills curriculum ) . Students ( N = 442 ) received either two years of the program or none , and completed individually-coded question naires . Repeated measures analysis of variance result ed in significant treatment by occasion interactions on the use of alcohol , cigarettes , marijuana , cocaine , and other drugs , as well as on knowledge . At the end of grade seven , program students ' rates of substance use had increased significantly less and knowledge of alcohol pressures , effects , and skills to resist had increased significantly more than those of comparison students The research community has criticized Drug Abuse Resistance Education ( D.A.R.E. ) because the extant literature indicates a lack of evidence that the elementary school program prevents drug use . Yet D.A.R.E. continues to be the most widely implemented drug use prevention program in the United States and has considerable community support . To date , the junior high D.A.R.E. program has not been evaluated . The Minnesota DARE PLUS Project is a r and omized trial of 24 schools and communities . During 1999 - 2001 , students in eight schools will receive the junior high D.A.R.E. curriculum in 7th grade ; eight schools also will receive the curriculum as well as additional parent involvement , peer leadership , and community components in the 7th and 8th grade s ; and eight schools will serve as controls . This article describes the background and conceptualization , the curriculum and additional intervention components , and the evaluation methods of the DARE PLUS Project OBJECTIVES This paper presents the 1-year outcomes evaluation of Project Towards No Drug Abuse ( Project TND ) , a large-scale indicated drug abuse prevention program in southern California applied to continuation high school youth , who are at high risk for drug abuse . METHODS The efficacy of nine-lesson health motivation -- social skills -- decision-making curriculum was evaluated in a three-condition experimental design . Twenty-one schools were r and omly assigned by block to one of three conditions -- st and ard care ( control ) , classroom program , and classroom program plus a semester-long school-as-community component . A pretest was followed by a 3-week-long drug abuse prevention program and then a posttest at 14 continuation high schools . The 7 st and ard care schools received only the pretest followed by the posttest ( same time duration ) . Subjects were followed up 1 year later . RESULTS Changes in use of cigarettes , alcohol , marijuana , and hard drugs were assessed in a pretest-1-year follow-up time interval . The follow-up rate was 67 % ( analysis n = 1,074 ) . Indicated preventive effects were found on alcohol and hard drug use . No differences were found across the two program conditions . CONCLUSIONS Project TND is the first program to demonstrate 1-year self-reported behavioral effects on alcohol use and hard drug use among older , high-risk youth by using a school-based , limited-session model OBJECTIVE To provide a review of the evidence from 3 experimental trials of Project Towards No Drug Abuse ( TND ) , a senior-high-school-based drug abuse prevention program . METHODS Theoretical concepts , subjects , design s , hypotheses , findings , and conclusions of these trials are presented . A total of 2,468 high school youth from 42 schools in southern California were surveyed . RESULTS The Project TND curriculum shows reductions in the use of cigarettes , alcohol , marijuana , hard drugs , weapon carrying , and victimization . Most of these results were replicated across the 3 trials . CONCLUSION Project TND is an effective drug and violence prevention program for older teens , at least for one-year follow-up An amenability to treatment model stipulates that interventions may be differentially effective for subgroups of individuals with similar characteristics . Using such a model , the present study tests the impact of two social-cognitive interventions implemented in the sixth ( Intervention I ) and eighth/ninth ( Intervention II ) grade s on students ' skill acquisition and on their ninth and tenth grade substance use . A r and omized factorial design was used to examine main and interaction effects within the context of student family household status and gender . Positive program effects were found for Intervention II on skill acquisition and overall drug involvement . Interaction effects of Intervention II x Family Household Status provided support for the amenability to treatment model , but no support for the model was observed based on student gender . Possible explanations for the study findings are presented and future research directions are proposed to address why differences emerge in amenability to intervention and why such differences occur for specific subgroups BACKGROUND Universal school-based prevention programs for alcohol , tobacco , and other drug use are typically design ed for all students within a particular school setting . However , it is unclear whether such broad-based programs are effective for youth at high risk for substance use initiation . METHOD The effectiveness of a universal drug abuse preventive intervention was examined among youth from 29 inner-city middle schools participating in a r and omized , controlled prevention trial . A sub sample of youth ( 21 % of full sample ) was identified as being at high risk for substance use initiation based on exposure to substance-using peers and poor academic performance in school . The prevention program taught drug refusal skills , antidrug norms , personal self-management skills , and general social skills . RESULTS Findings indicated that youth at high risk who received the program ( n = 426 ) reported less smoking , drinking , inhalant use , and polydrug use at the one-year follow-up assessment compared to youth at high risk in the control condition that did not receive the intervention ( n = 332 ) . Results indicate that a universal drug abuse prevention program is effective for minority , economically disadvantaged , inner-city youth who are at higher than average risk for substance use initiation . CONCLUSIONS Findings suggest that universal prevention programs can be effective for a range of youth along a continuum of risk Longitudinal studies aim ed at assessing the impact of interventions on disease risk factors often confront several statistical problems . These problems include 1 ) dependent variables measured by ordered categories , 2 ) numerous potentially relevant patterns of transition between outcome levels , 3 ) mixed units of analysis ( e.g. , assignment by social unit while theorizing in terms of individuals ) , 4 ) incomplete r and omization , and 5 ) correlated estimates for successive occasions of longitudinal measurement . Longitudinal data on use of cigarettes , alcohol , and marijuana among adolescents ( n = 1,244 , complete data ) from the Midwestern Prevention Project are used to demonstrate solutions to each of these problems : 1 ) a proportional odds regression model , 2 ) conditional logistic models of transitions with interactions between baseline level and intervention effect , 3 ) a logistic model estimated with linear regression methods on measures aggregated by social unit , 4 ) conditional and unconditional models of effect magnitude , and 5 ) a repeated measures logistic regression technique . Panel data fit to the various models yielded the following conclusions concerning intervention effects in the Midwestern Prevention Project : reduction in the prevalence of cigarette users in treatment schools compared with control schools ( 8 % vs. 18 % smoked in the last week at one year follow-up ) , mixed evidence of an effect on marijuana use , and no evidence of an effect on alcohol use This paper reports on the evaluation of a culturally grounded prevention intervention targeting substance use among urban middle-school students . The curriculum consists of 10 lessons promoting antidrug norms and teaching resistance and other social skills , reinforced by booster activities and a media campaign . Three versions were delivered : Mexican American , combined African American and European American , and Multicultural . Thirty-five middle schools were r and omly assigned to 1 of the 3 versions or the control . Students completed baseline and follow-up question naires over a 2-year period ( total 6,035 respondents ) . Analyses utilizing a generalized estimating equations approach assessed the overall effectiveness of cultural grounding and the cultural matching hypothesis . Support was found for the intervention 's overall effectiveness , with statistically significant effects on gateway drug use as well as norms , attitudes , and resistance strategies but with little support for the cultural matching hypothesis . Specific contrasts found the Mexican American and Multicultural versions impacted the most outcomes The entire early adolescent population of the 15 communities that constitute the Kansas City ( Kansas and Missouri ) metropolitan area has participated in a community-based program for prevention of drug abuse since September 1984 . The Kansas City area is the first of two major metropolitan sites being evaluated in the Midwestern Prevention Project , a longitudinal trial for primary prevention of cigarette , alcohol , and marijuana use in adolescents . The project includes mass media programming , a school-based educational program for youths , parent education and organization , community organization , and health policy components that are introduced sequentially into communities during a 6-year period . Effects of the program are determined through annual assessment s of adolescent drug use in schools that are assigned to immediate intervention or delayed intervention control conditions . In the first 2 years of the project , 22,500 sixth- and seventh- grade adolescents received the school-based educational program component , with parental involvement in homework and mass media coverage . Analyses of 42 schools indicate that the prevalence rates of use for all three drugs are significantly lower at 1-year follow-up in the intervention condition relative to the delayed intervention condition , with or without controlling for race , grade , socioeconomic status , and urbanicity ( 17 % vs 24 % for cigarette smoking , 11 % vs 16 % for alcohol use , and 7 % vs 10 % for marijuana use in the last month ) , and the net increase in drug use prevalence among intervention schools is half that of delayed intervention schools The long-term effectiveness of D.A.R.E. was assessed by contrasting 9th- grade students who received the program in the 6th grade with others who did not receive the program . Of 38 elementary schools eligible for D.A.R.E. programs , 21 received the program and 17 did not . A follow-up survey assessed central D.A.R.E. concepts such as self-esteem , resistance to peer pressure , delay of experimentation with drugs , and drug use . Employing latent variables to represent the concepts , no significant differences were found between D.A. R.E. participants and controls . The authors discuss attenuation of effects and the generally antidrug context of schools This paper describes a preventive intervention trial called EARLY ALLIANCE which is aim ed at reducing risk for three adverse outcomes in childhood and adolescence : conduct problems , substance abuse , and school failure . The structure of the prevention trial is unique because two linked design s are being implemented concurrently . The primary design focuses on children at elevated risk for adverse outcomes , and compares a targeted , multi context ual preventive intervention with family , classroom , peer relational , and academic components to a universal , schoolwide preventive intervention that emphasizes peaceful conflict management and serves as a " usual care " control condition . The secondary design focuses on children at lower risk for adverse outcomes and compares a universally administered classroom program to the control condition . The paper describes the theoretical foundation for EARLY ALLIANCE , the goals of the prevention trial , the rationale for design choices , and the methods employed OBJECTIVE We examined the generalizability of a successful classroom-based prevention program developed for youth at alternative high schools ( high risk ) to youth at general high schools . METHOD A replication of a previously tested prevention program in a general high school population was conducted with 1-year follow-up data . Classrooms within each of three schools were r and omly assigned to two conditions , classroom education or st and ard care control . RESULTS Statistically significant effects on alcohol and illicit drug use were achieved in this population through a 1-year period following the program , although effects were not achieved on cigarette smoking and marijuana use . CONCLUSIONS These results suggest that this program ( Project Towards No Drug Abuse ) has applicability to a wide range of older teens Examined the impact of two treatment strategies on children 's drug refusal skills and drug-related information . Fifty-seven third grade rs were r and omly assigned to one of three groups : rehearsal-plus , general information , and control . Children in the rehearsal-plus group were taught drug knowledge , assertiveness skills , decision-making skills , rationale and specific drug refusal skills in the context of a skills-based strategy . At a more global level , the general information group targeted all of the same components with the exception of rationale . Results indicated that children in the skills-based strategy ( rehearsal-plus ) showed significant improvement in behavioral skills , decision-making , and rationale , while children in the information/education-based strategy ( general information ) improved most on the measure of general knowledge . At follow-up , gains were generally maintained 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 OBJECTIVES This study investigated the secondary prevention effects of a substance abuse primary prevention program . METHODS Logistic regression analyses were conducted on 4 waves of follow-up data from sixth- and seventh- grade baseline users of cigarettes , alcohol , and marijuana taking part in a school-based program in Indianapolis . RESULTS The program demonstrated significant reductions in cigarette use at the initial follow-up ( 6 months ) and alcohol use at the first 2 follow-ups ( up to 1.5 years ) . Models considering repeated measures also showed effects on all 3 substances . CONCLUSIONS Primary prevention programs are able to reach and influence high-risk adolescents in a nonstigmatizing manner BACKGROUND This article reports the results of a 5-year , longitudinal evaluation of the effectiveness of Drug Abuse Resistance Education ( DARE ) , a school-based primary drug prevention curriculum design ed for introduction during the last year of elementary education . DARE is the most widely disseminated school-based prevention curriculum in the United States . METHOD Twenty-three elementary schools were r and omly assigned to receive DARE and 8 were design ated comparison schools . Students in the DARE schools received 16 weeks of protocol -driven instruction and students in the comparison schools received a drug education unit as part of the health curriculum . All students were pretested during the 6th grade prior to delivery of the programs , posttested shortly after completion , and resurveyed each subsequent year through the 10th grade . Three-stage mixed effects regression models were used to analyze these data . RESULTS No significant differences were observed between intervention and comparison schools with respect to cigarette , alcohol , or marijuana use during the 7th grade , approximately 1 year after completion of the program , or over the full 5-year measurement interval . Significant intervention effects in the hypothesized direction were observed during the 7th grade for measures of students ' general and specific attitudes toward drugs , the capability to resist peer pressure , and estimated level of drug use by peers . Over the full measurement interval , however , average trajectories of change for these outcomes were similar in the intervention and comparison conditions . CONCLUSIONS The findings of this 5-year prospect i ve study are largely consonant with the results obtained from prior short-term evaluations of the DARE curriculum , which have reported limited effects of the program upon drug use , greater efficacy with respect to attitudes , social skills , and knowledge , but a general tendency for curriculum effects to decay over time . The results of this study underscore the need for more robust prevention programming targeted specifically at risk factors , the inclusion of booster sessions to sustain positive effects , and greater attention to interrelationships between developmental processes in adolescent substance use , individual level characteristics , and social context 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 BACKGROUND This article reports follow-up results during grade 9 for a multisite drug prevention program that curbed both marijuana and cigarette use during junior high . Based on the social influence model of prevention , the curriculum sought to motivate young people against drug use and to teach them skills for resisting pro-drug pressures . METHODS Thirty schools drawn from eight urban , rural , and suburban communities in California and Oregon were r and omly assigned to three experimental conditions , two treatment groups and one control . Students in 20 schools received 11 lessons , 8 during grade 7 and 3 in grade 8 ; in 10 of the treatment schools , older teens assisted an adult teacher in program delivery . Students were pretested prior to the program ( grade 7 ) and post-tested 24 months later ( grade 9 ) . RESULTS Earlier effects on cognitive risk factors ( perceived consequences of drug use , normative beliefs , resistance self-efficacy , and expectations of future use ) persisted through grade 9 in the teen leader schools ; in the condition under which adults taught the lessons without teens , the prior beneficial effects on beliefs largely eroded . All of the earlier effects on actual use disappeared by grade 9 , regardless of who taught the lesions . CONCLUSION Continued reinforcement of earlier lessons may be required to sustain prevention gains through the transition to high school Prior investigations have linked behavioral competencies in primary school to a reduced risk of later drug involvement . In this r and omized prevention trial , we sought to quantify the potential early impact of two developmentally inspired universal preventive interventions on the risk of early-onset alcohol , inhalant , tobacco , and illegal drug use through early adolescence . Participants were recruited as they entered first grade within nine schools of an urban public school system . Approximately , 80 % of the sample was followed from first to eighth grade s. Two theory-based preventive interventions , ( 1 ) a family-school partnership ( FSP ) intervention and ( 2 ) a classroom-centered ( CC ) intervention , were developed to improve early risk behaviors in primary school . Generalized estimating equations ( GEE ) multivariate response profile regressions were used to estimate the relative profiles of drug involvement for intervention youths versus controls , i.e. youth in the st and ard educational setting . Relative to control youths , intervention youths were less likely to use tobacco , with modestly stronger evidence of protection associated with the CC intervention ( RR=0.5 ; P=0.008 ) as compared to protection associated with the FSP intervention ( RR=0.6 ; P=0.042 ) . Intervention status was not associated with risk of starting alcohol , inhalants , or marijuana use , but assignment to the CC intervention was associated with reduced risk of starting to use other illegal drugs by early adolescence , i.e. heroin , crack , and cocaine powder ( RR=0.32 , P=0.042 ) . This study adds new evidence on intervention-associated reduced risk of starting illegal drug use . In the context of ' gateway ' models , the null evidence on marijuana is intriguing and merits attention in future investigations A primary prevention research project is described which tests an intervention model based on cognitive and interpersonal skill enhancement . Thirty-two classrooms of sixth grade students were r and omly assigned to either Program or Control conditions , with Program classrooms receiving a twelve-session cognitive skill development curriculum aim ed at reducing rates of substance use as measured by a drug use survey . Students in Program classrooms showed greater decision-making skills , including the ability to generate alternatives and to consider consequences and risks , greater ability to utilize social networks , and greater underst and ing of group roles , behavior , and alternatives . In addition , Program students reported less use of tobacco in the past year than Control Group students , but no differences between groups were found in use of alcohol , marijuana , or other drugs except for a tendency on the part of Program students to show greater experimentation with alcohol . The effectiveness of the intervention in promoting skill development and factors influencing the impact of the intervention on substance use behavior are discussed BACKGROUND School-based drug prevention programs have been criticized on method ologic grounds because the unit of analysis is often not the unit of r and omization , thus increasing the likelihood of Type I errors . Application of multilevel analytic strategies appropriately corrects this biasing tendency . This study demonstrates the practical use of such analysis . METHODS Data from 2,370 seventh- grade students participating in a substance use prevention trial were analyzed using a multilevel strategy . We examined the effectiveness of a social pressure resistance training and a normative education ( NORM ) intervention against an information-only control group . RESULTS The NORM condition revealed 1-year program effects for cigarette and marijuana use with individuals as the unit of analysis and only marginal effects with classroom as the unit of analysis . No program effects were found using school as the analysis unit . A multilevel strategy revealed program effects for cigarettes and marijuana with both class and school as grouping levels . The effect for alcohol use was significant at the 2-year follow-up . CONCLUSIONS Interventions establishing conservative drug use norms in classrooms may be an effective strategy in reducing substance use onset among adolescents . Utilization of appropriate analytic strategies is important in the analysis and interpretation of data containing nested structures This study developed and tested skills- and community-based approaches to prevent substance abuse among Native American youth . After completing pretest measurements , 1,396 third- through fifth- grade Native American students from 27 elementary schools in five states were divided r and omly by school into two intervention arms and one control arm . Following intervention delivery , youths in all arms completed posttest measurements and three annual follow-up measurements . Youths in schools assigned to the intervention arms learned cognitive and behavioral skills for substance abuse prevention . One intervention arm additionally engaged local community residents in efforts to prevent substance use among Native American youth . Outcome assessment batteries measured youths ' reported use of smoked and smokeless tobacco , alcohol , and marijuana . Over the course of the 3.5-year study , increased rates of tobacco , alcohol , and marijuana use were reported by youths across the three arms of the study . Though cigarette use was unaffected by intervention , follow up rates of smokeless tobacco , alcohol , and marijuana use were lower for youths who received skills intervention than for youths in the control arm . Community intervention components appeared to exert no added beneficial influence on youths ' substance use , beyond the impact of skills intervention components alone . Finally , gender differences were apparent across substances , measurements , and study arms , with girls smoking more cigarettes and boys using more smokeless tobacco , alcohol , and marijuana Five hundred and eleven fourth , fifth , and sixth grade students and their parents from six schools in northwest Arkansas participated in this study . Students were blocked on school and grade level , then assigned r and omly by class to either the intervention Keep A Clear Mind ( KACM ) program or a waiting list control . KACM students received four weekly correspondence lessons design ed to be completed at home with a parent . KACM students reported significantly less perceived peer use of alcohol , tobacco , and marijuana , as well as significantly less peer pressure susceptibility to experiment with cigarettes . Mothers in the KACM program reported significantly more recent and frequent communication with their children about refusing drugs , and significantly greater discussion s with their children regarding how to resist peer pressure to use alcohol , tobacco , and marijuana . Intervention program fathers reported significantly more communication with their children concerning how to resist peer pressure to drink alcohol and use tobacco , and significantly greater motivation to help their children avoid drug use . No significant differences were found between groups on student intentions to use drugs . These data suggest a print medium that emphasizes parent-child activities holds promise for accessing families and enhancing drug prevention communication A two-year primary prevention program for junior high school students was evaluated . The program consisted of drug education , " alternatives , " and affective in- service training for the students ' teachers . Students in one junior high school received the intervention and students in another school served as a no-treatment control group . The students were pretested at the beginning of 7th grade and posttested at the end of 8th grade . Positive effects were found for females on several drug-related variables ; few effects were found for males . The findings are discussed with regard to the individual prevention strategies 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 reports outcome evaluation results from a segment of one of the most widely used drug education/prevention programs entitled “ Here 's Looking At You 2000 . ” HLAY 2000 was offered to the seventh and eighth grade students ( n = 463 ) by regular classroom teachers of Yadkin County Schools located in one of the rural areas in North Carolina . Six schools served as the experimental group while two r and omly selected schools served as a control group . The program was implemented during the 1990–91 school year Two longitudinal surveys based on r and om sample s of high school students in New York State indicate four stages in the sequence of involvement with drugs : beer or wine , or both ; cigarettes or hard liquor ; marihuana ; and other illicit drugs . The legal drugs are necessary intermediates between nonuse and marihuana . Whereas 27 percent of high school students who smoke and drink progress to marihuana within a 5- to 6-month follow-up period , only 2 percent of those who have not used any legal substance do so . Marihuana , in turn , is a crucial step on the way to other illicit drugs . While 26 percent of marihuana users progress to LSD , amphetamines , or heroin , only 1 percent of nondrug marihuana users and 4 percent of legal drug users do so . This sequence is found in each of the 4 years in high school and in the year after graduation . The reverse sequence holds for regression in drug use This paper describes the third and final evaluation of drug education conducted by the Napa Project . In the present course students were taught decision-making skills , personal goal setting , a motivational model , peer and media influences on behavior , assertiveness training , and information on the consequences of , and alternatives to , alcohol , cigarette , and marijuana use . The evaluation employed an experimental design in which seventh grade classes in two schools were matched and then r and omly assigned to experimental and control conditions . Pre- , post- , and follow-up tests covered drug knowledge ; drug attitudes ; perceived benefits and costs of substance use ; perceived peer attitudes toward , and use of , substances ; and intentions to use , current use and lifetime use of various substances . The posttest and follow-up data were analyzed using hierarchical analyses of covariance controlling for corresponding pretest scores . The course was found to have had no significant effect on girls and only a few effects at follow-up for boys A six-year , school-based prevention program , which modified classroom teacher practice s , offered parent training , and provided child social skills training , was evaluated for its effects on school failure , drug abuse , and delinquency among low-income urban children . Compared to a low-income control group , children in the intervention group showed enhanced school commitment and class participation . The girls in the group also evidence d lower rates of substance use initiation , while the boys exhibited increased social and school work skills An alternatives-oriented , school-based drug abuse prevention program , Positive Alternatives for Youth ( PAY ) , was evaluated over a 2-year period . Using a r and om-assignment , pretest-posttest control group design , 135 PAY students and 106 control group students were assessed on several attitudinal and behavioral measures of drug use . During the first year significant differences were detected between PAY and control students . Fewer differences were found in the second year , although a special analysis showed evidence of impact on PAY students rated as more involved in program activities . Reasons for specific results are discussed and implication s are drawn for the alternatives approach and the field of drug abuse prevention Two drug abuse prevention curricula were tested to determine their efficacy in preventing the onset of tobacco , alcohol , and marijuana use among adolescents . The first program focused on prevention through social pressure resistance training . The second featured affective education approaches to prevention . Curricula were tested on seventh grade students . Subjects were pretested just prior to the program and were post-tested at 12 and 24 months . Post-test analyses indicated that the social program delivered to seventh grade subjects was effective in delaying the onset of tobacco , alcohol , and marijuana use . No preventive effect of the affective education program was observed . By the final post-test , classrooms that had received the affective program had significantly more drug use than controls 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 OBJECTIVES Although several studies have reported short-term gains for drug-use prevention programs targeted at young adolescents , few have assessed the long-term effects of such programs . Such information is essential for judging how long prevention benefits last . This paper reports results over a 6-year period for a multisite r and omized trial that achieved reductions in drug use during the junior high school years . METHODS The 11-lesson curriculum , which was tested in 30 schools in eight highly diverse West Coast communities , focused on helping 7th and 8th grade students develop the motivation and skills to resist drugs . Schools were r and omly assigned to treatment and control conditions . About 4000 students were assessed in grade 7 and six times thereafter through grade 12 . Program effects were adjusted for pretest covariates and school effects . RESULTS Once the lessons stopped , the program 's effects on drug use stopped . Effects on cognitive risk factors persisted for a longer time ( many through grade 10 ) , but were not sufficient to produce corresponding reductions in use . CONCLUSIONS It is unlikely that early prevention gains can be maintained without additional prevention efforts during high school . Future research is needed to develop and test such efforts AIMS To examine the effects of the ' Healthy School and Drugs ' project , a Dutch school-based drug prevention project that was developed in the late 1980s and disseminated during the 1990s . This programme is currently being used by 64 - 73 % of Dutch secondary schools and it is estimated that at least 350000 high school students receive this intervention each year . DESIGN , SETTING AND PARTICIPANTS A quasi-experimental study in which students of nine experimental ( N = 1156 ) schools were compared with students of three control schools ( N = 774 ) . The groups were compared before the intervention , 1 year later , 2 years later and 3 years later . MEASUREMENTS Self-report measures of tobacco , alcohol and marijuana use , attitudes towards substance use , knowledge about substances and self-efficacy . FINDINGS Some effects on the use of tobacco , alcohol and cannabis were found . Two years after the intervention , significant effects could still be shown on alcohol use . Effects of the intervention were also found on knowledge , but there was no clear evidence for any effects on attitude towards substance use and on self-efficacy . CONCLUSIONS This study shows the Healthy School and Drugs project as implemented in Holl and may have some effect on drug use in the children exposed to it The cluster r and omized trial with a concurrent economic evaluation is considered the gold st and ard evaluative design for the conduct of implementation research evaluating different strategies to promote the transfer of research findings into clinical practice . This has implication s for the planning of such studies , as information is needed on the effects of clustering on both effectiveness and efficiency outcomes . This paper describes the design considerations specific to implementation research studies , focusing particularly on the estimation of sample size requirements and on the need for reliable information on intracluster correlation coefficients for both effectiveness and efficiency outcomes BACKGROUND Two strategies for preventing the onset of alcohol abuse , and marijuana and cigarette use were tested in junior high schools in Los Angeles and Orange Counties , California . The first strategy taught skills to refuse substance use offers . The second strategy corrected erroneous normative perceptions about prevalence and acceptability of use among peers and established conservative groups norms regarding use . METHODS Four experimental conditions were created by r and omly assigning schools to receive ( a ) neither of the experimental curricula ( placebo comparison ) , ( b ) resistance skill training alone , ( c ) normative education alone , or ( d ) both resistance skill training and normative education . Students were pretested prior to the program and post-tested 1 year following delivery of the program . RESULTS There were main effects of normative education for summary measures of alcohol ( P = 0.0011 ) , marijuana ( P = 0.0096 ) , and cigarette smoking ( P = 0.0311 ) . All individual dichotomous measures of alcohol , marijuana , and tobacco use indicated significant reductions in onset attributable to normative education . There were no significant main effects of resistance skill training . CONCLUSION These results suggest that establishing conservative norms is an effective strategy for preventing substance use A comprehensive , school-based , instructional and social competency promotion program to prevent problem behavior was attempted in a troubled middle school . The program included components aim ed at increasing social competencies as well as components to increase social bonding and school success . The evaluation of the 5-year effort showed that it was ineffective . The program never reached the expected levels of implementation , and no dependable effects on youth behaviors or attitudes were observed . The results are interpreted within the context of what is known about the quality of implementation and the organizational climate within which the demonstration was attempted The purpose of the research reported herein was to associate prevention activities in the schools with abusing behaviors of the students , after statistically controlling relevant variables . Discrete activities and clusters of activities ( " programs " or " models " ) were studied with a r and omly assigned control group design . This approach was selected so that effective activities could be identified even against an overall background of increasing abuse during and after the prevention experience Thirty-four schools ( n=7426 consented sixth grade rs , 71 % of the eligible population ) were r and omized to conditions to test the hypothesis that Skills for Adolescence ( SFA ) , a widely used comprehensive life skills training curriculum with a dedicated drug education unit , is more effective than st and ard care in deterring and delaying substance use through middle school . Two-year posttest ( 1-year post-intervention ) data were collected from 5691 eighth grade rs ( 77 % of those who completed the sixth- grade survey and 87 % of those who completed the seventh- grade survey ) . Lifetime and recent ( last 30 days ) use of five substances or combinations of substances was compared using mixed-model regression to control for school clustering . There were two significant treatment main effects at the end of the eighth grade : lifetime ( P=.05 ) and recent ( P<.03 ) marijuana use were lower in SFA than control schools with pretest usage and salient demographic and psychosocial variables controlled . There was also one significant Treatment x Pretest Usage interaction around binge drinking . Baseline binge drinkers in SFA schools were less likely to report recent binge drinking than students in control schools ( P<.01 ) ; there were no treatment differences among baseline nonbinge drinkers . Analyses of potential mediators of SFA treatment effects on eighth- grade binge drinking and marijuana use suggested that SFA increased self-efficacy around drug refusal skills , but did not affect behavioral intentions , perceptions of harm , or perceived peer norms . These 2-year ( 1-year post-intervention ) outcomes offer some additional support for SFA effectiveness and the general thrust of school-based , life skills-based prevention programs . The promising sixth- through eighth- grade findings for SFA , a commercially available program , provide a further step in bridging a major gap in the " research to practice " literature : theory-based interventions that have documented behavioral effects have not enjoyed large-scale implementation , while intuition-based programs that have no documented effects still enjoy wide exposure For the last three years , the University of New Mexico School of Medicine/Division of Emergency Medicine has sponsored an Alcohol and Substance Abuse Prevention Program ( ASAP ) . The program 's objectives were to expose youth to the " real-life " social and medical consequences of alcohol and substance abuse through visits and interviews with patients and their families at the University of New Mexico Emergency Department and Trauma Center . A pretest , post-test , and eight-month follow-up evaluation design was used to assess the program 's effects . Question naires were administered to r and omly selected experimental and control groups of seventh grade students ( n = 27 ) . Repeated- measures analysis of variance detected a significant experimental/control condition x time crossover interaction effect for stated perception of riskiness , F ( 2 , 31 ) = 3.20 , P = .049 . The data indicated that , over time , the experimental group perceived the riskiness of driving under the influence of drugs or alcohol to be greater , while the control group perceived such behavior to be less risky OBJECTIVES This paper describes the 2-year follow-up of a 12-session version of an indicated drug abuse prevention program , Project Towards No Drug Abuse ( TND ) . Self-instruction programming often is used to help youth that are at high risk for dropout and drug abuse to complete their high school education . However , a health educator-led program is much more interactive . METHODS The effects of self-instruction versus health educator-led versions of this curriculum were examined . Eighteen schools were r and omly assigned by block to one of three conditions -- st and ard care ( control ) , health educator-led classroom program , and self-instruction classroom program . Subjects were followed up 1 and 2 years later . Two-year results are reported here . RESULTS The self-instruction program produced no behavioral effects relative to the st and ard care control condition . The 2-year follow-up results indicated maintenance of program effects on cigarette smoking and hard drug use in the health educator-led version . CONCLUSIONS Project TND shows maintenance of effects on some drugs 2 years after program implementation , when most youth were young adults . More work is needed to learn how to maintain effects across substances . Continued exploration of modalities of implementation may be helpful National survey data indicate that illicit drug use has steadily increased among American adolescents since 1992 . This upward trend underscores the need for identifying effective prevention approaches capable of reducing the use of both licit and illicit drugs . The present study examined long-term follow-up data from a large-scale r and omized prevention trial to determine the extent to which participation in a cognitive-behavioral skills-training prevention program led to less illicit drug use than for untreated controls . Data were collected by mail from 447 individuals who were contacted after the end of the 12th grade , 6.5 years after the initial pretest . Results indicated that students who received the prevention program ( Life Skills Training ) during junior high school reported less use of illicit drugs than controls . These results also support the hypothesis that illicit drug use can be prevented by targeting the use of gateway drugs such as tobacco and alcohol The present study provides an implementation , process , and immediate outcomes evaluation of the classroom component of Project Towards No Drug Abuse ( TND ) . This project involves development and evaluation of a school-based drug abuse prevention curriculum for continuation high school youth , who are at relatively high risk for drug abuse . Three r and omized conditions were evaluated : a st and ard care , classroom only , and classroom plus school-as-community . The latter condition was an enhanced school-based condition which involved outside-of-classroom meetings and activities . Implementation was high in both program conditions even though this was a higher risk context . Process evaluation data were favorable and did not vary between the two program conditions . Immediate outcomes data ( knowledge ) was higher in the two program conditions than in the st and ard care condition . Regarding the classroom program , addition of extra-classroom activities does not appear to alter the quality of delivery of the program The effectiveness of a short-term prevention program to increase drug refusal behavior in a school-age population was assessed . Forty-two third- grade children were r and omly assigned to one of three groups : rehearsal-plus , traditional , or attention control . Children in the rehearsal-plus group were taught specific drug refusal techniques and appropriate social skills , and were provided a rationale for each response . This procedure included behavioral training and elaborative rehearsal . Training occurred in four socially vali date d situations corresponding to setting s where children were likely to be offered drugs . The traditional procedure consisted of instructions derived from a " Just Say No " drug program . Assessment focused on specific refusal behaviors , procedural knowledge , and self-efficacy . Significant gains in desired functioning and appropriate behavioral and social skills were found . The effectiveness of the rehearsal-plus procedure as a method of increasing adaptive responding in dangerous and /or anxiety-arousing situations is discussed |
12,333 | 10,353,408 | After the first dose of indomethacin , patients receiving furosemide had higher urine output , fractional excretion of sodium , and osmolar clearance than controls .
Thus , dehydration appears to be a contraindication for furosemide administration in premature infants treated with indomethacin for symptomatic PDA . | Abstract This study was design ed to assess : ( 1 ) whether furosemide modifies the incidence of failure to close a symptomatic patent ductus arteriosus ( PDA ) in response to indomethacin in premature infants , ( 2 ) whether furosemide decreases renal and hydromineral side effects of indomethacin , and ( 3 ) whether the effects of furosemide on renal function depend on initial extracellular volume [ assessed by blood urea nitrogen (BUN)/creatinine ratio ] . | Fifteen preterm infants with patent ductus arteriosus and respiratory distress syndrome were given indomethacin ( 0.2 mg/kg ) at 12 h intervals up to three times , either orally or intravenously , in an uncontrolled , non-r and omized study . Serum indomethacin concentrations were determined in blood sample s taken 12 h after dosing . There was considerable variability in the serum indomethacin concentrations , especially after oral administration , although the mean concentrations after each of the three doses were similar after both oral and intravenous administration . The frequency of closures and transient closures of the ductus arteriosus was also similar for both routes of administration . There was , however , no relation between concentration and effect in individual patients . The sustained exposure to indomethacin which appears to be necessary for ductal closure can sometimes be attained by oral administration To determine if dopamine would prevent the renal side effects of indomethacin , fifteen preterm infants were r and omized into two groups : seven received indomethacin alone , and eight received indomethacin together with low dose dopamine infusion . Infants who received indomethacin together with dopamine had significantly higher UV ( p less than 0.005 ) , CNa ( p less than 0.005 ) , Cosm ( p less than 0.005 ) and FENA ( p less than 0.005 ) than those of infants who received indomethacin alone . There was , however , no significant difference in Ccr and FNa between the groups . These data indicate that dopamine overcomes indomethacins renal side effects of tubular origin , but it can not prevent the renal vasoconstrictive action of vasoconstrictor hormones following the inhibition of prostagl and in synthesis by indomethacin . Considering that RBF and GFR turn to normal approximately 12 hours after the last dose of indomethacin , and that with the use of dopamine systemic blood pressure and peripheral circulation can also be normalized and to some extent myocardiac contractility improved , low doses of dopamine can be used instead of furosemide in the sick preterm infant with PDA when indomethacin therapy is indicated Furosemide stimulates the renal synthesis of prostagl and in E2 , a potent dilator of the ductus arteriosus . We administered this drug to 33 premature infants with the respiratory-distress syndrome , to determine whether it increased the incidence of patent ductus arteriosus . Chlorothiazide , a diuretic that does not stimulate prostagl and in E synthesis , was used as the control drug in 33 other infants . During the study , the incidence of patent ductus arteriosus was significantly higher ( P less than 0.02 ) in the furosemide group ( 18 of 33 infants ) than in the chlorothiazide group ( 8 of 33 ) . Eleven infants in the furosemide group and seven in the chlorothiazide group required ductal ligation ( P greater than 0.2 ) . An additional six infants ( all from the furosemide group ) who did not have evidence of a patent ductus during the study were later found to have one . Overall survival was 76 and 61 per cent in the furosemide and chlorothiazide groups , respectively ( P greater than 0.2 ) . Small ( less than twofold ) increases in the urinary excretion of prostagl and in E were seen after the initial dose of both drugs . When the analysis was repeated after the fifth day of life , prostagl and in E excretion tripled after furosemide administration , whereas no increase occurred with chlorothiazide . We conclude that furosemide increases the incidence of patent ductus arteriosus in premature infants with the respiratory-distress syndrome , probably through a prostagl and in-mediated process The relative potency of four non-steroidal anti-inflammatory drugs ( NSAIDs ) - indomethacin , flurbiprofen , sulindac and piroxicam - in inhibiting frusemide-stimulated natriuresis and creatinine clearance was investigated in a placebo controlled cross-over study using healthy volunteers . All four drugs tested significantly inhibited the action of frusemide and they were equipotent in their effects . If it is accepted that sulindac is renal sparing with respect to inhibition of prostagl and in synthesis , our observations raise two possibilities concerning the underlying mechanism of antagonism : a ) that inhibition of renal prostagl and in synthesis is not important ; b ) that sulindac interacts with frusemide in a manner different from other NSAIDs To determine if furosemide would prevent the renal side effects of indomethacin therapy in premature infants with patent ductus arteriosus , 19 premature infants were r and omized into two groups : nine received indomethacin alone , and ten received indomethacin followed immediately by furosemide . There was no significant difference between the groups in birth weight , gestational age , postnatal age , and in cardiopulmonary or renal status at the time of study . Infants who received indomethacin and furosemide had significantly higher urine output ( P less than 0.05 ) , higher FENa and FECl ( P less than 0.01 ) , and higher glomerular filtration rate ( P less than 0.05 ) than those of infants who received indomethacin alone . Seven infants in each group responded to indomethacin therapy with disappearance of PDA murmur and improvement of cardiovascular status . The results of this study suggest that furosemide may prevent the renal side effects of indomethacin therapy and yet not affect the efficacy of indomethacin in the closure of a PDA Renal function and changes in the activity of selected vasoactive hormones during prolonged indomethacin therapy ( 1 week ) were studied in 11 very-low-birth-weight infants with symptomatic patent ductus arteriosus . The initiation of indomethacin therapy was associated with a reduction in diuresis , a transient decrease in creatinine clearance , and an increase in body weight ( P less than 0.01 ) . Furthermore , there was a transient trend toward hyponatremia and hyperkalemia . This acute renal dysfunction was compatible with a complex picture of renal hypoperfusion associated with a fall of plasma renin activity from high levels prior to indomethacin treatment , with a transient rise in the plasma level of arginine vasopressin and with suppressed renal and systemic prostagl and in synthesis . During treatment , an effective circulatory volume was restored by closing the ductus . In parallel , PRA and AVP plasma concentrations returned to nearly normal values . Subsequently , kidney function was not further impaired despite continued indomethacin therapy . These observations suggest that prolonged indomethacin therapy for prevention of sPDA relapse probably constitutes no further risk to kidney function after successful pharmacologically induced ductal constriction To determine whether furosemide could prevent renal side effects of indomethacin ( INN , indometacin ) used for the pharmacologic closure of the patent ductus arteriosus ( PDA ) in preterm infants Nonsteroidal anti-inflammatory drugs ( NSAID ) suppress prostagl and in-dependent renal blood flow and furosemide-induced diuresis in patients with cirrhosis and ascites . Since sulindac may selectively spare inhibition of renal prostagl and ins , we evaluated the interactions of acute administration of sulindac or indomethacin with furosemide in 15 patients with cirrhosis and ascites . Prior to furosemide , indomethacin reduced creatinine clearance ( by 55 % ) , urinary volume ( by 82 % ) , sodium ( by 93 % ) , and prostagl and in E2 ( by 87 % ) ( all P less than 0.05 ) , whereas sulindac had no effect . However , both drugs reduced furosemide-induced diuresis . Indomethacin appeared slightly more potent in reducing the diuresis ( 55 % v 38 % ) , natriuresis ( 67 % v 52 % ) , and prostagl and in E2 ( PGE2 ) release ( 81 % v 74 % ) . In a similar protocol in healthy subjects , furosemide-induced diuresis and natriuresis were also blunted by both drugs . Thus , under conditions of enhanced prostagl and in activity from furosemide , sulindac does affect renal function . These data suggest that renal function should be monitored in patients with cirrhosis and ascites who receive sulindac as well as other NSAID |
12,334 | 29,781,564 | NSAIDs significantly improve time to gut recovery after elective colorectal surgery .
Current evidence is not adequate to identify whether selective or nonselective drugs should be recommended . | AIM Postoperative ileus causes significant patient morbidity after abdominal surgery .
Some evidence suggests nonsteroidal anti-inflammatory drugs ( NSAIDs ) may reduce time to gut recovery , but there has not been a meta- analysis to assess their efficacy .
This systematic review and meta- analysis aim ed to determine the benefit of NSAIDs for recovery of postoperative gut function in patients undergoing elective colorectal surgery . | BACKGROUND Radical cystectomy ( RC ) for bladder cancer is frequently associated with delayed gastrointestinal ( GI ) recovery that prolongs hospital length of stay ( LOS ) . OBJECTIVE To assess the efficacy of alvimopan to accelerate GI recovery after RC . DESIGN , SETTING , AND PARTICIPANTS We conducted a r and omized double-blind placebo-controlled trial in patients undergoing RC and receiving postoperative intravenous patient-controlled opioid analgesics . INTERVENTION Oral alvimopan 12 mg ( maximum : 15 inpatient doses ) versus placebo . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The two-component primary end point was time to upper ( first tolerance of solid food ) and lower ( first bowel movement ) GI recovery ( GI-2 ) . Time to discharge order written , postoperative LOS , postoperative ileus (POI)-related morbidity , opioid consumption , and adverse events ( AEs ) were evaluated . An independent adjudication of cardiovascular AEs was performed . RESULTS AND LIMITATIONS Patients were r and omized to alvimopan ( n=143 ) or placebo ( n=137 ) ; 277 patients were included in the modified intention-to-treat population . The alvimopan cohort experienced quicker GI-2 recovery ( 5.5 vs 6.8 d ; hazard ratio : 1.8 ; p<0.0001 ) , shorter mean LOS ( 7.4 vs 10.1 d ; p=0.0051 ) , and fewer episodes of POI-related morbidity ( 8.4 % vs 29.1 % ; p<0.001 ) . The incidence of opioid consumption and AEs or serious AEs ( SAEs ) was comparable except for POI , which was lower in the alvimopan group ( AEs : 7 % vs 26 % ; SAEs : 5 % vs 20 % , respectively ) . Cardiovascular AEs occurred in 8.4 % ( alvimopan ) and 15.3 % ( placebo ) of patients ( p=0.09 ) . Generalizability may be limited due to the exclusion of epidural analgesia and the inclusion of mostly high-volume centers utilizing open laparotomy . CONCLUSIONS Alvimopan is a useful addition to a st and ardized care pathway in patients undergoing RC by accelerating GI recovery and shortening LOS , with a safety profile similar to placebo . PATIENT SUMMARY This study examined the effects of alvimopan on bowel recovery in patients undergoing radical cystectomy for bladder cancer . Patients receiving alvimopan experienced quicker bowel recovery and had a shorter hospital stay compared with those who received placebo , with comparable safety . TRIAL REGISTRATION Clinical Trials.gov identifier NCT00708201 Background Postoperative ileus ( POI ) is observed in 20–30 % of patients undergoing colorectal cancer surgery , despite enhanced recovery programs ( ERPs ) . Cyclooxygenase (COX)-2 is identified as a key enzyme in POI , but other arachidonic acid pathway enzymes have received little attention despite their potential as selective targets to prevent POI . The objectives were to compare the expression of arachidonic acid metabolism ( AAM ) enzymes ( 1 ) between patients who underwent colorectal cancer surgery and followed an ERP or not ( NERP ) , ( 2 ) and between ERP patients who experimented POI or not and ( 3 ) to determine the ability of antagonists of these pathways to modulate contractile activity of colonic muscle . Methods This was a translational study . Main outcome measures were gastrointestinal motility recovery data , mRNA expressions of key enzymes involved in AAM ( RT-qPCR ) and ex vivo motility values of the circular colon muscle . Twenty-eight prospect ively included ERP patients were compared to eleven retrospectively included NERP patients that underwent colorectal cancer surgery . Results ERP reduced colonic mucosal COX-2 , microsomal prostagl and in E synthase ( mPGES1 ) and hematopoietic prostagl and in D synthase ( HPGDS ) mRNA expression . mPGES1 and HPGDS mRNA expression were significantly associated with ERP compliance ( respectively , r2 = 0.25 , p = 0.002 and r2 = 0.6 , p < 0.001 ) . In muscularis propria , HPGDS mRNA expression was correlated with GI motility recovery ( p = 0.002 ) . The pharmacological inhibition of mPGES1 increased spontaneous ex vivo contractile activity in circular muscle ( p = 0.03 ) . Conclusion The effects of ERP on GI recovery are correlated with the compliance of ERP and could be mediated at least in part by mPGES1 , HPGDS and COX-2 . Furthermore , mPGES1 shows promise as a therapeutic target to further reduce POI duration among ERP patients INTRODUCTION While enhanced recovery after surgery ( ERAS ) has been proven to improve results in colorectal operations with regard to morbidity and duration of hospital stay , its impact on recovery of bowel motility is poorly documented . The aims of this study were to assess the impact of ERAS on bowel motility recovery , and to assess the consequences of the definition of postoperative ileus on its reported incidence in the literature . MATERIAL AND METHODS This is a single-center prospect i ve observational study of consecutive patients who underwent colorectal resection with anastomosis over a period of 17 months . Global resumption of intestinal transit ( GROT ) was defined as passage of stool combined with alimentary tolerance of solid food . RESULTS One hundred and thirty-one patients were included . A median of 14 items ( range : 13 - 16 ) was complied out of 19 observable items in the protocol . Median time to passage of flatus ( MTPF ) was 2 days and the GROT was 3 days . The time interval to MTPF as well as to GROT decreased as adherence to the ERAS protocol increased ( respectively P<0.001 , r2=0.11 and P=0.04 , r2=0.06 ) . The incidence of postoperative " ileus " varied from 1.5 % to 61.8 % depending on the interval chosen to define ileus ( cut-off from 1 to 7 days ) . Adherence to≥85 % of the items in the ERAS protocol protected patients from " prolonged ileus " , i.e. , lasting≥4 days ( OR=0.35 ; 95 % CI=0.15 to 0.83 ) . CONCLUSION The implementation of and compliance with an ERAS protocol allowed a reduction in the time to GROT . There is a need for a consensual definition of postoperative ileus BACKGROUND : Nonsteroidal anti-inflammatory drugs have become an important component of narcotic-sparing postoperative pain management protocol s. However , conflicting evidence exists regarding the adverse association of nonsteroidal anti-inflammatory drug use with intestinal anastomotic healing in colorectal surgery . OBJECTIVE : This study compares patients receiving nonsteroidal anti-inflammatory drugs on postoperative day 1 with patients who did not receive nonsteroidal anti-inflammatory drugs with regard to the occurrence of anastomotic leaks . DESIGN : This is a retrospective study from a protocol -driven prospect ively collected statewide data base . A propensity score model was used to adjust for differences between the groups in patient demographics , characteristics , comorbidities , and laboratory values . SETTING S : The multicenter data set used in this analysis represents a variety of academic and community hospitals within the state of Michigan from July 2012 through February 2014 . PATIENTS : Nonpregnant patients over the age of 18 who underwent colon and rectal surgery with bowel anastomosis were selected . MAIN OUTCOME MEASURES : Occurrence of anastomotic leak , composite surgical site infection , sepsis , and death within 30 days of surgery were the primary outcomes measured . RESULTS : A total of 4360 patients met inclusion criteria , of which 1297 ( 29.7 % ) received nonsteroidal anti-inflammatory drugs and 3063 ( 70.3 % ) did not receive nonsteroidal anti-inflammatory drugs . There was no statistically significant difference between the 2 groups in the proportion of cases with anastomotic leak ( OR , 1.33 ; CI , 0.86–2.05 ; p = 0.20 ) , composite surgical site infection ( OR , 1.26 ; CI , 0.96–1.66 ; p = 0.09 ) , or death within 30 days ( OR , 0.58 ; CI , 0.28–1.19 ; p = 0.14 ) . There was a significantly greater risk of sepsis for patients given nonsteroidal anti-inflammatory drugs than for those patients not given nonsteroidal anti-inflammatory drugs ( OR , 1.47 ; CI , 1.05–2.06 ; p = 0.03 ) . LIMITATIONS : This is a nonr and omized study performed retrospectively , and it is based on data collected only within a subset of hospitals in the state of Michigan . CONCLUSIONS : No statistically significant increase in the proportion of patients with anastomotic leak was observed when prescribing nonsteroidal anti-inflammatory drugs for analgesia in the early postoperative period for patients undergoing elective colorectal surgery . Unexpectedly , there was an increased risk of sepsis that warrants further investigation ( see video , Supplemental Digital Content 1 , http://links.lww.com/DCR/A192 , for a synopsis of this 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 Endogenous prostagl and ins regulate smooth muscle activity ; prostagl and ins and cyclooxygenase ( COX ) inhibitors influence gastrointestinal motility in inflammatory states such as postoperative ileus in animal models . The objective of this study was to evaluate the effects of two COX-2 inhibitors on gastric emptying and intestinal transit in healthy humans . In a double-blind , placebo-controlled , parallel-group study , 66 healthy volunteers were r and omized to one of two commercially available oral COX-2 inhibitors ( celecoxib and rofecoxib ) , cisapride ( positive control ) , or placebo . Following 7 days on therapy , study participants underwent a test of gastric emptying and small bowel transit of liquids and solids using scintigraphy . Data were analysed using Kruskal-Wallis ( ANOVA on ranks ) and Mann-Whitney rank sum tests . There were significant group effects on transit of solids : gastric emptying ( ANOVA , P = 0.005 ) and small bowel transit ( ANOVA , P = 0.056 ) . However , neither COX-2 inhibitor significantly accelerated the liquid or solid gastric emptying or small bowel transit compared with placebo . The positive control , cisapride , accelerated gastric emptying of solids ( post-lag slope of gastric emptying , P < 0.05 ) , and small bowel transit of solids ( t10 % , P = 0.016 ) . At maximum clinical ly approved dosages , celecoxib and rofecoxib have no significant effects on gastric emptying or small intestinal transit in healthy humans . Cisapride accelerates gastric emptying and small bowel transit in healthy humans Abstract Currently , there is a paucity of study investigating postoperative ileus in gastric cancer surgery . This prospect i ve study aims to identify the risk factors for prolonged postoperative ileus ( PPOI ) and to use these risk factors to generate a risk stratification scoring system for the occurrence of PPOI . Patients who underwent radical gastrectomy for gastric cancer were included in this study . A multivariate logistic analysis was applied to identify independent risk factors for PPOI and to generate the scoring system . A receiver operating characteristic curve was generated and the area under the curve was calculated to demonstrate the predictive power of the scoring system . Finally , 296 patients were included and analyzed , of whom 96 ( 32.4 % ) developed PPOI . The multivariate analysis showed that age ≥65 years , operative duration ≥4 hours , tumor – node – metastasis ( TNM ) stage = III , open/converted operative technique , and total postoperative opiates dose ( TOD ) ≥0.3 mg/kg were independent risk factors for PPOI . Based on these factors , a risk stratification scoring system was generated , classified by low-risk ( score 0–2 ) , moderate-risk ( score 3–4 ) , and high-risk ( score 5–6 ) groups . The incidence of PPOI increased by 7.5-fold from low-risk to high-risk group . The area under the curve of the scoring system was 0.841 ( 95 % CI , 0.793–0.890 ) , indicating a good predictive capability for the occurrence of PPOI.We have identified independent risk factors for the occurrence of PPOI and used these factors to construct a risk stratification scoring system BACKGROUND Selective cyclooxygenase-2 ( COX-2 ) inhibitors have come under scrutiny because of reports suggesting an increased cardiovascular risk associated with their use . Experimental research suggesting that these drugs may contribute to a prothrombotic state provides support for this concern . METHODS We review ed all potentially serious cardiovascular events among 2035 patients with a history of colorectal neoplasia who were enrolled in a trial comparing two doses of celecoxib ( 200 mg or 400 mg twice daily ) with placebo for the prevention of colorectal adenomas . All deaths were categorized as cardiovascular or noncardiovascular , and nonfatal cardiovascular events were categorized in a blinded fashion according to a prespecified scheme . RESULTS For all patients except those who died , 2.8 to 3.1 years of follow-up data were available . A composite cardiovascular end point of death from cardiovascular causes , myocardial infa rct ion , stroke , or heart failure was reached in 7 of 679 patients in the placebo group ( 1.0 percent ) , as compared with 16 of 685 patients receiving 200 mg of celecoxib twice daily ( 2.3 percent ; hazard ratio , 2.3 ; 95 percent confidence interval , 0.9 to 5.5 ) and with 23 of 671 patients receiving 400 mg of celecoxib twice daily ( 3.4 percent ; hazard ratio , 3.4 ; 95 percent confidence interval , 1.4 to 7.8 ) . Similar trends were observed for other composite end points . On the basis of these observations , the data and safety monitoring board recommended early discontinuation of the study drug . CONCLUSIONS Celecoxib use was associated with a dose-related increase in the composite end point of death from cardiovascular causes , myocardial infa rct ion , stroke , or heart failure . In light of recent reports of cardiovascular harm associated with treatment with other agents in this class , these data provide further evidence that the use of COX-2 inhibitors may increase the risk of serious cardiovascular events OBJECTIVE Acute pain can lead to immune dysfunction , which can be partly ameliorated by successful pain management . Opioids , which are widely used for analgesia , can result in the deterioration of immune function . This study aim ed to investigate the influence of morphine with or without flurbiprofen as post-operative analgesics on the immune systems of patients undergoing gastric cancer surgery . METHODS 60 patients undergoing gastric cancer surgery were equally r and omized into two groups . They received post-operative patient-controlled intravenous ( IV ) analgesia using morphine either with or without flurbiprofen . Visual analogue scale ( VAS ) scores , Bruggemann comfort scale ( BCS ) scores , morphine consumption , time of first flatus , incidence of nausea/vomiting , and T-lymphocyte subsets ( CD3⁺ , CD4⁺ , and CD8⁺ ) and natural killer cells ( CD3⁻CD16⁺CD56⁺ ) were evaluated . RESULTS No significant difference was observed in the VAS scores , BCS scores , and nausea/vomiting incidence between groups . Less morphine was consumed and the time of first flatus was earlier in patients receiving morphine with flurbiprofen than morphine alone . The expression of CD3⁺ , CD4⁺ , CD4⁺/CD8⁺ , and CD3⁻CD16⁺CD56⁺ decreased at 2 hours after incision and , except for CD3⁻CD16⁺CD56⁺ , returned to baseline at 120 hours after surgery . Moreover , the expression of CD3⁻CD16⁺CD56⁺ at 2 hours after incision and the expression of CD3⁺ , CD4⁺ , CD4⁺/CD8⁺ , and CD3⁻CD16⁺CD56⁺ at 24 hours after surgery were higher in patients receiving morphine with flurbiprofen than morphine alone . CONCLUSION The combination of morphine and flurbiprofen ameliorates the immune depression in Tlymphocyte subsets and natural killer cells and provides a similar analgesic efficacy to morphine alone in patients undergoing gastric cancer surgery Background The objective of this study was to determine if intravenous ketorolac can reduce ileus following laparoscopic colorectal surgery , thus shortening hospital stay . Methods This was a prospect i ve , r and omized , double-blind , placebo-controlled , clinical trial of patients undergoing laparoscopic colorectal resection and receiving morphine patient controlled analgesia ( PCA ) and either intravenous ketorolac ( group A ) or placebo ( group B ) , for 48 h after surgery . Daily assessment s were made by a blinded assistant for level of pain control . Diet advancement and discharge were decided according to strictly defined criteria . Results From October 2002 to March 2005 , 190 patients underwent laparoscopic colorectal surgery . Of this total , 84 patients were eligible for this study and 70 consented . Another 26 patients were excluded , leaving 22 patients in each group . Two patients who suffered anastomotic leaks in the early postoperative period were excluded from further analysis . Median length of stay for the entire study was 4.0 days , with significant correlation between milligrams of morphine consumed and time to first flatus ( r = 0.422 , p = 0.005 ) , full diet ( r = 0.522 , p < 0.001 ) , and discharge ( r = 0.437 , p = 0.004 ) . There we no differences between groups in age , body mass index , or operating time . Patients in group A consumed less morphine ( 33 ± 31 mg versus 63 ± 41 mg , p = 0.011 ) , and had less time to first flatus ( median 2.0 days versus 3.0 days , p < 0.001 ) and full diet ( median 2.5 days versus 3.0 days , p = 0.033 ) . The reduction in length of stay was not significant ( mean 3.6 days versus 4.5 days , median 4.0 days versus 4.0 days , p = 0.142 ) . Pain control was superior in group A. Three patients required readmission for treatment of five anastomotic leaks ( 4 in group A versus 1 in group B , p = 0.15 ) . Two of them underwent reoperation . Conclusions Intravenous ketorolac was efficacious in improving pain control and reducing postoperative ileus when anastomotic leaks were excluded . This simple intervention shows promise in reducing hospital stay , although the outcome was not statistically significant . The high number of leaks is inconsistent with this group ’s experience and is of concern Purpose : Flurbiprofen axetil ( FA ) is a potent non-steroidal antiinflammatory drug ( NSAID ) . We examined the effects that perioperative intravenous administration of FA , combined with thoracic epidural anesthesia and postoperative patient-controlled epidural analgesia ( PCEA ) , have on bowel function , postoperative pain , and cytokine release , after open colorectal surgery . Methods : This was a prospect i ve , r and omized , double-blind , placebo-controlled study . Forty patients were r and omly assigned to one of two groups ( n=20 in each group ) . The FA group patients received FA 1 mg·kg−1iv , 30 min before and six hours after skin incision ; whereas the control group patients received an equal volume of intralipid . Blood cytokine levels were measured before FA administration , at the end of surgery , and six hours and 24 hr postoperatively . All patients received postoperative PCEA for pain control . Analgesic efficacy was evaluated for 72 hr postoperatively using visual analogue scale ( VAS ) pain scores both at rest and during coughing . Gastrointestinal motility was recorded . Temperature and leukocyte count were measured preoperatively , and 24 hr postoperatively . Results : The times to first bowel movement ( 87±23vs 105±19 hr , P=0.008 ) and first flatus ( 63±16vs 75±11 hr , P=0.01 ) were earlier in the FA group compared to the control group . For the first 24 hr , the pain scores in the FA group were also lower during coughing ( P<0.001 compared to control ) . The plasma concentrations of interleukin (IL)-6 and IL-8 in the FA group were lower , postoperatively ( P<0.01 and P<0.05 , respectively , compared to control ) . In contrast , the IL-10 levels were significantly increased at six hours , postoperatively , in the FA group ( P=0.009 ) . The total leukocyte count and the incidence of pyrexia were also lower in patients of the FA group ( P=0.001 0.001 and P=0.006 , respectively , compared to control ) . Conclusion : Flurbiprofen axetil may have an anti-inflammatory effect in major abdominal surgery . The combination of perioperative intravenous FA , intraoperative thoracic epidural anesthesia , and postoperative PCEA facilitated recovery of bowel function , enhanced analgesia , and attenuated the cytokine response . RésuméObjectif : Le flurbiprofène axétil ( FA ) est un agent antiinflammatoire non stéroïdien ( AINS ) puissant . Nous avons évalué les effets d’une administration intraveineuse périopératoire de FA , en présence d’une anesthésie péridurale thoracique et d’une analgésie péridurale contrôlée par le patient ( APCP ) postopératoire , sur la fonction intestinale , la douleur postopératoire et la libération de cytokines à la suite d’une chirurgie colorectale ouverte . Méthode : Nous avons mené une étude prospect i ve , r and omisée , à double insu et contrôlée par placebo . Quarante patients ont été r and omisés dans deux groupes ( n=20 dans chaque groupe ) . Les patients du groupe FA ont reçu du FA 1 mg·kg-1 iv 30 min avant et six heures après l’incision de la peau ; les patients du groupe témoin ont , quant à eux , reçu un volume équivalent d’Intralipide . Les niveaux de cytokines plasmatiques ont été mesurés avant l’administration de FA , à la fin de la chirurgie , et six et 24 h après l’opération . Tous les patients ont reçu une APCP pour le contrôle de la douleur . L’efficacité analgésique a été évaluée à 72 h après l’opération sur la base des scores de douleur sur une échelle visuelle analogue ( EVA ) au repos et à la toux . La motilité gastro-intestinale a été enregistrée . La température et la numération leucocytaire ont été mesurées avant l’opération et 24 h après l’opération . Résultats : Les temps jusqu’à la première défécation ( 87±23 vs 105±19 h , P=0,008 ) et jusqu’aux premières flatuosités ( 63±16 vs 75±11 h , P=0,01 ) étaient plus courts dans le groupe FA que dans le groupe témoin . Durant les 24 premières heures , les scores de douleur à la toux étaient également moindres dans le groupe FA ( P<0,001 par rapport au groupe témoin ) . Les concentrations plasmatiques d’interleukine (IL)-6 et IL-8 étaient plus basses dans le groupe FA après l’opération ( P<0,01 et P<0,05 , respectivement , par rapport au groupe témoin ) . En revanche , les niveaux IL-10 étaient significativement plus élevés à six heures après l’opération dans le groupe FA ( P=0,009 ) . La numération leucocytaire totale et l’incidence de pyrexie étaient également plus bas dans le groupe FA ( P=0,001 et P=0,006 , respectivement , par rapport au groupe témoin ) . Conclusion : Le flurbiprofène axétil pourrait avoir un effet antiinflammatoire lors de chirurgies abdominales majeures . La combinaison de FA intraveineux périopératoire , d’anesthésie péridurale thoracique peropératoire et d’APCP postopératoire a facilité le rétablissement de la fonction intestinale , amélioré l’analgésie , et atténué la sécrétion des cytokines Previous studies have shown that recovery of colonic transit is a major determinant of post‐operative ileus and clinical recovery after gastrointestinal surgery . Prucalopride is a highly selective 5‐hydroxytryptamine receptor‐4 agonist with colonic pro‐motility effects BACKGROUND Management strategies for prolonged postoperative ileus ( PPOI ) are principally conservative and it is therefore valuable to shift attention to prevention . This study aim ed to identify prospect ively the perioperative risk factors for the development of PPOI and create a tool to predict its occurrence . METHODS Patients undergoing elective colorectal surgery at Auckl and District Health Board between September 2012 and June 2014 were enrolled . In total , 92 variables were investigated prospect ively with uniform application of a st and ardized definition of PPOI . Logistic regression and area under receiver operating characteristic curves ( AUC ) were used to generate risk stratification models . RESULTS PPOI occurred in 88 of 327 patients ( 26.9 % ) . Independent predictors of PPOI were male gender ( odds ratio [ OR ] , 3.01 ) , decreasing preoperative albumin ( OR , 1.11 per g/L unit ) , open or converted technique ( OR , 6.37 [ vs laparoscopic ] ) , increasing wound size ( OR , 1.09 [ per cm ] ) , operative difficulty ( OR , 1.28 [ per unit on 10-point Likert scale ] ) , operative bowel h and ling ( OR , 1.38 [ per unit on 10-point Likert scale ] ) , red cell transfusion ( OR , 1.84 [ per unit ] ) , intravenous crystalloid administration ( OR , 1.55 [ per liter ] ) , and delayed first mobilization ( OR , 1.39 [ per day ] ) . The I-Score assimilated preoperative and intraoperative variables to generate a score out of 6 with a 7-fold increase in risk from low-risk to high-risk strata and fair predictive capacity ( AUC , 0.742 ; 95 % CI , 0.684 - 0.799 ) . CONCLUSION Independent predictors for the development of PPOI have been identified prospect ively and used to construct a novel risk stratification model Abstract Purpose To analyze postoperative complications after laparoscopic radical cystectomy ( LRC ) and evaluate its risk factors in a large prospect i ve cohort built by the ESUT across European centers involved in minimally invasive urology in the last decade . Methods Patients were prospect ively enrolled , and data were retrospectively analyzed . Only oncologic cases were included . There were no formal contraindications for LRC : Also patients with locally advanced tumors ( pT4a ) , serious comorbidities , and previous major abdominal surgery were enrolled . All procedures were performed via a st and ard laparoscopic approach , with no robotic assistance . Early and late postoperative complications were grade d according to the modified Clavien – Dindo classification . Multivariate logistic regression was performed to explore possible risk factors for developing complications . Results A total of 548 patients were available for final analysis , of which 258 ( 47 % ) experienced early complications during the first 90 days after LRC . Infectious , gastrointestinal , and genitourinary were , respectively , the most frequent systems involved . Postoperative ileus occurred in 51/548 ( 9.3 % ) patients . A total of 65/548 ( 12 % ) patients underwent surgical re-operation , and 10/548 ( 2 % ) patients died in the early postoperative period . Increased BMI ( p = 0.024 ) , blood loss ( p = 0.021 ) , and neoadjuvant treatment ( p = 0.016 ) were significantly associated with a greater overall risk of experiencing complications on multivariate logistic regression . Long-term complications were documented in 64/548 ( 12 % ) , and involved mainly stenosis of the uretero-ileal anastomosis or incisional hernias . Conclusions In this multicenter , prospect i ve , large data base , LRC appears to be a safe but morbid procedure . St and ardized complication reporting should be encouraged to evaluate objective ly a surgical procedure and permit comparison across studies A number of interventions have been used to decrease the incidence of post‐operative paralytic ileus . A secondary outcome of a r and omized controlled study showed that COX‐2 inhibitors decreased the incidence of paralytic ileus . We sought to study a large cohort of patients undergoing major abdominal operations who were treated with a COX‐2 inhibitor Objectives To evaluate the effect of postoperative use of non-steroidal anti-inflammatory drugs ( NSAIDs ) on anastomotic leakage requiring reoperation after colorectal resection . Design Cohort study based on data from a prospect i ve clinical data base and electronically registered medical records . Setting Six major colorectal centres in eastern Denmark . Participants 2766 patients ( 1441 ( 52 % ) men ) undergoing elective operation for colorectal cancer with colonic or rectal resection and primary anastomosis between 1 January 2006 and 31 December 2009 . Median age was 70 years ( interquartile range 62 - 77 ) . Intervention Postoperative use of NSAID ( defined as at least two days of NSAID treatment in the first seven days after surgery ) . Main outcome measures Frequency of clinical anastomotic leakage verified at reoperation ; mortality at 30 days . Results Of 2756 patients with available data and included in the final analysis , 1871 ( 68 % ) did not receive postoperative NSAID treatment ( controls ) and 885 ( 32 % ) did . In the NSAID group , 655 ( 74 % ) patients received ibuprofen and 226 ( 26 % ) received diclofenac . Anastomotic leakage verified at reoperation was significantly increased among patients receiving diclofenac and ibuprofen treatment , compared with controls ( 12.8 % and 8.2 % v 5.1 % ; P<0.001 ) . After unadjusted analyses and when compared with controls , more patients had anastomotic leakage after treatment with diclofenac ( 7.8 % ( 95 % confidence interval 3.9 % to 12.8 % ) ) and ibuprofen ( 3.2 % ( 1.0 % to 5.7 % ) ) . But after multivariate logistic regression analysis , only diclofenac treatment was a risk factor for leakage ( odds ratio 7.2 ( 95 % confidence interval 3.8 to 13.4 ) , P<0.001 ; ibuprofen 1.5 ( 0.8 to 2.9 ) , P=0.18 ) . Other risk factors for anastomotic leakage were male sex , rectal ( v colonic ) anastomosis , and blood transfusion . 30 day mortality was comparable in the three groups ( diclofenac 1.8 % v ibuprofen 4.1 % v controls 3.2 % ; P=0.20 ) . Conclusions Diclofenac treatment could result in an increased proportion of patients with anastomotic leakage after colorectal surgery . Cyclo-oxygenase-2 selective NSAIDs should be used with caution after colorectal resections with primary anastomosis . Large scale , r and omised controlled trials are urgently needed OBJECTIVE : While injectable nonsteroidal anti-inflammatory drugs ( NSAIDs ) are a key component of postoperative multimodal analgesia , renal safety concerns may limit use in some patients . This study examined the renal safety of injectable HPβCD-diclofenac when given for ≤ 5 days following orthopedic or abdominal/pelvic surgery . METHODS : Pooled analysis of data from two r and omized , placebo- and active comparator-controlled phase III trials in 608 total patients was conducted . Renal safety was assessed by examining treatment-emergent adverse events ( AEs ) and postoperative blood urea nitrogen ( BUN ) and serum creatinine shifts . RESULTS : There were three renal AEs each in the HPβCD-diclofenac ( n = 318 patients ) and placebo ( n = 148 patients ) groups , and two renal AEs in the ketorolac group ( n = 142 patients ) . No significant difference in renal AE risk was detected for patients receiving HPβCD-diclofenac ( RR : 1.40 [ 0.15,13.3 ] ; P = 0.75 ) or ketorolac ( RR : 2.08 [ 0.19,22.7 ] ; P = 0.56 ) versus placebo . All renal AEs were mild or moderate in severity , and a single renal AE ( acute renal failure in a patient receiving HPβCD-diclofenac ) was treatment-related . One incidence of postoperative shift to high ( > upper limit of normal ) serum creatinine occurred in the HPβCD-diclofenac group ( n = 2 in the ketorolac group ) . Mean changes in serum creatinine or BUN did not differ significantly between patients receiving HPβCD-diclofenac and placebo . CONCLUSIONS : While this analysis examined relatively brief exposure typical for parenterally administered analgesics in the postoperative setting in patients with largely normal renal function , the results suggest that HPβCD-diclofenac use for acute postoperative pain may not be associated with added renal safety risks over placebo in this patient population Objectives Postoperative ileus ( PI ) is one of many common complications in major abdominal surgery . PI results in patient discomfort , increased gastrointestinal leakage , prolonged hospital stay , and increased medical expenses . In this study , we have investigated the morphine-sparing effects of ketorolac and its correlation with the duration of PI in patients with colorectal surgeries . Methods We collected data from 102 patients who had received elective colorectal resection . The patients were r and omly allocated into 2 groups and received intravenous patient-controlled analgesia ( IVPCA ) morphine ( M group ) or IVPCA morphine plus ketorolac ( M+K group ) . Time-scale morphine consumption ( per 12 h ) , recovery of bowel functions ( the first bowel movement and passage of flatus ) , pain scores , and opioid-related side effects were then recorded . Results Patients in the M+K group received 18.3 % less morphine than those in the M group within 72 postoperative hours . The maximal opioid-sparing effects of ketorolac appeared in 12 to 24 postoperative hours . The onset of the first bowel movement and passage of flatus was significantly less in the M+K group than in the M group . The M group showed a 5.25 times greater risk of inducing PI , a result comparable with the M+K group in colorectal surgery patients . Discussion The addition of ketorolac to IVPCA morphine has demonstrated a clear opioid-sparing effect and benefits in regards to the shortening of the duration of bowel immobility . We suggest that adding ketorolac to morphine IVPCA be included in the multimodal postoperative rehabilitation program for the early restoration of normal bowel function Objective : Prolonged ileus — the failure of postoperative ileus to resolve within a few days after major abdominal surgery — leads to significant medical consequences for the patient and costs to the hospital system . The aim of this retrospective analysis of prospect ively collected data was to identify independent preoperative and intraoperative risk factors for prolonged ileus in a large consecutive series of patients who had undergone resection for colorectal cancer . Methods : Patients were drawn from a hospital registry of 2400 consecutive resections over the period 1995–2009 . Thirty-four potential predictors of prolonged ileus were analyzed by logistic regression . Results : Prolonged ileus occurred in 14.0 % of patients . Statistically significant independent predictors of prolonged ileus were male sex ( OR : 1.7 , P < 0.001 ) , peripheral vascular disease ( OR : 1.8 , P < 0.001 ) , respiratory comorbidity ( OR : 1.6 , P < 0.001 ) , resection at urgent operation ( OR : 2.2 , P < 0.001 ) , perioperative transfusion ( OR : 1.6 , P < 0.010 ) , stoma constructed ( OR : 1.4 , P < 0.001 ) , and operation lasting ≥3 hours ( OR : 1.6 , P < 0.001 ) . Conclusions : These features can be used to alert medical and nursing staff to patients likely to experience prolonged ileus after bowel resection so that they can be monitored closely in the postoperative period and available treatments targeted toward them . These features may also be useful in the research context to facilitate the more efficient selection of high-risk patients as subjects in clinical trials of prevention or treatment Background : Postoperative ileus ( PI ) is the transient impairment of bowel motility due to surgical trauma and the associated physiological responses . Postoperative ileus results in patient discomfort , increases gastrointestinal risks , prolongs hospital stay and increases medical expenses . In this study , we investigated the effect of patient‐controlled analgesia ( PCA ) morphine with or without ketorolac on bowel functions in patients after colorectal surgeries Objective : To examine the impact of alvimopan on outcomes and costs in a rigorous enhanced recovery colorectal surgery protocol . Background : Postoperative ileus remains a major source of morbidity and costs in colorectal surgery . Alvimopan has been shown to reduce incidence of postoperative ileus in enhanced recovery colorectal surgery ; however , data are equivocal regarding its benefit in reducing length of stay and costs . Methods : Patients undergoing major elective enhanced recovery colorectal surgery were identified from a prospect ively-collected data base ( 2010–2013 ) . Multivariable analyses were employed to compare outcomes and hospital costs among patients who had alvimopan versus no alvimopan by adjusting for demographic , clinical , and treatment characteristics . Results : A total of 660 patients were included ; 197 patients received alvimopan and 463 patients had no alvimopan . In unadjusted analysis , the alvimopan group had a faster return of bowel function , shorter length of stay , and lower rates of ileus , Foley re-insertion , and urinary tract infection ( all P < 0.01 ) . After adjustment , alvimopan was associated with a faster return of bowel function by 0.6 day ( P = 0.0006 ) , and lower incidence of postoperative ileus ( odds ratio 0.23 , P = 0.0002 ) . With adjustment , alvimopan was associated with a shorter length of stay by 1.6 days ( P = 0.002 ) , and a hospital cost savings of $ 1492 per patient ( P = 0.01 ) . Conclusions : Alvimopan administration as an element of enhanced recovery colorectal surgery is associated with faster return of bowel function , lower incidence of postoperative ileus , shorter hospitalization , and a significant cost savings . These results suggest that alvimopan is cost-effective in the setting of enhanced recovery colorectal surgery protocol s , and should therefore be considered in these programs BACKGROUND R and omized trials have found that alvimopan hastens return of bowel function and reduces length of stay ( LOS ) by 1 day among patients undergoing colorectal surgery . However , its effectiveness in routine clinical practice and its impact on hospital costs remain uncertain . STUDY DESIGN We performed a retrospective cohort study of patients undergoing elective colorectal surgery in Washington state ( 2009 to 2013 ) using data from a clinical registry ( Surgical Care and Outcomes Assessment Program ) linked to a statewide hospital discharge data base ( Comprehensive Hospital Abstract Reporting System ) . We used generalized estimating equations to evaluate the relationship between alvimopan and outcomes , and adjusted for patient , operative , and management characteristics . Hospital charges were converted to costs using hospital-specific charge to cost ratios , and were adjusted for inflation to 2013 US dollars . RESULTS Among 14,781 patients undergoing elective colorectal surgery at 51 hospitals , 1,615 ( 11 % ) received alvimopan . Patients who received alvimopan had a LOS that was 1.8 days shorter ( p < 0.01 ) and costs that were $ 2,017 lower ( p < 0.01 ) compared with those who did not receive alvimopan . After adjustment , LOS was 0.9 days shorter ( p < 0.01 ) , and hospital costs were $ 636 lower ( p = 0.02 ) among those receiving alvimopan compared with those who did not . CONCLUSIONS When used in routine clinical practice , alvimopan was associated with a shorter LOS and limited but significant hospital cost savings . Both efficacy and effectiveness data support the use of alvimopan in routine clinical practice , and its use could be measured as a marker of higher quality care |
12,335 | 28,525,522 | Moreover , they were less likely to receive counseling about their diseases from healthcare providers and modify their lifestyle ( eg , reduce their diet sodium intake , control their weight ) to manage their diseases than were other ethnic population s. Individual- , interpersonal- , community- , and societal-level influences contributed to the high prevalence of cardiovascular risk factors . | Background : Despite Korean Americans being one of the fastest growing immigrant groups in the United States , little is known about their cardiovascular health or cardiovascular disease risk factors .
Purpose : The purpose of this report is to describe the prevalence of cardiovascular disease risks and their contributing factors in Korean Americans and recommend future directions for the development of cardiovascular disease prevention or management research to meet the unique needs of this ethnic group . | Purpose and Methods . To describe medication profile , diet , and exercise/physical activity in hypertensive Korean Americans , a convenience sample of 100 hypertensive Korean Americans ( KAs ) at two KA health clinics were interviewed by bilingual Korean nurses using questions from the 1988 - 1994 Third National Health and Nutrition Examination Survey ( NHANES III ) . One hundred age- and gender-matched hypertensive non-Hispanic Whites and 100 Blacks were r and omly selected from the NHANES III data set , and results were compared to describe the health disparities in lifestyle choices among the three groups . Results . The medication profile among the three groups was similar . A majority of members of all three groups had been told by health professionals to exercise for hypertension . KAs made significantly less effort to reduce salt in their diets than did members of the other two groups ( p < .05 ) . Fewer KAs than non-Hispanic Whites or Blacks were following their health professionals’advice to control or lose weight for their high blood cholesterol levels . KAs had the lowest body mass index and were older and more educated than members of the other two groups . KAs ’ primary reasons for using the KA clinic were the respect they received and the use of the Korean language . Implication s. KA health professionals need to teach their patients more about the importance of health-promoting lifestyles for hypertension and its contributing factors . More KA hypertensive patients should follow the advice of health professionals on healthy lifestyles . Nurses should continue to treat patients with respect and provide care with sensitivity to language needs of patients INTRODUCTION Korean Americans are one of the most underserved ethnic/linguistic minority groups owing to cultural and institutional barriers ; there is an urgent need for culturally competent diabetes management programs in the Korean American community for those with type 2 diabetes . The purpose of this study was to test the effectiveness of a community-based , culturally tailored , multimodal behavioral intervention program in an ethnic/linguistic minority group with type 2 diabetes . DESIGN An RCT with waitlist comparison based on the Predisposing , Reinforcing , and Enabling Constructs in Education/environmental Diagnosis and Evaluation (PRECEDE)-Policy , Regulatory , and Organizational Constructs in Educational and Environmental Development ( PROCEED ) and self-help models . Data were collected between September 2010 and June 2013 and were analyzed in August-December 2014 . Statistical significance was set at p<0.05 . SETTING / PARTICIPANTS In a naturally occurring community setting , a total of 250 Korean Americans with type 2 diabetes were r and omized into an intervention group ( n=120 ) or a control group ( n=130 ) . INTERVENTION The intervention consisted of key self-management skill-building activities through 12 hours of group education sessions , followed by integrated counseling and behavioral coaching by a team of RNs and community health workers . MAIN OUTCOME MEASURES Primary ( clinical ) outcomes were hemoglobin A1c , glucose , total cholesterol , and low-density lipoprotein at baseline and at 3 , 6 , 9 , and 12 months . Secondary ( psychosocial and behavioral ) outcomes included diabetes-related quality of life , self-efficacy , adherence to diabetes management regimen , and health literacy . RESULTS During the 12-month project , the intervention group demonstrated 1.0%-1.3 % ( 10.9 - 14.2 mmol/mol ) reductions in hemoglobin A1c , whereas the control group achieved reductions of 0.5%-0.7 % ( 5.5 - 7.7 mmol/mol ) . The differences between the two groups were statistically significant . The intervention group showed statistically significant improvement in diabetes-related self-efficacy and quality of life when compared with the control group . CONCLUSIONS RN/community health worker teams equipped with culturally tailored training can be effective in helping an ethnic/linguistic minority group manage diabetes in the community Objectives To determine the relationship between the reduction in salt intake that occurred in Engl and , and blood pressure ( BP ) , as well as mortality from stroke and ischaemic heart disease ( IHD ) . Design Analysis of the data from the Health Survey for Engl and . Setting and participants Engl and , 2003 N=9183 , 2006 N=8762 , 2008 N=8974 and 2011 N=4753 , aged ≥16 years . Outcomes BP , stroke and IHD mortality . Results From 2003 to 2011 , there was a decrease in mortality from stroke by 42 % ( p<0.001 ) and IHD by 40 % ( p<0.001 ) . In parallel , there was a fall in BP of 3.0±0.33/1.4±0.20 mm Hg ( p<0.001/p<0.001 ) , a decrease of 0.4±0.02 mmol/L ( p<0.001 ) in cholesterol , a reduction in smoking prevalence from 19 % to 14 % ( p<0.001 ) , an increase in fruit and vegetable consumption ( 0.2±0.05 portion/day , p<0.001 ) and an increase in body mass index ( BMI ; 0.5±0.09 kg/m2 , p<0.001 ) . Salt intake , as measured by 24 h urinary sodium , decreased by 1.4 g/day ( p<0.01 ) . It is likely that all of these factors ( with the exception of BMI ) , along with improvements in the treatments of BP , cholesterol and cardiovascular disease , contributed to the falls in stroke and IHD mortality . In individuals who were not on antihypertensive medication , there was a fall in BP of 2.7±0.34/1.1±0.23 mm Hg ( p<0.001/p<0.001 ) after adjusting for age , sex , ethnic group , education , household income , alcohol consumption , fruit and vegetable intake and BMI . Although salt intake was not measured in these participants , the fact that the average salt intake in a r and om sample of the population fell by 15 % during the same period suggests that the falls in BP would be largely attributable to the reduction in salt intake rather than antihypertensive medications . Conclusions The reduction in salt intake is likely to be an important contributor to the falls in BP from 2003 to 2011 in Engl and . As a result , it would have contributed substantially to the decreases in stroke and IHD mortality OBJECTIVE We estimated the prevalence and incidence of diabetes among specific subgroups of Asians and Pacific Isl and ers ( APIs ) in a multiethnic U.S. population with uniform access to care . RESEARCH DESIGN AND METHODS This prospect i ve cohort analysis included 2,123,548 adult members of Kaiser Permanente Northern California , including 1,704,363 with known race/ethnicity ( white , 56.9 % ; Latino , 14.9 % ; African American , 8.0 % ; Filipino , 4.9 % ; Chinese , 4.0 % ; multiracial , 2.8 % ; Japanese , 0.9 % ; Native American , 0.6 % ; Pacific Isl and er , 0.5 % ; South Asian , 0.4 % ; and Southeast Asian , Korean , and Vietnamese , 0.1 % each ) . We calculated age-st and ardized ( to the 2010 U.S. population ) and sex-adjusted diabetes prevalence at baseline and incidence ( during the 2010 calendar year ) . Poisson models were used to estimate relative risks . RESULTS There were 210,632 subjects with prevalent diabetes as of 1 January 2010 and 15,357 incident cases of diabetes identified during 2010 . The crude diabetes prevalence was 9.9 % and the incidence was 8.0 cases per 1,000 person-years and , after st and ardizing by age and sex to the 2010 U.S. Census , 8.9 % and 7.7 cases per 1,000 person-years . There was considerable variation among the seven largest API subgroups . Pacific Isl and ers , South Asians , and Filipinos had the highest prevalence ( 18.3 , 15.9 , and 16.1 % , respectively ) and the highest incidence ( 19.9 , 17.2 , and 14.7 cases per 1,000 person-years , respectively ) of diabetes among all racial/ethnic groups , including minorities traditionally considered high risk ( e.g. , African Americans , Latinos , and Native Americans ) . CONCLUSIONS High rates of diabetes among Pacific Isl and ers , South Asians , and Filipinos are obscured by much lower rates among the large population of Chinese and several smaller Asian subgroups BACKGROUND National health in the United States is influenced by the dietary norms brought into the country by an increasing number of immigrants . OBJECTIVES This cross-sectional study aim ed to document dietary changes and disease prevalence in relation to the length of residence in the United States for Korean Americans in Michigan . DESIGN Of 1,860 question naires mailed out , 637 ( 34.3 % ) were returned with respondent-reported information , including demographics , weight and height , chronic diseases , and dietary patterns . SUBJECTS/ SETTING Included in the final analyses were 497 first-generation Korean-American immigrants ( 263 men , 234 women , aged 30 to 87 years ) . STATISTICAL ANALYSES PERFORMED Analysis of covariance with the Tukey test and logistic regression models provided sex-specific analysis of dietary changes and disease patterns . All statistical analyses were adjusted for age . RESULTS Chronic diseases reported most frequently by men and women , respectively , were hypertension , digestive diseases , arthritis , and diabetes . Length of residence in the United States ( < or=15 years , 16 to 25 years , or > or=26 years ) was inversely associated with the prevalence of digestive diseases in men ( P=0.017 ) and women ( P=0.001 ) , and positively with respiratory diseases in men and thyroid disease in women ( P<0.05 ) . Length of residence in the United States was inversely associated with intake of rice/rice dishes in both men ( servings per week , P<0.001 ) and women ( P=0.012 ) . The prevalence of digestive diseases associated inversely with length of residence and positively with servings of rice/rice dishes consumed for Korean-American men . The age-adjusted odds ratio for digestive diseases was highest among men who had the shortest length of residence in the United States ( < or=15 years ) and greater consumption of rice/rice dishes ( > 2 servings per day ) ( odds ratio 12.10 ; P=0.03 ) . CONCLUSIONS Dietary changes of Korean-American immigrants in the United States over time were associated with changes in their chronic disease patterns . These findings may help food and nutrition professionals who work with minority immigrants because they identify factors that affect changes in dietary patterns and work toward preventing diet-related diseases . Prospect i ve studies could address underlying mechanisms of the observed diet-disease relationship with subsequent generations of Korean Americans , as well as various ethnic minority immigrants in the United States |
12,336 | 28,225,501 | Our analysis also indicated that induction chemotherapy was as effect as consolidation chemotherapy for patients who received CCRT on overall response and OS .
Conclusion : Five year OS could be improved when induction chemotherapy was added into CCRT for patients of NSCLC .
Except low rate of leucopenia , induction chemotherapy was no difference compared to consolidation chemotherapy in patients with NSCLC treated by CCRT | Background : The efficacy and toxicity of induction chemotherapy followed by concurrent chemoradiotherapy ( CCRT ) in patients with locally advanced nonsmall cell lung cancer ( NSCLC ) is unclear , we performed a systematic review and meta- analysis of published papers to quantitatively evaluate the potential benefit of induction chemotherapy . | As concomitant chemoradiotherapy for stage III NSCLC is associated with survival advantage in comparison to a sequential approach , we conducted a phase III r and omised study aim ing to determine the best sequence and safety of chemotherapy ( CT ) and chemoradiotherapy ( CT-RT ) , using a regimen with cisplatin ( CDDP ) , gemcitabine ( GEM ) and vinorelbine ( VNR ) . Unresectable stage III NSCLC patients received CDDP ( 60 mg/m(2 ) ) , GEM ( 1g/m(2 ) , days 1 and 8) and VNR ( 25mg/m(2 ) , days 1 and 8) with reduced dosage of GEM and VNR during radiotherapy ( 66Gy ) . Two cycles of CT with radiotherapy followed by two further cycles of CT alone were administered in arm A or the reverse sequence in arm B. The study was prematurely closed for poor accrual due to administrative problems . Forty-nine eligible patients were r and omised . Response rates and median survival times were , respectively 57 % ( 95 % CI : 36 - 78 % ) and 17 months ( 95 % CI : 9.3 - 24.6 months ) in arm A and 79 % ( 95 % CI : 64 - 94 % ) and 23.9 months ( 95 % CI : 13.3 - 34.5 months ) in arm B ( p>0.05 ) . Chemotherapy dose-intensity was significantly reduced in arm A. Grade 3 - 4 oesophagitis occurred in 5 patients . One case of grade 5 radiation pneumonitis was observed . In conclusion , chemoradiotherapy with CDDP , GEM and VNR appears feasible as initial treatment or after induction chemotherapy . Consolidation chemoradiotherapy seems less toxic with a better observed response rates and survival although no valid conclusion can be drawn from the comparison of both arms PURPOSE We conducted a phase III study to compare the survival impact of concurrent versus sequential treatment with radiotherapy ( RT ) and chemotherapy ( CT ) in unresectable stage III non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS Patients were r and omly assigned to one of the two treatment arms . In the sequential arm , patients received induction CT with cisplatin ( 120 mg/m2 ) on days 1 , 29 , and 57 , and vinorelbine ( 30 mg/m2/wk ) from day 1 to day 78 , followed by thoracic RT at a dose of 66 Gy in 33 fractions ( 2 Gy per fraction and 5 fractions per week ) . In the concurrent arm , the same RT was started on day 1 with two concurrent cycles of cisplatin 20 mg/m2/d and etoposide 50 mg/m2/d ( days 1 to 5 and days 29 to 33 ) ; patients then received consolidation therapy with cisplatin 80 mg/m2 on days 78 and 106 and vinorelbine 30 mg/m2/wk from days 78 to 127 . RESULTS Two hundred five patients were r and omly assigned . Pretreatment characteristics were well balanced between the two arms . There were six toxic deaths in the sequential arm and 10 in the concurrent arm . Median survival was 14.5 months in the sequential arm and 16.3 months in the concurrent arm ( log-rank test P = .24 ) . Two- , 3- , and 4-year survival rates were better in the concurrent arm ( 39 % , 25 % , and 21 % , respectively ) than in the sequential arm ( 26 % , 19 % , and 14 % , respectively ) . Esophageal toxicity was significantly more frequent in the concurrent arm than in the sequential arm ( 32 % v 3 % ) . CONCLUSION Although not statistically significant , clinical ly important differences in the median , 2- , 3- , and 4-year survival rates were observed , with a trend in favor of concurrent chemoradiation therapy , suggesting that is the optimal strategy for patients with locally advanced NSCLC The optimal schedule and regimen of chemotherapy ( CT ) in association with chemoradiation has not been established in stage III non-small-cell lung cancer ( NSCLC ) . We have compared three schedules of non-platinum-based CT plus either radiotherapy or chemoradiation . From May 2001 to June 2006 , 158 patients with unresectable stage III NSCLC were enrolled in a r and omized phase II trial with overall response rate ( ORR ) as the primary endpoint . The initial design included three arms : sequential CT followed by thoracic radiation ( TRT ) ; concurrent CT/TRT followed by consolidation CT ; and induction CT followed by concurrent CT/TRT . However , based on the preliminary results of the RTOG 9410 trial , the sequential arm was closed when 19 patients had been enrolled . All patients received two cycles of docetaxel 40 mg/m(2 ) days 1 and 8 plus gemcitabine 1200 mg/m(2 ) days 1 and 8 , as either induction or consolidation therapy . Concurrent CT/TRT consisted of docetaxel 20 mg/m(2 ) and carboplatin AUC 2 weekly plus 60 Gy TRT . No differences were found in ORR between the two arms ( 56 % and 57 % ) . Hematological toxicity was mild but significantly superior with consolidation CT ; the esophagitis rate was similar in both arms ( 16 % and 15 % ) . With a median follow-up of 57 months , no differences were found in median survival ( 13.07 and 13.8 months ) or 5-year survival ( 16.4 % and 22 % ) . This regimen can not be recommended as an alternative to platinum-based CT/TRT although it has an acceptable toxicity profile and encouraging long-term survival data ( Clinical Trials.gov NCT01652820 ) Introduction : The aim of this multicenter phase II trial was to evaluate the combination of oral vinorelbine and cisplatin with radiotherapy ( RT ) after cisplatin-docetaxel induction chemotherapy ( CT ) in patients with locally advanced non-small cell lung cancer ( NSCLC ) . Patients and Methods : Patients with previously untreated , inoperable , histologically or cytologically confirmed stage IIIA or IIIB NSCLC , with performance status ≤1 and weight loss ≤10 % received two cycles of induction CT with cisplatin ( 75 mg/m2 ) and docetaxel ( 75 mg/m2 ) every 3 weeks . Patients with a tumor response or stabilization continued to receive cisplatin ( 80 mg/m2 ) and oral vinorelbine ( 40 mg/m2 ) on days 1 and 8 for two cycles , with concomitant thoracic RT ( 2 Gy/d , 5 d/wk , and total dose 66 Gy ) . Results : Fifty-six patients were enrolled . All patients ( n = 38 ) who received CT-RT were assessable for the tumor response . There were no complete responses . In the intent-to-treat analysis , the response rates were 32.1 % after induction CT and 41.1 % after CT-RT . The median progression-free and overall survival times were 9.2 months ( 95 % confidence interval : 7–14 ) and 20.8 months ( 95 % confidence interval : 13.7–24.1 ) , respectively . Adverse effects of RT-CT were grade s 3 to 4 neutropenia ( four patients ) and grade 3 esophageal toxicity ( one patient ) . No treatment-related deaths occurred . Conclusion : The oral vinorelbine-cisplatin combination with concurrent RT is feasible and has a favorable risk-benefit ratio in stage IIIA/IIIB NSCLC PURPOSE This phase II noncomparative r and omized trial was conducted to determine the optimal sequencing and integration of paclitaxel/carboplatin with st and ard daily thoracic radiation therapy ( TRT ) , in patients with locally advanced unresected stage III non-small-cell lung cancer ( NSCLC ) . Survival data were compared with historical st and ard sequential chemoradiotherapy data from the Radiation Therapy Oncology Group . PATIENTS AND METHODS Patients with unresected stages IIIA and IIIB NSCLC , with Karnofsky performance status > or = 70 % and weight loss < or = 10 % , received two cycles of induction paclitaxel ( 200 mg/m2)/carboplatin ( area under the plasma concentration time curve [ AUC ] = 6 ) followed by TRT 63.0 Gy ( arm 1 , sequential ) or two cycles of induction paclitaxel ( 200 mg/m2)/carboplatin ( AUC = 6 ) followed by weekly paclitaxel ( 45 mg/m2)/carboplatin ( AUC = 2 ) with concurrent TRT 63.0 Gy ( arm 2 , induction/concurrent ) , or weekly paclitaxel ( 45 mg/m2)/carboplatin ( AUC = 2)/TRT ( 63.0 Gy ) followed by two cycles of paclitaxel ( 200 mg/m2)/carboplatin ( AUC = 6 ; arm 3 , concurrent/consolidation ) . RESULTS With a median follow-up time of 39.6 months , median overall survival was 13.0 , 12.7 , and 16.3 months for arms 1 , 2 , and 3 , respectively . During induction chemotherapy , grade 3/4 granulocytopenia occurred in 32 % and 38 % of patients on study arms 1 and 2 , respectively . The most common locoregional grade 3/4 toxicity during and after TRT was esophagitis , which was more pronounced with the administration of concurrent chemoradiotherapy on study arms 2 and 3 ( 19 % and 28 % , respectively ) . CONCLUSION Concurrent weekly paclitaxel , carboplatin , and TRT followed by consolidation seems to be associated with the best outcome , although this schedule was associated with greater toxicity This is phase II study evaluating a non-platinum-containing regimen , used in conjunction with radiotherapy , in patients with locally advanced non-small cell lung cancer ( NSCLC ) . Patients with non-resectable stage III NSCLC were treated with two cycles of induction gemcitabine ( 1000mg/m(2 ) ) and vinorelbine ( 25mg/m(2 ) ) given on D(1,8 ) every 21 days , followed by thoracic radiotherapy ( 60 - 66Gy ) with concurrent weekly vinorelbine ( 15mg/m(2 ) ) . The primary objective was to assess response rate and secondary objectives to assess tolerability and to determine the progression-free survival ( PFS ) and overall survival ( OS ) . Of the 42 patients enrolled on the study , 15 ( 36 % ) achieved a partial response ( PR ) after induction chemotherapy . After chemo-radiotherapy , five patients had complete response ( CR ) and 19 patients had PR , giving an overall response rate of 52 % . The median PFS was 8 months and median OS was 17 months . The regimen was tolerable , with a 21 % grade 3/4 neutropenia rate and 38 % grade 2/3 esophagitis rate PURPOSE St and ard therapy for unresectable stage III non-small-cell lung cancer includes concomitant chemoradiotherapy . In Cancer and Leukemia Group B 39801 , we evaluated whether induction chemotherapy before concurrent chemoradiotherapy would result in improved survival . PATIENTS AND METHODS Between July 1998 and May 2002 , 366 patients were r and omly assigned to arm A , which involved immediate concurrent chemoradiotherapy with carboplatin area under the concentration-time curve ( AUC ) of 2 and paclitaxel 50 mg/m2 given weekly during 66 Gy of chest radiotherapy , or arm B , which involved two cycles of carboplatin AUC 6 and paclitaxel 200 mg/m2 administered every 21 days followed by identical chemoradiotherapy . The accrual goal was 360 patients . RESULTS Thirty-four percent of patients were female , 66 % were male , and the median age was 63 years . Grade 3 or 4 toxicities during induction chemotherapy on arm B consisted mainly of neutropenia ( 18 % and 20 % , respectively ) . During concurrent chemoradiotherapy , there was no difference in severity of in-field toxicities of esophagitis ( grade 3 and 4 were , respectively , 30 % and 2 % for arm A v 28 % and 8 % for arm B ) and dyspnea ( grade 3 and 4 were , respectively , 11 % and 3 % for arm A v 15 % and 4 % for arm B ) . Survival differences were not statistically significant ( P = .3 ) , with a median survival on arm A of 12 months ( 95 % CI , 10 to 16 months ) versus 14 months ( 95 % CI , 11 to 16 months ) on arm B and a 2-year survival of 29 % ( 95 % CI , 22 % to 35 % ) and 31 % ( 95 % CI , 25 % to 38 % ) . Age , weight loss before therapy , and performance status were statistically significant predictive factors . CONCLUSION The addition of induction chemotherapy to concurrent chemoradiotherapy added toxicity and provided no survival benefit over concurrent chemoradiotherapy alone . The median survival achieved in each of the treatment groups is low , and the routine use of weekly carboplatin and paclitaxel with simultaneous radiotherapy should be re-examined Introduction : Cisplatin in combination with vinorelbine has reported an optimal activity/tolerance ratio when used in combination with radiotherapy in locally advanced unresectable non-small cell lung cancer . The currently available oral formulation of vinorelbine should be easier to use assuming a similar activity profile . An international phase II trial with vinorelbine oral and cisplatin as induction followed by oral vinorelbine and cisplatin with concomitant radiotherapy was implemented to evaluate the efficacy in terms of objective response ( OR ) following this combination as primary end point and duration or response , progression-free survival , overall survival , and safety as secondary endpoints . Material and Methods : The study included patients between 18 and 75 years , with histologically proven untreated locally advanced inoperable stage IIIA/IIIB ( supraclavicular lymph nodes and pleural effusion excluded ) non-small cell lung cancer , adequate bone marrow , hepatic and renal function , Karnofsky performance status ≥80 % . Patients were treated with oral vinorelbine 60 mg/m2 day 1,8 cycle 1 and 80 mg/m2 day 1,8 cycle 2 ( if no grade 3 - 4 toxicity ) and cisplatin 80 mg/m2 day 1 every 3 weeks for 2 cycles as induction . Patients without progression received oral vinorelbine 40 mg/m2 day 1 , 8 and cisplatin 80 mg/m2 day 1 every 3 weeks for 2 more cycles with radiotherapy 66 Gy in 6.5 weeks . Results : Patient and disease characteristics ( n = 54 ) included : median age 57 years ; female sex 24 % ; stage IIIA 48 % and IIIB 52 % ; Squamous carcinoma 59 % , Karnofsky performance status 100 % ( range , 80 - 100 % ) 50 % , patients ≥5 % weight loss at baseline 7 % . Relative dose intensities of oral vinorelbine/cisplatin were 86%/93 % and 97%/98 % at induction and in combination with radiotherapy , respectively . Forty-one patients ( 76 % ) increased oral vinorelbine from 60 to 80 mg/m2 day during induction ( reasons for nonescalation : hematological 7 patients , nonhematological 2 patients , error 4 patients ) . After two cycles of chemotherapy induction , the OR intent-to-treat in the 54 patients was 37 % . Toxicities during induction were as follows : Neutropenia G3 - 4 ( 28 % ) , Febrile Neutropenia ( 7 % ) , nausea G3 ( 11 % ) , vomiting G3 - 4 ( 9 % ) , anorexia G3 ( 4 % ) , diarrhea G4 ( 2 % ) , constipation G3 ( 2 % ) . Forty-seven out of 54 ( 87 % ) patients received concomitant chemo-radiotherapy . Median radiotherapy delivered dose was 66 Gy . Tolerance : 9 % G3 Neutropenia ; 4 % G3 dysphagia/radiation ; 2 % G3 radiation dermatitis . Late pulmonary fibrosis was reported in one patient ( 1.8 % ) . One month after completion of chemo-radiotherapy , the overall OR intent-to-treat in the 54 patients was 54 % ( 95 % CI : 40 - 67 % ) . With a median follow-up of 37 months ( 95 % CI : 34 - 41 ) the median progression-free survival and overall survival were : 12.5 ( 95 % CI : 9.6 - 16.4 ) and 23.4 ( 95 % CI : 17.6 - 29.8 ) months , respectively . Conclusion : Oral vinorelbine in combination with cisplatin is an effective combination in stage IIIA/IIIB patients . The excellent tolerance profile allowed to complete concomitant chemo-radiotherapy in 87 % of patients . Oral vinorelbine in combination with cisplatin is a new and promising option that facilitates the administration of concomitant chemo-radiotherapy with high rates of treatment completion PURPOSE We compared 2 different chemotherapeutic agents in combination with cisplatin as induction chemotherapy ( ICT ) followed by chemoradiation therapy ( CHRT ) in patients with inoperable locally advanced non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS A total of 90 patients with inoperable locally advanced NSCLC received 3 courses of ICT consisting of gemcitabine 1200 mg/m2 on day 1 and day 8 every 3 weeks and cisplatin 75 mg/m2 on day 1 every 3 weeks ( group 1 ; n = 39 ) or docetaxel 75 mg/m2 on day 1 every 3 weeks and cisplatin 75 mg/m2 on day 1 every 3 weeks ( group 2 ; n = 51 ) followed by CHRT ( docetaxel 30 mg/m2 every week and cisplatin 20 mg/m2 every week with 6600 cGy radiation therapy ) . RESULTS After the ICT , the response rate for group 2 ( 88.2 % ) was significantly higher than that of the gemcitabine-cisplatin arm ( 64.1 % ; P = .017 ) . The response assessment performed on first month after CHRT revealed statistical difference for objective response rate in group 2 when compared with group 1 ( P = .04 ) . At the median follow-up of 15.7 months ( range , 5 - 36 months ) , median overall survival ( OS ) was 12 months in group 1 ( 95 % CI , 9.1 - 14.8 ) and 29.9 months in group 2 ( 95 % CI , 16 - 43 ) . Median progression-free survival ( PFS ) was 8 months in group 1 and 15 months in group 2 . There was statistically significant difference between the 2 groups regarding OS and PFS ( P = .043 ) . CONCLUSION Our results suggest that OS , PFS , and local control rate are significantly improved with ICT consisting of docetaxel and cisplatin when compared with gemcitabine-cisplatin in inoperable locally advanced NSCLC BACKGROUND We aim ed to compare overall survival after st and ard-dose versus high-dose conformal radiotherapy with concurrent chemotherapy and the addition of cetuximab to concurrent chemoradiation for patients with inoperable stage III non-small-cell lung cancer . METHODS In this open-label r and omised , two-by-two factorial phase 3 study in 185 institutions in the USA and Canada , we enrolled patients ( aged ≥ 18 years ) with unresectable stage III non-small-cell lung cancer , a Zubrod performance status of 0 - 1 , adequate pulmonary function , and no evidence of supraclavicular or contralateral hilar adenopathy . We r and omly assigned ( 1:1:1:1 ) patients to receive either 60 Gy ( st and ard dose ) , 74 Gy ( high dose ) , 60 Gy plus cetuximab , or 74 Gy plus cetuximab . All patients also received concurrent chemotherapy with 45 mg/m(2 ) paclitaxel and carboplatin once a week ( AUC 2 ) ; 2 weeks after chemoradiation , two cycles of consolidation chemotherapy separated by 3 weeks were given consisting of paclitaxel ( 200 mg/m(2 ) ) and carboplatin ( AUC 6 ) . R and omisation was done with permuted block r and omisation methods , stratified by radiotherapy technique , Zubrod performance status , use of PET during staging , and histology ; treatment group assignments were not masked . Radiation dose was prescribed to the planning target volume and was given in 2 Gy daily fractions with either intensity-modulated radiation therapy or three-dimensional conformal radiation therapy . The use of four-dimensional CT and image-guided radiation therapy were encouraged but not necessary . For patients assigned to receive cetuximab , 400 mg/m(2 ) cetuximab was given on day 1 followed by weekly doses of 250 mg/m(2 ) , and was continued through consolidation therapy . The primary endpoint was overall survival . All analyses were done by modified intention-to-treat . The study is registered with Clinical Trials.gov , number NCT00533949 . FINDINGS Between Nov 27 , 2007 , and Nov 22 , 2011 , 166 patients were r and omly assigned to receive st and ard-dose chemoradiotherapy , 121 to high-dose chemoradiotherapy , 147 to st and ard-dose chemoradiotherapy and cetuximab , and 110 to high-dose chemoradiotherapy and cetuximab . Median follow-up for the radiotherapy comparison was 22.9 months ( IQR 27.5 - 33.3 ) . Median overall survival was 28.7 months ( 95 % CI 24.1 - 36.9 ) for patients who received st and ard-dose radiotherapy and 20.3 months ( 17.7 - 25.0 ) for those who received high-dose radiotherapy ( hazard ratio [ HR ] 1.38 , 95 % CI 1.09 - 1.76 ; p=0.004 ) . Median follow-up for the cetuximab comparison was 21.3 months ( IQR 23.5 - 29.8 ) . Median overall survival in patients who received cetuximab was 25.0 months ( 95 % CI 20.2 - 30.5 ) compared with 24.0 months ( 19.8 - 28.6 ) in those who did not ( HR 1.07 , 95 % CI 0.84 - 1.35 ; p=0.29 ) . Both the radiation-dose and cetuximab results crossed protocol -specified futility boundaries . We recorded no statistical differences in grade 3 or worse toxic effects between radiotherapy groups . By contrast , the use of cetuximab was associated with a higher rate of grade 3 or worse toxic effects ( 205 [ 86 % ] of 237 vs 160 [ 70 % ] of 228 patients ; p<0.0001 ) . There were more treatment-related deaths in the high-dose chemoradiotherapy and cetuximab groups ( radiotherapy comparison : eight vs three patients ; cetuximab comparison : ten vs five patients ) . There were no differences in severe pulmonary events between treatment groups . Severe oesophagitis was more common in patients who received high-dose chemoradiotherapy than in those who received st and ard-dose treatment ( 43 [ 21 % ] of 207 patients vs 16 [ 7 % ] of 217 patients ; p<0.0001 ) . INTERPRETATION 74 Gy radiation given in 2 Gy fractions with concurrent chemotherapy was not better than 60 Gy plus concurrent chemotherapy for patients with stage III non-small-cell lung cancer , and might be potentially harmful . Addition of cetuximab to concurrent chemoradiation and consolidation treatment provided no benefit in overall survival for these patients . FUNDING National Cancer Institute and Bristol-Myers Squibb BACKGROUND The combination of chemotherapy with thoracic radiotherapy ( TRT ) compared with TRT alone has been shown to confer a survival advantage for good performance status patients with stage III non-small cell lung cancer . However , it is not known whether sequential or concurrent delivery of these therapies is the optimal combination strategy . METHODS A total of 610 patients were r and omly assigned to two concurrent regimens and one sequential chemotherapy and TRT regimen in a three-arm phase III trial . The sequential arm included cisplatin at 100 mg/m2 on days 1 and 29 and vinblastine at 5 mg/m2 per week for 5 weeks with 63 Gy TRT delivered as once-daily fractions beginning on day 50 . Arm 2 used the same chemotherapy regimen as arm 1 with 63 Gy TRT delivered as once-daily fractions beginning on day 1 [ corrected ] . Arm 3 used cisplatin at 50 mg/m2 on days 1 , 8 , 29 , and 36 with oral etoposide at 50 mg twice daily for 10 weeks on days 1 , 2 , 5 , and 6 with 69.6 Gy delivered as 1.2 Gy twice-daily fractions beginning on day 1 . The primary endpoint was overall survival , and secondary endpoints included tumor response and time to tumor progression . Kaplan-Meier analyses were used to assess survival , and toxic effects were examined using the Wilcoxon rank sum test . All statistical tests were two-sided . RESULTS Median survival times were 14.6 , 17.0 , and 15.6 months for arms 1 - 3 , respectively . Five-year survival was statistically significantly higher for patients treated with the concurrent regimen with once-daily TRT compared with the sequential treatment ( 5-year survival : sequential , arm 1 , 10 % [ 20 patients ] , 95 % confidence interval [ CI ] = 7 % to 15 % ; concurrent , arm 2 , 16 % [ 31 patients ] , 95 % CI = 11 % to 22 % , P = .046 ; concurrent , arm 3 , 13 % [ 22 patients ] , 95 % CI = 9 % to 18 % ) . With a median follow-up time of 11 years , the rates of acute grade 3 - 5 nonhematologic toxic effects were higher with concurrent than sequential therapy , but late toxic effects were similar . CONCLUSION Concurrent delivery of cisplatin-based chemotherapy with TRT confers a long-term survival benefit compared with the sequential delivery of these therapies BACKGROUND In stage III non-small-cell lung cancer ( NSCLC ) , the role of systemic chemotherapy preceding or following concurrent chemo-radiotherapy ( CT-RT ) is unclear . We carried out a r and omized phase II study to study the toxicity involved-field CT-RT with either induction or consolidation cisplatin-docetaxel ( Taxotere ) . PATIENTS AND METHODS Patients were r and omly assigned to receive two cycles of docetaxel ( D ) 75 mg/m(2 ) on day 1 and cisplatin ( C ) 40 mg/m(2 ) on days 1 and 2 , either preceding ( IND arm ) or following ( CON arm ) concurrent CT-RT , where 66 Gy was delivered using involved-fields concurrent with weekly D 20 mg/m(2 ) and C 20 mg/m(2 ) . Patients at higher risk for lung toxicity ( V(20 ) > 35 % ) crossed over to IND arm . Seventy patients were needed to exclude grade (G)3 - 4 esophagitis in > 25 % . RESULTS Of the 70 eligible patients , 26 were treated in IND and 34 CON ; five with V(20 ) > 35 % switched from CON to IND . The differences in G3 - 4 esophagitis observed ( 32/2 % IND versus 21/3 % CON ) were not significantly different from the hypothesized 25 % rate . Rates of G≥2 pneumonitis were similar , but IND arm had less G3 - 4 neutropenia . One-year survival was 63.2 % [ 95 % confidence interval ( CI ) 48.4 % to 78.0 % ] and 65.5 % ( 95 % CI 48.2 % to 82.8 % ) for the IND and CON arms , respectively . CONCLUSION Both study arms merit further testing in patients with limited volume stage III NSCLC PURPOSE The objective of this r and omised phase II study was to evaluate the impact in terms of response and toxicities of induction or consolidation chemotherapy respectively before or after concurrent chemoradiotherapy in unresectable stage III non-small-cell lung cancer . PATIENTS AND METHODS In the induction arm , patients received induction chemotherapy with cisplatin ( 80 mg/m(2 ) ) and paclitaxel ( 200 mg/m(2 ) ) on days 1 and 29 followed by a concurrent chemoradiotherapy ( 66 Gy in 33 fractions , cisplatin 80 mg/m(2 ) days 1 , 29 and 57 , vinorelbine 15 mg/m(2 ) days 1 , 8 , 29 , 36 , 57 and 64 ) . In consolidation arm , the same concurrent chemoradiotherapy began on day 1 followed by two cycles of cisplatin and paclitaxel . RESULTS One hundred twenty seven patients were r and omised . The intent to treat response rates in induction and consolidation arms were 58 % and 56 % respectively . Median survival was 19.6 months in induction arm and 16.3 months in consolidation arm and 4-year survival rates were 21 % and 30 % respectively . Haematologic and non-haematologic toxicities were similar in both arms , except grade 3/4 oesophagitis , more frequent in consolidation arm than in induction arm ( 17 % versus 10 % ) . CONCLUSION Cisplatin-based chemotherapy as induction or consolidation with concurrent chemoradiotherapy can be administrated safely . Response rates were similar in both arms with a trend in favour for consolidation arm for long-term survival |
12,337 | 29,929,949 | Documentation and inclusion of such vital information will foster a transparent and shared decision-making process that will ultimately lead to the development of practical and user-friendly self-management apps that can enhance the quality of life for diabetes patients | BACKGROUND There is increased research interest in the use of mobile phone apps to support diabetes management .
However , there are divergent views on what constitute the minimum st and ards for inclusion in the development of mobile phone apps .
Mobile phone apps require an evidence -based approach to development which will consequently impact on their effectiveness .
Therefore , comprehensive information on developmental considerations could help design ers and research ers to develop innovative and effective patient-centered self-management mobile phone apps for diabetes patients .
OBJECTIVE This systematic review examined the developmental considerations adopted in trials that engaged mobile phone applications for diabetes self-management . | OBJECTIVE To test whether adding mobile application coaching and patient/provider web portals to community primary care compared with st and ard diabetes management would reduce glycated hemoglobin levels in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS A cluster-r and omized clinical trial , the Mobile Diabetes Intervention Study , r and omly assigned 26 primary care practice s to one of three stepped treatment groups or a control group ( usual care ) . A total of 163 patients were enrolled and included in analysis . The primary outcome was change in glycated hemoglobin levels over a 1-year treatment period . Secondary outcomes were changes in patient-reported diabetes symptoms , diabetes distress , depression , and other clinical ( blood pressure ) and laboratory ( lipid ) values . Maximal treatment was a mobile- and web-based self-management patient coaching system and provider decision support . Patients received automated , real-time educational and behavioral messaging in response to individually analyzed blood glucose values , diabetes medications , and lifestyle behaviors communicated by mobile phone . Providers received quarterly reports summarizing patient ’s glycemic control , diabetes medication management , lifestyle behaviors , and evidence -based treatment options . RESULTS The mean declines in glycated hemoglobin were 1.9 % in the maximal treatment group and 0.7 % in the usual care group , a difference of 1.2 % ( P = 0.001 ) over 12 months . Appreciable differences were not observed between groups for patient-reported diabetes distress , depression , diabetes symptoms , or blood pressure and lipid levels ( all P > 0.05 ) . CONCLUSIONS The combination of behavioral mobile coaching with blood glucose data , lifestyle behaviors , and patient self-management data individually analyzed and presented with evidence -based guidelines to providers substantially reduced glycated hemoglobin levels over 1 year Background Numerous mobile applications have been developed to support diabetes-self-management . However , the majority of these applications lack a theoretical foundation and the involvement of people with diabetes during development . The aim of this study was to develop and test a mobile application ( app ) supporting diabetes self-management among people with newly diagnosed type 2 diabetes using design thinking . Methods The app was developed and tested in 2015 using a design -based research approach involving target users ( individuals newly diagnosed with type 2 diabetes ) , research scientists , healthcare professionals , design ers , and app developers . The research approach comprised three major phases : inspiration , ideation , and implementation . The first phase included observations of diabetes education and 12 in-depth interviews with users regarding challenges and needs related to living with diabetes . The ideation phrase consisted of four interactive workshops with users focusing on app needs , in which ideas were developed and prioritized . Finally , 14 users tested the app over 4 weeks ; they were interviewed about usability and perceptions about the app as a support tool . Results A multifunctional app was useful for people with newly diagnosed type 2 diabetes . The final app comprised five major functions : overview of diabetes activities after diagnosis , recording of health data , reflection games and goal setting , knowledge games and recording of psychological data such as sleep , fatigue , and well-being . Users found the app to be a valuable tool for support , particularly for raising their awareness about their psychological health and for informing and guiding them through the healthcare system after diagnosis . Conclusions The design thinking processes used in the development and implementation of the mobile health app were crucial to creating value for users . More attention should be paid to the training of professionals who introduce health apps . Trial registration : Danish Data Protection Agency : 2012 - 58 - 0004 . Registered 6 February 2016 Numerous diabetes-management systems and programs for improving glycemic control to meet guideline targets have been proposed , using IT technology . But all of them allow only limited-or no-real-time interaction between patients and the system in terms of system response to patient input ; few studies have effectively assessed the systems ' usability and feasibility to determine how well patients underst and and can adopt the technology involved . DialBetics is composed of 4 modules : ( 1 ) data transmission module , ( 2 ) evaluation module , ( 3 ) communication module , and ( 4 ) dietary evaluation module . A 3-month r and omized study was design ed to assess the safety and usability of a remote health- data monitoring system , and especially its impact on modifying patient lifestyles to improve diabetes self-management and , thus , clinical outcomes . Fifty-four type 2 diabetes patients were r and omly divided into 2 groups , 27 in the DialBetics group and 27 in the non-DialBetics control group . HbA1c and fasting blood sugar ( FBS ) values declined significantly in the DialBetics group : HbA1c decreased an average of 0.4 % ( from 7.1 ± 1.0 % to 6.7 ± 0.7 % ) compared with an average increase of 0.1 % in the non-DialBetics group ( from 7.0 ± 0.9 % to 7.1 ± 1.1 % ) ( P = .015 ) ; The DialBetics group FBS decreased an average of 5.5 mg/dl compared with a non-DialBetics group average increase of 16.9 mg/dl ( P = .019 ) . BMI improvement-although not statistically significant because of the small sample size-was greater in the DialBetics group . DialBetics was shown to be a feasible and an effective tool for improving HbA1c by providing patients with real-time support based on their measurements and inputs OBJECTIVE Widespread use of carbohydrate counting is limited by its complex education . In this study we compared a Diabetes Interactive Diary ( DID ) with st and ard carbohydrate counting in terms of metabolic and weight control , time required for education , quality of life , and treatment satisfaction . RESEARCH DESIGN AND METHODS Adults with type 1 diabetes were r and omly assigned to DID ( group A , n = 67 ) or st and ard education ( group B , n = 63 ) and followed for 6 months . A subgroup also completed the SF-36 Health Survey ( SF-36 ) and World Health Organization-Diabetes Treatment Satisfaction Question naire ( WHO-DTSQ ) at each visit . RESULTS Of 130 patients ( aged 35.7 ± 9.4 years ; diabetes duration 16.5 ± 10.5 years ) , 11 dropped out . Time for education was 6 h ( range 2–15 h ) in group A and 12 h ( 2.5–25 h ) in group B ( P = 0.07 ) . A1C reduction was similar in both groups ( group A from 8.2 ± 0.8 to 7.8 ± 0.8 % and group B from 8.4 ± 0.7 to 7.9 ± 1.1 % ; P = 0.68 ) . Nonsignificant differences in favor of group A were documented for fasting blood glucose and body weight . No severe hypoglycemic episode occurred . WHO-DTSQ scores increased significantly more in group A ( from 26.7 ± 4.4 to 30.3 ± 4.5 ) than in group B ( from 27.5 ± 4.8 to 28.6 ± 5.1 ) ( P = 0.04 ) . Role Physical , General Health , Vitality , and Role Emotional SF-36 scores improved significantly more in group A than in group B. CONCLUSIONS DID is at least as effective as traditional carbohydrate counting education , allowing dietary freedom for a larger proportion of type 1 diabetic patients . DID is safe , requires less time for education , and is associated with lower weight gain . DID significantly improved treatment satisfaction and several quality -of-life dimensions The dem and for new healthcare services is growing rapidly . Improving accessibility of the African population to diabetes care seems to be a big challenge in most countries where the number of care centers and medical staff is reduced . Information and communication technologies ( ICT ) have great potential to address some of these challenges faced by several countries in providing accessible , cost-effective , and high- quality health care services . This paper presents the Mobil Diab system which is a telemedical approach proposed for the management of long-term diseases . The system applies modern mobile and web technologies which overcome geographical barriers , and increase access to health care services . The idea of the system is to involve patients in the therapy process and motivate them for an active participation . For validation of the system in African context , a trial was conducted in the Democratic Republic of Congo . 40 Subjects with diabetes divided r and omly into control and intervention groups were included in the test . Results show that Mobil Diab is suitable for African countries and presents a number of benefits for the population and public health care system . It improves clinical management and delivery of diabetes care services by enhancing access , quality , motivation , reassurance , efficiency , and cost-effectiveness Background Self-management is crucial in the daily management of type 2 diabetes . It has been suggested that mHealth may be an important method for enhancing self-management when delivered in combination with health counseling . Objective The objective of this study was to test whether the use of a mobile phone – based self-management system used for 1 year , with or without telephone health counseling by a diabetes specialist nurse for the first 4 months , could improve glycated hemoglobin A1c ( HbA1c ) level , self-management , and health-related quality of life compared with usual care . Methods We conducted a 3-arm prospect i ve r and omized controlled trial involving 2 intervention groups and 1 control group . Eligible participants were persons with type 2 diabetes with an HbA1c level ≥7.1 % ( ≥54.1 mmol/mol ) and aged ≥18 years . Both intervention groups received the mobile phone – based self-management system Few Touch Application ( FTA ) . The FTA consisted of a blood glucose – measuring system with automatic wireless data transfer , diet manual , physical activity registration , and management of personal goals , all recorded and operated using a diabetes diary app on the mobile phone . In addition , one intervention group received health counseling based on behavior change theory and delivered by a diabetes specialist nurse for the first 4 months after r and omization . All groups received usual care by their general practitioner . The primary outcome was HbA1c level . Secondary outcomes were self-management ( heiQ ) , health-related quality of life ( SF-36 ) , depressive symptoms ( CES-D ) , and lifestyle changes ( dietary habits and physical activity ) . Data were analyzed using univariate methods ( t test , ANOVA ) and multivariate linear and logistic regression . Results A total of 151 participants were r and omized : 51 to the FTA group , 50 to the FTA-health counseling ( FTA-HC ) group , and 50 to the control group . Follow-up data after 1 year were available for 120 participants ( 79 % ) . HbA1c level decreased in all groups , but did not differ between groups after 1 year . The mean change in the heiQ domain skills and technique acquisition was significantly greater in the FTA-HC group after adjusting for age , gender , and education ( P=.04 ) . Other secondary outcomes did not differ between groups after 1 year . In the FTA group , 39 % were substantial users of the app ; 34 % of the FTA-HC group were substantial users . Those aged ≥63 years used the app more than their younger counterparts did ( OR 2.7 ; 95 % CI 1.02 - 7.12 ; P=.045 ) . Conclusions The change in HbA1c level did not differ between groups after the 1-year intervention . Secondary outcomes did not differ between groups except for an increase in the self-management domain of skill and technique acquisition in the FTA-HC group . Older participants used the app more than the younger participants did Purpose The purpose of this study was to determine the impact of diabetes self-management education ( DSME ) in improving processes and outcomes of diabetes care as measured by a five component diabetes bundle and HbA1c , in individuals with type 2 diabetes mellitus ( T2DM ) . Methods A retrospective analysis was performed for adult T2DM patients who received DSME training in 2011–2012 from an accredited American Diabetes Association center at Intermountain Healthcare ( IH ) and had an HbA1c measurement within the prior 3 months and 2–6 months after completing their first DSME visit . Control patients were selected from the same clinics as case- patients using r and om number generator to achieve a 1 to 4 ratio . Case and control patients were included if 1 ) pre-education HbA1c was between 6.0%–14.0 % ; 2 ) their main provider was a primary care physician ; 3 ) they met the national Healthcare Effectiveness Data and Information Set criteria for inclusion in the IH diabetes registry . The IH diabetes bundle includes retinal eye exam , nephropathy screening or prescription of angiotensin converting enzyme or angiotensin receptor blocker ; blood pressure < 140/90 mmHg , LDL < 100 mg/dL , HbA1c < 8.0 % . Results DSME patients had a significant difference in achievement of the five element IH diabetes bundle and in HbA1c % compared to those without DSME . After adjusting for possible confounders in a multivariate logistic regression model , DSME patients had a 1.5 fold difference in improvement in their diabetes bundle and almost a 3 fold decline in HbA1c compared to the control group . Conclusion St and ardized DSME taught within an IH American Diabetes Association center is strongly associated with a substantial improvement in patients meeting all five elements of a diabetes bundle and a decline in HbA1c beyond usual care . Given the low operating cost of the DSME program , these results strongly support the value adding benefit of this program in treating T2DM patients Background Persistently poor glycemic control in adult type 1 diabetes patients is a common , complex , and serious problem initiating significant damage to the cardiovascular , renal , neural , and visual systems . Currently , there is a plethora of low-cost and free diabetes self-management smartphone applications available in online stores . Objective The aim of this study was to examine the effectiveness of a freely available smartphone application combined with text-message feedback from a certified diabetes educator to improve glycemic control and other diabetes-related outcomes in adult patients with type 1 diabetes in a two-group r and omized controlled trial . Methods Patients were recruited through an online type 1 diabetes support group and letters mailed to adults with type 1 diabetes throughout Australia . In a 6-month intervention , followed by a three-month follow-up , patients ( n=72 ) were r and omized to usual care ( control group ) or usual care and the use of a smartphone application ( Glucose Buddy ) with weekly text-message feedback from a Certified Diabetes Educator ( intervention group ) . All outcome measures were collected at baseline and every three months over the study period . Patients ’ glycosylated hemoglobin levels ( HbA1c ) were measured with a blood test and diabetes-related self-efficacy , self-care activities , and quality of life were measured with online question naires . Results The mean age of patients was 35.20 years ( SD 10.43 ) ( 28 male , 44 female ) , 39 % ( 28/72 ) were male , and patients had been diagnosed with type 1 diabetes for a mean of 18.94 years ( SD 9.66 ) . Of the initial 72 patients , 53 completed the study ( 25 intervention , 28 control group ) . The intervention group significantly improved glycemic control ( HbA1c ) from baseline ( mean 9.08 % , SD 1.18 ) to 9-month follow-up ( mean 7.80 % , SD 0.75 ) , compared to the control group ( baseline : mean 8.47 % , SD 0.86 , follow-up : mean 8.58 % , SD 1.16 ) . No significant change over time was found in either group in relation to self-efficacy , self-care activities , and quality of life . Conclusions In adjunct to usual care , the use of a diabetes-related smartphone application combined with weekly text-message support from a health care professional can significantly improve glycemic control in adults with type 1 diabetes . Trial Registration Australian New Zeal and Clinical Trials Registry : ACTRN12612000132842 ; https://www.anzctr.org.au/Trial/ Registration /Trial Review .aspx?ACTRN=12612000132842 ( Archived by WebCite at http://www.webcitation.org/6Kl4jqn5u ) Aims : With the increase in the number of systematic review s available , a logical next step to provide decision makers in healthcare with the evidence they require has been the conduct of review s of existing systematic review s. Syntheses of existing systematic review s are referred to by many different names , one of which is an umbrella review . An umbrella review allows the findings of review s relevant to a review question to be compared and contrasted . An umbrella review 's most characteristic feature is that this type of evidence synthesis only considers for inclusion the highest level of evidence , namely other systematic review s and meta-analyses . A methodology working group was formed by the Joanna Briggs Institute to develop method ological guidance for the conduct of an umbrella review , including diverse types of evidence , both quantitative and qualitative . The aim of this study is to describe the development and guidance for the conduct of an umbrella review . Methods : Discussion and testing of the elements of methods for the conduct of an umbrella review were held over a 6-month period by members of a methodology working group . The working group comprised six participants who corresponded via teleconference , e-mail and face-to-face meeting during this development period . In October 2013 , the methodology was presented in a workshop at the Joanna Briggs Institute Convention . Workshop participants , review authors and method ologists provided further testing , critique and feedback on the proposed methodology . Results : This study describes the methodology and methods developed for the conduct of an umbrella review that includes published systematic review s and meta-analyses as the analytical unit of the review . Details are provided regarding the essential elements of an umbrella review , including presentation of the review question in a Population , Intervention , Comparator , Outcome format , nuances of the inclusion criteria and search strategy . A critical appraisal tool with 10 questions to help assess risk of bias in systematic review s and meta-analyses was also developed and tested . Relevant details to extract from included review s and how to best present the findings of both quantitative and qualitative systematic review s in a reader friendly format are provided . Conclusions : Umbrella review s provide a ready means for decision makers in healthcare to gain a clear underst and ing of a broad topic area . The umbrella review methodology described here is the first to consider review s that report other than quantitative evidence derived from r and omized controlled trials . The methodology includes an easy to use and informative summary of evidence table to readily provide decision makers with the available , highest level of evidence relevant to the question posed BACKGROUND National data find glycemic control is within target ( A1c<7.0 % ) for 37 % of patients with diabetes , and only 7 % meet recommended glycemic , lipid , and blood pressure goals . OBJECTIVES To compare active interventions and usual care for glucose control in a r and omized clinical trial ( RCT ) among persons with diabetes cared for by primary care physicians ( PCPs ) over the course of 1 year . METHODS Physician practice s ( n=36 ) in 4 geographic areas are r and omly assigned to 1 of 4 study groups . The intervention is a diabetes communication system , using mobile phones and patient/physician portals to allow patient-specific treatment and communication . All physicians receive American Diabetes Association ( ADA ) Guidelines for diabetes care . Patients with poor diabetes control ( A1c > or = 7.5 % ) at baseline ( n=260 ) are enrolled in study groups based on PCP r and omization . All study patients receive blood glucose ( BG ) meters and a year 's supply of testing material s. Patients in three treatment groups select one of two mobile phone models , receive one-year unlimited mobile phone data and service plan , register on the web-based individual patient portal and receive study treatment phone software based on study assignment . Control group patients receive usual care from their PCP . The primary outcome is mean change in A1c over a 12-month intervention period . CONCLUSION Traditional methods of disease management have not achieved adequate control for BG and other conditions important to persons with diabetes . Tools to improve communication between patients and PCPs may improve patient outcomes and be satisfactory to patients and physicians . This RCT is ongoing BACKGROUND Type 2 diabetes is an individual health challenge requiring ongoing self-management . Remote patient reporting of relevant health parameters and linked automated feedback via mobile telephone have potential to strengthen self-management and improve outcomes . This research involved development and evaluation of a mobile telephone-based remote patient reporting and automated telephone feedback system , guided by health behavior change theory , aim ed at improving self-management and health status in individuals with type 2 diabetes . SUBJECTS AND METHODS This research comprised a r and omized controlled trial . Inclusion criteria were diagnosis of type 2 diabetes , elevated glycosylated hemoglobin ( HbA1c ) levels ( range , 6.5 - 11 % ) or use of oral diabetes medication , and 30 - 70 years of age . Intervention subjects ( n=24 ) participated in remote patient reporting of health status parameters and linked health behavior change feedback . Control participants ( n=24 ) received st and ard of care including diabetes education and healthcare provider counseling . Patients were followed for approximately 10 months . RESULTS Intervention participants achieved , compared with controls and controlling for baseline , a significantly greater mean reduction in HbA1c of -0.40 % ( 95 % confidence interval [ CI ] -0.67 % to -0.14 % ) versus 0.036 % ( 95 % CI -0.23 % to 0.30 % ) ( P<0.03 ) and significantly greater weight reduction of -2.1 kg ( 95 % CI -3.6 to -0.6 kg ) versus 0.4 kg ( 95 % CI -1.1 to 1.9 kg ) . Nonsignificant trends for greater intervention compared with control improvement in systolic and diastolic blood pressure were observed . CONCLUSIONS Sophisticated information technology platforms for remote patient reporting linked with theory-based health behavior change automated feedback have potential to improve patient outcomes in type 2 diabetes and merit scaled-up research efforts OBJECTIVE To assess the effect of additional training of practice nurses and general practitioners in patient centred care on the lifestyle and psychological and physiological status of patients with newly diagnosed type 2 diabetes . DESIGN Pragmatic parallel group design , with r and omisation between practice teams to routine care ( comparison group ) or routine care plus additional training ( intervention group ) ; analysis at one year , allowing for practice effects and stratifiers ; self reporting by patients on communication with practitioners , satisfaction with treatment , style of care , and lifestyle . SETTING 41 practice s ( 21 in intervention group , 20 in comparison group ) in a health region in southern Engl and . SUBJECTS 250/360 patients ( aged 30 - 70 years ) diagnosed with type 2 diabetes and completing follow up at one year ( 142 in intervention group , 108 in comparison group ) . INTERVENTION 1.5 days ' group training for the doctors and nurses-introducing evidence for and skills of patient centred care and a patient held booklet encouraging questions . MAIN OUTCOME MEASURES Quality of life , wellbeing , haemoglobin A1c and lipid concentrations , blood pressure , body mass index ( kg/m2 ) . RESULTS Compared with patients in the C group , those in the intervention group reported better communication with the doctors ( odds ratio 2.8 ; 95 % confidence interval 1.8 to 4.3 ) and greater treatment satisfaction ( 1.6 ; 1.1 to 2.5 ) and wellbeing ( difference in means ( d ) 2.8 ; 0.4 to 5.2 ) . However , their body mass index was significantly higher ( d=2.0 ; 0.3 to 3.8 ) , as were triglyceride concentrations ( d=0.4 mmol/l ; 0.07 to 0.73 mmol/l ) , whereas knowledge scores were lower ( d=-2.74 ; -0.23 to -5.25 ) . Differences in lifestyle and glycaemic control were not significant . CONCLUSIONS The findings suggest greater attention to the consultation process than to preventive care among trained practitioners ; those committed to achieving the benefits of patient centred consulting should not lose the focus on disease management The American Diabetes Association ’s ( ADA ’s ) St and ards of Medical Care in Diabetes is up date d and published annually in a supplement to the January issue of Diabetes Care . Formerly called Clinical Practice Recommendations , the St and ards includes the most current evidence -based recommendations for diagnosing and treating adults and children with all forms of diabetes . ADA ’s grading system uses A , B , C , or E to show the evidence level that supports each recommendation . • A — Clear evidence from wellconducted , generalizable r and omized controlled trials that are adequately powered • B — Supportive evidence from well-conducted cohort studies • C — Supportive evidence from poorly controlled or uncontrolled studies • E — Expert consensus or clinical Background Mobile health ( mHealth ) has huge potential to deliver preventative health services . However , there is paucity of literature on theoretical constructs , technical , practical , and regulatory considerations that enable delivery of such services . Objectives The objective of this study was to outline the key considerations in the development of a text message-based mHealth program ; thus providing broad recommendations and guidance to future research ers design ing similar programs . Methods We describe the key considerations in design ing the intervention with respect to functionality , technical infrastructure , data management , software components , regulatory requirements , and operationalization . We also illustrate some of the potential issues and decision points utilizing our experience of developing text message ( short message service , SMS ) management systems to support 2 large r and omized controlled trials : TEXT messages to improve MEDication adherence & Secondary prevention ( TEXTMEDS ) and Tobacco , EXercise and dieT MEssages ( TEXT ME ) . Results The steps identified in the development process were : ( 1 ) background research and development of the text message bank based on scientific evidence and disease-specific guidelines , ( 2 ) pilot testing with target audience and incorporating feedback , ( 3 ) software-hardware customization to enable delivery of complex personalized programs using prespecified algorithms , and ( 4 ) legal and regulatory considerations . Additional considerations in developing text message management systems include : balancing the use of customized versus preexisting software systems , the level of automation versus need for human inputs , monitoring , ensuring data security , interface flexibility , and the ability for upscaling . Conclusions A merging of expertise in clinical and behavioral sciences , health and research data management systems , software engineering , and mobile phone regulatory requirements is essential to develop a platform to deliver and manage support programs to hundreds of participants simultaneously as in TEXT ME and TEXTMEDS trials . This research provides broad principles that may assist other research ers in developing mHealth programs BACKGROUND Less than 63 % of individuals with diabetes meet professional guidelines target of hemoglobin A1c < 7.0 % , and only 7 % meet combined glycemic , lipid , and blood pressure goals . The primary study aim was to assess the impact on A1c of a cell phone-based diabetes management software system used with web-based data analytics and therapy optimization tools . Secondary aims examined health care provider ( HCP ) adherence to prescribing guidelines and assessed HCPs ' adoption of the technology . METHODS Thirty patients with type 2 diabetes were recruited from three community physician practice s for a 3-month study and evenly r and omized . The intervention group received cell phone-based software design ed by endocrinologists and CDEs ( WellDoc Communications , Inc. , Baltimore , MD ) . The software provided real-time feedback on patients ' blood glucose levels , displayed patients ' medication regimens , incorporated hypo- and hyperglycemia treatment algorithms , and requested additional data needed to evaluate diabetes management . Patient data captured and transferred to secure servers were analyzed by proprietary statistical algorithms . The system sent computer-generated logbooks ( with suggested treatment plans ) to intervention patients ' HCPs . RESULTS The average decrease in A1c for intervention patients was 2.03 % , compared to 0.68 % ( P < 0.02 , one-tailed ) for control patients . Of the intervention patients , 84 % had medications titrated or changed by their HCP compared to controls ( 23 % , P = 0.002 ) . Intervention patients ' HCPs reported the system facilitated treatment decisions , provided organized data , and reduced logbook review time . CONCLUSIONS Adults with type 2 diabetes using WellDoc 's software achieved statistically significant improvements in A1c . HCP and patient satisfaction with the system was clinical ly and statistically significant We conducted a r and omized controlled trial using mobile health technology in an ethnically diverse sample of 137 patients with complicated diabetes . Patients in the intervention group ( n = 72 ) were trained to measure their blood glucose with a sensor which transmitted the readings to a mobile phone via a Bluetooth wireless link . Clinicians were then able to examine and respond to the readings which were viewed with a web-based application . Patients in the control arm of the study ( n = 65 ) did not transmit their readings and received care with their usual doctor in the outpatient and /or primary care setting . The mean follow-up period was 9 months in each group . The default rate was higher in the patients in the intervention arm due to technical problems . In an intention-to-treat analysis there were no differences in HbA1c between the intervention and control groups . In a sub-group analysis of the patients who completed the study , the telemonitoring group had a lower HbA1c than those in the control group : 7.76 % and 8.40 % , respectively ( P = 0.06 ) |
12,338 | 25,300,173 | AUTHORS ' CONCLUSIONS The findings of our review do not provide evidence that high-dose oxytocin increases either vaginal delivery within 24 hours or the caesarean section rate .
There is no significant decrease in induction to delivery time at meta- analysis but these results may be confounded by poor quality trials .
High-dose oxytocin was shown to increase the rate of uterine hyperstimulation but the effects of this are not clear . | BACKGROUND When women require induction of labour , oxytocin is the most common agent used , delivered by an intravenous infusion titrated to uterine contraction strength and frequency .
There is debate over the optimum dose regimen and how it impacts on maternal and fetal outcomes , particularly induction to birth interval , mode of birth , and rates of hyperstimulation .
Current induction of labour regimens include both high- and low-dose regimens and are delivered by either continuous or pulsed infusions , with both linear and non-linear incremental increases in oxytocin dose .
Whilst low-dose protocol s bring on contractions safely , their potentially slow induction to birth interval may increase the chance of fetal infection and chorioamnionitis .
Conversely , high-dose protocol s may cause undue uterine hyperstimulation and fetal distress . | Fifty-two women undergoing labor induction and vaginal delivery at term were r and omized between two oxytocin infusion protocol s , involving hourly versus quarter-hourly increases in dose . Potential differences were sought for duration of labor , amount of uterine activity generated , and amount of oxytocin required . Starting at 0.5 mU/minute , oxytocin infusion was increased regularly in small increments every hour or every 15 minutes , according to group assignment . No differences were observed in potentially confounding clinical and demographic factors between the groups , including time to ruptured membranes . There were no clinical ly or statistically significant differences found for the duration of any phase or stage of labor , quantitative assessment of uterine activity , incidence of hyperstimulation , or neonatal outcome . The average dose of oxytocin used was lower in the hourly than in the quarter-hourly protocol ( 4.4 versus 6.7 mU/minute ; P<.005 ) . Significantly fewer patients on the hourly protocol required a maximum infusion rate exceeding 8 mU/minute ( P<.05 ) . More patients on the hourly protocol either had oxytocin discontinued completely or were maintained at 4 mU/minute or less during the active phase of labor ( P<.05 and P<.001 , respectively ) . We conclude that a slower rate of increase in oxytocin administration via continuous infusion results in no prolongation of any phase of induced labor , while permitting lower infusion rates of the drug Summary . A r and omized prospect i ve controlled trial of an automatic feed‐back controlled oxytocin infusion system ( AIS ) for the induction of labour at term was carried out in three hospitals . In primiparae , a four‐fold reduction in the total dose of oxytocin infused , for the same induction‐delivery interval , was achieved with the AIS compared with st and ard labour ward protocol s relying on midwife control of oxytocin infusion rate . In multiparae , the total dose of oxytocin infused was almost halved when the AIS was used , while the mean duration of labour was increased by 1.6 h to 7.5 h. There were no differences in the mode of delivery or Apgar scores . It is concluded that the AIS is a safe technique for induction of labour . Its use has demonstrated that term labour can be induced efficiently with a mean oxytocin infusion rate between 2–5 and 3 mU/min ( max 8.8 mU/min ) and a total oxytocin dose infused of < 5 Abstract A total of 200 women planned for labour induction were r and omised to receive high-dose oxytocin ( 6 mU/min with similar increments every 45 min ) or intermediate-dose oxytocin ( 3 mU/min with similar increments every 45 min ) . Oxytocin solution was prepared with 30 units in 500 ml saline with which the infusion rate in ml/h is numerically equal to oxytocin in mU/min . We observed that the caesarean rate ( 18 % vs 6 % , p = 0.009 ) , contraction abnormalities ( 35 % vs 14 % , p = 0.0005 ) and neonatal bilirubin levels ( 7.99 ± 2.70 vs 6.80 ± 2.65 , p = 0.002 ) were higher with high-dose than with intermediate-dose . The induction – delivery interval ( IDI ) was similar ( 10 h 13 min with high-dose and 11 h 5 min with intermediate-dose ; p = 0.237 , NS ) . Nulliparous women benefited more with intermediate-dose as the caesarean rate was higher with high-dose ( 24.6 % vs 7.9 % , p = 0.011 ) . Although the caesarean rate was higher in multiparous women with high-dose oxytocin , it was statistically not significant ( 5.7 % vs 2.7 % ; p = 0.609 ) . Oxytocin regimens for labour induction are usually high-dose ( 4–6 mU/min ) or low-dose ( 1–1.5 mU/min ) . The former is associated with more contraction abnormalities and the latter with prolonged IDI ; both result in an increased caesarean rate . In order to offset these disadvantages , an intermediate- dose regimen was selected . The increment interval of 45 min was selected in accordance with the pharmacokinetics of oxytocin . We observed a lower caesarean rate when compared with the high-dose regimen , without any increase in the IDI . Hence , we propose that the intermediate-dose oxytocin regimen should be preferred to the high-dose regimen for labour induction OBJECTIVE The objective was to test the safety and efficacy of a pulsatile oxytocin infusion protocol in which a computer-controlled pump adjusts the oxytocin dose rate on the basis of uterine activity . STUDY DESIGN A total of 358 women were enrolled in , and 310 completed , a prospect i ve , r and omized clinical trial comparing three protocol s for the induction of labor with oxytocin : aggressively managed continuous infusion , conservatively managed continuous infusion , and computer-controlled pulsatile infusion . Results were analyzed with Student t and chi 2 " goodness-of-fit " tests . RESULTS Mean doses of oxytocin in the group receiving pulsed oxytocin were approximately 20 % of the dose rates in the continuous infusion protocol s. All protocol s effectively established labor in the majority of patients , although nulliparous women with unfavorable Bishop scores were more likely to fail to establish labor within a 24-hour period when treated with the aggressive continuous protocol . There were no differences in the rates of cesarean section , hyperstimulation , blood gases , or Apgar scores among the three treatment groups . CONCLUSIONS Oxytocin dosage was minimized by use of a computer-controlled pump . With the exception of aggressively managed nulliparous women , there were no differences in the percentages of patients with successful inductions among the three protocol s. The percentage of successful inductions was lower for aggressively managed nulliparous women than for other patient and protocol groups OBJECTIVE To determine whether pulsatile oxytocin infusion improves delivery outcome in women requiring induction or augmentation of labor . STUDY DESIGN Two related r and omized controlled trials undertaken in 2 inner-city United Kingdom university hospitals ( IS RCT N72773405 ; http://www.is rct n.org/ ) . Women were r and omly assigned to a pulsatile or continuous infusion protocol . PRIMARY OUTCOME cesarean section rate ( induction trial ) ; operative delivery rate ( augmentation trial ) . RESULTS For induction , cesarean section rates were similar in women receiving pulsatile ( n = 264 , 38.3 % ) vs continuous infusion of oxytocin ( n = 257 ; 37.7 % ; risk ratio , 1.01 ; 95 % confidence interval , 0.81 - 1.26 ; P = .903 ) , but associated with increased " infusion to time of delivery " intervals ( P < .001 ) in the pulsatile group . For augmentation , pulsatile infusion result ed in higher operative delivery rates ( 70.1 % , n = 251 ) vs continuous infusion ( 62.7 % , n = 249 ; risk ratio , 1.12 ; 95 % confidence interval , 0.99 - 1.27 ; P = .077 ) and increased neonatal morbidity . CONCLUSION For induction , pulsatile infusion of oxytocin is effective , but conferred little clinical benefit . Pulsatile infusion is not recommended for augmentation OBJECTIVE To compare the efficacy and safety of arithmetic and geometric increases in oxytocin infusion dosage during induction of labor . METHODS A total of 120 pregnant women requiring induction of labor at term were r and omly assigned to receive oxytocin at dosages increasing arithmetically or geometrically . Maternal demographics , labor delivery data , and newborn outcomes were compared . The setting was the maternity unit of the Obafemi Awolowo University Teaching Hospitals Complex , Ile-Ife , Nigeria . RESULTS The mean maximum rates of oxytocin delivery needed to achieve adequate uterine contractions were similar in the 2 groups ( 24.66+/-8.34 mU/min vs. 26.38+/-8.77 mU/min , P=0.24 ) . Labor duration was significantly shorter in the geometric progression group ( 496.33+/-54.77 min vs. 421.34+/-63.91 min , P<0.001 ) . There were no differences in the rates of cesarean sections , vaginal deliveries , or uterine hyperstimulation , or in neonatal outcomes . CONCLUSION A geometric rise in the rate of oxytocin infusion delivery reduced the duration of labor without affecting the rates of cesarean sections and uterine hyperstimulation , or newborn outcomes OBJECTIVE Our objective was to compare the safety and efficacy of two accepted oxytocin induction protocol s that differ in oxytocin dose increments . STUDY DESIGN At the Carolinas Medical Center in Charlotte , North Carolina , 151 women with indications for induction of labor were prospect ively r and omized into one of two oxytocin induction protocol s. Safety and efficacy of the two protocol s were analyzed with two-tailed t tests and chi 2 . RESULTS Time from induction to establishment of a regular labor pattern was significantly shorter in the experimental group compared with the traditional group ( p = 0.03 ) . However , no significant difference was seen from onset of induction to time of delivery . Incidences of hyperstimulation were not significantly different between the two protocol s , but there was a trend toward a higher incidence of fetal heart rate changes in the experimental group ( p = 0.08 ) . CONCLUSION These data suggest that induction with larger dose increments will shorten time to adequate labor without an associated increase in uterine hyperstimulation or poor neonatal outcome . The differences in heart rate changes are concerning and merit further investigation . If confirmed by further studies , an increased risk of cord compression could outweigh the benefit of a faster onset of contractions OBJECTIVE To investigate in women of low parity ( para 1 , 2 or 3 ) whether induction of labor using a regimen of intravenous oxytocin , increasing incrementally at 30-min intervals is safer than one increasing at 15-min intervals . METHOD Two hundred and forty-five women of low parity requiring induction of labor by infusion of oxytocin were r and omly allocated to incremental increases at 30-min intervals ( 123 women ) as experimental group or 15-min intervals ( 122 women ) as the control group . In both groups forewater amniotomy was performed synchronously with oxytocin infusion using the allocated regimen . RESULTS The 30-min incremental regimen result ed in less precipitate labor , uterine hyperstimulation and a reduced length of stay in hospital . The induction delivery interval was longer with the experimental group which also had less occurrence of postpartum hemorrhage , perineal tears and puerperal pyrexia . CONCLUSION Oxytocin infusion regimen with 30 min incremental increases is safer than the regimen with 15-min incremental increases The number of cesarean births for dystocia has increased dramatically in the United States . Central to the management of dystocia is correction of ineffective labor by oxytocin administration , and contemporary obstetric practice is to stimulate labor with a low-dose oxytocin regimen . We prospect ively compared a low-dose oxytocin regimen ( 1-mU/ minute dosage increments ) with a high-dose regimen ( 6-mll/ minute dosage increments ) in 2788 consecutive singleton cephalic pregnancies . The low-dose regimen was used first for 5 months in 1251 pregnancies , and the high-dose regimen in 1537 pregnancies during the subsequent 5 months . Indications for oxytocin stimulation were divided into augmentation ( N=1676 ) and induction ( N=1112 ) . Labor stimulation was more than 3 hours shorter ( P<.0001 ) with the high-dose oxytocin regimen and associated with a reduction in neonatal sepsis ( 0.2 versus 1.3 % ; P<.01 ) . Uterine hyperstimulation was more common ( 55 versus 42 % ; P<.0001 ) with the high-dose regimen , but no adverse fetal effects were observed . High-dose augmentation result ed in significantly fewer forceps deliveries ( 12 versus 16 % ; P=.03 ) and fewer cesareans for dystocia ( 9 versus 12 % ; P=.04 ) . Similarly , failed induction was less frequent with high-dose compared with low-dose oxytocin ( 14 versus 19 % ; P=.05 ) . Although the high-dose induction regimen was associated with a significantly increased cesarean incidence for fetal distress ( 6 versus 3 % ; P=.05 ) , the incidence of umbilical artery cord blood acidemia was not increased in this subset . Induction of labor with high-dose oxytocin is problematic because of risk-benefit considerations . Although induction failed less frequently with the high-dose regimen , cesarean for fetal distress was performed more frequently . In contrast , high-dose oxytocin to augment ineffective spontaneous labor minimized the number of cesareans done for dystocia OBJECTIVE To test the hypothesis that high-dose oxytocin , when used in a masked fashion , would result in shorter labors and less need for cesarean delivery . METHODS We conducted r and omized , double-masked trials of high-dose compared with low-dose oxytocin for augmentation and induction of labor . Patients were r and omly assigned to receive oxytocin by either a low-dose protocol ( 1.5 mU/minute initially , increased by 1.5 mU/minute every 30 minutes ) or a high-dose protocol ( 4.5 mU/minute initially , increased by 4.5 mU/minute every 30 minutes ) . Oxytocin solutions were prepared by a central pharmacy and infusion volumes ( mL/hour ) were identical , thus ensuring double masking . RESULTS A total of 1307 patients were r and omized ( induction , 816 ; augmentation , 491 ) . In the group receiving oxytocin for induction , high-dose oxytocin was associated with a significant shortening of labor ( oxytocin to complete dilatation : 9.7+/-0.3 compared with 7.8+/-0.2 hours , P<.001 ; oxytocin to delivery : 10.5+/-0.3 compared with 8.5+/-0.3 hours , P<.001 ) . The cesarean delivery rate with low-dose oxytocin was 15.0 % , compared with 11.3 % with high-dose oxytocin ( P = .17 ) . For nulliparous women undergoing induction , cesarean delivery rates were as follows : Total 17.3 % ( low dose ) compared with 11.7 % ( high dose ) , P = .15 ; cephalopelvic disproportion 11.9 % ( low dose ) compared with 5.9 % ( high dose ) , P = .06 . When used for augmentation , high-dose oxytocin again was associated with a significant shortening of labor without a significant difference in cesarean birth rates . No differences in neonatal outcomes were noted between the groups for either augmentation or induction . CONCLUSION When used in a double-masked fashion , high-dose oxytocin is associated with significantly shorter labors without any demonstrable adverse fetal or neonatal effects In a prospect i ve r and omized study , 20 patients with term pregnancies underwent induction of labor with either continuous or pulsed ( every 8 minutes ) intravenous oxytocin infusion . There were no significant differences with respect to induction-labor interval , induction-delivery interval , cesarean section rates , need for pain relief and Apgar scores . Sixty percent of patients receiving continuous oxytocin infusion developed uterine hyperstimulation but only 10 % receiving pulsed oxytocin did so . However , the difference was not significant . The mean + /- SEM total amount of oxytocin given by continuous infusion was 4237 + /- 1066 mU which was 70 % more than by pulsatile infusion ( 2454 + /- 808 mU ) . The highest rate of oxytocin infused was significantly lower by pulsatile administration ( 5.2 + /- 0.8 mU/min ) than by continuous infusion ( 9.2 + /- 1.8 mU/min , p = less than 0.05 ) . Our study demonstrates that pulsed administration of oxytocin every 8 minutes is as effective and safe as continuous intravenous infusion of oxytocin for induction of labor , requires less oxytocin with therefore , a wider margin of safety and is consistent with the pulsatile release of oxytocin during normal labor The objective of this study was to compare the efficacy and complications of intermittently pulsed oxytocin administration with continuous infusion in the induction of labor . Patients undergoing scheduled induction of labor at term were r and omized to a pulsatile group in which oxytocin was infused in boluses every 8 minutes or to a control group in which oxytocin was administered through a conventional continuous intravenous infusion . A total of 38 patients were studied . The groups were similar with respect to parity , gestational age , indication for induction , preinduction Bishop 's score , and the use of prostagl and in gel for cervical ripening . The average induction-to-delivery interval was similar in both groups ( 14 hours ) . The frequency of uterine hyperstimulation was similar in both groups , as was the frequency of uterine of decreases in the rate of oxytocin infusion for any reason . The rate of cesarean delivery was similar ( three in each group ) . The frequency of failed induction was similar with three in the pulsatile group and none in the continuous group . Pulsatile infusion of oxytocin was as efficacious as continuous infusion . However , it seems to offer no clinical advantage in this situation In a prospect i ve , r and omized study , 106 patients underwent induction of labor with either pulsed ( every 8 minutes ) ( n = 50 ) or continuous ( n = 56 ) intravenous infusion of oxytocin . Maternal characteristics , gestational age at induction , induction-delivery interval , analgesia for labor , cesarean section rates , and newborn characteristics were similar in both groups . The mean + /- SEM total oxytocin administered was significantly less in the pulsed group ( 3564 + /- 487 mU ) than in the continuous group ( 7684 + /- 844 mU ; p less than 0.0001 ) ; the average dose of oxytocin administered per minute was significantly lower in the pulsed group ( 3.9 + /- 0.3 mU/min ) than in the continuous group ( 7.8 + /- 0.4 mU/min ; p less than 0.0001 ) ; the peak or highest administered dose of oxytocin expressed per minute was also signficantly lower in the pulsed group ( 9.6 + /- 0.8 mU/min ) than in the continuous group ( 14.1 + /- 0.7 mU/min ; p less than 0.0001 ) . These significant differences persisted even when controlled for parity , Bishop 's score of the cervix , and number of days induction of labor was carried out . Uterine hyperstimulation occurred infrequently in both groups ( 3.6 % to 4.0 % ) . The pulsed group required a significantly smaller infusion volume ( 25 + /- 14 ml ) than the continuous group ( 780 + /- 84 ml ; p less than 0.0001 ) . Thus pulsatile administration uses significantly less oxytocin and infusion fluid but is as effective and safe as continuous infusion Objective : To compare the efficacy and safety of sustained-release dinoprostone vaginal pessary and concurrent high-dose oxytocin infusion with sustained-release dinoprostone vaginal pessary followed 6 h later by high-dose oxytocin infusion for cervical ripening and labor induction . Methods : A total of 500 nulliparous or multiparous women with a singleton pregnancy , Bishop score ≤4 and admitted for labor induction . Women were r and omly assigned to induction of labor using intravaginal dinoprostone with concurrent high-dose oxytocin ( n = 250 ) or intravaginal dinoprostone pessary followed 6 h later by high-dose oxytocin ( n = 250 ) . The primary outcome was the number of vaginal deliveries achieved within 24 h of labor induction . Results : Baseline characteristics of both groups were comparable . Vaginal delivery within 24 h of labor induction was significantly increased with sustained-release dinoprostone followed 6 h later by high-dose oxytocin infusion ( 92.8 vs. 82.0 % , RR 2.82 , 95 % CI 1.58–5.04 ) . There were more cesarean section deliveries in the dinoprostone with concurrent high-dose oxytocin group ( 16.8 vs. 6.8 % , RR 0.36 , 95 % CI 0.20–0.65 ) . Maternal outcomes did not differ significantly . An Apgar score of < 7 at 5 min was found more often in the dinoprostone with concurrent high-dose oxytocin group ( 3.6 % ) in comparison to dinoprostone pessary followed 6 h later by high-dose oxytocin ( 0.8 % ) , although this was not statistically different ( RR 0.21 , 95 % CI 0.04–1.01 ) . Conclusion : Sustained-release dinoprostone followed 6 h later by high-dose oxytocin infusion appears to be safer and more effective than sustained-release dinoprostone with concurrent high-dose oxytocin infusion in achieving cervical ripening and successful vaginal delivery One hundred twenty-three women were r and omized to receive either of two regimens of oxytocin for labor induction . Sixty-one received a low-dose regimen , with oxytocin increases at intervals of not less than 60 minutes . Patients with unripe cervices received prolonged low-dose oxytocin priming before membrane rupture . Sixty-two others received a traditional protocol , with oxytocin increased every 20 minutes as required . Both groups had amniotomy when deemed safe and feasible . Oxytocin was adjusted for uterine hyperstimulation or abnormal fetal heart rate patterns in 29 and 58 % of low-dose and traditional protocol subjects , respectively ( P<.001 , odds ratio 3.6 ) . No significant increase in time to delivery was seen with low-dose oxytocin infusion . Cesarean delivery and cesareans for fetal distress were more frequent in the traditional protocol group . This study demonstrates that a continuous low-dose protocol for oxytocin induction of labor is effective in establishing active labor and achieving vaginal delivery in women with both ripe and unripe cervices . It is also associated with fewer episodes of uterine hyperstimulation requiring adjustments of oxytocin infusion than is the traditional protocol of this institution Objective : To evaluate cervical ripening with foley balloon combined with a fixed vs. incremental low-dose oxytocin infusion . Methods : Women presenting for term labor induction were r and omized to fixed low-dose or st and ard incremental low-dose oxytocin infusion following foley balloon placement . The primary outcome was time from foley balloon placement to delivery . Results : Among 116 subjects , there was no difference in median time to delivery among subjects receiving fixed low-dose vs. st and ard incremental low-dose oxytocin during induction of labor with a foley balloon ( 23.7 vs. 19.2 hours ) . There were no differences between the two groups in median time to foley bulb extrusion , active labor and second stage of labor or incidence of uterine tachysystole , fetal heart rate abnormalities , mode of delivery or maternal hemorrhage . Conclusions : There is no difference in median time to delivery in women undergoing cervical ripening with a foley balloon combined with a fixed low-dose or st and ard incremental low-dose oxytocin EDITORIAL COMMENT : : The onset of labour is induced in approximately 1 in 5 women , and spontaneous labours are augmented with oxytocin infusions in 1 in 6A . At the Mercy Maternity Hospital , and presumably in many other midwifery hospitals , the incidence of surgical induction of labour is 23 % and 85 % of women having surgical induction receive an oxytocin infusionB. These statistics bear witness to the enormous workload imposed upon labour ward nursing staff whose duty it is to supervise the administration of oxytocin infusions Background . To assess the efficacy and safety of a high‐dosage oxytocin induction regimen Objective : To compare two low-dose oxytocin protocol s in terms of fetal distress , uterine hyperstimulation , cesarean delivery rate , maximum dose of oxytocin , and length of labor . Methods : We r and omized 865 patients into 15-minute ( incremental dose 1 mU/minute until 5 mU/minute , then 1 or 2 mU/minute ) or 40-minute ( incremental dose 1.5 mU/minute until 7 mU/minute , then 1.5 or 3.0 mU/minute ) low-dose protocol s. Before oxytocin use , all subjects were stratified according to parity and purpose of oxytocin , ie , for induction or augmentation of labor . Results : The 40-minute dosing protocol had a significantly lower maximum dose of oxytocin ( augmentation , 6.5 versus 8.2 mU/minute , P < .001 ; induction , 11.5 versus 14.5 mU/minute , P < .001 ) , a lower incidence of uterine hyperstimulation ( augmentation , 18.8 versus 31.8 % , P < .001 ; induction , 19.1 versus 33.0 % , P < .002 ) , and less fetal distress ( augmentation , 15.5 versus 26.1 % , P < .005 ) . No significant differences were found in the cesarean rate or length of labor . Conclusion : A dosing interval of 40 minutes led to lower incidences of uterine hyperstimulation and fetal distress , and decreased the maximum dose of oxytocin , without affecting the length of labor or the cesarean rate OBJECTIVES To compare the efficacy and complications of oxytocin dose increments at 20- and 60-min intervals for induction of labor in women with low parity . METHODS One hundred women of low parity requiring induction of labor were r and omly allocated to 20- and 60-min oxytocin dose increments , 50 patients in each group . The basal oxytocin dose was 1 milliunit/min and doubling of the oxytocin dose was done at intervals of 20 and 60 min . RESULTS The group with 60-min increments had a decreased incidence of uterine hyperstimulation , cesarean section and operative vaginal delivery . The induction-delivery interval was similar in both groups . CONCLUSION The oxytocin infusion regimen with increments at 60-min intervals is safer than and equally effective as 20-min incremental intervals Abstract Objective : To investigate the relationship of neonatal bilirubin levels to oxytocin infusion and the diluent used for oxytocin infusion . Material s and methods : The study was carried out as a prospect i ve , r and omized study in Istanbul University Cerrahpasa School of Medicine , Department of Obstetrics and Gynecology between January to December in 1995 . A total of 80 patients managed with oxytocin during labor , enrolled to the study . These patients r and omly divided into isotonic % 0.9 saline ( Group 1 ) and 5 % glucose solutions ( Group 2 ) by a consecutive order using a balanced block r and omization scheme . Forty multiparous patients delivering without oxytocin infusion formed the control group ( Group 3 ) . The details of maternal age , gestational age , labor duration , mode of delivery , birth weight of the babies , total volume of fluid administered until delivery and total oxytocin dose were noted in each case . Sodium and initial bilirubin levels were measured in the cord blood . Later on , capillary blood bilirubin and hematocrit concentrations were measured on day 1 and 2 in the newborn nursery . The groups were compared according to these parameters . Results : The data of 29 patients in Group 1 , 36 patients in Group 2 and 40 patients in Group 3 were suitable for analysis . The difference between study and control groups regarding the rate of hyponatremia , neonatal hyperbilirubinemia and neonatal jaundice was not statistically significant . Cord plasma sodium levels , cord plasma bilirubin levels and day 1 and 2 hematocrit and plasma bilirubin levels were not statistically different between the groups . Unrespectable of the diluent used , the cord plasma bilirubin levels and day 2 plasma bilirubin levels were significantly higher in the accelerated group . Conclusion : No significant effect of oxytocin infusion was revealed on neonatal hyperbilirubinemia unless oxytocin was for the augmentation of labor A r and omized controlled trial was mounted in which induction of labour at term was successfully accomplished in 12 patients by amniotomy and intermittent ( or pulsed ) oxytocin , compared with 16 patients receiving continuous oxytocin . In the pulsed group , oxytocin was infused for one minute in every ten using a modified Cardiff Infusion System Mark III in the automatic setting . Compared with the control group the induction‐delivery and induction‐to‐full‐dilatation intervals were similar but the total dose of oxytocin required was significantly lower in the pulsed group than in the control group In addition to membrane rupture , pharmacological doses of oxytocin ( 2.6 mU/minute rusing stepwise to 422.4 mU/minute ) were used in 134 patients and the results compared to those obtained in 144 patients given only physiological doses of oxytocin ( 2.6 to 13.2 mU/minute ) . Pharmacological doses of oxytocin gave better results in terms of induction-delivery intervals , incidence of failed inductions and puerperal morbidity . The incidence of hypertonus was similar in both groups and unrelated to oxytocin doses . A uterine activity of 276 Montevideo units , modified to 200 to 220 Montevideo units for gr and e multiparae , is defined as the goal of oxytocin treatment in induction of labour . A sign of imminent uterine tetany in the intrauterine pressure curve ( the ' damping sign ' ) is described Objective . To show that early discontinuation of oxytocin will not increase the mean duration of the active labor phase in a clinical ly significant way . Design . Controlled non‐inferiority study . Setting . Department of Obstetrics and Gynecology , University of Caen , Clémenceau Hospital , France . Population . A total of 138 women with singleton pregnancy and a vertex presentation of over 34 gestational weeks , presenting a medical indication of induction of labor or a dystocia at onset of labor , from May 2005 to June 2006 . Methods . Two parallel groups were compared : continuation of oxytocin until delivery versus discontinuation of oxytocin at the onset of the active phase . The clinical ly acceptable increase in mean duration of the active phase of labor ( non‐inferiority margin ) was set at 60 minutes . Main outcome measures . Primary outcome measure was duration of the active labor phase . Secondary outcome measures included total duration of labor , parameters concerning oxytocin use , rates of uterine hyperstimulation and fetal heart rate ( FHR ) abnormalities , and mode of delivery . Some neonatal outcomes were also analyzed . Results . Equivalence of the two strategies ( continuation vs. discontinuation of oxytocin ) was not demonstrated ( p = 0.97 testing for non‐inferiority ) , the active phase even being significantly longer by a mean of 113 minutes ( p = 0.0001 testing for superiority ) . The rates of cesarean sections , alterations of FHR and delivery hemorrhage were higher when oxytocin was continued , but not significantly . There were significantly more infants hospitalized in neonatology when oxytocin was continued ( p = 0.028 ) . Conclusions . Discontinuation of oxytocin at the onset of the active phase prolongs labor . We found no argument for discontinuing the infusion of oxytocin at the onset of the active phase Objective : To determine whether an increase in the oxytocin dosing interval would decrease the incidence of uterine hypers timulation . Methods : This study included 1801 consecutive pregnancies receiving high-dose oxytocin . Oxytocin was used for labor augmentation in 1167 and induction in 634 women . Twenty- and 40-minute dosage intervals were compared . The study period was based on an 80 % likelihood of detecting S and 10 % differences in the cesarean and hyperstimulation rates , respectively . Statistics were analyzed with X1 , Fisher , and Wilcoxon rank-sum tests where appropriate . Multivariate logistic regression and analysis of covariance were used to control for confounding demographic variables . Results : Comparison of the 20- and 40-minute regimens for labor induction yielded no differences in the rates of cesarean delivery for dystocia ( 16 versus 19%% ) or fetal distress ( 5 versus 6 % ) . The 20-minute regimen for augmentation was associated with a significant reduction in cesarean for dystocia ( 8 versus 12 % P=.05 ) . The incidence of uterine hyperstimulation was greater with the 20-minute than the 40-minute regimen for induction ( 40 versus 31 % P=.02 ) , but not for augmentation ( 31 versus 28 % ) . Neonatal outcomes were unaffected by the dosage interval for both augmentation and induction . Conclusion : A 40-minute dosing interval for high-dose oxytocin offers no clear advantage over a 20-minute interval . Both regimens were safe and efficient , with no differences in perinatal outcome . The 20-minute interval was associated with fewer cesareans for dystocia when used for labor augmentation , whereas the 40-minute interval result ed in less hyperstimulation when used for labor induction . ( Obstet Gynecol 1994;83:234r4 OBJECTIVE Our purpose was to compare the efficacy and safety of low-dose versus high-dose oxytocin regimens in the augmentation of labor . STUDY DESIGN Three hundred ten term pregnancies requiring augmentation of labor underwent r and omization to receive either a low-dose or high-dose oxytocin augmentation regimen . Maternal demographics , labor-delivery data , and neonatal outcome were compared . RESULTS The high-dose oxytocin group had a significantly lower cesarean section rate , regardless of parity ( 10.4 % vs 25.7 % , p < 0.001 ) , with no differences in maternal complications and neonatal outcomes . The time needed to correct the labor abnormality was also significantly decreased ( 1.24 + /- 1.4 hours vs 3.12 + /- 1.6 hours , p < 0.001 ) in the high-dose group . CONCLUSIONS The use of high-dose oxytocin regimen benefits both nulliparous and multiparous women requiring labor augmentation by significantly lowering both the time necessary to correct the labor abnormality and the need for cesarean section In a prospect i ve r and omized study , 560 pregnant women were subjected to labor induction with continuous or pulsed intravenous oxytocin infusion . There were no significant differences with respect to maternal history , Bishop score and perinatal morbidity . The mean induction to delivery interval was shorter in the pulsed infusion group than in the continuous infusion group ( 325 + /- 63 vs 433 + /- 67 min in primiparous , p < 0.001 and 204 + /- 52 vs 236 + /- 87 min in multiparous women , p < 0.01 ) . The mean amount of oxytocin administered in the pulsed infusion group was also significantly lower than in the continuous infusion group ( 4.7 + /- 0.6 mU/min versus 9.6 + /- 3.4 mU/min in primiparous , p < 0.001 and 2.1 + /- 0.4 mU/min versus 5.2 + /- 2.3 mU/min in multiparous women , p < 0.001 ) . Our study demonstrates that pulsatile administration of oxytocin is as safe as continuous intravenous infusion , requires less oxytocin and is more effective as it reduces labor duration OBJECTIVE The purpose of this study was to determine whether there is an increase in the cesarean delivery rate in women who undergo induction when oxytocin is discontinued in the active phase of labor . STUDY DESIGN We conducted a prospect i ve r and omized controlled trial of women who underwent induction of labor at term ; they were assigned r and omly to either routine oxytocin use ( routine ) or oxytocin discontinuation ( DC ) once in active labor . Analysis was by intention to treat . RESULTS Two hundred fifty-two patients were eligible for study analysis : 127 patients were assigned r and omly to the routine group and 125 patients were assigned r and omly to the DC group . Cesarean delivery rate was similar between the groups ( routine , 25.2 % [ n = 32 ] vs the DC group , 19.2 % [ n = 24 ] ; P = .25 ) . There was a higher chorioamnionitis rate and slightly longer active phase in those women who were assigned to the DC group . In adjusted analysis , the rate of chorioamnionitis was not different by r and omization group but was explained by the duration of membrane rupture and intrauterine pressure catheter placement . CONCLUSION Discontinuation of oxytocin in active labor after labor induction does not increase the cesarean delivery rate significantly Objective : To compare induction of labor by intravenous oxytocin in regimens increasing incrementally at 15- and 30-minute intervals . Methods : In a r and omized controlled trial , 124 primigravidas requiring induction of labor by oxytocin infusion were r and omly allocated to incremental increases at 30-minute intervals ( 62 patients ) or 15-minute intervals ( 62 patients ) . The main outcomes assessed were mode of delivery , complications of labor and delivery ( precipitate labor , hyperstimulation , postpartum hemorrhage , perineal tears , puerperal pyrexia ) , and number of days in the hospital . Results : The 30-minute incremental regimen result ed in less precipitate labor ( odds ratio 0.233 , 95 % confidence interval [ CI ] 0.042 - 0.55 , x1=4.133 ) , less uterine hyperstimulation ( odds ratio 0.17 , 95 % CI 0.015 - 1.906 ) , and reduced length of stay in the hospital ( difference in medians 3 days , 95 % CI for difference in medians 2 - 4 days ) . The inductiondelivery interval was longer with 30 minutes ( median 8 hours ) than with 15 minutes ( median 5 hours ) ( difference in medians 2 hours , 95 % CI for difference in medians 0 - 3 hours ) . With the 30-minute interval , there was a reduction in the occurrence of postpartum hemorrhage , perineal tears , and puerperal pyrexia , but these differences did not reach statistical significance . Conclusion : For the induction of labor in primigravidas , 30-minute incremental increases in the infusion rate of oxytocin were superior to a 15-minute incremental protocol in reducing the incidence of hyperstimulation and precipitous labor . ( Obstet Gynecol 1994;83:229 - 33 Objective To answer the question of whether oxytocin induction of labour should be discontinued when active labour begins OBJECTIVE To improve the safety and the effect on induction of labor with oxytocin . METHOD 112 cases were selected for labor induction with feedback pulsatile oxytocin under the monitoring of uterine contraction controller ( study group ) . 112 cases were selected with continuous intravenous infusion of oxytocin as a control ( control group ) . The dose of oxytocin and the pulse time-point were adjusted . The effects of labor induction in the 2 groups were compared . RESULTS The most suitable time-point was 1.5 minute after the uterine contraction . The best administration duration was 20 seconds . But the most suitable dose varied individually , generally 12 - 25 mU. The mean time to establish contraction in study group was significantly shorter ( 1.9 + /- 1.2 min ) than that of the control group ( 115.5 + /- 72.3 min , P < 0.001 ) . The average dose of oxytocin administered per hour was significantly less in the study group ( 312 + /- 64 mU ) than that of the control group ( 735 + /- 125 mU , P < 0.001 ) the success rate was 100 % in study group whereas only 90.2 % in control group ( P < 0.01 ) . The total duration of labor in the study group was 6.9 + /- 4.7 hours in contrast to 20.4 + /- 10.9 hours in the control group ( P < 0.001 ) . The occurrences of dystocia , postpartum hemorrhage and neonatal asphyxia were lower in study group . CONCLUSION This study proved that the administration of oxytocin with the feedback pulsatile oxytocin system is easier to establish the effective uterine contraction , and it is a more physiologic and effective regimen for induction of labor The ideal regimen for induction of labor with oxytocin with respect to the magnitude and frequency of dosage changes has not been defined . In spite of few data regarding labor induction with an unfavorable cervix , the initial dose recommended by the American College of Obstetricians and Gynecologists is lower than that of other commonly used protocol s. Eighty patients with unfavorable cervices and unruptured membranes , without evidence of labor , were r and omized to one of two protocol s and met criteria for data analysis . Patients in both protocol s were given an initial dose of oxytocin of 2 mU/min . Patients in protocol A ( n = 32 ) then received incremental increases of oxytocin of 1 mU/min at 30-minute intervals , while those in protocol B ( n = 48 ) received incremental increases of 2 mU/min at 15-minute intervals . Induction failures were higher among patients on protocol A ( 31 % vs 8 % , p less than 0.05 ) . Patients on protocol B had shorter times to delivery ( mean = 10 hours 57 minutes vs 8 hours 3 minutes ; p less than 0.05 ) . The number of operative deliveries were similar regardless of protocol . There were no significant differences ( p = NS ) among groups and protocol s in maternal and fetal complications , cesarean section rate , and uterine hyperstimulation . In this population a more aggressive protocol may lead to fewer induction failures and shorter induction-to-delivery intervals |
12,339 | 28,434,203 | This review does not provide sufficient evidence to support topiramate for the treatment of people with JME .
Based on the current limited available data , topiramate seems to be better tolerated than valproate , but there were no more benefits of efficacy in topiramate compared with valproate . | BACKGROUND Topiramate is a newer broad-spectrum antiepileptic drug ( AED ) .
Some studies have shown the benefits of topiramate monotherapy in the treatment of juvenile myoclonic epilepsy ( JME ) .
However , there are no current systematic review s to determine the efficacy and tolerability of topiramate monotherapy in people with JME .
OBJECTIVES To evaluate the efficacy and tolerability of topiramate monotherapy in the treatment of JME . | 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 PURPOSE To describe our experience with levetiracetam ( LEV ) as initial or conversion monotherapy treatment for juvenile myoclonic epilepsy ( JME ) . Valproate , the usual first line agent for JME , has chronic adverse effects , particularly for women of childbearing potential . Since JME requires lifetime treatment , chronic adverse effects of therapy are important consideration . METHODS We review ed the medical records of patients with JME treated with LEV in the first 4 years after marketing . We recorded demographic data , results of EEG and imaging studies , antiepileptic drug ( AED ) history , LEV initial dose and final dose , side effects related to LEV , and therapeutic response to treatment . We classified JME into definite and probable based on clinical and EEG criteria . The minimum duration of follow up was 1 year . RESULTS LEV was the first therapy in 12 patients and the initial appropriate agent in 16 . Fourteen patients had been treated with another appropriate AED . Eighty percent ( 24/30 ) of patients became seizure free with LEV monotherapy and two additional patients showed improved seizure control . Final therapeutic doses of LEV ranged from 12 to 50mg/(kgday ) . Complete seizure control using LEV was not predicted by previous AED use . Treatment failure with valproate also did not predict failure of LEV . Patients with definite JME responded best within the study group ( 11 of 11 seizure free , p<0.05 ) . CONCLUSIONS This study supports consideration of LEV for first line treatment of JME and suggests the need for a large prospect i ve trial OBJECTIVE The aim of this study was to evaluate the efficacy and tolerability of topiramate ( TPM ) in juvenile myoclonic epilepsy ( JME ) . METHOD We assessed seizure control and adverse effects of TPM in 22 patients ( 18 females ) aged 13 to 53 years . Target TPM dosage was up to 200 mg/day . The patients were subdivided into 3 groups : those treated with seizure control plus side effects ( n=4 ) ; treated with non-controlled seizures ( n=15 ) and with JME newly diagnosed ( n=3 ) . RESULTS Sixteen patients completed the first year of the follow-up . Generalized tonic-clonic seizures were completely controlled in 10 ( 62.5 % ) ; more than 50 % of reduction in 4 ( 25.0 % ) and less than 50 % in 2 ( 12.5 % ) . Myoclonia were controlled in 11 ( 68.8 % ) and persisted in 5 ( 31.2 % ) patients . Absence seizures were present in 5 ( 22.7 % ) of whom 2 ( 9.0 % ) showed more than 50 % of seizure reduction while 3 ( 13.6 % ) presented worsening . Discontinuations were due to inadequate seizure control and adverse events ( N=4 ) , low compliance and loss of follow-up ( N=2 ) and subject choice ( N=1 ) . CONCLUSION TPM showed to be an effective and well-tolerated drug in the treatment of JME . Although frequently observed , TPM side effects were tolerable and the drug could be maintained in the majority of patients BACKGROUND Topiramate is a broad-spectrum agent effective against primarily generalized tonic-clonic seizures ( PGTCS ) as well as partial-onset seizures . Juvenile myoclonic epilepsy is one of the most common idiopathic generalized epilepsies , with most patients experiencing PGTCS . OBJECTIVE To evaluate topiramate as add-on therapy in patients with juvenile myoclonic epilepsy . DESIGN Post-hoc analysis of a patient subset from 2 multicenter , double-blind , r and omized , placebo-controlled , parallel-group trials . SETTING Eighteen centers in the United States ; 10 centers in Europe ; 1 center in Costa Rica ( primary trials ) . PATIENTS A total of 22 patients with juvenile myoclonic epilepsy participating in placebo-controlled trials assessing topiramate ( target dose , 400 mg/d in adults ) in inadequately controlled PGTCS . MAIN OUTCOME MEASURE Reduction of PGTCS . RESULTS A 50 % or more reduction of PGTCS in 8 of 11 topiramate-treated patients ( 73 % ) and 2 of 11 placebo-treated patients ( 18 % ) ( P = .03 ) . Reductions in myoclonic , absence , and total generalized seizures were also observed , although topiramate vs placebo differences did not achieve statistical significance . CONCLUSION As a broad-spectrum agent , topiramate is an effective option for patients with juvenile myoclonic epilepsy Juvenile myoclonic epilepsy ( JME ) is managed with valproate in most patients ; however , valproate is an antiepileptic drug that has relatively severe adverse effects , especially in women . We performed a prospect i ve , open-label , r and omized observational study for comparison of efficacy and tolerability between topiramate and valproate in patients with JME . The inclusion criteria were patients with newly diagnosed JME or previously diagnosed JME with a history of a poor response or adverse effects to other antiepileptic drugs . The primary endpoint of this study was percentage of patients who were free of myoclonic seizures for 24 weeks in the two groups . The frequency and severity of adverse effects were also assessed . Sixteen patients were r and omized to topiramate and 17 to valproate . In the topiramate arm , 11 of 16 patients ( 68.9 % ) completed 24-week maintenance therapy and seven of the 11 ( 64 % ) were seizure-free . In the valproate arm , 16 of 17 patients ( 94.1 % ) completed 24-week follow-up and nine of 16 ( 56 % ) were seizure-free . The difference ( 64 % topiramate versus 56 % valproate ) did not reach statistical significance in this study group ( p = 0.08 , Fisher 's exact test ) . However , the severity of adverse effects was significantly different . Only 1 of 10 adverse effects from topiramate was ranked moderate-to-severe ( 10 % ) , in comparison with severe rankings for 10 of 17 adverse effects from valproate ( 59 % ) ( p = 0.018 , Fisher 's exact test ) . In summary , the efficacy of topiramate and valproate was not different , but the severity of adverse effects was favourable for topiramate . Our findings suggest that valproate may be replaced with topiramate , especially for the patients with JME who do not tolerate valproate Objectives – Based on dose predictions from animal and human volunteer studies , most patients enrolled in initial r and omized controlled trials of topiramate as adjunctive therapy in adults with partial‐onset seizures were r and omized to ≥ 600 mg/day topiramate . Subsequent experience suggests that dosage needs were overestimated . This double‐blind , placebo‐controlled study evaluated 200 mg/day topiramate in adults with treatment‐resistant partial‐onset seizures receiving a concurrent enzyme‐inducing antiepileptic agent ( carbamazepine ) . Material and methods – After a 4‐week baseline , 263 adults receiving carbamazepine who had at least three partial‐onset seizures during the baseline period were r and omized to placebo or one of two topiramate 200 mg/day treatment arms : topiramate escalated weekly 25 mg/day(8‐week escalation ) or 50 mg/day(4‐week escalation ) . Therapy was then maintained for the remainder of the 12‐week double‐blind study . Results – Median percent reduction in seizure frequency from baseline to study end was 44 % with topiramate and 20 % with placebo ( P ≤ 0.001 ) . A significant therapeutic effect was present at 2 weeks with a dose of 100 mg/day . The most common adverse events ( ≥10 % incidence in topiramate‐treated patients ) were somnolence , fatigue , paresthesia , nervousness and anorexia ; 8 % of topiramate‐treated patients and 2 % of placebo‐treated patients discontinued because of adverse events . As a result of the low incidence of adverse events , differences between titration rates in terms of tolerability were not detected . Conclusion – Topiramate 200 mg/day is an appropriate target dose as adjunctive therapy in adults with treatment‐resistant partial‐onset seizures , even when receiving an enzyme‐inducing agent ; 100 mg/day also appears to be effective . A significant therapeutic effect may be seen in the second week of treatment with a dose of 100 mg/day Few r and omized , controlled trials evaluating antiepileptic drug ( AED ) efficacy and tolerability have focused solely on patients with juvenile myoclonic epilepsy ( JME ) . We conducted a pilot , r and omized controlled trial comparing topiramate ( N=19 ) and valproate ( N=9 ) in adolescents/adults with JME to evaluate clinical response when these broad-spectrum agents are titrated to optimal effect . Rating scales were used to systematic ally assess tolerability . Among patients completing 26 weeks of treatment , 8 of 12 ( 67 % ) in the topiramate group and 4 of 7 ( 57 % ) in the valproate group were seizure-free during the 12-week maintenance period . Median daily dose was 250 mg topiramate or 750 mg valproate . Two ( 11 % ) topiramate-treated patients and one ( 11 % ) valproate-treated patient discontinued due to adverse events . Systemic toxicity scores , but not neurotoxicity scores , differed substantially between the two groups ; greater systemic toxicity was associated with valproate . Our preliminary findings that topiramate may be an effective , well-tolerated alternative to valproate warrant validation in a double-blind trial |
12,340 | 23,725,520 | No single method was shown to be better than the others , but the size of the studies makes it impossible to draw firm conclusions . | Background An emergency cricothyrotomy is the last-resort in most airway management protocol s and is performed when it is not possible to intubate or ventilate a patient .
This situation can rapidly prove fatal , making it important to identify the best method to establish a secure airway .
We conducted a systematic review to identify whether there exists superiority between available commercial kits versus traditional surgical and needle techniques . | Emergency physicians and registrars performed emergency cricothyroidotomy on an artificial airway model using a st and ard surgical approach and three common commercial products , participants had received no refresher training . The order in which the methods were used was r and omised to minimise any learning effect . Three methods ( st and ard surgical , Minitrach II , and Quicktrach ) were universally successful in obtaining ventilation within 150 s , whilst the Melker kit had a 26 % failure rate and significantly longer median time to ventilation ( 126 s vs≤48 s for other methods , p < 0.001 ) . Despite success in using the surgical method , the Quicktrach and Minitrach II were rated as first or second preference by the majority of operators ( 78 % and 70 % respectively ) . Without refresher training emergency physicians and registrars successfully performed emergency cricothyroidotomy using the st and ard surgical method , Quicktrach and Minitrach II kits however the use of the Melker kit under these conditions result ed in significant delays or failure to establish an airway Background To improve the ease and safety of cricothyroidotomy especially in the h and of the inexperienced , new instruments have been developed . In this study , we compared a new indicator-guided puncture technique ( PCK ) with st and ard surgical technique ( ST ) regarding success rate , performance time and complications . Methods Cricothyroidotomy in 30 human cadavers performed by 30 first year anaesthesia residents . The set chosen for use was r and omised : PCK-technique ( n=15 ) and ST ( n=15 ) . Success rates , insertion times and complications were compared . Traumatic lesions were anatomically confirmed after dissection . Results The ST-group had a higher success rate ( 100 % vs 67 % ; p=0.04 ) . There was no difference in time taken to complete the procedure ( PCK 82 s. vs ST 95 s. ; p=0.89 ) . There was a higher complication rate in the PCK-group ( 67 % vs 13 % ; p=0.04 ) . Most frequent complication in the PCK-group was injury to the posterior tracheal wall ( n=8 ) , penetration to the oesophageal lumen ( n=4 ) and injury to the thyroid and /or cricoid cartilage ( n=5 ) . In the ST-group in only 2 cases minor complications were observed ( small vessel injury ) . Conclusions In this human cadaver study the PCK technique produced more major complications and more failures than the ST . In the h and of the inexperienced operator the st and ard surgical approach seems to be a safe procedure , which can successfully be performed within an adequate time . The PCK technique can not be recommended for inexperienced operators BACKGROUND Emergency cricothyroidotomy is a potentially life-saving procedure in the ' can not intubate can not ventilate ( CICV ) ' scenario . Although surgical cricothyroidotomy remains the technique recommended in many ' CICV ' algorithms , the insertion of a tracheostomy as a cannula over a trocar , or using the Seldinger method , may have advantages as they are more familiar to the anaesthetist . We compared the utility of three cuffed cricothyroidotomy devices : cuffed Melker ® , Quicktrach 2 ® , and PCK ® devices , with surgical cricothyroidotomy . METHODS After ethical committee approval and written informed consent , 20 anaesthetists performed cricothyroidotomy with all four devices in r and om order , in a pig larynx and trachea model covered in cured pelt . The primary endpoints were the rate of successful placement of the cricothyroidotomy device into the trachea and the duration of the insertion attempt . RESULTS The Melker ® and Quicktrach 2 ® devices possessed advantages over the surgical approach , in contrast to the PCK ® device , which performed less well . All 20 participants inserted the Melker ® , with 19 being successful using the surgical approach and the Quicktrach 2 ® , whereas only 12 successfully inserted the PCK ® device ( PCK ® vs surgical , P=0.02 ) . The Quicktrach 2 ® had the fastest insertion times and caused least trauma to the posterior tracheal wall . The Melker ® was rated highest by the participants and was the only device rated higher than the surgical technique . CONCLUSIONS The Melker ® and Quicktrach 2 ® devices appear to hold particular promise as alternatives to surgical cricothyroidotomy . Further studies , in more clinical ly relevant models , are required to confirm these initial positive findings STUDY OBJECTIVE To compare the success rate , complication rate and time required for the rapid 4-step technique versus the st and ard technique for cricothyrotomy . METHODS We conducted a prospect i ve , r and omized crossover study . Twenty-seven emergency medicine interns , 1 junior medicine resident , and 4 senior medical students , without prior cricothyrotomy experience , were r and omly divided into 2 groups . Group 1 was initially instructed in and then performed the st and ard technique ; group 2 was initially instructed in and then performed the rapid 4-step technique . Each group was then instructed in and performed the alternate method . Cricothyrotomies were performed on preserved human cadavers . RESULTS A surgical airway was established in 28 of 32 attempts with the use of the rapid 4-step technique ( 88 % ) ; the average time elapsed before tube placement was 43 seconds . Thirty of 32 attempts involving the st and ard technique ( 94 % ) were successful ; the average time to tube placement was 134 seconds ( 95 % confidence interval for a difference of 91 seconds , 63 to 119 ; P < .001 ) . Complications were identified in 12 attempts involving the st and ard technique ( 38 % ; 1 considered major ) and in 12 involving the rapid four-step technique ( 38 % ; 3 considered major ) . The incidence of major complications was 6 % higher for the rapid 4-step technique ( 95 % confidence interval , -9 % to 21 % ) . CONCLUSION In a group of inexperienced subjects working on a preserved human cadaver model , the rapid 4-step technique for cricothyrotomy was performed in about one third the time required for performance of the st and ard technique . This finding was both clinical ly and statistically significant . Although the 2 techniques had similar success and complication rates , we noted a trend toward more severe complications in the rapid 4-step technique OBJECTIVE To compare the speeds and success rates of placement for percutaneous cricothyrotomy versus surgical or open cricothyrotomy . METHODS Twenty-two paramedics ( mean 9.7 years of experience ) , with training in both methods , were timed using a pig trachea in a crossover model . An emergency physician performed timing and documentation of success ; timing commenced after the equipment was ready and the membrane was identified . Paramedics were r and omly assigned by a coin toss to start in either group . All were actively employed by a municipal third-service emergency medical services ( EMS ) agency . Paramedics who did not complete one of the methods correctly were excluded from speed analysis . Data were analyzed using descriptive statistics , a t-test of paired sample s , and confidence intervals for matched sample s. RESULTS Placement of a surgical cricothyrotomy was significantly faster ( mean 28 seconds , range 10 - 78 seconds ) than the percutaneous method ( mean 123 seconds , range 58 - 257 seconds ) ( p < 0.001 ) . Mean difference between the 20 matched percutaneous versus surgical pairs was 93.75 seconds ( 95 % CI 72.3 , 115.2 ) . The surgical route had a 100 % success rate at obtaining airway control , whereas the percutaneous method had a 90.9 % success rate ( p = 0.1 ) . CONCLUSION In an animal model , surgical cricothyrotomy appeared to be a preferable method for establishing a definitive airway over the percutaneous method . Further research is required to define the optimal approach in the prehospital setting for the invasive airway Using an airway mannequin and artificial lung model , we compared surgical cricothyroidotomy with a 6.0‐mm cuffed Portex tracheostomy tube with wire‐guided cricothyroidotomy using a 5.0‐mm cuffed Melker or 6.0‐mm uncuffed Melker tube . The trial was carried out by 27 anaesthetists using a r and omised , crossover design . Surgical cricothyroidotomy proved significantly faster ( mean ( SD ) time to first breath 44.3 ( 12.5 ) s for Portex surgical , 87.2 ( 21.6 ) s for cuffed Melker , 87.8 ( 19.2 ) s for uncuffed Melker , p < 0.001 ) . With a st and ardised ventilator model , the cuffed tubes provided more effective ventilation ( mean ( SD ) tidal volume 446 ( 41 ) ml Portex , 436 ( 52 ) ml cuffed Melker , 19 ( 5 ) ml uncuffed Melker , p < 0.001 ) . Fourteen of the participants preferred the wire‐guided system . We conclude that , in this model , a cuffed device is preferable when cricothyroidotomy is needed . In addition , the surgical method is quicker than a wire‐guided approach The Rapid Four-Step Technique ( RFST ) has been demonstrated to be faster than st and ard open crico thyrotomy technique , but may have a higher incidence of cricoid injury with tracheal hook traction applied caudad . The " Bair Claw " is a novel device that may help eliminate these complications . This r and omized , experimental trial used a fresh-frozen cadaver model of cricothyrotomy to compare speed and safety between RFST using a Bair Claw and st and ard open technique . Outcome measures included time to definitive airway , size of largest endotracheal ( ET ) tube able to be passed , and incidence of complications . We observed that RFST using a Bair Claw was significantly faster than st and ard open technique . There was no significant difference with regard to size of ET tube able to be passed with RFST using a Bair Claw versus st and ard open technique , and there was no damage to trachea or larynx observed with either technique . We concluded that RFST using a Bair Claw is faster and appears to be equally safe when compared to st and ard open technique in a fresh-frozen cadaver model of cricothyrotomy . The two techniques were equal with regard to maximal ET tube size BACKGROUND : We compared two emergency cricothyroidotomy kits design ed to avoid lesions during insertion , one based on the Seldinger technique ( ST ) , the other based on the concept of a mechanical detection of the posterior wall of the larynx , with regard to insertion time , success rate , and complication rate . METHODS : Cricothyroidotomy was performed under fiberoptic control in 40 human cadavers embalmed according to Thiel ’s technique . The set chosen for use was r and omized : new technique ( NT ) or ST . Duration of the procedure , success rates , and incidence of laryngeal injuries were compared . Traumatic lesions observed with the fiberoptic bronchoscope were anatomically confirmed after dissection . RESULTS : The two groups had comparable epidemiological and anatomical records . Cricothyroidotomy was performed faster with the NT than with the ST ( median 54 vs 71 s , P = 0.01 ) . Failure rates were comparable between groups ( 4 vs 1 , P = 0.34 ) , and there were fewer major complications in the posterior tracheal wall with the ST ( 0 vs 8 , P = 0.003 ) . In the ST group , only minor punctiform lesions of the posterior trachea wall were observed in four cases . CONCLUSIONS : In this model , despite a shorter insertion time , the NT produced more lesions and more failures than the ST We compared a wire-guided cricothyrotomy technique vs. st and ard surgical cricothyrotomy in terms of accuracy in placement , complications , performance time , incision length , and user preference . We conducted a r and omized , crossover controlled trial in which Emergency Medicine ( EM ) attendings and residents performed cricothyrotomies by both st and ard and wire-guided techniques ( using a commercially available kit ) on human cadavers after a 15-min training session . Procedure time , incision length , and physician preference were recorded . Cadavers were inspected for accuracy of placement and complications . Airway placement was accurate in 13 of 15 cases for the st and ard technique ( 86.7 % ) , and 14 of 15 cases for the wire-guided technique ( 93.3 % ) . When comparing wire-guided vs. st and ard techniques , there were no differences in complication rates or performance times . The wire-guided technique result ed in a significantly smaller mean incision length than the st and ard technique ( 0.53 vs. 2.53 cm , respectively , p<0.0001 ) . Overall , 14 of 15 physicians stated that they preferred the wire-guided to the st and ard technique . Our data suggest that this wire-guided cricothyrotomy technique is as accurate and timely to use as the st and ard technique and is preferred by our physician operators . In addition , the technique results in a smaller incision on human cadaver models BACKGROUND Emergency cricothyrotomy is the final lifesaving option in " can not intubate-cannot ventilate " situations . Fast , efficient and safe management is indispensable to reestablish oxygenation , thus the quickest , most reliable and safest technique should be used . Several cricothyrotomy techniques exist , which can be grouped into two categories : anatomical-surgical and puncture . METHODS We studied success rate , tracheal tube insertion time and complications of different techniques , including a novel cricothyrotomy scissors technique in human cadavers . Sixty-three inexperienced health care providers were r and omly assigned to apply either an anatomical-surgical technique ( st and ard surgical technique , n=18 ; novel cricothyrotomy scissors technique , n=14 ) or a puncture technique ( catheter-over-needle technique , n=17 ; wire-guided technique , n=14 ) . RESULTS Airway access was almost always successful with the anatomical-surgical techniques ( success rate in st and ard surgical group 94 % , scissors group 100 % ) . In contrast , the success rate was smaller ( p<0.05 ) with the puncture techniques ( catheter-over-needle group 82 % , wire-guided technique 71 % ) . Tracheal tube insertion time was faster overall ( p<0.05 ) with anatomical-surgical techniques ( st and ard surgical 78s [ 54 - 135 ] , novel cricothyrotomy scissors technique 60s [ 42 - 82 ] ; median [ IQR ] ) than with puncture techniques ( catheter-over-needle technique 74s [ 48 - 145 ] , wire-guided technique 135s [ 116 - 307 ] ) . We observed fewer complications with anatomical-surgical techniques than with puncture techniques ( p<0.001 ) . CONCLUSIONS In inexperienced health care personnel , anatomical-surgical techniques showed a higher success rate , a faster tracheal tube insertion time and a lower complication rate compared with puncture techniques , suggesting that they may be the techniques of choice in emergencies INTRODUCTION In confined-space airway emergencies , prehospital personnel may need to perform cricothyrotomy when conventional airway techniques can not be utilized or have failed . This study is a prospect i ve , cross-over , r and omized controlled trial that compares two widely-known techniques using two commercially available kits . METHODS Twenty residents at Palmetto Health Richl and Department of Emergency Medicine participated in the study . Their performance was assessed using the time required to placement and correctness of placement for each device . The residents performed the procedures on an Air-Man ™ manikin that had been situated in a confined space . The residents also indicated which kit they would prefer in a confined-space , emergency airway situation . RESULTS All of the devices were placed in the airway . The mean time to placement for the Melker ™ and Quicktrach ™ kits was 108.5 seconds and 23.9 seconds , respectively . This yielded a mean difference of 84.5 seconds , which provided a t-statistic of 8.88 ( p < 0.0001).There was no evidence of a carry-over effect ( p = 0.292 ) or a period effect ( p = 0.973 ) . All residents preferred using the Quicktrach ™ kit . CONCLUSIONS Use of the Quicktrach ™ kit result ed in the fastest time to placement , was placed correctly in the airway , and was preferred by each of the residents . Its small , simple , and sturdy design , with few parts and easy manipulation , allow the Quicktrach ™ to be a valuable option in prehospital situations involving confined spaces . The Melker ™ kit , with its many parts , and need for greater manipulation , is not as easily utilized or preferred in a confined space scenario OBJECTIVES The objective was to compare time to completion , failure rate , and subjective difficulty of a new cricothyrotomy technique to the st and ard technique . The new bougie-assisted cricothyrotomy technique ( BACT ) is similar to the rapid four-step technique ( RFST ) , but a bougie and endotracheal tube are inserted rather than a Shiley tracheostomy tube . METHODS This was a r and omized controlled trail conducted on domestic sheep . During a 3-month period inexperienced residents or students were r and omized to perform cricothyrotomy on anesthetized sheep using either the st and ard technique or the BACT . Operators were trained with an educational video before the procedure . Time to successful cricothyrotomy was recorded . The resident or student was then asked to rate the difficulty of the procedure on a five-point scale from 1 ( very easy ) to 5 ( very difficult ) . RESULTS Twenty-one residents and students were included in the study : 11 in the st and ard group and 10 in the BACT group . Compared to the st and ard technique , the BACT was significantly faster with a median time of 67 seconds ( interquartile range [ IQR ] = 55 - 82 ) versus 149 seconds ( IQR = 111 - 201 ) for the st and ard technique ( p = 0.002 ) . The BACT was also rated easier to perform ( median = 2 , IQR = 1 - 3 ) than the st and ard technique ( median = 3 , IQR = 2 - 4 ; p = 0.04 ) . The failure rate was 1/10 for the BACT compared to 3/11 for the st and ard method ( p = NS ) . CONCLUSIONS This study demonstrates that the BACT is faster than the st and ard technique and has a similar failure rate when performed by inexperienced providers on anesthetized sheep In a r and omised crossover trial , we compared a wire‐guided cricothyrotomy technique ( Minitrach ) with a catheter‐over‐needle technique ( Quicktrach ) . Performance time , ease of method , accuracy in placement and complication rate were compared . Ten anaesthesiology and 10 ENT residents performed cricothyrotomies with both techniques on prepared pig larynxes . The catheter‐over‐needle technique was faster than the wire‐guided ( 48 compared to 150 s , p < 0.001 ) and subjectively easier to perform ( VAS‐score 2.1 vs. 5.6 , p < 0.001 ) . Correct positioning of the cannula could be achieved in 95 % and 85 % , respectively ( NS ) . There was one complication in the catheter‐over‐needle group compared to five in the wire‐guided group . We conclude that the wire‐guided minitracheotomy kit is unsuitable for emergency cricothyrotomies performed by inexperienced practitioners . On the other h and , the catheter‐over‐needle technique appears to be quick , safe and reliable BACKGROUND Prehospital Emergency Medical Services have demonstrated variable success with regards to prehospital airway management in U.S. civilian setting s. We attempted to identify the incidence of successful prehospital endotracheal intubations in the modern combat environment . METHODS This was a prospect i ve , observational study . Data collection occurred at Combat Support Hospitals ( CSH ) within Operation Iraqi Freedom locations between January 2005 and March 2007 . Military trauma physicians systematic ally examined casualties presenting to the CSH that received advanced prehospital airway management . Correct endotracheal tube ( ETT ) positioning was verified using an explicit combination of clinical findings and colorimetric end-tidal carbon dioxide detection . The primary outcome was correct placement of the ETTs by combat prehospital providers . RESULTS A total of 6,875 combat casualties presented to participating CSHs during the study period , of which there were 293 ( 4.2 % ) advanced prehospital airways , of which 282 ( 97.3 % ) were trauma patients . Prehospital airway management included : 253 endotracheal intubations ( 86.6 % ) ; 23 supraglottic airways ( 7.5 % ) , and 17 cricothyrotomies ( 5.8 % ) . Of the ETTs , upon arrival to the CSH , 242 ( 95.7 % ) were determined to be correctly placed . There were 11 incorrectly placed ETTs : 10 were in the right mainstem bronchus , and 1 was found to be dislodged in the hypopharynx . There were no unrecognized battlefield esophageal intubations . CONCLUSIONS Under combat conditions , the overall rate of correctly placed ETTs performed by military prehospital providers was comparable with that of published U.S. civilian paramedic data STUDY OBJECTIVE To determine the clinical characteristics of endotracheal intubation in the French emergency prehospital medical system and compare these data with those of other systems . METHODS This study was performed in lle de France ( Paris Region ) in mobile ICUs staffed by physicians . This prospect i ve , descriptive study involved completion of a question naire by the operator just after endotracheal intubation was performed . RESULTS Six hundred eighty-five ( 99.1 % ) of 691 consecutive prehospital intubations were performed successfully in the field . The orotracheal route was used in 96.0 % , and no surgical approaches such as cricothyroidotomy were used . Mechanical complications occurred in 84 patients , at a rate of 15.9 % for nonarrest patients and 8.1 % for arrest patients . A wide variety of sedation protocol s were used . Difficult intubations ( 10.8 % ) were comparable in incidence to the number seen in US emergency departments , not US prehospital systems . By the same token , intubation success rates ( 99.1 % ) were comparable to US EDs and much higher than US prehospital results . CONCLUSION The characteristics of French prehospital airway management differ significantly from those of other countries . These differences may be explained by differences in approach to prehospital management rather than differences of skill We describe the prevalence , primary indications and immediate complications of emergency cricothyrotomy ( cric ) techniques , in a single institution 's Emergency Department ( ED ) and associated air-medical transport service . This is a retrospective review at an academic , level-one trauma center with an annual ED census of 65,000 and an associated air-medical transport service ( AMTS ) . All patients undergoing cric in the field or in the ED between July 1995 and June 2000 were included . Expert review ers from Emergency Medicine , Trauma Surgery and the AMTS prospect ively defined the complication criteria . All charts with a possible complication underwent a blinded evaluation by review ers representing each of the three clinical services . Descriptive statistics were used to summarize the data . Fifty crics were performed over 5 years . Seventy-six percent of crics were performed in trauma patients . The prevalence of cric in patients requiring airway management in the ED was 1.1 % ( 95 % CI , 0.7 - 1.6 ) and 10.9 % ( 95 % CI , 6.9 - 16.1 ) in the field by the AMTS . The prevalence of complications was 14 % ( 95 % CI , 4 - 32.6 ) in ED patients and 54.5 % ( 95 % CI , 32 - 75.6 ) for prehospital patients . The overall inter-rater agreement for complication rate was excellent ( kappa = .87 ) . Overall , 77 % of crics were performed using the rapid four-step technique ( RFST ) . There were no reports of complications associated with the RFST when performed in the ED . Non-RFST crics in the ED had an associated complication rate of 25 % ( 95 % CI , 2.8 - 60 ) . Emergency cricothyrotomy was performed in approximately 1 % of all emergency airway cases in the ED and at a higher rate by the AMTS . The most frequent indications were trauma related . Additionally , the RFST was the most commonly used technique for cric at this institution . The complication rate of cric was significantly higher in the prehospital environment than in the ED STUDY OBJECTIVE We determine success rates of endotracheal intubation performed in emergency departments ( EDs ) by North American emergency medicine residents . METHODS During 58 months , physicians performing intubations at 31 university-affiliated EDs in 3 nations completed a data form that was entered into the National Emergency Airway Registry 2 data base . Included were all patients undergoing endotracheal intubation in the ED . The data form included patients ' age , sex , weight , indication for intubation , technique of airway management , names and dosages of all medications used to facilitate intubation , level of training and specialty of the intubator , number of attempts , success or failure , and adverse events . We queried this prospect ively gathered , observational data to analyze intubations done by US and Canadian emergency medicine residents . RESULTS Enrollment was incomplete ( eg , 85 % at the main study center ) , so the study sample did not include all consecutive patients . Emergency medicine residents performed 77 % ( 5768/7498 ; 95 % confidence interval [ CI ] 76 % to 78 % ) of all initial intubation attempts in the United States and Canada . The first intubator was successful in 90 % ( 5,193/5,757 ; 95 % CI 89 % to 91 % ) of cases , including 83 % ( 4,775/5,757 ; 95 % CI 82 % to 84 % ) on the first attempt . Success rates on the first attempt were as follows : postgraduate year 1 = 72 % ( 498/692 ; 95 % CI 68 % to 75 % ) , postgraduate year 2 = 82 % ( 2,081/2,544 ; 95 % CI 80 % to 83 % ) , postgraduate year 3 = 88 % ( 1,963/2,238 ; 95 % CI 86 % to 89 % ) , postgraduate year 4 + = 82 % ( 233/283 ; 95 % CI 77 % to 87 % ) , and attending physician = 89 % ( 689/772 ; 95 % CI 87 % to 91 % ) . Success rates by the first intubator were as follows : postgraduate year 1 = 80 % ( 553/692 ; 95 % CI 77 % to 83 % ) , postgraduate year 2 = 89 % ( 2,272/2,544 ; 95 % CI 88 % to 90 % ) , postgraduate year 3 = 94 % ( 2,105/2,238 ; 95 % CI 93 % to 95 % ) , postgraduate year 4 + = 93 % ( 263/283 ; 95 % CI 89 % to 96 % ) , and attending physician = 98 % ( 755/772 ; 95 % CI 96 % to 99 % ) . Rapid sequence intubation technique was used in 78 % ( 4,513/5,768 ; 95 % CI 77 % to 79 % ) of initial attempts : it result ed in 85 % ( 3,843/4,513 ; 95 % CI 84 % to 86 % ) success on the first attempt and 91 % ( 4,117/4,513 ; 95 % CI 90 % to 92 % ) success by the first intubator . The overall rate of cricothyrotomy for all emergency resident intubations was 0.9 % ( 50/5,757 ; 95 % CI 0.6 % to 1.1 % ) . When an initial intubator failed , 40 % ( 385/954 ; 95 % CI 37 % to 44 % ) of rescue attempts were performed by emergency medicine residents . Among emergency medicine residents , success on the first rescue attempt was 80 % ( 297/371 ; 95 % CI 76 % to 84 % ) , and success by the first rescue intubator was 88 % ( 328/371 ; 95 % CI 85 % to 91 % ) . CONCLUSION Success of initial intubation attempts increased over the first 3 years of residency . This large multicenter study demonstrates the success of airway management by emergency medicine residents in North America . Using rapid-sequence intubation predominantly , emergency medicine residents achieved high levels of success BACKGROUND According to various algorithms of airway management , emergency cricothyrotomy ( coniotomy ) represents the ultimate step for managing the difficult airway . As most physicians have limited experience with this technique several ready-to-use devices have emerged on the market with the aim of simplifying the procedure . However , they differ in details , such as configuration or the order of particular steps . Therefore , the intention of this r and omized and controlled feasibility study was to test various sets and compare them to the classical surgical approach . METHODS After obtaining informed consent German anesthesiologists who were also board-certified emergency physicians were asked to perform the cricothyrotomy procedure in a cervical mannequin ( Frova Crico-Trainer , VBM Medizintechnik ) in a r and omized order using a scalpel , peripheral intravenous cannula and the commercial devices TracheoQuick , Airfree , Portex-Crico-Kit , Quicktrach I and Quicktrach II . H and ling and duration of the procedures were analyzed utilizing the Wilcoxon signed-rank test . A p-value < 0.05 was considered significant . RESULTS A total of 20 anesthesiologists ( 11 residents and 9 specialists ) with a mean age of 34 years were included in this study and all had the additional qualification of emergency physician , which enabled them to work in prehospital emergency medicine in Germany . Participants had been working in this field for an average of 29.9 months ( range 6 - 84 months ) performing a mean of 1.9 24 h shifts per month ( range 1 - 6 shifts/month ) . Of the participants only 2 ( 10 % ) had performed a coniotomy in reality before . In this study surgical coniotomy required a median time of 35.4 s ( range 30.0 - 61.8 s ) . No significant differences were seen when the cuffed devices Quicktrach II ( median : 29.9 s , range 25.0 - 50.5 s ) and Portex-Crico-Kit ( median : 46.7 s , range 37.0 - 67.3 s ) were used . A significantly faster airway was established using the non-cuffed devices TracheoQuick ( median : 20.2 s , range 11.4 - 44.7 s ) , Airfree ( median : 22.8 s , range 14.3 - 33.2 s ) , Quicktrach I ( median : 21.1 s , range 14.5 - 32.4 s ) and the peripheral intravenous cannula ( median : 19.2 s , range 10.8 - 27.8 s ) . Incorrect tube placements were not observed . CONCLUSION This study allowed the comparison of surgical coniotomy to several ready-to-use devices in a st and ardized setting utilizing a reusable plastic mannequin . The interpretation for real emergency conditions is limited as individual anatomy , traumatic alterations of the neck or complications , such as bleeding or damage of important structures were not part of the study objectives . However , all participating emergency physicians successfully used the coniotomy sets provided at the first attempt . No device required significantly more time than the surgical approach . The procedures using cuffed devices lasted longer in comparison to procedures using uncuffed ones ; however , this difference would only play a minor role in reality as effective ventilation with minute volumes greater than 7 l/min will only be achieved by a cuffed cannula with a minimum internal diameter of 4 mm . Devices with no cuff or with tube diameters smaller than 4 mm will only allow oxygenation of the patient , which in turn requires an inspiratory oxygen concentration of 100 % and a relatively high ventilation frequency |
12,341 | 29,022,368 | Environmental design , which involves nurses , support staff , and physicians , is one of the critical factors that promotes the efficiency of teamwork and collaborative communication .
Layout design , visibility , and accessibility levels are the most cited aspects of design which can affect the level of communication and teamwork in healthcare facilities | The purpose of this systematic review is to investigate the current knowledge about the impact of healthcare facility design on teamwork and communication by exploring the relevant literature .
Teamwork and communication are behavioral factors that are impacted by physical design .
However , the effects of environmental factors on teamwork and communication have not been investigated extensively in healthcare design literature .
There are no published systematic review s on the current topic . | Objective : To determine if high fidelity simulation based team training can improve clinical team performance when added to an existing didactic teamwork curriculum . Setting : Level 1 trauma center and academic emergency medicine training program . Participants : Emergency department ( ED ) staff including nurses , technicians , emergency medicine residents , and attending physicians . Intervention : : ED staff who had recently received didactic training in the Emergency Team Coordination Course ( ETCC ® ) also received an 8 hour intensive experience in an ED simulator in which three scenarios of graduated difficulty were encountered . A comparison group , also ETCC trained , was assigned to work together in the ED for one 8 hour shift . Experimental and comparison teams were observed in the ED before and after the intervention . Design : Single , crossover , prospect i ve , blinded and controlled observational study . Teamwork ratings using previously vali date d behaviorally anchored rating scales ( BARS ) were completed by outside trained observers in the ED . Observers were blinded to the identification of the teams . Results : There were no significant differences between experimental and comparison groups at baseline . The experimental team showed a trend towards improvement in the quality of team behavior ( p = 0.07 ) ; the comparison group showed no change in team behavior during the two observation periods ( p = 0.55 ) . Members of the experimental team rated simulation based training as a useful educational method . Conclusion : High fidelity medical simulation appears to be a promising method for enhancing didactic teamwork training . This approach , using a number of patients , is more representative of clinical care and is therefore the proper paradigm in which to perform teamwork training . It is , however , unclear how much simulator based training must augment didactic teamwork training for clinical ly meaningful differences to become apparent OBJECTIVE To evaluate the effectiveness of training and institutionalizing teamwork behaviors , drawn from aviation crew re source management ( CRM ) programs , on emergency department ( ED ) staff organized into caregiver teams . STUDY SETTING Nine teaching and community hospital EDs . STUDY DESIGN A prospect i ve multicenter evaluation using a quasi-experimental , untreated control group design with one pretest and two posttests of the Emergency Team Coordination Course ( ETCC ) . The experimental group , comprised of 684 physicians , nurses , and technicians , received the ETCC and implemented formal teamwork structures and processes . Assessment s occurred prior to training , and at intervals of four and eight months after training . Three outcome constructs were evaluated : team behavior , ED performance , and attitudes and opinions . Trained observers rated ED staff team behaviors and made observations of clinical errors , a measure of ED performance . Staff and patients in the EDs completed surveys measuring attitudes and opinions . DATA COLLECTION Hospital EDs were the units of analysis for the seven outcome measures . Prior to aggregating data at the hospital level , scale properties of surveys and event-related observations were evaluated at the respondent or case level . PRINCIPAL FINDINGS A statistically significant improvement in quality of team behaviors was shown between the experimental and control groups following training ( p = .012 ) . Subjective workload was not affected by the intervention ( p = .668 ) . The clinical error rate significantly decreased from 30.9 percent to 4.4 percent in the experimental group ( p = .039 ) . In the experimental group , the ED staffs ' attitudes toward teamwork increased ( p = .047 ) and staff assessment s of institutional support showed a significant increase ( p = .040 ) . CONCLUSION Our findings point to the effectiveness of formal teamwork training for improving team behaviors , reducing errors , and improving staff attitudes among the ETCC-trained hospitals Objective To test an intervention to enhance collaborative communication among nurse and physician leaders ( eg , nurse manager , medical director , clinical nurse specialist ) in two diverse intensive care units ( ICUs ) . Background Collaborative communication is associated with positive patient , nurse , and physician outcomes . However , to date , intervention-focused research that seeks to improve collaborative communication is lacking . Methods A pretest – posttest repeated measures design incorporated baseline data collection , implementation of the intervention over 8 months , and immediate and 6-months-post data collection . Findings Communication skills of ICU nurse and physician leaders improved significantly . Leaders also reported increased satisfaction with their own communication and leadership skills . In addition , staff nurse and physician perceptions of nursing leadership and problem solving between groups increased . Staff nurses reported lower personal stress ( eg , more respect from co-workers , physicians , and managers ) , even though they perceived significantly more situational stress ( eg , less staffing and time ) . Conclusion Study findings provide evidence that nurse – physician collaborative communication can be improved Objective To determine the emergency department ( ED ) environmental factors associated with patient satisfaction . Methods A prospect i ve , observational study in a university-affiliated tertiary-referral ED and associated observation unit ( OU ) . The ED environment was evaluated with a structured question naire , scored using a 100-mm visual analogue scale . Patients who stayed in the ED over 8 h ( long-stay ED ; LSED ) were compared with those who stayed less than 4 h ( short-stay ED ; SSED ) and with a control group admitted to the OU . Results A total of 233 patients was enrolled , overall satisfaction in SSED was 81 % ( 95 % CI 70.1 to 88.7 ) , 69 % in LSED ( 95 % CI 57.4 to 78.7 ) and 84 % in OU ( 95 % CI 73.6 to 91.0 ) . The most important environmental factors were cleanliness ( median importance 95 , interquartile range ( IQR ) 81–98 ) and communication with medical staff ( 94 , IQR 80–98 ) and family ( 92 , IQR 74–98 ) . The least important factors were access to nature ( 38 , IQR 19–65 ) , a natural light source ( 50 , IQR 24–74 ) and ability to sit out of bed ( 52 , IQR 26–75 ) . Factors rated high for importance but low for satisfaction were ED noise levels ( median difference 40 , IQR 3–70 ) , ED trolley comfort ( 19 , IQR 6–50 ) and food quality ( 12 , IQR −4–29 ) . Conclusion Patients who spend over 8 h in the ED are less satisfied with their environment than either those who spend less than 4 h or patients in an OU . Importantly , distinct , amenable factors can be identified . These should be addressed to improve patients ’ overall ED management and satisfaction |
12,342 | 29,547,516 | However , after addressing heterogeneity , vitamin C showed a protective effect as well .
Especially , foods high in these vitamins ( e.g. , dark green vegetables ) were protective for OAG .
CONCLUSIONS Dietary intake of vitamin A and C showed a beneficial association with OAG ; however , findings on blood levels of vitamins do not show a clear relation with OAG | BACKGROUND The aim of is to determine the association of vitamins with glaucoma by performing a systematic review and meta-analyses . | Background This study was performed to compare levels of serum homocysteine ( Hcy ) , vitamin B12 and folic acid in patients with primary open-angle glaucoma ( POAG ) , pseudoexfoliative glaucoma ( PEXG ) , normotensive glaucoma ( NTG ) and healthy controls . Methods Twentyfive patients with POAG , 24 with PEXG , and 18 with NTG , along with 19 control healthy subjects were included this prospect i ve study . Levels of serum Hcy were measured using immunoassay , and those of serum vitamin B12 and folic acid were measured using competitive chemiluminescent enzyme immunoassay . Results The mean Hcy concentration in the PEXG group was significantly higher ( P < 0.001 ) as compared to the other groups . There were no significant differences with respect to the mean Hcy concentrations among other groups ( P > 0.05 ) . There were no statistical differences in serum vitamin B12 levels among POAG , PEXG , NTG and control subjects ( P > 0.05).The mean serum folic acid level was significantly lower in the subjects with PEXG ( P < 0.009 ) . However , the mean folic acid concentrations among the other groups did not differ significantly ( P > 0.05 ) . Conclusion Elevated levels of Hcy in PEXG may explain the role of endothelial dysfunction among patients with PEXG IMPORTANCE Nitric oxide signaling alterations in outflow facility and retinal blood flow autoregulation are implicated in primary open-angle glaucoma ( POAG ) . Nitric oxide donation has emerged as a POAG therapeutic target . An exogenous source of nitric oxide is dietary nitrates . OBJECTIVE To evaluate the association between dietary nitrate intake , derived mainly from green leafy vegetables , and POAG . DESIGN , SETTING , AND PARTICIPANTS We followed up participants biennially in the prospect i ve cohorts of the Nurses ' Health Study ( 63 893 women ; 1984 - 2012 ) and the Health Professionals Follow-up Study ( 41 094 men ; 1986 - 2012 ) at each 2-year risk period . Eligible participants were 40 years or older , were free of POAG , and reported eye examinations . EXPOSURES The primary exposure was dietary nitrate intake . Information on diet and potential confounders was up date d with vali date d question naires . MAIN OUTCOMES AND MEASURES The main outcome was the incidence of POAG and POAG subtypes ; 1483 cases were confirmed with medical records and classified into subtypes defined by intraocular pressure ( IOP ) ( ≥22 or < 22 mm Hg ) or by visual field ( VF ) loss pattern at diagnosis ( peripheral loss only or early para central loss ) . Cohort-specific and pooled multivariable rate ratios ( MVRRs ) and 95 % CIs were estimated . RESULTS During 1 678 713 person-years of follow-up , 1483 incident cases of POAG were identified . The mean ( SD ) age for the 1483 cases was 66.8 ( 8.3 ) . Compared with the lowest quintile of dietary nitrate intake ( quintile 1 : approximately 80 mg/d ) , the pooled MVRR for the highest quintile ( quintile 5 : approximately 240 mg/d ) was 0.79 ( 95 % CI , 0.66 - 0.93 ; P for trend = .02 ) . The dose response was stronger ( P for heterogeneity = .01 ) for POAG with early para central VF loss ( 433 cases ; quintile 5 vs quintile 1 MVRR = 0.56 ; 95 % CI , 0.40 - 0.79 ; P for trend < .001 ) than for POAG with peripheral VF loss only ( 835 cases ; quintile 5 vs quintile 1 MVRR = 0.85 ; 95 % CI , 0.68 - 1.06 ; P for trend = .50 ) . The association did not differ ( P for heterogeneity = .75 ) by POAG subtypes defined by IOP ( 997 case patients with IOP ≥22 mm Hg : quintile 5 vs quintile 1 MVRR = 0.82 ; 95 % CI , 0.67 - 1.01 ; P for trend = .11 ; 486 case patients with IOP < 22 mm Hg : quintile 5 vs quintile 1 MVRR = 0.71 ; 95 % CI , 0.53 - 0.96 ; P for trend = .12 ) . Green leafy vegetables accounted for 56.7 % of nitrate intake variation . Compared with consuming 0.31 servings per day , the MVRR for consuming 1.45 or more servings per day was 0.82 for all POAG ( 95 % CI , 0.69 - 0.97 ; P for trend = .02 ) and 0.52 for POAG with para central VF loss ( 95 % CI , 0.29 - 0.96 ; P for trend < .001 ) . CONCLUSIONS AND RELEVANCE Higher dietary nitrate and green leafy vegetable intake was associated with a lower POAG risk , particularly POAG with early para central VF loss at diagnosis Objective : To compare the levels of plasma homocysteine ( Hcy ) , vitamin B6 ( vit-B6 ) , serum vitamin B12 ( vit-B12 ) , and folate in healthy individuals and in patients with normal tension glaucoma ( NTG ) , pseudoexfoliative glaucoma ( PXG ) , or primary open-angle glaucoma ( POAG ) . Study design : A prospect i ve controlled trial . Participants and methods : Forty healthy subjects , 48 patients with NTG , 38 patients with PXG , and 34 patients with POAG were included in the study . Those who used vitamin supplements or medications affecting Hcy and vitamin levels were excluded from the study . The levels of Hcy and vit-B6 were measured by High Performance Liquid Chromatography ( HPLC ) . The levels of serum vit-B12 and folic acid were measured by competitive chemiluminescent enzyme immunoassay ( CEI ) . One-way analysis if variance ( ANOVA ) , analysis of covariance ( ANCOVA ) , and the Tukey honestly significant difference test were used for statistical analysis . Results : The mean Hcy level of the PXG group was 15.46 ± 9.27 μmol/L which was significantly higher ( P = 0.03 ) than that of the control group . There were no statistical differences in serum vit-B12 and folate levels among control subjects and NTG , PXG and POAG groups ( P > 0.05 ) . It was found that the mean plasma vit-B6 level was significantly higher in subjects with NTG ( P = 0.03 ) and POAG ( P = 0.025 ) versus controls . Mean vit-B6 levels in NTG and POAG were 30.50 ± 11.29 μg/L and 30 ± 12.15 μg/L , respectively . Conclusions : The plasma level of Hcy was found to be increased only in PXG patients and the plasma levels of vit-B6 were found to increase in the NTG and POAG sample groups . Using homocysteine and vit-B6 levels as the determinants of hyperhomocysteinemia still needs further research Open-angle glaucoma ( OAG ) is the commonest cause of irreversible blindness worldwide . Apart from an increased intraocular pressure ( IOP ) , oxidative stress and an impaired ocular blood flow are supposed to contribute to OAG . The aim of this study was to determine whether the dietary intake of nutrients that either have anti-oxidative properties ( carotenoids , vitamins , and flavonoids ) or influence the blood flow ( omega fatty acids and magnesium ) is associated with incident OAG . We investigated this in a prospect i ve population -based cohort , the Rotterdam Study . A total of 3502 participants aged 55 years and older for whom dietary data at baseline and ophthalmic data at baseline and follow-up were available and who did not have OAG at baseline were included . The ophthalmic examinations comprised measurements of the IOP and perimetry ; dietary intake of nutrients was assessed by vali date d question naires and adjusted for energy intake . Cox proportional hazard regression analysis was applied to calculate hazard ratios of associations between the baseline intake of nutrients and incident OAG , adjusted for age , gender , IOP , IOP-lowering treatment , and body mass index . During an average follow-up of 9.7 years , 91 participants ( 2.6 % ) developed OAG . The hazard ratio for retinol equivalents ( highest versus lowest tertile ) was 0.45 ( 95 % confidence interval 0.23–0.90 ) , for vitamin B1 0.50 ( 0.25–0.98 ) , and for magnesium 2.25 ( 1.16–4.38 ) . The effects were stronger after the exclusion of participants taking supplements . Hence , a low intake of retinol equivalents and vitamin B1 ( in line with hypothesis ) and a high intake of magnesium ( less unambiguous to interpret ) appear to be associated with an increased risk of OAG The relation between dietary antioxidant intake and primary open-angle glaucoma risk was examined in participants aged over 40 years in the Nurses ' Health Study ( n = 76,200 ) and the Health Professionals Follow-up Study ( n = 40,284 ) . They were followed biennially from 1980 and 1986 , respectively , to 1996 , during periods when they received an eye examination . Dietary intakes were measured repeatedly from 1980 in the Nurses ' Health Study and from 1986 in the Health Professionals Follow-up Study using vali date d food frequency question naires . The authors analyzed 474 self-reported glaucoma cases confirmed by medical chart review to have primary open-angle glaucoma with visual field loss . The authors used Cox proportional hazards models for cohort-specific multivariate analyses , and results were pooled using r and om effects models . The pooled multivariate rate ratios for primary open-angle glaucoma comparing the highest versus lowest quintile of cumulative up date d intake were 1.17 ( 95 % confidence interval ( CI ) : 0.87 , 1.58 ) for alpha-carotene , 1.10 ( 95 % CI : 0.82 , 1.48 ) for beta-carotene , 0.95 ( 95 % CI : 0.70 , 1.29 ) for beta-cryptoxanthin , 0.82 ( 95 % CI : 0.60 , 1.12 ) for lycopene , 0.92 ( 95 % CI : 0.69 , 1.24 ) for lutein/zeaxanthin , 1.05 ( 95 % CI : 0.59 , 1.89 ) for vitamin C , 0.97 ( 95 % CI : 0.62 , 1.52 ) for vitamin E , and 1.11 ( 95 % CI : 0.82 , 1.51 ) for vitamin A. In conclusion , the authors did not observe any strong associations between antioxidant consumption and the risk of primary open-angle glaucoma OBJECTIVE Open-angle glaucoma ( OAG ) is one of the major chronic diseases involving the optic nerve . However , little is known about the association between vitamin D and OAG . The present study was conducted to test the hypothesis that lower vitamin D status is associated with greater prevalence of OAG . DESIGN Cross-sectional study . Multivariable logistic regression was performed to examine the relationship between serum 25-hydroxyvitamin D ( 25(OH)D ) and OAG after adjusting for traditional potential confounders . OAG was defined by the criteria of the International Society for Geographical and Epidemiological Ophthalmology . SETTING The Fifth Korean National Health and Nutrition Examination Survey conducted in 2010 - 2011 . SUBJECTS Six thous and and ninety-four adult participants r and omly selected from 192 surveys in 131 locations in South Korea . RESULTS Multivariable-adjusted odds ratios of OAG across quintiles of decreasing 25(OH)D were 1.26 , 1.00 ( reference ) , 1.31 , 1.36 and 1.69 ( P for quadratic trend < 0.01 ) . The odds ratio for the lowest 25(OH)D quintile was significantly higher than that for the second quintile ( P < 0.01 ) . In addition , we discovered that the predictors for worsening of OAG , such as intraocular pressure or vertical and horizontal cup-to-disc ratios , had a significant relationship with 25(OH)D level . CONCLUSIONS There was a reverse J-shaped association between 25(OH)D levels and the risk of OAG , with significantly elevated risk at lower 25(OH)D. The findings of this research suggest that vitamin D deficiency should be considered as a potential risk factor for the development of OAG . To our knowledge , the present study is the first one that shows an association between vitamin D status and OAG IMPORTANCE Effective strategies for primary prevention are lacking for exfoliation glaucoma ( EG ) , which is the most common type of secondary glaucoma . OBJECTIVE To examine the association between B vitamin intake and EG or suspected EG ( EG/SEG ) risk . DESIGN , SETTING , AND PARTICIPANTS National prospect i ve cohort study using more than 20 years of follow-up data from the Nurses ' Health Study ( all female registered nurses ) and the Health Professionals Follow-up Study ( all male health professionals ) from June 1 , 1980 , to May 31 , 2010 ( Nurses ' Health Study ) and January 1 , 1986 , to December 31 , 2010 ( Health Professionals Follow-up Study ) . We included a subset of 78,980 Nurses ' Health Study women and 41,221 Health Professionals Follow-up Study men who were 40 years or older , free of glaucoma , had completed diet question naires , and reported eye examinations ( follow-up rate , > 85 % ) . EXPOSURES Cumulatively up date d intake of B vitamins ( folate , vitamin B6 , and vitamin B12 ) as ascertained by repeated administration of vali date d question naires . MAIN OUTCOMES AND MEASURES Incident cases of EG/SEG , totaling 399 ( 329 women and 70 men ) , were first identified with the question naires and were subsequently confirmed with medical records . Multivariable relative risks for EG/SEG were calculated in each cohort and then pooled with meta- analysis . RESULTS Vitamin B₆ and vitamin B₁₂ intake was not associated with EG/SEG risk in pooled analyses ( P = .52 and P = .99 for linear trend , respectively ) . However , a suggestive trend of a reduced risk was observed with higher intake of folate : compared with the lowest quintile of cumulatively averaged up date d total folate intake , the multivariable relative risk for EG/SEG for the highest quintile ( ≥654 μg/d ) was 0.75 ( 95 % CI , 0.54 - 1.04 ; P = .02 for linear trend ) . These results were not material ly altered after adjustment for vitamin B₆ and vitamin B₁₂ intake . An association was observed for supplemental folate intake but not for dietary folate only ( P = .03 and P = .64 for linear trend , respectively ) . Greater frequency of multivitamin use showed a modest suggestive inverse association ( current multivitamin use of ≥6 times per week vs nonuse multivariable relative risk , 0.84 ; 95 % CI , 0.64 - 1.11 ; P = .06 for linear trend ) . CONCLUSIONS AND RELEVANCE Higher total folate intake was associated with a suggestive lower risk for EG/SEG , supporting a possible causal role of homocysteine in EG/SEG PURPOSE To explore the association between consumption of fruits and vegetables and the presence of glaucoma in older African-American women . DESIGN Cross-sectional study . METHODS Disc photographs and suprathreshold visual fields were obtained from the 662 African-American participants in the Study of Osteoporotic Fractures . Masked , trained readers grade d all discs , and 2 glaucoma specialists review ed photographs and visual fields . The Block Food Frequency Question naire assessed food consumption . Relationships between selected fruit/vegetable/nutrient consumption and glaucoma were evaluated using logistic regression models after adjusting for potential confounders . RESULTS After excluding women missing Food Frequency Question naire and disc data , 584 African-American women ( 88.2 % of total African-American cohort ) were included . Glaucoma was diagnosed in at least 1 eye in 77 subjects ( 13 % ) . Women who ate 3 or more servings/day of fruits/fruit juices were 79 % ( odds ratio [ OR ] = 0.21 ; 95 % confidence interval [ CI ] : 0.08 - 0.60 ) less likely to have glaucoma than women who ate less than 1 serving/day . Women who consumed more than 2 servings/week of fresh oranges ( OR = 0.18 ; 95 % CI : 0.06 - 0.51 ) and peaches ( OR = 0.30 ; 95 % CI : 0.13 - 0.67 ) had a decreased odds of glaucoma compared to those consuming less than 1 serving/week . For vegetables , > 1 serving/week compared to ≤1 serving/month of collard greens/kale decreased the odds of glaucoma by 57 % ( OR = 0.43 ; 95 % CI : 0.21 - 0.85 ) . There was a protective trend against glaucoma in those consuming more fruit/fruit juices ( P = .023 ) , fresh oranges ( P = .002 ) , fresh peaches ( P = .002 ) , and collard greens/kale ( P = .014 ) . Higher consumption of carrots ( P = .061 ) and spinach ( P = .094 ) also showed some associations . Individual nutrient intake from food sources found protective trends with higher intakes of vitamin A ( P = .011 ) , vitamin C ( P = .018 ) , and α-carotene ( P = .021 ) , and close to statistically significant trends with β-carotene ( P = .052 ) , folate ( P = .056 ) , and lutein/zeaxanthin ( P = .077 ) . CONCLUSION Higher intake of certain fruits and vegetables high in vitamins A and C and carotenoids may be associated with a decreased likelihood of glaucoma in older African-American women . R and omized controlled trials are needed to determine whether the intake of specific nutrients changes the risk of glaucoma Purpose : To compare peripapillary retinal nerve fiber layer ( RNFL ) thicknesses measured by Cirrus HD optical coherence tomography ( OCT ) of patients with vitamin B12 deficiency with healthy controls and to evaluate the correlation between the peripapillary RNFL thickness and plasma vitamin B12 levels . Material s and Methods : Forty-five patients ( 19 male and 26 female ) with a diagnosis of vitamin B12 deficiency ( patient group ) and 45 age- and sex- matched healthy subjects ( control group ) were consecutively enrolled in this study . Average , temporal , nasal , inferior , and superior quadrant peripapillary RNFL thicknesses of each subject were obtained using the Cirrus HD OCT . Disc area ( DA ) and rim area ( RA ) , central subfield thickness ( CST ) , cube volume ( CV ) , and cube average thickness ( CAT ) were also measured . Results : Mean age of each group was 33.1 ± 6.5 years ( range : 21–45 years ) . Mean plasma vitamin B12 level was 114.8 ± 34.0 pg/mL in the patient group and was 405.1 ± 20.0 pg/mL in the control group ( p < 0.001 ) . The patient and control groups were similar regarding axial length , plasma folate levels , DA , RA , CST , CV , CAT , and RNFL thicknesses in superior , nasal , and inferior quadrants . However , average RNFL and RNFL in temporal quadrant were significantly thinner in the patient group than in the control group ( p = 0.013 and p < 0.001 , respectively ) . In addition , temporal ( r = 0.356 , p = 0.001 ) and average ( r = 0.212 , p = 0.045 ) peripapillary RNFL thicknesses were correlated with plasma vitamin B12 levels . Conclusion : We have shown that , as in other non-glaucomatous optic neuropathies , temporal quadrant RNFL thickness was thinner in patients with vitamin B12 deficiency and it was correlated with plasma vitamin B12 levels . Further studies are warranted to clarify the clinical relevance of these findings and the effects of vitamin B12 replacement therapy Purpose : To investigate the protective effects of vitamin A palmitate and carbomer gel on the morphology of conjunctival epithelium and density of goblet cells ( GCs ) in patients on long-term prostagl and in analogs ( PGAs ) application . Methods : In this prospect i ve cohort study , 23 primary open-angle glaucoma patients and 7 normal-tension glaucoma patients prescribed PGAs for > 1 year were enrolled into 3 identical clinical trials and r and omized into 3 groups ( 10 per group ) . Patients were treated twice daily with vitamin A palmitate eye gel 0.1 % , or carbomer eye gel 0.2 % , or no additional application of these 2 drugs . Ocular surface disease index question naires , Schirmer 1 test without anesthesia , tear break-up time test , and GCs density assessment by in vivo confocal microscopy and conjunctival impression cytology analysis were performed at baseline and at months 1 , 3 , and 6 of the study . Results : Both vitamin A palmitate and carbomer gel led to a significant improvement in ocular surface disease index question naires score and prevented the gradual decline in tear break-up time . Vitamin A palmitate significantly increased the GC density after treatment . The GC density assessed by in vivo confocal microscopy positively correlated with that measured by conjunctival impression cytology . Conclusions : Vitamin A palmitate and carbomer eye gel can effectively relieve dry eye symptom caused by long-term application of PGAs by increasing the GCs density and thereby reducing the toxicity to the conjunctiva . Vitamin A palmitate and carbomer eye gel may be valuable alternatives for glaucoma patients who prescribed long-term PGAs |
12,343 | 29,478,281 | In the subgroup analyses and meta‐regressions , use of non‐cotton devices for conventional cytology and use of a particular platform for LBC were associated with lower unsatisfactory rates .
Meta‐regression also suggested chronological improvement in unsatisfactory rates for both tests .
In Japanese cervical cancer screening programs , conventional cytology remains prevalent . | The Bethesda system ( TBS ) has been used for cervical cytological diagnosis in Japan since 2008 .
Evaluation of specimen adequacy is the most important aspect of quality assurance and for precise diagnosis in TBS . | Please cite this paper as : Castle P , Bulten J , Confortini M , Klinkhamer P , Pellegrini A , Siebers A , Ronco G , Arbyn M. Age‐specific patterns of unsatisfactory results for conventional Pap smears and liquid‐based cytology : data from two r and omised clinical trials . BJOG 2010;117:1067–1073 |
12,344 | 12,804,392 | Radiographic outcomes were improved by antibiotic treatment .
REVIEW ER 'S CONCLUSIONS For acute maxillary sinusitis confirmed radiographically or by aspiration , current evidence is limited but supports the use of penicillin or amoxicillin for 7 to 14 days . | BACKGROUND For adults seeking care in ambulatory medical practice s , sinusitis is the most common diagnosis treated with antibiotics .
OBJECTIVES We examined whether antibiotics are indicated for acute sinusitis , and if so , which antibiotic classes are most effective . | In the treatment of acute maxillary sinusitis , azithromycin offers an advantage over phenoxymethylpenicillin in that a complete course of treatment requires drug administration once daily for only three days . In this double-blind , parallel-group , multicenter study , 438 patients with radiographically verified maxillary sinusitis were r and omly assigned to receive either 500 mg azithromycin once daily for three days ( 221 patients ) or 1.3 g phenoxymethylpenicillin three times daily for ten days ( 217 patients ) . Nasal secretion , maxillary tenderness and pain , nasal obstruction , general malaise , and hyposmia , were assessed at the start of the study and on days 4 , 11 , and 25 of treatment . After 11 days 58 % of the patients in the azithromycin group were cured versus 51 % in the penicillin group ; after 25 days the cure rate was 79 % versus 76 % , respectively . When both cure and improvement were considered , the corresponding figures after 11 days were 97 % ( azithromycin ) and 95 % ( penicillin ) ; after 25 days they were 92 % and 88 % , respectively . Adverse events , predominantly gastrointestinal , occurred in 73 ( 33 % ) of the azithromycin-treated patients and in 87 ( 40.1 % ) of those treated with penicillin . No difference in efficacy was found between the two drugs in the treatment of acute maxillary sinusitis , and the adverse effects were comparable . The short duration of treatment with azithromycin offers a significant advantage over treatment with phenoxymethylpenicillin The clinical effect and the penetration of ampicillin into sinus secretion after oral administration of bacampicillin was studied in 47 patients with acute maxillary sinusitis allocated at r and om in treatment with 400 mg bacampicillin 3 times or 1200 mg twice daily . The overall clinical effect was similar and was assessed as " good " in 23/25 patients treated with 400 mg doses and in 19/22 treated with 1200 mg . Adverse reactions were reported by 4 patients . The concentrations of ampicillin obtained in sinus secretion were proportional to the dose given . The highest values after 400 mg bacampicillin were approximately 0.6 mg/l and after 1200 mg about 2 mg/l . Both dosages are applicable to treatment of acute maxillary sinusitis Respiratory tract pathogens ( beta-haemolytic streptococci groups A , C and G , Haemophilus influenzae , Branhamella catarrhalis or pneumococci ) , were isolated from nasopharyngeal and /or throat swabs in 73/138 ( 53 % ) patients greater than 10 years of age with a clinical diagnosis of acute sinusitis , acute tonsillitis , purulent nasopharyngitis or acute bronchitis . Serological evidence of a viral infection ( influenza A and B , parainfluenza 1 , 2 and 3 , respiratory syncytial virus , adenovirus ) or Mycoplasma pneumoniae infection was found in 10 % of the patients . The serum content of C-reactive protein ( S-CRP ) was increased ( greater than 12 mg/l ) in 26/33 ( 79 % ) patients with streptococci and in 22/59 ( 37 % ) patients without respiratory tract bacteria . In patients with a serological evidence of a virus tonsillitis , the S-CRP was also high ( 32 - 64 mg/l ) . At follow-up 10 - 12 days after the first visit , the clinical effect of erythromycin and penicillin V was judged to be similar ( 90 % clinical effect ) . Relapse or re-infection with group A streptococci were seen in 7 patients ( 4 on erythromycin , 3 on penicillin ) . In another 6 patients ( 3 on erythromycin , 3 on penicillin ) , antibiotic treatment was switched owing to persisting symptoms , probably due to H. Influenzae infection in 3 cases . The patients ' own estimates of their symptoms suggested treatment with erythromycin to have a more rapid effect than treatment with penicillin PURPOSE To compare the efficacy and tolerability of a 3-day course of azithromycin with a 10-day course of amoxicillin/clavulanic acid in the treatment of acute sinusitis in adults . PATIENTS AND METHODS One hundred adult patients with acute sinusitis were included in an open , r and omized study . Clinical diagnosis of sinusitis was confirmed by nasal endoscopy , sinus radiography , and ( when possible ) by culture of sinus aspirate . Patients were r and omized to receive azithromycin ( 500 mg once daily for 3 days ) or amoxicillin/clavulanate ( 625 mg every 8 hours for 10 days ) . RESULTS A significantly faster resolution of signs and symptoms of sinusitis was observed in the azithromycin-treated patients . By the end of therapy ( days 10 - 12 ) , 95 % of the patients in the azithromycin group and 74 % in the amoxicillin/clavulanate group were cured . The remaining patients ' conditions were improved . By the follow-up visit , cure was achieved in 98 % of the azithromycin-treated patients , and 91 % of the amoxicillin/clavulanate-treated patients . Treatment failure was observed in three patients from the amoxicillin/clavulanate group , and relapse occurred in one patient from each group . Bacteriologic eradication was achieved in 23 of 23 and 21 of 24 patients treated with azithromycin and amoxicillin/clavulanate , respectively . Both drugs were well tolerated . Two patients ( 4 % ) from the azithromycin group and five patients ( 10 % ) from the amoxicillin/clavulanate group reported mild gastrointestinal disturbances . CONCLUSIONS In adults with acute sinusitis , a 3-day course of azithromycin was as effective and well tolerated as a 10-day course of amoxicillin/clavulanic acid . A significantly simpler dosage regimen and faster clinical effect were the advantages of azithromycin Loracarbef is an oral synthetic beta-lactam antibiotic in the new carbacephem class . We conducted a multicenter , r and omized , double-blind , parallel-group study to compare the efficacy and safety of loracarbef 200 mg twice daily ( BID ) and 400 mg BID when given orally for 10 days to patients 12 years of age and older with acute maxillary sinusitis . Because sinus aspirates for culture are not routinely obtained in the management of acute maxillary sinusitis , antimicrobial therapy usually is selected empirically . This study was design ed to provide data simulating the usual clinical practice of treatment without sinus aspiration . Two hundred nine patients who met the entry criteria , which included abnormal pretherapy sinus radiographs compatible with acute maxillary sinusitis and symptoms of fewer than 4 weeks ' duration , qualified for the clinical analyses . Of the 106 clinical ly qualified patients assigned to the 200-mg BID group , favorable clinical responses ( cure and improvement ) were noted in 86 ( 81.1 % ) patients . Of the 103 clinical ly qualified patients assigned to the 400-mg BID group , 84 ( 81.6 % ) patients had favorable clinical responses . These results compare favorably with accepted clinical response rates of 70 % to 80 % for beta-lactams selected on an empiric basis . At the end of the treatment period , favorable radiologic responses ( resolved and improved ) and favorable clinical responses occurred in 55 ( 51.9 % ) of the 106 clinical ly qualified patients in the 200-mg BID group and in 57 ( 55.3 % ) of the 103 clinical ly qualified patients in the 400-mg BID group . Mean roentgenogram scores for the clinical ly qualified patients were 2.3 for both groups before therapy and 1.3 and 1.5 after therapy for the 200-mg BID and 400-mg BID groups , respectively . The mean change from pretherapy to posttherapy by patient was 1.0 for the 200-mg BID group and 0.8 for the 400-mg BID group . There were no statistically significant differences between treatment groups in the incidence of specific adverse events reported during therapy . These data suggest that loracarbef 200 mg BID is comparable in efficacy and safety to loracarbef 400 mg BID in the treatment of patients with acute maxillary sinusitis The efficacy , tolerability and safety of azithromycin and co-amoxiclav in the treatment of non-severe acute maxillary/ethmoidal sinusitis were compared in a r and omized , open clinical trial in 254 adult patients . The predominant pathogens were Streptococcus pneumoniae and Haemophilus influenzae ( 83 patients ) . Azithromycin was administered orally to 165 patients at a single daily dose of 500 mg for 3 days , and co-amoxiclav ( 4:1 ) to 89 patients , at a dose of 500 mg three times daily for 10 days . The overall clinical response rates were 87.5 % for azithromycin and 83.7 % for co-amoxiclav at follow-up ( day 21–28 ) . Microbiological responses to both drugs were good , with only five patients in each group having a persistent infection after treatment . Both drugs were well tolerated and produced similar incidences of adverse events , which were mostly gastrointestinal . Azithromycin was as effective , and as well tolerated as co-amoxiclav , and its shorter simpler dosing regime may offer advantages in compliance and cost In two ear , nose and throat ( ENT ) divisions , 74 patients affected by acute sinusitis of bacterial origin were selected and , after r and omization in two balanced groups following an open parallel group design , assigned to treatment with brodimorprim and roxithromycin . At the beginning , after 3 days , 7 days and at the end of treatment the following symptoms were evaluated , using a four-step score : intensity of facial pain , headache , nasal stiffness , hyposmia , nasal secretion . The mean treatment period was 8.7 days . Tolerability was evaluated through registration and analysis of side effects and laboratory blood tests . The comparison between groups showed a better activity of brodimoprim on facial pain , headache , nasal stiffness and nasal secretion . The presence of resistant bacterial strains was greater in the group treated with roxithromycin ( 30.8 % ) when compared with the brodimoprim group ( 12.5 % ) . Side effects were reported in 5 patients treated with brodimoprim and in 3 patients in the control group . Lab tests did not show serious variations BACKGROUND The treatment of acute , recurrent , and chronic sinusitis remains controversial because of the presence of a wide variety of aerobic and anaerobic bacteria in the sinuses . DESIGN This double-blind , r and omized trial compared cefaclor with amoxicillin in the treatment of acute , recurrent , and chronic maxillary sinusitis using clinical evaluation , roentgenography , and microbiologic evaluation of antral aspirates . SETTING Outpatient office of five otorhinolaryngologists in Salt Lake City , Utah . PATIENTS One hundred eight adult patients with acute , recurrent , or chronic maxillary sinusitis . INTERVENTION Oral treatment with cefaclor ( 500 mg ) twice daily or amoxicillin ( 500 mg ) three times daily for 10 days . MAIN OUTCOME MEASURE Clinical response to treatment with cefaclor vs amoxicillin . RESULTS Fifty-six patients with acute sinusitis , 25 with recurrent sinusitis , and 15 with chronic sinusitis were evaluable . Although multiple organisms were common in each group , patients with acute sinusitis were more likely to have Haemophilus influenzae or Streptococcus pneumoniae , and patients with recurrent or chronic sinusitis were more likely to have anaerobes in sinus aspirate . Whether treated with cefaclor or amoxicillin , clinical improvement occurred in 86 % of patients with acute sinusitis and 56 % of patients with recurrent sinusitis . Patients with chronic sinusitis were too few to allow statistical analysis of the differences in outcome between them and patients with recurrent or acute sinusitis . Resistance of the cultured organisms to the study drug used was unrelated to treatment outcome . CONCLUSIONS The rate of clinical improvement was high in patients with acute sinusitis but was less favorable in those with recurrent and chronic disease regardless of the study drug used . The susceptibility of organisms isolated to the study drugs was unrelated to outcome PURPOSE This multicenter study compared the clinical and bacteriologic efficacy of two oral antibiotics , cefuroxime axetil and amoxicillin/clavulanate , in the treatment of acute bacterial maxillary sinusitis . PATIENTS AND METHODS Three hundred seventeen patients with clinical and radiographic evidence of acute maxillary sinusitis were enrolled at nine centers and were r and omly assigned to receive 10 days of treatment with cefuroxime axetil 250 mg twice daily ( n = 157 ) or amoxicillin/clavulanate 500 mg three times daily ( n = 160 ) . Patients were assessed for both clinical and bacteriologic responses once during treatment ( 5 to 7 days ) and twice after treatment ( 1 to 3 days and 4 weeks ) . Bacteriologic assessment s were based on needle aspirates of the maxillary sinus obtained pretreatment and , when possible , at the first posttreatment visit . RESULTS Organisms were isolated from the pretreatment sinus aspirates of 198 of 317 ( 62 % ) patients , with the primary isolates being Streptococcus pneumoniae ( 22 % ) , Haemophilus spp . ( 17 % ) , Staphylococcus aureus ( 13 % ) , and Haemophilus influenzae ( 10 % ) . A satisfactory clinical outcome ( cure or improvement ) was achieved in 85 % ( 98 of 115 ) and 82 % ( 102 of 124 ) of the clinical ly evaluable patients treated with cefuroxime axetil or amoxicillin/clavulanate , respectively ( P = 0.446 ) . With respect to the eradication of the bacterial pathogens , a satisfactory outcome ( cure or presumed cure ) was obtained in 84 % ( 31 of 37 ) and 87 % ( 34 of 39 ) of bacteriologically evaluable patients treated with cefuroxime axetil or amoxicillin/clavulanate , respectively ( p = 0.567 ) . Treatment with amoxicillin/clavulanate was associated with a significantly higher incidence of drug-related adverse events ( 13 % versus 3 % , p = 0.001 ) , particularly diarrhea ( 8 % versus 1 % , p = 0.001 ) . Two patients in the cefuroxime axetil group and three patients in the amoxicillin/clavulanate group withdrew from the study due to adverse events . CONCLUSIONS Our results indicate that cefuroxime axetil twice a day is as effective as amoxicillin/clavulanate three times a day in the treatment of acute bacterial maxillary sinusitis but produces fewer adverse effects In this double-blind , parallel-group , multicenter study , 169 patients with symptoms of maxillary sinusitis but without radiographically confirmed empyema ( pus ) were r and omly assigned to receive either 500 mg azithromycin once daily for 3 days ( 87 patients ) or placebo daily for 3 days ( 82 patients ) . Nasal secretion , maxillary tenderness and pain , nasal obstruction , general malaise , and hyposmia were assessed at the start of the study and on days 4 , 11 , and 25 of treatment . After 11 days 58 % of the patients in the azithromycin group were cured versus 31 % in the placebo group ; after 25 days the cure rate was 79 % versus 67 % , respectively . When both cure and improvement were considered , the corresponding figures after day 25 were 90 % and 88 % , respectively . Adverse events , predominantly gastrointestinal , occurred in 24 ( 27 % ) of the azithromycin-treated patients and in 15 ( 18 % ) of those treated with placebo , but the difference was not statistically significant . There was a difference in efficacy in favor of azithromycin in the treatment of rhinitis with symptoms of maxillary sinusitis but without radiological signs of empyema ( pus ) . Antibiotics should only be used to alleviate symptoms in patients with moderate to severe symptoms , as the results after 25 days for both improvement and cure are equal . In the treatment of acute rhinitis with symptoms and signs of maxillary sinusitis but without empyema , treatment with azithromycin seems to result in a better cure rate after 10–12 days when compared with placebo In this prospect i ve r and omized clinical study a total of 59 patients of both sexes ( above 18 years of age ) were enrolled . Thirty patients with acute sinusitis were r and omly allocated to two treatment groups , one group receiving 1000 mg amoxicillin every 12h for 10 days and the other group receiving 500 mg amoxicillin every 8 h for 10 days . The median concentration of amoxicillin in nasal secretions was 2.34 µg/ml in the 12-h administration group and 1.95 µg/ml in the 8-h administration group . Median bioavailability of antibiotic at 8 - 24h did not show any statistical differences between the two treatment schemes [ probability ( Z ) = 0.2 ] . Twenty-nine patients with chronic sinusitis were then r and omly allocated to three groups , with patients receiving 1000 mg amoxicillin at 12 , 8 or 6 h before nasal and /or sinus surgery was carried out . The mean amoxicillin concentrations in mucosal tissues removed intraoperatively ranged from 0.69 to 0.99 µ/g sample . Statistical evaluation by analysis of variance did not show any statistically significant differences among the three treatment groups [ probability ( F ) = 0.1705 ] . In all cases of acute and chronic sinusitis , amoxicillin concentrations exceeded minimum inhibitory concentration values for pathogens common in sinusitis . Our results indicate that 1000 mg amoxicillin administered twice daily produces tissue concentrations high enough to be clinical ly effective in patients with either acute or chronic sinusitis The efficacy and tolerance of cefpodoxime proxetil were compared with those of cefaclor in a multicentre , international , prospect i ve , double-blind , placebo-controlled study in adult out patients suffering from acute sinusitis . At the end of treatment , cefpodoxime proxetil was more effective than cefaclor , producing complete clinical cure in 84 % of cases ( 102/122 ) vs 68 % of cases ( 77/114 ) in the cefaclor group ( P = 0.01 ) . The overall clinical efficacy ( cure + improvement ) was similar in the two groups with 95 % ( 116/122 ) satisfactory responses in the cefpodoxime proxetil group and 93 % ( 106/114 ) in the cefaclor group . Bacteriological response was similar with 95 % eradication in the cefpodoxime proxetil group ( 55/58 ) vs 91 % with cefaclor ( 63/69 ) In a double-blind , multicentre trial , 382 patients with a diagnosis of acute purulent sinusitis were r and omised to receive sparfloxacin 200 mg once daily for 5 days following a loading dose of 400 mg on day 1 ( n = 193 ) or cefuroxime axetil 250 mg twice daily for 8 days ( n = 189 ) . Patients were classified as success or failure according to clinical symptoms plus bacteriological and radiological data at the end of treatment and at a follow-up visit . In analyses of the intent-to-treat ( n = 374 ) and evaluable population s ( n = 304 ) , the 5 day course of sparfloxacin was at least as effective and well tolerated as the 8 day course of cefuroxime axetil . The success rates at the end of treatment in the evaluable population were 82.6 % and 83.2 % in the sparfloxacin and cefuroxime axetil groups , respectively . The pathogens isolated most frequently were Haemophilus influenzae ( 33 % ) and Streptococcus pneumoniae ( 28 % ) . Response rates according to the bacterial aetiology of the acute sinusitis were similar in the two treatment groups . Both drugs were well tolerated . The commonest adverse events were gastrointestinal and were reported in 2.6 % and 3.8 % of sparfloxacin- and cefuroxime axetil-treated patients , respectively We analysed 113 reports published in 1980 in a sample of medical journals to relate features of study design to the magnitude of gains attributed to new therapies over old . Overall we rated 87 per cent of new therapies as improvements over st and ard therapies . The mean gain ( measured by the Mann-Whitney statistic ) was relatively constant across study design s , except for non-r and omized controlled trials with sequential assignment to therapy , which showed a significantly higher likelihood that a patient would do better on the innovation than on st and ard therapy ( p = 0.004 ) . R and omized controlled trials that did not use a double-blind design had a higher likelihood of showing a gain for the innovation than did double-blind trials ( p = 0.02 ) . Any evaluation of an innovation may include both bias and the true efficacy of the new therapy , therefore we may consider making adjustments for the average bias associated with a study design . When interpreting an evaluation of a new therapy , readers should consider the impact of the following average adjustments to the Mann-Whitney statistic : for trials with non-r and om sequential assignment a decrease of 0.15 , for non-double-blind r and omized controlled trials a decrease of 0.11 The efficacy and tolerability of clarithromycin and amoxycillin in the treatment of acute maxillary sinusitis were compared in an open , Phase III multi-centre study . Sixty-one out- patients ( 40 males , 21 females ) received clarithromycin ( two 250 mg tablets twice daily ) and 59 ( 34 males , 25 females ) out- patients received amoxycillin ( two 500 mg capsules twice daily ) . Fifty-seven and 47 patients in the clarithromycin group were evaluable for clinical efficacy and bacteriological effectiveness , respectively . In the amoxycillin group , 57 and 40 patients were evaluated for clinical efficacy and bacteriological effectiveness , respectively . Body temperature , bacteriological culture results , blood and urine chemistries , and clinical signs and symptoms were evaluated prior to drug administration , between Days 4 to 6 and between Days 9 to 11 of treatment , and within 48 hours and , if required , 6 weeks after the end of treatment . Clinical signs and symptoms improved significantly ( p less than 0.001 ) in both treatment groups . When evaluated within 48 hours after the end of treatment , there was no significant difference between the clinical success rate for clarithromycin ( 91 % ) and amoxycillin ( 84 % ) nor in the number of patients whose original pathogen was eradicated ( 89 % clarithromycin , 93 % amoxycillin ) . Six patients reported adverse events , 2 with clarithromycin ( urticaria , gastro-intestinal ) and 4 with amoxycillin ( 2 urticaria , 2 gastro-intestinal ) . Clarithromycin was comparable to amoxycillin with respect to clinical efficacy and tolerability and offers a useful addition to the available therapies for the treatment of acute maxillary sinusitis Cefprozil is a beta-lactamase-stable oral cephalosporin with an antimicrobial spectrum that includes gram-positive and gram-negative pathogens commonly associated with acute bacterial sinusitis , one of the most common upper respiratory tract infections among adults . We conducted a multicenter , open-label study to compare the efficacy and safety of cefprozil and amoxicillin/clavulanate in the treatment of adults with severe acute bacterial sinusitis diagnosed by clinical and radiographic criteria . A total of 278 patients entered the study , 140 ( 59 males , 81 females ) in the cefprozil group and 138 ( 69 males , 69 females ) in the amoxicillin/clavulanate group . Patients were r and omized to 10 days of treatment with either cefprozil 500 mg BID or amoxicillin/clavulanate 500 mg/125 mg TID . Clinical severity was assessed at study entry , and patients were stratified based on symptom grade . Efficacy was evaluated using a 10-point question naire administered during , at the end of , and 2 weeks after completing therapy . At the end of treatment , 84.5 % ( 71/84 ) of patients with severe sinusitis treated with cefprozil had a satisfactory clinical response , which was not significantly different from the 89.9 % ( 80/89 ) of patients in the amoxicillin/clavulanate group who had a satisfactory clinical response . Two weeks after completing treatment , 80.8 % ( 63/78 ) of cefprozil-treated patients and 81.0 % ( 64/79 ) of amoxicillin/clavulanate-treated patients with severe sinusitis had a satisfactory response . Relapse was more common among amoxicillin/clavulanate patients ( 6/70 ; 8.6 % ) than among cefprozil patients ( 2/65 ; 3.1 % ) , but the difference was not statistically significant . Significantly more amoxicillin/clavulanate-treated patients experienced adverse events compared with cefprozil-treated patients ( P < 0.001 ) , including diarrhea ( P < 0.001 ) , nausea ( P < 0.042 ) , and rash ( P < 0.035 ) . Three times as many amoxicillin/clavulanate patients discontinued treatment because of adverse events . Cefprozil demonstrated comparable clinical efficacy to amoxicillin/clavulanate in the treatment of adults with severe sinusitis ; however , cefprozil was associated with a significantly lower incidence of diarrhea , nausea , and rash An open , multicentre study was undertaken in order to evaluate the efficacies and safety profiles of azithromycin and roxithromycin in 440 adults with acute otitis media , sinusitis or acute beta-haemiolytic streptococcal pharyngitis/tonsillitis . Treatment with 500 mg azithromycin , administered orally once daily for 3 days , produced a satisfactory clinical outcome ( cure or improvement ) in 51/52 ( 98 % ) patients with otitis media , 91/91 ( 100 % ) patients with pharyngitis/tonsillitis and 64/68 ( 94 % ) patients with sinusitis . Treatment with 150 mg roxithromycin , given orally twice daily for 10 days , produced satisfactory clinical responses in 54/55 ( 98 % ) , 91/92 ( 99 % ) and 69/73 ( 94 % ) patients with otitis media , pharyngitis/tonsillitis and sinusitis respectively . Of the 17 azithromycin-treated patients with sinusitis who were clinical ly and bacteriologically evaluable , Staphylococcus aureus persisted in two and Streptococcus pneumoniae in one . S. aureus also persisted in 1/12 clinical ly and bacteriologically-evaluable patient treated with roxithromycin . Of the 58 and 64 patients with pharyngitis/tonsillitis treated with azithromycin and roxithromycin , respectively , who were clinical ly and bacteriologically evaluable , Streptococcus pyogenes persisted at the end of treatment in 7/58 ( 12 % ) in the azithromycin group and in 13/64 ( 20 % ) in the roxithromycin group . At follow-up , there was no evidence of S. pyogenes reinfection in patients treated with azithromycin . Three episodes of reinfection occurred in the roxithromycin treatment group . Also , three patients showed evidence of clinical relapse at follow-up , although no pathogens were isolated . Azithromycin was associated with a lower incidence of adverse events . No azithromycin-treated patient was withdrawn prematurely because of a treatment-related event . Three roxithromycin-treated patients were withdrawn from treatment because of severe headache , thyroiditis or fatigue . In conclusion , for adults with acute upper respiratory tract infections , a 3-day course of once-daily azithromycin was found to be as effective and as well tolerated as a 10-day course of twice-daily roxithromycin The efficacy and tolerability of ceftibuten 400 mg o.d . or 200 mg b.i.d . was compared with amoxicillin/clavulanate ( AMX/CA , 500 mg/125 mg ) t.i.d . in the treatment of acute sinusitis . This was a multicenter , open , r and omized , parallel-group 8-day study . In total , 450 patients were evaluable for safety and 400 patients for efficacy . At day 10 , clinical cure rates were 83 % in the ceftibuten 400 mg o.d . group , 87 % in the ceftibuten 200 mg b.i.d . group and 89 % in the AMX/CA t.i.d . group ; the clinical /radiological cure rates were 52 , 44 and 56 % , respectively . Clinical and clinical /radiological cure rates at day 40 for the ceftibuten 400 mg o.d . group , ceftibuten 200 mg b.i.d . group and the AMX/CA t.i.d . group were similar , with clinical cure rates of 81 , 82 and 87 % , and clinical /radiological cure rates of 62 , 58 and 63 % , respectively . Most adverse events were mild . Ceftibuten , 400 mg o.d . or 200 mg b.i.d . , was equally effective and well tolerated as AMX/CA t.i.d . in the treatment of acute sinusitis Loracarbef ( LY 163892 ) , a β-lactam antibiotic ( carbacephem ) , was compared with amoxicillin/ clavulanate potassium in a 10-day , single-blind , r and omized parallel trial in the treatment of acute bacterial maxillary sinusitis . Based on posttherapy aspirate and culture , there was a 95.2 % bacteriologic cure rate in patients receiving loracarbef ( 400 mg twice daily ) and an 86.7 % cure rate in patients receiving amoxicillin/clavulanate ( 500/125 mg three times daily ) ( p = 0.359 ) . Loracarbef was comparable in efficacy to amoxicillin/clavulanate with a more desirable safety profile Summary A double-blind trial of doxycycline ( 200 mg . on the first day followed by 100 mg . daily for a total of 7 days ) and ampicillin ( 250 mg . 4-times daily for 7 days ) in 44 cases of acute and chronic sinusitis showed significantly superior results with doxycycline : 90 % of cases responded to doxycycline and 35 % to ampicillin . The incidence of side-effects was low , and these were of a minor nature , in no case necessitating discontinuance of treatment . The implication of these results for the treatment of chronic bronchitis is discussed The in vitro activity of and pathogen responses to sparfloxacin were compared with those of st and ard therapies for the treatment of patients with community-acquired pneumonia , complicated skin or skin-structure infections , urinary tract infections , acute bacterial exacerbations of chronic bronchitis , and acute maxillary sinusitis in 7 multicenter controlled trials in North America . Sparfloxacin was administered orally as a 400-mg loading dose followed by 200 mg once daily for up to 10 days . The bacteriologic efficacy of sparfloxacin ( 84 % to 95 % ) was comparable to that of comparator drugs ( 77 % to 100 % ) . Sparfloxacin was generally 2 to 8 times more active ( minimum inhibitory concentration for 90 % of strains tested [ MIC90 ] : 0.03 to 0.5 microg/mL ) than comparators against common pathogens isolated in community-acquired infections , especially Streptococcus pneumoniae , including penicillin-resistant strains ; Moraxella catarrhalis ; Haemophilus influenzae ; Streptococcus pyogenes ; and Staphylococcus aureus . Sparfloxacin was also effective against Chlamydia and Mycoplasma species . The emergence of resistance was uncommon during sparfloxacin therapy ( 0.3 % of 1100 cases ) . Higher area under the plasma concentration-time curve/MIC and maximum plasma concentration/MIC ratios for sparfloxacin were associated with clinical and bacteriologic efficacy , whereas lower ratios were associated with clinical and bacteriologic failure . The clinical efficacy of sparfloxacin ( 80 % to 95 % ) was comparable to that obtained with the comparator drugs ( 71 % to 92 % ) . In addition , sparfloxacin was well tolerated and had an overall frequency of related adverse events similar to that of the comparators . There was a higher frequency of photosensitivity reactions but a lower level of digestive adverse events with sparfloxacin compared with comparators . Sparfloxacin is a suitable therapeutic alternative for the empiric treatment of respiratory tract infections owing to its favorable pharmacokinetic profile and activity against typical and atypical respiratory tract pathogens , even in geographic areas with a high incidence of penicillin resistance The efficacy and safety of cefixime , the first oral third-generation cephalosporin , were evaluated in a multicenter clinical trial involving 118 adult patients with acute sinusitis or acute exacerbations of chronic sinusitis . Patients received a single daily dose of 400 mg of cefixime for a mean duration of 10 days ; 106 patients completed a course of therapy . Clinical cure and improvement were achieved in 90 % of these patients ( 61 % cured and 29 % improved ) . Among the patients evaluated again 2 weeks after therapy , 91 % had a sustained clinical cure or improvement . Sinus exu date specimens were obtained from all patients by transantral puncture before therapy . Pathogens were isolated from 76 patients ( 66 % ) , the most common pathogens being Haemophilus influenzae , α-hemolytic streptococci , and Streptococcus pneumoniae . Eighty-six percent of pathogens were presumed eradicated . Three patients discontinued therapy because of side effects . The most frequently reported adverse effects were gastrointestinal , with 20 % of patients reporting diarrhea . Cefixime was effective in the treatment of bacterial sinus infections in adults and was well tolerated In sinus empyema , H. influenzae is the most prevalent pathogen in some sub population s and in case of therapeutic failure . Cefixime , the first oral cephalosporin of the 3rd generation , is highly potent in vitro against H. influenzae . To study the efficacy and safety of cefixime in adults with acute sinusitis , a coordinated , double-blind multicenter trial was design ed for purulent cases , as confirmed by antral aspiration . A total of 364 patients were enrolled in the study with 125 cases r and omized to the reference group , assigned to treatment with cefaclor . Evaluation was based on clinical outcome and on antral reaspiration ( 86 % of the cases ) . No significant differences between the treatment groups were found , as regards short-term or long-term clinical outcome . However , the clinical examination overestimated the therapeutic results . Only 4 % of the patients were considered as failures , but the re-aspiration demonstrated remaining suppuration in 14 % of all cases ( p less than 0.001 ) . Based on re-aspiration , the failure rate among patients with initial growth of pathogens was lower for cefixime ( 8 % ) than for cefaclor ( 20 % ) ( p less than 0.05 ) . Such a difference was not found among patients with growth of H. influenzae . No serious adverse reactions were recorded , but loose stools and diarrhoea were significantly more frequent in the cefixime treatment group . Five patients ( 2 % ) in the cefixime treatment group discontinued their treatment due to adverse events Summary 80 adult out patients suffering from otitis media , sinusitis ( maxillaris or frontalis ) or peritonsillitis were treated with 500 mg ciprofloxacin b.i.d . ( n=40 ) or with 2 g penicillin V t.i.d . ( n=40 ) . The patients were r and omly allocated . Three groups of patients result ed , clinical ly and bacteriologically evaluable , or only clinical ly evaluable because the isolated strains were resistant to ciprofloxacin or penicillin V or because no strains were isolated . Ciprofloxacin was superior to penicillin V ; there were fewer resistant strains ( one compared to 11 ) , and the eradication rate ( 57 % compared to 43 % ) as well as the clinical efficacy ( 60 % compared to 48 % ) of ciprofloxacin were better than those of penicillin V — even in a daily dose of 6.0 g. Both treatments were well tolerated ; side effects were neither reported nor found . Zusammenfassung80 Erwachsene , die an Otitis media , Sinusitis ( maxillaris oder frontalis ) oder einer Peritonsillitis litten , wurden ambulant 12stündlich mit 500 mg Ciprofloxacin ( n=40 ) oder 8stündlich mit 2 g Penicillin V ( n=40 ) beh and elt . Die Zuteilung zu den Beh and lungsgruppen erfolgte r and omisiert . Es bildeten sich drei Gruppen von Patienten , die klinisch und bakteriologisch oder nur klinisch auswertbar waren , weil die Erreger sich resistent gegen Ciprofloxacin oder Penicillin V erwiesen oder weil keine Keime isoliert werden konnten . Ciprofloxacin war i m Vergleich zu Penicillin V überlegen wirksam ; es gab weniger resistente Erreger ( einer gegenüber 11 ) und die Erreger-Elimination ( 57 % gegenüber 43 % ) sowie die klinische Erfolgsrate ( 60 % i m Vergleich zu 48 % ) des Ciprofloxacin waren besser als diejenigen des Penicillin V — selbst bei einer Tagesdosis von 6,0 g. Die Verträglichkeit bei der Beh and lung war einw and frei ; Nebenwirkungen wurden weder berichtet noch gefunden Cyclacillin , a new aminosalicylic semisynthetic penicillin , was compared with amoxicillin for the therapy of acute bacterial maxillary sinusitis in 80 patients ( ages , 12 to 70 years ) in a prospect i ve , double-blind , r and omized clinical trial . Direct sinus aspirations for quantitative culture were done for all patients before and after 10 days of therapy . Both drugs were administered at a dosage of 500 mg orally three times daily . Among culture-positive patients , clinical cure was achieved in 23 of 26 patients and 25 of 27 patients treated with cyclacillin and amoxicillin , respectively , for an overall cure rate of 91 % . Bacteriologic failure occurred in 9 % ( 4 of 44 patients ) ; 3 of the 4 failures were in the cyclacillin group . There was no correlation between clinical or bacteriologic cure and the results of sinus transillumination ( clear , dark ) at follow-up . Initial direct sinus aspirates were positive in 57 of 80 cases ( 70 % ) : 25 ( 44 % ) of these were the result of Streptococcus pneumoniae and 23 ( 40 % ) were the result of Haemophilus influenzae . All of these isolates were susceptible ( MIC , less than or equal to 0.5 microgram/ml ) to both study drugs ; no ampicillin-resistant H. influenzae was recovered . On day 10 of therapy , mean concentrations of both drugs in serum were 2.5 to 2.7 micrograms/ml , but no antibiotic was detectable in 20 of 21 simultaneous sinus aspirates . Adverse effects ( rash , diarrhea ) were infrequent and similar in both groups . Cyclacillin appears equivalent to amoxicillin in the therapy of acute maxillary sinusitis Seventy-eight patients participated in this multicenter , third-party-blinded study comparing a single daily dose of azithromycin for 5 days ( 500 mg on day 1 followed by 250 mg/day for days 2 - 5 ) with amoxicillin ( 500 mg three times daily ) for 10 days in the treatment of acute bacterial maxillary sinusitis . A total of 38 evaluable patients contributed to the efficacy analysis . The overall clinical response rate was 100 % for both antibiotics . The clinical cure rate , as determined by the investigator , was 73.9 % for azithromycin and 73.3 % for amoxicillin ; improvement was seen in 26.1 % and 26.7 % of patients , respectively . The bacteriologic cure rate in these 38 patients was 100 % in both groups . Both antibiotics were well tolerated ; side effects were reported by 4.9 % of patients in the azithromycin group compared with 8.1 % in the amoxicillin group . Most of these side effects were gastrointestinal disturbances that were reported by four of five ( three amoxicillin , one azithromycin ) patients experiencing side effects . All side effects were mild , and in both groups only minor abnormalities in laboratory data were detected . No patient discontinued the study because of treatment-related side effects . In this study , a 5-day course ( one dose per day ) of azithromycin proved to have efficacy , safety , and tolerability that was equal to a 10-day course ( three doses per day ) of amoxicillin in the treatment of acute bacterial sinusitis OBJECTIVE To compare efficacy and tolerability of brodimoprim tablets with doxycycline tablets in adults with acute sinusitis . DESIGN Open , r and omized , controlled phase III study , with parallel groups . PATIENTS Of the 70 enrolled patients , 56 adults of both sexes with a mean age of 33 years were evaluable . STUDY DRUGS : One brodimoprim 200 mg tablet or one doxycycline 100 mg tablet was administered once daily for 8 to 12 days ( on the first treatment day all patients received the loading dose consisting of 2 tablets of the corresponding compound ) . CLINICAL OUTCOME In the brodimoprim group 96.4 % of the patients were judged cured/improved ; in the doxycycline group 96.2 % . BACTERIOLOGICAL OUTCOME : Eradication of the causative pathogen/s was achieved in 87.5 % of the patients treated with brodimoprim and in 60 % of the doxycycline group . SAFETY OUTCOME : Tolerability was judged as very good/good in 89.7 % of the patients treated with brodimoprim and in all patients receiving doxycycline . Gastrointestinal skin , CNS and various other reactions were reported by 13 patients ; 3 of them had to discontinue treatment . Discontinuation of therapy : 8 more patients withdrew from the study due to inactivity of the compound or reasons unrelated to the drugs . CONCLUSION Brodimoprim was shown to be effective in the treatment of acute sinusitis in adults , its efficacy being equal to that of doxycycline . The assessment s showed a positive clinical response to the medication in 96.4 % of the patients treated with brodimoprim and 96.2 % of the patients taking doxycycline . Both compounds were well tolerated and all side effects were of mild nature and reversible OBJECTIVE To compare the safety and efficacy of a combination of amoxicillin and clavulanate potassium given orally every 12 hours ( amoxicillin , 875 mg ; clavulanate , 125 mg ) with that given every 8 hours ( amoxicillin , 500 mg ; clavulanate , 125 mg ) for the treatment of patients with acute bacterial maxillary sinusitis . DESIGN Multicenter double-blind r and omized double-dummy controlled trial . SETTING Physicians ' offices and ambulatory care clinics . PATIENTS One hundred seventy patients at least 18 years of age with acute bacterial maxillary sinusitis who could be treated with an oral antimicrobial agent were r and omized , and data from 134 were suitable for evaluation . Four patients were withdrawn from this study because of adverse effects . INTERVENTIONS Patients received a combination of amoxicillin and clavulanate orally every 12 hours ( amoxicillin , 875 mg ; clavulanate , 125 mg ) or every 8 hours ( amoxicillin , 500 mg ; clavulanate , 125 mg ) for 14 days . MAIN OUTCOME MEASURE Clinical success at the end of therapy . RESULTS Clinical success at the end of therapy was similar for the 2 treatment groups , 93 % and 88 % of patients in the every 12-hour and every 8-hour groups , respectively ( P = .76 ; 95 % confidence interval , -4.0 % to 15.6 % ) . Clinical success rates at follow-up 2 to 4 weeks after the end of therapy were also similar in the 2 groups . Adverse events related to treatment were reported with similar frequency in the 2 groups . CONCLUSION Amoxicillin and clavulanate given every 12 hours is as effective and as safe as administration every 8 hours for the treatment of acute bacterial maxillary sinusitis BACKGROUND The diagnosis of sinusitis is difficult and there are few controlled studies of customary therapies . In particular , the possible role of topical intranasal steroid as an adjunct to antibiotic treatment has not been evaluated . METHODS The study was a multicenter , double-blind , r and omized , parallel trial in which patients aged 14 years or older were recruited from allergy practice s. All patients had maxillary sinusitis documented by radiographs . Treatment consisted of amoxicillin/clavulanate potassium 500 mg combined with nasal spray of either 100 micrograms flunisolide or placebo to each nostril three times a day for 3 weeks ( phase I ) followed by administration of flunisolide or placebo nasal spray alone three times a day for 4 weeks ( phase II ) . RESULTS Clinical symptoms and signs decreased significantly in both treatment groups during phase I ( p < 0.01 ) . There was a trend to greater improvement in the patients treated with flunisolide , but only the decrease in turbinate swelling/obstruction was statistically significant at the end of phase I when compared with placebo ( p = 0.041 ) . Patients ' global assessment of overall effectiveness of treatment was higher for flunisolide than placebo after phase I ( p = 0.007 ) and after phase II ( p = 0.08 ) . Maxillary sinus radiographs showed improvement in both treatment groups during phase I ( p < 0.004 ) with somewhat greater regression of abnormal findings in patients treated with flunisolide after phase II ( p = 0.066 ) . However , 80 % of radiographs were still abnormal at the end of phase I. All types of inflammatory cells were significantly decreased in nasal cytograms in patients treated with flunisolide in comparison with those treated with placebo . Flare-up of sinusitis during phase II occurred in 26 % of with those treated with placebo . Flare-up of sinusitis during phase II occurred in 26 % of patients treated with flunisolide and 35 % of those treated with placebo and tended to be more severe in the latter , although these differences were not statistically significant . Adverse events , mainly gastrointestinal symptoms and headache , were similar in both groups and more frequent in phase I than in phase II , ( 42 vs 15 patients ) ; these side effects were probably due to the antibiotic . CONCLUSION The addition of flunisolide topical nasal spray as an adjunct to antibiotic therapy was most effective in global evaluations , tended to improve symptoms , to decrease inflammatory cells in nasal cytograms , to normalize ultrasound scans , and to aid regression of radiographic abnormalities compared with placebo spray Summary In 50 adults with bacterial sinusitis , cyclacillin ( 1500 mg . per day for 7 days ) proved significantly more effective than placebo in eliminating the signs and symptoms and in eradicating the causative microorganisms , ( Staphylococcus aureus , Proteus mirabilis , and Staph , epidermidis were most frequently isolated in this series ) . Sixty percent of the cultures in the cyclacillin series were sterilized , compared with only 10 % in the placebo series . Globally , 93 % of the cyclacillin-treated patients and only 55 % of the placebo-treated patients were considered improved . Of the P. mirabilis strains encountered , 72 % were eradicated by cyclacillin ( only 40 % by placebo ) despite the relatively high cyclacillin M.I.C.s for this microorganism ( 50 to 100 μg/ml . ) . Cyclacillin was much more effective in treating human sinusitis than would have been anticipated from the M.I.C.s alone 76 patients with acute maxillary sinusitis were treated with oral erythromycin stearate ( 500 mg twice or 3 times a day for 10 days ) . The mean concentration of erythromycin in the sinus secretion after 3 - 5 days ' treatment was 0.6 mug/ml with the lower dosage and 1.3 mug/ml with the higher . The concentration of erythromycin in the sinus secretion was , on the average , 10 - 20 times higher than the minimum inhibitory concentration ( MIC ) for group A streptococci and pneumococci , and reached MIC values for 15 - 30 % of 100 examined strains of Haemophilus influenzae . 81 % of the patients given the smaller and 94 % of those given the larger dose improved or recovered . Radiological improvement was demonstrated in both groups . The infections with H. influenzae tended to respond somewhat less to the treatment than those with pneumococci . Comparisons of the roentgen findings and the findings at aspiration showed good agreement . An extra projection taken with the patient recumbent and the affected side downwards gave no information above that obtained from the routine projections . The large dose caused side effects more often ( in 17/41 patients ) than the smaller one ( 4/35 patients ) . In 10 patients treatment was discontinued because of side effects ; 8 of them had received the larger dose Seven-day courses of either pivmecillinam 200 mg plus pivampicillin 250 mg ( Miraxid ) or a combination of tetracycline hydrochloride , Chlortetracycline hydrochloride and demeclocycline hydrochloride ( Deteclo ) 300 mg , both given twice daily , were compared in a multicentre general practice study in 408 patients with symptoms of upper or lower respiratory tract infection . Patients were stratified into four diagnostic groups : sinusitis , otitis media , throat infections , and acute bronchitis and r and omly allocated to treatment within these groups . Assessment at 7 days showed no difference in clinical efficacy between the two treatments where 193 of the 208 infections receiving Miraxid ( 93 % ) were rated as either cured or improved compared with 181 of the 201 infections treated with Deteclo ( 90 % ) . At 7 days , the percentage of patients completely free of symptoms was the same for both groups ( 66 % ) . The mean time for symptoms to clear was 3·9 days in the Miraxid group and 4·0 days in the Deteclo group . Side-effects were reported by significantly fewer patients in the Miraxid group ( 9·3 % ) than the Deteclo group ( 17·5 % ) ( p < 0·05 ) and six patients in the latter group failed to complete the course of treatment . Miraxid given twice daily for respiratory tract infections is as effective as Deteclo but causes significantly fewer side-effects Cefuroxime axetil was compared with amoxycillin in the treatment of acute and acute on chronic sinusitis in a multicentre general practice study . A total of 160 patients were r and omized to receive 250 mg cefuroxime axetil orally twice daily , or 250 mg amoxycillin orally three times daily for 10 days . Of the 45 assessable patients with acute sinusitis 43 ( 96 % ) were cured or improved using cefuroxime axetil compared with 49 ( 94 % ) of the assessable patients in the amoxycillin-treated group . In patients with acute on chronic sinusitis , cefuroxime axetil result ed in an 80 % ( 16/20 ) cure or improvement , with a 68 % ( 13/19 ) response in the case of amoxycillin . Adverse events were mainly gastro-intestinal and none was considered serious in either treatment group , although three patients receiving cefuroxime axetil were withdrawn from treatment . It is concluded that cefuroxime axetil is at least as clinical ly efficacious as amoxycillin in the treatment of acute sinusitis in adults Summary The objective of this multicentre , r and omised , open-label , general practice ( GP ) study was to evaluate the efficacy and tolerability of cefprozil ( Cefzil ™ , Bristol-Myers Squibb ) compared with that of cefuroxime axetil ( Ceftin ® , Glaxo Wellcome ) in the treatment of adult subjects with acute sinusitis . Typical of the GP setting , diagnosis was made based solely on clinical signs and symptoms of acute disease . Sinus radiography was performed post-r and omisation . A total of 381 adolescent and adult patients were r and omly assigned to 10 days ’ treatment with either cefprozil , 500 mg orally twice daily ( n = 191 ) , or cefuroxime axetil , 250 mg orally twice daily ( n = 190 ) . Based on predefined criteria , treatments were found to be equally effective in terms of proportions of patients in the per- protocol population that were cured , improved or failed ( p = 0.20 ) . Similar results were observed when the evaluation was performed on the subset of patients with radiographic evidence of sinusitis and when the evaluation was based on the investigator 's judgement . Similar rates of adverse events were observed in the two treatment groups . In summary , cefprozil 500 mg twice daily is as well tolerated and as effective as cefuroxime axetil 250 mg twice daily for the treatment of adolescent and adult patients with clinical signs and symptoms of acute sinusitis PURPOSE To compare the safety and efficacy of orally administered clarithromycin , a new macrolide antimicrobial , and amoxicillin in the treatment of patients with acute maxillary sinusitis . PATIENTS AND METHODS One hundred forty-two consecutive out patients treated at four primary care centers for acute maxillary sinusitis were r and omly assigned to receive oral clarithromycin ( 500 mg twice daily ) or oral amoxicillin ( 500 mg three times daily ) for 7 to 14 days . Clinical and roentgenographic responses to the antibiotic therapy were determined within 48 hours after the last dose and 6 weeks later . RESULTS The success rates of clarithromycin and amoxicillin were comparable . A clinical success rate of 91 % and a roentgenographic success rate of 78 % were achieved in the clarithromycin group at the final visit ; comparable results for the amoxicillin group were 89 % and 92 % , respectively . Differences between the two groups were not statistically significant ( P = .766 and .064 , respectively ) . No serious adverse events were reported , although both drugs caused mild gastrointestinal distress . Dropout rates were low in both groups : 3 % for clarithromycin and 4 % for amoxicillin . No clinical ly significant changes in laboratory studies were observed in either group . CONCLUSION Clarithromycin twice daily is effective and well tolerated in patients with acute maxillary sinusitis BACKGROUND In general practice , acute sinusitis is frequently diagnosed and treated with antibiotics . OBJECTIVE This study aim ed to determine the evidence for the effectiveness of antibiotic treatment in acute maxillary sinusitis in adults by assessing the method ological quality of placebo-controlled double-blind r and omized trials . METHOD An evaluation by four raters through a 35-item scoring-scale for internal and external validity of all placebo-controlled double-blind r and omized trials on acute sinusitis found between January 1966 and July 1996 . RESULTS Eighty-five trials were excluded because they were not placebo-controlled , double-blind , r and omized , or were carried out in patients with chronic sinusitis or in children . The three remaining trials were performed in different population s ( one in general practice ) between 1973 and 1978 . Only one study cl aim ed superiority of antibiotic treatment . Different inclusion criteria and major outcome measures were used by the authors . The reliability of major outcome events was reported poorly or not at all and in two studies outcome measures were clinical ly inappropriate . The studies scored 30 - 62 % of the maximum attainable score for internal validity and 10 - 20 % for external validity . CONCLUSION The effectiveness of antibiotic treatment in acute maxillary sinusitis in a general practice population is not based sufficiently on evidence Abstract Objective : To compare the effectiveness of penicillin V and amoxycillin with placebo in treatment of adult patients with acute sinusitis . Design : R and omised , double blind , placebo controlled trial . Setting : Norwegian general practice . Subjects : 130 adult patients with a clinical diagnosis of acute sinusitis confirmed by computed tomography . Main outcome measures : Subjective status after three and 10 days of treatment , difference in clinical severity score between day 0 and day 10 as evaluated by the general practitioner , difference in score from computed tomography on day 0 and day 10 , and duration of sinusitis . Results : Amoxycillin and penicillin V led to significantly faster and better recovery than placebo . By day 10 , 71 patients receiving antibiotic treatment ( 86 % ) considered themselves to be recovered or much better compared with 25 ( 57 % ) receiving placebo . The mean ( 95 % confidence interval ) reductions in clinical severity scores by day 10 were 5.4 ( 5.0 to 5.8 ) for penicillin V , 5.5 ( 4.9 to 6.0 ) for amoxycillin , and 3.4 ( 2.8 to 4.0 ) for placebo . For the antibiotic groups combined the number of patients with the greatest degree of improvement on computed tomography ( scale 0 - 16)—that is , score 5 - 16 on day 10—was 31/83 ( 37 % ) compared with 10/44 ( 23 % ) receiving placebo . The median duration of the sinusitis was nine days in the amoxycillin group , 11 days in the penicillin V group , and 17 days in the placebo group . Conclusion : Penicillin V and amoxycillin are significantly more effective than placebo in the treatment of acute sinusitis . Key messages The median duration of sinusitis with different treatment was nine days for amoxycillin , 11 days for penicillin V , and 17 days for placebo More than half of the patients receiving antibiotic treatment reported side effects but few gave severe discomfort Half of the patients receiving placebo tablets felt restored or much better after 10 This double-masked , multicenter , r and omized clinical trial compared the efficacy and tolerability of cefuroxime axetil and amoxicillin/clavulanate in the treatment of acute bacterial maxillary sinusitis . A total of 263 patients with acute bacterial maxillary sinusitis were r and omly assigned to receive 10 days of treatment with either cefuroxime axetil 250 mg twice daily ( n = 132 ) or amoxicillin/clavulanate 500/125 mg 3 times daily ( n = 131 ) . Patients ' responses to treatment were assessed once during treatment ( 6 to 8 days after the start of treatment ) , at the end of treatment ( 1 to 3 days posttreatment ) , and at follow-up ( 26 to 30 days after cessation of treatment ) . Clinical success , defined as cure or improvement , was equivalent in the cefuroxime axetil and amoxicillin/ clavulanate groups at the end-of-treatment and follow-up assessment s. Patients in both groups showed improvements in symptoms of acute sinusitis at the during-treatment visit . Treatment with amoxicillin/clavulanate was associated with a significantly higher incidence of drug-related adverse events than treatment with cefuroxime axetil ( 29 % vs 17 % ) , primarily reflecting a higher incidence of gastrointestinal adverse events ( 23 % vs 11 % ) , particularly diarrhea . Two patients in the cefuroxime axetil group and 8 patients in the amoxicillin/clavulanate group withdrew from the study due to adverse events ( P = 0.06 ) . These results indicate that cefuroxime axetil 250 mg twice daily is as effective as amoxicillin/clavulanate 500 mg 3 times daily in the treatment of acute sinusitis and produces fewer gastrointestinal adverse events . cefuroxime axetil , amoxicillin/clavulanate , acute sinusitis In an open r and omized comparative study , the clinical and bacteriological efficacy and safety of spiramycin were compared with those of doxycycline in patients with acute sinusitis . Spiramycin was given at a dose of 1 g bd for 10 days and doxycycline at 200 mg once a day on day 1 and 100 mg once a day from day 2 to day 10 . Clinical and bacteriological evaluations of efficacy were carried out at the end of therapy . In case of clinical cure , a last follow-up visit was made 15 days after the end of therapy . Adverse effects were recorded . To date 12 assessable patients have been treated with spiramycin and 15 with doxycycline . In the spiramycin group , nine patients were clinical ly cured at the end of therapy ( with no relapse at the last follow-up visit ) . In the doxycycline group , nine patients were clinical ly cured at the end of therapy ( with no relapse at the last follow-up visit ) . The data so far available from this study suggest that spiramycin presents an alternative to doxycycline in the treatment of acute sinusitis In a primary care setting , the efficacy and safety of ciprofloxacin ( CIP ) 500 mg b.i.d . were compared with those of cefuroxime axetil ( CA ) 250 mg b.i.d . , each given for 10 days , in a nationwide , open , prospect i ve , r and omized trial of 1414 adults with acute sinusitis . Patients were enrolled if they had clinical ly documented acute sinusitis ( ie , rhinosinusitis ) ( < 4 weeks ' duration ) , based on the 1997 American Academy of Otorhinolaryngology -- Head and Neck Surgery criteria of either two major or one major and two minor symptoms . The primary efficacy variable was clinical response ( resolution or failure ) at the posttherapy assessment on study days 14 through 26 . The most common presenting major signs and symptoms of acute rhinosinusitis were facial congestion , nasal drainage/purulence , facial pain/pressure , and nasal obstruction/blockage . The minor symptom , headache , was more common and severe than was nasal obstruction/blockage . A total of 1219 patients were clinical ly evaluable . Clinical resolution was observed in 559 of 613 ( 91.2 % ) CIP-treated patients and 546 of 606 ( 90 . 1 % ) CA-treated patients . The two regimens were statistically equivalent ( 95 % confidence interval , -2.16 % to 4.71 % ) . There were 80 drug-related adverse events reported in the CIP-treated patients and 81 drug-related adverse events reported in the CA-treated patients . The main adverse events were nausea ( n = 18 ) and diarrhea ( n = 7 ) in patients treated with CIP and diarrhea ( n = 14 ) , nausea ( n = 12 ) , headache ( n = 7 ) , and vaginitis ( n = 7 ) in those treated with CA . CIP 500 mg b.i.d . was found to be statistically equivalent to CA 250 mg b.i.d . in the treatment of acute rhinosinusitis Abstract Cefdinir is a new , extended-spectrum , orally active , third-generation cephalosporin that is resistant to bacterial β-lactamase production . To evaluate efficacy and safety of the antibiotic in maxillary sinusitis , its use was compared with amoxicillin/clavulanate ( amox/clav ) , which is a well-accepted β-lactamase-resistant antibiotic . In this investigator-blinded multicenter phase III clinical study , 569 patients were r and omly assigned to one of three treatment regimens : one daily dose of cefdinir ¶600 mg ( OD ) , cefdinir 300 mg every 12 h ( BD ) , and amox/clav 500/125 mg every 8 h. All antibiotics were administered orally for 10 days . Maxillary sinusitis was documented by typical clinical signs and symptoms and was confirmed by X-ray imaging . Before treatment , the genus and species of any pathogens were determined from sinus aspirates . Cultures were tested for β-lactmase production and in vitro resistance to cefdinir and amox/clav . The ¶effectiveness of antibiotic treatment was evaluated 7–¶14 days after therapy and whether or not recurrent clinical symptoms or persistent infection was determined 21–¶35 days post-therapy . The appearance of any adverse events was classified as associated or not associated with the medication of the study . Present findings showed that the in vitro susceptibility of pathogens to cefdinir and amox/clav was similar . Cefdinir OD or BD was therapeutically as effective as or better than amox/clav , although cefdinir BD was not as useful as amox/clav clinical ly . Cefdinir OD and BD and amox/clav were well tolerated . The statistical incidence of adverse events was the same among the three treatment groups , although cefdinir OD treatment had significantly fewer treatment discontinuations due to adverse events than BD and amox/clav Six groups , each containing 50 patients with acute maxillary sinusitis , were treated with ampicillin plus nasal decongestant , ampicillin plus irrigation , cephradine plus nasal decongestant , cephradine plus irrigation , erythromycinestolate plus nasal decongestant , erythromycinestolate plus irrigation . The diagnosis was radiologically established and the healing likewise radiologically assessed on the fifth , tenth and fifteenth day . Treatment was given for 10 days . All groups demonstrated a similar radiological healing except cephradine plus nasal decongestant which was inferior to the others . Contrarily , side effects were least frequent in the cephradine groups and most frequent in patients cured with ampicillin . The difficulty in choosing the best treatment is discussed in relation to such factors as therapeutic results , side effects , long-term consequences of antibiotic treatment , establishment of any bacterial etiology and penetration characteristics of antibiotics into the diseased sinus The efficacy and safety of minocycline were compared with that of amoxicillin in the treatment of 58 patients with acute bacterial sinusitis . The most frequently isolated pathogens were streptococci , staphylococci , and Haemophilus influenzae . After therapy for a mean time of 11 days , clinical cure or improvement and bacterial eradication were evident in 100 % of the patients treated with minocycline and in 95 % of the patients treated with amoxicillin . Roentgenographic results indicated clearing or improvement in 91 % of the minocycline recipients and in 70 % of those who received amoxicillin . These differences between treatments were not statistically significant . A low incidence of generally mild adverse clinical experiences occurred in both treatment groups . Thus , minocycline and amoxicillin were equally safe and effective in the treatment of these patients with acute bacterial sinusitis In order to evaluate the clinical efficacy and tolerance of cefpodoxime proxetil , compared with that of amoxicillin in the treatment of acute bacterial maxillary sinusitis , a r and omized , double-blind , parallel group comparative study was performed . A total of 286 adults patients were included at 12 centres , each treatment group consisting of 143 patients . Each patient was treated for 10 days and observed before and after treatment . The observations included clinical , roentgenological , bacteriological and laboratory examinations . At inclusion , the most common pathogens were Haemophilus influenzae ( 24 % ) and Streptococcus pneumoniae ( 17 % ) . In the per protocol analysis , 117 patients in the cefpodoxime group and 113 in the amoxicillin group were evaluable for clinical efficacy . The clinical response rates were 96 % and 91 % , respectively . The corresponding figures in the intent-to-treat analysis were 130 and 128 patients , with clinical response rates of 93 % and 88 % , respectively . Cefpodoxime proxetil proved clinical ly as effective as amoxicillin in the treatment of acute bacterial maxillary sinusitis . It was more effective in eradicating H. influenzae and was more efficient in improving the radiological score . Adverse events were reported in 20 % of cefpodoxime cases and in 16 % of amoxicillin cases . There was no statistically significant difference between the groups In an open , r and omized study of 60 patients with acute or recurrent sinusitis , the bacteriological and clinical efficacy of roxithromycin 150 mg bd were compared with those of po co-amoxiclav ( 625 mg ) tds . Of 52 patients who underwent sinus puncture for isolation of causative organisms , 48 had pathogens sensitive to both antibiotics . Satisfactory clinical response was obtained in 93.1 % ( 27/29 ) evaluable patients receiving roxithromycin and 88.8 % ( 24/27 ) receiving co-amoxiclav . Tolerability was significantly better in the roxithromycin group , with 1/29 ( 3.4 % ) patients in this group experiencing gastrointestinal side-effects , compared with 7/27 ( 25.9 % ) patients in the co-amoxiclav group ( P < 0.05 ) . Although the study had limited power to detect differences , roxithromycin demonstrated clinical , bacteriological and overall efficacy similar to that of co-amoxiclav , but with better tolerability . Roxithromycin thus appears to be an effective and well-tolerated drug for the treatment of acute and recurrent sinusitis A new macrolide drug , clarithromycin ( Biaxin ® ) was compared with amoxicillin/clavulanate ( Augmentin ® ) in a single-blind ( investigator-blind ) , r and omized , multicenter study of 497 out patients with acute maxillary sinusitis ; treatment was 500 mg clarithromycin bid ( n = 246 ) or 500 mg amoxicillin/clavulanate tid ( n = 251 ) . Pathogens included Streptococcus pneumoniae in 22 % of patients , Staphylococcus aureus in 16 % , Haemophilus influenzae in 10 % , and Moraxella catarrhalis in 7 % . For evaluable patients , clinical success ( cure or improvement ) was noted for 97 % ( 128/132 ) of clarithromycin recipients and 93 % ( 119/128 ) amoxicillin/clavulanate recipients . Clinical ly significant improvement in signs and symptoms was comparable between groups . Bacteriologic cure rates were 87 % ( 115/132 ) and 90 % ( 115/128 ) , respectively . Respective pathogen eradication rates were 87 % ( 125/143 ) and 90 % ( 125/139 ) . Adverse events not due to concurrent conditions occurred in 41 % of the former and 46 % of the latter group ; most were mild to moderate gastrointestinal upsets ( 21 % and 38 % , respectively ; P ≤ 0.001 ) . We conclude that clarithromycin appears to be as effective as amoxicillin/clavulanate in acute maxillary sinusitis and may cause fewer gastrointestinal upsets In 16 controlled , r and omized , comparative studies a total of 953 patients were treated for urinary tract infection , sinusitis , otitis media or chronic bronchitis . The aim was to evaluate the efficacy and safety of bacampicillin in a twice daily dosage , compared with three times daily dosages of bacampicillin , ampicillin , amoxycillin and a twice daily dosage of co-trimoxazole . Bacampicillin was given in amounts of either 400 or 800 mg to 422 of the patients in these studies . The twice daily dosage of bacampicillin eradicated 89 % of the causative bacteria of urinary tract infections compared to 86 % with the other regimens . In acute sinusitis 92 % and 96 % of the patients were either cured or improved when treated with 400 and 800 mg bacampicillin twice daily respectively . Similar percentages occurred in the groups given the three times daily dosages . In exacerbation of chronic bronchitis , 800 mg bacampicillin twice daily was the minimum effective dosage and 84 % of the patients were either cured or improved with this regimen . Adverse drug reactions due to bacampicillin at all dose levels were less frequent than those of other anti-microbials . The lowest frequency of diarrhoea , 2.4 % , was seen in the group given 400 mg bacampicillin twice daily . Dosages of 400 or 800 mg bacampicillin twice daily had a reliable efficacy combined with a low frequency of adverse reactions in respiratory and urinary tract infections In a r and omized double-blind study fifty-four patients suffering from acute maxillary sinusitis were treated for 10 days with daily doses of sulphadiazine/trimethopim ( 1 g ) and sulphamethoxazole/trimethoprim ( 1.92 g ) , respectively . The efficacy was evaluated clinical ly at two follow-up visits . X-ray investigations were performed at admission and after the therapy . Of thirty-nine patients finally evaluated , thirty-seven showed a favourable result . After 6–8 days of therapy there was significant difference in cure rates in favour of sulphadiazine/trimethoprim ( p < 0.05 ) while the outcome as evaluated after treatment was similar for both drugs Five hundred four patients were enrolled in a r and omized , double-masked , multicenter study comparing the efficacy and tolerability of a 10-day regimen of sparfloxacin with a 14-day regimen of clarithromycin in the treatment of acute maxillary sinusitis . Two hundred fifty-two patients received sparfloxacin as a single 400-mg dose on day 1 and 200 mg once daily for 9 additional days , and 252 patients received clarithromycin 500 mg twice daily for 14 days . In the all-treated population , clinical success was observed at 6 to 10 days after therapy in approximately 82 % of the patients in each treatment group . A total of 430 patients met the inclusion criteria for clinical assessment . The success rates in these patients were also comparable , at 83.1 % and 83.4 % for the sparfloxacin and clarithromycin groups , respectively . Sustained clinical success rates in the all-treated population 3 to 4 weeks after therapy were 71.6 % for the sparfloxacin group and 68.6 % for the clarithromycin group . All treated patients were included in the tolerability analysis . The frequency of adverse events in the clarithromycin and sparfloxacin groups was 57.9 % and 48.4 % , respectively . The most frequently noted adverse events were diarrhea , photosensitivity reaction , taste perversion , nausea , and abdominal pain ; > 96 % of adverse events in the sparfloxacin group and 94 % of adverse events in the clarithromycin group were of mild or moderate severity . Among adverse events at least possibly related to study drug , photosensitivity reaction was more common in the sparfloxacin group ( 9.5 % vs. 0.4 % ) , whereas taste perversion ( 8.7 % vs. 0.8 % ) and abdominal pain ( 3.6 % vs. 1.6 % ) were more common in the clarithromycin group . Thus the sparfloxacin 's more convenient regimen was as effective as clarithromycin in the treatment of acute bacterial maxillary sinusitis , and the overall frequency of adverse events with sparfloxacin was comparable to that with clarithromycin Seven-day courses of either 200 mg pivmecillinam plus 250 mg pivampicillin or co-trimoxazole ( 800 mg sulphamethoxazole plus 160 mg trimethoprim ) given twice daily were compared in a multi-centre general practice study in 318 patients with signs and symptoms of upper or lower respiratory tract infection . Patients were stratified into four diagnostic groups ( sinusitis , otitis media , throat infections , and acute bronchitis ) and r and omly allocated to treatment within these groups . Assessment s at Day 7 showed that both treatments were equally effective clinical ly , 154 ( 91 % ) patients in the pivmecillinam plus pivampicillin group showing clinical cure or improvement and 142 ( 88 % ) patients in the co-trimoxazole group . Side-effects were reported by 19 ( 11.9 % ) patients in the pivmecillinam plus pivampicillin group and by 24 ( 15.8 % ) patients in the co-trimoxazole group . Two patients in the pivmecillinam plus pivampicillin group and 4 patients in the co-trimoxazole group stopped treatment BACKGROUND The value of antibiotics in acute rhinosinusitis is uncertain . Although maxillary sinusitis is commonly diagnosed and treated in general practice , no effectiveness studies have been done on unselected primary -care patients . We used a r and omised , placebo-controlled design to test the hypothesis that there would be an improvement associated with amoxycillin treatment for acute maxillary sinusitis patients presenting to general practice . METHODS Adult patients with suspected acute maxillary sinusitis were referred by general practitioners for radiographs of the maxillary sinus . Those with radiographic abnormalities ( n = 214 ) were r and omly assigned treatment with amoxycillin ( 750 mg three times daily for 7 days ; n = 108 ) or placebo ( n = 106 ) . Clinical course was assessed after 1 week and 2 weeks , and reported relapses and complications were recorded during the following year . FINDINGS After 2 weeks , symptoms had improved substantially or disappeared in 83 % of patients in the study group and 77 % of patients taking placebo . Amoxycillin did not influence the clinical course of maxillary sinusitis nor the frequency of relapses during the 1-year follow-up . Radiographs had no prognostic value , nor were they an effect modifier . Side-effects were recorded in 28 % of patients given amoxycillin and in 9 % of those taking placebo ( p < 0.01 ) . The occurrence of relapses was similar in both groups ( 21 vs 17 % ) during the follow-up year . INTERPRETATION Antibiotic treatment did not improve the clinical course of acute maxillary sinusitis presenting to general practice . For these patients , an initial radiographic examination is not necessary and initial management can be limited to symptomatic treatment . Whether antibiotics are necessary in more severe cases warrants further study Cefdinir is an extended-spectrum oral cephalosporin that is active against pathogens commonly seen in acute community-acquired bacterial sinusitis ( ACABS ) , including Streptococcus pneumoniae , Haemophilus influenzae , and Moraxella catarrhalis . Two r and omized , investigator-blind , multicenter trials ( one in the United States and one in Europe ) compared two dosage regimens of cefdinir ( 600 mg once a day for 10 days and 300 mg twice a day for 10 days ) to amoxicillin-clavulanate ( A-C ) ( 500 mg three times a day for 10 days ) for adult and adolescent patients with ACABS . Twelve hundred twenty-nine patients entered the U.S. study , 698 with antral puncture ; 569 patients entered the European study , all with antral puncture . Clinical response ( cure or improvement ) was determined 7 to 14 days and 3 to 5 weeks posttherapy . Microbiologic eradication rates were determined 10 to 30 days posttherapy in a subset of patients who underwent pre- and posttherapy sinus aspirate culture . Rates of adverse events and treatment discontinuations due to adverse events were examined . Cefdinir , given once or twice daily , was as effective clinical ly ( approximately 90 % cure rate ) as amoxicillin-clavulanate given three times daily in the treatment of ACABS . Microbiologic eradication rates were also similar in the three groups . The major side effect was mild diarrhea , occurring in approximately 20 % of each group . Cefdinir caused fewer adverse events requiring treatment discontinuation Cefetamet , an oral third-generation cephalosporin , was investigated in a prospect i ve , r and omized , open , comparative trial in 41 out- patients with acute sinusitis . The efficacy of 500 mg cefetamet given orally twice daily for 7 days to 22 patients was compared with that of 500 mg cefaclor given orally three times daily for 7 days to 19 patients . Sinus punctures were performed before antimicrobial therapy in 10 patients from each treatment group . A successful bacteriological response was obtained in all the 21 assessable patients treated with cefetamet and in the cefaclor-treated group 18 assessable patients were cured and two were improved , but one failed to respond to therapy . The tolerability of both drugs was good and no withdrawals from treatment were necessary Roxithromycin 300 mg once daily was compared with clarithromycin 250 mg b.i.d . in an open r and omized trial in 200 patients with upper respiratory tract infection : sinusitis , pharyngotonsillitis , and otitis media . Average treatment duration was 9 days . Roxithromycin was more effective ( p less than 0.01 ) particularly in otitis media and pharyngotonsillitis , and better tolerated ( only 4 % side effects , p less than 0.05 ) Summary Three hundred and one patients with maxillary sinusitis participated in a double-blind , r and omized study at 11 ENT-clinics in Europe . Sinusitis was diagnosed by the presence of at least two signs and symptoms and sinus X-ray showing more than 6 mm swelling of the maxillary mucosa . A microbiological specimen was obtained by intrasinusal aspiration . The patients were r and omly assigned to treatment either with bacampillin 800 mg b. i. d. or with amoxicillin 500 mg t. i. d. for ten days . The most frequently isolated bacteria wereHaemophilus influenzae ( 94 strains),Streptococcus pneumoniae ( 66 strains ) and Branhamella catarrhalis ( 12 strains ) . In 96 of the patients , no microorganisms could be isolated . Beta-lactamase production was found in oneH. influenzae strain and in threeB. catarrhalis strains . Two hundred and seventy-one patients could be evaluated for efficacy at the follow-up visit day 8–25 . The overall clinical outcome was the same in both treatment groups . Adverse events such as skin reactions and upper and lower gastrointestinal reactions occurred in 17.4 % of the amoxicillin treated patients and in 10.8 % of the bacampicillin treated patients (p=0.101).Zusammenfassung301 Patienten mit Sinusitis maxillaris wurden in eine r and omisiete Doppelblindstudie aufgenommen , an der 11 europäische Hals-Nasen-Ohren-Kliniken beteiligt waren . Die Diagnose der Sinusitis basierte auf mindestens zwei objektiven und subjektiven Symptomen und Röntgenaufnahmen der Nebenhöhlen mit Schwellung der Kieferhöhlenschleimhaut auf mehr als 6 mm Dicke . Durch Kieferhöhlenpunktion wurde eine Probe für die mikrobiologische Untersuchung entnommen . Die Patienten wurden zufallsgemäß zehn Tage lang entweder mit 800 mg Bacampicillin zweimal täglich oder mit 500 mg Amoxicillin dreimal täglich beh and elt . Die häufigsten bakteriellen Isolate warenHaemophilus influenzae ( 94 Stämme),Streptococcus pneumoniae ( 66 Stämme ) undBranhamella catarrhalis ( 12 Stämme ) . Bei 96 Patienten konnte kein Mikroorganismus isoliert werden . Bei einem Stamm vonH. influenzae und bei drei Stämmen vonB. catarrhalis wurde Betalaktamasebildung nachgewiesen . 271 Patienten konnten i m Hinblick auf das Therapieergebnis durch Kontrolluntersuchungen am 8.–25 . Tag ausgewertet werden . Das klinische Gesamtergebnis war bei beiden Therapiegruppen gleich . Nebenwirkungen wie Hautreaktionen oder Beschwerden von seiten des oberen oder unteren Verdauungstraktes traten bei 17,4 % der mit Amoxicillin und bei 10,8 % der mit Bacampicillin beh and elten Patienten auf ( p=0,101 ) The efficacy and safety of azithromycin and clarithromycin were compared in an open multicentre study involving 380 adult patients with acute otitis media , acute sinusitis , or acute streptococcal pharyngitis or tonsillitis . Patients were assigned r and omly to receive azithromycin as a single dose of 500 mg daily for three days , or clarithromycin 250 mg bid for ten days . Overall clinical efficacy was found to be similar in each treatment group at day 10 - 14 , with a satisfactory outcome ( cured or improved ) in 95 % of azithromycin and 96 % of clarithromycin patients . Bacteriological efficacy was also similar , with eradication of the pathogen in 94 % and 95 % of isolates , respectively , in the azithromycin and clarithromycin groups . In otitis media , a satisfactory clinical response was seen in 97 % of patients in each treatment group . Azithromycin therapy result ed in a clinical response rate of 93 % in sinusitis patients , with bacteriological eradication in 93 % of patients . Two patients ( who were cured clinical ly ) had persistent pathogens . Similarly , clarithromycin achieved clinical response and bacteriological eradication in 95 % and 92 % of sinusitis patients , respectively . Pathogens persisted in two patients with clinical cure , and in one case of clinical failure . In pharyngitis or tonsillitis , Streptococcus pyogenes was eradicated successfully in 95 % of patients in both groups , and the clinical success rates were 96 % and 97 % for azithromycin and clarithromycin , respectively . No case of clinical failure was associated with persistence of S. pyogenes infection . At the follow-up assessment of this diagnosis group , reinfection had occurred in three ( 8 % ) azithromycin patients and one ( 3 % ) clarithromycin patient , and all but one patient remained asymptomatic . Both drugs were well-tolerated , with 8.4 % of patients on azithromycin and 7.4 % on clarithromycin reporting adverse events , mainly gastrointestinal . It was concluded that a three-day course of azithromycin was as effective and well-tolerated as a ten-day course of clarithromycin in adults with acute upper respiratory tract infections Very few investigations comparing the results of different therapeutic measures in acute sinusitis have been reported . The present investigation is an attempt to evaluate objective ly the clinical course in treated acute maxillary sinusitis by the aid of radiological registration of the sinus state . Difficulties were encountered in establishing a radiological gradation corresponding to the clinical state in the diseased sinus . A radiological gradation is suggested . A group treated with nasal decongestant only , may be regarded as a control group . The results of the treatment by nasal decongestant combined with irrigation or penicillin V or lincomycin respectively were similar and significantly better than in the control group . The patient 's evaluation of the treatment after 5 days did not correlate with the radiological state but did so after 10 days The aim of this prospect i ve , multicenter , r and omized , double-masked clinical trial was to compare the efficacy and safety of moxifloxacin with those of cefuroxime axetil for the treatment of community-acquired acute sinusitis . Five hundred forty-two adult patients with symptoms and radiographic evidence of acute maxillary sinusitis received a 10-day oral regimen of either moxifloxacin ( 400 mg once daily ) or cefuroxime axetil ( 250 mg twice daily ) . Acute signs and symptoms at presentation had lasted > 7 days but < 4 weeks . Clinical response at the end of therapy ( 7 to 14 days after treatment ) was the primary efficacy variable . Four hundred fifty-seven of the patients ( 223 moxifloxacin , 234 cefuroxime axetil ) were included in the clinical efficacy analysis . Moxifloxacin was found to be similar in effectiveness to cefuroxime axetil at the end-of-therapy visit ( 90 % vs. 89 % , respectively ; 95 % confidence interval , -5.1 % to 6.2 % ) . Clinical relapse at the follow-up visit was reported for only 8 patients ( 3 moxifloxacin , 5 cefuroxime axetil ) . No clinical ly significant differences were observed with respect to the number of patients experiencing a successful clinical response based on demographic or infection characteristics . Five of the 542 enrolled patients were lost to follow-up . Of the 537 patients in the intent-to-treat population , drug-related adverse events were reported in 37 % of moxifloxacin-treated patients and in 26 % of cefuroxime axetil-treated patients ( P = 0.006 ) . Adverse-event profiles were comparable in the 2 treatment groups , with the exception of nausea , which was reported by 11 % of moxifloxacin-treated patients compared with 4 % of cef uroxime axetil-treated patients ( P = 0.003 ) . In this study , moxifloxacin was as effective as cefuroxime axetil in the treatment of community-acquired acute sinusitis PURPOSE To evaluate the efficacy and safety of levofloxacin ( 500 mg orally once daily for 10 to 14 days ) in treating adult out patients with acute bacterial sinusitis . PATIENTS AND METHODS A total of 329 patients enrolled in the study at 24 centers . All patients had a pre-therapy Gram 's stain and culture of sinus exu date obtained by antral puncture or nasal endoscopy . Clinical response was assessed on the basis of signs and symptoms and sinus radiograph or computed tomography results . Microbiologic cure rates were determined on the basis of presumed plus documented eradication of the pre-therapy pathogen(s ) . RESULTS The most common pathogens were Haemophilus influenzae , Streptococcus pneumoniae , Staphylococcus aureus , and Moraxella catarrhalis . Of 300 clinical ly evaluable patients , 175 ( 58 % ) were cured and 90 ( 30 % ) were improved at the post-therapy evaluation , result ing in a clinical success rate of 88 % . Thirty-five patients ( 12 % ) clinical ly failed treatment . The microbiologic eradication rate ( presumed plus documented ) among 138 microbiologically evaluable patients was 92 % . Microbiologic eradication rates ( presumed plus documented ) of the most common pathogens ranged from 93 % ( M. catarrhalis ) to 100 % ( S. pneumoniae ) at the post-therapy visit . All but one of the 265 patients who were cured or improved at post-therapy returned for a long-term follow-up visit ; 243 ( 92 % ) remained well 4 to 6 weeks after therapy ; and 21 ( 8 % ) had a relapse of symptoms . Adverse events considered to be related to levofloxacin administration were reported by 29 patients ( 9 % ) . The most common drug-related adverse events were diarrhea , flatulence , and nausea ; most adverse events were mild to moderate in severity . CONCLUSION The results of this study indicate that levofloxacin 500 mg once daily is an effective and safe treatment for acute bacterial sinusitis The efficacy and safety of clarithromycin and amoxycillin in the treatment of acute maxillary sinusitis were compared in a single-blind , multicentre outpatient study . Fifty patients were r and omly assigned to receive either clarithromycin 500 mg 12-hourly or amoxycillin 500 mg 8-hourly orally . Clinical signs and symptoms , sinus culture and blood and urine laboratory profiles were assessed prior to treatment , at four to six days during treatment , and within 48 h of the end of therapy ( usually 9 - 11 days ) . Patients from whom beta-lactamase producing strains were isolated were excluded from the study . Both antibiotics achieved a clinical success rate of 91 % within 48 h post-treatment ; radiological resolution or improvement was observed in 91 % of patients treated with clarithromycin and 89 % of patients who received amoxycillin . Bacteriological cure was achieved in 88 % and 91 % of evaluable patients for clarithromycin and amoxycillin , respectively . Adverse events were reported for 16 % of patients in the clarithromycin group compared to 26 % in the amoxycillin group . Gastrointestinal disturbance was the most commonly occurring adverse event in both groups . The results of this study suggest that clarithromycin is as effective and well tolerated as amoxycillin in the treatment of acute maxillary sinusitis OBJECTIVE To compare the effectiveness of penicillin V with placebo in the treatment of adult patients with acute maxillary sinusitis in general practice . DESIGN R and omised , double blind , placebo controlled trial . SETTING 26 Danish general practice s. PATIENTS 133 adult patients with a clinical diagnosis of acute maxillary sinusitis based on maxillary pain and raised values of either C-reactive protein ( CRP ) or erythrocyte sedimentation rate ( ESR ) . MAIN OUTCOME MEASURES Pain score and illness score as well as measurement of CRP and ESR values after initiation of treatment . RESULTS Penicillin V led to a better recovery than did placebo . The difference was statistically significant 3 days after the initiation of treatment with regard to pain reduction , whereas no significant difference was found with regard to the reduction in the sense of illness . At the end of the study , significantly more patients in the penicillin group were completely free of pain compared to the placebo group . This difference was only found in patients with an initial pain score of more than three . The cure rate was 71 % in the penicillin group and 37 % in the placebo group . Significantly more patients achieved normal CRP values when treated with penicillin ( 88 % ) as opposed to placebo ( 75 % ) . CONCLUSION Penicillin V is more effective than placebo in the treatment of acute maxillary sinusitis in adults in general practice , but only in patients with pronounced pain In two r and omized , multicentre studies patients with upper respiratory tract infections treated with 1.5 g azithromycin in five or six doses over 5 days were compared with patients treated with 10 g erythromycin in 40 doses over 10 days or 15 g amoxycillin in 30 doses over 10 days . The majority of azithromycin- ( 65 % ) and erythromycin- ( 67 % ) treated patients in the azithromycin/erythromycin study and all patients in the azithromycin/amoxycillin study had sinusitis . Clinical cure was recorded in 83 % of azithromycin- and 79 % of erythromycin-treated patients , and in 81 % and 87 % , respectively , of azithromycin- and amoxycillin-treated patients . There was no significant difference in bacteriological eradication between the treatments . Adverse events , predominantly mild or moderate gastro-intestinal complaints , occurred in 17 % and 15 % , respectively , of azithromycin- and erythromycin-treated patients , and in 5 % and 11 % , respectively , of azithromycin- and amoxycillin-treated patients but there were no serious laboratory safety abnormalities . Azithromycin appeared to be an effective , simplified treatment for upper respiratory tract infections and may improve patient compliance compared with st and ard therapies In this guideline , we will present the supporting evidence for and make specific recommendations on how clinicians evaluating acute sinusitis can differentiate bacterial causes from viral causes and how they can determine when the use of antibiotics is beneficial . The numbers in square brackets are cross-references to the numbered sections in the accompanying background paper , Principles of Appropriate Antibiotic Use for Acute Rhinosinusitis in Adults : Background , which is part 2 of this guideline ( see pages 498 - 505 ) . Acute Sinusitis The term sinusitis refers to inflammation of the mucosa of the paranasal sinuses . Because sinusitis is invariably accompanied by inflammation of the contiguous nasal mucosa , rhinosinusitis has become the preferred term . Rhinosinusitis is one of the 10 most common diagnoses in ambulatory practice and is the fifth most common diagnosis for which an antibiotic is prescribed . Primary care physicians tend to think of sinusitis as an acute bacterial infection and prescribe an antibiotic in 85 % to 98 % of cases . However , sinusitis is frequently caused by viral infection . It will often resolve in most patients without antibiotic treatment , even if it is bacterial in origin [ 1.0 ] . Acute rhinosinusitis is defined by symptom duration of less than 4 weeks . Acute bacterial sinusitis is usually a secondary infection result ing from sinus ostia obstruction , impaired mucus clearance mechanisms caused by an acute viral upper respiratory tract infection , or both . According to epidemiologic estimates , only 0.2 % to 2 % of viral upper respiratory tract infections in adults are complicated by bacterial rhinosinusitis . The gold st and ard for diagnosis of bacterial sinusitis is sinus puncture , and Streptococcus pneumoniae and Haemophilus influenzae are the bacteria most commonly isolated from infected maxillary sinuses . However , sinus puncture is an invasive procedure seldom performed in primary care . Because no simple and accurate office-based test for acute bacterial sinusitis exists , clinicians rely on clinical findings to make the diagnosis . However , signs and symptoms of acute bacterial sinusitis and those of prolonged viral upper respiratory tract infections are very similar , result ing in frequent misclassification of viral cases [ 1.1 , 1.2 ] . Diagnosis : Bacterial Compared with Viral Overdiagnosis of acute bacterial rhinosinusitis is not surprising , considering the lack of specific clinical features that distinguish it from nonbacterial upper respiratory tract infections . Often , patients and physicians believe that an upper respiratory tract infection has gone on too long and that antibiotic treatment is therefore needed . In a study of the natural history of rhinovirus illness , length of illness ranged from 1 to 33 days . Most patients were well or nearly well in 7 to 10 days , and one fourth of patients were still symptomatic after 14 days . Bacterial rhinosinusitis is not common in patients whose symptoms have lasted less than 7 days ; therefore , presence of symptoms for at least 7 days is a moderately sensitive but nonspecific predictor of bacterial rhinosinusitis [ 3.0 ] . Since 1976 , seven investigators have published reports attempting to identify signs and symptoms specific to acute bacterial rhinosinusitis . All of these studies have limitations , such as a suboptimal gold st and ard or selection criteria that allowed the inclusion of patients whose symptoms had been present for more than 1 month . However , considering the results of all seven studies , purulent nasal discharge along with maxillary tooth or facial pain ( especially when unilateral ) , unilateral sinus tenderness , and worsening of symptoms after initial improvement seem to be helpful findings for predicting a higher likelihood of bacterial infection in patients with rhinosinusitis-like symptoms [ 3.2 ] . Several investigators have studied the accuracy of sinus radiography in predicting the presence of purulent sinus fluid by using complete opacification , air-fluid level , or various degrees of mucosa thickening as the diagnostic criteria . Complete opacification and air-fluid level are the most specific findings , with specificities of 85 % ( range , 76 % to 91 % ) and 80 % ( range , 71 % to 87 % ) , respectively . The finding of mucosal thickening has a low specificity , probably no better than that of skilled clinical judgment , which is 40 % to 50 % . The absence of all three findings has an estimated sensitivity of approximately 90 % and is helpful in ruling out bacterial rhinosinusitis . Given these test characteristics and the known high prevalence of abnormal radiography findings in patients with viral rhinosinusitis , sinus radiography has limited value in routine diagnosis of acute bacterial rhinosinusitis [ 4.0 ] . Treatment For acute bacterial rhinosinusitis , r and omized , double-blind , placebo-controlled trials of antibiotic treatment using pretreatment and post-treatment culture of sinus aspirates have not been performed . Five r and omized , double-blind clinical trials with good methods have compared antibiotic treatment with placebo for acute rhinosinusitis in adults . Two recent meta-analyses , one under the auspices of the Cochrane Collaboration and the other under contract from the Agency for Healthcare Research and Quality ( AHRQ ) , have recently been published . Both concluded that although antibiotics are statistically more efficacious than placebo in reducing or eliminating symptoms at 10 and 14 days , the effect size ( degree of benefit ) is relatively small . Moreover , most patients who receive placebo improve without antibiotic therapy . The AHRQ report pointed out that symptoms improved or resolved in 69 % ( CI , 57 % to 79 % ) of patients by 14 days without any antibiotic treatment at all . When the 40 % to 50 % prevalence of bacterial rhinosinusitis in patients whose diagnosis is determined by signs and symptoms and the modest effectiveness of antibiotic treatment were considered , a cost-effectiveness model sponsored by the AHRQ favored antibiotic treatment for patients with moderate to severe symptoms and symptomatic treatment for those with mild symptoms [ 5.05.3 ] . Summary In summary , most cases of acute rhinosinusitis diagnosed in ambulatory care are caused by uncomplicated viral upper respiratory tract infections . Bacterial and viral rhinosinusitis are difficult to differentiate on clinical grounds . The clinical diagnosis of acute bacterial rhinosinusitis should be reserved for patients with rhinosinusitis symptoms lasting 7 days or more who have purulent nasal secretions and maxillary facial or tooth pain or tenderness . Patients who have symptoms of rhinosinusitis for less than 7 days are unlikely to have bacterial infection . Sinus radiography is not recommended for diagnosis in routine cases . Acute bacterial rhinosinusitis resolves without antibiotic treatment in most cases . Symptomatic treatment and reassurance are the preferred initial management strategy for patients with mild symptoms . Antibiotic therapy should be reserved for patients with severe symptoms who meet the criteria for the clinical diagnosis of acute bacterial rhinosinusitis , regardless of duration of illness . Initial antibiotic treatment should be with narrow-spectrum agents . On the basis of clinical trials , amoxicillin , doxycycline , and trimethoprimsulfamethoxazole are the favored antibiotics [ 5.4 , 5.5 ] . Recommendations Recommendation 1 . Sinus radiography is not recommended for the diagnosis of uncomplicated sinusitis . The greatest barrier to efficient antibiotic treatment of acute bacterial rhinosinusitis is lack of a simple and accurate diagnostic test . Until a better test is widely available in office practice , the office diagnosis of acute bacterial rhinosinusitis will remain imprecise . Duration of illness is a useful clinical criterion because acute bacterial sinusitis is not common in patients whose symptoms last for less than 7 days . Patients who do not have persistent purulent nasal drainage , maxillary facial or tooth pain or tenderness , or both are unlikely to have bacterial rhinosinusitis , regardless of duration of illness . Recommendation 2 . Acute bacterial sinusitis does not require antibiotic treatment , especially if symptoms are mild or moderate . Because most patients with a clinical diagnosis of rhinosinusitis improve without antibiotic treatment , symptomatic treatment or reassurance is the preferred initial management strategy . Appropriate doses of analgesics , antipyretics , and decongestants should be offered , as well as patient education about the chosen management strategy . Recommendation 3 . Patients with severe or persistent moderate symptoms and specific findings of bacterial sinusitis should be treated with antibiotics . Narrow-spectrum antibiotics are reasonable first-line agents . In most cases , antibiotics should be used only for patients with the specific findings of persistent purulent nasal discharge and facial pain or tenderness who are not improving after 7 days or those with severe symptoms of rhinosinusitis , regardless of duration . On the basis of clinical trials , amoxicillin , doxycycline , or trimethoprimsulfamethoxazole are the favored antibiotics The efficacy and safety of a once-daily oral regimen of 400 mg ceftibuten was compared with oral co-amoxiclav 500 mg three times daily in a multicentre , single-blind study . In patients with a bacteriologically confirmed infection , a successful clinical outcome was reported in 25 of 25 patients treated with ceftibuten and 10 of 10 patients treated with co-amoxiclav . In a further group of 88 patients , most of whom had been excluded from the primary efficacy evaluation because no pathogen was isolated pretreatment , overall successful clinical outcomes of 87 % and 88 % were reported for ceftibuten and co-amoxiclav , respectively . The duration of treatment and the time to resolution of the signs and symptoms of sinusitis were not significantly different in the two treatment groups . The incidence of adverse events was higher in the co-amoxiclav-treated patients ( 31 % versus 15 % in the ceftibuten group ) as was the incidence of severe events ( 10 % for co-amoxiclav-treated patients versus < 1 % in the ceftibuten group ) . In summary , once-daily ceftibuten can be considered a safe and effective treatment for acute bacterial sinusitis Azithromycin and cefaclor were compared for the treatment of acute otitis media , streptococcal pharyngitis/tonsillitis , or sinusitis in an open multicentre study conducted in 530 adults . At the end of therapy ( day 11 - 15 ) , 228/245 ( 93 % ) patients treated with azithromycin 500 mg once daily for 3 days and 233/241 ( 97 % ) treated with cefaclor 250 mg given three times daily for 10 days were considered to have responded satisfactorily ( cured or improved ) . In bacteriologically evaluable patients with pharyngitis/ tonsillitis , Streptococcus pyogenes was eradicated in 116/117 ( 99 % ) azithromycin- and in 115/119 ( 97 % ) cefaclor-treated patients at day 11 - 15 ; one patient in each group had become reinfected after initial eradication of the pathogen . When followed up on day 25 - 30 , S. pyogenes infection had recurred in 5/105 ( 5 % ) azithromycin and 4/108 ( 3 % ) cefaclor patients who had responded satisfactorily at day 11 - 15 , and whose baseline pathogen had been eradicated . Of these patients , two in the azithromycin and one in the cefaclor group also relapsed clinical ly ; the others remained asymptomatic . Patients tolerated both treatments well ; treatment-related adverse events were recorded in 11 % of the 267 azithromycin- and 10 % of the 263 cefaclor-treated patients assessed for safety . One azithromycin patient and five cefaclor patients withdrew because of adverse events . The results of the study show that a 3-day regimen of azithromycin , given once daily , is as effective and well tolerated as a multiple-daily , 10-day cefaclor regimen for the treatment of upper respiratory tract infections in adults Sixty-one patients , 39 females and 22 males , with bacterial and sterile acute maxillary sinusitis were subjected to study in order to decide whether or not an oral antibiotic is necessary in the treatment of this condition when it is administered simultaneously with irrigation and nose drops . Using a double-blind method , one group of patients were given doxicycline and one group a placebo . Changes in secretion were followed macroscopically and changes in the ostial patency , rhinomanometrically . Significant differences between the recovery time of patients belonging to the doxicycline and placebo groups were not observed , neither did the sensitivity of bacteria from the secretion to doxicycline correlate with the speed of recovery in either group . The results do not indicate that recovery time in acute maxillary sinusitis can be shortened with oral administration of doxicycline Seven-day courses of either pivampicillin ( Pondocillin ) 500 mg twice daily or amoxycillin ( Amoxil ) 250 mg three times daily were compared in a multicentre general practice study in 463 patients with symptoms of upper or lower respiratory tract infections . Patients were stratified into four diagnostic groups : sinusitis , otitis media , throat infections , and acute bronchitis , and r and omly allocated to treatment within these groups . There was an over-all response of 93 % in the 227 patients receiving 12-hourly pivampicillin compared with 90 % for the 236 patients receiving 8-hourly amoxycillin . Patients suffering from acute bronchitis responded significantly better to pivampicillin ( Pondocillin ) than to amoxycillin . Side-effects were reported by 15·6 % of patients in the amoxycillin group and 14·0 % in the pivampicillin group As part of the Pan-European multi-centre trial of doxycycline in the treatment of respiratory tract infections during the winter of 1973/1974 , a field trial was carried out in Austria . 95 physicians provided 540 case reports for evaluation . Very good or good results were obtained in 93.9 % of patients and the rate of improvement as indicated by fall in temperature , reduction in cough , sputum and pain , and easing of inflammatory symptoms was rapid ; 77.8 % of patients showed complete remission of acute symptoms after 3 days of treatment . Only 5.6 % of patients suffered from side-effects which were mostly mild . Comparison with a previous field trial in Austria in 1968/1969 showed that doxycycline has retained its efficacy over the years In this r and omized trial , 100 patients received ceftriaxone or amoxicillin-clavulanic acid in phlegmonous or abscess-forming ENT infections . Clinical and bacteriological results confirm that both antibiotics are equally effective , the advantage of ceftriaxone being one administration a day . Drainage surgery is necessary when an abscess has already formed . In 4 cases ( ceftriaxone : 3 ; amoxicillin-clavulanic acid : 1 ) , no positive response could be observed . Systemic and local tolerance was , as a general rule , excellent , and side effects were reported in 3 cases of the ceftriaxone group and in 3 cases of the amoxicillin-clavulanic acid group A double-blind comparative clinical trial of doxycycline ( 200 mg on the first day followed by 100 mg daily for a total of 7 days ) and ampicillin ( 250 mg 4 times daily for 7 days ) was performed in 44 patients with acute or chonic sinusitis . Significantly superior results were observed with doxycycline ; 90 % of the patients responded to doxycycline and 35 % to ampicillin . The incidence of side-effects was low and these were of a minor nature , in no case with either drug was discontinuance of treatment necessary . These results imply that in treating chronic bronchitis an antibiotic should be given which is effective not only against the responsible organisms but which is able also to penetrate those tissues ( such as the sinuses ) that act as a reservoir for these organisms . Doxycycline meets these requirements |
12,345 | 26,118,801 | There is some evidence to suggest that hs-CTn testing may provide an effective and cost-effective approach to early rule-out of AMI . | BACKGROUND Early diagnosis of acute myocardial infa rct ion ( AMI ) can ensure quick and effective treatment but only 20 % of adults with emergency admissions for chest pain have an AMI .
High-sensitivity cardiac troponin ( hs-cTn ) assays may allow rapid rule-out of AMI and avoidance of unnecessary hospital admissions and anxiety .
OBJECTIVE To assess the clinical effectiveness and cost-effectiveness of hs-cTn assays for the early ( within 4 hours of presentation ) rule-out of AMI in adults with acute chest pain . | OBJECTIVE The study objective was to compare the incidence and prognosis of acute myocardial infa rct ion when using high-sensitivity cardiac troponin assays instead of a st and ard cardiac troponin assay for the diagnosis of acute myocardial infa rct ion . METHODS In a prospect i ve international multicenter study , we enrolled 1124 consecutive patients presenting with suspected acute myocardial infa rct ion . Final diagnoses were adjudicated by 2 independent cardiologists 2 times using all available clinical information : first using st and ard cardiac troponin levels and second using high-sensitivity cardiac troponin T levels for adjudication . Patients were followed up for a mean of 19±9 months . RESULTS The use of high-sensitivity cardiac troponin T instead of st and ard cardiac troponin result ed in an increase in the incidence of acute myocardial infa rct ion from 18 % to 22 % ( 242 vs 198 patients ) , a relative increase of 22 % . Of the 44 additional acute myocardial infa rct ions , 35 were type 1 acute myocardial infa rct ions and 9 were type 2 acute myocardial infa rct ions . This was accompanied by a reciprocal decrease in the incidence of unstable angina ( unstable angina , 11 % vs 13 % ) . The most pronounced increase was observed in patients adjudicated with cardiac symptoms of origin other than coronary artery disease with cardiomyocyte damage ( 83 vs 31 patients , relative increase of 268 % ) . Cumulative 30-month mortality rates were 4.8 % in patients without acute myocardial infa rct ion , 16.4 % in patients with a small acute myocardial infa rct ion detected only by high-sensitivity cardiac troponin T but not st and ard cardiac troponin , and 23.9 % in patients with a moderate/large acute myocardial infa rct ion according to st and ard cardiac troponin assays and high-sensitivity cardiac troponin T ( P<.001 ) . CONCLUSIONS The introduction of high-sensitivity cardiac troponin assays leads to only a modest increase in the incidence of acute myocardial infa rct ion . The novel sensitive assays identify an additional high-risk group of patients with increased mortality , therefore appropriately classified with acute myocardial infa rct ion ( Advantageous Predictors of Acute Coronary Syndromes Evaluation ; NCT00470587 ) OBJECTIVES To evaluate the clinical effectiveness and cost-effectiveness of using a point-of-care cardiac marker panel in patients presenting to the emergency department ( ED ) with suspected but not proven acute myocardial infa rct ion ( AMI ) . DESIGN Multicentre pragmatic open r and omised controlled trial and economic evaluation . SETTING Six acute hospital EDs in the UK . PARTICIPANTS Adults presenting to hospital with chest pain due to suspected but not proven myocardial infa rct ion , and no other potentially serious alternative pathology or comorbidity . INTERVENTIONS Participants were allocated using an online r and omisation system to receive either ( 1 ) diagnostic assessment using the point-of-care biochemical marker panel or ( 2 ) conventional diagnostic assessment without the panel . All tests and treatments other than the panel were provided at the discretion of the clinician . MAIN OUTCOME MEASURES The primary outcome was the proportion of patients successfully discharged home after ED assessment , defined as patients who had ( 1 ) either left the hospital or were awaiting transport home with a discharge decision having been made at 4 hours after initial presentation and ( 2 ) suffered no major adverse event ( as defined below ) during the following 3 months . Secondary outcomes included length of initial hospital stay and total inpatient days over 3 months , and major adverse events ( death , non-fatal AMI , life-threatening arrhythmia , emergency revascularisation or hospitalisation for myocardial ischaemia ) . Economic analysis estimated mean costs and quality -adjusted life-years ( QALYs ) , and then estimated the probability of cost-effectiveness assuming willingness to pay of £ 20,000 per QALY gained . RESULTS We r and omised 1132 participants to point of care and 1131 to st and ard care , and analysed 1125 and 1118 , respectively [ mean age 54.5 years , 1307/2243 ( 58 % ) male and 269/2243 ( 12 % ) with known coronary heart disease ( CHD ) ] . In the point-of-care group 358/1125 ( 32 % ) were successfully discharged compared with 146/1118 ( 13 % ) in the st and ard-care group [ odds ratio ( OR ) adjusted for age , gender and history of CHD 3.81 ; 95 % confidence interval ( CI ) 3.01 to 4.82 , p < 0.001 ] . Mean length of the initial hospital stay was 29.6 hours versus 31.8 hours ( mean difference = 2.1 hours ; 95 % CI -3.7 to 8.0 hours , p = 0.462 ) , while median length of initial hospital stay was 8.8 hours versus 14.2 hours ( p < 0.001 ) . More patients in the point-of-care group had no inpatient days recorded during follow-up ( 54 % vs 40 % , p < 0.001 ) , but mean inpatient days did not differ between the two groups ( 1.8 vs 1.7 , p = 0.815 ) . More patients in the point-of-care group were managed on coronary care [ 50/1125 ( 4 % ) vs 31/1118 ( 3 % ) , p = 0.041 ] . There were 36 ( 3 % ) patients with major adverse events in the point-of-care group and 26 ( 2 % ) in the st and ard-care group ( adjusted OR 1.31 ; 95 % CI 0.78 to 2.20 , p = 0.313 ) . Mean costs per patient were £ 1217 with point-of-care versus £ 1006 with st and ard care ( p = 0.056 ) , while mean QALYs were 0.158 versus 0.161 ( p = 0.250 ) . The probability of st and ard care being dominant ( i.e. cheaper and more effective ) was 0.888 . CONCLUSIONS Point-of-care testing increases the proportion of patients successfully discharged home and reduces the median ( but not mean ) length of hospital stay . It is more expensive than st and ard care and unlikely to be considered cost-effective . TRIAL REGISTRATION Current Controlled Trials IS RCT N37823923 . FUNDING This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol . 15 , No. 23 . See the HTA programme website for further project information Objective To investigate whether a high-sensitivity troponin assay , shown to improve early detection of acute myocardial infa rct ion ( AMI ) , permits accelerated rule-in/rule-out of AMI . Methods Patients who presented to the emergency department within 4 h of the onset of chest pain suggestive of acute coronary syndrome were prospect ively recruited from November 2007 to April 2010 . Blood sample s were taken at 0 , 1 , 2 and 12–24 h after presentation and were analysed for clinical ly applied troponin I and for high-sensitivity troponin T ( hsTnT ) . The dynamic change in hsTnT levels between time points was measured . The primary outcome was admission diagnosis of AMI . Results Of the 385 patients recruited , 82 ( 21.3 % ) had AMI . The sensitivity of hsTnT by 2 h was 95.1 % ( 88.7–98.1 % ) , specificity 75.6 % ( 73.8–76.5 % ) , positive predictive value 53.8 % ( 50.2–55.5 % ) and negative predictive value 98.3 % ( 96.0–99.3 % ) . The sensitivity was not statistically different between peak values at 2 h and 24 h. Adding ECG results reduced the false negative rate to 1.2 % . The additional application of ≥20 % delta criterion over the 2 h period for 0–2 h sample s increased specificity to 92.4 % ( 90.2–94.3 % ) but reduced sensitivity to 56.1 % ( 48.0–63.2 % ) . Conclusion hsTnT taken at 0 and 2 h after presentation , together with ECG results , could identify patients suitable for early stress testing with a false negative rate for AMI of 1.2 % . Further trials of such an approach are warranted . The specificity of hsTnT for diagnosing AMI could be improved by the use of a delta of ≥20 % , but at the cost of major reductions in sensitivity Abstract Background : Current hospital practice involves protracted observation of chest-pain patients to rule out myocardial infa rct ion . Concurrent measurement of multiple biomarkers may increase sensitivity and make rapid diagnosis feasible . Objective : We sought to determine the optimal biomarker strategy for highly sensitive , early diagnosis of myocardial injury . Study Design : A prospect i ve evaluation of 171 acute coronary syndrome patients admitted to a single university medical center was performed . Blood tests for creatine kinase ( CK ) , CK myocardial b and isoenzyme ( CK-MB ) , and troponin T were obtained at 0 , 3 , 6 , 8 , and 16 hours after presentation to the emergency department . Myocardial injury was defined as a troponin T level of ≥0.03 ng/mL. Results : Troponin T had sensitivities of 79.7 % , 95.7 % , and 98.4 % at the time of initial presentation , 3 and 6 hours after presentation , respectively . Using a combination of troponin T and CK-MB relative index , sensitivity on presentation was increased to 90.6 % . The sensitivity was improved to 97.9 % and 100 % at 3 and 6 hours , respectively . Conclusion : This study demonstrates that the diagnosis of myocardial injury can be accurately excluded within 6 hours of admission with high sensitivity using troponin T. The combination of troponin T and CK-MB relative index provided the largest improvement in diagnostic sensitivity at patient arrival . These results support the feasibility of rapid , efficient triage for the emergent presentation of patients with chest pain BACKGROUND Cardiac troponin T measured by a high-sensitivity assay ( hs-cTnT ) recently proved to be of prognostic value in several population s. The hs-cTnT assay may also improve risk stratification in acute dyspnea . METHODS We prospect ively studied the prognostic value of hs-cTnT in 678 consecutive patients presenting to the emergency department with acute dyspnea . On the basis of conventional cardiac troponin T assay ( cTnT ) and hs-cTnT assay measurements , patients were divided into 3 categories : ( 1 ) neither assay increased ( cTnT<0.03 μg/L , hs-cTnT<0.016 μg/L ) , ( 2 ) only hs-cTnT increased≥0.016 μg/L ( cTnT<0.03 μg/L ) , and ( 3 ) both assays increased ( cTnT≥0.03 μg/L , hs-cTnT≥0.016 μg/L ) . Moreover , the prognostic value of hs-cTnT was investigated if cTnT was not detectable ( < 0.01 ) . RESULTS One hundred seventy-two patients were in the lowest , 282 patients in the middle , and 223 patients in the highest troponin category . Patients in the second and third categories had significantly higher mortality compared to those in the first category ( 90-day mortality rate 2 % , 10 % , and 26 % in groups 1 , 2 , and 3 , respectively , P<0.001 ; 1-year mortality rate 9 % , 21 % , and 39 % , P<0.001 ) . Importantly , in patients with undetectable cTnT ( n=347 , 51 % ) , increased hs-cTnT indicated worse outcome [ 90-day mortality , odds ratio 4.26 ( 95 % CI 1.19 - 15.21 ) ; 1-year mortality , hazard ratio 2.27 ( 1.19 - 4.36 ) , P=0.013 ] , whereas N-terminal pro-brain-type natriuretic peptide ( NT-proBNP ) was not predictive of short-term outcome . CONCLUSIONS hs-cTnT is associated with mortality in patients presenting with acute dyspnea . hs-cTnT concentrations provide additional prognostic information to cTnT and NT-proBNP testing in patients with cTnT concentrations below the detection limit . In particular , the hs-cTnT cutoff of 0.016 μg/L enables identification of low-risk patients OBJECTIVES The goal of this study was to determine the ability of a single , resting high-sensitivity troponin T ( hsTnT ) measurement to predict abnormal myocardial perfusion imaging ( MPI ) in patients presenting with acute chest pain to the emergency department ( ED ) . BACKGROUND HsTnT assays precisely detect very low levels of troponin T , which may be a surrogate for the presence and extent of myocardial ischemia . METHODS We included all patients from the ROMICAT I ( Rule Out Myocardial Infa rct ion Using Computer Assisted Tomography ) trial , an observational cohort study , who underwent both single-photon emission computed tomography (SPECT)-MPI stress testing and 64-slice computed tomography angiography ( CTA ) and in whom hsTnT measurements were available . We assessed the discriminatory value of hsTnT for abnormal SPECT-MPI and the association of reversible myocardial ischemia by SPECT-MPI and the extent of coronary atherosclerosis by CTA to hsTnT levels . RESULTS Of the 138 patients ( mean age 54 ± 11 years , 46 % male ) , 19 ( 13.7 % ) had abnormal SPECT-MPI . Median hsTnT levels were significantly different between patients with normal and abnormal SPECT-MPI ( 9.41 pg/ml [ interquartile range ( IQR ) : 5.73 to 19.20 pg/ml ] vs. 4.89 pg/ml [ IQR : 2.34 to 7.68 pg/ml ] , p = 0.001 ) . Sensitivity of 80 % and 90 % to detect abnormal SPECT-MPI was reached at hsTnT levels as low as 5.73 and 4.26 pg/ml , respectively . Corresponding specificity was 62 % and 46 % , and negative predictive value was 96 % and 96 % , respectively . HsTnT levels had good discriminatory ability for prediction of abnormal SPECT-MPI ( area under the curve : 0.739 , 95 % confidence interval : 0.609 to 0.868 ) . Both reversible myocardial ischemia and the extent of coronary atherosclerosis ( combined model r(2 ) = 0.19 with partial of r(2 ) = 0.12 and r(2 ) = 0.05 , respectively ) independently and incrementally predicted the measured hsTnT levels . CONCLUSIONS In patients with acute chest pain , myocardial perfusion abnormalities and coronary artery disease are predicted by resting hsTnT levels . Prospect i ve evaluations are warranted to confirm whether resting hsTnT could serve as a powerful triage tool in chest pain patients in the ED before diagnostic testing and improve the effectiveness of patient management BACKGROUND The rapid and reliable diagnosis of acute myocardial infa rct ion is a major unmet clinical need . METHODS We conducted a multicenter study to examine the diagnostic accuracy of new , sensitive cardiac troponin assays performed on blood sample s obtained in the emergency department from 718 consecutive patients who presented with symptoms suggestive of acute myocardial infa rct ion . Cardiac troponin levels were determined in a blinded fashion with the use of four sensitive assays ( Abbott-Architect Troponin I , Roche High-Sensitive Troponin T , Roche Troponin I , and Siemens Troponin I Ultra ) and a st and ard assay ( Roche Troponin T ) . The final diagnosis was adjudicated by two independent cardiologists . RESULTS Acute myocardial infa rct ion was the adjudicated final diagnosis in 123 patients ( 17 % ) . The diagnostic accuracy of measurements obtained at presentation , as quantified by the area under the receiver-operating-characteristic curve ( AUC ) , was significantly higher with the four sensitive cardiac troponin assays than with the st and ard assay ( AUC for Abbott-Architect Troponin I , 0.96 ; 95 % confidence interval [ CI ] , 0.94 to 0.98 ; for Roche High-Sensitive Troponin T , 0.96 ; 95 % CI , 0.94 to 0.98 ; for Roche Troponin I , 0.95 ; 95 % CI , 0.92 to 0.97 ; and for Siemens Troponin I Ultra , 0.96 ; 95 % CI , 0.94 to 0.98 ; vs. AUC for the st and ard assay , 0.90 ; 95 % CI , 0.86 to 0.94 ) . Among patients who presented within 3 hours after the onset of chest pain , the AUCs were 0.93 ( 95 % CI , 0.88 to 0.99 ) , 0.92 ( 95 % CI , 0.87 to 0.97 ) , 0.92 ( 95 % CI , 0.86 to 0.99 ) , and 0.94 ( 95 % CI , 0.90 to 0.98 ) for the sensitive assays , respectively , and 0.76 ( 95 % CI , 0.64 to 0.88 ) for the st and ard assay . We did not assess the effect of the sensitive troponin assays on clinical management . CONCLUSIONS The diagnostic performance of sensitive cardiac troponin assays is excellent , and these assays can substantially improve the early diagnosis of acute myocardial infa rct ion , particularly in patients with a recent onset of chest pain . ( Clinical Trials.gov number , NCT00470587 . Objective To analyse whether levels of high-sensitivity cardiac troponin ( hs-cTn ) below their respective 99th percentile can be used as a single parameter to rule out acute myocardial infa rct ion ( AMI ) at presentation . Design Prospect i ve , multicentre study . Main outcome measures We measured hs-cTn using four different methods ( hs-cTnT Roche , hs-cTnI Siemens , hs-cTnI Beckman Coulter and hs-cTnI Abbott ) in consecutive patients presenting to the emergency department with acute chest pain . Two independent cardiologists adjudicated the final diagnosis . Patients were followed for death or AMI during a mean period of 24 months . Results Among 2072 consecutive patients with hs-cTnT measurements available , 21.4 % had an adjudicated diagnosis of AMI ( sensitivity 89.6 % , 95 % CI 86.4 % to 92.3 % , negative predictive value ( NPV ) : 96.5 % , 95 % CI 95.4 % to 97.4 % ) . Among 1180 consecutive patients with hs-cTnI Siemens measurements available , 20.0 % had AMI ( sensitivity 94.1 % , 95 % CI 90.3 % to 96.7 % , NPV : 98.0 % , 95 % CI : 96.6 % to 98.9 % ) . Among 1151 consecutive patients with hs-cTnI Beckman Coulter measurements available , 19.7 % had AMI ( sensitivity 92.1 % , 95 % CI 87.8 % to 95.2 % , NPV : 97.5 % , 95 % CI 96.0 % to 98.5 % ) . Among 1567 consecutive patients with hs-cTnI Abbott measurements available , 20.0 % had AMI ( sensitivity 77.2 % , 95 % CI 72.1 % to 81.7 % , NPV : 94.3 % , 95 % CI 92.8 % to 95.5 % ) . Conclusions Normal hs-cTn levels at presentation should not be used as a single parameter to rule out AMI as 6%–23 % of adjudicated AMI cases had normal levels of hs-cTn levels at presentation . Our data highlight the lack of st and ardisation among hs-cTnI assays result ing in substantial differences in sensitivity and NPV at the 99th percentile Background Current guidelines define acute myocardial infa rct ion ( AMI ) by the rise and /or fall of cardiac troponin with ≥1 value above the 99th percentile . Past troponin assays have been unreliable at the lower end of the range . Highly sensitive assays have therefore been developed to increase the clinical sensitivity for detection of myocardial injury . Methods Three hundred and thirty-two patients with chest pain suggestive of AMI were prospect ively recruited between November 2006 and April 2007 . Serial blood sample s were analysed to compare Roche Elecsys high sensitivity troponin T ( hsTnT ) , Abbott Architect troponin I 3rd generation ( TnI 3 ) and Roche Elecsys troponin T ( TnT ) for the diagnosis of AMI . Results One hundred and ten ( 33.1 % ) patients were diagnosed with AMI . Test performance for the diagnosis of AMI , as quantified by receiver operating characteristic area under the curve ( 95 % confidence intervals ) for baseline/follow-up troponins were as follows : hsTnT 0.90 (0.87–0.94)/0.94 ( 0.91–0.97 ) , TnI 3 0.88 (0.84–0.92)/0.93 ( 0.90–0.96 ) and TnT 0.80 (0.74–0.85)/0.89 ( 0.85–0.94 ) . hsTnT was superior to TnT ( P < 0.001/0.013 at baseline/follow-up ) but equivalent to TnI 3 . For patients with a final diagnosis of AMI , baseline troponins were raised in more patients for hsTnT ( 83.6 % ) than TnI 3 ( 74.5 % ) and TnT ( 62.7 % ) . A delta troponin of ≥20 % increased the specificity of hsTnT from 80.6 % to 93.7 % but reduced sensitivity from 90.9 % to 71.8 % . Conclusion hsTnT was superior to TnT but equivalent to TnI 3 for the diagnosis of AMI . Serial troponin measurement increased test performance . hsTnT was the most likely to be raised at baseline in those with AMI . A delta troponin increases specificity but reduces sensitivity OBJECTIVES Chest pain due to suspected myocardial infa rct ion ( MI ) is responsible for many hospital admissions and consumes substantial health care re sources . The R and omized Assessment of Treatment using Panel Assay of Cardiac markers ( RATPAC ) trial showed that diagnostic assessment using a point-of-care ( POC ) cardiac biomarker panel consisting of CK-MB , myoglobin , and troponin increased the proportion of patients successfully discharged after emergency department ( ED ) assessment . In this economic analysis , the authors aim ed to determine whether POC biomarker panel assessment reduced health care costs and was likely to be cost-effective . METHODS The RATPAC trial was a multicenter individual patient r and omized controlled trial comparing diagnostic assessment using a POC biomarker panel ( CK-MB , myoglobin , and troponin , measured at baseline and 90 minutes ) to st and ard care without the POC panel in patients attending six EDs with acute chest pain due to suspected MI ( n = 2,243 ) . Individual patient re source use data were collected from all participants up to 3 months after hospital attendance using self-completed question naires at 1 and 3 months and case note review . ED staff and POC testing costs were estimated through a microcosting study of 246 participants . Re source use was valued using national unit costs . Health utility was measured using the EQ-5D self-completed question naire , mailed at 1 and 3 months . Quality -adjusted life-years ( QALYs ) were calculated by the trapezium rule using the EQ-5D tariff values at all follow-up points . Mean costs per patient were compared between the two treatment groups . Cost-effectiveness was estimated in terms of probability of dominance and incremental cost per QALY . RESULTS Point-of-care panel assessment was associated with higher ED costs , coronary care costs , and cardiac intervention costs , but lower general inpatient costs . Mean costs per patient were £ 1217.14 ( st and ard deviation [ SD ] ± 3164.93 ) , or $ 1,987.14 ( SD ±$4,939.25 ) , with POC versus £ 1005.91 ( SD ±£1907.55 ) , or $ 1,568.64 ( SD ±$2,975.78 ) , with st and ard care ( p = 0.056 ) . Mean QALYs were 0.158 ( SD ± 0.052 ) versus 0.161 ( SD ± 0.056 ; p = 0.250 ) . The probability of st and ard care being dominant ( i.e. , cheaper and more effective ) was 0.888 , while the probability of the POC panel being dominant was 0.004 . These probabilities were not markedly altered by sensitivity analysis varying the costs of the POC panel and excluding intensive care costs . CONCLUSIONS Point-of-care panel assessment does not reduce costs despite reducing admissions and may even increase costs . It is unlikely to be considered a cost-effective use of health care re sources AIMS Angiogenic factors play an important role in the development of atherosclerosis and show pronounced changes during acute myocardial infa rct ion ( AMI ) . We analysed the impact of placental growth factor ( PlGF ) and its endogen opponent , soluble fms-like tyrosine kinase-1 ( sFlt-1 ) , on clinical outcome and the early diagnosis of AMI . METHODS AND RESULTS This multicentre study enrolled patients presenting with symptoms suggestive of AMI . The final diagnosis was adjudicated by two independent physicians . Levels of sFlt-1 and PlGF were compared with results of a st and ard troponin T and a novel high-sensitive troponin ( hsTnT ) assay . Of the 763 patients enrolled , 132 were diagnosed with AMI . Multivariable Cox regression analysis demonstrated sFlt-1 > 84 ng/L [ hazard ratios ( HR ) 2.6 , 95 % confidence intervals ( CI ) 1.2 - 5.4 , P=0.01 ] and PlGF > 20 ng/L ( HR 3.6 , 95 % CI 1.3 - 10.4 , P=0.02 ) as predictors for mortality during 1-year follow-up , independent from information provided by troponin T and N-terminal pro-B-type natriuretic peptide ( NT-proBNP ) . However , only sFlt-1 persisted as independent predictor for mortality when analysed together with hsTnT and NT-proBNP , and after adjusting for significant clinical parameters . For the diagnosis of AMI , the combination of troponin T and sFlt-1 improved the performance of troponin T alone and led to a negative predictive value of 98.3 % already at time of presentation . However , sFlt-1 and PlGF added only limited diagnostic information when used together with hsTnT. CONCLUSION Only sFlt-1 but not PlGF provides overall independent prognostic information in patients presenting with symptoms suggestive of AMI . After the introduction of hsTnT in clinical routine , sFlt-1 and PlGF can only add limited diagnostic information for the detection or exclusion of AMI . CLINICAL TRIAL REGISTRATION INFORMATION Clinical Trials.gov , NCT00470587 BACKGROUND Earlier trials have shown that a routine invasive strategy improves outcomes in patients with acute coronary syndromes without ST-segment elevation . However , the optimal timing of such intervention remains uncertain . METHODS We r and omly assigned 3031 patients with acute coronary syndromes to undergo either routine early intervention ( coronary angiography < or = 24 hours after r and omization ) or delayed intervention ( coronary angiography > or = 36 hours after r and omization ) . The primary outcome was a composite of death , myocardial infa rct ion , or stroke at 6 months . A prespecified secondary outcome was death , myocardial infa rct ion , or refractory ischemia at 6 months . RESULTS Coronary angiography was performed in 97.6 % of patients in the early-intervention group ( median time , 14 hours ) and in 95.7 % of patients in the delayed-intervention group ( median time , 50 hours ) . At 6 months , the primary outcome occurred in 9.6 % of patients in the early-intervention group , as compared with 11.3 % in the delayed-intervention group ( hazard ratio in the early-intervention group , 0.85 ; 95 % confidence interval [ CI ] , 0.68 to 1.06 ; P=0.15 ) . There was a relative reduction of 28 % in the secondary outcome of death , myocardial infa rct ion , or refractory ischemia in the early-intervention group ( 9.5 % ) , as compared with the delayed-intervention group ( 12.9 % ) ( hazard ratio , 0.72 ; 95 % CI , 0.58 to 0.89 ; P=0.003 ) . Prespecified analyses showed that early intervention improved the primary outcome in the third of patients who were at highest risk ( hazard ratio , 0.65 ; 95 % CI , 0.48 to 0.89 ) but not in the two thirds at low-to-intermediate risk ( hazard ratio , 1.12 ; 95 % CI , 0.81 to 1.56 ; P=0.01 for heterogeneity ) . CONCLUSIONS Early intervention did not differ greatly from delayed intervention in preventing the primary outcome , but it did reduce the rate of the composite secondary outcome of death , myocardial infa rct ion , or refractory ischemia and was superior to delayed intervention in high-risk patients . ( Clinical Trials.gov number , NCT00552513 . Background : High-sensitivity troponin assays are now available for clinical use . We investigated whether early measurement with such an assay is superior to a conventional assay in the evaluation of acute coronary syndromes . Methods : Patients presenting to an emergency department with chest pain who did not have ST-segment elevation were prospect ively recruited from November 2007 to December 2010 . Patients underwent serial testing with a conventional cardiac troponin I assay . Sample s were also obtained at presentation and two hours later for measurement of troponin T levels using a high-sensitivity assay . The primary outcome was diagnosis of myocardial infa rct ion on admission ; secondary outcomes were death , myocardial infa rct ion and heart failure at one year . Results : Of the 939 patients enrolled in the study , 205 ( 21.8 % ) had myocardial infa rct ion . By two hours after presentation , the high-sensitivity troponin T assay at the cut-off point of the 99th percentile of the general population ( 14 ng/L ) had a sensitivity of 92.2 % ( 95 % confidence interval [ CI ] 88.1%–95.0 % ) and a specificity of 79.7 % ( 95 % CI 78.6%–80.5 % ) for the diagnosis of non – ST-segment myocardial infa rct ion . The sensitivity of the assay at presentation was 100 % among patients who presented four to six hours after symptom onset . By one year , the high-sensitivity troponin T assay was found to be superior than the conventional assay in predicting death ( hazard ratio [ HR ] 5.4 , 95 % CI 2.7–10.7 ) and heart failure ( HR 27.8 , 95 % CI 6.6–116.4 ) , whereas the conventional assay was superior in predicting nonfatal myocardial infa rct ion ( HR 4.0 , 95 % CI 2.4–6.7 ) . Interpretation : The high-sensitivity troponin T assay at the cut-off point of the 99th percentile was highly sensitive for the diagnosis of myocardial infa rct ion by two hours after presentation and had prognostic utility beyond that of the conventional assay . To rule out myocardial infa rct ion , the optimal time to test a second sample using the high-sensitivity troponin T level may be four to six hours after symptom onset , but this finding needs verification in future studies before it can become routine practice Objectives To determine whether using a point-of-care cardiac biomarker panel would increase the rate of successful discharge home after emergency department assessment , and affect the use of cardiac tests and treatments , subsequent attendance at or admission to hospital and major adverse events . Design and setting Pragmatic multicentre r and omised controlled trial in six acute hospitals in the UK . Participants Patients attending with acute chest pain due to suspected myocardial infa rct ion ( N=2243 ) . Interventions Diagnostic assessment using a point-of-care biomarker panel consisting of creatine kinase , myocardial type , myoglobin and troponin I measured at baseline and 90 min compared with st and ard care without the point-of-care panel . Main outcome measures The primary outcome was successful discharge home , defined as having left hospital or awaiting transport home by 4 h after attendance and no major adverse events up to 3 months . Secondary outcome measures included length of stay , use of coronary care , cardiac interventions and inpatient beds , emergency department attendances , subsequent admissions , outpatient visits and major adverse events . Results Point-of-care panel assessment was associated with an increased rate of successful discharge ( 358/1125 ( 32 % ) vs 146/1118 ( 13 % ) ; OR 3.81 , 95 % CI 3.01 to 4.82 ; p<0.001 ) , reduced median length of initial hospital stay ( 8.8 vs 14.2 h ; p<0.001 ) and greater use of coronary care ( 50/1125 ( 4.0 % ) vs 31/1118 ( 3.0 % ) ; p=0.041 ) , but no difference in mean length of initial stay ( 29.6 vs 31.7 h ; p=0.462 ) , mean inpatient days over follow-up ( 1.8 vs 1.7 ; p=0.815 ) or major adverse events ( 36 ( 3 % ) vs 26 ( 2 % ) ; OR 1.31 , 95 % CI 0.78 to 2.20 ; p=0.313 ) . Conclusions Point-of-care panel assessment increases successful discharge home and reduces median length of stay , but does not alter overall hospital bed use . Trial registration Current controlled trials IS RCT N37823923 BACKGROUND Two recent clinical trials showed that adding copeptin to a conventional cardiac troponin assay improved diagnostic performance for patients with chest pain early after symptom onset . We prospect ively tested whether copeptin adds information to that provided by a high-sensitivity cardiac troponin T ( hscTnT ) assay in the early evaluation of patients with suspected acute myocardial infa rct ion , particularly non-ST-segment elevation myocardial infa rct ion ( non-STEMI ) . METHODS We enrolled 503 patients with suspected acute coronary syndrome and onset of chest pain occurring within the previous 12 h. Copeptin was measured on presentation , and hscTnT was measured serially at baseline and after 3 and 6 h. We used ROC curve analysis and likelihood ratio χ² statistics for nested models . Diagnostic sensitivities , specificities , positive predictive values ( PPVs ) , and negative predictive values ( NPVs ) were calculated for admission values of copeptin alone , hscTnT alone , and the combination of both markers . RESULTS For ruling out non-STEMI ( after excluding STEMI ) , an hscTnT concentration < 14 ng/L ( 99th percentile ) plus a copeptin concentration < 14 pmol/L yielded a diagnostic sensitivity of 97.7 % ( 95 % CI , 91.9%-99.7 % ) , an NPV of 99.03 % ( 95 % CI , 96.6%-99.9 % ) , a diagnostic specificity of 55.9 % ( 95 % CI , 50.6%-61.0 % ) , and a PPV of 34.4 % ( 95 % CI , 28.5%-40.7 % ) . ROC curve analysis of the continuous biomarker values on admission demonstrated no added value of using this marker combination for ruling out non-STEMI when hscTnT was used as the st and ard for diagnosing non-STEMI . CONCLUSIONS A strategy using copeptin with hscTnT at prespecified cutoffs improves the ruling out of non-STEMI , compared with using hscTnT alone ; thus , this strategy could help to obviate a prolonged stay in the emergency department Objective To assess the impact of triple marker testing on patient management and the diagnostic efficiencies of different biomarker strategies examined . Design A prospect i ve r and omised trial of triple marker testing by point-of-care testing ( POCT ) ; the R and omised Assessment of Panel Assay of Cardiac markers ( RATPAC ) study . Setting Six emergency departments . Patients Low-risk patients presenting with chest pain to diagnostic assessment with a cardiac panel measured by POCT or to diagnosis when biomarker measurement was based on central laboratory testing . Interventions 1125 patients were r and omly assigned to POCT measurement of the triple marker panel of cardiac troponin I ( cTnI ) , myoglobin and the MB isoenzyme of creatine kinase ( CK-MB ) on admission and 90 min from admission . Main Outcome Measures Myocardial infa rct ion ( MI ) was defined by the universal definition of MI . The following diagnostic strategies were compared by receiver operator characteristic ( ROC ) curve analysis and comparison of area under the curve ( AUC ) : individual marker values , change ( Δ ) in CK-MB and myoglobin and the combination of presentation or 90 min value plus Δ value . Results Admission sample measurement of cTnI was the most diagnostically efficient AUC 0.96 ( 0.93–0.98 ) with areas under the ROC curve statistically significantly greater than CK-MB 0.85 ( 0.80–0.90 ) and myoglobin 0.75 ( 0.68–0.81 ) . At 90 min cTnI measurement had the highest AUC 0.95 ( 0.87–1.00 ) but was statistically significantly different only from Δmyoglobin and ΔCK-MB . Conclusion Measurement of cTnI alone is sufficient for diagnosis . Measurement of a marker panel does not facilitate diagnosis Abstract Background : Identifying older patients with non-ST- elevation myocardial infa rct ion ( NSTEMI ) within the very large proportion with elevated high-sensitive cardiac troponin T ( hs-cTnT ) is a diagnostic challenge because they often present without clear symptoms or electrocardiographic features of acute coronary syndrome to the emergency department ( ED ) . We prospect ively investigated the diagnostic and prognostic performance of copeptin ultra-sensitive ( copeptin-us ) and hs-cTnT compared to hs-cTnT alone for NSTEMI at prespecified cut-offs in unselected older patients . Methods : We consecutively enrolled 306 non-surgical patients ≥70 years presenting to the ED . In addition to clinical examination , copeptin-us and hs-cTnT were measured at admission . Two cardiologists independently adjudicated the final diagnosis of NSTEMI after review ing all available data . All patients were followed up for cardiovascular-related death within the following 12 months . Results : NSTEMI was diagnosed in 38 ( 12 % ) patients ( age 81±6 years ) . The combination of copeptin-us ≥14 pmol/L and hs-cTnT ≥0.014 µg/L compared to hs-cTnT ≥0.014 µg/L alone had a positive predictive value of 21 % vs. 19 % to rule in NSTEMI . The combination of copeptin-us < 14 pmol/L and hs-cTnT < 0.014 µg/L compared to hs-cTnT < 0.014 µg/L alone had a negative predictive value of 100 % vs. 99 % to rule out NSTEMI . Hs-cTnT ≥0.014 µg/L alone was significantly associated with outcome . When copeptin-us ≥14 pmol/L was added , the net reclassification improvement for outcome was not significant ( p=0.809 ) . Conclusions : In unselected older patients presenting to the ED , the additional use of copeptin-us at predefined cut-offs may help to reliably rule out NSTEMI but may not help to increase predicted risk for outcome compared to hs-cTnT alone BACKGROUND Growth differentiation factor-15 ( GDF-15 ) is a stress-responsive marker that might aid in the early diagnosis and risk stratification of patients with suspected acute myocardial infa rct ion ( AMI ) . METHODS In a prospect i ve , international multicenter study , GDF-15 , high-sensitivity cardiac troponin T ( hs-cTnT ) , and B-type natriuretic peptide ( BNP ) were measured in 646 unselected patients presenting to the emergency department with acute chest pain . The final diagnosis was adjudicated by 2 independent cardiologists . The primary prognostic end point was all-cause mortality during a median follow-up of 26 months . RESULTS AMI was the adjudicated final diagnosis in 115 patients ( 18 % ) . GDF-15 concentrations at presentation were significantly higher in AMI patients compared to patients with other diagnoses . The diagnostic accuracy of GDF-15 at presentation for the diagnosis of AMI as quantified by the area under the ROC curve ( AUC ) was lower ( AUC 0.69 , 95 % CI 0.64 - 0.74 ) compared to hs-cTnT ( AUC 0.96 , 95 % CI 0.94 - 0.98 , P < 0.001 ) and BNP ( AUC 0.74 , 95 % CI 0.69 - 0.80 , P = 0.02 ) . A total of 55 deaths occurred during follow-up . GDF-15 predicted all-cause mortality independently of and more accurately than hs-cTnT [ AUC 0.85 ( 95 % CI 0.81 - 0.90 ) vs 0.77 ( 95 % CI 0.72 - 0.83 ) , P = 0.002 ] and BNP ( AUC 0.75 , 95 % CI 0.68 - 0.82 , P = 0.007 ) . Net reclassification improvement was 0.15 ( P = 0.01 ) , and the absolute integrated discrimination improvement was 0.07 , yielding a relative integrated discrimination improvement of 0.36 ( P = 0.07 ) . CONCLUSIONS GDF-15 predicts all-cause mortality in unselected patients with acute chest pain independently of and more accurately than hs-cTnT and BNP . However , GDF-15 does not seem to help in the early diagnosis of AMI Background — We hypothesized that high-sensitivity cardiac troponin ( hs-cTn ) and its early change are useful in distinguishing acute myocardial infa rct ion ( AMI ) from acute cardiac noncoronary artery disease . Methods and Results — In a prospect i ve , international multicenter study , hs-cTn was measured with 3 assays ( hs-cTnT , Roche Diagnostics ; hs-cTnI , Beckman-Coulter ; hs-cTnI Siemens ) in a blinded fashion at presentation and serially thereafter in 887 unselected patients with acute chest pain . Accuracy of the combination of presentation values with serial changes was compared against a final diagnosis adjudicated by 2 independent cardiologists . AMI was the adjudicated final diagnosis in 127 patients ( 15 % ) ; cardiac noncoronary artery disease , in 124 ( 14 % ) . Patients with AMI had higher median presentation values of hs-cTnT ( 0.113 & mgr;g/L [ interquartile range , 0.049–0.246 & mgr;g/L ] versus 0.012 & mgr;g/L [ interquartile range , 0.006–0.034 & mgr;g/L ] ; P<0.001 ) and higher absolute changes in hs-cTnT in the first hour ( 0.019 & mgr;g/L [ interquartile range , 0.007–0.067 & mgr;g/L ] versus 0.001 & mgr;g/L [ interquartile range , 0–0.003 & mgr;g/L ] ; P<0.001 ) than patients with cardiac noncoronary artery disease . Similar findings were obtained with the hs-cTnI assays . Adding changes of hs-cTn in the first hour to its presentation value yielded a diagnostic accuracy for AMI as quantified by the area under the receiver-operating characteristics curve of 0.94 for hs-cTnT ( 0.92 for both hs-cTnI assays ) . Algorithms using ST-elevation , presentation values , and changes in hs-cTn in the first hour accurately separated patients with AMI and those with cardiac noncoronary artery disease . These findings were confirmed when the final diagnosis was readjudicated with the use of hs-cTnT values and vali date d in an independent validation cohort . Conclusion — The combined use of hs-cTn at presentation and its early absolute change excellently discriminates between patients with AMI and those with cardiac noncoronary artery disease . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00470587 BACKGROUND High-sensitivity cardiac troponin ( hs-cTn ) assays seem to improve the early diagnosis of acute myocardial infa rct ion ( AMI ) , but it is unknown how to best use them in clinical practice . Our objective was to develop and vali date an algorithm for rapid rule-out and rule-in of AMI . METHODS A prospect i ve multicenter study enrolling 872 unselected patients with acute chest pain presenting to the emergency department . High-sensitivity cardiac troponin T ( hs-cTnT ) was measured in a blinded fashion at presentation and after 1 hour . The final diagnosis was adjudicated by 2 independent cardiologists . An hs-cTnT algorithm incorporating baseline values as well as absolute changes within the first hour was derived from 436 r and omly selected patients and vali date d in the remaining 436 patients . The primary prognostic end point was death during 30 days of follow-up . RESULTS Acute myocardial infa rct ion was the final diagnosis in 17 % of patients . After applying the hs-cTnT algorithm developed in the derivation cohort to the validation cohort , 259 patients ( 60 % ) could be classified as " rule-out , " 76 patients ( 17 % ) as " rule-in , " and 101 patients ( 23 % ) as in the " observational zone " within 1 hour . Overall , this result ed in a sensitivity and negative predictive value of 100 % for rule-out , a specificity and positive predictive value of 97 % and 84 % , respectively , for rule-in , and a prevalence of AMI of 8 % in the observational zone group . Cumulative 30-day survival was 99.8 % , 98.6 % , and 95.3 % ( P < .001 ) in patients classified as rule-out , observational zone , and rule-in , respectively . CONCLUSIONS Using a simple algorithm incorporating hs-cTnT baseline values and absolute changes within the first hour allowed a safe rule-out as well as an accurate rule-in of AMI within 1 hour in 77 % of unselected patients with acute chest pain . This novel strategy may obviate the need for prolonged monitoring and serial blood sampling in 3 of 4 patients OBJECTIVES This paper sought to evaluate whether high sensitivity troponin ( hs-cTnT ) can immediately exclude acute myocardial infa rct ion ( AMI ) at a novel ' rule out ' cut-off . BACKGROUND Subgroup analysis of recent evidence suggests that undetectable hs-cTnT may exclude AMI at presentation . METHODS In a cohort study , we prospect ively enrolled patients with chest pain , evaluating them with st and ard troponin T and testing for hs-cTnT ( Roche Diagnostics , Basel , Switzerl and ) at presentation . The primary outcome was a diagnosis of AMI . We also followed up patients for adverse events within 6 months . After subsequent clinical implementation of hs-cTnT , we again evaluated whether initially undetectable hs-cTnT ruled out a subsequent rise . RESULTS Of 703 patients in the cohort study , 130 ( 18.5 % ) had AMI , none of whom initially had undetectable hs-cTnT ( sensitivity : 100.0 % , 95 % confidence interval [ CI ] : 95.1 % to 100.0 % , negative predictive value : 100.0 % , 95 % CI : 98.1 % to 100.0 % ) . This strategy would rule out AMI in 27.7 % of patients , 2 ( 1.0 % ) of whom died or had AMI within 6 months ( 1 periprocedural AMI , 1 noncardiac death ) . We evaluated this approach in an additional 915 patients in clinical practice . Only 1 patient ( 0.6 % ) with initially undetectable hs-cTnT had subsequent elevation ( to 17 ng/l ) , giving a sensitivity of 99.8 % ( 95 % CI : 99.1 % to 100.0 % ) and a negative predictive value of 99.4 % ( 95 % CI : 96.6 % to 100.0 % ) . CONCLUSIONS Undetectable hs-cTnT at presentation has very high negative predictive value , which may be considered to rule out AMI , identifying patients at low risk of adverse events . Pending further validation , this strategy may reduce the need for serial testing and empirical treatment , enabling earlier reassurance for patients and fewer unnecessary evaluations and hospital admissions BACKGROUND High-sensitivity cardiac troponin assays have better analytical precision and sensitivity than earlier-generation assays when measuring cardiac troponin at low concentrations . We evaluated whether use of a high-sensitivity assay could further improve risk stratification compared with a st and ard cardiac troponin assay . METHODS We enrolled consecutive patients presenting with acute chest pain , 30 % of whom were diagnosed with acute coronary syndrome . Blood sample s were drawn at the time of presentation . We measured cardiac troponin T with a st and ard fourth-generation assay ( cTnT ) and a high-sensitivity assay ( hs-cTnT ) ( both Roche Diagnostics ) and followed the patients for 24 months . RESULTS Of the 1159 patients , 76 died and 42 developed an acute myocardial infa rct ion ( AMI ) . Prognostic accuracy of hs-cTnT for death was significantly higher [ area under ROC curve ( AUC ) 0.79 , 95 % CI 0.74 - 0.84 ] than that of cTnT ( AUC 0.69 , 95 % CI 0.62 - 0.76 ; P < 0.001 ) . After adjustment for Thrombolysis in Myocardial Infa rct ion ( TIMI ) risk score ( that included the cTnT assay result ) , hs-cTnT above the 99th percentile ( 0.014 μg/L ) was associated with a hazard ratio for death of 2.60 ( 95 % CI 1.42 - 4.74 ) . Addition of hs-cTnT to the risk score improved the reclassification of patients ( net reclassification improvement 0.91 ; 95 % CI 0.67 - 1.14 ; P < 0.001 ) . Subgroup analyses showed that this effect result ed from the better classification of patients without AMI at time of testing . hs-cTnT outperformed cTnT in the prediction of AMI during follow-up ( P=0.02 ) , but was not independently predictive for this endpoint . CONCLUSIONS Concentrations of hs-cTnT > 0.014 μg/L improve the prediction of death but not subsequent AMI in unselected patients presenting with acute chest pain Background —Activation of leukocytes with release of myeloperoxidase ( MPO ) has been linked to acute coronary disease . To date , studies investigating the diagnostic and prognostic performance of circulating MPO in patients with chest pain ( CP ) are mainly retrospective , of low size , and lack a cut-off value for MPO . Herein , we prospect ively assess the diagnostic and prognostic properties of MPO compared with sensitive troponin I ( sTNI ) in patients admitted to the emergency room with CP . Methods and Results —One thous and , eight hundred and eighteen consecutive patients ( mean age , 61.4±13.5 years ; 33.6 % female ) admitted for CP underwent determination of MPO , sTnI , and B-natriuretic peptide plasma levels at admission and 3 hours and 6 hours thereafter . A cut-off for MPO was defined in 5000 population -based subjects . Baseline MPO levels were elevated in patients with acute myocardial infa rct ion compared with patients with noncoronary CP . For all time-points accuracy of MPO was inferior to sTNI for predicting AMI . The sensitivity of MPO to diagnose AMI at presentation was 73.5 % compared with 90.7 % for sTNI , and the specificity of MPO was 45.5 % as opposed to 90.2 % . B-natriuretic peptide levels also failed to demonstrate independent diagnostic information . Both MPO and B-natriuretic peptide were predictive for increased risk of adverse events at 30 days and 6 months , whereas their predictive value was weakened after covariate adjustment . Conclusions —The data demonstrate that MPO and B-natriuretic peptide fail to provide incremental information for patients with acute onset CP when added to sensitive troponin . However , there is a potential value for both biomarkers as prognostic markers Background The combination of the new high sensitivity troponin T ( hsTnT ) assays and copeptin , a biomarker of endogenous stress , has been suggested to have the potential of early rule-out of acute coronary syndrome ( ACS ) . The aim of this study was to examine the ability of this combination to rule out ACS in patients presenting with chest pain and to compare the diagnostic performance to hsTnT alone . Method In this prospect i ve observational study , patients with chest pain admitted for observation were consecutively included . Patients presenting with ST elevation were excluded . Copeptin and hsTnT were analyzed at admission and hsTnT was thereafter determined approximately every 3rd hour as long as clinical ly indicated . The follow-up period was 60 days . A combined primary endpoint of ACS , non-elective percutanous coronary intervention , non-elective coronary artery bypass surgery and death of all causes was used . Results 478 patients were included . 107 ( 22 % ) patients were diagnosed with ACS during hospital stay . 70 ( 14 % ) had non-ST-segment elevation myocardial infa rct ion ( NSTEMI ) and 37 ( 8 % ) had unstable angina pectoris (UAP).The combination of hsTnT > 14 ng/L or copeptin ≥14 pmol/L at admission identified ACS with a higher sensitivity than hsTnT alone : 0.83 ( 95 % confidence interval ( CI ) : 0.74 - 0.89 ) versus 0.69 ( 95 % CI : 0.59 - 0.77 ) , p < 0.001 . Negative predictive values ( NPV ) 91 % ( 95 % CI : 86 - 94 ) versus 89 % ( 95 % CI : 84 - 92 ) . A repeated hsTnT analyzed 3 - 4 hours after admission result ed in a sensitivity of : 0.77 ( 95 % CI : 0.65 - 0.86 ) , p = 0.031 for comparison with the combination analyzed at admission . Conclusions In patients presenting with chest pain admitted for observation , the combination of hsTnT and copeptin analyzed at admission had a significantly higher sensitivity to diagnose ACS than hsTnT alone . We report a sensitivity of 83 % and a NPV of 91 % for the combination of hsTnT and copeptin and we conclude that biomarkers alone are not sufficient to rule out ACS . However , the combination of hsTnT and copeptin seems to have a significantly higher sensitivity to identify ACS than a repeated hsTnT test , and thus enables an earlier risk stratification of chest pain patients . This can be time-saving and beneficial for the individual patient by contributing to early decisions on treatment , need of further assessment and level of care OBJECTIVES The purpose of this study was to determine whether a new accelerated diagnostic protocol ( ADP ) for possible cardiac chest pain could identify low-risk patients suitable for early discharge ( with follow-up shortly after discharge ) . BACKGROUND Patients presenting with possible acute coronary syndrome ( ACS ) , who have a low short-term risk of adverse cardiac events may be suitable for early discharge and shorter hospital stays . METHODS This prospect i ve observational study tested an ADP that included pre-test probability scoring by the Thrombolysis In Myocardial Infa rct ion ( TIMI ) score , electrocardiography , and 0 + 2 h values of laboratory troponin I as the sole biomarker . Patients presenting with chest pain due to suspected ACS were included . The primary endpoint was major adverse cardiac event ( MACE ) within 30 days . RESULTS Of 1,975 patients , 302 ( 15.3 % ) had a MACE . The ADP classified 392 patients ( 20 % ) as low risk . One ( 0.25 % ) of these patients had a MACE , giving the ADP a sensitivity of 99.7 % ( 95 % confidence interval [ CI ] : 98.1 % to 99.9 % ) , negative predictive value of 99.7 % ( 95 % CI : 98.6 % to 100.0 % ) , specificity of 23.4 % ( 95 % CI : 21.4 % to 25.4 % ) , and positive predictive value of 19.0 % ( 95 % CI : 17.2 % to 21.0 % ) . Many ADP negative patients had further investigations ( 74.1 % ) , and therapeutic ( 18.3 % ) or procedural ( 2.0 % ) interventions during the initial hospital attendance and /or 30-day follow-up . CONCLUSIONS Using the ADP , a large group of patients was successfully identified as at low short-term risk of a MACE and therefore suitable for rapid discharge from the emergency department with early follow-up . This approach could decrease the observation period required for some patients with chest pain . ( An observational study of the diagnostic utility of an accelerated diagnostic protocol using contemporary central laboratory cardiac troponin in the assessment of patients presenting to two Australasian hospitals with chest pain of possible cardiac origin ; ACTRN12611001069943 ) We compared the sensitivity of three commonly used cardiac markers between two sub population s , those who came to the Emergency Department ( ED ) late ( 6 - 24 h ) after their symptoms began , and those who arrived earlier ( < 6 h ) , in a prospect i ve comparative trial . Among all adult patients who presented to our ED with symptoms suggestive of acute myocardial infa rct ion ( MI ) , we drew serum for myoglobin , CK-MB , and troponin I upon arrival ( time 0 ) and 2 h later . Outcomes , including acute MI , were determined . Sensitivities for all three markers between the sub population s who arrived fewer than 6 h from symptom onset were compared to those who arrived later ( 6 - 24 h ) . We enrolled 346 eligible subjects , 36 % of whom described cardiac symptoms as beginning 6 or more hours earlier ; 14 % suffered acute MIs . For time 0 , the sensitivity of all three markers for acute MI was significantly higher among those subjects with symptoms of 6 or more hours ' duration as compared to those with less . For troponin I , the increase in sensitivity between these two sub population s approached 300 % . At the time of the 2-h sample , the differences in sensitivities were much less and were not statistically significant . We conclude that cardiac marker values obtained at time 0 among Emergency Department patients who arrive 6 or more hours after cardiac symptom onset provide significantly higher sensitivities as compared to those obtained in patients who arrive earlier . For troponin I , the increase in sensitivity approaches threefold Concerns have been raised about the performance of highly sensitive cardiac troponin assays to accurately detect acute myocardial infa rct ion ( AMI ) , particularly in non-ST segment elevation ( NSTEMI ) , in elderly patients , and in patients with renal failure . We evaluated whether increased age and low estimated glomerular filtration rate ( eGFR ) alter diagnostic performance of high-sensitivity cardiac troponin T ( HScTnT ) . In a prospect i ve multicentric study , HScTnT levels were measured blindly at presentation in patients with acute chest pain . Three hundred and sixty-seven patients were enrolled , including 84 patients ≥70 years . Final diagnosis was AMI for 57 patients ( 16 % ) and NSTEMI for 43 patients ( 12 % ) . NSTEMI was more frequent in elderly patients ( p = 0.008 ) . Sensitivity and specificity of HScTnT > 14 ng/L at admission for AMI were 96 % and 51 % in patients ≥70 years versus 91 % ( NS ) and 88 % ( p < 0.0001 ) in younger patients ; the same observations were done for the diagnosis of NSTEMI . Given an HScTnT > 53.5 ng/L for the diagnosis of AMI and NSTEMI , respective sensitivities were 87 % and 84 % and respective specificities were 87 % and 87 % in elderly patients . Using a cutoff at 35.8 ng/L ( for AMI ) or 43.2 ng/L ( for NSTEMI ) , sensitivities were 94 % and 92 % , and specificities were 86 % and 88 % in patients with low eGFR . Older age , but not low eGFR , was an independent predictive factor of an elevated HScTnT at admission ( odds ratio 2.2 [ 1.2 - 3.9 ] , p = 0.007 ) . In conclusion , adapted thresholds of HScTnT are required for an accurate diagnosis of AMI/NSTEMI in patients aged ≥70 and in those with low eGFR Objective : To assess if the combination of cardiac troponin ( cTn ) and Ischemia Modified Albumin ( IMA ) can be used for early exclusion of acute myocardial infa rct ion ( AMI ) . Methods : Prospect i ve consecutive admissions to the emergency department ( ED ) with undifferentiated chest pain were assessed clinical ly and by electrocardiography . A total of 539 patients ( 335 men , 204 women ; median age 51.9 years ) considered at low risk of AMI had blood drawn on admission . If the first sample was less than 12 hours from onset of chest pain , a second sample was drawn two hours later , at least six hours from onset of chest pain . Creatine kinase MB isoenzyme ( CKMB ) mass was measured on the first sample and CKMB mass and cTnT on the second sample . An aliquot from the first available sample was frozen and subsequently analysed for IMA . If cTnT had not been measured on the original sample cTnI was measured ( n = 189 ) . Results : Complete data were available for 538/539 patients . IMA or cTn was elevated in the admission sample of all patients with a final diagnosis of AMI ( n = 37 ) with IMA alone elevated in 2/37 , cTn alone in 19/37 , and both in 16/37 . In 173/501 patients in whom AMI was excluded both tests were negative . In the non-AMI group 22 patients had elevation of both IMA and cTn in the initial sample , suggesting ischaemic disease . Conclusion : Admission measurement of cardiac troponin plus IMA can be used for early classification of patients presenting to the ED to assist in patient triage BACKGROUND Elevated ST2 predicts future heart failure and /or death in patients with pulmonary diseases , heart failure , acute dyspnea , and acute coronary syndromes . This study assesses both diagnostic and prognostic utility of ST2 in patients with chest pain . METHODS AND RESULTS From November 2007 to April 2010 , 995 patients attending the Emergency Department with chest pain were prospect ively recruited . Troponin I ( TnI ) , B-type natriuretic peptide ( BNP ) , creatine kinase-myocardial b and ( CKMB ) , myoglobin , and ST2 were measured at 0 and 2 hours . The diagnostic utility of ST2 for heart failure and prognostic utility for primary outcome of death and /or heart failure by 18 months was assessed . Elevated ST2 had sensitivity 73.5 % ( 55.8%-86.4 % ) and specificity 79.6 % ( 79.0%-80.1 % ) for acute heart failure ( n = 34 ) [ compared with BNP sensitivity 88.2 % ( 73.6%-95.3 % ) , specificity 66.2 % ( 65.7%-66.4 % ) ] . Elevated ST2 conveyed risk of 18-month primary outcome ( n = 110 ) , with an adjusted hazard ratio ( HR ) of 1.9 ( 1.2 - 3.2 ) , compared with BNP HR 2.8 ( 1.4 - 5.7 ) , myoglobin HR 1.9 ( 1.1 - 3.3 ) , TnI HR 1.7 ( 1.0 - 2.7 ) , and CKMB HR 0.9 ( 0.5 - 1.7 ) . When ST2 and BNP were both elevated , risk was greater than if either marker was elevated in isolation ( P < .001 ) . CONCLUSIONS ST2 was more specific for acute heart failure than BNP . ST2 is independently predictive of future death and /or heart failure and has incremental utility in combination with BNP Rapid identification and treatment of patients with a myocardial infa rct ion ( MI ) is m and atory . We studied the diagnostic capacities of a sensitive troponin assay for detection of MI in emergency department patients within 2 hours after arrival . The study included 157 patients suspected of having non-ST-elevation acute coronary syndrome . Blood was drawn on arrival ( T0 ) and 2 ( T2 ) , 6 , and 12 hours later . At T2 , a troponin concentration above the MI cutoff is 87 % sensitive and 100 % specific for MI detection ( positive predictive value [ PPV ] , 100 % ; negative predictive value [ NPV ] , 96 % ) . If a difference of more than 30 % between the troponin measurements at T0 and T2 in the absence of an absolute troponin increase above the 99th percentile of a reference population is also considered indicative of MI , the sensitivity increases to 100 % and specificity decreases to 87 % ( PPV , 70 % ; NPV , 100 % ) . Sensitivity and specificity of creatine kinase-MB and myoglobin are lower than those of troponin . By using a sensitive troponin assay and simple algorithms , the diagnosis of MI can be determined within 2 hours after arrival at the emergency department . Measurement of myoglobin and creatine kinase-MB has no added value BACKGROUND The aim of the present study was to evaluate the diagnostic accuracy of high-sensitivity troponin T ( hsTnT ) in patients with suspected acute coronary syndrome ( ACS ) in comparison to heart fatty acid-binding protein ( H-FABP ) , high-sensitivity C-reactive protein , myeloperoxidase ( MPO ) , and pentraxin 3 ( PTX3 ) . METHODS AND RESULTS Patients ( n=432 ) with chest pain were recruited for the analysis . ACS was diagnosed in 298 patients ( 69 % ) . The diagnostic accuracy of measurements obtained at presentation , as quantified by the area under the receiver operating curve ( AUC ) , was highest for hsTnT ( AUC=0.82 ; 95 % confidence interval [ CI ] : 0.78 - 0.87 ) and H-FABP ( AUC=0.83 ; 95%CI : 0.78 - 0.87 ) . Sensitivity ( 87.9 % ) and negative likelihood ( LH ; 0.2 ) for hsTnT were the highest and lowest , respectively , but H-FABP had the highest specificity ( 78.5 % ) and positive LH ( 3.6 ) . Among patients who presented within 2h after the onset of chest pain , MPO had the highest AUC ( 0.82 ; 95%CI : 0.69 - 0.94 ) . Combined use of H-FABP and MPO measurements yielded a sensitivity of 69.2 % , specificity of 84.2 % , positive LH of 4.4 , and negative LH of 0.4 . CONCLUSIONS The hsTnT assay offers excellent diagnostic performance to rule out ACS , but it is prone to false-positive results . H-FABP offers similar overall diagnostic performance , while the combination of H-FABP and MPO assays may improve the diagnosis of ACS , particularly in patients with recent onset of chest pain Troponin T ( TpT ) is a protein implicated in skeletal muscle contractions , including myocardium . It was shown that the presence of troponin TpT in unstable angina patients ' blood is associated with poor prognosis . In the present study amongst 25 patients with unstable angina 12 were found to have TpT present in their blood . TpT concentration was higher in patients with III and IVo CCS symptoms in comparison with class I and IIo CCS symptoms : 0.207 + /- 0.275 and 0.144 + /- 0.186 ng/mL respectively ( p = 0.053 ; nonparametric Kolmogorow-Smirnov test ) . Patients were subjected to percutaneous transluminal coronary angioplasty ( PTCA ) . After 3 months of follow up 17 patients ( the rest of them dropped out ) were assigned to two groups : A ( n = 8)--without and B ( n = 9)--with clinical and electrocardiographic signs of restenosis . Retrospective analysis revealed the presence of TpT before PTCA in 6 group B patients and 2 group A patients . Relative risk of stenocardia recurrence was calculated as 2.25 . TpT was present in the blood of 20 patients in the first 24 hours after PTCA , and group B patients had higher mean TpT concentration ; that could result from reperfusion of more ischaemic myocardium . It seems that the presence of TpT in unstable angina patients ' blood may be an important factor characterizing patients with more serious prognosis BACKGROUND We examined whether undetectable levels of high-sensitivity cardiac Troponin ( hs-cTn ) can be used to rule out acute myocardial infa rct ion ( AMI ) with a single blood draw at presentation to the emergency department ( ED ) . METHODS AND RESULTS In a prospect i ve multicenter study we used 4 different hs-cTn assays ( hs-cTnT Roche , and hs-cTnI Siemens , hs-cTnI Beckman Coulter and hs-cTnI Abbott ) in consecutive patients presenting with acute chest pain . The final diagnosis of AMI was adjudicated by two independent cardiologists using all available data including serial hs-cTnT levels . Mean follow up was 24 months . Among 2072 consecutive patients with available hs-cTnT levels , 21 % had an adjudicated diagnosis of AMI . Among AMI patients , 98.2 % had initially detectable levels of hs-cTnT ( sensitivity 98.2 % , 95%CI 96.3%-99.2 % , negative predictive value ( NPV ) 98.6 % , 95%CI 97.0%-99.3 % ) . Undetectable levels of hs-cTnT ruled out AMI in 26.5 % of patients at presentation . The NPV was similar with the three hs-cTnI assays : among 1180 consecutive patients with available hs-cTnI ( Siemens ) , the NPV was 98.8 % ; among 1151 consecutive patients with available hs-cTnI ( Beckman Coulter ) , the NPV was 99.2 % ; among 1567 consecutive patients with available hs-cTnI ( Abbott ) , the NPV was 100.0 % . The percentage of patients with undetectable levels of hs-cTnI was similar among the three hs-cTnI assays and ranged from 11.4 % to 13.9 % . CONCLUSIONS Undetectable levels of hs-cTn at presentation have a very high NPV and seem to allow the simple and rapid rule out of AMI . This criteria applies to much more patients with hs-TnT as compared to the investigated hs-cTnI assays Objective To investigate the diagnostic and prognostic role of heart-type fatty acid-binding protein ( hFABP ) compared with copeptin and in addition to high-sensitivity cardiac troponin T ( hs-cTnT ) in patients with chest pain suspected of acute myocardial infa rct ion ( AMI ) . Design Diagnostic and prognostic performances of hFABP , copeptin and hs-cTnT were evaluated and compared . The final diagnosis was adjudicated by two independent cardiologists . Setting This prospect i ve observational multicentre study took place in four primary and one secondary hospital from April 2006 to September 2009 . Patients We enrolled 1247 consecutive patients with suspected AMI to the emergency department . For analysis , patients were included , if baseline levels for hs-cTnT and hFABP were available ( n=1074 ) , patients with ST-segment elevation myocardial infa rct ion ( STEMI ) were excluded for the diagnostic analysis ( n=43 ) . Interventions Treatment was left to the discretion of the emergency physician . Main outcome measures AMI and mortality . Results 4 % of the patients had STEMI and 16 % of the patients had non-STEMI . Patients with AMI had significantly higher levels of hFABP at presentation ( p<0.001 ) . Neither the combination with hFABP nor with copeptin increased the diagnostic accuracy of hs-cTnT at admission , quantified by the area under the receiver operating characteristic curve ( AUC ) ( p>0.05 ) . The negative predictive value regarding 90-day , 1-year and 2-year mortality was 100 % ( 99–100 ) , 99 % ( 98–100 ) and 98 % ( 96–99 ) , respectively , for hFABP levels below the median ( p<0.001 ) . The accuracy of hFABP to predict 90-day mortality was moderate ( AUC 0.83 ; 95 % CI 0.77 to 0.90 ) . Conclusions hFABP and copeptin do not improve the diagnosis of patients with chest pain without ST-segment elevation , but may be useful for risk stratification beyond BACKGROUND High-sensitivity cardiac troponin assays have improved the detection of acute coronary syndrome . AIM To examine the possible incremental value of copeptin in the detection of acute coronary syndrome . METHODS We design ed a prospect i ve cohort study to compare the performance of high-sensitivity cardiac troponin T ( hs-cTnT ) measured at admission in combination with copeptin , and the performance of hs-cTnT alone , measured at admission , 3 hours and 6 hours , in patients with suspected acute coronary syndrome of < 6 hours ' duration after onset of symptoms ( exclusion of patients with ST-segment elevation myocardial infa rct ion ) . RESULTS Fifty-eight consecutive patients fulfilled our criteria and were included . After detailed investigations , the final adjudicated diagnosis was acute coronary syndrome in 30 patients ( including acute myocardial infa rct ion in 13 and unstable angina in 17 ) and non-acute coronary syndrome in 28 patients . Measured on admission , hs-cTnT concentration was > 14 ng/mL ( 99 th percentile ) in 22 patients with acute coronary syndrome ; repetition of the measurement at 3 hours and 6 hours identified three and four additional patients , respectively . The combination of copeptin with hs-cTnT determined on admission identified 26 patients with acute coronary syndrome , with a negative predicted value of 82.6 % . The area under the receiver operating characteristic curve was 0.90 for hs-cTnT measured on admission , and 0.94 if repeated at 3 hours and 6 hours or combined with copeptin measurement at admission ( non-significant difference ) . CONCLUSIONS This prospect i ve study demonstrated that a dual marker strategy that combines hs-cTnT with copeptin increased slightly the detection of acute coronary syndrome at admission OBJECTIVES To determine if an algorithm implementing a serial high-sensitive cardiac troponin T ( hs-cTnT ) measurement at presentation ( 0 h ) and at 3 hours after presentation ( 3h ) is helpful for early diagnosis of non-ST-elevation myocardial infa rct ion ( NSTEMI ) in older patients . DESIGN Prospect i ve observational cohort study . SETTING An emergency department ( ED ) of a city hospital covering a population of approximately 1 million in Germany . PARTICIPANTS A total of 332 consecutive unselected patients were recruited , of whom 25 had one or more of the prespecified exclusion criteria and 1 had a missing hs-cTnT at 3h , result ing in a final population of 306 patients . MEASUREMENTS In addition to clinical examination , hs-cTnT was measured at 0 h and 3 h. The final diagnosis of NSTEMI was adjudicated by two independent consultants and an algorithm for rule-in and rule-out of NSTEMI was developed using classification and regression tree analysis . All patients were followed-up for cardiovascular outcome within 12 months . RESULTS Among 306 patients ( mean age 81 ± 6 years ) , 38 ( 12 % ) patients had NSTEMI . Accuracy to diagnose NSTEMI was significantly higher for hs-cTnT measurements at 3 h versus 0 h ( area under the receiver operating characteristic curve [ AUC ] 0.88 vs. 0.82 , P = .0038 ) and for absolute versus relative hs-cTnT delta changes ( AUC 0.89 versus 0.69 , P < .001 ) . A diagnostic algorithm using hs-cTnT values at presentation and absolute delta changes values ruled-in NSTEMI in 23 % and ruled-out NSTEMI in 35 % of patients . For patients neither fulfilling the rule-in nor the rule-out criteria , an observational zone was established . Cumulative 1-year survival was 79.4 % , 88.5 % , and 99.1 % in patients classified as rule-in , observational zone , and rule-out , respectively . CONCLUSION In older patients , serial hs-cTnT measurements and absolute delta-changes at 3h were valuable for early diagnosis of NSTEMI . An algorithm ruled-in NSTEMI in one quarter of patients with high risk and ruled-out NSTEMI in one-third with low risk BACKGROUND Although highly sensitive assays for troponin T ( hs-TnT ) have been developed , the sensitivity and specificity of hs-TnT for diagnosing acute coronary syndrome ( ACS ) remains imperfect . We evaluated the diagnostic value of a new biomarker of plaque vulnerability ( soluble lectin-like oxidized low-density lipoprotein receptor-1 , sLOX-1 ) as compared with hs-TnT in the emergency room ( ER ) . METHODS AND RESULTS Plasma sLOX-1 and serum hs-TnT levels were measured in 200 consecutive patients presenting with chest symptoms and ECG abnormalities in the ER ( 116 ST elevation ACS [ STEACS ] , 44 non-ST elevation ACS [ NSTEACS ] , 40 non-ACS ) . The non-ACS group consisted of patients with cardiovascular diseases such as coronary spastic angina pectoris , pulmonary thromboembolism , perimyocarditis and takotsubo cardiomyopathy . Levels of sLOX-1 and hs-TnT were significantly higher in STEACS and NSTEACS than in non-ACS patients . The receiver-operating characteristic ( ROC ) curves of sLOX-1 and hs-TnT for detecting ACS , using the non-ACS patients as negative references , showed that the area under the curve ( AUC ) values of sLOX-1 and hs-TnT were 0.769 and 0.739 , respectively . In the lower hs-TnT ( < 0.0205ng/ml ) subgroup , the AUC value of the ROC curve of sLOX-1 for detecting ACS was 0.869 . CONCLUSIONS The diagnostic value for ACS was comparable between sLOX-1 and hs-TnT , and the accuracy of ACS diagnosis appeared to improve when sLOX-1 and hs-TnT were measured in combination BACKGROUND Absolute changes in high-sensitivity cardiac troponin T ( hs-cTnT ) seem to have higher diagnostic accuracy in the early diagnosis of acute myocardial infa rct ion compared with relative changes . It is unknown whether the same applies to high-sensitivity cardiac troponin I ( hs-cTnI ) assays and whether the combination of absolute and relative change might further increase accuracy . METHODS In a prospect i ve , international multicenter study , high-sensitivity cardiac troponin ( hs-cTn ) was measured with 3 novel assays ( hs-cTnT , Roche Diagnostics Corp , Indianapolis , Ind ; hs-cTnI , Beckman Coulter Inc , Brea , Calif ; hs-cTnI , Siemens , Munich , Germany ) in a blinded fashion at presentation and after 1 and 2 hours in a blinded fashion in 830 unselected patients with suspected acute myocardial infa rct ion . The final diagnosis was adjudicated by 2 independent cardiologists . RESULTS The area under the receiver operating characteristic curve for diagnosing acute myocardial infa rct ion was significantly higher for 1- and 2-hour absolute versus relative hs-cTn changes for all 3 assays ( P < .001 ) . The area under the receiver operating characteristic curve of the combination of 2-hour absolute and relative change ( hs-cTnT 0.98 [ 95 % confidence interval { CI } , 0.97 - 0.99 ] ; hs-cTnI , Beckman Coulter Inc , 0.97 [ 95 % CI , 0.96 - 0.99 ] ; hs-cTnI , Siemens , 0.96 [ 95 % CI , 0.93 - 0.99 ] ) were high and provided some benefit compared with the use of absolute change alone for hs-cTnT , but not for the hs-cTnI assays . Reclassification analysis confirmed the superiority of absolute changes versus relative changes . CONCLUSIONS Absolute changes seem to be the preferred metrics for both hs-cTnT and hs-cTnI in the early diagnosis of acute myocardial infa rct ion . The combination of absolute and relative changes provides a small added value for hs-cTnT , but not for BACKGROUND AND OBJECTIVE Publication bias and other sample size effects are issues for meta-analyses of test accuracy , as for r and omized trials . We investigate limitations of st and ard funnel plots and tests when applied to meta-analyses of test accuracy and look for improved methods . METHODS Type I and type II error rates for existing and alternative tests of sample size effects were estimated and compared in simulated meta-analyses of test accuracy . RESULTS Type I error rates for the Begg , Egger , and Macaskill tests are inflated for typical diagnostic odds ratios ( DOR ) , when disease prevalence differs from 50 % and when thresholds favor sensitivity over specificity or vice versa . Regression and correlation tests based on functions of effective sample size are valid , if occasionally conservative , tests for sample size effects . Empirical evidence suggests that they have adequate power to be useful tests . When DORs are heterogeneous , however , all tests of funnel plot asymmetry have low power . CONCLUSION Existing tests that use st and ard errors of odds ratios are likely to be seriously misleading if applied to meta-analyses of test accuracy . The effective sample size funnel plot and associated regression test of asymmetry should be used to detect publication bias and other sample size related effects BACKGROUND Accelerated diagnostic pathways for risk stratification of patients presenting to the emergency department with potential acute coronary syndromes may identify very-low-risk patients safe for early discharge to outpatient care . METHODS Patients presenting with potential acute coronary syndrome to the emergency department were prospect ively enrolled between November 2007 and April 2010 . Patient characteristics in conjunction with 0- and 2-hour biomarkers and electrocardiograms were analyzed according to a 2-hour thrombolysis in myocardial infa rct ion ( TIMI ) score and 9 other accelerated diagnostic pathways . The primary outcome was acute coronary syndrome by 30 days . RESULTS Of 1,000 patients , 362 ( 36.2 % ) had a primary outcome . A pathway comprising electrocardiogram , prior ischemic heart disease , 0/2-hour troponin/creatine kinase MB fraction/myoglobin identified the highest proportion ( 25.0 % ) as low risk , with 96.1 % sensitivity for the primary outcome . A pathway comprising electrocardiogram , history of ischemic heart disease , typical vs atypical symptoms , 0/2-hour troponin was the safest , with 99.7 % sensitivity for the primary outcome , but only 9.0 % were low risk . A pathway comprising the TIMI score with 0/2-hour troponin and electrocardiograms identified 15.5 % as low risk , with a sensitivity of 99.2 % for the primary outcome . This compares with st and ard care in which none were for outpatient care but , 3.3 % had a primary outcome postdischarge within 30 days . CONCLUSION In this relatively high-risk population , a 2-hour TIMI score safely identified significant numbers of patients suitable for early discharge to outpatient care BACKGROUND Discharging patients with acute myocardial infa rct ion or unstable angina from the emergency department because of missed diagnoses can have dire consequences . We studied the incidence of , factors related to , and clinical outcomes of failure to hospitalize patients with acute cardiac ischemia . METHODS We analyzed clinical data from a multicenter , prospect i ve clinical trial of all patients with chest pain or other symptoms suggesting acute cardiac ischemia who presented to the emergency departments of 10 U.S. hospitals . RESULTS Of 10,689 patients , 17 percent ultimately met the criteria for acute cardiac ischemia ( 8 percent had acute myocardial infa rct ion and 9 percent had unstable angina ) , 6 percent had stable angina , 21 percent had other cardiac problems , and 55 percent had noncardiac problems . Among the 889 patients with acute myocardial infa rct ion , 19 ( 2.1 percent ) were mistakenly discharged from the emergency department ( 95 percent confidence interval , 1.1 to 3.1 percent ) ; among the 966 patients with unstable angina , 22 ( 2.3 percent ) were mistakenly discharged ( 95 percent confidence interval , 1.3 to 3.2 percent ) . Multivariable analysis showed that patients who presented to the emergency department with acute cardiac ischemia were more likely not to be hospitalized if they were women less than 55 years old ( odds ratio for discharge , 6.7 ; 95 percent confidence interval , 1.4 to 32.5 ) , were nonwhite ( odds ratio , 2.2 ; 1.1 to 4.3 ) , reported shortness of breath as their chief symptom ( odds ratio , 2.7 ; 1.1 to 6.5 ) , or had a normal or nondiagnostic electrocardiogram ( odds ratio , 3.3 ; 1.7 to 6.3 ) . Patients with acute infa rct ion were more likely not to be hospitalized if they were nonwhite ( odds ratio for discharge , 4.5 ; 95 percent confidence interval , 1.8 to 11.8 ) or had a normal or nondiagnostic electrocardiogram ( odds ratio , 7.7 ; 95 percent confidence interval , 2.9 to 20.2 ) . For the patients with acute infa rct ion , the risk-adjusted mortality ratio for those who were not hospitalized , as compared with those who were , was 1.9 ( 95 percent confidence interval , 0.7 to 5.2 ) , and for the patients with unstable angina , it was 1.7 ( 95 percent confidence interval , 0.2 to 17.0 ) . CONCLUSIONS The percentage of patients who present to the emergency department with acute myocardial infa rct ion or unstable angina who are not hospitalized is low , but the discharge of such patients is associated with increased mortality . Failure to hospitalize is related to race , sex , and the absence of typical features of cardiac ischemia . Continued efforts to reduce the number of missed diagnoses are warranted BACKGROUND The aim of this study was to compare the clinical performance of 2 sensitive cTnI assays with 10 % CV imprecision below the 99th percentile upper reference limit . METHODS We measured cardiac troponin and N-terminal pro-brain natriuretic peptide ( NT-proBNP ) concentrations in a r and om sample of the Global Use of Strategies To Open Occluded Coronary Arteries ( GUSTO ) IV cohort ( n = 1251 ) . Outcome data of 1-year mortality and the composite endpoint DMI [ death and /or myocardial infa rct ion ( MI ) within 30 days ] were available in all patients . The 99th percentile of a healthy population was estimated from the Sweden Women and Men and Ischemic Heart Disease ( SWISCH ) cohort ( n = 442 ) . We measured cardiac troponin I ( cTnI ) using the Access AccuTnI ( Beckman Coulter ) and Centaur TnI Ultra ( Siemens Healthcare Diagnostics ) and NT-proBNP using the Elecsys 2010 ( Roche Diagnostics ) . RESULTS Applying the 10 % CV cutoff , the sensitivity of the Access AccuTnI assay in identifying DMI and death was higher than that of the Centaur TnI Ultra ( P = 0.02 and P < 0.001 ) , and the AccuTnI assay also identified more patients at risk ( P < 0.001 ) and with poor outcome . Applying the 99th percentile cutoffs , AccuTnI identified more patients at risk than the Centaur TnI ( P < 0.001 ) and with significant differences in outcome . Significantly more patients with cardiac troponins below the cutoffs as measured by Centaur TnI had increased NT-proBNP concentrations ( P < 0.001 ) compared with AccuTnI. CONCLUSIONS The AccuTnI assay identified more patients at risk than the Centaur cTnI Ultra assay . Our results demonstrate the clinical potential of high-sensitivity cardiac troponin assays for the identification of patients at risk of dying from cardiovascular disease BACKGROUND Concerns have been raised about possible gender disparities in cardiac investigations and /or outcome . This study sought to examine and compare the diagnostic and prognostic performance of selected cardiac biomarkers in women versus men . METHODS In a prospect i ve , multicenter cohort of patients with acute chest pain cardiac troponin T ( cTnT ) ( fourth-generation Roche assay ) , high-sensitivity cTnT ( hs-cTnT ) , and copeptin were measured at presentation . RESULTS Of 1,247 patients , 420 were women and 827 were men . Although the rate of acute myocardial infa rct ion was similar in women ( 14.5 % ) and men ( 16.6 % , P = .351 ) , women more frequently had cardiac but noncoronary causes of chest pain ( 17.4 % vs 10.8 % , P = .001 ) and less frequently had unstable angina ( 8.8 % vs 16.6 % , P = .002 ) than men . Diagnostic accuracy as quantified by the area under the receiver operating characteristic curve ( AUC ) for acute myocardial infa rct ion in women was 0.90 ( 95 % CI 0.84 - 0.95 ) for cTnT , which was lower than the AUC for hs-cTnT alone ( 0.94 , 95 % CI [ 0.91 - 0.98 ] ) , the combination of cTnT with copeptin ( 0.96 , 95 % CI [ 0.94 - 0.98 ] ) or the combination of hs-cTnT with copeptin ( 0.96 , 95 % CI [ 0.93 - 0.98 ] ) ( P = .008 , P = .006 , and P = .002 , respectively ) . Prognostic accuracy as quantified by the AUCs for 1-year mortality was 0.69 ( 0.56 - 0.83 ) , 0.86 ( 0.79 - 0.93 ) , 0.87 ( 0.81 - 0.94 ) , and 0.87 ( 0.80 - 0.94 ) , respectively . No relevant gender differences in AUCs were observed . CONCLUSION The diagnostic and prognostic performance of cTnT , hs-cTnT , and copeptin is as good in women as in men . High-sensitivity cTnT and the combination of cTnT and copeptin outperform cTnT alone , both in women and men Background : Assessment of the relative diagnostic accuracy of investigation strategies for patients with suspected acute coronary syndromes ( ACS ) . Methods : A prospect i ve observational study followed two groups of patients over a 3-month period in a UK district general hospital . Group one : all admissions with suspected ACS ( n = 576 ) ; group two : non-cardiac in- patients who were suspected of developing ACS ( n = 87 ) . Both were investigated by full clinical history , examination and serial electrocardiographs ( ECGs ) . Conventional World Health Organization ( WHO ) criteria for myocardial damage were compared with diagnosis based on cardiac troponin T ( cTnT ) . Clinical discharge diagnosis based on conventional WHO criteria was compared with the review diagnosis based on measurement of cTnT. Results : Diagnosis based on WHO criteria missed 58 patients ( 8·7 % ) admitted with suspected ACS who had high risk unstable angina . Thirty-three patients ( 5 % of all admissions ) who were diagnosed as non-Q wave acute myocardial infa rct ion ( AMI ) were found to have normal troponin values and to have been incorrectly classified as AMI . Conclusions : Diagnostic strategies based on WHO criteria are inaccurate . The measurement of cTnT in all patients with suspected ACS would have increased the number of those with a diagnosis of AMI by 58 ( 8·7 % ) , while avoiding inaccurate diagnosis in 33 ( 5 % ) , therefore producing an absolute increase of 25/663 ( 3·8 % ) but a relative increase of 58/138 ( 42 % ) . In patients with a primary diagnosis of suspected ACS , the overall increase in patients with a diagnosis of AMI will be 55 ( 9·5 % ) , a relative increase of 55/118 ( 46·6 % ) but an absolute increase of 36/576 ( 6·3 % ) OBJECTIVES To test the diagnostic accuracy for detecting an acute myocardial infa rct ion ( AMI ) using highly sensitive troponin assays and a range of new cardiac biomarkers of plaque destabilisation , myocardial ischaemia and necrosis ; to test the prognostic accuracy for detecting adverse cardiac events using highly sensitive troponin assays and this range of new cardiac biomarkers ; and to estimate the cost-effectiveness of using highly sensitive troponin assays or this range of new cardiac biomarkers instead of an admission and 10- to 12-hour troponin measurement . DESIGN Sub study of the point-of-care arm of the RATPAC ( R and omised Assessment of Treatment using Panel Assay of Cardiac markers ) trial . SETTING The emergency departments of six hospitals . PARTICIPANTS Prospect i ve admissions with chest pain and a non-diagnostic electrocardiogram r and omised to point-of-care assessment or conventional management . INTERVENTIONS Blood sample s taken on admission and 90 minutes from admission for measurement of cardiac markers [ cardiac troponin I ( cTnI ) , myoglobin and creatine kinase MB isoenzyme ( CK-MB ) ] by point-of-care testing . An additional blood sample was taken at admission and 90 minutes from admission for analysis of high-sensitivity cTnI ( two methods ) and cardiac troponin T ( cTnT ) , myoglobin , heart-type fatty acid-binding protein ( H-FABP ) , copeptin and B-type natriuretic peptide ( NTproBNP ) . MAIN OUTCOME MEASURES 1 . Diagnostic accuracy compared with the universal definition of myocardial infa rct ion utilising laboratory measurements of cardiac troponin performed at the participating sites together with measurements performed in a core laboratory . 2 . Ability of biomarker measurements to predict major adverse cardiac events ( death , non-fatal AMI , emergency revascularisation or hospitalisation for myocardial ischaemia ) at 3 months ' follow-up . 3 . Comparison of incremental cost per quality -adjusted life-year ( QALY ) of different biomarker measurement strategies for the diagnosis of myocardial infa rct ion . RESULTS Sample s were available from 850 out of 1132 patients enrolled in the study . Measurement of admission myoglobin [ area under the curve ( AUC ) 0.76 ] and CK-MB ( AUC 0.84 ) was diagnostically inferior and did not add to the diagnostic efficiency of cTnI ( AUC 0.90 - 0.94 ) or cTnT ( AUC 0.92 ) measurement on admission . Simultaneous measurement of H-FABP and cTnT or cTnI did improve admission diagnostic sensitivity to 0.78 - 0.92 , but only to the same level as that achieved with troponin measured on admission and at 90 minutes from admission ( 0.78 - 0.95 ) . Copeptin ( AUC 0.62 ) and NTproBNP ( AUC 0.85 ) measured on admission were not useful as diagnostic markers . As a prognostic marker , troponin measured on admission using a high-sensitivity assay ( AUC 0.73 - 0.83 ) was equivalent to NTproBNP measurement ( AUC 0.77 ) on admission , but superior to copeptin measurement ( AUC 0.58 ) . From modelling , 10-hour troponin measurement is likely to be cost-effective compared with rapid rule-out strategies only if a £ 30,000 per QALY threshold is used and patients can be discharged as soon as a negative result is available . CONCLUSIONS The measurement of high-sensitivity cardiac troponin is the best single marker in patients presenting with chest pain . Additional measurements of myoglobin or CK-MB are not clinical ly effective or cost-effective . The optimal timing for measurement of cardiac troponin remains to be defined . Copeptin measurement is not recommended . H-FABP requires further investigation before it can be recommended for simultaneous measurement with high-sensitivity troponin in patients with acute chest pain . TRIAL REGISTRATION IS RCT N37823923 . FUNDING This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol . 17 , No. 15 . See the HTA programme website for further project information AIM Troponin assays have high diagnostic value for myocardial infa rct ion ( MI ) , but sensitivity has been weak early after chest pain onset . New , so-called ' sensitive ' troponin assays have recently been introduced . Two studies report high sensitivity for assays taken at ED presentation , but studied selected population s. Our aim was to evaluate the diagnostic performance for MI of a sensitive troponin assay measured at ED presentation in an unselected chest pain population without ECG evidence of ischaemia . METHODS This is a sub- study of a prospect i ve cohort study of adult patients with potentially cardiac chest pain who underwent evaluation for acute coronary syndrome . Patients with clear ECG evidence of acute ischaemia or an alternative diagnosis were excluded . Data collected included demographic , clinical , ECG , biomarker and outcome data . A ' positive ' troponin was defined as > 99th percentile of the assay used . MI diagnosis was as judged by the treating cardiologist . The outcomes of interest were sensitivity , specificity and likelihood ratios ( LR ) for positive troponin assay taken at ED presentation . Data were analysed by clinical performance analysis . RESULTS Totally 952 were studied . Median age was 61 years ; 56.4 % were male and median TIMI score was 2 . There were 129 MI ( 13.6 , 95 % CI 11.5 - 15.9 ) . Sensitivity of TnI at ED presentation was 76.7 % ( 95 % CI 68.5 - 83.7 % ) , specificity 93.6 % ( 95 % CI 91.7 - 95.1 % ) , with LR positive 11.92 and LR negative 0.25 . CONCLUSION Sensitive TnI assay at ED presentation has insufficient diagnostic accuracy for detection of MI . Serial biomarker assays in patients with negative initial TnI are required STUDY OBJECTIVE The emergency department ( ED ) evaluation of chest pain patients with potential acute coronary syndrome is limited by the initial sensitivity of cell injury markers . BNP is increased during myocardial ischemia and is associated with adverse outcomes . We determine whether the addition of B-type natriuretic peptide ( BNP ) to troponin I , creatine kinase-MB ( CK-MB ) , and myoglobin increases the sensitivity and negative predictive value ( NPV ) for acute myocardial infa rct ion , acute coronary syndrome , and 30-day adverse events among chest pain patients with potential acute coronary syndrome . METHODS A convenience sample of patients aged 30 years or older and presenting to an urban academic ED with nontraumatic chest pain , thus prompting an ECG , was enrolled , and consent was obtained . Blood sample s were drawn at 0 and 90 minutes . Thirty-day follow-up was performed for all enrolled patients . Main outcomes were acute myocardial infa rct ion , acute coronary syndrome , and 30-day events ( death , acute myocardial infa rct ion , or revascularization ) . BNP cutoffs were derived from receiver operator characteristics curves . The sensitivity , specificity , positive predictive value ( PPV ) , and NPV with 95 % confidence intervals ( CIs ) were calculated with and without BNP . Differences in sensitivity and specificity with the addition of BNP were calculated with 95 % CIs , and McNemar 's test was performed to compare sensitivities and specificities . RESULTS Four hundred twenty-six patients were enrolled and analyzed . The cohort was 54.7+/-13.9 years old , 47.7 % men , and 63.5 % black . The outcomes were acute myocardial infa rct ion , 39 ( 9.2 % ) , acute coronary syndrome , 101 ( 23.7 % ) , and 30-day adverse cardiovascular events 52 ( 12.2 % ) . BNP cutoffs derived were 51 , 31 , and 31 pg/mL for acute myocardial infa rct ion , acute coronary syndrome , and 30-day events , respectively . The addition of BNP showed increased sensitivity at the cost of decreased specificity for all 3 outcomes , as follows : ( 1 ) acute myocardial infa rct ion : sensitivity : 87.2 % ( 95 % CI 72.6 % to 95.7 % ) to 97.4 % ( 95 % CI 86.5 % to 100 % ) , difference 10.3 % ( 95 % CI-0.2 % to 24.6 % ) , P=.125 ; specificity : 62.3 % ( 95 % CI 57.2 % to 67.1 % ) to 47.8 % ( 95 % CI 42.7 % to 52.9 % ) , difference 14.5 % ( 95 % CI 11.1 % to % 18.4 ) , P<.0001 ; ( 2 ) acute coronary syndrome : sensitivity : 75.2 % ( 95 % CI 65.7 % to 83.3 % ) to 88.1 % ( 95 % CI 80.2 % to 93.7 % ) , difference 12.9 % ( 95 % CI 7.0 % to 21.0 % ) , P=.0002 ; specificity : 68.0 % ( 95 % CI 62.6 % to 73.0 % ) to 48.6 % ( 95 % CI 43.1 % to 54.2 % ) , difference 19.4 % ( 95 % CI 15.2 % to 24.1 % ) , P<.0001 ; ( 3 ) 30-day events : sensitivity : 71.2 % ( 95 % CI 56.9 % to 82.9 % ) to 88.5 % ( 95 % CI 76.6 % to 95.7 % ) , difference 17.3 % ( 95 % CI 7.7 % to 30.3 % ) , P=.004 ; specificity : 61.8 % ( 95 % CI 56.6 % to 66.7 % ) to 43.9 % ( 95 % CI 38.8 % to 49.0 % ) , difference 17.9 % ( 95 % CI 14.2 % to 22.2 % ) , P<.0001 . There were trends toward increased NPV and decreased PPV for all outcomes , and the addition of BNP achieved a NPV of 99.5 % ( 95 % CI 97.0 % to 100 % ) compared with 98.0 % ( 95 % CI 95.3 % to 99.3 % ) for acute myocardial infa rct ion . CONCLUSION The addition of BNP as a dichotomous test to troponin I , CK-MB , and myoglobin produces increased sensitivity at a cost of decreased specificity for acute myocardial infa rct ion , acute coronary syndrome , and 30-day adverse events . Because of this tradeoff , BNP can not be recommended for use among all ED chest pain patients . However , the improved sensitivity may make this test useful in selected cohorts when the decreased specificity is less important OBJECTIVE We sought to evaluate the added value of ultrasensitive copeptin ( us-copeptin ) for early rule out of acute myocardial infa rct ion in a prospect i ve cohort of emergency department ( ED ) patients with acute chest pain . METHODS This was a prospect i ve study including consecutive patients with acute chest pain presenting to the ED within 12 hours of symptom onset . High-sensitivity cardiac troponin T ( hs-cTnT , Roche Diagnostics , Meylan , France ) and us-copeptin ( ThermoFisher Scientific , Clichy , France ) were blindly assayed from venous blood sample s obtained at admission . Diagnosis was made by 2 ED physicians using all available data and serial cardiac troponin I as the biochemical st and ard . Diagnostic performances of us-copeptin combined with hs-cTnT were assessed using logistic regression . Analysis was conducted in all patients and in patients without ST-elevation myocardial infa rct ion . RESULTS A total of 194 patients were included ( age , 61 [ 48 - 75 ] years ; male sex , 63 % ) . Acute myocardial infa rct ion occurred in 52 ( 27 % ) patients , including non-ST-elevation myocardial infa rct ion ( NSTEMI ) in 25 ( 13 % ) . Patients with acute myocardial infa rct ion had higher levels of hs-cTnT ( 50 [ 95 % confidence interval , 19 - 173 ] ng/L ) and us-copeptin ( 30 [ 13 - 113 ] pmol/L ) at admission compared with those without ( P < .05 ) . Combination of markers significantly improved receiver operating characteristic area under the curve ( from 0.89 [ 0.85 - 0.92 ] for hs-cTnT alone to 0.93 [ 0.89 - 0.97 ] , P = .018 ) . Sensitivity and negative predictive value were increased , particularly for NSTEMI diagnosis ( sensitivity , 76 % [ 54.9 - 90.6 ] to 96 % [ 79.6 - 99.9 ] ; negative predictive value , 95 % [ 90.4 - 98.3 ] to 98.9 % [ 94.2 to 100 ] ) . CONCLUSION Assessment of us-copeptin combined with hs-cTnT on ED admission could allow safe and early rule out of NSTEMI for patients with negative results on both markers and help identify patients who may be suitable for discharge We aim ed to assess the additive diagnostic value of measuring the serum levels of soluble human heart-type fatty acid binding protein ( H-FABP ) in the early diagnosis of acute myocardial infa rct ion ( AMI ) in unselected patients with chest pain . A total of 97 consecutive patients with acute ischemic-type chest pain were prospect ively enrolled and classified according to the American Heart Association/American College of Cardiology guidelines . The test characteristics of H-FABP and cardiac troponin T serum levels at admission revealed a greater sensitivity of H-FABP in the first 4 hours of symptoms ( 86 % vs 42 % , p < 0.05 ) . Combining H-FABP and cardiac troponin T also improved the sensitivity in the detection of AMI ( 97 % vs 71 % , p < 0.05 ) but demonstrated a greater misclassification rate ( 25 % vs 9 % , p < 0.05 ) . The specificity of H-FABP was poor ( 65 % , 95 % confidence interval 58 % to 71 % ) . Receiver operating characteristics revealed a poor performance of H-FABP in patients with non-ST-elevation myocardial infa rct ion . Classification tree analysis demonstrated that an H-FABP-related improvement in the early definite rule-out of AMI ( reduction of false-negative rate from 11 % to 3 % ) was at the expense of an increase in the false-positive rate to 5 % . In conclusion , measurement of H-FABP , in addition to cardiac troponin T , serum levels within the first 4 hours of symptoms improves the sensitivity and negative predictive value for the detection of AMI at the cost of test accuracy and precision , especially in patients with non-ST-elevation myocardial infa rct ion OBJECTIVES Early identification of myocardial infa rct ion in chest pain patients is crucial to identify patients at risk and to maintain a fast treatment initiation . BACKGROUND The aim of the current investigation is to test whether determination of copeptin , an indirect marker for arginin-vasopressin , adds diagnostic information to cardiac troponin in early evaluation of patients with suspected myocardial infa rct ion . METHODS Between January 2007 and July 2008 , patients with suspected acute coronary syndrome were consecutively enrolled in this multicenter study . Copeptin , troponin T ( TnT ) , myoglobin , and creatine kinase-myocardial b and were determined at admission and after 3 and 6 h. RESULTS Of 1,386 ( 66.4 % male ) enrolled patients , 299 ( 21.6 % ) had the discharge diagnosis of acute myocardial infa rct ion , 184 ( 13.3 % ) presented with unstable angina , and in 903 ( 65.2 % ) an acute coronary syndrome could be excluded . Combined measurement of copeptin and TnT on admission improved the c-statistic from 0.84 for TnT alone to 0.93 in the overall population and from 0.77 to 0.9 in patients presenting within 3 h after chest pain onset ( CPO ) ( p < 0.001 ) . In this group the combination of copeptin with a conventional TnT provided a negative predictive value of 92.4 % . CONCLUSIONS In triage of chest pain patients , determination of copeptin in addition to troponin improves diagnostic performance , especially early after CPO . Combined determination of troponin and copeptin provides a remarkable negative predictive value virtually independent of CPO time and therefore aids in early and safe rule-out of myocardial infa rct ion OBJECTIVES The study objective was to vali date a new high-sensitivity troponin I ( hs-TnI ) assay in a clinical protocol for assessing patients who present to the emergency department with chest pain . BACKGROUND Protocol s using sensitive troponin assays can accelerate the rule out of acute myocardial infa rct ion in patients with low-risk ( suspected ) acute coronary syndrome ( ACS ) . METHODS This study evaluated 2 prospect i ve cohorts of patients in the emergency department with ACS in an accelerated diagnostic pathway integrating 0- and 2-h hs-TnI results , Thrombolysis In Myocardial Infa rct ion ( TIMI ) risk scores , and electrocardiography . Strategies to identify low-risk patients incorporated TIMI risk scores= 0 or ≤ 1 . The primary endpoint was a major adverse cardiac event ( MACE ) within 30 days . RESULTS In the primary cohort , 1,635 patients were recruited and had 30-day follow-up . A total of 247 patients ( 15.1 % ) had a MACE . The finding of no ischemic electrocardiogram and hs-TnI ≤ 26.2 ng/l with the TIMI = 0 and TIMI ≤ 1 pathways , respectively , classified 19.6 % ( n = 320 ) and 41.5 % ( n = 678 ) of these patients as low risk ; 0 % ( n = 0 ) and 0.8 % ( n = 2 ) had a MACE , respectively . In the secondary cohort , 909 patients were recruited . A total of 156 patients ( 17.2 % ) had a MACE . The TIMI = 0 and TIMI ≤ 1 pathways classified 25.3 % ( n = 230 ) and 38.6 % ( n = 351 ) , respectively , of these patients as low risk ; 0 % ( n = 0 ) and 0.8 % ( n = 1 ) had a MACE , respectively . Sensitivity , specificity , and negative predictive value for TIMI = 0 in the primary cohort were 100 % ( 95 % confidence interval [ CI ] : 98.5 % to 100 % ) , 23.1 % ( 95 % CI : 20.9 % to 25.3 % ) , and 100 % ( 95 % CI : 98.8 % to 100 % ) , respectively . Sensitivity , specificity , and negative predictive value for TIMI ≤ 1 in the primary cohort were 99.2 ( 95 % CI : 97.1 to 99.8 ) , 48.7 ( 95 % CI : 46.1 to 51.3 ) , and 99.7 ( 95 % CI : 98.9 to 99.9 ) , respectively . Sensitivity , specificity , and negative value for TIMI ≤ 1 in the secondary cohort were 99.4 % ( 95 % CI : 96.5 to 100 ) , 46.5 % ( 95 % CI : 42.9 to 50.1 ) , and 99.7 % ( 95 % CI : 98.4 to 100 ) , respectively . CONCLUSIONS An early-discharge strategy using an hs-TnI assay and TIMI score ≤ 1 had similar safety as previously reported , with the potential to decrease the observation periods and admissions for approximately 40 % of patients with suspected ACS . ( Advantageous Predictors of Acute Coronary Syndromes Evaluation [ APACE ] Study , NCT00470587 ; A 2 hr Accelerated Diagnostic Protocol to Assess patients with chest Pain symptoms using contemporary Troponins as the only biomarker [ ADAPT ] : a prospect i ve observational validation study , ACTRN12611001069943 ) Objective The early diagnosis of acute myocardial infa rct ion ( AMI ) can be particularly challenging in patients with known coronary artery disease ( CAD ) due to pre-existing ECG changes and chronic increases in cardiac troponin ( cTn ) levels . Design Of 1170 consecutive patients presenting with symptoms suggestive of AMI , 433 ( 37 % ) with pre-existing CAD were analysed in a prospect i ve multicentre study and the diagnostic and prognostic impact of copeptin in combination with either fourth generation cardiac troponin T ( cTnT ) or high-sensitivity cTnT ( hs-cTnT ) was evaluated . Results AMI was the final diagnosis in 78 patients with pre-existing CAD ( 18 % ) . Copeptin was significantly higher in patients with AMI than in those without ( 26 pmol/l ( IQR 9–71 ) vs 7 pmol/l ( IQR 4–16 ) , p<0.001 ) . The diagnostic accuracy for AMI as quantified by the area under the receiver operating characteristic curve ( AUC ) was significantly higher for the combination of copeptin and cTnT than for cTnT alone ( 0.94 vs 0.86 , p<0.001 ) . The combination of copeptin and hs-cTnT ( 0.94 ) was trending to superiority compared with hs-cTnT alone ( 0.92 , p=0.11 ) . The combination of copeptin and the cTn assays was able to improve the negative predictive value up to 99.5 % to rule out AMI . Copeptin was a strong and independent predictor of 1-year mortality ( HR 4.18–4.63 ) . Irrespective of cTn levels , patients with low levels of copeptin had an excellent prognosis compared with patients with raised levels of both copeptin and cTn ( 360-day mortality 2.8–3.6 % vs 23.1–33.8 % , p<0.001 ) . Conclusion In patients with pre-existing CAD , copeptin significantly improves the diagnostic accuracy if used in addition to cTnT , but only trended to superiority compared with hs-cTnT alone . Copeptin provides independent prognostic information , largely by overcoming the challenging interpretation of mild increases in hs-cTnT. Clinical trial registration number Clinical Trials Gov number NCT00470587 |
12,346 | 19,960,231 | Abstract Should whole brain radiation therapy ( WBRT ) be used as the sole therapy in patients with newly-diagnosed , surgically accessible , single brain metastases , compared with WBRT plus surgical resection , and in what clinical setting s?Target population This recommendation applies to adults with newly diagnosed single brain metastases amenable to surgical resection ; however , the recommendation does not apply to relatively radiosensitive tumors histologies ( i.e. , small cell lung cancer , leukemia , lymphoma , germ cell tumors and multiple myeloma ) .
RecommendationS urgical resection plus WBRT versus WBRT aloneLevel 1 Class I evidence supports the use of surgical resection plus post-operative WBRT , as compared to WBRT alone , in patients with good performance status ( functionally independent and spending less than 50 % of time in bed ) and limited extra-cranial disease .
There is insufficient evidence to make a recommendation for patients with poor performance scores , advanced systemic disease , or multiple brain metastases .
Recommendation Level 1 Class I evidence suggests that altered dose/fractionation schedules of WBRT do not result in significant differences in median survival , local control or neurocognitive outcomes when compared with “ st and ard ” WBRT dose/fractionation . (
If WBRT is used , what impact does tumor histopathology have on treatment outcomes ?
Recommendation Given the extremely limited data available , there is insufficient evidence to support the choice of any particular dose/fractionation regimen based on histopathology .
RecommendationS urgical resection plus WBRT versus surgical resection aloneLevel 1 Surgical resection followed by WBRT represents a superior treatment modality , in terms of improving tumor control at the original site of the metastasis and in the brain overall , when compared to surgical resection alone | null | null |
12,347 | 22,007,076 | We found no evidence that statins were associated with intracerebral hemorrhage ; if such a risk is present , its absolute magnitude is likely to be small and outweighed by the other cardiovascular benefits of these drugs | BACKGROUND A recent large , r and omized trial suggested that statins may increase the risk of intracerebral hemorrhage .
Accordingly , we systematic ally review ed the association of statins with intracerebral hemorrhage in r and omized and observational data . | Background — Prior primary prevention trials of statin therapy that used cholesterol criteria for enrollment have not reported significant decreases in stroke risk . We evaluated whether statin therapy might reduce stroke rates among individuals with low levels of cholesterol but elevated levels of high-sensitivity C-reactive protein . Methods and Results — In Justification for the Use of statins in Prevention : an Intervention Trial Evaluating Rosuvastatin ( JUPITER ) , 17 802 apparently healthy men and women with low-density lipoprotein cholesterol levels < 130 mg/dL and high-sensitivity C-reactive protein levels ≥2.0 mg/L were r and omly allocated to rosuvastatin 20 mg daily or placebo and then followed up for the occurrence of a first stroke . After a median follow-up of 1.9 years ( maximum , 5.0 years ) , rosuvastatin result ed in a 48 % reduction in the hazard of fatal and nonfatal stroke as compared with placebo ( incidence rate , 0.18 and 0.34 per 100 person-years of observation , respectively ; hazard ratio 0.52 ; 95 % confidence interval , 0.34 to 0.79 ; P=0.002 ) , a finding that was consistent across all examined subgroups . This finding was due to a 51 % reduction in the rate of ischemic stroke ( hazard ratio , 0.49 ; 95 % confidence interval , 0.30 to 0.81 ; P=0.004 ) , with no difference in the rates of hemorrhagic stroke between the active and placebo arms ( hazard ratio , 0.67 ; 95 % confidence interval , 0.24 to 1.88 ; P=0.44 ) . Conclusion — Rosuvastatin reduces by more than half the incidence of ischemic stroke among men and women with low levels of low-density lipoprotein cholesterol levels who are at risk because of elevated levels of high-sensitivity C-reactive protein . Clinical Trial Registration — clinical trial.gov . Unique identifier : NCT00239681 Background Patients with end-stage renal disease ( ESRD ) are at high risk of cardiovascular events . Multiple risk factors for atherosclerosis are present in ESRD and may contribute to the increased risk of cardiovascular mortality in this population . In contrast to patients with normal renal function , the benefits of modifying lipid levels on cardiovascular outcomes in patients with ESRD on haemodialysis have yet to be confirmed in large prospect i ve r and omised trials . A study to evaluate the Use of Rosuvastatin in subjects On Regular haemodialysis : an Assessment of survival and cardiovascular events ( AURORA ) will be the first large-scale international trial to assess the effects of statin therapy on cardiovascular morbidity and mortality in ESRD patients on chronic haemodialysis . Methods More than 2,750 ESRD patients who have been receiving chronic haemodialysis treatment for at least 3 months have been r and omised ( 1:1 ) , irrespective of baseline lipid levels , to treatment with rosuvastatin 10 mg or placebo . The primary study endpoint is the time to a major cardiovascular event ( first occurrence of cardiovascular death , non-fatal myocardial infa rct ion or non-fatal stroke ) . Secondary endpoints include all-cause mortality , major cardiovascular event-free survival time , time to cardiovascular death , time to non-cardiovascular death , cardiovascular interventions , tolerability of treatment and health economic costs per life-year saved . Study medication will be given until 620 subjects have experienced a major cardiovascular event . Conclusion Our hypothesis is that results from AURORA will establish the clinical efficacy and tolerability of rosuvastatin in patients with ESRD receiving chronic haemodialysis and guide the optimal management of this exp and ing population BACKGROUND Clopidogrel is a more potent antiplatelet agent than aspirin , result ing in greater clinical efficacy in patients with atherothrombotic disease . Furthermore , the combination of clopidogrel plus aspirin has been demonstrated to be superior to aspirin alone in the treatment of patients with acute coronary syndromes and after coronary stenting . Whether dual antiplatelet therapy is superior to aspirin monotherapy for high-risk primary prevention and secondary prevention is unknown . METHODS AND RESULTS The Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization , Management , and Avoidance ( CHARISMA ) study was design ed to evaluate the efficacy and safety of clopidogrel plus aspirin versus placebo plus aspirin in patients with established coronary , cerebral , or peripheral arterial disease or in patients with multiple risk factors for atherothrombosis who have not yet sustained an ischemic event . This r and omized , international , multicenter , double-blinded , placebo-controlled study has finished enrolling patients worldwide . A total of 15,603 patients will be followed long term . The primary end point will be the composite of vascular death , myocardial infa rct ion , or stroke . Rates of severe bleeding will also be compared between the two arms of the study . CONCLUSIONS This large-scale trial of patients at high risk for atherothrombotic events will allow determination of the value of a strategy of adding clopidogrel to the current st and ard of care , including low-dose aspirin , for a wide spectrum of patients with atherothrombosis Background and Purpose — Intracerebral hemorrhage ( ICH ) has a 30-day mortality rate of 40 % to 50 % and lacks a proven treatment . We report a preplanned , midpoint analysis of the first population -based , case-control study that examines both genetic and environmental risk factors of ICH . Methods — We prospect ively identified cases of hemorrhagic stroke at all 16 hospitals in the Greater Cincinnati/Northern Kentucky region . All cases underwent medical record and neuroimaging review . Cases enrolled in the direct interview and genetic sampling arm of the study were matched to population -based control subjects by age , race , and sex . Multivariable logistic regression was performed to identify significant independent risk factors . Results — We enrolled 188 cases of ICH ( 67 lobar , 121 nonlobar ) and 366 control subjects in the direct interview arm of the study . Significant independent risk factors for lobar ICH included the presence of an apolipoprotein E2 or E4 allele , frequent alcohol use , prior stroke , and first-degree relative with ICH . Significant independent risk factors for nonlobar ICH were hypertension , prior stroke , and first-degree relative with ICH . An increasing level of education was associated with a decreased risk of nonlobar ICH . The attributable risk of apolipoprotein E2 or E4 for lobar ICH was 29 % , and the attributable risk of hypertension for nonlobar ICH was 54 % . Conclusions — There is significant epidemiological evidence that the pathophysiology of ICH varies by location . We estimate that a third of all cases of lobar ICH are attributable to possession of an apolipoprotein E4 or E2 allele and that half of all cases of nonlobar ICH are attributable to hypertension BACKGROUND The role of lipid modification in stroke prevention is controversial , although increasing evidence suggests that HMG-CoA reductase inhibition may reduce cerebrovascular events in patients with prevalent coronary artery disease . METHODS AND RESULTS To test the hypothesis that cholesterol reduction with pravastatin may reduce stroke incidence after myocardial infa rct ion , we followed 4159 subjects with average total and LDL serum cholesterol levels ( mean , 209 and 139 mg/dL , respectively ) who had sustained an infa rct ion an average of 10 months before study entry and who were r and omized to pravastatin 40 mg/d or placebo in the Cholesterol and Recurrent Events ( CARE ) trial . Using prospect ively defined criteria , we assessed the incidence of stroke , a prespecified secondary end point , and transient ischemic attack ( TIA ) over a median 5-year follow-up period . Patients were well matched for stroke risk factors and the use of antiplatelet agents ( 85 % of subjects in each group ) . Compared with placebo , pravastatin lowered total serum cholesterol by 20 % , LDL cholesterol by 32 % , and triglycerides by 14 % and raised HDL cholesterol by 5 % over the course of the trial . A total of 128 strokes ( 52 on pravastatin , 76 on placebo ) and 216 strokes or TIAs ( 92 on pravastatin , 124 on placebo ) were observed , representing a 32 % reduction ( 95 % CI , 4 % to 52 % , P=0.03 ) in all-cause stroke and 27 % reduction in stroke or TIA ( 95 % CI , 4 % to 44 % , P=0.02 ) . All categories of strokes were reduced , and treatment effect was similar when adjusted for age , sex , history of hypertension , cigarette smoking , diabetes , left ventricular ejection fraction , and baseline total , HDL , and LDL cholesterol and triglyceride levels . There was no increase in hemorrhagic stroke in patients on pravastatin compared with placebo ( 2 versus 6 , respectively ) . CONCLUSIONS Pravastatin significantly reduced stroke and stroke or TIA incidence after myocardial infa rct ion in patients with average serum cholesterol levels despite the high concurrent use of antiplatelet therapy Background —This report describes the effect of intensive cholesterol lowering with atorvastatin on the incidence of nonfatal stroke , a secondary end point , in a r and omized , placebo-controlled trial of patients with unstable angina or non-Q-wave myocardial infa rct ion . The primary end point , a composite of death , nonfatal myocardial infa rct ion , resuscitated cardiac arrest , or recurrent symptomatic myocardial ischemia with objective evidence requiring emergency rehospitalization , was reduced from 17.4 % in the placebo group to 14.8 % in the atorvastatin group over the 16 weeks of the trial ( P = 0.048 ) . Methods and Results —Strokes were adjudicated by a blinded end-point committee using st and ard clinical and imaging criteria . The outcomes of nonfatal stroke and fatal plus nonfatal stroke were analyzed by time to first occurrence during the 16-week trial . Of 38 events ( in 36 patients ) adjudicated as fatal or nonfatal strokes , 3 were classified as hemorrhagic , one as embolic , and 29 as thrombotic or embolic ; 5 could not be categorized . Nonfatal stroke occurred in 9 patients in the atorvastatin group and 22 in the placebo group ( relative risk , 0.40 ; 95 % confidence intervals , 0.19 to 0.88;P = 0.02 ) . Fatal or nonfatal stroke occurred in 12 atorvastatin patients and 24 placebo patients ( relative risk , 0.49 ; 95 % confidence intervals , 0.24 to 0.98;P = 0.04 ) . All 3 hemorrhagic strokes occurred in the placebo group . Conclusion —Intensive cholesterol lowering with atorvastatin over 16 weeks in patients with acute coronary syndromes reduced the overall stroke rate by half and did not cause hemorrhagic stroke . These findings need to be confirmed in future trials The FAST MI registry was design ed to evaluate the ' real world ' management of patients with acute myocardial infa rct ion ( MI ) , and to assess their in-hospital , medium- and long-term outcomes . Patients were recruited consecutively from intensive care units over a period of one month ( from October 2005 ) , with an additional one-month recruitment period for diabetic patients . The study included 3059 MI patients in phase 1 and an additional 611 diabetic patients in phase 2 . Altogether , 53 % of the patients had a final diagnosis of Q wave MI and 47 % had non Q wave MI . Patients with Q wave MI were more likely to be men , younger , more frequently with a family history or a history of smoking . Patients with non Q wave MI had worst baseline demographic and clinical characteristics mainly explained by their older age . Time from symptom onset to hospital admission was less than three hours for 22 % of the patients with Q wave MI and for 14 % of the non Q wave MI patients . Among patients with Q wave MI , 64 % received reperfusion therapy , 35 % with primary percutaneous coronary interventions , 19 % with pre-hospital thrombolysis and 10 % with in-hospital thrombolysis . Over 70 % of patients received statin therapy during the hospital stay and over 90 % anti platelet agents . In-hospital mortality was 5.8 % in patients with Q wave MI and 4.9 % in patients with non Q Wave MI . At discharge beta-adrenergic blockers and statins and , to a lesser extent , medications of the renin angiotensin system were commonly prescribed . Over 90 % received antiplatelet agents BACKGROUND Platelets play a key role in the pathogenesis of atherosclerosis , thrombosis , and acute coronary and cerebrovascular syndromes . Inhibition of platelet function by acetylsalicylic acid ( aspirin ) has been shown to reduce the incidence atherothrombotic events in patients with coronary , cerebrovascular , or peripheral vascular disease . Thienopyridine agents , however , including ticlopidine and clopidogrel , inhibit the adenosine diphosphate receptor and have modestly superior effects compared with aspirin on reduction of death , myocardial infa rct ion , and stroke among a broad group of patients with vascular disease . More effective antithrombotic agents are still required to treat patients at high risk for recurrent vascular events . METHODS Lotrafiban , a selective , nonpeptide antagonist of the human platelet fibrinogen receptor ( glycoprotein [ GP ] IIb/IIIa [ alphaIIb/beta3 integrin ] ) , blocks the binding of fibrinogen to the GP IIb/IIIa receptor , which is the final common pathway of platelet aggregation . Lotrafiban at doses of up to 50 mg twice daily was well-tolerated in a 12-week , double-blind , placebo-controlled , dose-ranging study in patients with recent myocardial infa rct ion , unstable angina , transient ischemic attack , or stroke when added to aspirin therapy . On the basis of these results , a dosing regimen was selected for the phase III Blockage of the Glycoprotein IIb/IIIa Receptor to Avoid Vascular Occlusion ( BRAVO ) trial based on pharmacodynamics and drug tolerability . In the pivotal BRAVO study , lotrafiban therapy is being evaluated in patients who have had a recent myocardial infa rct ion , unstable angina , transient ischemic attack , or ischemic stroke , or who present at any time after a diagnosis of peripheral vascular disease combined with either cardiovascular or cerebrovascular disease . RESULTS The efficacy evaluation will be based on a composite end point of clinical events ( death by any cause , myocardial infa rct ion , stroke , recurrent ischemia requiring hospitalization , or urgent ischemia-driven revascularization ) . The target enrollment is 9200 patients worldwide . Approximately 700 centers will participate and will be distributed within 30 countries across North America , Europe , Australia , and Asia The goal of the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering ( MIRACL ) study is to determine whether early , rapid , and profound cholesterol lowering therapy with atorvastatin can reduce early recurrent ischemic events in patients with unstable angina or non-Q-wave acute myocardial infa rct ion . Within 1 to 4 days of hospitalization for one of these conditions , 2,100 patients will be r and omly assigned to receive atorvastatin , 80 mg/day , or placebo in a double-blind design . Both groups receive dietary counseling . Over a 16-week follow-up period , the primary outcome measure is the time to occurrence of an ischemic event , defined as death , nonfatal acute myocardial infa rct ion , cardiac arrest with resuscitation , or recurrent symptomatic myocardial ischemia requiring emergency rehospitalization . Secondary outcome measures are the time to occurrence and incidence of each of the primary outcome components , as well as nonfatal stroke , worsening angina , congestive heart failure requiring hospitalization , and need for coronary revascularization not anticipated before r and omization . The sample size of 1,050 patients in each group is expected to provide 95 % power to detect a 30 % reduction in the primary outcome measure with a 5 % level of significance . The results of the MIRACL study will determine the utility of profound cholesterol lowering as an early intervention in acute coronary syndromes OBJECTIVE The primary aim of the Perindopril Protection Against Recurrent Stroke Study ( PROGRESS ) is to determine the effects of a long-term angiotensin converting enzyme (ACE)-inhibitor-based blood-pressure-lowering regimen on the risk of stroke among patients with a history of stroke or transient ischaemic attack ( TIA ) . Secondary aims include investigation of the effects of treatment on total cardiovascular events , dementia and disability . DESIGN AND METHODS PROGRESS is a double-blind , placebo-controlled r and omized trial . Patients were r and omly assigned to treatment with the ACE inhibitor perindopril ( and the diuretic indapamide for those with no definite indication or contraindication to treatment with a diuretic ) versus matching placebo(s ) . Both hypertensive and non-hypertensive patients were eligible for inclusion . Follow-up is scheduled for completion in 2001 . The study is being conducted in 172 centres in 10 countries ( Australia , Belgium , China , France , Italy , Irel and , Japan , New Zeal and , Sweden and the United Kingdom ) . RESULTS Recruitment was completed in November 1997 , with 6105 patients r and omized . Mean age of participants at study entry was 64 years , 30 % of whom were female , 84 % had an entry diagnosis of stroke , and the remainder had an entry diagnosis of TIA alone . Mean baseline blood pressure was 147/86 mm Hg , with about half the patients reporting current drug treatment for hypertension . At r and omization , 58 % of patients were assigned to combination treatment with both study drugs versus placebos , and 42 % were assigned to perindopril alone versus placebo . CONCLUSIONS The successful completion of recruitment , together with current indicators of statistical power , suggest that PROGRESS should achieve its primary aim on schedule The Heart and Estrogen/progestin Replacement Study ( HERS ) is a r and omized , double-blind , placebo-controlled trial design ed to test the efficacy and safety of estrogen plus progestin therapy for prevention of recurrent coronary heart disease ( CHD ) events in women . The participants are postmenopausal women with a uterus and with CHD as evidence d by prior myocardial infa rct ion , coronary artery bypass graft surgery , percutaneous transluminal coronary angioplasty , or other mechanical revascularization or at least 50 % occlusion of a major coronary artery . Between February 1993 and September 1994 , 20 HERS centers recruited and r and omized 2763 women . Participants ranged in age from 44 to 79 years , with a mean age of 66.7 ( SD 6.7 ) years . Most participants were white ( 89 % ) , married ( 57 % ) , and had completed high school or some college ( 80 % ) . As expected , the prevalence of coronary risk factors was high : 62 % were past or current smokers , 59 % had hypertension , 90 % had serum LDL-cholesterol of 100 mg/dL or higher , and 23 % had diabetes . Each woman was r and omly assigned to receive one tablet containing 0.625 mg conjugated estrogens plus 2.5 mg medroxyprogesterone acetate daily or an identical placebo . Participants will be evaluated every 4 months for an average of 4.2 years for the occurrence of CHD events ( CHD death and nonfatal myocardial infa rct ion ) . We will also assess other major CHD endpoints , including revascularization and hospitalization for unstable angina . The primary analysis will compare the rate of CHD events in women assigned to active treatment with the rate in those assigned to placebo . The trial was design ed to have power greater than 90 % to detect a 35 % reduction in the incidence of CHD events , assuming a 50 % lag in effect for 2 years and a 5 % annual event rate in the placebo group . The design , analysis , and conduct of the study are controlled by the Steering Committee of Principal Investigators and coordinated at the University of California , San Francisco . HERS is the largest trial of any intervention to reduce the risk of recurrent CHD events in women with heart disease and is the first controlled trial to seek evidence of the efficacy and safety of postmenopausal hormone therapy to prevent recurrent CHD events BACKGROUND Previous prospect i ve outcome studies of statins have not provided any guidance on benefit-risk in patients with heart failure . AIM The primary objective is to determine whether rosuvastatin ( 10 mg ) reduces the combined endpoint of cardiovascular mortality , non-fatal myocardial infa rct ion or non-fatal stroke ( time to first event ) . The first secondary endpoint is all-cause mortality . METHODS CORONA is a r and omized , double-blind , placebo-controlled trial . Briefly , men and women , aged > or = 60 years with chronic symptomatic systolic heart failure of ischemic aetiology and ejection fraction < or = 0.40 ( NYHA class III and IV ) or < or = 0.35 ( NYHA class II ) were eligible if they were not using or in need of cholesterol lowering drugs . RESULTS Mean age was 73 years ( n=5016 ; 24 % women ) , with 37 % in NYHA II and 62 % in NYHA III , ejection fraction 0.31 , total cholesterol 5.2 mmol/L. Sixty percent have a history of myocardial infa rct ion , 63 % hypertension , and 30 % diabetes . Patients are well treated for heart failure with 90 % on loop or thiazide diuretics , 42 % aldosterone antagonists , 91 % ACE inhibitor or AT-I blocker , 75 % beta-blockers , and 32 % digitalis . CONCLUSION CORONA is important for three main reasons : ( 1 ) A positive result is very important because of the high risk of the population studied , the increasing prevalence of elderly patients with chronic symptomatic systolic heart failure in our society , and the health economic issues involved . ( 2 ) If negative , new mechanistic questions about heart failure have to be raised . ( 3 ) If neutral we can avoid unnecessary polypharmacy This report describes the design and baseline results of the Kyushu Lipid Intervention Study ( KLIS ) . The study aims to test the hypothesis that the long term reduction of serum total cholesterol by pravastatin will lead to a decrease in coronary heart disease ( CHD ) events . The trial was design ed to include a r and om 6,000 male patients aged 45 - 74 years with serum total cholesterol of 220 mg/dl ( 5.69 mmol/l ) or greater and without a history of myocardial infa rct ion , coronary surgery or angioplasty , to undertake either pravastatin or conventional treatment ( including hypolipidemic drugs other than HMG CoA reductase inhibitors , probucol and bezafibrate ) , and to follow up each patient for 5 years . Primary endpoints are fatal and nonfatal myocardial infa rct ion , coronary bypass surgery and angioplasty , cardiac death , and sudden and unexpected death . During the period from May 1990 to September 1993 , a total of 5,640 male patients aged 45 - 74 were recruited by 902 participating physicians throughout Kyushu . R and omization was , however , neglected by study physicians ; the numbers of patients enrolled were 3,061 in the pravastatin group and 2,579 in the conventional treatment group . Patients allocated to the pravastatin treatment were generally unfavorable regarding coronary risk factors . Baseline mean levels of serum total cholesterol were 259 mg/dl ( 6.70 mmol/l ) in the pravastatin group and 246 mg/dl ( 6.36 mmol/l ) in the conventional treatment group ( p < 0.001 ) . Although the trial was regarded as a prospect i ve observational study , the KLIS provides valuable quantitative data regarding cholesterol lowering and reduction in CHD events as well as safety data of the long-term use of a statin in Japanese men with hypercholesterolemia BACKGROUND Stroke is a rare but serious event that complicates the course of patients with acute coronary syndromes ( ACS ) . The type , outcome , and risk factors of stroke occurring in stabilized patients with ACS have not been previously reported . METHODS We evaluated stroke incidence , subtypes , and outcomes , in addition to demographics and clinical risk characteristics associated with stroke among patients enrolled in the Sibrafiban versus Aspirin to Yield Maximum Protection from Ischemic Heart Events Post-acute Coronary Syndromes ( SYMPHONY ) and 2nd SYMPHONY trials . RESULTS Of 15,904 stabilized patients with ACS , 113 ( 0.71 % ) had a stroke over a median follow-up of 90 days . The majority of strokes occurred within 30 days of presentation , and the time course for stroke occurrence paralleled that of myocardial (re)infa rct ion . Most strokes were ischemic ( 78 % ) , and 52 % result ed in moderate or severe disability or death . Patients with stroke were older and more often had hypertension , diabetes , peripheral vascular disease , and atrial fibrillation . Among patients with stroke who had cardiac catheterization , percutaneous coronary intervention , or coronary artery bypass grafting , stroke occurred predominantly after the procedure . No difference in occurrence or type of stroke was observed in the assigned treatment groups . In multivariable modeling age , heart failure , prior stroke , left bundle branch block , and systolic blood pressure predicted the occurrence of stroke . CONCLUSIONS In patients stabilized after presenting with a spectrum of ACS and treated with sibrafiban and /or aspirin , stroke occurred in fewer than 1 % within 90 days but carried a significant mortality and morbidity risk Are newer types of antihypertensive agents , which are currently more costly to purchase on average , as good or better than diuretics in reducing coronary heart disease incidence and progression ? Will lowering LDL cholesterol in moderately hypercholesterolemic older individuals reduce the incidence of cardiovascular disease and total mortality ? These important medical practice and public health questions are to be addressed by the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial ( ALLHAT ) , a r and omized , double-blind trial in 40,000 high-risk hypertensive patients . ALLHAT is design ed to determine whether the combined incidence of fatal coronary heart disease ( CHD ) and nonfatal myocardial infa rct ion differs between persons r and omized to diuretic ( chlorthalidone ) treatment and each of three alternative treatments -- a calcium antagonist ( amlodipine ) , an angiotensin converting enzyme inhibitor ( lisinopril ) , and an alpha-adrenergic blocker ( doxazosin ) . ALLHAT also contains a r and omized , open-label , lipid-lowering trial design ed to determine whether lowering LDL cholesterol in 20,000 moderately hypercholesterolemic patients ( a subset of the 40,000 ) with a 3-hydroxymethylglutaryl coenzyme A ( HMG CoA ) reductase inhibitor , pravastatin , will reduce all-cause mortality compared to a control group receiving " usual care . " ALLHAT 's main eligibility criteria are : 1 ) age 55 or older ; 2 ) systolic or diastolic hypertension ; and 3 ) one or more additional risk factors for heart attack ( eg , evidence of atherosclerotic disease or type II diabetes ) . For the lipid-lowering trial , participants must have an LDL cholesterol of 120 to 189 mg/dL ( 100 to 129 mg/dL for those with known CHD ) and a triglyceride level below 350 mg/dL. The mean duration of treatment and follow-up is planned to be 6 years . Further features of the rationale , design , objectives , treatment program , and study organization of ALLHAT are described in this article Background . The incidence of stroke and risk factors for different subtypes of cerebrovascular ( CBV ) events in renal transplant recipients have not been examined in any large prospect i ve controlled trial . Methods . The Assessment of Lescol in Renal Transplantation was a r and omized , double-blind , placebo-controlled study of the effect of fluvastatin ( 40–80 mg ) daily on cardiovascular , and renal outcomes in renal transplant recipients . Patients initially r and omized to fluvastatin or placebo in the 5 to 6 year trial was offered open-label fluvastatin in a 2-year extension to the original study . We investigated the incidence of stroke and risk factors for ischemic and hemorrhagic CBV events in 2102 renal graft recipients participating in the Assessment of Lescol in Renal Transplantation core and extension trial with a mean follow-up of 6.7 years . Results . The incidence and type of CBV events did not differ between the lipid lowering arm and the placebo arm . A total of 184 ( 8.8 % , 95 % confidence interval 4.6–12.9 ) of 2102 patients experienced a CBV event during follow-up , corresponding to an incidence of 1.3 % CBV event per year . The mortality for patients experiencing a hemorrhagic stroke was 48 % ( 13 of 27 ) , whereas the mortality for ischemic strokes was 6.0 % ( 8 of 133 ) . Diabetes mellitus , previous CBV event , age , and serum creatinine were independent risk factors for cerebral ischemic events . The risk of a hemorrhagic cerebral event was increased by diabetes mellitus , polycystic kidney disease , left ventricular hypertrophy , and systolic blood pressure . Interpretation . Risk factors for CBV events in renal transplant recipients differ according to subtype Recent clinical trials of primary and secondary prevention of cardiovascular disease have demonstrated that lowering plasma cholesterol decreases the incidence of coronary heart disease in patients with elevated plasma cholesterol . However , it is not known whether patients with established coronary artery disease and normal plasma cholesterol can be benefited . Several previous prevention trials review ed in this report found that patients who had plasma cholesterol levels at baseline in the upper portion of the eligibility range ( e.g. , greater than 240 mg/dl ) received greater benefit from hypolipidemic diet or drug therapy than patients who had lower plasma cholesterol levels at baseline . The recent availability of drugs that are more potent and less prone to cause adverse reactions than previous regimens permits this important question to be addressed . The Cholesterol and Recurrent Events trial is testing whether pravastatin , a hydroxymethylglutaryl coenzyme A reductase inhibitor , will decrease the sum of fatal coronary heart disease and nonfatal myocardial infa rct ion ( MI ) in patients who have recovered from a MI and who have normal total cholesterol levels . Fatal cardiovascular disease and total mortality are important secondary end points . The trial is enrolling 4,000 men and women from 80 centers throughout North America , age 21 to 75 years , who have survived MI for 3 to 20 months , who have plasma total cholesterol less than 240 mg/dl ( 6.2 mmol/liter ) and low-density cholesterol of 115 to 174 mg/dl ( 3.0 to 4.5 mmol/liter ) , and who are representative of the general population of patients with MI . Patients are r and omized to either active or inactive drug therapy . Active therapy consists of pravastatin , 40 mg/day , design ed to achieve an average decrease in low-density lipoprotein cholesterol of approximately 30 % , and an increase in high-density lipoprotein of 5 % . The average duration of follow-up will be greater than or equal to 5 years . To protect against a lower than expected rate of recurrent events , the trial will be continued until a predetermined fixed number of coronary heart disease events occurs in the entire cohort so that the original sensitivity of the trial will be maintained BACKGROUND The GISSI Heart Failure project is a large-scale , r and omized , double-blind study design ed to investigate the effects of n-3 polyunsaturated fatty acids and rosuvastatin on mortality and morbidity in patients with symptomatic heart failure . METHODS AND RESULTS Patients with New York Heart Association classes II to IV heart failure , already receiving optimized recommended therapy , will be recruited in a nation-wide network of more than 300 cardiology and internal medicine services to be r and omly allocated to treatment with n-3 polyunsaturated fatty acids ( 1 g daily ) or the corresponding placebo . Patients with no clear indication or contraindication to cholesterol-lowering therapy will be further r and omized to receive low-dose rosuvastatin ( 10 mg daily ) or placebo . According to data available in heart failure registries , it is expected that 70 % of the patients will be suitable to enter both components of the trial , which assume the same co- primary endpoints : ( a ) 15 % reduction of all-cause mortality and ( b ) 20 % reduction of all-cause mortality or cardiovascular hospitalizations . The trial is event-driven and will continue either until at least 1252 deaths have been recorded or a reduction of all-cause mortality will satisfy the significance boundaries , which have been established to stop the study . The recruitment of the planned sample size of approximately 7000 patients r and omized in the n-3 PUFA trial is expected to be completed within 18 months from the trial start . As of February 29 , 2004 , 4624 heart failure patients have been included in the trial . CONCLUSION The GISSI-HF project , with its protocol articulated into two independent r and omization schemes , has the aim and the power to verify the hypothesis that n-3 polyunsaturated fatty acids and rosuvastatin can favorably modify the prognosis of patients with symptomatic heart failure BACKGROUND Long-term statin treatment reduces the frequency of cardiovascular events , but safety and efficacy in patients with abnormal liver tests is unclear . We assessed whether statin therapy is safe and effective for these patients through post-hoc analysis of the Greek Atorvastatin and Coronary Heart Disease Evaluation ( GREACE ) study population . METHODS GREACE was a prospect i ve , intention-to-treat study that r and omly assigned by a computer-generated r and omisation list 1600 patients with coronary heart disease ( aged < 75 years , with serum concentrations of LDL cholesterol > 2·6 mmol/L and triglycerides < 4·5 mmol/L ) at the Hippokration University Hospital , Thessaloniki , Greece to receive statin or usual care , which could include statins . The primary outcome of our post-hoc analysis was risk reduction for first recurrent cardiovascular event in patients treated with a statin who had moderately abnormal liver tests ( defined as serum alanine aminotransferase or aspartate aminotransferase concentrations of less than three times the upper limit of normal ) compared with patients with abnormal liver tests who did not receive a statin . This risk reduction was compared with that for patients treated ( or not ) with statin and normal liver tests . FINDINGS Of 437 patients with moderately abnormal liver tests at baseline , which were possibly associated with non-alcoholic fatty liver disease , 227 who were treated with a statin ( mainly atorvastatin 24 mg per day ) had substantial improvement in liver tests ( p<0·0001 ) whereas 210 not treated with a statin had further increases of liver enzyme concentrations . Cardiovascular events occurred in 22 ( 10 % ) of 227 patients with abnormal liver tests who received statin ( 3·2 events per 100 patient-years ) and 63 ( 30 % ) of 210 patients with abnormal liver tests who did not receive statin ( 10·0 events per 100 patient-years ; 68 % relative risk reduction , p<0·0001 ) . This cardiovascular disease benefit was greater ( p=0·0074 ) than it was in patients with normal liver tests ( 90 [ 14 % ] events in 653 patients receiving a statin [ 4·6 per 100 patient-years ] vs 117 [ 23 % ] in 510 patients not receiving a statin [ 7·6 per 100 patient-years ] ; 39 % relative risk reduction , p<0·0001 ) . Seven ( < 1 % ) of 880 participants who received a statin discontinued statin treatment because of liver-related adverse effects ( transaminase concentrations more than three-times the upper limit of normal ) . INTERPRETATION Statin treatment is safe and can improve liver tests and reduce cardiovascular morbidity in patients with mild-to-moderately abnormal liver tests that are potentially attributable to non-alcoholic fatty liver disease . FUNDING None Objective To test the primary hypothesis that a newer antihypertensive treatment regimen ( calcium channel blocker ± an angiotensin converting enzyme inhibitor ) is more effective than an older regimen ( β-blocker ± a diuretic ) in the primary prevention of coronary heart disease ( CHD ) . To test a second primary hypothesis that a statin compared with placebo will further protect against CHD endpoints in hypertensive subjects with a total cholesterol ⩽ 6.5 mmol/l . Design Prospect i ve , r and omized , open , blinded endpoint trial with a double-blinded 2 × 2 factorial component . Setting Patients were recruited mainly from general practice s. Patients Men and women aged 40–79 were eligible if their blood pressure was ⩾160 mmHg systolic or ⩾ 100 mmHg diastolic ( untreated ) or ⩾140 mmHg systolic or ⩾ 90 mmHg diastolic ( treated ) at r and omization . Interventions Patients received either amlodipine ( 5/10 mg ) ± perindopril ( 4/8 mg ) or atenolol ( 50/100 mg ) ± bendroflumethiazide ( 1.25/2.5 mg ) + K+ with further therapy as required to reach a blood pressure of ⩽140 mmHg systolic and 90 mmHg diastolic . Patients with a total cholesterol of ⩽ 6.5 mmol/l were further r and omized to receive either atorvastatin 10 mg or placebo daily . Main outcome measure Non-fatal myocardial infa rct ion ( MI ) and fatal coronary heart disease ( CHD ) . Results 19 342 men and women were initially r and omized , of these 10 297 were also r and omized into the lipid-lowering limb . All patients had three or more additional cardiovascular risk factors . Conclusions The study has 80 % power ( at the 5 % level ) to detect a relative difference of 20 % in CHD endpoints between the calcium channel blocker-based regimen and the β-blocker-based regimen . The lipid-lowering limb of the study has 90 % power at the 1 % level to detect a relative difference of 30 % in CHD endpoints between groups Background Recent clinical trials of primary and secondary prevention of cardiovascular disease have demonstrated that lowering plasma cholesterol with 3-hydroxy-3-methylglutaryl coenzyme A ( HMG CoA ) reductase inhibitors ( ‘ statins ’ ) reduces morbidity and mortality from coronary heart disease in diverse patient population s. Study aims The aim of the present ALERT ( Assessment of Lescol ® in Renal Transplantation ) study is to determine whether renal transplant recipients would also benefit from statin therapy . ALERT is a multicentre , r and omized , double-blind , placebo-controlled trial to assess the effect of fluvastatin in renal transplant recipients with mild-to-moderate hypercholesterolaemia . The primary objective is to investigate the effects of fluvastatin on major adverse cardiac events ( MACE ) . In addition , the effects on cardiovascular and all-cause mortality , as well as renal function , will be addressed . Study population The study population contains patients with functioning renal allografts of more than 6 months ' duration , recruited from 75 centres in Northern Europe and Canada . Patients of both sexes , aged 30 - 75 years , with a total cholesterol level of 4.0 - 9.0 mmol/l ( 155 - 348 mg/dl ) were included , except for those with a history of myocardial infa rct ion , where the upper limit for inclusion was 7.0∗∗∗mmol/l ( 270 mg/dl ) . Study design A total of 2100 patients were recruited by the end of October 1997 and will be followed for up to 6 years . This report presents the design features of the study ( recruitment , follow-up , sample size , data analysis and study organization ) , along with baseline results . ALERT is the first large-scale prospect i ve , r and omized , double-blind study to address the prevention of cardiovascular mortality in renal transplant patients receiving an HMGCoA reductase inhibitor The Air Force/Texas Coronary Atherosclerosis Prevention Study ( AFCAPS/TexCAPS ) is a r and omized , double-blind , placebo-controlled primary prevention trial . It is design ed to test the hypothesis that in addition to a lipid-lowering diet , treatment with lovastatin is more effective than placebo in reducing acute major coronary events ( i.e. , sudden cardiac death , fatal and nonfatal myocardial infa rct ion , and unstable angina ) in a cohort with normal to mildly elevated total ( 180 to 264 mg/dl ) and low-density lipoprotein ( LDL ) cholesterol ( 130 to 190 mg/dl ) and low high-density lipoprotein ( HDL ) cholesterol ( < or = 45 mg/dl for men and < or = 47 mg/dl for women ) . Two sites in Texas , Lackl and Air Force Base in San Antonio and the University of North Texas Health Science Center in Fort Worth , will conduct the study . After at least 12 weeks of an American Heart Association Step 1 diet and 2 weeks placebo run-in , 6,605 men and women , ages 45 to 73 and 55 to 73 years , respectively , without clinical evidence of coronary heart disease , are r and omized in equal numbers to either lovastatin ( 20 mg/day ) or placebo . Study procedures maintain the blind , allowing titration of lovastatin from 20 to 40 mg/day to achieve an LDL cholesterol goal of < or = 110 mg/dl . All participants are followed until study completion , when 320 participants have had a primary end point or a minimum of 5 years after the last participant is r and omized , whichever occurs last . All end points are adjudicated by an independent committee using prespecified criteria . Unique features of this trial are ( 1 ) the inclusion of unstable angina in the primary end point to reflect the increasing trend to treat coronary heart disease aggressively before a myocardial infa rct ion has occurred , ( 2 ) aggressive pharmacologic intervention , with titration , to attain an LDL cholesterol goal less than the current National Cholesterol Education Panel guidelines for primary prevention , and ( 3 ) a cohort that includes women , the elderly , and those with mild to moderate hyperlipidemia and low HDL cholesterol . Compared with earlier studies , results will be applicable to a broader population and may help clarify the role of aggressive LDL cholesterol reduction measures in primary prevention . Treatment of this population is likely to realize the greatest cumulative long-term benefit in the prevention of acute major coronary events BACKGROUND Despite progress , atherosclerotic vascular disease remains a major cause of morbidity and mortality . Intravenous therapy with platelet glycoprotein ( GP ) IIb/IIIa receptor antagonists improves outcome in patients with acute coronary syndromes ( ACS ) . Whether potent long-term antiplatelet therapy with oral GP IIb/IIIa antagonists will further improve outcome at a dose that is tolerable in long-term treatment is unknown . TRIAL DESIGN SYMPHONY ( Sibrafiban versus aspirin to Yield Maximum Protection from ischemic Heart events post-acute cOroNary syndromes ) was a r and omized , double-blind , aspirin-controlled trial with 2 concentration regimens of sibrafiban , an oral peptidomimetic GP IIb/IIIa antagonist , for long-term treatment instead of aspirin in patients after an ACS . Patients were eligible for SYMPHONY if they presented within 7 days of an ACS ( > /=20 minutes of ischemic symptoms ) , had been clinical ly stable for at least 12 hours , and met one of the following inclusion criteria : ST-segment depression or elevation of at least 0.5 mm or new left bundle branch block with the ACS or elevated creatinine kinase MB more than the upper limit of normal and > 3 % of total creatine kinase or , if creatine kinase MB was not measured , an elevated level of troponin T or I. Approximately 9000 patients post ACS were r and omized 1:1:1 to treatment with either aspirin ( 80 mg every 12 hours ) or high-dose or low-dose sibrafiban every 12 hours . Assignment of tablet strength ( 3 , 4.5 , or 6 mg ) within the sibrafiban arms was based on body weight and renal function to achieve a target steady-state plasma concentration . The duration of study drug therapy was 90 days . Patients who had intracoronary stenting during the course of the study initially received a blinded stent medication assignment for 2 to 4 weeks based on their initial r and omization as follows : aspirin/ticlopidine 250 mg twice daily , low-dose sibrafiban/ticlopidine placebo twice daily , and high-dose sibrafiban/ticlopidine placebo twice daily . After the second interim safety assessment by the Data and Safety Monitoring Board the stent regimen for the low-dose group was modified to include ticlopidine 250 mg twice daily . END POINTS The primary efficacy end point of SYMPHONY was the 90-day incidence of a composite of all-cause mortality , myocardial infa rct ion or reinfa rct ion , and severe recurrent ischemia . A clinical events classification committee was established to determine the end points of reinfa rct ion and severe recurrent ischemia . The primary safety end points were the incidence of major bleeding or minor bleeding and the combined incidence of major and minor bleeding . Bleeding classification was done by computer algorithm . Tolerability was assessed by the rate of study drug discontinuation from bleeding Evidence suggests that statin therapy reduces the risk of stroke in patients with coronary heart disease ( CHD ) , but its benefit for patients with cerebrovascular disease and no history of CHD remains uncertain . The Stroke Prevention by Aggressive Reduction in Cholesterol Levels ( SPARCL ) Study is a prospect i ve , multi-centre , double-blind , r and omised , placebo-controlled trial design ed to evaluate the effects of atorvastatin 80 mg/day in patients who previously experienced a stroke or transient ischaemic attack , but who have no known CHD . A total of 4,732 patients have been enrolled , and the data collection phase of the study is expected to be completed by October 2004 . SPARCL is the first study primarily design ed to prospect ively evaluate the effect of statin treatment in secondary stroke prevention |
12,348 | 27,580,614 | RCT results support the efficacy of the Clubhouse Model in promoting employment , reducing hospitalization(s ) , and improving quality of life . | The Clubhouse Model has been in existence for over sixty-five years ; however , a review that synthesizes the literature on the model is needed . | Consumers with serious mental illness ( N=166 ) enrolling in two community-based mental health programs , a vocational Program of Assertive Community Treatment and a clubhouse certified by the International Center for Clubhouse Development ( ICCD ) , were asked about their interest in work . About one third of the new enrollees expressed no interest in working . Equivalent supported employment services were then offered to all participants in each program . Stated interest in work and receipt of vocational services were statistically significant predictors of whether a person would work and how long it would take to get a job . Two thirds of those interested in work and half of those with no initial interest obtained a competitive job if they received at least one hour of vocational service . Once employed , these two groups held comparable jobs for the same length of time . These findings demonstrate the importance of making vocational services continuously available to all people with serious mental illness , and the viability of integrating these services into routine mental health care OBJECTIVE This purpose of this study was to determine whether participation in the Work-Ordered Day program of the Clubhouse model has a positive effect on vocational outcomes . METHOD The longitudinal study followed a group of individuals with severe mental illness who were r and omly assigned either to a Clubhouse program or a Program of Assertive Community Treatment team . Study participants were tracked for 135 weeks . These analyses evaluated the relationship between Work-Ordered Day participation and employment duration for the 43 study participants enrolled in the Clubhouse program who were active throughout the study and competitively employed during the study . RESULTS Participation in the Work-Ordered Day program had a significant positive impact on average duration of employment . On average , a 1-hr increase in participation prior to employment led to an increase of 2.3 weeks in competitive employment . CONCLUSIONS AND IMPLICATION S FOR PRACTICE Participants with more Work-Ordered Day program participation prior to employment had significantly longer average competitive employment duration even when controlling for prior work history . Participation in the Work-Ordered Day program is likely to improve work readiness . Further research is warranted to study which elements of the program may foment employment success . This could lead to increased implementation of the Work-Ordered Day program and its elements as precursors to employment for adults with severe mental illness Background Tobacco remains a seemingly intractable problem for individuals living with severe and persistent mental illness . This study evaluated the implementation , technical assistance , and perceived impact of a model curriculum ( " Learning About Healthy Living " ) to promote wellness and motivation to quit tobacco use in psychosocial rehabilitation clubhouses . Methods We used semi-structured interviews ( n = 9 ) with clubhouse staff ( n = 12 ) and a survey of participating clubhouse members ( n = 271 ) in nine clubhouses . Results Fifty-eight percent of clubhouse participants completed surveys . Results showed tobacco users open to tobacco-free policies ( 62 % ) and perceiving more discussion s about quitting tobacco with healthcare providers ( 69 % ) . Analyses of staff interviews and member surveys revealed four key themes : ( 1 ) the curriculum was successfully implemented and appreciated ; ( 2 ) technical assistance kept implementation on track ; ( 3 ) adding wellness content and interactive components should enhance the curriculum ; and , ( 4 ) the curriculum advanced other healthful policies and practice s. Conclusions Mental health setting s are important locations for implementing programs to address tobacco use . In this real-world implementation of a model curriculum in psychosocial rehabilitation clubhouses , the curriculum tested well , was feasible and well-received , and suggests potential impact on tobacco use outcomes . Revision , dissemination , and a r and omized controlled trial evaluation of the model curriculum should now occur The Program Environment Scale ( PES ) was developed for use with clients of community-based programs for the severely mentally ill . It is intended to fill the gap in available tools for assessing clients ' perceptions of program functioning as it affects their “ quality of life ” in a program . Formal pretests were conducted with 121 clients at 12 r and omly selected programs near Washington , DC . The final field test used a revised form ( 29 domains ; 129 items ) with 221 clients in 22 programs selected r and omly throughout the U.S. , including Clubhouse , day treatment , psychosocial rehabilitation , and social club programs . Twenty-three subscales met at least five of eight psychometric criteria for internal consistency and discriminant validity . A 24th subscale was retained because of its substantive importance . Successful subscales cover program atmosphere and interactions ( program cares about me , energy level , friendliness , openness , staff-client and client-client respect , reasonable rules , availability of positive physical contact , protection from bad touch , staff investment in their jobs , and confidentiality ) , client empowerment/staff-client e quality ( program and treatment empowerment , egalitarian space use ) , and service components ( support for paid work , work importance , emergency access , family activities , housing , public benefits , community activities , medications , substance abuse , and continuity ) . Subscale validity is indicated by associations of specific service offerings with scores on scales measuring client perceptions of those services , and by an ability to differentiate among program models ( i.e. , Clubhouses , day treatment programs , and psychosocial rehabilitation programs look different from each other ) . Subscale scores were not influenced by client characteristics ( gender , race , age , diagnosis , number of hospitalizations , length of time in program ) . The final scale has 97 items and takes about 25 minutes to complete . The PES succeeds in measuring different aspects of programs as clients perceive them . In the programs we visited , directors felt the PES covers the important things they want to know about how clients perceive their program . The PES should become a useful tool both for research ers interested in how client responses to programs may influence their therapeutic outcomes , and for practitioners interested in improving their clients ' program experiences and /or increasing convergence of staff and client views of their program OBJECTIVE Despite the large number of Latinos living in the United States , little research has evaluated the effectiveness of different vocational rehabilitation programs for individuals with severe mental illness in this rapidly growing minority population . This article presents a secondary analysis of a r and omized , controlled trial comparing supported employment with 2 other vocational rehabilitation programs in 3 ethnic/racial groups of participants with severe mental illness : Latinos , non-Latino African Americans , and non-Latino Whites . METHOD The data were drawn from a previously published r and omized , controlled trial comparing supported employment with st and ard vocational rehabilitation services and a psychosocial clubhouse program in persons with severe mental illness ( Mueser et al. , 2004 ) , including 64 Latinos , 91 non-Latino African Americans , and 43 non-Latino Whites . Comparisons were made between the 3 groups at baseline on demographic characteristics , clinical and psychosocial functioning , and quality of life . Within each ethnic/racial group , competitive employment and all paid employment outcomes were compared between the 3 vocational rehabilitation programs over the 2-year study period . RESULTS At baseline , the Latino participants had lower levels of education and disability income , were less likely to have worked competitively over the previous 5 years , had more severe symptoms , and worse psychosocial functioning than the non-Latino African American or non-Latino White participants . Latinos r and omized to supported employment had better competitive and all-paid work outcomes than those assigned to either st and ard services or the psychosocial clubhouse program , similar to the non-Latino consumers . Rates of competitive work for consumers in supported employment were comparable across all 3 racial/ethnic groups . DISCUSSION Supported employment is effective at improving competitive work in Latinos with severe mental illness . Efforts should be made to increase access to supported employment in the growing population of Latinos with severe mental illness A r and omized trial comparing a facility-based Clubhouse ( N = 83 ) to a mobile Program of Assertive Community Treatment ( PACT ; N = 84 ) tested the widely held belief that competitive employment improves global quality of life for adults with severe mental illness . R and om regression analyses showed that , over 24 months of study participation , competitively employed Clubhouse participants reported greater global quality of life improvement , particularly with the social and financial aspects of their lives , as well as greater self-esteem and service satisfaction , compared to competitively employed PACT participants . However , there was no overall association between global quality of life and competitive work , or work duration . Future research will determine whether these findings generalize to other certified Clubhouses or to other types of supported employment . Multi-site studies are needed to identify key mechanisms for quality of life improvement in certified Clubhouses , including the possibly essential role of Clubhouse employer consortiums for providing high-wage , socially integrated jobs The authors compared 3 approaches to vocational rehabilitation for severe mental illness ( SMI ) : the individual placement and support ( IPS ) model of supported employment , a psychosocial rehabilitation ( PSR ) program , and st and ard services . Two hundred four unemployed clients ( 46 % African American , 30 % Latino ) with SMI were r and omly assigned to IPS , PSR , or st and ard services and followed for 2 years . Clients in IPS had significantly better employment outcomes than clients in PSR and st and ard services , including more competitive work ( 73.9 % vs. 18.2 % vs. 27.5 % , respectively ) and any paid work ( 73.9 % vs. 34.8 % vs. 53.6 % , respectively ) . There were few differences in nonvocational outcomes between programs . IPS is a more effective model than PSR or st and ard brokered vocational services for improving employment outcomes in clients with SMI Service fit , defined as consistency between mental health services judged needed and services received was measured for a r and om sample of service recipients in a public mental health system ( N = 6588 ) . A variant of small area analysis was used to measure the relationship between catchment area mortality rates from natural causes , suicide , and medicolegal causes and area fit scores for a variety of services . We tested the theory-based hypothesis that service fit would predict interarea variations in mortality better than simple measures of amount of service prescribed and received . We also tested the hypothesis that , controlling for relevant demographic and clinical factors , fit would be protective for mortality from all causes . Findings supported the first hypothesis . With respect to the second , service fit for only certain services was protective . Housing and clubhouses services were particularly protective , suggesting the importance of services providing social support 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 OBJECTIVE In a r and omized controlled trial , a vocationally integrated program of assertive community treatment ( ACT ) was compared with a certified clubhouse in the delivery of supported employment services . METHODS Employment rates , total work hours , and earnings for 121 adults with serious mental illness interested in work were compared with published benchmark figures for exemplary supported employment programs . The two programs were then compared on service engagement , retention , and employment outcomes in regression analyses that controlled for background characteristics , program preference , and vocational service receipt . RESULTS Outcomes for 63 ACT and 58 clubhouse participants met or exceeded most published outcomes for specialized supported employment teams . Compared with the clubhouse program , the ACT program had significantly ( p<.05 ) better service engagement ( ACT , 98 percent ; clubhouse , 74 percent ) and retention ( ACT , 79 percent ; clubhouse , 58 percent ) over 24 months , but there was no significant difference in employment rates ( ACT , 64 percent ; clubhouse , 47 percent ) . Compared with ACT participants , clubhouse participants worked significantly longer ( median of 199 days versus 98 days ) for more total hours ( median of 494 hours versus 234 hours ) and earned more ( median of $ 3,456 versus $ 1,252 total earnings ) . Better work performance by clubhouse participants was partially attributable to higher pay . CONCLUSIONS Vocationally integrated ACT and certified clubhouses can achieve employment outcomes similar to those of exemplary supported employment teams . Certified clubhouses can effectively provide supported employment along with other rehabilitative services , and the ACT program can ensure continuous integration of supported employment with clinical care OBJECTIVE This study determined whether the clubhouse model of community support and psychiatric rehabilitation can produce competitive employment outcomes that are comparable or superior to those of the Program of Assertive Community Treatment ( PACT ) model . METHODS This longitudinal study followed a group of 170 individuals with severe mental illness who were r and omly assigned either to the experimental design , a clubhouse program ( N=86 ) , or to the control design , a PACT team ( N=84 ) . Study participants were tracked for 30 months , and employment outcome data were collected . RESULTS After 30 months , 72 clubhouse and 76 PACT participants remained active in the project . After 30 months , 74 percent of PACT participants and 60 percent of clubhouse participants had been placed in at least one job . The average clubhouse participant worked 21.8 weeks per job and earned $ 7.38 per hour , whereas the average PACT participant worked 13.1 weeks per job and earned $ 6.30 per hour . CONCLUSIONS Participants from both the PACT and clubhouse models achieved high employment levels , with no significant differences in weekly employment or 30-month job placement rates over the course of the study . During this time , clubhouse participants earned significantly higher wages and remained competitively employed for significantly more weeks per job than PACT participants 1 . Noncompliance with psychotropic medications is a primary reason for recidivism to inpatient hospitalization . It is a great contributor to the " Revolving door syndrome . " 2 . Psychosocial rehabilitation clubhouses can decrease inpatient hospitalization in patients with chronic mental illness . Their supportive , vocational , and educational functions are worth the investment in terms of improving quality of life and functioning skills . 3 . Patients on oral psychotropic medications were more compliant in this study than those on injectable neuroleptic regimens if they attended the clubhouse program . It is presumed that the clubhouse atmosphere " normalizes " the routine of taking psychotropic medications and enhances compliance The purpose of this study was to examine the social support characteristics and correlates of peer networks for Clubhouse members . A r and om sample of 126 members from one Clubhouse was requested to nominate social network members and asked a series of questions about characteristics of supports provided by each network member . Respondents with both peers and non-peers in their network , three fifths of the sample , had more frequent contacts with peers than with non-peers and were more satisfied with peer relationships than with non-peer relationships . Those respondents also reported that peers were less critical than non-peers . Among all respondents , being Caucasian and having better quality of social life were correlated with having a peer network while higher degree of reliance on others and more Clubhouse visits were correlated with having a Clubhouse network . Longitudinal studies are needed to further investigate the relationship between quality and benefits of peer support |
12,349 | 22,513,938 | The two small trials that administered trastuzumab for less than six months did not differ in efficacy from longer studies , but found fewer cardiac toxicities .
Trastuzumab significantly improves OS and DFS in HER2-positive women with early and locally advanced breast cancer , although it also significantly increases the risk of CHF and LVEF decline .
Studies that administered trastuzumab concurrently or sequentially did not differ significantly in efficacy . | BACKGROUND Approximately one-fifth of women who develop early breast cancer have HER2-positive tumours , which if untreated , have a worse prognosis than HER2-negative tumours .
Trastuzumab is a selective treatment targeting the HER2 pathway .
Although the results on efficacy seem to support its use , there are potential cardiac toxicities which need to be considered , especially for women at lower risk of recurrence , or those at increased cardiovascular risk .
OBJECTIVES To assess the evidence on the efficacy and safety of therapy with trastuzumab , overall and in relation to its duration , concurrent or sequential administration with the st and ard chemotherapy regimen in patients with HER2-positive early breast cancer . | 632 Background : Following the BCIRG 001 , PACS 01 and HERA trials , this r and omised , multicentre , open-label , Phase III trial was design ed to demonstrate the benefit of concomitant docetaxel and epirubicin versus anthracyclines , and evaluate the use of sequential trastuzumab . METHODS Patients ( pts ) with localised , resectable , unilateral breast cancer who met the following criteria were eligible : age < 65 years , ≥1 positive node , M0 , adequate heart and organ functions . Pts were r and omised to receive either 6 cycles of 5-fluorouracil-epirubicin-cyclophosphamide ( FEC100 : F and C , 500 mg/m2 , E 100 mg/m2 ) ( Arm A ) or epirubicin-docetaxel ( ET75 : E 75 mg/m2 , T 75 mg/m2 ) ( Arm B ) . Primary prophylaxis with G-CSF was not planned . Radiotherapy was m and atory after conservative surgery and tamoxifen was required in pts with hormone receptor-positive tumours . Pts with HER2-positive disease were then further r and omised to observation only or to 1 year of trastuzumab monotherapy ( 6 mg/kg iv every 3 weeks ) . In HER2-positive pts receiving trastuzumab , left ventricular ejection fraction ( LVEF ) was determined at Cycles 2 , 4 , 8 , 13 , 18 and after 2 years . Otherwise , LVEF was determined at baseline and at 1 year post-surgery . RESULTS Of the 3010 pts recruited ( 2622 evaluable for safety to date ) , 1518 received FEC100 and 1492 received ET75 after the first r and omisation . Haematologic toxicity was the most frequent toxicity in both arms . Grade 3 - 4 toxicities were similar for Arms A and B , except febrile neutropenia ( 10.3 % and 31.4 % , respectively ) and nausea/vomiting ( 13.2 % and 7.5 % , respectively ) . Grade 2 clinical cardiac toxicity ( decreased LVEF ) was observed in 4 pts in Arm A and 5 in Arm B , with median LVEF scores of 63 % in both arms at the end of chemotherapy . HER2-positive pts ( n=500 ) were then r and omised to either receive trastuzumab ( n=259 ) or observation only ( n=241 ) . CONCLUSIONS These preliminary safety data indicate that FEC100 and ET75 were both well tolerated , with acceptable cardiac safety values . The trial is ongoing and further analysis regarding the use of trastuzumab in this setting will be presented . [ Table : see text ] PURPOSE We investigated the incidence of cardiac adverse events in patients with early breast cancer in the Herceptin Adjuvant ( HERA ) trial who were treated with 1 year of trastuzumab after completion of (neo)adjuvant chemotherapy . PATIENTS AND METHODS The HERA trial is a three-group , r and omized trial that compared 1 year or 2 years of trastuzumab with observation in women with human epidermal growth factor receptor-2 ( HER2 ) -positive early breast cancer . Eligible patients had normal left ventricular ejection fraction ( LVEF ; > or= 55 % ) after completion of (neo)adjuvant chemotherapy with or without radiotherapy . Cardiac function was monitored throughout the trial . This analysis considers patients r and omly assigned to 1 year of trastuzumab treatment or observation . RESULTS There were 1,698 patients r and omly assigned to observation and 1,703 r and omly assigned to 1 year of trastuzumab treatment ; 94.1 % of patients had been treated with anthracyclines . The incidence of discontinuation of trastuzumab because of cardiac disorders was low ( 5.1 % ) . At a median follow-up of 3.6 years , the incidence of cardiac end points remained low , though it was higher in the trastuzumab group than in the observation group ( severe CHF , 0.8 % v 0.0 % ; confirmed significant LVEF decreases , 3.6 % v 0.6 % ) In the trastuzumab group , 59 of 73 patients with a cardiac end point reached acute recovery ; of these 59 patients , 52 were considered by the cardiac advisory board ( CAB ) to have a favorable outcome from the cardiac end point . CONCLUSION The incidence of cardiac end points remains low even after longer-term follow-up . The cumulative incidence of any type of cardiac end point increases during the scheduled treatment period of 1 year , but it remains relatively constant thereafter BACKGROUND We present the combined results of two trials that compared adjuvant chemotherapy with or without concurrent trastuzumab in women with surgically removed HER2-positive breast cancer . METHODS The National Surgical Adjuvant Breast and Bowel Project trial B-31 compared doxorubicin and cyclophosphamide followed by paclitaxel every 3 weeks ( group 1 ) with the same regimen plus 52 weeks of trastuzumab beginning with the first dose of paclitaxel ( group 2 ) . The North Central Cancer Treatment Group trial N9831 compared three regimens : doxorubicin and cyclophosphamide followed by weekly paclitaxel ( group A ) , the same regimen followed by 52 weeks of trastuzumab after paclitaxel ( group B ) , and the same regimen plus 52 weeks of trastuzumab initiated concomitantly with paclitaxel ( group C ) . The studies were amended to include a joint analysis comparing groups 1 and A ( the control group ) with groups 2 and C ( the trastuzumab group ) . Group B was excluded because trastuzumab was not given concurrently with paclitaxel . RESULTS By March 15 , 2005 , 394 events ( recurrent , second primary cancer , or death before recurrence ) had been reported , triggering the first scheduled interim analysis . Of these , 133 were in the trastuzumab group and 261 in the control group ( hazard ratio , 0.48 ; P<0.0001 ) . This result crossed the early stopping boundary . The absolute difference in disease-free survival between the trastuzumab group and the control group was 12 percent at three years . Trastuzumab therapy was associated with a 33 percent reduction in the risk of death ( P=0.015 ) . The three-year cumulative incidence of class III or IV congestive heart failure or death from cardiac causes in the trastuzumab group was 4.1 percent in trial B-31 and 2.9 percent in trial N9831 . CONCLUSIONS Trastuzumab combined with paclitaxel after doxorubicin and cyclophosphamide improves outcomes among women with surgically removed HER2-positive breast cancer . ( Clinical Trials.gov numbers , NCT00004067 and NCT00005970 . PURPOSE To evaluate the efficacy and safety of docetaxel , cisplatin , and trastuzumab as primary systemic therapy for human epidermal growth factor receptor 2 ( HER2 ) -positive , locally advanced breast cancer ( LABC ) . PATIENTS AND METHODS Forty-eight patients with immunohistochemistry-confirmed HER2-positive LABC or inflammatory breast cancer received 12 weeks of docetaxel , cisplatin , and trastuzumab with filgrastim , followed by surgery , adjuvant doxorubicin and cyclophosphamide , and locoregional radiotherapy with or without tamoxifen . The primary end point was pathologic complete response ( pCR ) in breast . RESULTS Baseline mean tumor size was 9.2 cm ( range , 4 to 32 cm ) . pCR occurred in breast in 11 patients ( 23 % ; 95 % CI , 12 % to 37 % ) and breast and axilla in eight patients ( 17 % ; 95 % CI , 8 % to 30 % ) . pCR rates in breast ( HER2 positive , seven of 30 patients , 23 % v HER2 negative , four of 18 patients , 22 % ; P > .05 ) and breast and axilla ( four of 30 patients , 13 % v four of 18 patients , 22 % , respectively ; P > .05 ) were similar regardless of HER2 status by fluorescence in situ hybridization ( FISH ) . At a median follow-up time of 43 months , 4-year progression-free survival ( PFS ) rate was 81 % ( 95 % CI , 64 % to 90 % ) ; overall survival ( OS ) rate was 86 % ( 95 % CI , 71 % to 94 % ) . In patients with pCR in breast and axilla , PFS and OS rates were 100 % ( 95 % CI , inestimable ) . In patients without pCR , PFS rate was 76 % ( 95 % CI , 57 % to 88 % ; P = .15 , log-rank test ) , and OS rate was 83 % ( 95 % CI , 66 % to 92 % ; P = .21 ) . Survival rates were similar regardless of FISH status . There were only two grade 4 adverse events . CONCLUSION Twelve weeks of docetaxel , cisplatin , and trastuzumab is clinical ly active and leads to excellent survival in patients with large , HER2-positive tumors BACKGROUND Trastuzumab ( T ) combined with chemotherapy has been recently shown to improve outcome in HER2-positive breast cancer ( BC ) . The aim of this study was to evaluate the toxic effects of concurrent radiation therapy ( RT ) and T administration in the adjuvant setting . PATIENTS AND METHODS Data of 146 patients with stages II-III HER2-positive BC were recorded . Median age was 46 years . In all , 32 ( 23 % ) and 114 ( 77 % ) patients received a weekly and a 3-week T schedule , respectively . A median dose of 50 Gy was delivered after surgery . Internal mammary chain ( IMC ) was irradiated in 103 ( 71 % ) patients . RESULTS Grade > 2 dermatitis and esophagitis were noted in 51 % and 12 % , respectively . According to the Common Toxicity Criteria v3.0 scale and HERA ( HERceptin Adjuvant ) trial criteria , respectively , 10 % and 6 % of the patients had a grade > /=2 of left ventricular ejection fraction ( LVEF ) decrease after RT . Multivariate analyses revealed two independent prognostic factors : weekly T administration ( for LVEF decrease ) and menopausal status ( for dermatitis ) . Higher level of T cumulative dose ( > 1600 mg ) was only borderline of statistical significance for acute esophagitis toxicity . CONCLUSION We showed that weekly concurrent T and RT are feasible in daily clinical practice with , however , a decrease of LVEF . Cardiac volume sparing and patient selection s for IMC irradiation are highly recommended . Longer follow-up is warranted to evaluate late toxic effects Despite important progress in underst and ing the molecular factors underlying the development of cancer and the improvement in response rates with new drugs , long-term survival is still disappointing for most common solid tumours . This might be because very little of the modest gain for patients is the result of the new compounds discovered and marketed recently . An assessment of the regulatory agencies ' performance may suggest improvements . The present analysis summarizes and evaluates the type of studies and end points used by the EMEA to approve new anticancer drugs , and discusses the application of current regulations . This report is based on the information available on the EMEA web site . We identified current regulatory requirements for anticancer drugs promulgated by the agency and retrieved them in the relevant directory ; information about empirical evidence supporting the approval of drugs for solid cancers through the central ised procedure were retrieved from the European Public Assessment Report ( EPAR ) . We surveyed documents for drug applications and later extensions from January 1995 , when EMEA was set up , to December 2004 . We identified 14 anticancer drugs for 27 different indications ( 14 new applications and 13 extensions ) . Overall , 48 clinical studies were used as the basis for approval ; r and omised comparative ( clinical ) trial ( RCT ) and Response Rate were the study design and end points most frequently adopted ( respectively , 25 out of 48 and 30 out of 48 ) . In 13 cases , the EPAR explicitly reported differences between arms in terms of survival : the range was 0–3.7 months , and the mean and median differences were 1.5 and 1.2 months . The majority of studies ( 13 out of 27 , 48 % ) involved the evaluation of complete and /or partial tumour responses , with regard to the end points supporting the 27 indications . Despite the recommendations of the current EMEA guidance documents , new anticancer agents are still often approved on the basis of small single arm trials that do not allow any assessment of an ‘ acceptable and extensively documented toxicity profile ’ and of end points such as response rate , time to progression or progression-free survival which at best can be considered indicators of anticancer activity and are not ‘ justified surrogate markers for clinical benefit ’ . Anticipating an earlier than ideal point along the drug approval path and the use of not fully vali date d surrogate end points in nonr and omised trials looks like a dangerous shortcut that might jeopardise consumers ' health , leading to unsafe and ineffective drugs being marketed and prescribed . The present Note for Guidance for new anticancer agents needs revising . Drugs must be rapidly released for patients who need them but not be at the expense of adequate knowledge about the real benefit of the drugs BACKGROUND Trastuzumab ( Herceptin(R ) ) improves disease-free survival ( DFS ) and overall survival for patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer . We aim ed to assess the magnitude of its clinical benefit for sub population s defined by nodal and steroid hormone receptor status using data from the Herceptin Adjuvant ( HERA ) study . PATIENTS AND METHODS HERA is an international multicenter r and omized trial comparing 1 or 2 years of trastuzumab treatment with observation after st and ard chemotherapy in women with HER2-positive breast cancer . In total , 1703 women r and omized to 1-year trastuzumab and 1698 women r and omized to observation were included in these analyses . Median follow-up was 23.5 months . The primary endpoint was DFS . RESULTS The overall hazard ratio ( HR ) for trastuzumab versus observation was 0.64 [ 95 % confidence interval ( CI ) 0.54 - 0.76 ; P < 0.0001 ] , ranging from 0.46 to 0.82 for subgroups . Estimated improvement in 3-year DFS in subgroups ranged from + 11.3 % to + 0.6 % . Patients with the best prognosis ( those with node-negative disease and tumors 1.1 - 2.0 cm ) had benefit similar to the overall cohort ( HR 0.53 , 95 % CI 0.26 - 1.07 ; 3-year DFS improvement + 4.6 % , 95 % CI -4.0 % to 13.2 % ) . CONCLUSIONS Adjuvant trastuzumab therapy reduces the risk of relapse similarly across subgroups defined by nodal status and steroid hormone receptor status , even those at relatively low risk for relapse PURPOSE To assess whether trastuzumab ( H ) with radiotherapy ( RT ) increases adverse events ( AEs ) after breast-conserving surgery or mastectomy . PATIENTS AND METHODS Patients with early-stage resected human epidermal growth factor receptor 2 ( HER-2 ) -positive breast cancer ( BC ) were r and omly assigned to doxorubicin ( A ) and cyclophosphamide ( C ) , followed by weekly paclitaxel ( T ; AC-T-H or AC-TH-H ) . RT criteria ( with or without nodal RT ) were postlumpectomy breast or ( optional ) postmastectomy chest wall . RT of internal mammary nodes was prohibited . RT commenced within 5 weeks after T , concurrently with H. Analysis included 1,503 irradiated patients for RT-associated AEs across treatment arms . Rates of cardiac events ( CEs ) with and without RT were compared within arms . RESULTS No significant differences among arms were found in incidence of acute skin reaction , pneumonitis , dyspnea , cough , dysphagia , or neutropenia . A significant difference occurred in incidence of leukopenia , with higher rates for AC-T-H versus AC-T ( odds ratio = 1.89 ; 95 % CI , 1.25 to 2.88 ) . At a median follow-up of 3.7 years ( range , 0 to 6.5 years ) , RT with H did not increase relative frequency of CEs regardless of treatment side . The cumulative incidence of CEs with AC-T-H was 2.7 % with or without RT . With AC-TH-H , the cumulative incidence was 1.7 % v 5.9 % with or without RT , respectively . CONCLUSION Concurrent adjuvant RT and H for early-stage BC was not associated with increased acute AEs . Further follow-up is required to assess late AEs PURPOSE The purpose of this analysis was to investigate trastuzumab-associated cardiac adverse effects in breast cancer patients after completion of (neo)adjuvant chemotherapy with or without radiotherapy . PATIENTS AND METHODS The Herceptin Adjuvant ( HERA ) trial is a three-group , multicenter , open-label r and omized trial that compared 1 or 2 years of trastuzumab given once every 3 weeks with observation in patients with HER-2-positive breast cancer . Only patients who after completion of (neo)adjuvant chemotherapy with or without radiotherapy had normal left ventricular ejection fraction ( LVEF > or = 55 % ) were eligible . A repeat LVEF assessment was performed in case of cardiac dysfunction . RESULTS Data were available for 1,693 patients r and omly assigned to 1 year trastuzumab and 1,693 patients r and omly assigned to observation . The incidence of trastuzumab discontinuation due to cardiac disorders was low ( 4.3 % ) . The incidence of cardiac end points was higher in the trastuzumab group compared with observation ( severe congestive heart failure [ CHF ] , 0.60 % v 0.00 % ; symptomatic CHF , 2.15 % v 0.12 % ; confirmed significant LVEF drops , 3.04 % v 0.53 % ) . Most patients with cardiac dysfunction recovered in fewer than 6 months . Patients with trastuzumab-associated cardiac dysfunction were treated with higher cumulative doses of doxorubicin ( 287 mg/m(2 ) v 257 mg/m(2 ) ) or epirubicin ( 480 mg/m(2 ) v 422 mg/m(2 ) ) and had a lower screening LVEF and a higher body mass index . CONCLUSION Given the clear benefit in disease-free survival , the low incidence of cardiac adverse events , and the suggestion that cardiac dysfunction might be reversible , adjuvant trastuzumab should be considered for treatment of breast cancer patients who fulfill the HERA trial eligibility criteria PURPOSE To determine whether ( 1 ) immunohistochemical ( IHC ) HER2 status ( ie , 2 + or 3 + ) , ( 2 ) degree of fluorescence in situ hybridization ( FISH ) amplification according to ( 2a ) HER2/CEP17 ratio or ( 2b ) HER2 gene copy number , or ( 3 ) polysomy significantly influenced clinical outcome for patients with human epidermal growth factor receptor 2 ( HER2 ) -positive breast cancer enrolled in the Herceptin Adjuvant trial of trastuzumab versus no trastuzumab administered after completion of chemotherapy . PATIENTS AND METHODS IHC and /or FISH analyses were performed locally and required central confirmation as indicating HER2 positivity for trial entry . FISH data from the central HER2 analysis on patients in the 1-year trastuzumab and no trastuzumab arms were assessed in relation to disease-free survival ( DFS ) after a median 2 years of follow-up . RESULTS Central FISH results were available for 2,071 ( 61 % ) of the 3,401 patients r and omized to the 2 arms . Among patients with FISH-positive disease , ( 1 ) the hazard ratios for trastuzumab versus no trastuzumab were 0.56 ( 95 % CI , 0.32 to 0.99 ) for locally IHC2 + cases ( n = 340 ) and 0.80 ( 95 % CI , 0.40 to 1.61 ) for central ly IHC2 + cases ( n = 299 ) . There was no significant prognostic relationship between ( 2a ) HER2 FISH ratio , ( 2b ) HER2 copy number , or ( 3 ) polysomy and DFS in the control arm or predictive relationship defining differential benefit from trastuzumab . CONCLUSION There was no evidence for reduced benefit of trastuzumab in HER2 IHC2+FISH+ cases . The degree of HER2 amplification does not influence prognosis or benefit from adjuvant trastuzumab in patients treated with prior adjuvant chemotherapy PURPOSE To evaluate the efficacy of trastuzumab in patients with node-positive breast cancer treated with surgery , adjuvant chemotherapy , radiotherapy , and hormone therapy if applicable . PATIENTS AND METHODS Three thous and ten patients with operable node-positive breast cancer were r and omly assigned to receive adjuvant anthracycline-based chemotherapy with or without docetaxel . Patients who presented human epidermal growth factor receptor 2 ( HER2 ) -overexpressing tumors were secondary r and omly assigned to either a sequential regimen of trastuzumab ( 6 mg/kg every 3 weeks ) for 1 year or observation . The primary end point was disease-free survival ( DFS ) . RESULTS Overall 528 patients were r and omly assigned between trastuzumab ( n = 260 ) and observation ( n = 268 ) arm . Of the 234 patients ( 90 % ) who received at least one administration of trastuzumab , 196 ( 84 % ) received at least 6 months of treatment , and 41 ( 18 % ) discontinued treatment due to cardiac events ( any grade ) . At the date of analysis ( October 2007 ) , 129 DFS events were recorded . R and om assignment to the trastuzumab arm was associated with a nonsignificant 14 % reduction in the risk of relapse ( hazard ratio , 0.86 ; 95 % CI , 0.61 to 1.22 ; P = .41 , log-rank stratified on pathologic node involvement ) . Three-year DFS rates were 78 % ( 95 % CI , 72.3 to 82.5 ) and 81 % ( 95 % CI , 75.3 to 85.4 ) in the observation and trastuzumab arms , respectively . CONCLUSION After a 47-month median follow-up , 1 year of trastuzumab given sequentially after adjuvant chemotherapy was not associated with a statistically significant decrease in the risk of relapse BACKGROUND The monoclonal antibody trastuzumab has survival benefit when given with chemotherapy to patients with early , operable , and metastatic breast cancer that has HER2 ( also known as ERBB2 ) overexpression or amplification . We aim ed to assess event-free survival in patients with HER2-positive locally advanced or inflammatory breast cancer receiving neoadjuvant chemotherapy with or without 1 year of trastuzumab . METHODS We compared 1 year of treatment with trastuzumab ( given as neoadjuvant and adjuvant treatment ; n=117 ) with no trastuzumab ( 118 ) , in women with HER2-positive locally advanced or inflammatory breast cancer treated with a neoadjuvant chemotherapy regimen consisting of doxorubicin , paclitaxel , cyclophosphamide , methotrexate , and fluorouracil . R and omisation was done with a computer program and minimisation technique , taking account of geographical area , disease stage , and hormone receptor status . Investigators were informed of treatment allocation . A parallel cohort of 99 patients with HER2-negative disease was included and treated with the same chemotherapy regimen . Primary endpoint was event-free survival . Analysis was by intention to treat . This study is registered , number IS RCT N86043495 . FINDINGS Trastuzumab significantly improved event-free survival in patients with HER2-positive breast cancer ( 3-year event-free survival , 71 % [ 95 % CI 61 - 78 ; n=36 events ] with trastuzumab , vs 56 % [ 46 - 65 ; n=51 events ] without ; hazard ratio 0.59 [ 95 % CI 0.38 - 0.90 ] ; p=0.013 ) . Trastuzumab was well tolerated and , despite concurrent administration with doxorubicin , only two patients ( 2 % ) developed symptomatic cardiac failure . Both responded to cardiac drugs . INTERPRETATION The addition of neoadjuvant and adjuvant trastuzumab to neoadjuvant chemotherapy should be considered for women with HER2-positive locally advanced or inflammatory breast cancer to improve event-free survival , survival , and clinical and pathological tumour responses . FUNDING F Hoffmann-La Roche BACKGROUND Trastuzumab , a recombinant monoclonal antibody against HER2 , has clinical activity in advanced breast cancer that overexpresses HER2 . We investigated its efficacy and safety after excision of early-stage breast cancer and completion of chemotherapy . METHODS This international , multicenter , r and omized trial compared one or two years of trastuzumab given every three weeks with observation in patients with HER2-positive and either node-negative or node-positive breast cancer who had completed locoregional therapy and at least four cycles of neoadjuvant or adjuvant chemotherapy . RESULTS Data were available for 1694 women r and omly assigned to two years of treatment with trastuzumab , 1694 women assigned to one year of trastuzumab , and 1693 women assigned to observation . We report here the results only of treatment with trastuzumab for one year or observation . At the first planned interim analysis ( median follow-up of one year ) , 347 events ( recurrence of breast cancer , contralateral breast cancer , second nonbreast malignant disease , or death ) were observed : 127 events in the trastuzumab group and 220 in the observation group . The unadjusted hazard ratio for an event in the trastuzumab group , as compared with the observation group , was 0.54 ( 95 percent confidence interval , 0.43 to 0.67 ; P<0.0001 by the log-rank test , crossing the interim analysis boundary ) , representing an absolute benefit in terms of disease-free survival at two years of 8.4 percentage points . Overall survival in the two groups was not significantly different ( 29 deaths with trastuzumab vs. 37 with observation ) . Severe cardiotoxicity developed in 0.5 percent of the women who were treated with trastuzumab . CONCLUSIONS One year of treatment with trastuzumab after adjuvant chemotherapy significantly improves disease-free survival among women with HER2-positive breast cancer . ( Clinical Trials.gov number , NCT00045032 . BACKGROUND We compared docetaxel with vinorelbine for the adjuvant treatment of early breast cancer . Women with tumors that overexpressed HER2/neu were also assigned to receive concomitant treatment with trastuzumab or no such treatment . METHODS We r and omly assigned 1010 women with axillary-node-positive or high-risk node-negative cancer to receive three cycles of docetaxel or vinorelbine , followed by ( in both groups ) three cycles of fluorouracil , epirubicin , and cyclophosphamide . The 232 women whose tumors had an amplified HER2/neu gene were further assigned to receive or not to receive nine weekly trastuzumab infusions . The primary end point was recurrence-free survival . RESULTS Recurrence-free survival at three years was better with docetaxel than with vinorelbine ( 91 percent vs. 86 percent ; hazard ratio for recurrence or death , 0.58 ; 95 percent confidence interval , 0.40 to 0.85 ; P=0.005 ) , but overall survival did not differ between the groups ( P=0.15 ) . Within the subgroup of patients who had HER2/neu-positive cancer , those who received trastuzumab had better three-year recurrence-free survival than those who did not receive the antibody ( 89 percent vs. 78 percent ; hazard ratio for recurrence or death , 0.42 ; 95 percent confidence interval , 0.21 to 0.83 ; P=0.01 ) . Docetaxel was associated with more adverse effects than was vinorelbine . Trastuzumab was not associated with decreased left ventricular ejection fraction or cardiac failure . CONCLUSIONS Adjuvant treatment with docetaxel , as compared with vinorelbine , improves recurrence-free survival in women with early breast cancer . A short course of trastuzumab administered concomitantly with docetaxel or vinorelbine is effective in women with breast cancer who have an amplified HER2/neu gene . ( International St and ard R and omised Controlled Trial number , IS RCT N76560285 . ) PURPOSE The objective of this study was to determine whether the addition of trastuzumab to chemotherapy in the neoadjuvant setting could increase pathologic complete response ( pCR ) rate in patients with human epidermal growth factor receptor 2 ( HER2 ) -positive disease . PATIENTS AND METHODS Forty-two patients with HER2-positive disease with operable breast cancer were r and omly assigned to either four cycles of paclitaxel followed by four cycles of fluorouracil , epirubicin , and cyclophosphamide or to the same chemotherapy with simultaneous weekly trastuzumab for 24 weeks . The primary objective was to demonstrate a 20 % improvement in pCR ( assumed 21 % to 41 % ) with the addition of trastuzumab to chemotherapy . The planned sample size was 164 patients . RESULTS Prognostic factors were similar in the two groups . After 34 patients had completed therapy , the trial 's Data Monitoring Committee stopped the trial because of superiority of trastuzumab plus chemotherapy . pCR rates were 25 % and 66.7 % for chemotherapy ( n = 16 ) and trastuzumab plus chemotherapy ( n = 18 ) , respectively ( P = .02 ) . The decision was based on the calculation that , if study continued to 164 patients , there was a 95 % probability that trastuzumab plus chemotherapy would be superior . Of the 42 r and omized patients , 26 % in the chemotherapy arm achieved pCR compared with 65.2 % in the trastuzumab plus chemotherapy arm ( P = .016 ) . The safety of this approach is not established , although no clinical congestive heart failure was observed . A more than 10 % decrease in the cardiac ejection fraction was observed in five and seven patients in the chemotherapy and trastuzumab plus chemotherapy arms , respectively . CONCLUSION Despite the small sample size , these data indicate that adding trastuzumab to chemotherapy , as used in this trial , significantly increased pCR without clinical congestive heart failure PURPOSE To assess cardiac safety and potential cardiac risk factors associated with trastuzumab in the NCCTG N9831 Intergroup adjuvant breast cancer trial . PATIENTS AND METHODS Patients with HER2-positive operable breast cancer were r and omly assigned to doxorubicin plus cyclophosphamide ( AC ) followed by either weekly paclitaxel ( arm A ) ; paclitaxel then trastuzumab ( arm B ) ; or paclitaxel plus trastuzumab then trastuzumab alone ( arm C ) . Left ventricular ejection fraction ( LVEF ) was evaluated at registration and 3 , 6 , 9 , and 18 to 21 months . RESULTS Of 2,992 patients completing AC , 5.0 % had LVEF decreases disallowing trastuzumab ( decrease below normal : 2.4 % , decrease > 15 % : 2.6 % ) . There were 1,944 patients with satisfactory or no LVEF evaluation who proceeded to post-AC therapy . Cardiac events ( congestive heart failure [ CHF ] or cardiac death [ CD ] ) : arm A , n = 3 ( 2 CHF , 1 CD ) ; arm B , n = 19 ( 18 CHF , 1 CD ) ; arm C , n = 19 ( all CHF ) ; 3-year cumulative incidence : 0.3 % , 2.8 % , and 3.3 % , respectively . Cardiac function improved in most CHF cases following trastuzumab discontinuation and cardiac medication . Factors associated with increased risk of a cardiac event in arms B and C : older age ( P < .003 ) , prior/current antihypertensive agents ( P = .005 ) , and lower registration LVEF ( P = .033 ) . Incidence of asymptomatic LVEF decreases requiring holding trastuzumab was 8 % to 10 % ; LVEF recovered and trastuzumab was restarted in approximately 50 % . CONCLUSION The cumulative incidence of post-AC cardiac events at 3 years was higher in the trastuzumab-containing arms versus the control arm , but by less than 4 % . Older age , lower registration LVEF , and antihypertensive medications are associated with increased risk of cardiac dysfunction in patients receiving trastuzumab following AC BACKGROUND Trastuzumab -- a humanised monoclonal antibody against HER2 - -has been shown to improve disease-free survival after chemotherapy in women with HER2-positive early breast cancer . We investigated the drug 's effect on overall survival after a median follow-up of 2 years in the Herceptin Adjuvant ( HERA ) study . METHODS HERA is an international multicentre r and omised trial that compared 1 or 2 years of trastuzumab treatment with observation alone after st and ard neoadjuvant or adjuvant chemotherapy in women with HER2-positive node positive or high-risk node negative breast cancer . 5102 women participated in the trial ; we analysed data from 1703 women who had been r and omised for treatment with trastuzumab for 1 year and 1698 women from the control group , with median follow-up of 23.5 months ( range 0 - 48 months ) . The primary endpoint of the trial was disease-free survival . Here , we assess overall survival , a secondary endpoint . Analyses were done on an intent-to-treat basis . This trial is registered with the European Clinical Trials Data base , number 2005 - 002385 - 11 . FINDINGS 97 ( 5.7 % ) patients r and omised to observation alone and 58 ( 3.4 % ) patients r and omised to 1 year of treatment with trastuzumab were lost to follow-up . 172 women stopped trastuzumab prematurely . 59 deaths were reported for trastuzumab and 90 in the control group . The unadjusted hazard ratio ( HR ) for the risk of death with trastuzumab compared with observation alone was 0.66 ( 95 % CI 0.47 - 0.91 ; p=0.0115 ) . 218 disease-free survival events were reported with trastuzumab compared with 321 in the control group . The unadjusted HR for the risk of an event with trastuzumab compared with observation alone was 0.64 ( 0.54 - 0.76 ; p<0.0001 ) . INTERPRETATION Our results show that 1 year of treatment with trastuzumab after adjuvant chemotherapy has a significant overall survival benefit after a median follow-up of 2 years . The emergence of this benefit after only 2 years reinforces the importance of trastuzumab in the treatment of women with HER2-positive early breast cancer Trastuzumab , a monoclonal antibody against the HER2 receptor , is currently approved as a part of adjuvant therapy for patients with HER2-overexpressing breast tumors . The Short-HER study is a phase III r and omized , multicentric Italian trial aim ed at testing the optimal duration of adjuvant trastuzumab . In this trial , 2500 patients with HER2-positive breast cancer will be r and omized to receive the following : ( arm A , long ) 4 courses of anthracycline- based chemotherapy ( doxorubicin/cyclophosphamide or epidoxorubicin/cyclophosphamide ) followed by 4 courses of docetaxel or paclitaxel in combination with trastuzumab , followed by 14 additional courses of trastuzumab administered every 3 weeks ( for a total of 18 3-weekly doses of trastuzumab ) ; or ( arm B , short ) 3 courses of 3-weekly docetaxel in combination with weekly trastuzumab ( for a total of 9 weekly doses of trastuzumab ) followed by 3 courses of 5-fluorouracil/epirubicin/cyclophosphamide . The primary objective is disease-free survival BACKGROUND Trastuzumab improves survival in the adjuvant treatment of HER-positive breast cancer , although combined therapy with anthracycline-based regimens has been associated with cardiac toxicity . We wanted to evaluate the efficacy and safety of a new nonanthracycline regimen with trastuzumab . METHODS We r and omly assigned 3222 women with HER2-positive early-stage breast cancer to receive doxorubicin and cyclophosphamide followed by docetaxel every 3 weeks ( AC-T ) , the same regimen plus 52 weeks of trastuzumab ( AC-T plus trastuzumab ) , or docetaxel and carboplatin plus 52 weeks of trastuzumab ( TCH ) . The primary study end point was disease-free survival . Secondary end points were overall survival and safety . RESULTS At a median follow-up of 65 months , 656 events triggered this protocol -specified analysis . The estimated disease-free survival rates at 5 years were 75 % among patients receiving AC-T , 84 % among those receiving AC-T plus trastuzumab , and 81 % among those receiving TCH . Estimated rates of overall survival were 87 % , 92 % , and 91 % , respectively . No significant differences in efficacy ( disease-free or overall survival ) were found between the two trastuzumab regimens , whereas both were superior to AC-T. The rates of congestive heart failure and cardiac dysfunction were significantly higher in the group receiving AC-T plus trastuzumab than in the TCH group ( P<0.001 ) . Eight cases of acute leukemia were reported : seven in the groups receiving the anthracycline-based regimens and one in the TCH group subsequent to receiving an anthracycline outside the study . CONCLUSIONS The addition of 1 year of adjuvant trastuzumab significantly improved disease-free and overall survival among women with HER2-positive breast cancer . The risk-benefit ratio favored the nonanthracycline TCH regimen over AC-T plus trastuzumab , given its similar efficacy , fewer acute toxic effects , and lower risks of cardiotoxicity and leukemia . ( Funded by Sanofi-Aventis and Genentech ; BCIRG-006 Clinical Trials.gov number , NCT00021255 . ) BACKGROUND Treatment with adjuvant trastuzumab for 1 year improves disease-free survival and overall survival in patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer . We aim ed to assess disease-free survival and overall survival after a median follow-up of 4 years for patients enrolled on the Herceptin Adjuvant ( HERA ) trial . METHODS The HERA trial is an international , multicentre , r and omised , open-label , phase 3 trial comparing treatment with trastuzumab for 1 and 2 years with observation after st and ard neoadjuvant , adjuvant chemotherapy , or both in patients with HER2-positive early breast cancer . The primary endpoint was disease-free survival . After a positive first interim analysis at a median follow-up of 1 year for the comparison of treatment with trastuzumab for 1 year with observation , event-free patients in the observation group were allowed to cross over to receive trastuzumab . We report trial outcomes for the 1-year trastuzumab and observation groups at a median follow-up of 48·4 months ( IQR 42·0 - 56·5 ) and assess the effect of the extensive crossover to trastuzumab . Our analysis was by intention-to-treat . The HERA trial is registered with the European Clinical Trials Data base , number 2005 - 002385 - 11 . FINDINGS The HERA trial population comprised 1698 patients r and omly assigned to the observation group and 1703 to the 1-year trastuzumab group . Intention-to-treat analysis of disease-free survival showed a significant benefit in favour of patients in the 1-year trastuzumab group ( 4-year disease-free survival 78·6 % ) compared with the observation group ( 4-year disease-free survival 72·2 % ; hazard ratio [ HR ] 0·76 ; 95 % CI 0·66 - 0·87 ; p<0·0001 ) . Intention-to-treat analysis of overall survival showed no significant difference in the risk of death ( 4-year overall survival 89·3%vs 87·7 % , respectively ; HR 0·85 ; 95 % CI 0·70 - 1·04 ; p=0·11 ) . Overall , 885 patients ( 52 % ) of the 1698 patients in the observation group crossed over to receive trastuzumab , and began treatment at median 22·8 months ( range 4·5 - 52·7 ) from r and omisation . In a non-r and omised comparison , patients in the selective-crossover cohort had fewer disease-free survival events than patients remaining in the observation group ( adjusted HR 0·68 ; 95 % CI 0·51 - 0·90 ; p=0·0077 ) . Higher incidences of grade 3 - 4 and fatal adverse events were noted on 1-year trastuzumab than in the observation group . The most common grade 3 or 4 adverse events , each in less than 1 % of patients , were congestive cardiac failure , hypertension , arthralgia , back pain , central -line infection , hot flush , headache , and diarrhoea . INTERPRETATION Treatment with adjuvant trastuzumab for 1 year after chemotherapy is associated with significant clinical benefit at 4-year median follow-up . The substantial selective crossover of patients in the observation group to trastuzumab was associated with improved outcomes for this cohort . FUNDING F Hoffmann-La Roche , Michelangelo Foundation PURPOSE Docetaxel has not been compared with vinorelbine as adjuvant treatment of early breast cancer . Efficacy and long-term safety of a short course of adjuvant trastuzumab administered concomitantly with chemotherapy for human epidermal growth factor receptor 2 ( HER2 ) -positive cancer are unknown . PATIENTS AND METHODS One thous and ten women with axillary node-positive or high-risk node-negative breast cancer were r and omly assigned to receive three cycles of docetaxel or vinorelbine , followed in both groups by three cycles of fluorouracil , epirubicin , and cyclophosphamide ( FEC ) . Women with HER2-positive cancer ( n = 232 ) were further assigned to either receive or not receive trastuzumab for 9 weeks with docetaxel or vinorelbine . The median follow-up time was 62 months after r and om assignment . RESULTS Women assigned to docetaxel had better distant disease-free survival ( DDFS ) than those assigned to vinorelbine ( hazard ratio [ HR ] = 0.66 ; 95 % CI , 0.49 to 0.91 ; P = .010 ) . In the subgroup of HER2-positive disease , patients treated with trastuzumab tended to have better DDFS than those treated with chemotherapy only ( HR = 0.65 ; 95 % CI , 0.38 to 1.12 ; P = .12 ; with adjustment for presence of axillary nodal metastases , HR = 0.57 ; P = .047 ) . In exploratory analyses , docetaxel , trastuzumab , and FEC improved DDFS compared with docetaxel plus FEC ( HR = 0.32 ; P = .029 ) and vinorelbine , trastuzumab , and FEC ( HR = 0.31 ; P = .020 ) . The median left ventricular ejection fraction of trastuzumab-treated patients remained unaltered during the 5-year follow-up ; only one woman treated with trastuzumab was diagnosed with a heart failure . CONCLUSION Adjuvant treatment with docetaxel improves DDFS compared with vinorelbine . A brief course of trastuzumab administered concomitantly with docetaxel is safe and effective and warrants further evaluation PURPOSE Trastuzumab , a humanized antibody against the human epidermal growth factor receptor type 2 ( HER2 ) , has shown high efficacy in breast cancer . We prospect ively investigated its efficacy given simultaneously with anthracycline-taxane-based neoadjuvant chemotherapy . PATIENTS AND METHODS Patients with operable or locally advanced , HER2-positive tumors were treated preoperatively with four cycles of epirubicin/cyclophosphamide followed by four cycles of docetaxel with or without capecitabine ( EC-T[X ] ) and trastuzumab 6 mg/kg ( with a loading dose of 8 mg/kg ) every 3 weeks during all chemotherapy cycles . Patients with HER2-negative tumors treated in the same study with the same chemotherapy but without trastuzumab were used as a reference group . Results Of 1,509 participants , 445 had HER2-positive tumors treated with trastuzumab and chemotherapy . Pathologic complete response ( pCR ; defined as no invasive or in situ residual tumors in the breast ) rate was 31.7 % , which was 16 % higher than that in the reference group ( 15.7 % ) . HER2-positive patients without response to the first four cycles of EC showed an unexpectedly high pCR rate of 16.6 % ( 3.3 % in the reference group ) . Breast conservation rate was 63.1 % and comparable to that of the reference group ( 64.7 % ) . EC-T(X ) plus trastuzumab was associated with more febrile neutropenia and conjunctivitis , but with a comparable short-term cardiac toxicity profile as the reference group . CONCLUSION This trial confirms that combining trastuzumab with anthracycline-taxane-based neoadjuvant chemotherapy results in a high pCR rate without clinical ly relevant early toxicity . Combination of chemotherapy with trastuzumab should be considered when neoadjuvant treatment is given to patients with HER2-positive breast cancer |
12,350 | 16,856,090 | AUTHORS ' CONCLUSIONS The evidence suggests that symptom-based WAP are superior to peak flow WAP for preventing acute care visits although there is insufficient data to firmly conclude whether the observed superiority is conferred by greater adherence to the monitoring strategy , earlier identification of onset of deteriorations , higher threshold for presentation to acute care setting s , or the specific treatment recommendations | BACKGROUND While all asthma consensus statements recommend the use of written action plan ( WAP ) as a central part of asthma management , a recent systematic review of r and omised trials highlighted the paucity of trials where the only difference between groups was the provision or not of a written action plan .
OBJECTIVES The objectives of this review were firstly to evaluate the independent effect of providing versus not providing a written action plan in children and adolescents with asthma , and secondly to compare the effect of different written action plans . | Evidence -based practice involves the use of evidence from systematic review s and r and omised controlled trials , but the extent of this evidence in physiotherapy has not previously been surveyed . The aim of this survey is to describe the quantity and quality of r and omised controlled trials and the quantity of systematic review s relevant to physiotherapy . The Physiotherapy Evidence Data base ( PEDro ) was search ed . The quality of trials was assessed with the PEDro scale . The search identified a total of 2,376 r and omised controlled trials and 332 systematic review s. The first trial was published in 1955 and the first review was published in 1982 . Since that time , the number of trials and review s has grown exponentially . The mean PEDro quality score has increased from 2.8 in trials published between 1955 and 1959 to 5.0 for trials published between 1995 and 1999 . There is a substantial body of evidence about the effects of physiotherapy . However , there remains scope for improvements in the quality of the conduct and reporting of clinical trials 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 This study was conducted to test the efficacy of AIR WISE , an individually administered asthma self-management program . Subjects were paired and r and omly assigned to either an experimental group ( N = 7 ) or a control group ( N = 7 ) . The frequency of experimental group emergency visits , analyzed over a 12-month posttreatment period , was substantially less than those of the control group , supporting the hypothesis that AIR WISE is effective in high-utilizer children through improved self-management The treatment of an acute asthma attack usually includes bronchodilators and often steroids . We studied 70 children who were r and omly assigned to receive either single dose steroids ( oral prednisone : 20–40 mg ) or placebo on a double blind basis . The time course of the observation was 72 h. We demonstrate that a single dose of steroids , given orally in paediatric community clinics during an acute mild to moderate asthma attack , significantly improves the patient 's course ; deterioration was prevented , symptoms were relieved faster , and hospitalization was not required . We encourage paediatricians in the ambulatory clinics to follow this treatment modality and to give , in addition to other conventional therapy , a single oral dose of steroids early in the asthma attack , in order to relieve and shorten the child 's distress An educational training program for children with asthma , aged between 8 and 13 years , was evaluated in an 18-month r and omized , controlled experiment , including three follow-up evaluations . The objective of the program is to improve coping with asthma in daily life . The program , ten 1-hour sessions , is a combination of self-management training and cognitive behaviour therapy in a group , using games and learning material s specifically design ed for this age group . From 195 asthmatic children , 112 with inadequate self-management abilities were selected ; these children were r and omly divided into an experimental group and two control groups . The results indicated highly significant differences in favor of the experimental group on the psychological and medical variables . There were no drop-outs during the program . The conclusion is that this multi-faceted program is an effective method of teaching children how to cope with their asthma and helping them to achieve a less anxious and more realistic attitude towards their illness Twenty children with severe asthma using continual oral beta 2 agonists were r and omized equally into either a behavioral intervention group or a control group . The behavioral intervention consisted of : symptom discrimination of asthma signals , self-management techniques of breathlessness , and contingency management of asthma-related behavior . The purpose of the study was to evaluate the effects of the behavioral treatment when superimposed on a regular medical treatment . The design consisted of a four-week baseline period , a four-week intervention period , and a four-week follow-up period . Results showed that the group receiving the behavioral intervention significantly reduced their use of beta 2 agonist spray doses and days of school absenteeism without increasing the number of asthma symptoms compared with the control group . It was concluded that children with severe asthma may benefit substantially from a behavioral program in addition to their regular medical treatment Care of asthmatic children is often episodic and more therapeutic than preventive . A 2-year r and omized , controlled trial involving 95 children measured the impact of a comprehensive home and ambulatory program for pediatric asthma management using objective outcome measures . Interventions for the study group during the first year included 3-month clinic visits , education , and home visits by a specially trained research nurse . Control subjects continued to receive regular care from a family physician or pediatrician . Eight-nine subjects ( 93 % ) completed the study . Study subjects had less school absenteeism than control subjects ( 10.7 vs. 16.0 days , P = .04 ) and showed significantly better small airway function after 1 year . Asthma severity improved in 13 study subjects and worsened in 5 . The reverse was true for control subjects . Study subjects exhibited better metered aerosol technique than control subjects ( P = .0005 ) . Fewer days were spent in hospital by the study subjects admitted compared with control subjects ( 3.67 vs 11.2 days , P = .02 ) . After 1 year , more study than control families ( 72.1 % vs 33.1 % , P = .006 ) reported that their asthmatic child took responsibility for the asthma management . The intervention failed to reduce exposure to secondh and smoke or to household pets . There were no significant differences in medical visits , theophylline levels , or records of asthma symptoms . One year after discontinuing the intervention , a marked " washout " effect was observed . Comprehensive ambulatory programs of childhood asthma management can improve objective measures of illness severity but must be sustained 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 A r and omized control trial of a curriculum , A.C.T. ( Asthma Care Training ) for Kids , was conducted . Seventy-six children between the ages of 8 and 12 years , whose asthma required treatment with medications at least 25 % of the days per month , were r and omly assigned to control and experimental groups . The control group received 4 1/2 hours of lecture presentations on asthma and its management . The experimental groups ( consisting of four to seven children and their parents ) received five 1-hour sessions comprising " the treatment . " Children and their parents were interviewed before the sessions and 3 , 6 , and 12 months after the completion of the experimental treatment . Use of emergency rooms and hospitals was determined by review ing the records of these patients ( all members of the Los Angeles Kaiser Permanente health care system ) for the period of 1 year before and 1 year after the treatment . Results include ( 1 ) equivalent increases in knowledge and changes in beliefs in both groups , ( 2 ) significant changes in the self-reported compliance behaviors of the experimental group only , and ( 3 ) significant reductions in emergency room visits and days of hospitalization among those receiving the experimental treatment , compared with the control group . These changes represent an estimated savings of approximately $ 180 per child per year for those in the experimental group Children with asthma are at special risk for problems in psychological functioning , as are children with other chronic illnesses . We conducted a controlled trial of a combined education and stress management program among children ages 6 to 14 years with asthma . Eighty-one children were r and omly assigned to an intervention or a control group ; 56 children completed data collection , 29 intervention and 27 control . Psychological status was assessed by the Child Behavior Checklist ( CBCL ) before and after the intervention , as were children 's knowledge of asthma , stress ( as measured by children 's life events ) , and functional status ( as indicated by such activities as school attendance , time playing with friends , and daily chore performance ) . Children in the intervention group had a significant improvement in the total Behavior Problems score ( p < .04 ) and Internalizing scale ( p < .01 ) on the CBCL and a significant increase in daily chores ( p < .04 ) compared with the control group . Before intervention , the two groups had statistically significant positive relationships between negative life events and behavior problem scores . After intervention , children in the control group still demonstrated a significant relationship between negative life events and total and Internalizing Behavior Problem scores , although participation in the intervention group negated that relationship . Children in the intervention group whose knowledge of asthma increased were more likely to report an increase in daily chores ( p < .02 ) . We conclude that the intervention had a beneficial effect on psychological status and on children 's daily activities . The effect may have occurred in part by decreasing the likelihood that perceived stress from negative life events led to poorer adjustment OBJECTIVE To conduct a controlled trial of a home-based education program for low-income caregivers of young children with asthma . METHODS Participants were r and omized to treatment-eight weekly asthma education sessions adapted from the Wee Wheezers program ( n = 49)-or usual care ( n = 46 ) . Baseline and 3- and 12-month follow-up data were gathered from caregivers and from children 's medical records . RESULTS Treatment was associated with less bother from asthma symptoms , more symptom-free days , and better caregiver quality of life at follow-up for children 1 - 3 , but not those 4 - 6 , years of age . Treatment and control groups did not differ in caregiver asthma management behavior or children 's acute care utilization . CONCLUSIONS This home-based asthma education program was most effective with younger children ; perhaps their caregivers were more motivated to learn about asthma management . Targeting psychosocial factors associated with asthma morbidity might also enhance the efficacy of asthma education for these families A r and omized trial of an instructional method was conducted in which school nurses taught children asthma self-management principles and skills , including peak flow monitoring , in 20-min , individual sessions over an 8-week period . Thirty-six children participated . An intervention group of 18 children received the teaching sessions . A control group of 18 children received regular care by the nurses , but no teaching sessions . The sample included 64 % boys , 69 % African-Americans , and 69 % Medicaid recipients . The average age of subjects was 10.2 years . The two groups were demographically similar , but despite r and om assignment , the control group had a significantly earlier age of onset of asthma and tended to have had more asthma attacks in the preceding year . These factors were statistically controlled in outcome analyses . Results of group comparisons showed no significant differences in the number of postintervention emergency room visits and days absent from school . However , nurses reported that children who practice d breathing exercises had less anxiety during exacerbations , and the nurses ' knowledge of the children 's baseline peak expiratory flow rates facilitated care of the children . Nurses expressed the opinion that the individual sessions with students might be useful in motivating them to participate effectively in later group sessions . The intervention was well accepted by students , parents , and nurses . We believe that this intervention is promising as a practical , low-cost approach to enhancing children 's asthma self-management skills and warrants further testing in a larger sample , with the intervention conducted over a longer period Great emphasis is placed on educating asthmatics to use action plans to achieve better control of symptoms . The use of peak flow meters ( PFM ) has been recommended as an important part of self-management plans . We studied 92 ( 47 F ) adult patients with asthma in a primary care setting to compare the effectiveness of action plans using either peak flow monitoring or symptoms to guide self-management . Each patient was instructed in the use of the action plan in the context of a 6-mo asthma education program taught by a nurse . Patients were already using inhaled corticosteroids or were newly prescribed corticosteroids by their family physician . Forty-four patients were r and omized to the PFM group and 48 to the symptoms group . Spirometry , symptom scores , quality of life , medication use , and measures of health care utilization and morbidity ( emergency department visits , hospitalizations , unscheduled doctor visits , and days lost from work or school ) were recorded at baseline and throughout the study period . PC20 methacholine was measured at the first and at the final visits . There were significant improvements within groups for FEV1 , symptoms score , PC20 methacholine , and quality of life , but no between-group differences . A significant shift from higher to lower daily use of beta-agonists ( p < 0.008 for both groups ) and significant shifts to higher daily doses of inhaled steroids ( p < 0.001 ) occurred in each group . Adherence to the self-management plans was only 65 % in the PFM group and 52 % in the symptoms group . Outcomes for health care utilization were similar except for fewer patients making unscheduled doctor visits within the PFM group . Our findings show that education , regular follow-up , and an action plan are effective in improving asthma control and quality of life , but the routine use of PFM to guide interventions is not the only way to accomplish these objectives This study was design ed to answer three main questions : 1 ) Does asthma self-management education reduce asthma morbidity ? 2 ) Are the two programmes " Living With Asthma " and " Open Airways " equally effective in doing so ? 3 ) Is a shortened version of these programmes ( 4 weeks ) as effective as the longer original programme ( 8 weeks ) ? Twelve Italian centres of paediatric bronchopneumology selected 312 children with asthma , who were stratified by disease severity , gender and age , and then r and omly assigned to an Experimental group which received an educational programme or to a Comparison group , which did not . Of the 312 children selected , 209 ( 114 Experimental and 95 Comparison ) completed the educational protocol and a 1 year follow-up . Data recorded during the last 2 months of follow-up , 10 months after the educational intervention , showed that the Experimental group required significantly fewer emergency treatments : this reduction was more evident in the more severe asthma cases . In the Experimental , but not in the Comparison group , patients with more severe asthma consumed more medications than patients with milder asthma " Open Airways " yielded , in some cases , better results than " Living with Asthma " : but a type 2 error is possible . The st and ard and the shortened programmes proved equally effective . In conclusion , following education , regardless of receiving a short or long educational programme , asthma patients use emergency care services less and use medications more appropriately in comparison with st and ard care without education . This suggests that short educational programmes can be highly cost-effective in children with asthma 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 Background : Previous guidelines recommend doubling the daily dose of maintenance inhaled corticosteroid to treat or prevent progression of exacerbations of asthma . Methods : Over a 6 month period a cohort of patients were evaluated prospect ively and r and omised in a double blind controlled trial to treatment with either a continued maintenance dose ( MD ) of inhaled corticosteroid or doubling the dose ( DD ) at the time of an exacerbation . Results : A total of 290 patients were r and omised ( 33 % male ) and 98 ( DD , n = 46 ) experienced evaluable asthma exacerbations during the study period . Mean ( SD ) baseline characteristics at r and omisation ( age 33.5 ( 14.0 ) years ; forced expiratory volume in 1 second ( FEV1 ) 2.8 ( 0.7 ) l ; peak expiratory flow ( PEF ) 422.9 ( 110.5 ) l/min ) were similar in both groups . In the DD group 41 % of patients were considered treatment failures because they either required systemic steroids ( n = 12 ) , had an unscheduled visit to a physician ( n = 1 ) , or their asthma did not return to baseline ( n = 6 ) . This did not differ from the MD group in which 40 % were treatment failures ( n = 9 , 0 , and 12 , respectively ; p = 0.94 ) . Conclusions : In patients who regularly take an inhaled corticosteroid , doubling the maintenance dose may not affect the pattern of the exacerbation BACKGROUND --Peak flow based asthma self-management plans have been strongly advocated in consensus statements , but convincing evidence for the effectiveness of this approach has been largely lacking . METHODS --A r and omised controlled trial was conducted in 25 general practice s comparing an asthma self-management programme based on home peak flow monitoring and surgery review by a general practitioner or practice nurse with a programme of planned visits for surgery review only over a six month period . RESULTS --Seventy two subjects ( 33 in the self-management group and 39 in the planned visit group ) completed the study protocol , but diary card data for at least three months were available on a total of 84 ( 39 in the self-management group and 45 in the planned visit group ) . Teaching self-management took longer than the planned visit review . In the self-management group home peak flow monitoring was felt to be useful by doctors and patients in 28 ( 85 % ) and 27 ( 82 % ) cases , respectively . There were no between group differences during the study period in terms of lung function , symptoms , quality of life , and prescribing costs . Only within the self-management group were improvements noted in disturbance of daily activities and quality of life . Possible explanations for these negative results include small numbers of subjects , the mild nature of their asthma , and inappropriate self-management strategies for such patients . CONCLUSIONS -- Rigid adherence to long term daily peak flow measurement in the management of mild asthma in general practice does not appear to produce large changes in outcomes . Self-management and the use of prescribed peak flow meters need to be tailored to individual circumstances We prospect ively recruited patients admitted to the hospital with severe asthma to comprehensively evaluate the association of historical and physiologic features with the risk of near-fatal asthma ( NFA ) . A case-control study design was used . All patients admitted with NFA ( cases ) were identified prospect ively and compared with asthma patients admitted during the same period without respiratory failure ( controls ) . Nineteen cases ( age : 40.2 + /- 12.0 yr ) ( mean + /- SD ) and 80 controls ( age : 36 + /- 13.5 yr ) were enrolled . Duration of asthma , gender , smoking status , ethnicity , and prevalence of atopy were similar in the case and control groups . More than 80 % of patients in both groups reported worsening symptoms for more than 48 h before admission , and more than 50 % were worse for longer than 7 d. There was no difference in degree of airways obstruction or bronchial hyperresponsiveness ( PC20 ) . Perception of dyspnea was similar in the cases and controls , but among cases the males had greater impairment than the females ( Borg score : 1.9 + /- 1 . 4 versus 3.9 + /- 1.2 : p = 0.05 ) . Univariate analysis identified a history of previous mechanical ventilation ( OR : 27.5 ; 95 % CI : 6.60 to 113.7 ) , admission to the intensive care unit ( ICU ) ( OR : 9.9 ; 95 % CI : 3.0 to 32.9 ) , history of worse asthma during January and February ( OR : 3.5 ; 95 % CI : 1.0 to 11.8 ) , and use of air-conditioning ( OR : 15.0 ; 95 % CI : 1.3 to 166 ) as risk factors for NFA . Of concern was the dependence of most patients ( 59.8 % ) on the emergency department ( ED ) for initial care , and the small number of cases ( 16 % ) in which patients visited a physician before admission to the hospital . We have confirmed risk factors identified previously in retrospective studies of fatal and NFA , and have also shown that hospitalized patients with asthma , irrespective of severity of their asthma , share several characteristics , especially in terms of their failure to respond to worsening asthma We have assessed the effects of intervention on medication compliance in asthmatic children . The intervention comprised both written information about the medications and behavioural strategies effected by the physician . Children were assigned at r and om to either control ( received no intervention ) or test ( received the intervention ) groups . Compliance was assessed by question naire . The mean compliance for the test ( 78.0 % ; n = 93 ) and for the control ( 54.5 % ; n = 103 ) groups differed significantly ( P less than 0.001 ; Mann-Whitney U-test ) . The test group had a better knowledge of asthma and of the medications , and was more satisfied with the physician and with the regimen than was the control group . These variables were also related to good compliance . This study demonstrates that a programme of intervention can significantly improve medication compliance and can be accompanied by increases in the knowledge of , and satisfaction with , treatment BACKGROUND Accurate symptom evaluation is a critical component of asthma management . Limited data are available about the accuracy of symptom evaluation by children with asthma and their parents , or the impact of various symptom-monitoring strategies on asthma morbidity outcomes . OBJECTIVE The purpose of this r and omized clinical trial was to evaluate the effect of three different intensities of symptom monitoring on asthma morbidity outcomes . METHODS One hundred sixty-eight children ( ages 6 to 19 ) of diverse racial , geographic , and socioeconomic background s were r and omized to 1 of 3 treatment groups ( subjective symptom evaluation , symptom-time peak expiratory flow rate ( PEFR ) monitoring , daily PEFR monitoring ) in this longitudinal , clinical trial . Outcome measures included a summary asthma severity score , forced expiratory volume in 1 second , symptom days , and health care utilization . RESULTS Children who used PEFR meters ( PFMs ) when symptomatic had a lower asthma severity score , fewer symptom days , and less health care utilization than children in the other two treatment groups . Minority and poor children had the greatest amount of improvement using PFMs when symptomatic . Results were much less striking in white families . Thirty percent of families in the PFM treatment groups discontinued use entirely by 1 year postexit , whereas the majority of families who continued use ( 94 % ) used them only when symptomatic to inform symptom interpretation and management decisions . CONCLUSIONS Not every child with asthma needs a PFM . Children and families facing extra challenges as a result of illness severity , sociodemographic , or health care system characteristics clearly benefited most from PFM use BACKGROUND Asthma is common and is often poorly controlled in adolescent subjects . OBJECTIVE To determine the impact of an age-specific asthma program on asthma control , particularly on exacerbations of asthma requiring emergency department treatment , and on the quality of life of adolescents with asthma . METHODS The present r and omized , controlled trial included patients who were 15 to 20 years of age and had visited emergency departments for management of their asthma . The interventional group attended an age-specific asthma program that included assessment , education and management by a team of asthma educators , respiratory therapists and respiratory physicians . In the control group , spirometry was performed , and the patients continued to receive usual care from their regular physicians . The outcomes were assessed by a question naire six months after entry into the study . RESULTS Ninety-three subjects entered the study and were r and omly assigned to the intervention or control group . Of these , only 62 patients were available for review after six months . Subjects in both the control and the intervention groups showed a marked improvement in their level of asthma control , reflected primarily by a 73 % reduction in the rate of emergency department attendance for asthma . Other indexes of disease control , including disease-specific quality of life , as assessed by question naires , were improved . There was , however , no discernible difference between the subjects in the two groups , with the exception of an improvement in favour of the intervention group in the symptom ( actual difference 0.7 , P=0.048 ) and emotional ( actual difference 0.8 , P=0.028 ) domains of the asthma quality of life question naire . The overall quality of life score favoured the intervention group by a clinical ly relevant difference of 0.6 , but this difference did not reach statistical significance ( P=0.06 ) . CONCLUSIONS Although all subjects demonstrated a significant improvement in asthma control and quality of life , the improvement attributable to this intervention was limited to two domains in disease-specific quality of life A small , controlled trial of joint treatment of childhood asthma by a doctor , a physiotherapist , a psychologist , and a social worker , working together in the family setting , demonstrated an improvement in ventilatory capacity . The limited scope of this trial does not permit more general conclusions as to the effect of such treatment on the severity and frequency of attacks , but the observation that some measurable physiological improvement occurred suggests that the place of multidisciplinary nonpharmaceutical management of childhood asthma should be investigated in more detail The objective of the present study was to evaluate the effects of a self-management educational program on 29 children between 6 and 14 years old and their parents implemented in an office setting in Venezuela . Children were r and omly assigned to experimental and control group . Children 's asthma knowledge , self-management abilities , index morbidity , parents ' asthma knowledge and management abilities were measured . The program consisted of six sessions of information giving and cognitive-behavioral strategies for the children , and two talks and an informative brochure for the parents . Results of t tests indicate that the experimental group experienced a statistical significant effects on children 's asthma knowledge ( P < 0.001 ) and practice of self-management abilities ( P < 0.000 ) and in parents ' knowledge ( P < 0.008 ) compared to the control group . The educational Self-management program had a significant impact on the Morbidity Index of the study group at post-test ( P < 0.05 ) . Younger children benefited more from the program compared to older ones ( P < 0.09 ) . Children 's age is highlighted as a critical variable in design ing asthma educational programs . Results suggest the effectiveness on these programs independently of the cultural context OBJECTIVE To explore children 's and parents ' assessment of children 's asthma . DESIGN Prospect i ve 2-month cohort study in which children and parents were review ed at baseline and 1-month intervals . SETTING Mid-sized , English-speaking , industrial community serving an urban and regional rural population . PATIENTS OR PARTICIPANTS Fifty-two children , 7 to 17 years old , with a wide range of asthma severity , and their parents . INTERVENTIONS We offered patients with inadequately controlled asthma additional inhaled steroid . MAIN OUTCOME MEASURES Children and parents provided global ratings of change in childhood symptoms and children completed spirometry and the Paediatric Asthma Quality of Life Question naire at clinic visits . Patients recorded peak flow rates , symptoms , and medication use in a daily diary . The diary symptom report , medication use , and spirometry were combined to form an asthma control score . RESULTS In children younger than 11 , children 's global rating of change in symptoms correlated strongly with changes in quality of life ( 0.54 to .67 ) but not with measures of airway caliber or asthma control , while parents ' global ratings did not correlate with children 's quality of life but showed moderate correlations with airway caliber ( 0.29 to .48 ) and asthma control ( 0.50 ) . In children over the age of 11 , correlations with all clinical variables were higher for their own than their parents ' global ratings . CONCLUSIONS In children under 11 , clinicians can gain complementary information from question ing children and parents . For children over 11 , parents can provide little if any information beyond that obtained through question ing the child BACKGROUND Episodic wheeze triggered by viral colds is common in children aged between 1 and 5 years ( preschool viral wheeze ) . Most affected children are asymptomatic by age 6 years . Persistence of wheeze is associated with above-average systemic eosinophil priming . Use of parental-initiated oral prednisolone is recommended at the first sign of preschool viral wheeze . However , evidence for this treatment strategy is conflicting . We therefore aim ed to assess the efficacy of a short course of oral prednisolone for preschool viral wheeze , with stratification for systemic eosinophil priming . METHODS Children aged 1 - 5 years admitted to hospital with viral wheeze were allocated to either a high-primed or low-primed stratum according to amounts of serum eosinophil cationic protein and eosinophil protein X , and r and omised to parent-initiated prednisolone ( 20 mg one daily for 5 days ) or placebo for the next episode . The primary outcomes were the 7-day mean daytime and night-time respiratory symptom scores , which were analysed by mean differences between treatment groups . FINDINGS 108 children were r and omised to placebo and 109 to prednisolone . Outcome data were available for 120 ( 78 % ) of 153 children who had a further episode of viral wheeze , of whom 51 received prednisolone and 69 placebo . Mean daytime ( difference in means -0.01 [ -0.22 to 0.20 ] ) and night-time ( 0.10 [ -0.12 to 0.32 ] ) respiratory symptom scores and need for hospital admission did not differ between treatment groups . Within the high-primed ( n=59 ) and low-primed ( n=61 ) strata there was no difference in primary outcome between treatment groups . INTERPRETATION There is no clear benefit of a short course of parent-initiated oral prednisolone for viral wheeze in children aged 1 - 5 years even in those with above-average eosinophil priming BACKGROUND Although inhaled glucocorticosteroids are recommended for persistent asthma , their long-term effect on recent onset , mild , persistent asthma has yet to be established . METHODS We did a r and omised , double-blind clinical trial in 7241 patients in 32 countries to assess the effects of budesonide in patients who had had mild persistent asthma for less than 2 years and who had not had previous regular treatment with glucocorticosteroids . Patients aged 5 - 66 years received either budesonide or placebo once daily for 3 years in addition to their usual asthma medications . The daily budesonide dose was 400 microg , or 200 microg for children younger than 11 years . The primary outcome was time to first severe asthma-related event , and analysis was by intention to treat . FINDINGS 198 of 3568 patients on placebo and 117 of 3597 on budesonide had at least one severe asthma exacerbation ; hazard ratio 0.56 ( 95 % CI 0.45 - 0.71 , p<0.0001 ) . Patients on budesonide had fewer courses of systemic corticosteroids and more symptom-free days than did those on placebo . Compared with placebo , budesonide increased postbronchodilator forced expiratory volume in 1 s ( FEV1 ) from baseline by 1.48 % ( p<0.0001 ) after 1 year and by 0.88 % ( p=0.0005 ) after 3 years ( expressed as percent of the predicted value ) . The corresponding increase in prebronchodilator FEV1 was 2.24 % after 1 year and 1.71 % after 3 years ( p<0.0001 at both timepoints ) . The effect of treatment on all outcome variables was independent of the baseline lung function ( prebronchodilator or postbronchodilator ) or baseline medication . In children younger than 11 years , 3-year growth was reduced in the budesonide group by 1.34 cm . The reduction was greatest in the first year of treatment ( 0.58 cm ) than years 2 and 3 ( 0.43 cm and 0.33 cm , respectively ) . INTERPRETATION Long-term , once-daily treatment with low-dose budesonide decreases the risk of severe exacerbations and improves asthma control in patients with mild persistent asthma of recent onset OBJECTIVE To investigate the efficacy of an increased dose of inhaled steroid used within the context of an asthma self management plan for treating exacerbations of asthma . DESIGN R and omised , double blind , placebo controlled , crossover trial . METHODS Twenty eight children aged 6–14 years with asthma of mild to moderate severity were studied for six months . Eighteen pairs of exacerbations were available for analysis , during which subjects took an increased dose of inhaled steroids or continued on the same dose . RESULTS There was no significant difference between increasing inhaled steroids or placebo on morning or evening peak expiratory flow rates ( PEFRs ) , diurnal peak flow variability , or symptom scores in the two weeks following an asthma exacerbation . Difference ( 95 % confidence intervals ) in baseline PEFR on days 1–3 were 3.4 % ( −3.5 % to 10.4 % ) and −0.9 % ( −4.7 % to 2.9 % ) for inhaled steroid and placebo , respectively . Spirometric function and the parents ’ opinion of the effectiveness of asthma medications at each exacerbation were also not significantly different between inhaled steroid or placebo . CONCLUSION This study suggests that increasing the dose of inhaled steroids at the onset of an exacerbation of asthma is ineffective and should not be included in asthma self management plans The effectiveness of an educational program to increase compliance with cromolyn sodium was assessed in 31 children and adolescents 6 to 17 years of age . Patients were r and omly assigned to an education or noneducation group . A st and ard education program regarding asthma and asthma medications was provided to the education group during four monthly visits . At each visit , all patients were assessed in terms of knowledge of asthma and medications , asthma-related symptoms , and pulmonary function . Patients were also asked to self-rate their compliance . The education program increased the patients ' knowledge of cromolyn , and appeared to result in increased cromolyn compliance . Post-hoc analyses , however , suggested that increased compliance did not correspond to improved medical status unless the quality of management ( by physician and parents ) of the child 's asthma was taken into account . These results suggest that inadequate management of asthma in children may be a more serious problem than patient noncompliance OBJECTIVE To compare the use of patient-performed peak expiratory flow ( PEFR ) and symptom monitoring as asthma self-management tools initiated from community pharmacies . DESIGN AND SETTING 110 patients over 6 years of age were recruited from five private-sector community pharmacies . Patients were identified from pharmacist recall as having ' asthma ' . Information on the frequency of their asthma symptoms , medication use , level of physical activity , school or work attendance and lung function was obtained using a question naire to classify patients as either mild , moderate or severe . Each patient was alternately assigned to either the symptom or PEFR monitoring procedure in the order they were recruited . Patients performing symptom monitoring used a visual analogue scale to assess symptoms , whereas those in the PEFR monitoring group assessed symptoms and used a pocket-size peak flow meter to measure lung function . Both self-monitoring groups were required to adhere to an individualized management plan based on guideline recommendations and to record their monitored data in a diary card for 2 months . Data from the diary cards were review ed , collated , transcribed and analysed using the Student t and Mann-Whitney tests . OUTCOME MEASURES The average monthly frequency of appropriate patient responses determined from their adherence to the self-management plan was used to compare the usefulness of symptom and PEFR self-monitoring . In particular , appropriate use of medication and need for medical consultation was compared . RESULTS 21 symptom and 40 PEFR-assigned patients completed 2 months ' monitoring . The average monthly frequency of appropriate responses in patients using PEFR ( 0.76 ) was significantly higher than that of patients using symptom monitoring ( 0.53 , P < 0.006 ) . Patients applying symptom monitoring had a higher monthly frequency ( 0.39 ) of inappropriate medication use compared to the PEFR group ( 0.14 ) . Furthermore , the patients ' mean daily symptom scores ( 2.85 ) were significantly lower than that estimated by the research er ( 4.12 , P < 0.03 ) . For all three asthma severity groups a higher monthly average of appropriate responses was observed in patients using PEFR monitoring compared to those who used symptom monitoring . CONCLUSION PEFR self-monitoring proved to be a more useful asthma tool than symptom self-monitoring . Patients applying symptom monitoring tend to underestimate the severity of their condition and use medication inappropriately . Active involvement of community pharmacists in facilitating and reinforcing out-patient self-monitoring would help to optimize asthma management OBJECTIVE --To compare a peak flow self management plan for asthma with a symptoms only plan . DESIGN --R and omisation to one of the self management plans and follow up for a year . SETTING --Four partner , rural training practice in Norfolk . SUBJECTS--115 Patients ( 46 children and 69 adults ) with asthma who were having prophylactic treatment for asthma and attending a nurse run asthma clinic . MAIN OUTCOME MEASURES --The number of doctor consultations , courses of oral steroids , and short term nebulised salbutamol treatments and the number of patients who required doctor consultations , courses of oral steroids , and short term nebulised salbutamol . RESULTS --Both self management plans produced significant reductions in the outcome measures but there were no significant differences in the degree of improvement between the groups . The results were similar for children and adults . The proportions of patients requiring a doctor consultation fell from 98 % ( 50/51 ) to 66 % ( 34/51 ) in the peak flow group and from 97 % ( 62/64 ) to 53 % ( 34/64 ) in the symptoms only group and the proportions requiring oral steroids from 73 % ( 34/46 ) to 47 % ( 21/46 ) and 52 % ( 31/60 ) to 12 % ( 7/60 ) . The median number of doctor consultations was reduced from 8.0 to 2.0 in the peak flow group and from 4.5 to 1.0 in the symptoms only group . CONCLUSIONS --The peak flow meter was not the crucial ingredient in the improved illness of the two groups . Teaching patients the importance of their symptoms and the appropriate action to take when their asthma deteriorates is the key to effective management of asthma . Simply prescribing peak flow meters without a system of self management and regular review will be unlikely to improve patient care A clinic supervised by a nurse , using principles originally developed in general practice , was established in the paediatric department of a district general hospital . A r and omised controlled study was conducted comparing children admitted with asthma or attending out patients who were given a patient education programme and self management plan ( intervention group ) with a control group . The study comprised 91 patients aged 3 - 14 years admitted for asthma or attending a hospital outpatient department from November 1989 to November 1990 . Seventy seven patients completed the study and kept diaries for a median of 283 days . Patients in the intervention group had significantly less restriction of activity ( 95 % confidence interval ( CI ) -0.27 to -0.01 ) and fewer episodes of peak flow below 30 % of best ( 95 % CI 0.03 to 1.17 ) . Patients in the intervention group were more likely to make the correct response to an acute exacerbation of their asthma than the control group ( 71 % v 47 % , 95 % CI 9.51 to 39.1 ) . The intervention group had fewer school absences and fewer home visits by a general practitioner . There was an increase in the readmission rate for the intervention group . A subgroup of patients who self managed by doubling their use of inhaled steroids during an exacerbation performed better than those patients who only increased their bronchodilator or were managed on salbutamol or sodium cromoglycate alone . Improvements in patient follow up and the structure of the self management plans used , particularly changing the peak flow level at which inhaled steroids are doubled , may further improve the outcome of patients attending the asthma clinic The Self-Care Rehabilitation in Pediatric Asthma ( SCRPA ) project was design ed to ascertain ( 1 ) the level to which children with asthma are able to acquire the asthma knowledge and skills presented in a self-management training program conducted by the American Lung Association of Utah and ( 2 ) the effect of such training on the asthma experience . The preschool SCRPA Curriculum ( ages 2 - 5 ) consisted of six 1-hour classes scheduled twice a week for 3 weeks . The first and last classes were for one or both parents only , and the middle four sessions were for the child and parent(s ) . The school-age SCRPA curriculum ( ages 6 - 14 ) consisted of eight 90-minute classes for both child and parent(s ) scheduled twice a week for 4 weeks . Private physicians referred 21 preschool children and 38 school-age children into the program . The school-age children were r and omly assigned to a study or control group , and the preschool children served as their own controls . A comparison of asthma episodes during the 3 months before and after training showed a statistically significant decrease in the number of episodes but no change in severity in the preschool , school study , and school control groups . The decrease in episodes for the control groups suggest that the family record keeping required of all subjects may have a beneficial effect , a phenomenon worth further investigation . Also , the school-age group , in pre- and posttesting , demonstrated that the SCRPA curriculum increased knowledge and skills in the study group , changes not found in the control group To address the recent rise in asthma morbidity and mortality in Russia , an intervention study was conducted to improve asthma diagnosis , treatment and prevention . US recommendations for asthma management were adapted for use in educating Moscow families with children with asthma . Two hundred and fifty-two children with asthma aged 4 - 14 years receiving health care in eight Moscow public health clinics together with their parents were enrolled in the study to see whether US teaching manuals for asthma management would be acceptable and effective in Russia . Children at four of the clinics with recent asthma attacks were r and omly assigned to either the education or control group to test if patient education and guided asthma care would improve outcomes for patients . Modern medications were made available to both groups to see if training in the US guidelines was necessary to get physicians to use the medications . Children with recent asthma attacks at the other four clinics were defined as comparison group 1 to control for the possible effect of medication availability . All children at the eight clinics who had no asthma attacks composed comparison group 2 to see if the outcomes for these children would change over time . One-year follow-up results showed significant improvement in asthma self-management skills of children and parents , in terms of asthma treatment , only among those in the education group . Significant increases were observed in the subgroup of children in the education group using anti-inflammatory drugs for asthma control . Children in the education group had markedly increased peak flow rates and reduced daily peak flow variability as compared to control and comparison groups . There was a significantly greater reduction in doctor visits by the education group of children compared to control . Presumably , changes in parents ' and children 's behaviour in terms of asthma treatment and prevention skills , proper treatment of the disease and access to medications could be responsible for reducing asthma morbidity in children BACKGROUND We have previously reported a high prevalence of current asthma-related symptoms affecting predominantly Hispanic , socioeconomically disadvantaged schoolchildren in Southeast San Diego . OBJECTIVE We sought to assess the impact of a school-based education program on asthma outcomes . METHODS In cooperation with the San Diego Unified Schools , we developed and implemented a school-based asthma education program . Based on the National Heart , Lung , and Blood Institute consensus guidelines for asthma , the five-session bilingual , interactive curriculum was conducted in 20-minute segments . Asthma knowledge was tested before and after the education program , and asthma severity was prospect ively assessed at monthly intervals . Outcome parameters were compared in educated and control ( noneducated ) fourth grade students with asthma by using nonparametric techniques . RESULTS After asthma education , students demonstrated improvement with increases in mean scores for : asthma knowledge quiz from 9.9 ( SEM = 0.44 , n = 34 ) to 13.7 ( SEM = 0.30 ) ; peak flowmeter technique from 3.9 ( SEM = 0.33 , n = 32 ) to 6.4 ( SEM = 0.29 ) ; and inhaler technique from 2.3 ( SEM = 0.26 , n = 32 ) to 4.3 ( SEM = 0.26 ) . All changes were highly significant ( p < or = 0.00001 as determined by Wilcoxon matched-pairs signed-rank test ) . Mean score comparisons for asthmatic control students given paired examinations after a time interval matched with the educated students , did not reach statistical significance : quiz score of 11.3 ( SEM = 0.80 , n = 11 ) versus 10.9 ( SEM = 0.68 ) , peak flowmeter technique score of 2.6 ( SEM = 0.50 , n = 18 ) versus 3.1 ( SEM = 0.37 ) , and inhaler technique score of 2.5 ( SEM = 0.37 , n = 18 ) versus 2.2 ( SEM = 0.31 ) . Prospect i ve monthly data were collected on 27 educated and 15 control asthmatic subjects . Severity of asthma was not significantly different between groups at entry to the study . Symptom question naires , vali date d for functional asthma severity , revealed a significant reduction in mean symptom scores at 180 days for the educated ( 2.87 , SEM = 0.447 ) versus the control ( 4.36 , SEM = 0.573 ) groups ( p = 0.0188 as determined by the Mann-Whitney U test ) . CONCLUSION Child-centered asthma education can be successfully conducted in the school setting , result ing in increased asthma knowledge , improved skills for peak flowmeter and inhaler use , and a reduction in the severity of asthma symptoms We asked whether the addition of PEF recordings to a symptom-based self-management plan improved outcome in school children with asthma . In an open-r and omized , parallel-group , controlled trial , we studied children aged 7 - 14 years with moderate asthma . After a 4-week run-in , 90 children were r and omized to receive either PEF plus symptom-based management or symptom-based management alone for 12 weeks . Thresholds for action based on PEF were 70 % of best ( for increasing inhaled steroids ) and 50 % of best ( for commencing prednisolone ) . Children were asked to perform twice-daily spirometry at home ( using an electronic recording spirometer that revealed only PEF to the study group alone ) and to record a symptom diary . The mean daily symptom score was the main outcome . There were no differences between groups in mean symptom score or in spirometric lung function , PEF , quality of life score , or reported use of health services over 12 weeks . During acute episodes , children responded to changes in symptoms by increasing their inhaled steroids at a mean value of PEF of greater than 70 % of best so that overall PEF did not contribute to this important self-management decision . Knowledge of PEF did not enhance self-management even during acute exacerbations To affect asthma-related knowledge , behavior , and morbidity , research ers tested a new educational intervention for children with asthma : an asthma-specific computer game called Asthma Comm and , which was specifically design ed for this study . Sixty-five children with moderately severe asthma were r and omly assigned to one of two groups , and 54 completed the study . Both groups were seen approximately six times during the 1 year of the study . Control subjects ( n = 29 ) played routine computer games . Experimental subjects ( n = 25 ) played Asthma Comm and . Compared with children in the control group , experimental subjects showed improvement in knowledge about asthma ( P less than .001 ) , behavior related to the management of asthma ( P less than .008 ) , and a trend toward the reduction of acute visits due to asthma ( P less than .13 ) . Children in the experimental group also scored higher on the assessment of behaviors related to the management of asthma that were specifically addressed by the intervention provided by Asthma Comm and ( P less than .01 ) . Differences between the control and experimental groups showed a greater improvement in the experimental group in 21 ( 84 % ) of the 25 outcome variables in the study ( P = .004 , Sign test ) . The study indicates that an asthma-specific computer game can significantly affect knowledge and behavior and may potentially affect morbidity in childhood asthma From 1988 onwards inpatient asthma training courses have been conducted in Berlin and Osnabrück . A controlled study on asthma training was carried out from 1990 to 1992 at both centres with the support of the Robert Bosch Foundation . In the first intervention group a subsequent training course of 6 months ' duration was conducted with the inclusion and participation of the relevant family doctors in addition to the main training course . Scrutiny of the result was done before ( T1 ) , directly after ( T2 ) and 12 months subsequent to the training course ( T3 ) . Improvements are seen in somatic data or cost-relevant data ( emergency referral to the hospital or family physician , inpatient hospital periods , referral because of mild obstruction , days of non-attendance in school due to illness , severity of asthma , incidence of symptoms , stress endurance in sports ) . There is also a marked improvement in the self- assessment ability of the children and in the management of asthma , as well as a decrease in the asthma-specific feeling of anxiety . Self-reliance and independence , as well as early intervention , are improved as seen by the parents , whereas on the other h and unfavourable factors such as arguments on the proper asthma therapy are diminished . Especially with regard to confidence in controls on the state of health or disease there are significant changes that are more marked in the group subjected to subsequent training than in the group without such additional training , compared with the control group . Structured asthma training exercises a strongly positive effect on the daily management of asthma bronchiale by the families on different planes of coping with the disease . These effects are enhanced by subsequent aftercare by the family physician . Intensive care in the asthma outpatient wards alone does not sufficiently modify the factors contributing to good coping with the disease OBJECTIVE Caring for a child with asthma can affect the parent 's coping and well-being and coping strategies . This study examined the influence of a home-based asthma health education program on parental coping and quality of life . DESIGN R and omized controlled non-blinded clinical trial . SETTING Northern community pediatrician 's office . PATIENTS Families whose children , under the age of 11 , had chronic stable asthma , and who presented to the pediatrician 's office for continuing care ; those with an acute exacerbation of asthma were excluded . INTERVENTIONS Families were r and omly assigned to receive either a single two-hour , st and ardized home-based asthma health education session or a booklet representing conventional care . MAIN OUTCOME MEASURES One and three-months following the intervention , assessment s were obtained for coping measured by Hymovich 's Parent Perception Inventory ( PPI ) , quality of life measured by the Pediatric Asthma Caregiver Quality of Life Question naire ( PACQLQ ) and change in asthma measured by the Caregiver Perception of Change ( CPC ) survey . RESULTS Forty families were recruited and r and omized ; baseline characteristics were similar between groups . At the final follow-up , reduction in parental need for asthma information ( p = 0.04 ) , reduction in parental concerns ( p = 0.02 ) and increased use of coping strategies ( p = 0.04 ) were observed in the home-based care group . Improvement was noted in the parent 's perception of their child 's asthma in the home-based asthma education group ( p = 0.01 ) . Quality of life as measured by the PACQLQ remained unchanged over the intervention period ( p > 0.05 ) . CONCLUSIONS These results suggest the use of a one-time , flexible , home-based intervention to assist families caring for children with asthma should be considered and appears effective 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 Asthma guidelines recommend increasing or doubling inhaled corticosteroid ( ICS ) dose to treat mild and moderate exacerbations of asthma in adults . AIM To : ( i ) compare the effectiveness of doubling existing daily ICS dose ( fluticasone ) with maintaining usual ICS dose and usual daily ICS dose accompanied by oral steroids ( OS ) ( dexamethasone ) during mild and moderately severe exacerbations of asthma in adults ; ( ii ) examine determinants of success and failure ; and ( iii ) compare side-effect profiles . METHODS A r and omized , double-blind , placebo-controlled ( double-dummy ) , triple crossover trial . Participants acted as their own control . Outcome measures included treatment success/failure , peak expiratory flow ( PEF ) after 7 days therapy or at treatment failure , and side-effects . RESULTS From 22 participants ( nine males and 13 females ) , 18 pairs of data were available for maintaining usual ICS versus doubling ICS and doubling ICS versus OS , and 19 for maintaining usual ICS versus OS . Median ( fifth-95th percentile ) age was 46.5 ( 32 - 64 ) years and forced expiratory volume in one second ( FEV(1 ) ) 73 % ( 29 - 97 % ) predicted . The outcome after doubling ICS was not superior to maintaining usual ICS , with 11 ( 61 % ) failures in both arms ( P = 0.66 ) . OS , with only 5 ( 26 % ) failures , was superior to maintaining usual ICS with 12 ( 63 % ) failures ( P = 0.04 ) , and to doubling ICS with 5 ( 28 % ) versus 11 ( 61 % ) failures ( P = 0.07 ) . Median PEF ( as percentage of run-in best ) at end-points were 90.5 % ( 57.1 - 177.1 ) for OS , 78.3 % ( 39.5 - 103.1 ) for maintaining usual ICS and 77.9 ( 27.7 - 110.3 ) for doubling ICS . Neither gender nor PEF at exacerbation were predictive of failure . Although doubling ICS was not an effective therapy overall , ICS dose at exacerbation were predictive of success in the doubling ICS arm ( P = 0.04 ) . Treatment failures when doubling daily ICS dose were more common if achieved fluticasone dose was less than 2000 microg ( three of 11 , 73 % ) compared to 2000 microg or greater ( eight of eight , 37.5 % ) . Increasing age and the presence of an upper respiratory tract infection ( URTI ) were predictive of failure with OS . Side-effects were more commonly reported with OS ( 52.6 % ) than doubling ICS ( 42.1 % ) or maintaining usual ICS ( 19.1 % ) with the most common being mood changes ( 36.8 % ) , sleep disturbance ( 31.6 % ) and changes in appetite ( 26.3 % ) . CONCLUSIONS Doubling daily ICS dose per se is not effective for the treatment of mild to moderately severe exacerbations of asthma in adults . Success may depend on achieved ICS dose . Oral steroids are effective , but side-effects are common . A review of current guidelines may be warranted A research project , which looks at the value of health education in the prevention of childhood asthma , is described . The project was a controlled trial by a health visitor focused within the community . This exploratory research looked at three groups of children over a 2-year period , and compared the effect of : ( a ) individual health education , and ( b ) group health education . During the first year , two groups were active , one receiving individual health education , the other collecting data of the same type . During the second year , a third group was involved in health education sessions . The findings have been similar in both cases , in that both groups have demonstrated a good improvement in knowledge of asthma and its treatment . Through the active involvement of using a peakflow meter and diary records in the health education programme , both groups receiving health education have shown a significant improvement in the morbidity indicators related to night symptoms and restricted activities . The qualitative analysis of the research also highlighted the value parents of asthmatic children place on counselling A sample of 310 low income urban children with asthma from 290 families was r and omized into a control group and an experimental group that received health education to improve asthma management at home . No significant decreases in subsequent health care use were observed when the experimental group was compared to the control group without regard to previous hospitalization . When the comparison was restricted to children who had been hospitalized during the preceding year , however , the experimental group was found to have decreased its use of the emergency room significantly more than the control group ( p less than 0.05 ) and to have experienced a significantly greater reduction in the mean number of hospitalizations ( p less than 0.05 ) during the year of follow-up . The program reduced health care costs for children with one or more hospitalizations , saving $ 11.22 for every $ 1.00 spent to deliver health education PURPOSE To examine the relationship between self-reported and electronically monitored adherence to a recommended asthma treatment and to assess the accuracy of the diary data reported by school-age children . DESIGN A r and omized , controlled clinical trial of the effectiveness of an asthma self-management program . The relationship between self-reported and electronically recorded daily peak expiratory flow rate ( PEFR ) adherence was assessed in a sample of 42 children , ages 7 through 11 years with moderate to severe asthma in one community in West Virginia , USA . Cognitive social learning theory served as the framework for the intervention . METHODS At-home adherence to PEFR monitoring during the 5-week study was evaluated using the self-report Asthma Diary and an electronic PEFR meter . Recommended twice daily ( morning and evening ) PEFR monitoring was measured . RESULTS Self-reported and electronically recorded PEFR adherence were modestly correlated . Self-reported adherence was significantly higher than electronically monitored adherence during Week 5 . Accuracy of the self-reported PEFR declined over time , and over half of the children fabricated at least one PEFR value during the final week of the study . CONCLUSIONS Clinicians often evaluate the efficacy of prescribed treatment for children with chronic conditions based on the children 's self-reported diary data . The findings indicate that these children 's self-reported adherence behaviors contained errors . Parent education regarding supervision of children 's adherence , including validating the accuracy of diary data , is critical for successful self-management in children with chronic conditions OBJECTIVE To evaluate a family-focused asthma intervention design ed for inner-city children 5 to 11 years old with moderate to severe asthma . STUDY DESIGN R and omized , multisite , controlled trial to minimize symptom days ( wheeze , loss of sleep , reduction in play activity ) measured by a 2-week recall assessed at 2-month intervals over a 2-year follow-up period . The intervention was tailored to each family 's individual asthma risk profile assessed at baseline . RESULTS Averaged over the first 12 months , participants in the intervention group ( n = 515 ) reported 3.51 symptom days in the 2 weeks before each follow-up interview compared with 4.06 symptom days for the control group ( n = 518 ) , a difference of 0.55 ( 95 % CI , 0.18 to 0.92 , P = .004 ) . The reduction among children with severe asthma was approximately 3 times greater ( 1.54 d/2 wk ) . More children in the control group ( 18.9 % ) were hospitalized during the intervention compared with children in the intervention group ( 14 . 8 % ) , a decrease of 4.19 % ( CI , -8.75 to 0.36 , P = .071 ) . These improvements were maintained in the intervention group during the second year of follow-up , during which they did not have access to the asthma counselor . CONCLUSIONS We demonstrated that an individually tailored , multifaceted intervention carried out by Masters-level social workers trained in asthma management can reduce asthma symptoms among children in the inner city An educational program for children with asthma design ed to reduce emergency room ( ER ) use enrolled all eligible children ( n = 253 primarily low-income Black ) within a health maintenance organization ( HMO ) who had used the hospital or ER for asthma during the pre-enrollment period and r and omized them into two groups . Twenty-four of the experimental group patients had 55 ER visits and 18 of the control patients had 39 ER visits during the first 12 months post-intervention . This program did not achieve its goal PURPOSE Adherence to peak expiratory flow rate monitoring by children with asthma was evaluated , and a behavioral strategy to enhance adherence to daily monitoring was tested . DESIGN AND METHODS Forty-two 7- through 11-year-old children with persistent asthma were recruited into a 5-week r and omized , controlled clinical trial . Adherence data were collected electronically by PeakLog and the self-report Asthma Diary . RESULTS Adherence declined over time . At week 5 , intervention group adherence ( Median = 79 % ) was higher than the usual care group adherence ( Median = 64 % ) , but the difference was not statistically significant . The effect size did suggest that differences between groups were present . CONCLUSIONS Even small improvements in adherence to asthma treatment may be clinical ly significant in light of the alarming increases in asthma morbidity and mortality . Contingency management shows promise for improving adherence outcomes . Future research should engage larger sample sizes and increase the number and intensity of sessions to teach behavioral strategies Abstract Objective : To compare the efficacy of self management of asthma with traditional treatment . Design : 12 month prospect i ve r and omised trial . Setting : Outpatient clinics in Finl and . Subjects : 115 patients with mild to moderately severe asthma . Interventions : Patient education and adjustment of anti-inflammatory therapy guided by peak flow measurements . Main outcome measures : Unscheduled admissions to hospital and outpatient visits , days off work , courses of antibiotics and prednisolone , lung function , and quality of life . Results : The mean number of unscheduled visits to ambulatory care facilities ( 0.5 v 1.0 ) , days off work ( 2.8 v 4.8 ) , and courses of antibiotics ( 0.4 v 0.9 ) and prednisolone ( 0.4 v 1.0 ) per patient were lower and the quality of life score ( 16.6 v 8.4 at 12 months ) higher in the self management group than in the traditionally treated group . In both groups admissions for asthma were rare . Conclusions : Self management reduces incidents caused by asthma and improves quality of life . Key messages Key messages This trial of 115 patients with mild to moderately severe disease r and omised half to a traditional care and half to a self management programme consisting of education about asthma and daily peak flow readings Intervention thresholds of < 85 % of the optimal peak flow for doubling the dose of inhaled steroid for two weeks and of < 70 % of the optimal peak flow for starting a course of oral steroids worked well The self management group had fewer incidents ( consultations , days off work , courses of prednisolone or antibiotics ) than the traditionally treated group and better quality of life scores Adherence of patients to the self management instructions was better than BACKGROUND Inhaled medications are the mainstay of asthma therapy , but significant deficiencies exist in the knowledge and skills of physicians regarding use of metered-dose inhalers ( MDI ) and spacer devices . OBJECTIVE We developed , implemented , and evaluated the effects of a physician-targeted educational program on inhaled therapy in a group of pediatric residents in our institution . METHODS Patient-directed instruction sheets on aerosol therapy were developed on the basis of literature review and expert guidelines . These served to establish a consistent foundation for the educational curriculum . The program was delivered through one-on-two teaching sessions ( 45 minutes ) . Residents were provided with a summary of theoretical and practical information and with devices for practice ( a placebo MDI , InspirEase and AeroChamber holding chambers , and the AeroChamber device with mask ) . Each session included review of an educational monograph , demonstration of proper technique , and practice with the different devices . The program was evaluated by a r and omized-control design . Assessment of practical skills included number of correct steps for the use of MDI ( maximum score , 7 ) , InspirEase ( maximum , 7 ) and AeroChamber ( maximum , 6 ) . Theoretical knowledge was assessed with 25 multiple-choice questions . RESULTS Pretest scores in the experimental group ( n = 24 ) were 3.7 of 7 , 1.9 of 7 , and 0.3 of 6 steps correct for MDI , InspirEase , and AeroChamber devices , respectively , and 13 of 25 for the theoretical knowledge assessment . The control group ( n = 26 ) had similar pretest scores . After the program the experimental group significantly improved in all parameters : 6.3 of 7 , 5.9 of 7 , and 4.5 of 6 steps correct for MDI , InspirEase , and AeroChamber devices , respectively , and 18 of 25 questions correct ( p < 0.01 for all parameters ) . CONCLUSIONS Implementation of a simple educational program among pediatric residents can significantly increase their skills in the use of inhalational therapy We hypothesized that an educational intervention based on a readiness model would lead to improved health outcomes among patients with asthma . Within a r and omized control design in an urban Latino and African-American community , we conducted an intensive three-month pediatric intervention . A Family Coordinator provided patient education based on a readiness-to-learn model , and facilitated improved interactions between the patient and the doctor . Family education addressed the most basic learning needs of patients with asthma by improving their perception of asthma symptom persistence using asthma diaries and peak flow measures . The physician intervention focused clinicians ’ attention on patients ’ diary records and peak flow measures , and encouraged physicians to use stepped action plans . Patients were also tested for allergic sensitization and provided strategies to reduce contact with allergens and other asthma triggers . The results showed significant improvements by intervention group families on measures of knowledge , health beliefs , self-efficacy , self- regulatory skill , and adherence ; decreases in symptom persistence and activity restriction ; and increased prescription of anti-inflammatory medication by the physicians of the intervention group families OBJECTIVE --To determine whether an intervention programme based on existing school and community re sources can reduce school absence and improve participation in games lessons and sport in children with unrecognised or undertreated asthma . DESIGN --Parallel group controlled intervention study . SETTING --102 primary schools in Nottingham : 49 were r and omised to receive the intervention and 53 to be control schools . SUBJECTS -- All children aged 5 to 10 years with parent reported absence from school because of wheezing in the previous year and taking no treatment or beta agonists only . INTERVENTIONS --Children with asthma were referred to their general practitioner for assessment of symptoms and treatment . Teachers were given education on asthma by the school nurse in 44 of the 49 intervention schools . MAIN OUTCOME MEASURES --Changes in school absence and missed games and swimming lessons because of wheezing , and schools ' policy towards management of asthma in school . RESULTS --Of 17,432 children screened , 451 met the entry criteria --228 in intervention schools and 223 in control schools . 152 ( 67 % ) children in intervention schools visited their general practitioner , of whom 39 ( 26 % ) were given a new diagnosis of asthma and 58 ( 38 % ) had treatment for asthma increased or changed . Over the next academic year mean ( SE ) parent reported school absence due to wheezing fell significantly , but to a similar extent , in both intervention and control schools ( 0.82 ( 0.11 ) and 1.09 ( 0.21 ) weeks respectively ) . There was little change in school recorded absence or participation in games lessons and swimming lessons in either group . At the end of the study intervention schools were more likely to have improved aspects of management of asthma in school . CONCLUSION --The intervention result ed in a majority of children being assessed by their general practitioner and improved teachers ' underst and ing and management of asthma , but it did not result in any appreciable reduction in morbidity Abstract Twenty-one asthmatic children , aged 15 months to 13 years and from low-income families , who used the emergency room as their primary source of asthma care , were evaluated by the physicians of the Pediatric Allergy Division at baseline . These children were then r and omly assigned to either a control group or a clinical nurse specialist group . All children were scheduled for follow-up in the hospital clinic with pediatric residents and staff ( control group ) or with the clinical nurse specialist ( CNS ) . After assessing individual family needs , the CNS counseled each family regarding preventive health measures , focusing on early recognition of asthma exacerbations and self-care . During the 12-month study period , the frequency of allergy physician contacts and the total number of outpatient department visits were similar in both groups . However , compared with the 12-month period prior to enrollment , the CNS group subjects demonstrated a significant reduction in the frequency of emergency room ( ER ) visits ( 2.6 ± 1.1 versus 0.6 ± 0.9 ER visits per patient ; A r and omized control trial of the Wee Wheezers asthma education program was conducted with 76 children < 7 years of age , 31 % of whom were on a medication regimen consistent with mild , 51 % with moderate , and 18 % with moderately severe/severe asthma . Treatment children showed improved morbidity at 3-month follow-up relative to the changes in the controls : increased symptom-free days in the preceding 2 weeks ( mean change of + 2.2 vs. -2.6 in the controls ; p = .004 ) and month ( + 2.0 vs. -3.8 ; p < .02 ) , fewer nights of parental sleep interruption in a typical week ( + 0.7 vs. + 1.8 ; p < or = .05 ) , and a trend toward fewer asthma sick days ( -0.2 vs + 0.7 ; p = ns ) . These improvements were accompanied by significantly better parental asthma management compared with controls ( more consistent use of preventive medications , p < or = .01 ; early symptom intervention , [ corrected ] p < or = .05 ) and trends toward more restrictions on smoking in the home ( p < .07 ) and decreased parental confusion about asthma treatment ( p < .11 ) . This study provides evidence that a multisession program of asthma education for parents can improve parental asthma management and clinical outcomes in very young children and provides information on the validity and sensitivity of various asthma outcome measures in this age group A one year study on a r and om sample of 1225 Swiss children aged 0 - 5 years was conducted in four different areas ( two urban , one suburban and one rural ) of Switzerl and to investigate the relationship between air pollution and respiratory symptoms . For each child daily symptoms over a six week period were recorded by their parents in the form of a st and ard diary and air pollution was assessed by personal NO2- sample rs . 20 % of the diaries were vali date d by comparison with the attending pediatrician 's case-notes and showed good agreement ( 87 % ) . The frequency of respiratory symptoms per child per day was found to increase with increasing levels of NO2 measured outdoors , but not with NO2 concentration indoors ( when other indoor sources for NO2 where present ) . Possible other factors were accounted for by multiple regression analysis and the variables " season " and " child 's susceptibility to colds " also showed a significant association with respiratory symptoms . But the relationship between NO2 outdoors and respiratory symptoms per child per day remained statistically significant . The multiple regression model explains 7 % of the total variability . The result indicates that air pollution is a contributory factor in the development of respiratory symptoms in children This study evaluated the benefits produced by " Superstuff " , a self-help program for asthmatic children aged 7 - 12 . Forty-three children with a confirmed diagnosis of moderate to severe asthma were r and omly assigned to either the totally self-administered Superstuff condition or to a nocontact Control condition . Self-report , parental , physician , and school data were collected at pre-intervention , and two , six , and twelve months post-intervention . Children receiving Superstuff reported increased asthma self-control skills , but no gains in general self-control abilities or self-esteem . Superstuff subjects also evidence d fewer interruptions of parents , greater improvement in the progression of asthma as reported by physicians ( but not in the severity of the disease or intensity of average attack ) , and tended toward decreased school absenteeism . Superstuff did not reduce scheduled or emergency medical contacts . The demonstration of important , but modest , benefits from a low-cost , easily disseminated , self-administered intervention is discussed in the context of self-help treatment in general International consensus guidelines [ 1 - 4 ] recommend that patients with asthma be given written instructions that detail when and how to increase treatment during an exacerbation of asthma [ an action plan ] . The purpose of an action plan is to allow the early recognition and treatment of an asthma exacerbation by the patient , thereby avoiding treatment delays and minimizing the severity of the exacerbation . The two essential components of an action plan are 1 ) an action point that indicates when to increase treatment and 2 ) an action treatment instruction that indicates how to increase treatment [ 5 ] . Action plans have received little controlled evaluation . The action treatment instruction can be evaluated by a r and omized , controlled trial of treatment . For instance , several studies [ 1 , 2 ] have established a role for increased corticosteroid therapy during an exacerbation of asthma . The evaluation of action points has received little attention [ 6 ] . Action points should enable the patient to detect asthma exacerbations reliably and accurately : If an action plan performs poorly , it may delay treatment . Delay in using corticosteroid therapy for an exacerbation of asthma is a feature common to severe and fatal exacerbations [ 7 , 8 ] . Alternatively , an action point may falsely detect an exacerbation ( a false-positive result ) and lead to unnecessary therapy . The published recommendations for action points vary widely . For example , the action point recommended in the International Guidelines [ 2 ] is a peak expiratory flow value less than 80 % of the patient 's best peak flow . In contrast , other guidelines recommend using values less than 60 % , 70 % , or 90 % of a patient 's best peak flow or predicted peak expiratory flow [ 6 , 9 , 10 ] . It is unclear which of these action points is most appropriate for the detection of an asthma exacerbation . It is also unclear whether the same action point applies equally well to all patients or whether action points should be individualized for particular patients . Intuitively , individualized action points seem better , but ways of defining these points have received little attention . We reasoned that an action point can be viewed as a diagnostic test , the aim of which is to detect or diagnose an exacerbation of asthma . The relative value of an action point can be assessed by its ability to accurately predict such an exacerbation . We examined the operating characteristics of action points in adults who developed spontaneous exacerbations of asthma . In addition to evaluating published action points , we applied the techniques of quality control analysis to peak expiratory flow records to estimate an individualized and statistically valid action point for each patient . We hypothesized that this would be a more sensitive and specific approach to the detection of asthma exacerbations . Methods The data for analysis were collected from patients attending an asthma management and education program . Adult patients with asthma who were enrolled in the John Hunter Hospital Asthma Management Service and who kept peak expiratory flow diaries were eligible for entry into the study . The Asthma Management Service is a st and ardized education and management program that is offered to adults who have had an emergency presentation to the hospital with asthma . Patients are seen in an ambulatory care setting four to five times in a 3-month period . The program involves visits with a respiratory physician and a nurse educator . Its aims are to optimize asthma control ; to provide instruction in asthma management skills , such as inhaler technique ; to improve knowledge of asthma and asthma medication ; and to instruct patients in the self-monitoring of symptoms and peak expiratory flow . Patients used a mini-Wright peak expiratory flow meter ( Clement Clarke International , United Kingdom ) and recorded the best of three values obtained before and 15 minutes after inhaled bronchodilator therapy in the morning and in the evening . Values were recorded in a daily diary , which was review ed at clinic visits and collected when the patient was discharged from the Asthma Management Service . Between scheduled visits , if symptoms worsened , patients could contact a nurse educator to obtain an earlier physician review appointment . At the completion of the program , action plans were written for the patients and the patients were discharged back into the care of the physician who had referred them to the program . The records of 150 patients registered in the Asthma Management Service were screened for exacerbations of asthma . Exacerbations were defined as new medication courses of increased corticosteroid therapy ( oral or high-dose inhaled corticosteroid ) . These courses were prescribed after assessment by a respiratory physician and used for deteriorating asthma as reflected by an increase in asthma symptoms , an increase in 2-agonist requirements , and a decrease in lung function . Forty-three exacerbations were identified in 35 patients . Diary data were extracted for three time periods : an exacerbation period , a baseline period , and a pre-exacerbation period . The 3-day exacerbation period comprised the day before a corticosteroid course was started , the day it was started , and the day after it was started . A stable baseline period was identified after a scheduled clinic visit that occurred more than 6 weeks after hospital discharge and at which therapy was not altered . Diary data for the 8 to 10 days after this visit were used as baseline data . A preexacerbation period was defined as the 7-day period immediately before the exacerbation period . Patient demographic characteristics , treatment details , and diary data were extracted using st and ardized forms and entered into a computerized data base . Predicted peak expiratory flow values were taken from published guidelines [ 3 ] . The best peak expiratory flow for an individual person was the highest peak flow recorded in the person 's diary during the stable baseline period . Statistical Analysis Quality -control analysis was done using the statistical process control procedures in Minitab statistical software , release 8 ( State College , Pennsylvania ) . Control charts were used to study variations in peak expiratory flow over time . A summary statistic , such as the mean peak expiratory flow , was calculated for each sample ( day ) and plotted over time ( in days ) . Three lines were drawn on the chart : the center line , which was an estimate of the average value of the summary statistic ; a lower control limit , which was drawn 3 st and ard deviations below the center line ; and a third line , which was drawn 2 st and ard deviations below the center line . If a process is in control it is very unlikely ( < 3 in a 100 chance ) that a point will fall outside the lower control limit . In this study , we used the lower control limit to define significant decreases in peak expiratory flow . St and ard quality -control tests were used to identify deviations in the control charts . A single point falling below the lower control limit indicated that a change may have occurred ( special cause ) and that investigation was needed ( test 1 ) . Two other st and ard tests were used . Test 2 was reached when 2 of 3 points occurred in a row in a zone between 2 and 3 st and ard deviations from the center line . Test 3 was reached when four of five points in a row fell between 1 and 2 st and ard deviations from the center line or beyond ( Figure 1 ) . Figure 1 . An example of a quality -control chart ( x-bar chart ) of peak expiratory flow recordings from a patient with asthma . Action points were obtained from published literature and from quality -control analysis . The published action points that were evaluated included a peak expiratory flow of less than 80 % of predicted peak expiratory flow ; a peak expiratory flow of less than 80 % of a patient 's best peak flow ; a peak flow of less than 60 % of predicted peak expiratory flow ; a peak flow of less than 60 % of a patient 's best peak flow ; nocturnal waking because of asthma ; and use of 2-agonist therapy more than four times a day . Three tests for special causes were used to define action points from quality -control analysis and were separately applied to peak flow before and after bronchodilator therapy . An action point was defined as a success if it was reached by the patient during the exacerbation period . An action point was defined as a failure if it was reached during the baseline period or if it was not reached during an exacerbation . The successes and failures were totaled for the study group . The success rate is similar to the sensitivity of a diagnostic test . The failure rate from each action point during the baseline period is similar to the false-positive rate , and its complement is specificity . The McNemar test was used to compare the overall error rate ( successes and failures ) of two published action points ( peak flow less than 60 % of that predicted and peak flow less than 80 % of that predicted ) with the overall error rate from quality -control analysis , test 2 . The significance level was P < 0.05 . Results Thirty-five patients had a total of 43 asthma exacerbations ( Table 1 ) . Two patients required hospitalization for their exacerbations . Most patients ( 69 % ) received oral prednisolone for management ( mean dose , 40 14 mg ; mode , 50 mg ) . Each patient also received increased aerosol bronchodilator therapy . High-dose inhaled corticosteroid therapy was given to 94 % of patients and was continued for as long as 14 days . The average dose of inhaled corticosteroid used during the exacerbations was 3.9 1.9 mg of either beclomethasone dipropionate ( through pressurized metered-dose inhaler and valved holding chamber ) or budesonide ( through Turbuhaler [ Astra Pharmaceuticals , North Ryde , Australia ] , a dry-powder metered-dose inhaler ) . Table 1 . Patient Characteristics The performance characteristics of the action points are shown in Table 2 and Figure 2 . The action points from published guidelines had varying success rates . An |
12,351 | 28,156,882 | Conclusions Social characteristics like sex/gender remain hidden from analyses and interpretation in RCTs , with loss of information and embedding of error all along the path from design to interpretation , and therefore , to uptake in clinical practice . | Background Although observational data show social characteristics such as gender or socio-economic status to be strong predictors of health , their impact is seldom investigated in r and omised controlled studies ( RCTs ) .
Objective & design Using a r and om sample of recent RCTs from high-impact journals , we examined how the most often recorded social characteristic , sex/gender , is considered in design , analysis , and interpretation . | BACKGROUND Actinic keratosis is a common precursor to sun-related squamous-cell carcinoma . Treating actinic keratoses and the surrounding skin area ( i.e. , field therapy ) can eradicate clinical and sub clinical actinic keratoses . Topical field therapy currently requires weeks or months of treatment . We investigated the efficacy and safety of a new topical field therapy for actinic keratosis , ingenol mebutate gel ( 0.015 % for face and scalp and 0.05 % for trunk and extremities ) . METHODS In four multicenter , r and omized , double-blind studies , we r and omly assigned patients with actinic keratoses on the face or scalp or on the trunk or extremities to receive ingenol mebutate or placebo ( vehicle ) , self-applied to a 25-cm(2 ) contiguous field once daily for 3 consecutive days for lesions on the face or scalp or for 2 consecutive days for the trunk or extremities . Complete clearance ( primary outcome ) was assessed at 57 days , and local reactions were quantitatively measured . RESULTS In a pooled analysis of the two trials involving the face and scalp , the rate of complete clearance was higher with ingenol mebutate than with placebo ( 42.2 % vs. 3.7 % , P<0.001 ) . Local reactions peaked at day 4 , with a mean maximum composite score of 9.1 on the local-skin-response scale ( which ranges from 0 to 4 for six types of reaction , yielding a composite score of 0 to 24 , with higher numbers indicating more severe reactions ) , rapidly decreased by day 8 , and continued to decrease , approaching baseline scores by day 29 . In a pooled analysis of the two trials involving the trunk and extremities , the rate of complete clearance was also higher with ingenol mebutate than with placebo ( 34.1 % vs. 4.7 % , P<0.001 ) . Local skin reactions peaked between days 3 and 8 and declined rapidly , approaching baseline by day 29 , with a mean maximum score of 6.8 . Adverse events were generally mild to moderate in intensity and resolved without sequelae . CONCLUSIONS Ingenol mebutate gel applied topically for 2 to 3 days is effective for field treatment of actinic keratoses . ( Funded by LEO Pharma ; Clinical Trials.gov numbers , NCT00742391 , NCT00916006 , NCT00915551 , and NCT00942604 . ) BACKGROUND In r and omized trials , fecal occult-blood testing reduces mortality from colorectal cancer . However , the duration of the benefit is unknown , as are the effects specific to age and sex . METHODS In the Minnesota Colon Cancer Control Study , 46,551 participants , 50 to 80 years of age , were r and omly assigned to usual care ( control ) or to annual or biennial screening with fecal occult-blood testing . Screening was performed from 1976 through 1982 and from 1986 through 1992 . We used the National Death Index to obtain up date d information on the vital status of participants and to determine causes of death through 2008 . RESULTS Through 30 years of follow-up , 33,020 participants ( 70.9 % ) died . A total of 732 deaths were attributed to colorectal cancer : 200 of the 11,072 deaths ( 1.8 % ) in the annual-screening group , 237 of the 11,004 deaths ( 2.2 % ) in the biennial-screening group , and 295 of the 10,944 deaths ( 2.7 % ) in the control group . Screening reduced colorectal-cancer mortality ( relative risk with annual screening , 0.68 ; 95 % confidence interval [ CI ] , 0.56 to 0.82 ; relative risk with biennial screening , 0.78 ; 95 % CI , 0.65 to 0.93 ) through 30 years of follow-up . No reduction was observed in all-cause mortality ( relative risk with annual screening , 1.00 ; 95 % CI , 0.99 to 1.01 ; relative risk with biennial screening , 0.99 ; 95 % CI , 0.98 to 1.01 ) . The reduction in colorectal-cancer mortality was larger for men than for women in the biennial-screening group ( P=0.04 for interaction ) . CONCLUSIONS The effect of screening with fecal occult-blood testing on colorectal-cancer mortality persists after 30 years but does not influence all-cause mortality . The sustained reduction in colorectal-cancer mortality supports the effect of polypectomy . ( Funded by the Veterans Affairs Merit Review Award Program and others . ) BACKGROUND Women 's groups and health education by peer counsellors can improve the health of mothers and children . We assessed their effects on mortality and breastfeeding rates in rural Malawi . METHODS We did a 2 × 2 factorial , cluster-r and omised trial in 185,888 people in Mchinji district . 48 equal-sized clusters were r and omly allocated to four groups with a computer-generated number sequence . 24 facilitators guided groups through a community action cycle to tackle maternal and child health problems . 72 trained volunteer peer counsellors made home visits at five timepoints during pregnancy and after birth to support breastfeeding and infant care . Primary outcomes for the women 's group intervention were maternal , perinatal , neonatal , and infant mortality rates ( MMR , PMR , NMR , and IMR , respectively ) ; and for the peer counselling were IMR and exclusive breastfeeding ( EBF ) rates . Analysis was by intention to treat . The trial is registered as IS RCT N06477126 . FINDINGS We monitored outcomes of 26,262 births between 2005 and 2009 . In a factorial model adjusted only for clustering and the volunteer peer counselling intervention , in women 's group areas , for years 2 and 3 , we noted non-significant decreases in NMR ( odds ratio 0.93 , 0.64 - 1.35 ) and MMR ( 0.54 , 0.28 - 1.04 ) . After adjustment for parity , socioeconomic quintile , and baseline measures , effects were larger for NMR ( 0.85 , 0.59 - 1.22 ) and MMR ( 0.48 , 0.26 - 0.91 ) . Because of the interaction between the two interventions , a stratified analysis was done . For women 's groups , in adjusted analyses , MMR fell by 74 % ( 0.26 , 0.10 - 0.70 ) , and NMR by 41 % ( 0.59 , 0.40 - 0.86 ) in areas with no peer counsellors , but there was no effect in areas with counsellors ( 1.09 , 0.40 - 2.98 , and 1.38 , 0.75 - 2.54 ) . Factorial analysis for the peer counselling intervention for years 1 - 3 showed a fall in IMR of 18 % ( 0.82 , 0.67 - 1.00 ) and an improvement in EBF rates ( 2.42 , 1.48 - 3.96 ) . The results of the stratified , adjusted analysis showed a 36 % reduction in IMR ( 0.64 , 0.48 - 0.85 ) but no effect on EBF ( 1.18 , 0.63 - 2.25 ) in areas without women 's groups , and in areas with women 's groups there was no effect on IMR ( 1.05 , 0.82 - 1.36 ) and an increase in EBF ( 5.02 , 2.67 - 9.44 ) . The cost of women 's groups was US$ 114 per year of life lost ( YLL ) averted and that of peer counsellors was $ 33 per YLL averted , using stratified data from single intervention comparisons . INTERPRETATION Community mobilisation through women 's groups and volunteer peer counsellor health education are methods to improve maternal and child health outcomes in poor rural population s in Africa . FUNDING Saving Newborn Lives , UK Department for International Development , and Wellcome Trust BACKGROUND Venous thromboembolism is a common , potentially avoidable cause of death and morbidity in patients in hospital , including those with stroke . In surgical patients , intermittent pneumatic compression ( IPC ) reduces the risk of deep vein thrombosis ( DVT ) , but no reliable evidence exists about its effectiveness in patients who have had a stroke . We assessed the effectiveness of IPC to reduce the risk of DVT in patients who have had a stroke . METHODS The CLOTS 3 trial is a multicentre parallel group r and omised trial assessing IPC in immobile patients ( ie , who can not walk to the toilet without the help of another person ) with acute stroke . We enrolled patients from day 0 to day 3 of admission and allocated them via a central r and omisation system ( ratio 1:1 ) to receive either IPC or no IPC . A technician who was masked to treatment allocation did a compression duplex ultrasound ( CDU ) of both legs at 7 - 10 days and , wherever practical , at 25 - 30 days after enrolment . Caregivers and patients were not masked to treatment assignment . Patients were followed up for 6 months to determine survival and later symptomatic venous thromboembolism . The primary outcome was a DVT in the proximal veins detected on a screening CDU or any symptomatic DVT in the proximal veins , confirmed on imaging , within 30 days of r and omisation . Patients were analysed according to their treatment allocation . TRIAL REGISTRATION IS RCT N93529999 . FINDINGS Between Dec 8 , 2008 , and Sept 6 , 2012 , 2876 patients were enrolled in 94 centres in the UK . The included patients were broadly representative of immobile stroke patients admitted to hospital and had a median age of 76 years ( IQR 67 - 84 ) . The primary outcome occurred in 122 ( 8·5 % ) of 1438 patients allocated IPC and 174 ( 12·1 % ) of 1438 patients allocated no IPC ; an absolute reduction in risk of 3·6 % ( 95 % CI 1·4 - 5·8 ) . Excluding the 323 patients who died before any primary outcome and 41 without any screening CDU , the adjusted OR for the comparison of 122 of 1267 patients vs 174 of 1245 patients was 0·65 ( 95 % CI 0·51 - 0·84 ; p=0·001 ) . Deaths in the treatment period occurred in 156 ( 11 % ) patients allocated IPC and 189 ( 13 % ) patients allocated no IPC died within the 30 days of treatment period ( p=0·057 ) ; skin breaks on the legs were reported in 44 ( 3 % ) patients allocated IPC and in 20 ( 1 % ) patients allocated no IPC ( p=0·002 ) ; falls with injury were reported in 33 ( 2 % ) patients in the IPC group and in 24 ( 2 % ) patients in the no-IPC group ( p=0·221 ) . INTERPRETATION IPC is an effective method of reducing the risk of DVT and possibly improving survival in a wide variety of patients who are immobile after stroke . FUNDING National Institute of Health Research ( NIHR ) Health Technology Assessment ( HTA ) programme , UK ; Chief Scientist Office of Scottish Government ; Covidien ( MA , USA ) BACKGROUND We previously reported that integrating antiretroviral therapy ( ART ) with tuberculosis treatment reduces mortality . However , the timing for the initiation of ART during tuberculosis treatment remains unresolved . METHODS We conducted a three-group , open-label , r and omized , controlled trial in South Africa involving 642 ambulatory patients , all with tuberculosis ( confirmed by a positive sputum smear for acid-fast bacilli ) , human immunodeficiency virus infection , and a CD4 + T-cell count of less than 500 per cubic millimeter . Findings in the earlier-ART group ( ART initiated within 4 weeks after the start of tuberculosis treatment , 214 patients ) and later-ART group ( ART initiated during the first 4 weeks of the continuation phase of tuberculosis treatment , 215 patients ) are presented here . RESULTS At baseline , the median CD4 + T-cell count was 150 per cubic millimeter , and the median viral load was 161,000 copies per milliliter , with no significant differences between the two groups . The incidence rate of the acquired immunodeficiency syndrome ( AIDS ) or death was 6.9 cases per 100 person-years in the earlier-ART group ( 18 cases ) as compared with 7.8 per 100 person-years in the later-ART group ( 19 cases ) ( incidence-rate ratio , 0.89 ; 95 % confidence interval [ CI ] , 0.44 to 1.79 ; P=0.73 ) . However , among patients with CD4 + T-cell counts of less than 50 per cubic millimeter , the incidence rates of AIDS or death were 8.5 and 26.3 cases per 100 person-years , respectively ( incidence-rate ratio , 0.32 ; 95 % CI , 0.07 to 1.13 ; P=0.06 ) . The incidence rates of the immune reconstitution inflammatory syndrome ( IRIS ) were 20.1 and 7.7 cases per 100 person-years , respectively ( incidence-rate ratio , 2.62 ; 95 % CI , 1.48 to 4.82 ; P<0.001 ) . Adverse events requiring a switching of antiretroviral drugs occurred in 10 patients in the earlier-ART group and 1 patient in the later-ART group ( P=0.006 ) . CONCLUSIONS Early initiation of ART in patients with CD4 + T-cell counts of less than 50 per cubic millimeter increased AIDS-free survival . Deferral of the initiation of ART to the first 4 weeks of the continuation phase of tuberculosis therapy in those with higher CD4 + T-cell counts reduced the risks of IRIS and other adverse events related to ART without increasing the risk of AIDS or death . ( Funded by the U.S. President 's Emergency Plan for AIDS Relief and others ; SAPIT Clinical Trials.gov number , NCT00398996 . ) BACKGROUND Early termination of prolonged seizures with intravenous administration of benzodiazepines improves outcomes . For faster and more reliable administration , paramedics increasingly use an intramuscular route . METHODS This double-blind , r and omized , noninferiority trial compared the efficacy of intramuscular midazolam with that of intravenous lorazepam for children and adults in status epilepticus treated by paramedics . Subjects whose convulsions had persisted for more than 5 minutes and who were still convulsing after paramedics arrived were given the study medication by either intramuscular autoinjector or intravenous infusion . The primary outcome was absence of seizures at the time of arrival in the emergency department without the need for rescue therapy . Secondary outcomes included endotracheal intubation , recurrent seizures , and timing of treatment relative to the cessation of convulsive seizures . This trial tested the hypothesis that intramuscular midazolam was noninferior to intravenous lorazepam by a margin of 10 percentage points . RESULTS At the time of arrival in the emergency department , seizures were absent without rescue therapy in 329 of 448 subjects ( 73.4 % ) in the intramuscular-midazolam group and in 282 of 445 ( 63.4 % ) in the intravenous-lorazepam group ( absolute difference , 10 percentage points ; 95 % confidence interval , 4.0 to 16.1 ; P<0.001 for both noninferiority and superiority ) . The two treatment groups were similar with respect to need for endotracheal intubation ( 14.1 % of subjects with intramuscular midazolam and 14.4 % with intravenous lorazepam ) and recurrence of seizures ( 11.4 % and 10.6 % , respectively ) . Among subjects whose seizures ceased before arrival in the emergency department , the median times to active treatment were 1.2 minutes in the intramuscular-midazolam group and 4.8 minutes in the intravenous-lorazepam group , with corresponding median times from active treatment to cessation of convulsions of 3.3 minutes and 1.6 minutes . Adverse-event rates were similar in the two groups . CONCLUSIONS For subjects in status epilepticus , intramuscular midazolam is at least as safe and effective as intravenous lorazepam for prehospital seizure cessation . ( Funded by the National Institute of Neurological Disorders and Stroke and others ; Clinical Trials.gov number , Clinical Trials.gov NCT00809146 . ) BACKGROUND In women with a multiple pregnancy , spontaneous preterm delivery is the leading cause of perinatal morbidity and mortality . Interventions to reduce preterm birth in these women have not been successful . We assessed whether a cervical pessary could effectively prevent poor perinatal outcomes . METHODS We undertook a multicentre , open-label r and omised controlled trial in 40 hospitals in the Netherl and s. We r and omly assigned women with a multiple pregnancy between 12 and 20 weeks ' gestation ( 1:1 ) to pessary or control groups , using a web-based application with a computer-generated list with r and om block sizes of two to four , stratified by hospital . Participants and investigators were aware of group allocation . For women in the pessary group , a midwife or obstetrician inserted a cervical pessary between 16 and 20 weeks ' gestation . Women in the control group did not receive the pessary , but otherwise received similar obstetrical care to those in the pessary group . The primary outcome was a composite of poor perinatal outcome : stillbirth , periventricular leucomalacia , severe respiratory distress syndrome , bronchopulmonary dysplasia , intraventricular haemorrhage , necrotising enterocolitis , proven sepsis , and neonatal death . Analyses were by modified intention to treat . This trial is registered in the Dutch trial registry , number NTR1858 . FINDINGS Between Sept 21 , 2009 , and March 9 , 2012 , 813 women underwent r and omisation , of whom 808 were analysed ( 401 in the pessary group ; 407 in the control group ) . At least one child of 53 women ( 13 % ) in the pessary group had poor perinatal outcome , compared with 55 ( 14 % ) in the control group ( relative risk 0·98 , 95 % CI 0·69 - 1·39 ) . INTERPRETATION In unselected women with a multiple pregnancy , prophylactic use of a cervical pessary does not reduce poor perinatal outcome . FUNDING The Netherl and s Organisation for Health Research and Development BACKGROUND Treatment with prasugrel and aspirin improves outcomes compared with clopidogrel and aspirin for patients with acute coronary syndrome who have had angiography and percutaneous coronary intervention ; however , no clear benefit has been shown for patients managed first with drugs only . We assessed outcomes from the TRILOGY ACS trial based on whether or not patients had coronary angiography before treatment was chosen . METHODS TRILOGY ACS ( Clinical Trials.gov number NCT00699998 ) was a r and omised controlled trial , done at more than 800 sites worldwide . Patients with non-ST-elevation acute coronary syndrome who were selected for management without [ corrected ] revascularisation were r and omly assigned to clopidogrel or prasugrel . The primary endpoint was cardiovascular death , myocardial infa rct ion , or stroke at 30 months . In the present analysis we assessed differences in the primary endpoint by angiography status and whether the effects of treatment on the primary endpoint differed between patients who had angiography before enrolment and those who had not . FINDINGS 7243 patients younger than 75 years were included in the TRILOGY ACS primary analysis . 3085 ( 43 % ) had angiography at baseline , 4158 ( 57 % ) had not . Fewer patients who had angiography reached the primary endpoint at 30 months compared with those who did not have angiography , according to Kaplan-Meier analysis ( 281/3085 [ 12·8 % ] vs 480/4158 [ 16·5 % ] , adjusted hazard ratio [ HR ] 0·63 , 95 % CI 0·53 - 0·75 ; p<0·0001 ) . The proportion of patients who reached the primary endpoint was lower in the prasugrel group than in the clopidogrel group for those who had angiography ( 122/1524 [ 10·7 % ] vs 159/1561 [ 14·9 % ] , HR 0·77 , 95 % CI 0·61 - 0·98 ; p=0·032 ) but did not differ between groups in patients who did not have angiography ( 242/2096 [ 16·3 % ] vs 238/2062 [ 16·7 % ] , HR 1·01 , 0·84 - 1·20 ; p=0·94 ; pinteraction=0·08 ) . Overall , TIMI major bleeding and GUSTO severe bleeding were rare . Bleeding outcomes tended to be higher with prasugrel but did not differ significantly between treatment groups in either angiography cohort . INTERPRETATION Among patients who had angiography who took prasugrel there were fewer cardiovascular deaths , myocardial infa rct ions , or strokes than in those who took clopidogrel . This result needs to be corroborated , but it is consistent with previous trials of more versus less intensive antiplatelet treatment . When angiography is done for acute coronary syndrome and anatomic coronary disease confirmed , the benefits and risks of intensive antiplatelet treatment exist whether the patient is treated with drugs or percutaneous coronary intervention . FUNDING Daiichi Sankyo , Eli Lilly BACKGROUND Dalcetrapib modulates cholesteryl ester transfer protein ( CETP ) activity to raise high-density lipoprotein cholesterol ( HDL-C ) . After the failure of torcetrapib it was unknown if HDL produced by interaction with CETP had pro-atherogenic or pro-inflammatory properties . dal-PLAQUE is the first multicentre study using novel non-invasive multimodality imaging to assess structural and inflammatory indices of atherosclerosis as primary endpoints . METHODS In this phase 2b , double-blind , multicentre trial , patients ( aged 18 - 75 years ) with , or with high risk of , coronary heart disease were r and omly assigned ( 1:1 ) to dalcetrapib 600 mg/day or placebo for 24 months . R and omisation was done with a computer-generated r and omisation code and was stratified by centre . Patients and investigators were masked to treatment . Co primary endpoints were MRI-assessed indices ( total vessel area , wall area , wall thickness , and normalised wall index [ average carotid ] ) after 24 months and (18)F-fluorodeoxyglucose ( (18)F-FDG ) PET/CT assessment of arterial inflammation within an index vessel ( right carotid , left carotid , or ascending thoracic aorta ) after 6 months , with no-harm boundaries established before unblinding of the trial . Analysis was by intention to treat . This trial is registered at Clinical Trials.gov , NCT00655473 . FINDINGS 189 patients were screened and 130 r and omly assigned to placebo ( 66 patients ) or dalcetrapib ( 64 patients ) . For the co primary MRI and PET/CT endpoints , CIs were below the no-harm boundary or the adverse change was numerically lower in the dalcetrapib group than in the placebo group . MRI-derived change in total vessel area was reduced in patients given dalcetrapib compared with those given placebo after 24 months ; absolute change from baseline relative to placebo was -4·01 mm(2 ) ( 90 % CI -7·23 to -0·80 ; nominal p=0·04 ) . The PET/CT measure of index vessel most-diseased-segment target-to- background ratio ( TBR ) was not different between groups , but carotid artery analysis showed a 7 % reduction in most-diseased-segment TBR in the dalcetrapib group compared with the placebo group ( -7·3 [ 90 % CI -13·5 to -0·8 ] ; nominal p=0·07 ) . Dalcetrapib did not increase office blood pressure and the frequency of adverse events was similar between groups . INTERPRETATION Dalcetrapib showed no evidence of a pathological effect related to the arterial wall over 24 months . Moreover , this trial suggests possible beneficial vascular effects of dalcetrapib , including the reduction in total vessel enlargement over 24 months , but long-term safety and clinical outcomes efficacy of dalcetrapib need to be analysed . FUNDING F Hoffmann-La Roche BACKGROUND In a phase 1 - 2 trial of albumin-bound paclitaxel ( nab-paclitaxel ) plus gemcitabine , substantial clinical activity was noted in patients with advanced pancreatic cancer . We conducted a phase 3 study of the efficacy and safety of the combination versus gemcitabine monotherapy in patients with metastatic pancreatic cancer . METHODS We r and omly assigned patients with a Karnofsky performance-status score of 70 or more ( on a scale from 0 to 100 , with higher scores indicating better performance status ) to nab-paclitaxel ( 125 mg per square meter of body-surface area ) followed by gemcitabine ( 1000 mg per square meter ) on days 1 , 8 , and 15 every 4 weeks or gemcitabine monotherapy ( 1000 mg per square meter ) weekly for 7 of 8 weeks ( cycle 1 ) and then on days 1 , 8 , and 15 every 4 weeks ( cycle 2 and subsequent cycles ) . Patients received the study treatment until disease progression . The primary end point was overall survival ; secondary end points were progression-free survival and overall response rate . RESULTS A total of 861 patients were r and omly assigned to nab-paclitaxel plus gemcitabine ( 431 patients ) or gemcitabine ( 430 ) . The median overall survival was 8.5 months in the nab-paclitaxel-gemcitabine group as compared with 6.7 months in the gemcitabine group ( hazard ratio for death , 0.72 ; 95 % confidence interval [ CI ] , 0.62 to 0.83 ; P<0.001 ) . The survival rate was 35 % in the nab-paclitaxel-gemcitabine group versus 22 % in the gemcitabine group at 1 year , and 9 % versus 4 % at 2 years . The median progression-free survival was 5.5 months in the nab-paclitaxel-gemcitabine group , as compared with 3.7 months in the gemcitabine group ( hazard ratio for disease progression or death , 0.69 ; 95 % CI , 0.58 to 0.82 ; P<0.001 ) ; the response rate according to independent review was 23 % versus 7 % in the two groups ( P<0.001 ) . The most common adverse events of grade 3 or higher were neutropenia ( 38 % in the nab-paclitaxel-gemcitabine group vs. 27 % in the gemcitabine group ) , fatigue ( 17 % vs. 7 % ) , and neuropathy ( 17 % vs. 1 % ) . Febrile neutropenia occurred in 3 % versus 1 % of the patients in the two groups . In the nab-paclitaxel-gemcitabine group , neuropathy of grade 3 or higher improved to grade 1 or lower in a median of 29 days . CONCLUSIONS In patients with metastatic pancreatic adenocarcinoma , nab-paclitaxel plus gemcitabine significantly improved overall survival , progression-free survival , and response rate , but rates of peripheral neuropathy and myelosuppression were increased . ( Funded by Celgene ; Clinical Trials.gov number , NCT00844649 . ) OBJECTIVES Gender and ethnicity are factors affecting the incidence and severity of vascular disease as well as subsequent treatment outcomes . Although well studied in other fields , balanced enrollment of patients with relevant demographic characteristics in vascular surgery r and omized controlled trials ( RCTs ) is not well known . This study describes the reporting of gender and ethnicity data in vascular surgery RCTs and analyzes whether these studies adequately represent our diverse patient population . METHODS We conducted a retrospective review of United States-based RCTs from 1983 through 2007 for three broadly defined vascular procedures : aortic aneurysm repair ( AAR ) , carotid revascularization ( CR ) , and lower extremity revascularization ( LER ) . Included studies were examined for gender and ethnicity data , study parameters , funding source , and geographic region . The Nationwide Inpatient Sample ( NIS ) data base was analyzed to obtain group-specific procedure frequency as an estimate of procedure frequency in the general population . RESULTS We review ed 77 studies , and 52 met our inclusion criteria . Only 85 % reported gender , and 21 % reported ethnicity . Reporting of ethnicity was strongly associated with larger ( > 280 participants ) , multicenter , government-funded trials ( P < .001 for all ) . Women are disproportionately under-represented in RCTs for all procedure categories ( AAR , 9.0 % vs 21.5 % ; CR , 30.0 % vs 42.9 % ; LER , 22.4 % vs 41.3 % ) . Minorities are under-represented in AAR studies ( 6.0 % vs 10.7 % ) and CR studies ( 6.9 % vs 9.5 % ) but are over-represented in LER studies ( 26.0 % vs 21.8 % , P < .001 for all ) . CONCLUSIONS Minority ethnicity and female gender are under-reported and under-represented in vascular surgery RCTs , particularly in small , non-government-funded and single-center trials . The generalizability of some trial results may not be applicable to these population s. Greater effort to enroll a balanced study population in RCTs may yield more broadly applicable results BACKGROUND Arthroscopic partial meniscectomy is one of the most common orthopedic procedures , yet rigorous evidence of its efficacy is lacking . METHODS We conducted a multicenter , r and omized , double-blind , sham-controlled trial in 146 patients 35 to 65 years of age who had knee symptoms consistent with a degenerative medial meniscus tear and no knee osteoarthritis . Patients were r and omly assigned to arthroscopic partial meniscectomy or sham surgery . The primary outcomes were changes in the Lysholm and Western Ontario Meniscal Evaluation Tool ( WOMET ) scores ( each ranging from 0 to 100 , with lower scores indicating more severe symptoms ) and in knee pain after exercise ( rated on a scale from 0 to 10 , with 0 denoting no pain ) at 12 months after the procedure . RESULTS In the intention-to-treat analysis , there were no significant between-group differences in the change from baseline to 12 months in any primary outcome . The mean changes ( improvements ) in the primary outcome measures were as follows : Lysholm score , 21.7 points in the partial-meniscectomy group as compared with 23.3 points in the sham-surgery group ( between-group difference , -1.6 points ; 95 % confidence interval [ CI ] , -7.2 to 4.0 ) ; WOMET score , 24.6 and 27.1 points , respectively ( between-group difference , -2.5 points ; 95 % CI , -9.2 to 4.1 ) ; and score for knee pain after exercise , 3.1 and 3.3 points , respectively ( between-group difference , -0.1 ; 95 % CI , -0.9 to 0.7 ) . There were no significant differences between groups in the number of patients who required subsequent knee surgery ( two in the partial-meniscectomy group and five in the sham-surgery group ) or serious adverse events ( one and zero , respectively ) . CONCLUSIONS In this trial involving patients without knee osteoarthritis but with symptoms of a degenerative medial meniscus tear , the outcomes after arthroscopic partial meniscectomy were no better than those after a sham surgical procedure . ( Funded by the Sigrid Juselius Foundation and others ; Clinical Trials.gov number , NCT00549172 . ) BACKGROUND Bevacizumab has been suggested to have similar effectiveness to ranibizumab for treatment of neovascular age-related macular degeneration . The Inhibition of VEGF in Age-related choroidal Neovascularisation ( IVAN ) trial was design ed to compare these drugs and different regimens . Here , we report the findings at the prespecified 2-year timepoint . METHODS In a multicentre , 2 × 2 factorial , non-inferiority r and omised trial , we enrolled adults aged at least 50 years with active , previously untreated neovascular age-related macular degeneration and a best corrected distance visual acuity ( BCVA ) of at least 25 letters from 23 hospitals in the UK . Participants were r and omly assigned ( 1:1:1:1 ) to intravitreal injections of ranibizumab ( 0·5 mg ) or bevacizumab ( 1·25 mg ) in continuous ( every month ) or discontinuous ( as needed ) regimens , with monthly review . Study participants and clinical assessors were masked to drug allocation . Allocation to continuous or discontinuous treatment was masked up to 3 months , at which point investigators and participants were unmasked . The primary outcome was BCVA at 2 years , with a prespecified non-inferiority limit of 3·5 letters . The primary safety outcome was arterial thrombotic event or hospital admission for heart failure . Analyses were by modified intention to treat . This trial is registered , number IS RCT N92166560 . FINDINGS Between March 27 , 2008 , and Oct 15 , 2010 , 628 patients underwent r and omisation . 18 were withdrawn ; 610 received study drugs ( 314 ranibizumab ; 296 bevacizumab ) and were included in analyses . 525 participants reached the visit at 2 years : 134 ranibizumab in continuous regimen , 137 ranibizumab in discontinuous regimen , 127 bevacizumab in continuous regimen , and 127 bevacizumab in discontinuous regimen . For BCVA , bevacizumab was neither non-inferior nor inferior to ranibizumab ( mean difference -1·37 letters , 95 % CI -3·75 to 1·01 ; p=0·26 ) . Discontinuous treatment was neither non-inferior nor inferior to continuous treatment ( -1·63 letters , -4·01 to 0·75 ; p=0·18 ) . Frequency of arterial thrombotic events or hospital admission for heart failure did not differ between groups given ranibizumab ( 20 [ 6 % ] of 314 participants ) and bevacizumab ( 12 [ 4 % ] of 296 ; odds ratio [ OR ] 1·69 , 95 % CI 0·80 - 3·57 ; p=0·16 ) , or those given continuous ( 12 [ 4 % ] of 308 ) and discontinuous treatment ( 20 [ 7 % ] of 302 ; 0·56 , 0·27 - 1·19 ; p=0·13 ) . Mortality was lower with continuous than discontinuous treatment ( OR 0·47 , 95 % CI 0·22 - 1·03 ; p=0·05 ) , but did not differ by drug group ( 0·96 , 0·46 - 2·02 ; p=0·91 ) . INTERPRETATION Ranibizumab and bevacizumab have similar efficacy . Reduction in the frequency of retreatment result ed in a small loss of efficacy irrespective of drug . Safety was worse when treatment was administered discontinuously . These findings highlight that the choice of anti-VEGF treatment strategy is less straightforward than previously thought . FUNDING UK National Institute for Health Research Health Technology Assessment programme 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 . ) Summary Background Intensive treatment of multiple cardiovascular risk factors can halve mortality among people with established type 2 diabetes . We investigated the effect of early multifactorial treatment after diagnosis by screening . Methods In a pragmatic , cluster-r and omised , parallel-group trial done in Denmark , the Netherl and s , and the UK , 343 general practice s were r and omly assigned screening of registered patients aged 40–69 years without known diabetes followed by routine care of diabetes or screening followed by intensive treatment of multiple risk factors . The primary endpoint was first cardiovascular event , including cardiovascular mortality and morbidity , revascularisation , and non-traumatic amputation within 5 years . Patients and staff assessing outcomes were unaware of the practice 's study group assignment . Analysis was done by intention to treat . This study is registered with Clinical Trials.gov , number NCT00237549 . Findings Primary endpoint data were available for 3055 ( 99·9 % ) of 3057 screen-detected patients . The mean age was 60·3 ( SD 6·9 ) years and the mean duration of follow-up was 5·3 ( SD 1·6 ) years . Improvements in cardiovascular risk factors ( HbA1c and cholesterol concentrations and blood pressure ) were slightly but significantly better in the intensive treatment group . The incidence of first cardiovascular event was 7·2 % ( 13·5 per 1000 person-years ) in the intensive treatment group and 8·5 % ( 15·9 per 1000 person-years ) in the routine care group ( hazard ratio 0·83 , 95 % CI 0·65–1·05 ) , and of all-cause mortality 6·2 % ( 11·6 per 1000 person-years ) and 6·7 % ( 12·5 per 1000 person-years ; 0·91 , 0·69–1·21 ) , respectively . Interpretation An intervention to promote early intensive management of patients with type 2 diabetes was associated with a small , non-significant reduction in the incidence of cardiovascular events and death . Funding National Health Service Denmark , Danish Council for Strategic Research , Danish Research Foundation for General Practice , Danish Centre for Evaluation and Health Technology Assessment , Danish National Board of Health , Danish Medical Research Council , Aarhus University Research Foundation , Wellcome Trust , UK Medical Research Council , UK NIHR Health Technology Assessment Programme , UK National Health Service R&D , UK National Institute for Health Research , Julius Center for Health Sciences and Primary Care , University Medical Center , Utrecht , Novo Nordisk , Astra , Pfizer , GlaxoSmithKline , Servier , HemoCue , Merck BACKGROUND It is unclear whether an evaluation incorporating coronary computed tomographic angiography ( CCTA ) is more effective than st and ard evaluation in the emergency department in patients with symptoms suggestive of acute coronary syndromes . METHODS In this multicenter trial , we r and omly assigned patients 40 to 74 years of age with symptoms suggestive of acute coronary syndromes but without ischemic electrocardiographic changes or an initial positive troponin test to early CCTA or to st and ard evaluation in the emergency department on weekdays during daylight hours between April 2010 and January 2012 . The primary end point was length of stay in the hospital . Secondary end points included rates of discharge from the emergency department , major adverse cardiovascular events at 28 days , and cumulative costs . Safety end points were undetected acute coronary syndromes . RESULTS The rate of acute coronary syndromes among 1000 patients with a mean ( ±SD ) age of 54±8 years ( 47 % women ) was 8 % . After early CCTA , as compared with st and ard evaluation , the mean length of stay in the hospital was reduced by 7.6 hours ( P<0.001 ) and more patients were discharged directly from the emergency department ( 47 % vs. 12 % , P<0.001 ) . There were no undetected acute coronary syndromes and no significant differences in major adverse cardiovascular events at 28 days . After CCTA , there was more downstream testing and higher radiation exposure . The cumulative mean cost of care was similar in the CCTA group and the st and ard-evaluation group ( $ 4,289 and $ 4,060 , respectively ; P=0.65 ) . CONCLUSIONS In patients in the emergency department with symptoms suggestive of acute coronary syndromes , incorporating CCTA into a triage strategy improved the efficiency of clinical decision making , as compared with a st and ard evaluation in the emergency department , but it result ed in an increase in downstream testing and radiation exposure with no decrease in the overall costs of care . ( Funded by the National Heart , Lung , and Blood Institute ; ROMICAT-II Clinical Trials.gov number , NCT01084239 . ) BACKGROUND Catheter-associated urinary tract infection ( CAUTI ) is a major preventable cause of harm for patients in hospital . We aim ed to establish whether short-term routine use of antimicrobial catheters reduced risk of CAUTI compared with st and ard polytetrafluoroethylene ( PTFE ) catheterisation . METHODS In our parallel , three group , multicentre , r and omised controlled superiority trial , we enrolled adults ( aged ≥16 years ) requiring short-term ( ≤14 days ) catheterisation at 24 hospitals in the UK . Participants were r and omly allocated 1:1:1 with a remote computer allocation to receive a silver alloy-coated catheter , a nitrofural-impregnated catheter , or a PTFE-coated catheter ( control group ) . Patients undergoing unplanned catheterisation were also included and consent for participation was obtained retrospectively . Participants and trial staff were unmasked to treatment assignment . Data were collected by trial staff and by patient-reported question naires for 6 weeks after r and omisation . The primary outcome was incidence of symptomatic urinary tract infection for which an antibiotic was prescribed by 6 weeks . We postulated that a 3·3 % absolute reduction in CAUTI would represent sufficient benefit to recommend routine use of antimicrobial catheters . This study is registered , number IS RCT N75198618 . FINDINGS 708 ( 10 % ) of 7102 r and omly allocated participants were not catheterised , did not confirm consent , or withdrew , and were not included in the primary analyses . Compared with 271 ( 12·6 % ) of 2144 participants in the control group , 263 ( 12·5 % ) of 2097 participants allocated a silver alloy catheter had the primary outcome ( difference -0·1 % [ 95 % CI -2·4 to 2·2 ] ) , as did 228 ( 10·6 % ) of 2153 participants allocated a nitrofural catheter ( -2·1 % [ -4·2 to 0·1 ] ) . Rates of catheter-related discomfort were higher in the nitrofural group than they were in the other groups . INTERPRETATION Silver alloy-coated catheters were not effective for reduction of incidence of symptomatic CAUTI . The reduction we noted in CAUTI associated with nitrofural-impregnated catheters was less than that regarded as clinical ly important . Routine use of antimicrobial-impregnated catheters is not supported by this trial . FUNDING UK National Institute for Health Research Health Technology Assessment Programme BACKGROUND The higher prevalence and cost of depression for women compared with men and the possible gender differences in treatment response dem and the inclusion of women in clinical trials of depression treatments . The 1993 National Institutes of Health ( NIH ) Revitalization Act set a new st and ard , requiring investigators to consider the inclusion of women and analyze outcomes by gender , yet compliance with these st and ards in depression research has not been examined systematic ally . The purpose of this study is to examine the inclusion of women and gender-specific analyses in recent r and omized clinical trials ( RCTs ) for depression . METHODS RCTs were identified through a MEDLINE search for trials published between January 1 and December 31 , 2007 , and a Clinical trials.gov search of self-identified interventional studies to treat depression . RESULTS Of the 150 RCTs for depression published in 2007 , 15 % did not report the gender composition of their sample , 50 % of studies did not analyze outcomes by gender , and 12 % controlled for gender but did not analyze for gender differences . Of the 768 trials review ed on Clinical trials.gov , 89 % reported recruiting male and female participants , yet < 1 % reported an intention to analyze results by gender . CONCLUSIONS Many recent studies of depression treatments include women but do not examine outcomes by gender . Underst and ing how women differ from men in response to treatment is critical for enhancing treatment efficacy for the greatest number of adults with depression BACKGROUND In trachoma control programmes , azithromycin is distributed to treat the strains of chlamydia that cause ocular disease . We aim ed to compare the effect of annual versus twice-yearly distribution of azithromycin on infection with these strains . METHODS We did a cluster-r and omised trial in 24 subdistricts in northern Ethiopia , which we r and omly assigned to receive annual or twice-yearly treatment for all residents of all ages . R and om assignment was done with the R AND OM and SORT functions of Microsoft Excel . All individuals were offered their assigned treatment of a single , directly observed , oral dose of azithromycin . A 6 week course of topical 1 % tetracycline ointment , applied twice daily to both eyes but not directly observed , was offered as an alternative to azithromycin in patients younger than 12 months , and in patients with self-reported pregnancy , with allergy , or who refused azithromycin . Our primary , prespecified outcome was the prevalence of ocular chlamydial infection in a r and om sample of children aged 0 - 9 years at baseline and every 6 months for a total of 42 months within sentinel villages . Our analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT00322972 . FINDINGS Antibiotic coverage of children aged 1 - 9 years was greater than 80 % ( range 80·9 to 93·0 ) at all study visits . In the groups treated annually , the prevalence of infection in children aged 0 - 9 years was reduced from a mean 41·9 % ( 95 % CI 31·5 to 52·2 ) at baseline to 1·9 % ( 0·3 to 3·5 ) at 42 months . In the groups treated twice yearly , the prevalence of infection was reduced from a mean 38·3 % ( 29·0 to 47·6 ) at baseline to 3·2 % ( 0·0 to 6·5 ) at 42 months . The prevalence of ocular chlamydial infection in children aged 0 - 9 years in groups treated annually was not different from that of the groups treated twice yearly at 18 , 30 , and 42 months ( pooled regression p>0·99 , 95 % CI -0·06 to 0·06 ) . The mean elimination time in the twice-yearly treatment group was 7·5 months earlier ( 2·3 to 17·3 ) than that of the annual group ( p=0·10 , Cox proportional hazards model ) . INTERPRETATION After 42 months of treatment , the prevalence of ocular infection with chlamydia was similar in the groups treated annually and twice yearly . However , elimination of infection might have been more rapid in the groups of villages that received treatment twice yearly . FUNDING National Institutes of Health ( NEI U10 EY016214 ) BACKGROUND Atherosclerotic renal-artery stenosis is a common problem in the elderly . Despite two r and omized trials that did not show a benefit of renal-artery stenting with respect to kidney function , the usefulness of stenting for the prevention of major adverse renal and cardiovascular events is uncertain . METHODS We r and omly assigned 947 participants who had atherosclerotic renal-artery stenosis and either systolic hypertension while taking two or more antihypertensive drugs or chronic kidney disease to medical therapy plus renal-artery stenting or medical therapy alone . Participants were followed for the occurrence of adverse cardiovascular and renal events ( a composite end point of death from cardiovascular or renal causes , myocardial infa rct ion , stroke , hospitalization for congestive heart failure , progressive renal insufficiency , or the need for renal-replacement therapy ) . RESULTS Over a median follow-up period of 43 months ( interquartile range , 31 to 55 ) , the rate of the primary composite end point did not differ significantly between participants who underwent stenting in addition to receiving medical therapy and those who received medical therapy alone ( 35.1 % and 35.8 % , respectively ; hazard ratio with stenting , 0.94 ; 95 % confidence interval [ CI ] , 0.76 to 1.17 ; P=0.58 ) . There were also no significant differences between the treatment groups in the rates of the individual components of the primary end point or in all-cause mortality . During follow-up , there was a consistent modest difference in systolic blood pressure favoring the stent group ( -2.3 mm Hg ; 95 % CI , -4.4 to -0.2 ; P=0.03 ) . CONCLUSIONS Renal-artery stenting did not confer a significant benefit with respect to the prevention of clinical events when added to comprehensive , multifactorial medical therapy in people with atherosclerotic renal-artery stenosis and hypertension or chronic kidney disease . ( Funded by the National Heart , Lung and Blood Institute and others ; Clinical Trials.gov number , NCT00081731 . ) BACKGROUND Powders containing iron and other micronutrients are recommended as a strategy to prevent nutritional anaemia and other micronutrient deficiencies in children . We assessed the effects of provision of two micronutrient powder formulations , with or without zinc , to children in Pakistan . METHODS We did a cluster r and omised trial in urban and rural sites in Sindh , Pakistan . A baseline survey identified 256 clusters , which were r and omly assigned ( within urban and rural strata , by computer-generated r and om numbers ) to one of three groups : non-supplemented control ( group A ) , micronutrient powder without zinc ( group B ) , or micronutrient powder with 10 mg zinc ( group C ) . Children in the clusters aged 6 months were eligible for inclusion in the study . Powders were to be given daily between 6 and 18 months of age ; follow-up was to age 2 years . Micronutrient powder sachets for groups B and C were identical except for colour ; investigators and field and supervisory staff were masked to composition of the micronutrient powders until trial completion . Parents knew whether their child was receiving supplementation , but did not know whether the powder contained zinc . Primary outcomes were growth , episodes of diarrhoea , acute lower respiratory tract infection , fever , and incidence of admission to hospital . This trial is registered with Clinical Trials.gov , number NCT00705445 . RESULTS The trial was done between Nov 1 , 2008 , and Dec 31 , 2011 . 947 children were enrolled in group A clusters , 910 in group B clusters , and 889 in group C clusters . Micronutrient powder administration was associated with lower risk of iron-deficiency anaemia at 18 months compared with the control group ( odds ratio [ OR ] for micronutrient powder without zinc=0·20 , 95 % CI 0·11 - 0·36 ; OR for micronutrient powder with zinc=0·25 , 95 % CI 0·14 - 0·44 ) . Compared with the control group , children in the group receiving micronutrient powder without zinc gained an extra 0·31 cm ( 95 % CI 0·03 - 0·59 ) between 6 and 18 months of age and children receiving micronutrient powder with zinc an extra 0·56 cm ( 0·29 - 0·84 ) . We recorded strong evidence of an increased proportion of days with diarrhoea ( p=0·001 ) and increased incidence of bloody diarrhoea ( p=0·003 ) between 6 and 18 months in the two micronutrient powder groups , and reported chest indrawing ( p=0·03 ) . Incidence of febrile episodes or admission to hospital for diarrhoea , respiratory problems , or febrile episodes did not differ between the three groups . INTERPRETATION Use of micronutrient powders reduces iron-deficiency anaemia in young children . However , the excess burden of diarrhoea and respiratory morbidities associated with micronutrient powder use and the very small effect on growth recorded suggest that a careful assessment of risks and benefits must be done in population s with malnourished children and high diarrhoea burdens . FUNDING Bill & Melinda Gates Foundation BACKGROUND It is not known whether low-dose radioiodine ( 1.1 GBq [ 30 mCi ] ) is as effective as high-dose radioiodine ( 3.7 GBq [ 100 mCi ] ) for treating patients with differentiated thyroid cancer or whether the effects of radioiodine ( especially at a low dose ) are influenced by using either recombinant human thyrotropin ( thyrotropin alfa ) or thyroid hormone withdrawal . METHODS At 29 centers in the United Kingdom , we conducted a r and omized noninferiority trial comparing low-dose and high-dose radioiodine , each in combination with either thyrotropin alfa or thyroid hormone withdrawal before ablation . Patients ( age range , 16 to 80 years ) had tumor stage T1 to T3 , with possible spread to nearby lymph nodes but without metastasis . End points were the rate of success of ablation at 6 to 9 months , adverse events , quality of life , and length of hospital stay . RESULTS A total of 438 patients underwent r and omization ; data could be analyzed for 421 . Ablation success rates were 85.0 % in the group receiving low-dose radioiodine versus 88.9 % in the group receiving the high dose and 87.1 % in the thyrotropin alfa group versus 86.7 % in the group undergoing thyroid hormone withdrawal . All 95 % confidence intervals for the differences were within ±10 percentage points , indicating noninferiority . Similar results were found for low-dose radioiodine plus thyrotropin alfa ( 84.3 % ) versus high-dose radioiodine plus thyroid hormone withdrawal ( 87.6 % ) or high-dose radioiodine plus thyrotropin alfa ( 90.2 % ) . More patients in the high-dose group than in the low-dose group were hospitalized for at least 3 days ( 36.3 % vs. 13.0 % , P<0.001 ) . The proportions of patients with adverse events were 21 % in the low-dose group versus 33 % in the high-dose group ( P=0.007 ) and 23 % in the thyrotropin alfa group versus 30 % in the group undergoing thyroid hormone withdrawal ( P=0.11 ) . CONCLUSIONS Low-dose radioiodine plus thyrotropin alfa was as effective as high-dose radioiodine , with a lower rate of adverse events . ( Funded by Cancer Research UK ; Clinical Trials.gov number , NCT00415233 . ) BACKGROUND Prospect i ve assessment of pharmacogenetic strategies has been limited by an inability to undertake bedside genetic testing . The CYP2C19 * 2 allele is a common genetic variant associated with increased rates of major adverse events in individuals given clopidogrel after percutaneous coronary intervention ( PCI ) . We used a novel point-of-care genetic test to identify carriers of the CYP2C19 * 2 allele and aim ed to assess a pharmacogenetic approach to dual antiplatelet treatment after PCI . METHODS Between Aug 26 , 2010 , and July 7 , 2011 , 200 patients were enrolled into our prospect i ve , r and omised , proof-of-concept study . Patients undergoing PCI for acute coronary syndrome or stable angina were r and omly assigned to rapid point-of-care genotyping or to st and ard treatment . Individuals in the rapid genotyping group were screened for the CYP2C19 * 2 allele . Carriers were given 10 mg prasugrel daily , and non-carriers and patients in the st and ard treatment group were given 75 mg clopidogrel daily . The primary endpoint was the proportion of CYP2C19 * 2 carriers with high on-treatment platelet reactivity ( P2Y12 reactivity unit [ PRU ] value of more than 234 ) after 1 week of dual antiplatelet treatment , which is a marker associated with increased adverse cardiovascular events . Interventional cardiologists and data analysts were masked to genetic status and treatment . Patients were not masked to treatment allocation . All analyses were by intention to treat . This study is registered with Clinical Trials.gov , NCT01184300 . FINDINGS After r and omisation , 187 patients completed follow-up ( 91 rapid genotyping group , 96 st and ard treatment ) . 23 individuals in each group carried at least one CYP2C19 * 2 allele . None of the 23 carriers in the rapid genotyping group had a PRU value of more than 234 at day 7 , compared with seven ( 30 % ) given st and ard treatment ( p=0·0092 ) . The point-of-care genetic test had a sensitivity of 100 % ( 95 % CI 92·3 - 100 ) and a specificity of 99·3 % ( 96·3 - 100 ) . INTERPRETATION Point-of-care genetic testing after PCI can be done effectively at the bedside and treatment of identified CYP2C19 * 2 carriers with prasugrel can reduce high on-treatment platelet reactivity . FUNDING Spartan Biosciences BACKGROUND Autologous fat grafting is increasingly used in reconstructive surgery . However , resorption rates ranging from 25 % to 80 % have been reported . Therefore , methods to increase graft viability are needed . Here , we report the results of a triple-blind , placebo-controlled trial to compare the survival of fat grafts enriched with autologous adipose-derived stem cells ( ASCs ) versus non-enriched fat grafts . METHODS Healthy participants underwent two liposuctions taken 14 days apart : one for ASC isolation and ex-vivo expansion , and another for the preparation of fat grafts . Two purified fat grafts ( 30 mL each ) taken from the second liposuction were prepared for each participant . One graft was enriched with ASCs ( 20 × 10(6 ) cells per mL fat ) , and another graft without ASC enrichment served as a control . The fat grafts were injected subcutaneously as a bolus to the posterior part of the right and left upper arm according to the r and omisation sequence . The volumes of injected fat grafts were measured by MRI immediately after injection and after 121 days before surgical removal . The primary goal was to compare the residual graft volumes of ASC-enriched grafts with those of control grafts . This study is registered at www . clinical trialsregister.eu , number 2010 - 023006 - 12 . FINDINGS 13 participants were enrolled , three of whom were excluded . Compared with the control grafts , the ASC-enriched fat grafts had significantly higher residual volumes : 23·00 ( 95 % CI 20·57 - 25·43 ) cm(3 ) versus 4·66 ( 3·16 - 6·16 ) cm(3 ) for the controls , corresponding to 80·9 % ( 76·6 - 85·2 ) versus 16·3 % ( 11·1 - 21·4 ) of the initial volumes , respectively ( p<0·0001 ) . The difference between the groups was 18·34 ( 95 % CI 15·70 - 20·98 ) cm(3 ) , equivalent to 64·6 % ( 57·1 - 72·1 ; p<0·0001 ) . No serious adverse events were noted . INTERPRETATION The procedure of ASC-enriched fat grafting had excellent feasibility and safety . These promising results add significantly to the prospect of stem cell use in clinical setting s , and indicate that ASC graft enrichment could render lipofilling a reliable alternative to major tissue augmentation , such as breast surgery , with allogeneic material or major flap surgery . FUNDING Danish Cancer Society , Centre of Head and Orthopaedics Rigshospitalet , and Moalem Weitemeyer Bendtsen BACKGROUND We aim ed to investigate the safety and efficacy of dutasteride , a 5α-reductase inhibitor , on prostate cancer progression in men with low-risk disease who chose to be followed up with active surveillance . METHODS In our 3 year , r and omised , double-blind , placebo-controlled study , undertaken at 65 academic medical centres or outpatient clinics in North America , we enrolled men aged 48 - 82 years who had low-volume , Gleason score 5 - 6 prostate cancer and had chosen to be followed up with active surveillance . We r and omly allocated participants in a one-to-one ratio , stratified by site and in block sizes of four , to receive once-daily dutasteride 0·5 mg or matching placebo . Participants were followed up for 3 years , with 12-core prostate biopsy sample s obtained after 18 months and 3 years . The primary endpoint was time to prostate cancer progression , defined as the number of days between the start of study treatment and the earlier of either pathological progression ( in patients with ≥1 biopsy assessment after baseline ) or therapeutic progression ( start of medical therapy ) . This trial is registered with Clinical Trials.gov , number NCT00363311 . FINDINGS Between Aug 10 , 2006 , and March 26 , 2007 , we r and omly allocated 302 participants , of whom 289 ( 96 % ) had at least one biopsy procedure after baseline and were included in the primary analysis . By 3 years , 54 ( 38 % ) of 144 men in the dutasteride group and 70 ( 48 % ) of 145 controls had prostate cancer progression ( pathological or therapeutic ; hazard ratio 0·62 , 95 % CI 0·43 - 0·89 ; p=0·009 ) . Incidence of adverse events was much the same between treatment groups . 35 ( 24 % ) men in the dutasteride group and 23 ( 15 % ) controls had sexual adverse events or breast enlargement or tenderness . Eight ( 5 % ) men in the dutasteride group and seven ( 5 % ) controls had cardiovascular adverse events , but there were no prostate cancer-related deaths or instances of metastatic disease . INTERPRETATION Dutasteride could provide a beneficial adjunct to active surveillance for men with low-risk prostate cancer . FUNDING GlaxoSmithKline BACKGROUND Dolutegravir ( S/GSK1349572 ) , a once-daily , unboosted integrase inhibitor , was recently approved in the United States for the treatment of human immunodeficiency virus type 1 ( HIV-1 ) infection in combination with other antiretroviral agents . Dolutegravir , in combination with abacavir-lamivudine , may provide a simplified regimen . METHODS We conducted a r and omized , double-blind , phase 3 study involving adult participants who had not received previous therapy for HIV-1 infection and who had an HIV-1 RNA level of 1000 copies per milliliter or more . Participants were r and omly assigned to dolutegravir at a dose of 50 mg plus abacavir-lamivudine once daily ( DTG-ABC-3TC group ) or combination therapy with efavirenz-tenofovir disoproxil fumarate (DF)-emtricitabine once daily ( EFV-TDF-FTC group ) . The primary end point was the proportion of participants with an HIV-1 RNA level of less than 50 copies per milliliter at week 48 . Secondary end points included the time to viral suppression , the change from baseline in CD4 + T-cell count , safety , and viral resistance . RESULTS A total of 833 participants received at least one dose of study drug . At week 48 , the proportion of participants with an HIV-1 RNA level of less than 50 copies per milliliter was significantly higher in the DTG-ABC-3TC group than in the EFV-TDF-FTC group ( 88 % vs. 81 % , P=0.003 ) , thus meeting the criterion for superiority . The DTG-ABC-3TC group had a shorter median time to viral suppression than did the EFV-TDF-FTC group ( 28 vs. 84 days , P<0.001 ) , as well as greater increases in CD4 + T-cell count ( 267 vs. 208 per cubic millimeter , P<0.001 ) . The proportion of participants who discontinued therapy owing to adverse events was lower in the DTG-ABC-3TC group than in the EFV-TDF-FTC group ( 2 % vs. 10 % ) ; rash and neuropsychiatric events ( including abnormal dreams , anxiety , dizziness , and somnolence ) were significantly more common in the EFV-TDF-FTC group , whereas insomnia was reported more frequently in the DTG-ABC-3TC group . No participants in the DTG-ABC-3TC group had detectable antiviral resistance ; one tenofovir DF-associated mutation and four efavirenz-associated mutations were detected in participants with virologic failure in the EFV-TDF-FTC group . CONCLUSIONS Dolutegravir plus abacavir-lamivudine had a better safety profile and was more effective through 48 weeks than the regimen with efavirenz-tenofovir DF-emtricitabine . ( Funded by ViiV Healthcare ; SINGLE Clinical Trials.gov number , NCT01263015 . ) BACKGROUND The National Institutes of Health ( NIH ) Revitalization Act of 1993 requires that NIH-funded clinical trials include women and minorities as participants ; other federal agencies have adopted similar guidelines . The objective of this study is to determine the current level of compliance with these guidelines for the inclusion , analysis , and reporting of sex and race/ethnicity in federally funded r and omized controlled trials ( RCTs ) and to compare the current level of compliance with that from 2004 , which was reported previously . METHODS RCTs published in nine prominent medical journals in 2009 were identified by PubMed search . Studies where individuals were not the unit of analysis , those begun before 1994 , and those not receiving federal funding were excluded . PubMed search located 512 published articles . After exclusion of ineligible articles , 86 ( 17 % ) remained for analysis . RESULTS Thirty studies were sex specific . The median enrollment of women in the 56 studies that included both men and women was 37 % . Seventy-five percent of the studies did not report any outcomes by sex , including 9 studies reporting < 20 % women enrolled . Among all 86 studies , 21 % did not report sample sizes by racial and ethnic groups , and 64 % did not provide any analysis by racial or ethnic groups . Only 3 studies indicated that the generalizability of their results may be limited by lack of diversity among those studied . There were no statistically significant changes in inclusion or reporting of sex or race/ethnicity when compared with 2004 . CONCLUSIONS Ensuring enhanced inclusion , analysis , and reporting of sex and race/ethnicity entails the efforts of NIH , journal editors , and the research ers themselves BACKGROUND Maintenance therapy , often with azathioprine or mycophenolate mofetil , is required to consoli date remission and prevent relapse after the initial control of lupus nephritis . METHODS We carried out a 36-month , r and omized , double-blind , double-dummy , phase 3 study comparing oral mycophenolate mofetil ( 2 g per day ) and oral azathioprine ( 2 mg per kilogram of body weight per day ) , plus placebo in each group , in patients who met response criteria during a 6-month induction trial . The study group underwent repeat r and omization in a 1:1 ratio . Up to 10 mg of prednisone per day or its equivalent was permitted . The primary efficacy end point was the time to treatment failure , which was defined as death , end-stage renal disease , doubling of the serum creatinine level , renal flare , or rescue therapy for lupus nephritis . Secondary assessment s included the time to the individual components of treatment failure and adverse events . RESULTS A total of 227 patients were r and omly assigned to maintenance treatment ( 116 to mycophenolate mofetil and 111 to azathioprine ) . Mycophenolate mofetil was superior to azathioprine with respect to the primary end point , time to treatment failure ( hazard ratio , 0.44 ; 95 % confidence interval , 0.25 to 0.77 ; P = 0.003 ) , and with respect to time to renal flare and time to rescue therapy ( hazard ratio , < 1.00 ; P < 0.05 ) . Observed rates of treatment failure were 16.4 % ( 19 of 116 patients ) in the mycophenolate mofetil group and 32.4 % ( 36 of 111 ) in the azathioprine group . Adverse events , most commonly minor infections and gastrointestinal disorders , occurred in more than 95 % of the patients in both groups ( P = 0.68 ) . Serious adverse events occurred in 33.3 % of patients in the azathioprine group and in 23.5 % of those in the mycophenolate mofetil group ( P = 0.11 ) , and the rate of withdrawal due to adverse events was higher with azathioprine than with mycophenolate mofetil ( 39.6 % vs. 25.2 % , P = 0.02 ) . CONCLUSIONS Mycophenolate mofetil was superior to azathioprine in maintaining a renal response to treatment and in preventing relapse in patients with lupus nephritis who had a response to induction therapy . ( Funded by Vifor Pharma [ formerly Aspreva ] ; ALMS Clinical Trials.gov number , NCT00377637 . ) BACKGROUND Exclusive breastfeeding ( EBF ) is reported to be a life-saving intervention in low-income setting s. The effect of breastfeeding counselling by peer counsellors was assessed in Africa . METHODS 24 communities in Burkina Faso , 24 in Ug and a , and 34 in South Africa were assigned in a 1:1 ratio , by use of a computer-generated r and omisation sequence , to the control or intervention clusters . In the intervention group , we scheduled one antenatal breastfeeding peer counselling visit and four post-delivery visits by trained peers . The data gathering team were masked to the intervention allocation . The primary outcomes were prevalance of EBF and diarrhoea reported by mothers for infants aged 12 weeks and 24 weeks . Country-specific prevalence ratios were adjusted for cluster effects and sites . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT00397150 . FINDINGS 2579 mother-infant pairs were assigned to the intervention or control clusters in Burkina Faso ( n=392 and n=402 , respectively ) , Ug and a ( n=396 and n=369 , respectively ) , and South Africa ( n=535 and 485 , respectively ) . The EBF prevalences based on 24-h recall at 12 weeks in the intervention and control clusters were 310 ( 79 % ) of 392 and 139 ( 35 % ) of 402 , respectively , in Burkina Faso ( prevalence ratio 2·29 , 95 % CI 1·33 - 3·92 ) ; 323 ( 82 % ) of 396 and 161 ( 44 % ) of 369 , respectively , in Ug and a ( 1·89 , 1·70 - 2·11 ) ; and 56 ( 10 % ) of 535 and 30 ( 6 % ) of 485 , respectively , in South Africa ( 1·72 , 1·12 - 2·63 ) . The EBF prevalences based on 7-day recall in the intervention and control clusters were 300 ( 77 % ) and 94 ( 23 % ) , respectively , in Burkina Faso ( 3·27 , 2·13 - 5·03 ) ; 305 ( 77 % ) and 125 ( 34 % ) , respectively , in Ug and a ( 2·30 , 2·00 - 2·65 ) ; and 41 ( 8 % ) and 19 ( 4 % ) , respectively , in South Africa ( 1·98 , 1·30 - 3·02 ) . At 24 weeks , the prevalences based on 24-h recall were 286 ( 73 % ) in the intervention cluster and 88 ( 22 % ) in the control cluster in Burkina Faso ( 3·33 , 1·74 - 6·38 ) ; 232 ( 59 % ) and 57 ( 15 % ) , respectively , in Ug and a ( 3·83 , 2·97 - 4·95 ) ; and 12 ( 2 % ) and two ( < 1 % ) , respectively , in South Africa ( 5·70 , 1·33 - 24·26 ) . The prevalences based on 7-day recall were 279 ( 71 % ) in the intervention cluster and 38 ( 9 % ) in the control cluster in Burkina Faso ( 7·53 , 4·42 - 12·82 ) ; 203 ( 51 % ) and 41 ( 11 % ) , respectively , in Ug and a ( 4·66 , 3·35 - 6·49 ) ; and ten ( 2 % ) and one ( < 1 % ) , respectively , in South Africa ( 9·83 , 1·40 - 69·14 ) . Diarrhoea prevalence at age 12 weeks in the intervention and control clusters was 20 ( 5 % ) and 36 ( 9 % ) , respectively , in Burkina Faso ( 0·57 , 0·27 - 1·22 ) ; 39 ( 10 % ) and 32 ( 9 % ) , respectively , in Ug and a ( 1·13 , 0·81 - 1·59 ) ; and 45 ( 8 % ) and 33 ( 7 % ) , respectively , in South Africa ( 1·16 , 0·78 - 1·75 ) . The prevalence at age 24 weeks in the intervention and control clusters was 26 ( 7 % ) and 32 ( 8 % ) , respectively , in Burkina Faso ( 0·83 , 0·45 - 1·54 ) ; 52 ( 13 % ) and 59 ( 16 % ) , respectively , in Ug and a ( 0·82 , 0·58 - 1·15 ) ; and 54 ( 10 % ) and 33 ( 7 % ) , respectively , in South Africa ( 1·31 , 0·89 - 1·93 ) . INTERPRETATION Low-intensity individual breastfeeding peer counselling is achievable and , although it does not affect the diarrhoea prevalence , can be used to effectively increase EBF prevalence in many sub-Saharan African setting s. FUNDING European Union Sixth Framework International Cooperation-Developing Countries , Research Council of Norway , Swedish International Development Cooperation Agency , Norwegian Programme for Development , Research and Education , South African National Research Foundation , and Rockefeller Brothers Foundation BACKGROUND Bacteraemia is an important cause of morbidity and mortality in critically ill children . Our objective was to assess whether daily bathing in chlorhexidine gluconate ( CHG ) compared with st and ard bathing practice s would reduce bacteraemia in critically ill children . METHODS In an unmasked , cluster-r and omised , two-period crossover trial , ten paediatric intensive-care units at five hospitals in the USA were r and omly assigned a daily bathing routine for admitted patients older than 2 months , either st and ard bathing practice s or using a cloth impregnated with 2 % CHG , for a 6-month period . Units switched to the alternative bathing method for a second 6-month period . 6482 admissions were screened for eligibility . The primary outcome was an episode of bacteraemia . We did intention-to-treat ( ITT ) and per- protocol ( PP ) analyses . This study is registered with Clinical Trials.gov ( identifier NCT00549393 ) . FINDINGS 1521 admitted patients were excluded because their length of stay was less than 2 days , and 14 refused to participate . 4947 admissions were eligible for analysis . In the ITT population , a non-significant reduction in incidence of bacteraemia was noted with CHG bathing ( 3·52 per 1000 days , 95 % CI 2·64 - 4·61 ) compared with st and ard practice s ( 4·93 per 1000 days , 3·91 - 6·15 ; adjusted incidence rate ratio [ aIRR ] 0·71 , 95 % CI 0·42 - 1·20 ) . In the PP population , incidence of bacteraemia was lower in patients receiving CHG bathing ( 3·28 per 1000 days , 2·27 - 4·58 ) compared with st and ard practice s ( 4·93 per 1000 days , 3·91 - 6·15 ; aIRR 0·64 , 0·42 - 0·98 ) . No serious study -related adverse events were recorded , and the incidence of CHG-associated skin reactions was 1·2 per 1000 days ( 95 % CI 0·60 - 2·02 ) . INTERPRETATION Critically ill children receiving daily CHG bathing had a lower incidence of bacteraemia compared with those receiving a st and ard bathing routine . Furthermore , the treatment was well tolerated . FUNDING Sage Products , US National Institutes of Health BACKGROUND Stroke is common during the first few weeks after a transient ischemic attack ( TIA ) or minor ischemic stroke . Combination therapy with clopidogrel and aspirin may provide greater protection against subsequent stroke than aspirin alone . METHODS In a r and omized , double-blind , placebo-controlled trial conducted at 114 centers in China , we r and omly assigned 5170 patients within 24 hours after the onset of minor ischemic stroke or high-risk TIA to combination therapy with clopidogrel and aspirin ( clopidogrel at an initial dose of 300 mg , followed by 75 mg per day for 90 days , plus aspirin at a dose of 75 mg per day for the first 21 days ) or to placebo plus aspirin ( 75 mg per day for 90 days ) . All participants received open-label aspirin at a clinician-determined dose of 75 to 300 mg on day 1 . The primary outcome was stroke ( ischemic or hemorrhagic ) during 90 days of follow-up in an intention-to-treat analysis . Treatment differences were assessed with the use of a Cox proportional-hazards model , with study center as a r and om effect . RESULTS Stroke occurred in 8.2 % of patients in the clopidogrel-aspirin group , as compared with 11.7 % of those in the aspirin group ( hazard ratio , 0.68 ; 95 % confidence interval , 0.57 to 0.81 ; P<0.001 ) . Moderate or severe hemorrhage occurred in seven patients ( 0.3 % ) in the clopidogrel-aspirin group and in eight ( 0.3 % ) in the aspirin group ( P=0.73 ) ; the rate of hemorrhagic stroke was 0.3 % in each group . CONCLUSIONS Among patients with TIA or minor stroke who can be treated within 24 hours after the onset of symptoms , the combination of clopidogrel and aspirin is superior to aspirin alone for reducing the risk of stroke in the first 90 days and does not increase the risk of hemorrhage . ( Funded by the Ministry of Science and Technology of the People 's Republic of China ; CHANCE Clinical Trials.gov number , NCT00979589 . ) BACKGROUND Rheumatoid arthritis is a heterogeneous chronic disease , and no therapeutic agent has been identified which is universally and persistently effective in all patients . We investigated the effectiveness of tofacitinib ( CP-690,550 ) , a novel oral Janus kinase inhibitor , as a targeted immunomodulator and disease-modifying therapy for rheumatoid arthritis . METHODS We did a 6-month , double-blind , parallel-group phase 3 study at 82 centres in 13 countries , including North America , Europe , and Latin America . 399 patients aged 18 years or older with moderate-to-severe rheumatoid arthritis and inadequate response to tumour necrosis factor inhibitors ( TNFi ) were r and omly assigned in a 2:2:1:1 ratio with an automated internet or telephone system to receive twice a day treatment with : tofacitinib 5 mg ( n=133 ) ; tofacitinib 10 mg ( n=134 ) ; or placebo ( n=132 ) , all with methotrexate . At month 3 , patients given placebo advanced to either tofacitinib 5 mg twice a day ( n=66 ) or 10 mg twice a day ( n=66 ) . Primary endpoints included American College of Rheumatology (ACR)20 response rate , mean change from baseline in Health Assessment Question naire-Disability Index ( HAQ-DI ) , and rates of disease activity score (DAS)28 - 4(ESR ) less than 2·6 ( referred to as DAS28<2·6 ) , all at month 3 . The full analysis set for the primary analysis included all r and omised patients who received at least one dose of study medication and had at least one post-baseline assessment . This trial is registered with www . Clinical Trials.gov , number NCT00960440 . FINDINGS At month 3 , ACR20 response rates were 41·7 % ( 55 of 132 [ 95 % CI vs placebo 6·06 - 28·41 ] ; p=0·0024 ) for tofacitinib 5 mg twice a day and 48·1 % ( 64 of 133 ; [ 12·45 - 34·92 ] ; p<0·0001 ) for tofacitinib 10 mg twice a day versus 24·4 % ( 32 of 131 ) for placebo . Improvements from baseline in HAQ-DI were -0·43 ( [ -0·36 to -0·15 ] ; p<0·0001 ) for 5 mg twice a day and -0·46 ( [ -0·38 to -0·17 ] ; p<0·0001 ) for 10 mg twice a day tofacitinib versus -0·18 for placebo ; DAS28<2·6 rates were 6·7 % ( eight of 119 ; [ 0 - 10·10 ] ; p=0·0496 ) for 5 mg twice a day tofacitinib and 8·8 % ( 11 of 125 [ 1·66 - 12·60 ] ; p=0·0105 ) for 10 mg twice a day tofacitinib versus 1·7 % ( two of 120 ) for placebo . Safety was consistent with phase 2 and 3 studies . The most common adverse events in months 0 - 3 were diarrhoea ( 13 of 267 ; 4·9 % ) , nasopharyngitis ( 11 of 267 ; 4·1 % ) , headache ( 11 of 267 ; 4·1 % ) , and urinary tract infection ( eight of 267 ; 3·0 % ) across tofacitinib groups , and nausea ( nine of 132 ; 6·8 % ) in the placebo group . INTERPRETATION In this treatment-refractory population , tofacitinib with methotrexate had rapid and clinical ly meaningful improvements in signs and symptoms of rheumatoid arthritis and physical function over 6 months with manageable safety . Tofacitinib could provide an effective treatment option in patients with an inadequate response to TNFi . FUNDING Pfizer BACKGROUND Interim results from the children with HIV early antiretroviral ( CHER ) trial showed that early antiretroviral therapy ( ART ) was life-saving for infants infected with HIV . In view of the few treatment options and the potential toxicity associated with lifelong ART , in the CHER trial we compared early time-limited ART with deferred ART . METHODS CHER was an open-label r and omised controlled trial of HIV-infected asymptomatic infants younger than 12 weeks in two South African trial sites with a percentage of CD4-positive T lymphocytes ( CD4 % ) of 25 % or higher . 377 infants were r and omly allocated to one of three groups : deferred ART ( ART-Def ) , immediate ART for 40 weeks ( ART-40W ) , or immediate ART for 96 weeks ( ART-96W ) , with subsequent treatment interruption . The r and omisation schedule was stratified by clinical site with permuted blocks of r and om sizes to balance the numbers of infants allocated to each group . Criteria for ART initiation in the ART-Def group and re-initiation after interruption in the other groups were CD4 % less than 25 % in infancy ; otherwise , the criteria were CD4 % less than 20 % or Centers for Disease Control and Prevention severe stage B or stage C disease . Combination therapy of lopinavir-ritonavir , zidovudine , and lamivudine was the first-line treatment regimen at ART initiation and re-initiation . The primary endpoint was time to failure of first-line ART ( immunological , clinical , or virological ) or death . Comparisons were done by intention-to-treat analysis , with use of time-to-event methods . This trial is registered with Clinical Trials.gov , number NCT00102960 . FINDINGS 377 infants were enrolled , with a median age of 7·4 weeks , CD4 % of 35 % , and HIV RNA log 5·7 copies per mL. Median follow-up was 4·8 years ; 34 infants ( 9 % ) were lost to follow-up . Median time to ART initiation in the ART-Def group was 20 weeks ( IQR 16 - 25 ) . Time to restarting of ART after interruption was 33 weeks ( 26 - 45 ) in ART-40W and 70 weeks ( 35 - 109 ) in ART-96W ; at the end of the trial , 19 % of patients in ART-40W and 32 % of patients in ART-96W remained off ART . Proportions of follow-up time spent on ART were 81 % in the ART-Def group , 70 % in the ART-40W group , and 69 % in the ART-96W group . 48 ( 38 % ) of 125 children in the ART-Def group , 32 ( 25 % ) of 126 in the ART-40W group , and 26 ( 21 % ) of 126 in the ART-96W group reached the primary endpoint . The hazard ratio , relative to ART-Def , was 0·59 ( 95 % CI 0·38 - 0·93 , p=0·02 ) for ART-40W and 0·47 ( 0·27 - 0·76 , p=0·002 ) for ART-96W . Three children in ART-Def , three in ART-40W , and one in ART-96W switched to second-line ART . INTERPRETATION Early time-limited ART had better clinical and immunological outcomes than deferred ART , with no evidence of excess disease progression during subsequent treatment interruption and less overall ART exposure than deferred ART . Longer time on primary ART permits longer subsequent interruption , with marginally better outcomes . FUNDING US National Institutes of Health BACKGROUND Mortality among patients with severe acute alcoholic hepatitis is high , even among those treated with glucocorticoids . We investigated whether combination therapy with glucocorticoids plus N-acetylcysteine would improve survival . METHODS We r and omly assigned 174 patients to receive prednisolone plus N-acetylcysteine ( 85 patients ) or only prednisolone ( 89 patients ) . All patients received 4 weeks of prednisolone . The prednisolone-N-acetylcysteine group received intravenous N-acetylcysteine on day 1 ( at a dose of 150 , 50 , and 100 mg per kilogram of body weight in 250 , 500 , and 1000 ml of 5 % glucose solution over a period of 30 minutes , 4 hours , and 16 hours , respectively ) and on days 2 through 5 ( 100 mg per kilogram per day in 1000 ml of 5 % glucose solution ) . The prednisolone-only group received an infusion in 1000 ml of 5 % glucose solution per day on days 1 through 5 . The primary outcome was 6-month survival . Secondary outcomes included survival at 1 and 3 months , hepatitis complications , adverse events related to N-acetylcysteine use , and changes in bilirubin levels on days 7 and 14 . RESULTS Mortality was not significantly lower in the prednisolone-N-acetylcysteine group than in the prednisolone-only group at 6 months ( 27 % vs. 38 % , P = 0.07 ) . Mortality was significantly lower at 1 month ( 8 % vs. 24 % , P = 0.006 ) but not at 3 months ( 22 % vs. 34 % , P = 0.06 ) . Death due to the hepatorenal syndrome was less frequent in the prednisolone-N-acetylcysteine group than in the prednisolone-only group at 6 months ( 9 % vs. 22 % , P = 0.02 ) . In a multivariate analysis , factors associated with 6-month survival were a younger age ( P<0.001 ) , a shorter prothrombin time ( P<0.001 ) , a lower level of bilirubin at baseline ( P<0.001 ) , and a decrease in bilirubin on day 14 ( P<0.001 ) . Infections were less frequent in the prednisolone-N-acetylcysteine group than in the prednisolone-only group ( P = 0.001 ) ; other side effects were similar in the two groups . CONCLUSIONS Although combination therapy with prednisolone plus N-acetylcysteine increased 1-month survival among patients with severe acute alcoholic hepatitis , 6-month survival , the primary outcome , was not improved . ( Funded by Programme Hospitalier de Recherche Clinique ; AAH-NAC Clinical Trials.gov number , NCT00863785 . ) BACKGROUND Most patients who have had a stroke are dependent on informal caregivers for activities of daily living . The TRACS trial investigated a training programme for caregivers ( the London Stroke Carers Training Course , LSCTC ) on physical and psychological outcomes , including cost-effectiveness , for patients and caregivers after a disabling stroke . METHODS We undertook a pragmatic , multicentre , cluster r and omised controlled trial with a parallel cost-effectiveness analysis . Stroke units were eligible if four of five criteria used to define a stroke unit were met , a substantial number of patients on the unit had a diagnosis of stroke , staff were able to deliver the LSCTC , and most patients were discharged to a permanent place of residence . Stroke units were r and omly assigned to either LSCTC or usual care ( control group ) , stratified by geographical region and quality of care , and using blocks of size 2 . Patients with a diagnosis of stroke , likely to return home with residual disability and with a caregiver providing support were eligible . The primary outcome for patients was self-reported extended activities of daily living at 6 months , measured with the Nottingham Extended Activities of Daily Living ( NEADL ) scale . The primary outcome for caregivers was self-reported burden at 6 months , measured with the caregivers burden scale ( CBS ) . We combined patient and caregiver costs with primary outcomes and quality -adjusted life-years ( QALYs ) to assess cost-effectiveness . This trial is registered with controlled-trials.com , number IS RCT N 49208824 . FINDINGS We assessed 49 stroke units for eligibility , of which 36 were r and omly assigned to either the intervention group or the control group . Between Feb 27 , 2008 , and Feb 9 , 2010 , 928 patient and caregiver dyads were registered , of which 450 were in the intervention group , and 478 in the control group . Patients ' self-reported extended activities of daily living did not differ between groups at 6 months ( adjusted mean NEADL score 27·4 in the intervention group versus 27·6 in the control group , difference -0·2 points [ 95 % CI -3·0 to 2·5 ] , p value=0·866 , ICC=0·027 ) . The caregiver burden scale did not differ between groups either ( adjusted mean CBS 45·5 in the intervention group versus 45·0 in the control group , difference 0·5 points [ 95 % CI -1·7 to 2·7 ] , p value=0·660 , ICC=0·013 ) . Patient and caregiver costs were similar in both groups ( length of the initial stroke admission and associated costs were £ 13,127 for the intervention group and £ 12,471 for the control group ; adjusted mean difference £ 1243 [ 95 % CI -1533 to 4019 ] ; p value=0·380 ) . Probabilities of cost-effectiveness based on QALYs were low . INTERPRETATION In a large scale , robust evaluation , results from this study have shown no differences between the LSCTC and usual care on any of the assessed outcomes . The immediate period after stroke might not be the ideal time to deliver structured caregiver training . FUNDING Medical Research Council Differential enrollment into clinical trials by gender has been described previously . In 1993 , the National Institutes of Health ( NIH ) Revitalization Act was enacted to promote the inclusion of women in clinical trials . The purpose of this study was to review patterns in clinical trial enrollment among studies published in a major medical journal to determine the effects of this policy . A systematic search was conducted of all articles published in the Original Articles section of The New Engl and Journal of Medicine from 1994 to 1999 . Two independent observers abstract ed information from the r and omized clinical trials using st and ardized forms . All r and omized clinical trials in which the primary end point was total mortality or included mortality in a composite end point were considered for review . Trials were analyzed for enrollment of women with respect to disease state , funding source , site of trial performance , and use of gender-specific data analysis . From 1994 to 1999 , 1322 original articles were published in The New Engl and Journal of Medicine , including 442 r and omized , controlled trials of which 120 met our inclusion criteria . On average , 24.6 % women were enrolled . Gender-specific data analysis was performed in 14 % of the trials . The NIH Revitalization Act does not appear to have improved gender-balanced enrollment or promoted the use of gender-specific analyses in clinical trials published in an influential medical journal . Overcoming this trend will require rigorous efforts on the part of funding entities , trial investigators , and journals disseminating study results BACKGROUND Current treatment recommendations for patients with polycythemia vera call for maintaining a hematocrit of less than 45 % , but this therapeutic strategy has not been tested in a r and omized clinical trial . METHODS We r and omly assigned 365 adults with JAK2-positive polycythemia vera who were being treated with phlebotomy , hydroxyurea , or both to receive either more intensive treatment ( target hematocrit , < 45 % ) ( low-hematocrit group ) or less intensive treatment ( target hematocrit , 45 to 50 % ) ( high-hematocrit group ) . The primary composite end point was the time until death from cardiovascular causes or major thrombotic events . The secondary end points were cardiovascular events , cardiovascular hospitalizations , incidence of cancer , progression to myelofibrosis , myelodysplasia or leukemic transformation , and hemorrhage . An intention-to-treat analysis was performed . RESULTS After a median follow-up of 31 months , the primary end point was recorded in 5 of 182 patients in the low-hematocrit group ( 2.7 % ) and 18 of 183 patients in the high-hematocrit group ( 9.8 % ) ( hazard ratio in the high-hematocrit group , 3.91 ; 95 % confidence interval [ CI ] , 1.45 to 10.53 ; P=0.007 ) . The primary end point plus superficial-vein thrombosis occurred in 4.4 % of patients in the low-hematocrit group , as compared with 10.9 % in the high-hematocrit group ( hazard ratio , 2.69 ; 95 % CI , 1.19 to 6.12 ; P=0.02 ) . Progression to myelofibrosis , myelodysplasia or leukemic transformation , and bleeding were observed in 6 , 2 , and 2 patients , respectively , in the low-hematocrit group , as compared with 2 , 1 , and 5 patients , respectively , in the high-hematocrit group . There was no significant between-group difference in the rate of adverse events . CONCLUSIONS In patients with polycythemia vera , those with a hematocrit target of less than 45 % had a significantly lower rate of cardiovascular death and major thrombosis than did those with a hematocrit target of 45 to 50 % . ( Funded by the Italian Medicines Agency and others ; Clinical Trials.gov number , NCT01645124 , and EudraCT number , 2007 - 006694 - 91 . ) 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 . ) BACKGROUND Among patients with Alzheimer 's disease who have had a response to antipsychotic medication for psychosis or agitation-aggression , the risk of a recurrence of symptoms after discontinuation of the medication has not been established . METHODS Patients with Alzheimer 's disease and psychosis or agitation-aggression received open-label treatment with risperidone for 16 weeks . Those who had a response to risperidone therapy were then r and omly assigned , in a double-blind fashion , to one of three regimens : continued risperidone therapy for 32 weeks ( group 1 ) , risperidone therapy for 16 weeks followed by placebo for 16 weeks ( group 2 ) , or placebo for 32 weeks ( group 3 ) . The primary outcome was the time to relapse of psychosis or agitation . RESULTS A total of 180 patients received open-label risperidone ( mean dose , 0.97 mg daily ) . The severity of psychosis and agitation were reduced , although there was a mild increase in extrapyramidal signs ; 112 patients met the criteria for response to treatment , of whom 110 underwent r and omization . In the first 16 weeks after r and omization , the rate of relapse was higher in the group that received placebo than in the groups that received risperidone ( 60 % [ 24 of 40 patients in group 3 ] vs. 33 % [ 23 of 70 in groups 1 and 2 ] ; P=0.004 ; hazard ratio with placebo , 1.94 ; 95 % confidence interval [ CI ] , 1.09 to 3.45 ; P=0.02 ) . During the next 16 weeks , the rate of relapse was higher in the group that was switched from risperidone to placebo than in the group that continued to receive risperidone ( 48 % [ 13 of 27 patients in group 2 ] vs. 15 % [ 2 of 13 in group 1 ] ; P=0.02 ; hazard ratio , 4.88 ; 95 % CI , 1.08 to 21.98 ; P=0.02 ) . The rates of adverse events and death after r and omization did not differ significantly among the groups , although comparisons were based on small numbers of patients , especially during the final 16 weeks . CONCLUSIONS In patients with Alzheimer 's disease who had psychosis or agitation that had responded to risperidone therapy for 4 to 8 months , discontinuation of risperidone was associated with an increased risk of relapse . ( Funded by the National Institutes of Health and others ; Clinical Trials.gov number , NCT00417482 . ) BACKGROUND Alzheimer 's disease is characterized by the presence of cortical amyloid-beta ( Aβ ) protein plaques , which result from the sequential action of β-secretase and γ-secretase on amyloid precursor protein . Semagacestat is a small-molecule γ-secretase inhibitor that was developed as a potential treatment for Alzheimer 's disease . METHODS We conducted a double-blind , placebo-controlled trial in which 1537 patients with probable Alzheimer 's disease underwent r and omization to receive 100 mg of semagacestat , 140 mg of semagacestat , or placebo daily . Changes in cognition from baseline to week 76 were assessed with the use of the cognitive subscale of the Alzheimer 's Disease Assessment Scale for cognition ( ADAS-cog ) , on which scores range from 0 to 70 and higher scores indicate greater cognitive impairment , and changes in functioning were assessed with the Alzheimer 's Disease Cooperative Study -Activities of Daily Living ( ADCS-ADL ) scale , on which scores range from 0 to 78 and higher scores indicate better functioning . A mixed-model repeated- measures analysis was used . RESULTS The trial was terminated before completion on the basis of a recommendation by the data and safety monitoring board . At termination , there were 189 patients in the group receiving placebo , 153 patients in the group receiving 100 mg of semagacestat , and 121 patients in the group receiving 140 mg of semagacestat . The ADAS-cog scores worsened in all three groups ( mean change , 6.4 points in the placebo group , 7.5 points in the group receiving 100 mg of the study drug , and 7.8 points in the group receiving 140 mg ; P=0.15 and P=0.07 , respectively , for the comparison with placebo ) . The ADCS-ADL scores also worsened in all groups ( mean change at week 76 , -9.0 points in the placebo group , -10.5 points in the 100-mg group , and -12.6 points in the 140-mg group ; P=0.14 and P<0.001 , respectively , for the comparison with placebo ) . Patients treated with semagacestat lost more weight and had more skin cancers and infections , treatment discontinuations due to adverse events , and serious adverse events ( P<0.001 for all comparisons with placebo ) . Laboratory abnormalities included reduced levels of lymphocytes , T cells , immunoglobulins , albumin , total protein , and uric acid and elevated levels of eosinophils , monocytes , and cholesterol ; the urine pH was also elevated . CONCLUSIONS As compared with placebo , semagacestat did not improve cognitive status , and patients receiving the higher dose had significant worsening of functional ability . Semagacestat was associated with more adverse events , including skin cancers and infections . ( Funded by Eli Lilly ; Clinical Trials.gov number , NCT00594568 . BACKGROUND Interferon-free regimens would be a major advance in the treatment of patients with chronic hepatitis C virus ( HCV ) infection . METHODS In this phase 2b , r and omized , open-label trial of faldaprevir ( a protease inhibitor ) and deleobuvir ( a nonnucleoside polymerase inhibitor ) , we r and omly assigned 362 previously untreated patients with HCV genotype 1 infection to one of five groups : faldaprevir at a dose of 120 mg once daily and deleobuvir at a dose of 600 mg three times daily , plus ribavirin , for 16 , 28 , or 40 weeks ( TID16W , TID28W , or TID40W , respectively ) ; faldaprevir at a dose of 120 mg once daily and deleobuvir at a dose of 600 mg twice daily , plus ribavirin , for 28 weeks ( BID28W ) ; or faldaprevir at a dose of 120 mg once daily and deleobuvir at a dose of 600 mg three times daily , without ribavirin , for 28 weeks ( TID28W-NR ) . The primary end point was a sustained virologic response 12 weeks after the completion of therapy . RESULTS The primary end point was met in 59 % of patients in the TID16W group , 59 % of patients in the TID28W group , 52 % of patients in the TID40W group , 69 % of patients in the BID28W group , and 39 % of patients in the TID28W-NR group . The sustained virologic response 12 weeks after the completion of therapy did not differ significantly according to treatment duration or dosage among ribavirin-containing regimens . This response was significantly higher with TID28W than with TID28W-NR ( P=0.03 ) . Rates of a sustained virologic response 12 weeks after the completion of therapy were 56 to 85 % among patients with genotype 1b infection versus 11 to 47 % among patients with genotype 1a infection and 58 to 84 % among patients with IL28B CC versus 33 to 64 % with non-CC genotypes . Rash , photosensitivity , nausea , vomiting , and diarrhea were the most common adverse events . CONCLUSIONS The rate of a sustained virologic response 12 weeks after the completion of therapy was 52 to 69 % among patients who received interferon-free treatment with faldaprevir in combination with deleobuvir plus ribavirin . ( Funded by Boehringer Ingelheim ; SOUND-C2 Clinical Trials.gov number , NCT01132313 . ) BACKGROUND The treatment of relapsed chronic lymphocytic leukemia ( CLL ) has result ed in few durable remissions . Bruton 's tyrosine kinase ( BTK ) , an essential component of B-cell-receptor signaling , mediates interactions with the tumor microenvironment and promotes the survival and proliferation of CLL cells . METHODS We conducted a phase 1b-2 multicenter study to assess the safety , efficacy , pharmacokinetics , and pharmacodynamics of ibrutinib ( PCI-32765 ) , a first-in-class , oral covalent inhibitor of BTK design ed for treatment of B-cell cancers , in patients with relapsed or refractory CLL or small lymphocytic lymphoma . A total of 85 patients , the majority of whom were considered to have high-risk disease , received ibrutinib orally once daily ; 51 received 420 mg , and 34 received 840 mg . RESULTS Toxic effects were predominantly grade 1 or 2 and included transient diarrhea , fatigue , and upper respiratory tract infection ; thus , patients could receive extended treatment with minimal hematologic toxic effects . The overall response rate was the same in the group that received 420 mg and the group that received 840 mg ( 71 % ) , and an additional 20 % and 15 % of patients in the respective groups had a partial response with lymphocytosis . The response was independent of clinical and genomic risk factors present before treatment , including advanced-stage disease , the number of previous therapies , and the 17p13.1 deletion . At 26 months , the estimated progression-free survival rate was 75 % and the rate of overall survival was 83 % . CONCLUSIONS Ibrutinib was associated with a high frequency of durable remissions in patients with relapsed or refractory CLL and small lymphocytic lymphoma , including patients with high-risk genetic lesions . ( Funded by Pharmacyclics and others ; Clinical Trials.gov number , NCT01105247 . ) BACKGROUND For patients with smoldering multiple myeloma , the st and ard of care is observation until symptoms develop . However , this approach does not identify high-risk patients who may benefit from early intervention . METHODS In this r and omized , open-label , phase 3 trial , we r and omly assigned 119 patients with high-risk smoldering myeloma to treatment or observation . Patients in the treatment group received an induction regimen ( lenalidomide at a dose of 25 mg per day on days 1 to 21 , plus dexamethasone at a dose of 20 mg per day on days 1 to 4 and days 12 to 15 , at 4-week intervals for nine cycles ) , followed by a maintenance regimen ( lenalidomide at a dose of 10 mg per day on days 1 to 21 of each 28-day cycle for 2 years ) . The primary end point was time to progression to symptomatic disease . Secondary end points were response rate , overall survival , and safety . RESULTS After a median follow-up of 40 months , the median time to progression was significantly longer in the treatment group than in the observation group ( median not reached vs. 21 months ; hazard ratio for progression , 0.18 ; 95 % confidence interval [ CI ] , 0.09 to 0.32 ; P<0.001 ) . The 3-year survival rate was also higher in the treatment group ( 94 % vs. 80 % ; hazard ratio for death , 0.31 ; 95 % CI , 0.10 to 0.91 ; P=0.03 ) . A partial response or better was achieved in 79 % of patients in the treatment group after the induction phase and in 90 % during the maintenance phase . Toxic effects were mainly grade 2 or lower . CONCLUSIONS Early treatment for patients with high-risk smoldering myeloma delays progression to active disease and increases overall survival . ( Funded by Celgene ; Clinical Trials.gov number , NCT00480363 . ) BACKGROUND To assess potentially elevated cardiovascular risk related to new antihyperglycemic drugs in patients with type 2 diabetes , regulatory agencies require a comprehensive evaluation of the cardiovascular safety profile of new antidiabetic therapies . We assessed cardiovascular outcomes with alogliptin , a new inhibitor of dipeptidyl peptidase 4 ( DPP-4 ) , as compared with placebo in patients with type 2 diabetes who had had a recent acute coronary syndrome . METHODS We r and omly assigned patients with type 2 diabetes and either an acute myocardial infa rct ion or unstable angina requiring hospitalization within the previous 15 to 90 days to receive alogliptin or placebo in addition to existing antihyperglycemic and cardiovascular drug therapy . The study design was a double-blind , noninferiority trial with a prespecified noninferiority margin of 1.3 for the hazard ratio for the primary end point of a composite of death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke . RESULTS A total of 5380 patients underwent r and omization and were followed for up to 40 months ( median , 18 months ) . A primary end-point event occurred in 305 patients assigned to alogliptin ( 11.3 % ) and in 316 patients assigned to placebo ( 11.8 % ) ( hazard ratio , 0.96 ; upper boundary of the one-sided repeated confidence interval , 1.16 ; P<0.001 for noninferiority ) . Glycated hemoglobin levels were significantly lower with alogliptin than with placebo ( mean difference , -0.36 percentage points ; P<0.001 ) . Incidences of hypoglycemia , cancer , pancreatitis , and initiation of dialysis were similar with alogliptin and placebo . CONCLUSIONS Among patients with type 2 diabetes who had had a recent acute coronary syndrome , the rates of major adverse cardiovascular events were not increased with the DPP-4 inhibitor alogliptin as compared with placebo . ( Funded by Takeda Development Center Americas ; EXAMINE Clinical Trials.gov number , NCT00968708 . ) BACKGROUND Although P2Y12 antagonists are effective in patients with non-ST-segment elevation ( NSTE ) acute coronary syndromes , the effect of the timing of administration -- before or after coronary angiography -- is not known . We evaluated the effect of administering the P2Y12 antagonist prasugrel at the time of diagnosis versus administering it after the coronary angiography if percutaneous coronary intervention ( PCI ) was indicated . METHODS We enrolled 4033 patients with NSTE acute coronary syndromes and a positive troponin level who were scheduled to undergo coronary angiography within 2 to 48 hours after r and omization . Patients were r and omly assigned to receive prasugrel ( a 30-mg loading dose ) before the angiography ( pretreatment group ) or placebo ( control group ) . When PCI was indicated , an additional 30 mg of prasugrel was given in the pretreatment group at the time of PCI and 60 mg of prasugrel was given in the control group . RESULTS The rate of the primary efficacy end point , a composite of death from cardiovascular causes , myocardial infa rct ion , stroke , urgent revascularization , or glycoprotein IIb/IIIa inhibitor rescue therapy ( glycoprotein IIb/IIIa bailout ) through day 7 , did not differ significantly between the two groups ( hazard ratio with pretreatment , 1.02 ; 95 % confidence interval [ CI ] , 0.84 to 1.25 ; P=0.81 ) . The rate of the key safety end point of all Thrombolysis in Myocardial Infa rct ion ( TIMI ) major bleeding episodes , whether related or not related to coronary-artery bypass grafting ( CABG ) , through day 7 was increased with pretreatment ( hazard ratio , 1.90 ; 95 % CI , 1.19 to 3.02 ; P=0.006 ) . The rates of TIMI major bleeding and life-threatening bleeding not related to CABG were increased by a factor of 3 and 6 , respectively . Pretreatment did not reduce the rate of the primary outcome among patients undergoing PCI ( 69 % of the patients ) but increased the rate of TIMI major bleeding at 7 days . All the results were confirmed at 30 days and in prespecified subgroups . CONCLUSIONS Among patients with NSTE acute coronary syndromes who were scheduled to undergo catheterization , pretreatment with prasugrel did not reduce the rate of major ischemic events up to 30 days but increased the rate of major bleeding complications . ( Funded by Daiichi Sankyo and Eli Lilly ; ACCOAST Clinical Trials.gov number , NCT01015287 . ) BACKGROUND Idiopathic pulmonary fibrosis ( IPF ) is a progressive , fatal disorder of unknown cause with no effective treatment . Cough affects up to 80 % of patients with IPF , is frequently disabling , and lacks effective therapy . OBJECTIVE To determine the efficacy of thalidomide in suppressing cough in patients with IPF . DESIGN 24-week , double-blind , 2-treatment , 2-period crossover trial . ( Clinical Trials.gov registration number : NCT00600028 ) SETTING 1 university center . PARTICIPANTS 98 participants were screened , 24 were r and omly assigned , 23 received treatment ( 78.3 % men ; mean age , 67.6 years ; mean FVC , 70.4 % predicted ) , and 20 completed both treatment periods . MEASUREMENTS The primary end point was cough-specific quality of life measured by the Cough Quality of Life Question naire ( CQLQ ) . Secondary end points were visual analogue scale of cough and the St. George 's Respiratory Question naire ( SGRQ ) . For all measures , lower scores equaled improved cough or respiratory quality of life . RESULTS CQLQ scores significantly improved with thalidomide ( mean difference vs. placebo , -11.4 [ 95 % CI , -15.7 to -7.0 ] ; P < 0.001 ) . Thalidomide also significantly improved scores on the visual analogue scale of cough ( mean difference vs. placebo , -31.2 [ CI , -45.2 to -17.2 ] ; P < 0.001 ) . In participants receiving thalidomide , scores from the total SGRQ , SGRQ symptom domain , and SGRQ impact domain improved compared with those of participants receiving placebo . Adverse events were reported in 74 % of patients receiving thalidomide and 22 % receiving placebo ; constipation , dizziness , and malaise were more frequent with thalidomide . LIMITATION This was a single-center study of short duration and small sample size focused on symptom-specific quality of life . CONCLUSION Thalidomide improved cough and respiratory quality of life in patients with IPF . A larger trial is warranted to assess these promising results . PRIMARY FUNDING SOURCE Celgene Corporation BACKGROUND The role of aspirin in thromboprophylaxis after total hip arthroplasty ( THA ) is controversial . OBJECTIVE To compare extended prophylaxis with aspirin and dalteparin for prevention of symptomatic venous thromboembolism ( VTE ) after THA . DESIGN Multicenter r and omized , controlled trial with a noninferiority design based on a minimal clinical ly important difference of 2.0 % . R and omization was electronically generated ; patients were assigned to a treatment group through a Web-based program . Patients , physicians , study coordinators , health care team members , outcome adjudicators , and data analysts were blinded to interventions . ( Current Controlled Trials : IS RCT N11902170 ) . SETTING 12 tertiary care orthopedic referral centers in Canada . PATIENTS 778 patients who had elective unilateral THA between 2007 and 2010 . INTERVENTION After an initial 10 days of dalteparin prophylaxis after elective THA , patients were r and omly assigned to 28 days of dalteparin ( n = 400 ) or aspirin ( n = 386 ) . MEASUREMENTS Symptomatic VTE confirmed by objective testing ( primary efficacy outcome ) and bleeding . RESULTS Five of 398 patients ( 1.3 % ) r and omly assigned to dalteparin and 1 of 380 ( 0.3 % ) r and omly assigned to aspirin had VTE ( absolute difference , 1.0 percentage point [ 95 % CI , -0.5 to 2.5 percentage points ] ) . Aspirin was noninferior ( P < 0.001 ) but not superior ( P = 0.22 ) to dalteparin . Clinical ly significant bleeding occurred in 5 patients ( 1.3 % ) receiving dalteparin and 2 ( 0.5 % ) receiving aspirin . The absolute between-group difference in a composite of all VTE and clinical ly significant bleeding events was 1.7 percentage points ( CI , -0.3 to 3.8 percentage points ; P = 0.091 ) in favor of aspirin . LIMITATION The study was halted prematurely because of difficulty with patient recruitment . CONCLUSION Extended prophylaxis for 28 days with aspirin was noninferior to and as safe as dalteparin for the prevention of VTE after THA in patients who initially received dalteparin for 10 days . Given its low cost and greater convenience , aspirin may be considered a reasonable alternative for extended thromboprophylaxis after THA . PRIMARY FUNDING SOURCE Canadian Institutes of Health Research BACKGROUND Social networking technologies are an emerging tool for HIV prevention . OBJECTIVE To determine whether social networking communities can increase HIV testing among African American and Latino men who have sex with men ( MSM ) . DESIGN R and omized , controlled trial with concealed allocation . ( Clinical Trials.gov : NCT01701206 ) . SETTING Online . PATIENTS 112 MSM based in Los Angeles , more than 85 % of whom were African American or Latino . INTERVENTION Sixteen peer leaders were r and omly assigned to deliver information about HIV or general health to participants via Facebook groups over 12 weeks . After participants accepted a request to join the group , participation was voluntary . Group participation and engagement were monitored . Participants could request a free , home-based HIV testing kit and completed question naires at baseline and 12-week follow-up . MEASUREMENTS Participant acceptance of and engagement in the intervention and social network participation , rates of home-based HIV testing , and sexual risk behaviors . RESULTS Almost 95 % of intervention participants and 73 % of control participants voluntarily communicated using the social platform . Twenty-five of 57 intervention participants ( 44 % ) requested home-based HIV testing kits compared with 11 of 55 control participants ( 20 % ) ( difference , 24 percentage points [ 95 % CI , 8 to 41 percentage points ] ) . Nine of the 25 intervention participants ( 36 % ) who requested the test took it and mailed it back compared with 2 of the 11 control participants ( 18 % ) who requested the test . Retention at study follow-up was more than 93 % . LIMITATION Only 2 Facebook communities were included for each group . CONCLUSION Social networking communities are acceptable and effective tools to increase home-based HIV testing among at-risk population s. PRIMARY FUNDING SOURCE National Institute of Mental Health |
12,352 | 30,404,728 | Electronic data bases ( EMBASE , PsycINFO , PubMed , and SCOPUS ) were search ed for studies using experience sampling methodology to investigate daily associations between sleep and mood in naturalistic environments in healthy and clinical sample s. Findings of the included studies supported the notion of a reciprocal relationship between subjective sleep variables ( sleep quality , sleep duration and sleep latency ) and daytime affective states over the short term , and highlight the potential clinical importance of daily sleep disturbance in the prediction and prevention of the development of psychopathology in the future | An intimate relationship exists between sleep and affective states .
Disturbances in sleep are common across a spectrum of psychopathologies , and are recognised as precipitating or prodromal factors for mood disorders .
Conversely , affective states can impact sleep quality and ability to fall asleep .
However , one of the main limitations of this literature is that studies have typically assessed sleep and mood at one time point and studies are often laboratory-based , where measurement of both sleep and mood has dubious ecological validity .
The aim of the current review was to systematic ally examine the evidence for associations between day-to-day fluctuations in sleep and mood in naturalistic studies using ambulatory diary techniques . | OBJECTIVE The present study was performed to determine whether high levels of trait-anger ( T-Anger ) are independently associated with sleep disturbances and quantitative and qualitative measurements of sleep in middle-aged adults . METHODS Enrolled in the study were 2404 men and 2291 women derived from the Korean Health and Genome Study ( KHGS ) , which is an ongoing population -based prospect i ve study . The Spielberger Trait Anger Scale was used to measure T-Anger . RESULTS Sleep disturbances , including difficulty in initiating and maintaining sleep ( DIS and DMS , respectively ) and early morning awakening ( EMA ) , significantly increased with increasing levels of T-Anger ( P<.05 by test for trend ) . Nonrestorative feelings in the morning and excessive daytime sleepiness were also strongly associated with higher levels of T-Anger . After adjusting for other potential risk factors , the high and /or moderate T-Anger showed 40 % to 70 % increases in the odds for sleep disturbances . CONCLUSION The present study provides evidence that high levels of T-Anger are independently associated with symptoms of disturbed sleep in middle-aged adult population Objectives . We explored the prospect i ve , microlevel relationship between nightly sleep quality ( SQ ) and the subsequent day 's stress on positive ( PA ) and negative affect ( NA ) as well as the moderating relationships between nightly SQ , subsequent stress , and subsequent PA on NA . We investigated whether age moderated these relationships . Method . We collected 56 days of sleep , stress , and affect data using daily diary question naires ( N = 552 ) . We used multilevel modeling to assess relationships at the between- and within-person levels . Results . Daily increases in SQ and decreases in stress interacted to predict higher daily PA and lower daily NA . Better SQ in older adults enhanced the benefits of PA on the stress-NA relationship more during times of low stress , whereas better sleep in younger adults enhanced the benefits of PA more during times of high stress . Between-person effects were stronger predictors of well-being outcomes than within-person variability . Discussion . The combination of good SQ and higher PA buffered the impact of stress on NA . The moderating impact of age suggests that sleep and stress play different roles across adulthood . Targeting intervention and prevention strategies to improve SQ and enhance PA could disrupt the detrimental relationship between daily stress and NA The aim of this pilot study was to quantify the impact of sleep deprivation on psychophysiological reactivity to emotional stimuli . Following an adaptation night of sleep in the lab , healthy young adults were r and omly assigned to either one night of total sleep deprivation or to a normal sleep control condition . The next afternoon , responses to positive , negative , and neutral picture stimuli were examined with pupillography , an indicator of cognitive and affective information processing . Only the sleep-deprived group displayed significantly larger pupil diameter while viewing negative pictures compared to positive or neutral pictures . The sleep-deprived group also showed anticipatory pupillary reactivity during blocks of negative pictures . These data suggest that sleep deprivation is associated with increased reactions to negative emotional information . Such responses may have important implication s for psychiatric disorders , which may be triggered or characterized by sleep disturbances The present study investigates whether interepisode mood regulation impairment contributes to disturbances in sleep onset latency ( SOL ) and rapid eye movement ( REM ) sleep . Individuals with interepisode bipolar disorder ( n = 28 ) and healthy controls ( n = 28 ) slept in the laboratory for 2 baseline nights , a happy mood induction night , and a sad mood induction night . There was a significant interaction whereby on the happy mood induction night the bipolar group exhibited significantly longer SOL than did the control group , while there was no difference on the baseline nights . In addition , control participants exhibited shorter SOL on the happy mood induction night compared to the baseline nights , a finding that was not observed in the bipolar group . On the sad mood induction night , participants in both groups had shorter SOL and increased REM density when compared to the baseline nights . Bipolar participants exhibited heightened REM density compared to control participants on both nights . These results raise the possibility that regulation of positive stimuli may be a contributor to difficulties with SOL , while hyperactivity may be characteristic of REM sleep BACKGROUND Insomnia and major depressive disorder ( MDD ) can coexist . This study evaluated the effect of adding eszopiclone to fluoxetine . METHODS Patients who met DSM-IV criteria for both MDD and insomnia ( n = 545 ) received morning fluoxetine and were r and omized to nightly eszopiclone 3 mg ( ESZ+FLX ) or placebo ( PBO+FLX ) for 8 weeks . Subjective sleep and daytime function were assessed weekly . Depression was assessed with the 17-item Hamilton Rating Scale for Depression ( HAM-D-17 ) and the Clinical Global Impression Improvement ( CGI-I ) and Severity items ( CGI-S ) . RESULTS Patients in the ESZ+FLX group had significantly decreased sleep latency , wake time after sleep onset ( WASO ) , increased total sleep time ( TST ) , sleep quality , and depth of sleep at all double-blind time points ( all p < .05 ) . Eszopiclone co-therapy also result ed in : significantly greater changes in HAM-D-17 scores at Week 4 ( p = .01 ) with progressive improvement at Week 8 ( p = .002 ) ; significantly improved CGI-I and CGI-S scores at all time points beyond Week 1 ( p < .05 ) ; and significantly more responders ( 59 % vs. 48 % ; p = .009 ) and remitters ( 42 % vs. 33 % ; p = .03 ) at Week 8 . Treatment was well tolerated , with similar adverse event and dropout rates . CONCLUSIONS In this study , eszopiclone/fluoxetine co-therapy was relatively well tolerated and associated with rapid , substantial , and sustained sleep improvement , a faster onset of antidepressant response on the basis of CGI , and a greater magnitude of the antidepressant effect STUDY OBJECTIVES ( 1 ) To describe the prevalence and prospect i ve course of insomnia in a representative young-adult sample and ( 2 ) to describe the cross-sectional and longitudinal associations between insomnia and depression . DESIGN Longitudinal cohort study . SETTING Community of Zurich , Switzerl and . PARTICIPANTS Representative stratified population sample . INTERVENTIONS None . MEASUREMENTS AND RESULTS The Zurich Study prospect ively assessed psychiatric , physical , and sleep symptoms in a community sample of young adults ( n=591 ) with 6 interviews spanning 20 years . We distinguished 4 duration -based subtypes of insomnia : 1-month insomnia associated with significant distress , 2- to 3-week insomnia , recurrent brief insomnia , and occasional brief insomnia . The annual prevalence of 1-month insomnia increased gradually over time , with a cumulative prevalence rate of 20 % and a greater than 2-fold risk among women . In 40 % of subjects , insomnia developed into more chronic forms over time . Insomnia either with or without comorbid depression was highly stable over time . Insomnia lasting 2 weeks or longer predicted major depressive episodes and major depressive disorder at subsequent interviews ; 17 % to 50 % of subjects with insomnia lasting 2 weeks or longer developed a major depressive episode in a later interview . " Pure " insomnia and " pure " depression were not longitudinally related to each other , whereas insomnia comorbid with depression was longitudinally related to both . CONCLUSIONS This longitudinal study confirms the persistent nature of insomnia and the increased risk of subsequent depression among individuals with insomnia . The data support a spectrum of insomnia ( defined by duration and frequency ) comorbid with , rather than secondary to , depression Although previous research has suggested that presleep negative cognitive activities are associated with poor sleep quality , there is little evidence regarding the association between negative thoughts and sleep in real-life setting s. The present study used experience sampling and long-term sleep monitoring with actigraphy to investigate the relationships among negative repetitive thought , mood , and sleep problems . During a 1-week sampling period , 43 undergraduate students recorded their thought content and mood eight times a day at semir and om intervals . In addition to these subjective reports , participants wore actigraphs on their wrists in order to measure sleep parameters . Analyses using multilevel modeling showed that repetitive thought in the evening was significantly associated with longer sleep-onset latency , decreased sleep efficiency , and reduced total sleep time . Furthermore , impaired sleep quality was significantly associated with reduced positive affect the next morning , and decreased positive affect was indirectly associated with increased repetitive thought in the evening . These findings suggest the existence of a self-reinforcing cycle involving repetitive thought , mood , and impaired sleep quality , highlighting the importance of cognitive and emotional factors in enhancement and maintenance of good- quality sleep BACKGROUND Sleep and mood disturbances in women have often been linked to the menstrual cycle , implying an ovarian hormonal causation . However , most studies in this area have used self-reported menstrual cycle phase rather than direct measurement of ovarian hormone concentrations . Further , many studies have focused primarily on peri- and postmenopausal population s reporting clinical sleep difficulty . In this study , we examined the associations among sleep quality , mood , and ovarian hormone concentration in a r and om sample of community-dwelling , non clinical women of reproductive age . METHODS Our sample consisted of 19 non-help-seeking women aged 18 - 43 years , each contributing an average of 39.5 nights of data . Over the 42 days of the study , we collected self-reported and actigraphic sleep- quality data , concentrations of urinary estrogen and progesterone metabolites ( estrone-3-glucuronide ( E1 G ) and pregnanediol-3-glucuronide [ PdG ] , respectively ) , and daily mood ratings . Linear-mixed models were used to estimate associations , clustering longitudinal observations by the participant . RESULTS We found a significant positive association between Sleep Efficiency and E1 G , and a significant negative association between Sleep Efficiency and PdG. Otherwise , the self-reported and actigraphic sleep measures were not associated with ovarian hormone concentrations . Self-reported sleep was strongly associated with mood , whereas actigraphic sleep was associated with only two of the 11 individual mood items , " Feeling on Top of Things " and " Difficulty Coping . " CONCLUSIONS In this community sample of women of reproductive age , ovarian hormones play little , if any , role in day-to-day sleep quality . Our findings additionally highlight the different associations that self-reported and actigraphic sleep show with hormones and mood Rapid eye movement ( REM ) sleep and dreaming may be implicated in cross-night adaptation to emotionally negative events . To evaluate the impact of REM sleep deprivation ( REMD ) and the presence of dream emotions on a possible emotional adaptation ( EA ) function , 35 healthy subjects r and omly assigned to REMD ( n = 17 ; mean age 26.4 + /- 4.3 years ) and control ( n = 18 ; mean age 23.7 + /- 4.4 years ) groups underwent a partial REMD and control nights in the laboratory , respectively . In the evening preceding and morning following REMD , subjects rated neutral and negative pictures on scales of valence and arousal and EA scores were calculated . Subjects also rated dream emotions using the same scales and a 10-item emotions list . REMD was relatively successful in decreasing REM% on the experimental night , although a mean split procedure was applied to better differentiate subjects high and low in REM% . High and low groups differed - but in a direction contrary to expectations . Subjects high in REMD% showed greater adaptation to negative pictures on arousal ratings than did those low in REMD% ( P < 0.05 ) , even after statistically controlling sleep efficiency and awakening times . Subjects above the median on EA(valence ) had less intense overall dream negativity ( P < 0.005 ) and dream sadness ( P < 0.004 ) than subjects below the median . A correlation between the emotional intensities of the morning dream and the morning picture ratings supports a possible emotional carry-over effect . REM sleep may enhance morning reactivity to negative emotional stimuli . Further , REM sleep and dreaming may be implicated in different dimensions of cross-night adaptation to negative emotions The present study investigated the daily fluctuation of ruminative thinking and its individual differences by using the experience sampling method . Participants recorded their thought contents and negative affect eight times a day for a week at semir and om intervals . High-trait ruminators showed high levels of self-focus , unpleasantness , and uncontrollability in their thoughts over the sampling course . These variables were interacted to predict the levels of concurrent negative affect : Self-focus was strongly associated with increased levels of negative affect when the thought was highly unpleasant and uncontrollable . A composite measure of rumination , including self-focus , unpleasantness , and uncontrollability , exhibited diurnal variation , which was assimilated by a quadratic function of time of day . However , there were differences in the estimated parameters of diurnal trajectories between high and low levels of depression , which indicated that individuals with higher levels of depression are more likely to engage in rumination in the evening , not in the morning , than those with lower levels of depression . These findings suggest that rumination in the evening would play an important role in the exacerbation and maintenance of depression The current study investigated how night-to-night variations in sleep duration relate to affective well-being the next morning as well as how the relationship varies for people of different ages . Using an Experience Sampling approach , 397 participants aged 12 to 88 years reported their sleep duration and their momentary affect on 9 mornings , on average . Associations between sleep duration during the previous night and morning affect differed depending on the participants ' age . For adolescents , for example , affective well-being in the morning was worse the shorter participants had slept the previous night . For adults aged over 20 years , however , affective well-being was worse following nights with shorter or longer than average sleep duration . This effect was more pronounced the older the participants were . The findings demonstrate that the importance of sleep duration for daily affective well-being is better understood when considering the age of the sleeper . In adults , but not adolescents , not only sleeping less but also sleeping more than one 's average can be associated with lower affective well-being Background In spite of the apparently bidirectional relationship between daytime emotions and nocturnal sleep quality , relatively few studies have examined the day-to-day co-variation of daytime emotional states and sleep quality . Purpose In order to address this issue , we used a 7-day prospect i ve design allowing for the simultaneous investigation of the bidirectional link between sleep quality and affective states . MethodS eventy-five healthy university students completed a daily log during 7 days , reporting subjective sleep quality after their final morning awakenings . Eight hours later , they completed the Positive and Negative Affect Schedule measuring daytime affective states . Multilevel modeling was applied in order to examine level 1 ( day-to-day co-variation of sleep quality and affective states within individuals ) as well as level 2 ( averaged between-subjects ) effects . Results Individuals reporting poor sleep quality ( on average ) were characterized by lower positive and higher negative affect during daytime . Similarly , higher positive and lower negative affect ( on average ) predicted better subjective sleep quality during the assessment period . Moreover , daily ratings of positive and negative affect were related to the subjective sleep quality of the preceding night : On occasions in which participants reported poor ( below average ) sleep quality , they also reported lower positive and higher negative affect during the day . Nevertheless , daytime positive and negative affective states did not predict subsequent sleep quality ratings . Conclusion These findings suggest daily dynamic associations between subjective sleep quality and next day ’s emotional states in a group of healthy individuals , while in the inverse , the co-variation between daytime affective states and subsequent sleep quality was not supported |
12,353 | 21,563,141 | Women using COCs containing second-generation progestogens may be less likely to discontinue than those using COCs containing first-generation progestogens . | BACKGROUND The progestogen component of combined oral contraceptives ( COC ) has undergone changes since it was first recognised that it 's chemical structure could influence the spectrum of minor adverse and beneficial effects .
The major determinants of effectiveness are compliance and continuation which may be influenced by cycle control and common side effects .
The rationale of this review is to provide a systematic comparison of COCs containing the progestogens currently in use worldwide .
OBJECTIVES To compare currently available low-dose COCs containing ethinyl estradiol and different progestogens in terms of contraceptive effectiveness , cycle control , side effects and continuation rates . | Objective : To investigate the effect of a combiphasic oral contraceptive containing ethinylestradiol and desogestrel ( combiphasic EE/DSG ) on acne , compared with a preparation containing ethinylestradiol and cyproterone acetate ( EE35/CPA ) . Methods : An open , r and omized , group-comparative , multicenter study was carried out , with 172 women r and omized to treatment with either combiphasic EE/DSG ( 25 μg desogestrel and 40 μg ethinylestradiol for 7 days followed by 125 μg desogestrel and 30 μg ethinylestradiol for 15 days ) or EE35/CPA ( 2.0 mg cyproterone acetate and 35 μg ethinylestradiol for 21 days ) . Assessment s were performed at pretreatment and after cycles 3 and 6 . Results : The number of comedones , papules , pustules and nodules significantly decreased in both groups over the 6-month study . Compared with pretreatment (= 100 % ) , the relative numbers of comedones , papules , pustules and nodules at cycle 6 significantly decreased to 37 % , 38 % , 19 % and 12.5 % in the combiphasic EE/DSG group and to 24 % , 36 % , 17 % and 1 % in the EE35/CPA group , respectively . All reductions were statistically significant ( p ≤ 0.003 ) at both cycles 3 and 6 , except for nodules at cycle 6 with combiphasic EE/DSG , which probably result ed from differences between the treatment groups at baseline . There were no statistically significant differences between the two treatments . In both groups , the majority of women with severe acne shifted to a less severe acne category . Conclusions : Combiphasic EE/DSG progressively reduced the number and severity of acne lesions during the six cycles of treatment . The reduction in acne with the combiphasic oral contraceptive was comparable to a preparation containing the anti and rogen cyproterone acetate To evaluate and compare the contraceptive efficacy , bleeding pattern , side effects and other positive effects of a combined oral contraceptive ( COC ) containing drospirenone ( DRSP ) [ Yasmin ] with those of a COC containing desogestrel ( DSG ) in healthy Chinese women . This was a r and omized , open-label , controlled , multicentre study of 768 healthy Chinese women requiring contraception . The subjects were r and omized to ethinylestradiol ( EE ) 30 microg/DRSP 3 mg ( n = 573 ) or EE 30 microg/ DSG 150 microg ( n = 195 ) , at a ratio of 3 : 1 . Each individual was treated for 13 cycles . Further visits were required at cycle 4 , cycle 7 , cycle 10 and cycle 13 of treatment . Weight , height and body mass index were evaluated at each visit . The Menstrual Distress Question naire ( MDQ ) was administered at baseline , visit 3 ( cycle 7 ) and visit 5 ( after cycle 13 ) . Baseline characteristics were similar between the two groups ( p > 0.05 ) . The Pearl Index ( method failure ) for EE/DRSP was 0.208 per 100 women-years , which was lower than that for EE/DSG ( 0.601 per 100 women-years ) . There were no significant differences between the treatment groups with regard to bleeding patterns . According to the MDQ subscale , improvements in water retention and increases in appetite during the intermenstrual period and in water retention and general well-being during the menstrual period in the EE/DRSP group ( -0.297 , -0.057 , 0.033 and 0.150 , respectively ) were significantly improved compared with the EE/DSG group ( -0.108 , 0.023 , 0.231 and -0.023 , respectively ) [ all p < 0.05 ] . Other values that improved in both groups , particularly improvement in breast pain and tenderness and skin condition , were more evident in the EE/DRSP group ( 18.0 % , 89/494 ; 12.6 % , 62/494 ) than in the EE/DSG group ( 11.3 % , 19/168 ; 5.4 % , 9/168 ) . Mean weight increased in the EE/DSG group ( 0.57 kg ) while there was a significant decrease in mean weight ( -0.28 kg ) in the EE/DRSP group ( p < 0.01 ) . Both EE/DRSP and EE/DSG have good contraceptive efficacy and a comparable bleeding pattern . EE/DRSP had a more favourable effect on weight and premenstrual symptoms than EE/DSG This was an open-label multicenter study to compare the cycle control and effect on well-being of two oral contraceptives containing gestodene and one containing desogestrel . A total of 2419 healthy women ≤ 41 years of age were r and omized to receive oral contraceptives containing monophasic gestodene ( Minulet ® ; n = 806 , mean age 24.5 years ) , triphasic gestodene ( Tri-Minulet ® ; n = 808 , mean age 24.6 years ) or monophasic desogestrel ( Mercilon ® ; n = 805 , mean age 24.6 years ) . Subjects were to participate in the study for up to 13 treatment cycles . A modified Moos Menstrual Distress Question naire was used to evaluate menstrual symptoms and to assess overall well-being . A total of 698 women were withdrawn from the study , 154 due to adverse events . Cycle control with gestodene was superior to that with desogestrel at almost all time points , particularly for breakthrough bleeding and /or spotting , which occurred significantly less frequently with gestodene than with desogestrel at cycles 1–1 and 9–11 ( p < 0.05 ) . Generally , the proportion of subjects with breakthrough bleeding and /or spotting was almost twice as great with desogestrel as with gestodene . The duration of bleeding was not consistently different between the gestodene and desogestrel groups ; however , the intensity of bleeding was greater with gestodene at all time points ( p < 0.05 ) . The latent period before withdrawal bleeding was significantly longer for monophasic gestodene at cycles 1–5 and 8–10 ( p < 0.05 ) . Treatment significantly improved overall well-being at cycles 6 and 9 with triphasic gestodene and at cycle 13 with desogestrel ; however , no statistically significant differences among treatment groups in overall well-being scores or individual factors of well-being could be identified . All three treatments were well tolerated . The most common drug-related adverse events were headache ( 14.2 % ) , breast pain ( 6.2 % ) , nausea ( 4.1 % ) , metrorrhagia ( 5.9 % ) and abdominal pain ( 3.5 % ) . The incidence of adverse events in all treatment groups was similar , with the exception of metrorrhagia , which occurred in more patients in the desogestrel group than in the gestodene treatment groups ( p < 0.05 ) To study the question of whether one br and of oral contraceptives may be as acceptable as another for use of publicly-assisted family planning programs , a double blind study of two well-known br and s , Ovral and Norinyl , was undertaken in Costa Rica and Trinidad . The pills were r and omly assigned to 1,200 women . Common side effects - nausea , dizziness , vomiting , headaches - were associated with both Norinyl and Ovral . Differences in event rates for these conditions were much more marked by country than by the pill used . Ovral was associated with increases in skin problems , notably chloasma , in Cost Rica . A higher percentage of women using Norinyl reported intermenstrual bleeding and spotting in both countries . In Costa Rica continuation rates for Norinyl were adversely affected by this . With these exceptions there appear to be no important differences between the br and s that would affect their use in family planning programs BACKGROUND Oral contraceptive is the most commonly used method of fertility control . Yasmin is a combination of a novel progestogen with anti- and rogenic and anti-mineralcorticoid activities ( 3 mg Drospirenone ( DRSP ) and 30 microg ethinylestradiol ( EE ) ) . It has been shown in many clinical trials that Yasmin is an efficacious oral contraceptive , lacking undesired effects as with other oral contraceptives such as weight gain . However the effects of Yasmin on sexual desire and libido have not been intensively investigated so far OBJECTIVE Investigate the effects of Yasmin on sexual desire , libido and changes in the free and rogen index ( FAI ) compare to Meliane ( 75 microg gestodene + 20 microg ethinylestradiol ) . MATERIAL AND METHOD The authors ' report the results of a double blind r and omized controlled study using a translated version of the Female Sexual Function Index question naire ( FSFI ) for the assessment of the sexual function . The free and rogen index was calculated from measurements of testosterone and sexual hormone binding globulin . RESULT The result shows statistically significant improvements regarding sexual desire , arousal and overall satisfaction in the Yasmin group . Additionally , an increased frequency of orgasms in the Meliane group was reported . Statistically significant differences between the two treatments regarding changes in the FSFI score and changes in the free and rogen index have not been observed . CONCLUSION The novel oral contraceptive containing drospirenone ( Yasmin ) and the non-anti- and rogenic progestin containing oral contraceptive ( Meliane ) do not show unfavorable effects on sexual response and libido Side effects of combined oral contraceptives are the most common reason why women discontinue them . Over the past half century , an elaborate mythology about these ill effects has evolved , fueled by rumor , gossip and poor- quality research . In contrast , placebo-controlled r and omized trials document that nonspecific side effects are not significantly more common with combined oral contraceptives than with inert pills . These reported nonspecific side effects may reflect the nocebo phenomenon ( the inverse of a placebo ) : if women are told to expect noxious side effects , these complaints occur because of the power of suggestion . Alternatively , nonspecific complaints may simply reflect their background prevalence in the population . Because Level I evidence documents no important increase in nonspecific side effects with oral contraceptives , counseling about these side effects or including them in package labeling is unwarranted and probably unethical . When in doubt , clinicians should err on the side of optimism Three hundred thirteen women participated in an open , multicenter comparison of the incidence of intermenstrual bleeding ( breakthrough bleeding and or spotting ) associated with the use of three triphasic oral contraceptives . Triphasil ( n = 107 ) , containing levonorgestrel and ethinyl estradiol , and Ortho-Novum 7/7/7 ( n = 97 ) and Tri-Norinyl ( n = 109 ) , both of which contain norethindrone and ethinyl estradiol , were administered over four cycles for a total of 1141 cycles . The total incidence of intermenstrual bleeding was significantly lower with Triphasil ( 17.2 % ) than with Ortho-Novum 7/7/7 ( 39.5 % ) or Tri-Norinyl ( 49.0 % ) . The pattern remained the same when findings were analyzed cycle by cycle and for breakthrough bleeding and spotting separately . The incidence of other side effects was comparable for all regimens . Results of this study demonstrate superior cycle control with Triphasil compared with Ortho-Novum 7/7/7 and Tri-Norinyl during the first four cycles of use Norgestimate ( NGM ) , a derivative of 19‐nortestosterone with very specific affinity for the progesterone receptor , has been used in combination with ethinyl estradiol ( EE ) at low doses in both monophasic and triphasic oral contraceptives ( OCs ) . An open‐label comparative clinical trial was conducted with 4,234 healthy women using triphasic levonorgestrel (LNG)/EE and NGM/EE through a total of 22,312 menstrual cycles . Contraceptive efficacy was excellent with both preparations , with no statistically significant between‐regimen differences in pregnancy rates . The theoretical Pearl index was 0.12 for the NGM/EE triphasic , and 0.34 for the LNG/EE triphasic . Adverse experiences in both groups were typical of those that may occur among women taking low‐dose OC agents . The percentage of subjects discontinuing treatment because of use‐related adverse experiences was similar with the two preparations : 8.6 % for the NGM/EE triphasic and 6.8 % for the LNG/EE triphasic . In a separate mechanism of action study , specific endocrine parameters were investigated in 20 subjects using the NGM/EE triphasic for 4 cycles . Ovulation suppression was demonstrated in statistically significant decreases from pre‐treatment values in serum levels of luteinizing hormone , follicle‐stimulating hormone , progesterone , and estradiol . Significant on‐treatment increases in serum levels of sex hormone binding globulin evidence d minimal and rogenicity . All hormonal values returned to or toward normal in the post‐treatment cycle . The study results support those obtained in large noncomparative studies of the NGM/EE triphasic . This phased‐dose combination suppresses ovulation and is a very effective , minimally and rogenic contraceptive agent with a good safety profile This open-label r and omized study compared the effects of two combined oral contraceptives ( OCs ) containing 3 mg drospirenone (DRSP)/30 microg ethinyl estradiol ( EE ) with 150 microg levonorgestrel (LNG)/30 microg EE on the prevalence and changes from baseline of premenstrual symptoms after six cycles . The symptoms were measured using the Women 's Health Assessment Question naire . Subjects receiving DRSP/EE had fewer prevalence of premenstrual symptoms than those receiving LNG/EE after six cycles . A significantly lower score of negative affect category in the premenstrual phase was demonstrated in those receiving DRSP/EE more than LNG/EE . The DRSP/EE group showed a greater improvement of mean scores from baseline in the premenstrual phase compared with those who received LNG/EE on negative affect as seen in the items on anxiety , irritability , feeling sad or blue and weight gain in the category of water retention . In conclusion , OCs containing DRSP have beneficial effects in reducing the prevalence of premenstrual symptoms especially the symptoms of negative affect and weight gain , particularly when compared to LNG/EE . Hence , it should be recommended for women who are susceptible to these adverse symptoms BACKGROUND This Phase 3 , r and omized , open-label , multicenter study conducted at 44 sites in Europe evaluated the safety and efficacy of a continuous , daily regimen of levonorgestrel ( LNG ) 90 mcg/ethinyl estradiol ( EE ) 20 mcg compared with a 21-day , cyclic LNG 100 mcg/EE 20 mcg regimen . STUDY DESIGN Three hundred twenty-three healthy women were r and omized to continuous LNG 90 mcg/EE 20 mcg and 318 subjects to cyclic LNG 100 mcg/EE 20 mcg for 1 year ( 13 pill packs ) . Pearl index , adverse event ( AE ) incidence and bleeding profiles were assessed . RESULTS No pregnancies occurred with the continuous oral contraceptive ( OC ) ( Pearl index=0.00 ) . As the study progressed , the percentage of women who achieved amenorrhea during each 28-day pill pack increased : 40 % at pill pack 7 , 53 % at pill pack 13 . The percentage of women with no bleeding [ with or without spotting ( defined as not requiring sanitary protection ) ] was 50 % , 69 % and 79 % at pill packs 3 , 7 and 13 , respectively . The incidence of AEs was similar to that of the cyclic OC ( except for metrorrhagia and vaginal bleeding in the first 6 months ) . CONCLUSIONS Continuous LNG 90 mcg/EE 20 mcg was shown to be a safe and effective OC in this direct comparison to a cyclic OC . Suppression of menses and the potential for no bleeding requiring sanitary protection may be provided by this continuous , low-dose OC BACKGROUND A prospect i ve r and omized trial was conducted to compare efficacy of a drospirenone-containing combined oral contraceptives ( COC ) with desogestrel-containing COC in women with polycystic ovary-syndrome ( PCOS ) not desirous of child-bearing . STUDY DESIGN Sixty women were r and omized into study group [ ethinylestradiol ( EE ) 30 mcg+drospirenone 3 mg ] and control group ( EE 30 mcg+desogestrel 150 mcg ) , treated for 6 months and followed up at 1 month , 3 months , 6 months , during treatment and 3 and 6 months post-treatment . Acne and hirsutism scoring , bodyweight , body mass index ( BMI ) , blood pressure ( BP ) , ultrasound parameters , lipid profile , glycemic profile and hormonal profile were compared . RESULTS Cycles were regular in both groups during treatment . Effect of regular cycles persisted in 44.83 % ( 13/30 ) vs. 17.24 % ( 5/30 ) in study vs. control group at 6 months post-treatment with 33.3 % decreased hirsutism score in the study group ( versus no change in control group ) even at 6 months after stopping treatment . With treatment , BMI fell by 0.52 kg/m(2 ) in the study group ; systolic and diastolic BP fell in the study group while it rose in the control group . Low-density lipoprotein significantly decreased and high-density lipoprotein was elevated in the study group ( p<.05 ) . The study group showed a significant fall in fasting/postpr and ial blood sugar and insulin and total testosterone against a rise in the control group . CONCLUSION In women with PCOS , a drospirenone containing COC has better outcome in terms of persistent regular cycles , anti and rogenic effect , fall in BMI and BP , better lipid profile , favorable glycemic and hormonal profile than desogestrel-containing COC The efficacy and acceptability of two third generation oral contraceptives in Thai women were evaluated in a prospect i ve , open , group-comparative , r and omized , multicenter trial of women asking for contraception . In six Family Planning Centers and Outpatient Gynaecological Clinics in urban areas in Thail and , 783 healthy women who were at risk for pregnancy and did not have contraindications to oral contraceptive use were r and omly allocated to one of the two study groups . An oral contraceptive containing 30 mcg ethinylestradiol and 150 mcg desogestrel was given to 394 women and an oral contraceptive with the same amount of ethinylestradiol and 75 mcg gestodene to 389 women during 6 cycles . Criteria of cycle control , side effects and the presence and severity of acne vulgaris were assessed and blood pressure and body weight measured at pretreatment and after cycles 1 , 3 and 6 . Furthermore , the efficacy was evaluated after the last cycle . No pregnancies occurred with either of the contraceptives . The incidences of irregular bleeding and minor side effects in both groups were very low and decreased after an initial increase in the first cycle . Acne improved in both groups . Blood pressure and body weight remained unchanged . The two oral contraceptives were found to be effective and acceptable in Thai women . Compared to Caucasian women , the incidences of irregular bleeding and side effects were apparently lower in these Asian women . Furthermore , the effects of both oral contraceptives were comparable Two monophasic oral contraceptives containing gestodene ( GTD , 75 micrograms ) and ethinylestradiol ( EE , 30 micrograms ) or norgestimate ( NGS , 250 micrograms ) and EE ( 35 micrograms ) were compared during the first six cycles of use . The subjects were r and omly assigned to receive either type : 97 received GTD/EE and 92 NGS/EE . Six women in the GTD/EE group and nine in the NGS/EE group withdrew from the study ; three ( 3 % ) and two ( 2 % ) , respectively , withdrew because of adverse reactions . A total of 562 cycles for GTD/EE and 523 for NGS/EE were available . No woman became pregnant during the study . Overall , 94.4 % of cycles in the GTD/EE group and 92.8 % in the NGS/EE group were normal . A similar incidence of breakthrough bleeding ( 0.2 % of cycles for GTD and 1.6 % for NGS ) and spotting ( 5.4 % vs. 5.6 % ) was observed . Amenorrhea was never reported . Duration of withdrawal bleeding tended to be slightly longer in the NGS/EE group , significantly so for cycles 2 ( 0.5 days , p = 0.016 ) , 4 ( 0.5 days , p = 0.031 ) and 5 ( 0.4 days , p = 0.045 ) . Cycle 2 was significantly longer in the GTD/EE group ( 0.3 days , p = 0.027 ) . Side-effects were reported by 12 ( 12 % ) women in the GTD/EE group and 13 ( 14 % ) in the NGS/EE group . The most common side-effects were headache ( five cases ( 5 % ) in the GTD/EE group and two ( 2 % ) in the NGS/EE group ) and breast pain ( three ( 3 % ) and eight ( 9 % ) cases respectively ) . There were no statistically significant differences between the two groups with respect to change in body weight or changes in blood pressure and in laboratory data . ( ABSTRACT TRUNCATED AT 250 WORDS This trial was design ed to determine the differences in effectiveness , clinical acceptability , and one-year discontinuation rates of two low-dose oral contraceptives : Lo-Estrin ( norethindrone acetate 1.5 mg plus ethinyl estradiol 0.030 mg ) and Lo-Femenal ( norgestrel 0.30 mg plus ethinyl estradiol 0.030 mg ) in 148 Mexican women . In addition , the effects of both oral contraceptive preparations on blood lipids were prospect ively evaluated in a subgroup of 41 women . The results indicated that there were no differences in pregnancy rates , discontinuation or clinical acceptability between the two groups . The lipid changes observed were minimal for the Lo-Femenal subgroup and somewhat greater for the Lo-Estrin group , mainly an increase in serum triglycerides . These changes were interpreted as estrogen induced effects of norethindrone-containing oral contraceptives . Overall , the data indicate that both Lo-Femenal and Lo-Estrin are effective and safe combined oral contraceptives . RésuméCette étude , menée auprès de 148 Mexicaines avait pour but de déterminer les différences entre deux contraceptifs oraux faiblement dosés : Lo-Estrin ( 1,5 mg d'acétate de noréthindrone plus 0,030 mg d'éthynil oestradiol ) et Lo-Femenal ( 0,30 mg de norgestrel plus 0,030 mg d'éthynil oestradiol ) , du point de vue de l'efficacité , de la tolérance clinique et du taux d'ab and on au cours de la première année . Ont et outre été évalués , dans une étude prospect i ve chez un sous-groupe de 41 femmes , les effects éventuels de ces deux contraceptifs oraux sur les lipides sanguins . Les résultats n'indiquent pas de différence entre les deux groupes quant au nombre de grossesses , au taux d'ab and on ou à la tolérance . Les modifications lipidiques étaient minimes pour le sous-groupe L-Femenal et légèrement plus importantes pour le groups Lo-Estrin , essentiellement sous la forme d'une augmentation des triglycérides sériques . On a attribué ces modifications aux effects oestrogènes des contraceptifs oraux contenant du noréthindrone . Dans l'ensemble , les résultats ont indiqué que ces deux contraceptifs combinés sont efficaces et sans danger . ResumenEste estudio , realizado entre 148 mexicanas , tuvo por objeto determinar las diferencias entre dos anticonceptivos orales de dosis baja : Lo-Estrin ( 1,5 mg de acetato de noretindrona más 0,030 mg de etinil estradiol ) y Lo-Femenal ( 0,30 mg de norgestrel más 0,030 mg de etinil estradiol ) , desde el punto de vista de la eficacia , tolerancia clínica y proporción de ab and ono en el primer año . Además , se evaluaron , en un estudio prospect ivo de un subgrupo de 41 mujeres , los efectos de estos dos anticonceptivos sobre los lípidos sanguíneos . Los result ados indicaron que no había diferencias entre los dos grupos en cuanto al número de embarazos , proporción de ab and ono o tolerancia . Las modificaciones de los lípidos eran mínimas en el subgrupo Lo-Femenal y ligeramente más importantes en el grupo Lo-Estrin , principalmente bajo la forma de un incremento de los triglicéridos séricos . Estas modificaciones se han atribuido a los efectos de los estrógenos de los anticonceptivos orales que contienen noretindrona . En general , los result ados indicaron que estos dos anticonceptivos combinados son eficaces y carecen de peligro BACKGROUND This retrospective analysis evaluated the association of age and weight with cycle control in women using either of two formulations of low-estrogen-dose oral contraceptives . STUDY DESIGN Data for this secondary analysis were derived from a r and omized multicenter trial assessing the efficacy and safety of norgestimate ( NGM ) 180/215/250 mcg/ethinyl estradiol ( EE ) 25 mcg ( n=1506 ) and norethindrone acetate 1 mg/EE 20 mcg ( n=1057 ) . In this retrospective analysis , the incidence of breakthrough bleeding/spotting ( BTB/S ) was evaluated in women stratified by age ( 18 - 24 , 25 - 34 and > 34 years ) and weight ( < or=123 , 124 - 155 and > 155 lb ) . RESULTS A lower percentage of women experienced BTB/S with NGM/EE during most cycles , regardless of age or weight , compared with norethindrone acetate/EE . At Cycle 6 , the incidences of BTB/S for NGM/EE versus norethindrone acetate/EE were as follows : 18 - 24 years , 10.9 % versus 29.7 % ( p<.0001 ) ; 25 - 34 years , 10.9 % versus 18.6 % ( p<.001 ) ; > 34 years , 8.1 % versus 19.1 % ( p<.005 ) ; < or=123 lb , 11.0 % versus 25.4 % ( p<.0001 ) ; 124 - 155 lb , 10.0 % versus 22.5 % ( p<.0001 ) ; and > 155 lb , 10.0 % versus 18.3 % ( p<.01 ) . CONCLUSION NGM/EE provided better cycle control as defined by BTB/S compared with norethindrone acetate/EE , regardless of subject age or weight for six cycles In a Swedish multicenter study , a total number of 835 women completed a total of 6472 treatment cycles . Half of them were allotted at r and om to use the monophasic oral contraceptive Neovletta , also known as Microgynon 30 ( 30 micrograms ethinyl oestradiol + 150 micrograms levonorgestrel in each tablet ) . The second half was allotted to Trionetta , also known as Triquilar , Trigynon and Logynon ( 6 tablets with 30 micrograms ethinyl oestradiol + 50 micrograms levonorgestrel , 5 tablets with 40 micrograms ethinyl oestradiol + 75 micrograms levonorgestrel and 10 tablets with 30 micrograms ethinyl oestradiol + 125 micrograms levonorgestrel ) . The latter version was also present in a 28-day version containing in addition 7 " placebo " tablets to be used in the otherwise tablet-free interval . The contraceptive reliability was excellent although one pregnancy occurred in the three-phase version . It could be attributed to patient failure . In all aspects of bleeding control , the three-phasic pill proved to be superior to the reference monophasic preparation . The extreme low incidence of missed withdrawal bleeding and stability already during the first months of use are noteworthy features . For both preparations , continuation rate was at six months of use about 85 % and at 12 months it was a similar figure . The most common reason for withdrawal was bleeding , about 5 % each for both preparation . No serious side-effects were reported . The study clearly indicates that the three-phasic version is a major improvement in spite of a considerably decreased total dose of the gestagen The efficacy , cycle-control and tolerance of Microgynon-30 , a widely prescribed levonorgestrel containing oral contraceptive , and Femodene , a new oral-contraceptive containing gestodene , were compared in a r and omised , double-blind study involving 456 healthy women over a 6 month period . 229 women were allocated to receive Femodene and 227 received Microgynon-30 . No differences between the groups in terms of obstetric and gynaecological history , previous contraceptive history , smoking habits , blood-pressure or body weight at admission were observed . No pregnancies were reported in either group , despite tablet-taking errors recorded in 6.3 % of the Femodene group and 7.6 % of the Microgynon-30 group . Both oral contraceptives were compared in terms of cycle length , intensity of the withdrawal bleed and side effects . Cycle-control was similar in the two groups . However , significantly fewer subjects reported breakthrough bleeding ( with or without spotting ) in the Femodene group ( 18 % of patients ) compared with the Microgynon-30 group ( 26 % of patients ) . The incidence of absent withdrawal bleeds was 1 % or less in both groups and no significant effects on body weight or blood pressure were observed OBJECTIVE To compare the cycle control and tolerability of two oral contraceptives containing 20 micrograms ethinylestradiol and either 150 micrograms desogestrel or 75 micrograms gestodene . METHODS A r and omized , multicenter study was conducted in which 1016 healthy adult women received the desogestrel ( n = 509 ) or the gestodene ( n = 507 ) preparation for six treatment cycles . RESULTS No significant differences in bleeding patterns were detected between the two treatments . The incidence and duration of irregular bleeding decreased markedly , and to a similar extent , during each treatment . The occurrence of irregular bleeding per cycle decreased from 24.6 to 9.4 % in the desogestrel group and from 19.7 to 8.6 % in the gestodene group . Its duration fell from 1.1 to 0.2 days and from 0.9 to 0.3 days , respectively . There was a consistently low incidence of amenorrhea ( 1.0 - 2.8 % ) . There were no significant differences between treatments for the incidence , intensity or emergence of dysmenorrhea . During both treatments , the incidence of premenstrual syndrome and complaints such as breast tenderness , nausea and headache dropped markedly . CONCLUSION Ultra low-dose oral contraceptives containing desogestrel or gestodene offer equivalent , good cycle control and improvements in dysmenorrhea and premenstrual syndrome and have similar , excellent tolerability profiles OBJECTIVE The primary objective of this study was to compare the safety , contraceptive efficacy , and menstrual cycle patterns in women using triphasic oral contraceptive pills , namely CTR-05 , containing 50/100/150 micrograms desogestrel and 35/30/30 micrograms ethinylestradiol , and Orthonovum777 containing 500/750/1000 micrograms norethindrone and 35/35/35 micrograms ethinylestradiol . METHOD Forty-six female volunteers , satisfying the selection criteria , were evaluated for six cycles , in an open-label , r and omized study . Volunteers using CTR-05 were studied for 13 additional cycles for efficacy and safety . RESULTS No serious adverse effects were observed in either group . The incidences of other drug-related adverse effects , such as headache and nausea , were transient in both groups . CTR-05 did not lower levels of high density lipoprotein ( HDL ) cholesterol . This may be attributed to the lower and rogenicity of its progestin component , desogestrel . No pregnancies were reported in either group . Clinical and laboratory parameters remained within normal limits in both groups . In the CTR-05 group , the lower dose of ethinylestradiol did not affect the safety , efficacy and acceptability of the product . CONCLUSION Desogestrel , with little estrogenic activity and only minimal and rogenic activity , leads to lipoprotein changes , result ing in a favorable cardiovascular profile , as well as minimal and rogen-related effects , such as hirsutism and acne BACKGROUND This analysis investigated the association of oral contraceptive efficacy with body weight and body mass index ( BMI ) for hypothesis-generating purpose s. STUDY DESIGN Data were from a r and omized , parallel-group trial of 180/215/250 mcg of norgestimate (NGM)/25 mcg of ethinyl estradiol ( EE ) ( given to 1671 women ) and 1 mg of norethindrone acetate (NETA)/20 mcg of EE ( given to 1139 women ) . Pregnancies were evaluated across BMI deciles and by BMI and body weight dichotomies . A Pearl index was calculated for each treatment group . The relative risk ( RR ) of pregnancy was calculated with a Cox proportional hazards model . RESULTS The Pearl index for women who received NGM/EE was 2.36 [ 95 % confidence interval (CI)=1.33 - 3.40 ] ; for those who received NETA/EE , the Pearl index was 3.29 ( 95 % CI=1.81 - 4.77 ) . Consistent , weak positive associations between weight and pregnancy risk were found . Overall , for women with a BMI > or=25 kg/m(2 ) ( compared with women with a BMI < 25 kg/m(2 ) ) , the RR of pregnancy was 1.84 ( 95 % CI=0.98 - 3.45 ) ; that for women who received NGM/EE was 1.39 ( 95 % CI=0.57 - 3.40 ) , whereas that for women who received NETA/EE was 2.49 ( 95 % CI=1.01 - 6.13 ) . For women with a body weight > or=70 kg ( compared with women with a body weight < 70 kg ) , the RR was 1.25 ( 95 % CI=0.63 - 2.46 ) ; that for women who received NGM/EE was 1.41 ( 95 % CI=0.56 - 3.54 ) , whereas that for women who received NETA/EE was 1.12 ( 95 % CI=0.40 - 3.12 ) . CONCLUSION Women in the higher body weight or BMI category showed a small increase in the risk of pregnancy with these oral contraceptives , but this increase was not statistically significant overall or for either formulation studied OBJECTIVE The objective of this study was to compare cycle control , tolerability and sexual well-being with the use of three hormonal contraceptives . METHODS In this prospect i ve r and omized study , the effects of two combined oral contraceptives [ 20 microg of ethinylestradiol (EE)/100 microg of levonorgestrel and 15 microg of EE/60 microg of gestodene ] were compared with those of the vaginal ring ( 15 microg of EE/120 microg of etonogestrel ) . One-year data from 280 women were obtained . We investigated the pattern of menstrual cycle and the incidence of weight gain , nausea , headache , breast tenderness , irritability , depression and vaginal dryness . Moreover , desire and sexual satisfaction were evaluated . Finally , the cumulative rate of discontinuation in the three groups was estimated . CONCLUSION The analysis of adverse events revealed two crucial points for acceptability , compliance and continuation : poor cycle control and disturbance of sexual intercourse due to vaginal dryness and loss of desire BACKGROUND The study was conducted to compare cycle control , bleeding pattern and efficacy of two low-dose combined oral contraceptives . STUDY DESIGN Four hundred fifty-three women were r and omized to receive a 24/4 regimen of drospirenone 3 mg/ethinyl estradiol 20 mcg ( drsp 3 mg/EE 20 mcg ; n=230 ) or a 21/7 regimen of desogestrel 150 mcg/EE 20 mcg ( DSG 150 mcg/EE 20 mcg ; n=223 ) , and recorded bleeding daily over 7 treatment cycles . RESULTS The duration [ mean 4.7 ( SD 1.5)-5.2 ( SD 2.2 ) days in the drsp 3 mg/EE 20 mcg 24/4 group and 5.1 ( SD 1.5)-5.4 ( SD 2.1 ) days in the DSG 150 mcg/ EE 20 mcg group ] and maximum intensity ( " normal bleeding " for > 50 % of all subjects ) of scheduled bleeding in Cycles 1 - 6 was comparable between treatment groups . The incidence of unscheduled bleeding during Cycles 2 - 6 was also similar between the two groups ( drsp 3 mg/EE 20 mcg , 8.8 - 17.3 % ; DSG 150 mcg/ EE 20 mcg , 9.4 - 16.3 % ) . CONCLUSION Drsp 3 mg/EE 20 mcg 24/4 achieved an acceptable bleeding profile with reliable cycle control , comparable with an established formulation OBJECTIVE : To assess ovarian suppression during oral contraceptive pill ( OCP ) use among normal-weight and obese women using two OCP doses . METHODS : This was a prospect i ve , double-blind , r and omized trial of two 21-day monophasic OCP formulations ( 20-microgram ethinyl estradiol [E2],/100-microgram levonorgestrel compared with 30-microgram ethinyl E2/150-microgram levonorgestrel ) among normal-weight ( body mass index 19.0–24.9 ) and obese ( body mass index 30.0–39.9 ) women with regular menses and normal ovarian ultrasonography . Participants underwent transvaginal ultrasonography and phlebotomy twice weekly for 4 weeks during the third or fourth OCP cycle . We assessed OCP compliance using serum levonorgestrel levels . Outcomes included follicular development , endogenous E2 levels , ovulation , and self-reported bleeding patterns . RESULTS : Two hundred twenty-six women enrolled . One hundred eighty-one participants completed the study ; we retained 150 consistent OCP users in the main analysis ( 96 normal weight , 54 obese ) . Consistent users of either OCP dose had substantial suppression of follicular development ; obesity and follicular development were not related . Among the consistent OCP users , 2.7 % ovulated during the study cycle ( 3 of 96 normal-weight and 1 of 54 obese participants ) . Two ovulations occurred with each OCP formulation . Inconsistent OCP use or nonuse during the study cycle was associated with more ovulation ( P<.001 ) . Normal-weight and obese participants had similar follicular development , endogenous estradiol levels , Hoogl and scores , and bleeding patterns . CONCLUSION : Normal-weight and obese participants who were consistent OCP users experienced substantial and comparable ovarian suppression during OCP use . Higher OCP failure rates among obese women reported elsewhere are thus unlikely to be attributable to physiological differences in OCP effect . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov ; NCT00827632 . LEVEL OF EVIDENCE : Objective The aim of this study is to compare the effect of ethinyl estradiol 0.03 mg/gestodene 0.075 mg ( EE/GSD ) with ethinylestradiol 0.03 mg/drospirenone 3 mg ( EE/DRSP ) administered according to conventional 21/7 regimen on body mass index ( BMI ) , blood pressure ( BP ) , lipid metabolism and hemostatic parameters . Method In this study , 160 healthy women were r and omized to EE/GSD mg or EE/DRSP for 12 months . Mean differences in BMI , high density lipoprotein-cholesterol ( HDL-C ) and low density lipoprotein-cholesterol ( LDL-C ) , total cholesterol ( TC ) levels and BP compared to baseline were assessed . Results One hundred and forty-five ( 89 % ) of the women completed all 12 treatment cycles . The subjects r and omly assigned into two treatment groups . Group EE/GSD ( n = 71 ) and group EE/DRSP ( n = 72 ) . In group B , BMI values were significantly lower than baseline at the sixth cycle . DRSP/EE had more favorable effects on BP than GSD/EE with the mean systolic and diastolic BPs remaining lower in the DRSP/EE group . The difference between the two preparations was not statistically significant at the end of the study . TC levels remained similar in both groups throughout the study period . In both groups LDL-C levels decreased , triglyceride and HDL-C levels significantly increased from baseline levels . These changes result in increasing HDL-C/LDL-C ratio , demonstrating anti-atherogenic effect . Menstrual cycle patterns and the incidence of adverse events were similar between groups . The duration of withdrawal bleeding decreased during the study for both groups and was similar . Conclusion The EE/DRSP regimen provides good cycle control with reliable contraceptive efficacy and low incidence of adverse events . Compared with the EE/GSD preparation , the EE/DRSP preparation demonstrated a more favorable effect on BMI and BP with the mean BMI and mean BP remaining lower than baseline mean . The new formulation may be especially beneficial for women susceptible to body weight gain and rise in BP Oral contraceptives have the highest theoretic efficacy of all reversible forms of contraception , yet in practice they have an actual failure rate equivalent to that of some barrier methods . The efficacy of oral contraceptives depends primarily on patient compliance . So-called " nuisance " side effects , such as intermenstrual bleeding ( breakthrough bleeding or spotting ) , play a major role in their discontinuation . The Triphasic R and omized Clinical Trial compared the incidence of these side effects in three groups of subjects taking NET ( A ) ( Ortho-Novum 7/7/7 ) , LNG ( Tri-Levlen ) , or NET ( B ) ( Tri-Norinyl ) . Subjects taking NET ( A ) had the highest incidence of intermenstrual bleeding ( 63 % ) followed by NET ( B ) ( 44 % ) and LNG ( 33 % ) . Only the difference between NET ( A ) and LNG attained statistical significance ( p less than 0.030 ) . Control subjects had no breakthrough bleeding and a 4 % incidence of spotting . Further research is warranted to establish the cause of the disparity in the incidence of intermenstrual bleeding among patient groups assigned to the three oral triphasic contraceptives The contraceptive efficacy , cycle control , safety , and subject acceptance of the new contraceptive ( OC ) preparations containing gestodene ( GTD ) plus ethinyl estradiol ( EE ) are being compared with the combination containing desogestrel ( DSG ) plus EE in a r and omized , open-label outpatient study . Interim data from six cycles of this ongoing study were obtained for 378 women receiving 75 micrograms GTD + 30 micrograms EE per day and 384 women receiving 150 micrograms DSG + 30 micrograms EE per day . Each group received OCs for 21 days per cycle . There were no pregnancies in subjects receiving either OC during 1,658 cycles of GTD + EE or 1,707 cycles of DSG + EE use . The continuation rates were similar in the two groups , and no major differences in type or incidence of side effects were observed . There were also no clinical ly significant changes in blood pressure or body weight in either group . Slightly better cycle control was observed for subjects taking GTD + EE , since the incidence of spotting and breakthrough bleeding was slightly greater for women taking DSG + EE . The incidence of amenorrhea ( missed periods ) tended to be lower for the subjects taking the GTD-containing preparation : 7 ( 0.5 % ) cycles compared with 12 ( 0.9 % ) DSG + EE cycles . The GTD + EE-treated subjects also had a lighter menstrual flow . Fewer subjects taking GTD + EE withdrew because of side effects typically associated with OCs . The data from this study indicate that the new combination of GTD + EE provides safe and effective oral contraception , with good tolerance and cycle control The contraceptive efficacy , cycle control , and safety of a new low-dose , triphasic desogestrel/ethinyl estradiol oral contraceptive ( CTR 77 , Cyclessa(TM ) ) was compared to that of a marketed , triphasic norethindrone/ethinyl estradiol oral contraceptive ( Ortho-Novum(R ) 7/7/7 ) . Two identical multicenter , open-label , r and omized , parallel group , comparative Phase III 6-cycle trials were design ed to each enroll 4200 healthy women . The combined comparative data for Cyclessa versus Ortho-Novum 7/7/7 for both studies are reported here . Cyclessa and Ortho-Novum 7/7/7 had comparable contraceptive efficacy . Despite a lower ethinyl estradiol dose ( 25 microg/day vs. 35 microg/day ) , the Cyclessa group had significantly improved cycle control in comparison to the Ortho-Novum 7/7/7 group for presence of a withdrawal bleed ( p = 0.001 ) , lack of early withdrawal bleed ( p = 0.01 ) , and breakthrough bleeding/spotting ( p = 0.001 ) . For each of the months of the study , the incidence of breakthrough bleeding/spotting was lower in the Cyclessa group than the Ortho-Novum 7/7/7 group ( breakthrough bleeding , p = 0.006 ; breakthrough spotting , p = 0.001 ) . The incidence of other adverse events was similar among treatment groups , an observation that supports the safety of both formulations . There was significantly less weight gain ( p = 0.0002 ) and less increase in the body mass index ( BMI ) ( p = 0.0002 ) in the Cyclessa group . The contraceptive efficacy and safety of Cyclessa is comparable to Ortho-Novum 7/7/7 . Cyclessa provides significantly improved cycle control with no weight gain OBJECTIVE To assess the contraceptive efficacy , cycle control and acceptability of two monophasic oral contraceptives containing either 30 micrograms ethinylestradiol plus 150 micrograms desogestrel or 30 micrograms ethinylestradiol plus 75 micrograms gestodene . METHODS In a r and omized , open-label , six-cycle , group-comparative , multicenter study performed in Brazil , pregnancies , cycle-control parameters , incidence of side-effects and the presence and severity of acne vulgaris were assessed , and blood pressure and body weight were measured at pretreatment and after one , three and six cycles of oral contraceptive use . RESULTS Of the 595 women enrolled , 274 ( 86.7 % ) in the desogestrel/ethinylestradiol group and 227 ( 81.4 % ) in the gestodene/ethinylestradiol group completed the six cycles , providing data for 1753 and 1487 treatment cycles , respectively . Two pregnancies occurred , one of which ( in the desogestrel/ethinylestradiol group ) was attributed to user failure , whilst the other ( in the gestodene/ethinylestradiol group ) was thought to result from method failure . Cycle control was observed to be excellent ; the incidences of irregular bleeding and minor side-effects were low in both groups and decreased after an initial increase in the first cycle . Pre-existing acne improved in both groups , whereas blood pressure and body weight remained essentially unchanged . CONCLUSIONS Both desogestrel/ethinylestradiol and gestodene/ethinylestradiol provide effective oral contraception with comparable cycle control and acceptability OBJECTIVE Oral contraceptive pills ( OCPs ) are one of the most effective reversible and accessible contraceptives , and patient acceptance for their use depends partly on the unfavorable adverse effects . The present study compared the two kinds of OCPs ( monophasic ; levonorgestrel (LNG)-ethinyl estradiol ( EE ) 150/30 versus triphasic ; LNG-EE 50 - 75 - 125/30 - 40 - 30 ) for adverse effects and patient satisfaction . STUDY DESIGN A r and omized clinical trial was performed on 314 women who used OCPs for the first time , as their contraception , for 6 months . Overall , 1884 cycles were studied . In the monophasic group ( n=159 who finally finished the study ) , monophasic pills LNG-EE 150/30mcg , and in the triphasic group ( n=155 who finally finished the study ) , triphasic pills LNG-EE 50 - 75 - 125/30 - 40 - 30 mcg were used . Statistical analysis was performed using SPSS 10 : Chi square test , Fisher exact test and Student 's t-test were used . RESULTS There were no significant differences between the two groups for common side effects , including nausea , headache , nervousness , facial hyperpigmentation ( chloasma ) , and body weight ( increase or decrease ) but breakthrough bleeding and spotting ( BTB/S ) were less in the triphasic group , occurring in 30 cycles ( 18.86 % ) versus 10 cycles ( 6.45 % ) , P=0.009*. Patient satisfaction for the two OCPs was similar and high . The rates of side effects were low . CONCLUSION It seems that the monophasic and triphasic pills are similar according to patient satisfaction and side effects ; therefore there is no benefit of one over the other except for BTB/S , for which triphasic is superior OBJECTIVE To assess the contraceptive reliability , cycle control and tolerance of a new monophasic oral contraceptive ( Yasmin ) containing 30 microg ethinylestradiol and 3 mg drospirenone and compare it with a preparation containing an equal dose of ethinylestradiol combined with 150 microg desogestrel ( Marvelon ) . METHODS A multicenter , open-label , r and omized study was carried out in 26 European centers . Contraceptive efficacy , cycle control and tolerance ( including body weight , blood pressure and heart rate ) were assessed over 26 cycles , plus a 3-month follow-up period . RESULTS Of 900 women who were r and omized , 887 started treatment and 627 completed the 26 cycles plus follow-up ( 310 in the ethinylestradiol/drospirenone group and 317 in the ethinylestradiol/desogestrel group ) . Both study preparations were found to be effective with regard to contraceptive reliability and cycle control was good . There were six pregnancies ( three in each group ) , but none were considered to have been the result of method failures . The subjective and objective tolerances were good in both groups . A statistically significant difference was found in body weight changes between the two groups . While there was an increase in mean body weight in the ethinylestradiol/desogestrel group from cycle 5 onward , the mean body weight per cycle in the ethinylestradiol/drospirenone group was slightly below the baseline value throughout the study . The incidence ofpremenstrual symptoms was higher in the ethinylestradiol/drospirenone group than in the ethinylestradiol/desogestrel group during the 6 months prior to the study , but lower during treatment . The rates ofdysmenorrhea were identical under both treatments but the symptoms were more often mild and less often severe in the ethinylestradiol/drospirenone group . CONCLUSION The combination of 30 microg ethinylestradiol combined with 3 mg drospirenone provides effective oral contraception and good cycle control , and is well tolerated . Ethinylestradiol/drospirenone had a more favorable effect on body weight than ethinylestradiol/desogestrel , with the mean body weight remaining lower than baseline for the majority of the women OBJECTIVE : To estimate real-life effectiveness of oral contraceptive pills by progestogen , length of pill-free interval , and body mass index while focusing on the effect of progestogens with a long half-life and on 24-day oral contraceptive pills regimens . METHODS : Outcome data from 52,218 U.S. participants in the International Active Surveillance of Women Taking Oral Contraceptives — a large , prospect i ve , controlled , noninterventional , long-term cohort study with active surveillance of the study participants —were used to analyze contraceptive failure in association with oral contraceptive pills use . Low loss to follow-up is ensured by a comprehensive follow-up procedure . Contraceptive failure rates are described by Pearl Index and life-table analysis . Inferential statistics for contraceptive failure are based on Cox regression models . RESULTS : Analyses are based on 1,634 unintended pregnancies during 73,269 woman-years of oral contraceptive pills exposure . Life-table estimates of contraceptive failure for a 24-day regimen of drospirenone and ethinyl estradiol and 21-day regimens of other progestogens were 2.1 % and 3.5 % after the first study year , and 4.7 % and 6.7 % after the third year . The adjusted hazard ratio was 0.7 ( 95 % confidence interval 0.6–0.8 ) . Direct comparisons of the 24-day and 21-day regimens of drospirenone and norethisterone , respectively , showed also lower contraceptive failure rates for 24-day regimens . Contraceptive failure rates adjusted for age , parity and educational level showed a slight increase with higher body mass index . CONCLUSION : The 24-day oral contraceptive regimens containing a progestogen with a long half-life show higher contraceptive effectiveness under routine medical conditions compared with conventional 21-day regimens . Obesity seems to be associated with a slight reduction of contraceptive effectiveness . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00335257 . LEVEL OF EVIDENCE : A study of three combined oral contraceptives , Norinyl 1/35 , Lo-Ovral and Noriday 1/50 , was conducted at the University of Ibadan Teaching Hospital , Ibadan , Nigeria , to determine if there were differences in continuation rates and reasons for discontinuation . This report includes analysis of 150 women , all of whom were interval patients , r and omly allocated to one of the above oral contraceptives between May 1984 and February 1985 . Follow-up visits were scheduled at 1 , 4 and 8 months after admission . Significantly more women in the Norinyl 1/35 group ( P less than 0.05 ) reported intermenstrual bleeding , as well as an increase in the occurrence of intermenstrual bleeding compared to women in the Lo-Ovral group . There were no other differences between the groups for side-effects . The continuation rates at 8 months were 90.8 % for the Norinyl 1/35 group , 94.4 % for the Lo-Ovral group and 87.1 % for the Noriday 1/50 group . The corresponding rates for those lost to follow-up were 26.0 , 40.8 and 17.7 . The rate for total discontinuations ( all discontinuations including women lost to follow-up ) was 34.0 % for the Norinyl 1/35 group , 44.9 % for the Lo-Ovral group and 29.4 % for the Noriday 1/50 group . There was a significant difference in lost to follow-up rates between the Lo-Ovral group and the Noriday 1/50 group ( P less than 0.05 ) . There were no other significant differences between the groups for life table rates ( P greater than 0.05 ) . There were no pregnancies reported during the study period Objective To assess the contraceptive reliability , cycle control and tolerability of a new monophasic oral contraceptive containing 30 g ethinylestradiol plus 3 mg drospirenone ( Yasmin , Schering AG , Berlin , Germany ) , it was compared with an established oral contraceptive containing 30 g ethinylestradiol plus 150 g desogestrel ( Marvelon , NV Organon , Oss , The Netherl and s ) . Methods A r and omized , open-label , 13–cycle study was performed at 80 European centers . Contraceptive reliability , cycle control , blood pressure , body weight , the incidence of adverse events and skin condition were assessed during 13 cycles of oral contraceptive use , and at follow-up . Subjects recorded body weight on three consecutive days pretreatment and weekly thereafter . Results Of 2069 women who started the study and received the trial preparations in a ratio of 4:1 ( ethinylestradiol/drospirenone , n = 1657 ; ethinylestradiol/desogestrel , n = 412 ) , 1615 completed the 13 cycles plus follow-up , providing data for over 23 000 evaluable cycles . Eleven pregnancies occurred during treatment , only one of which ( in the ethinylestradiol/ drospirenone group ) could not be ascribed to user failure or interaction with other factors . Both preparations provided effective contraception and cycle control . Pre-existing acne and seborrhea were improved and blood pressure was essentially unchanged . The two treatments differed in their effect on body weight , the difference being statistically significant . In the ethinylestradiol/drospirenone group , there was a distinct decrease over the whole treatment phase , while a subtle and less distinct decrease was documented in the ethinylestradiol/desogestrel group . Conclusions The combination of 30 g ethinylestradiol/3 mg drospirenone provides effective oral contraception , excellent cycle control , good tolerability and a level of weight loss that may have a significant beneficial effect on compliance in women with a tendency to weight gain due to water retention Cycle control was studied comparing the monophasic oral contraceptive Loestrin with three low-dose phasic preparations ( Triphasil , Ortho 10/11 and Ortho 7/7/7 ) in 391 women of whom 300 completed 6 cycles . Loestrin subjects had a rate of occurrence ( 31 % of cycles ) for intermenstrual bleeding ( IMB ) comparable to the rates for subjects on the phasic preparations ( 36 % , 37 % and 37 % , respectively ) . Triphasil subjects had lower rates than the Ortho 10/11 and Ortho 7/7/7 subjects ( p less than 0.01 ) in cycle one when all subjects were analyzed and in pre- study users when continuing menstrual flow ( CMF ) episodes were not included as IMB . IMB was a cause for dropping out of the study in 7 % of subjects who were evenly distributed between groups . There were no differences between groups for BTB when perceived by subjects as a side effect . Spotting was perceived as a side effect more often with Ortho 10/11 and Ortho 7/7/7 use than with Triphasil ( p less than 0.01 ) . Loestrin , Ortho 10/11 and Ortho 7/7/7 subjects were more likely to report amenorrhea ( p less than 0.001 ) and less likely to report leg cramps ( p less than 0.01 ) compared to those on Triphasil . Triphasil subjects were less likely to report acne than subjects on Ortho 7/7/7 ( p less than 0.01 ) Objective : To compare a new triphasic oral contraceptive ( OC ) containing desogestrel and ethinyl estradiol ( DSG/EE ) with triphasic norethindrone/ethinyl estradiol ( NE/EE ) regarding effects on clinical efficacy , cycle control , and safety indices . Methods : In an open‐label , comparative multicenter study , 407 subjects were r and omized to a triphasic preparation containing DSG/EE and 405 subjects to a triphasic preparation containing NE/EE . The women were observed during six cycles of OC use . Results : The contraceptive efficacy of the triphasic DSG/EE OC was at least comparable to that of triphasic NE/EE . No pregnancies were reported with DSG/EE , whereas there were two pregnancies with NE/EE , both user failures . Cycle control with triphasic DSG/EE was statistically superior to that with triphasic NE/EE . Acceptability was excellent with both preparations as measured by the low discontinuation rates ( particularly for adverse menstrual experiences ) . No thromboembolic or other serious drugrelated adverse experiences were reported . The incidence of other drug‐related adverse experiences was generally low and decreased with time in both groups . No adverse effects were seen in terms of blood pressure , body weight , laboratory indices , cervical cytology , and breast nodularity . Conclusion : Triphasic DSG/EE is an effective and safe OC with excellent acceptability and cycle control superior to that of triphasic NE/EE . ( Obstet Gynecol 1994;83:679‐85 Abstract Objective : To compare the cycle control , efficacy , and safety of a new low-dose combined oral contraceptive containing ethinylestradiol 20μg and drospirenone 3 mg with an established formulation containing ethinylestradiol 20μg and desogestrel 150μg . Methods : This was a r and omized , open-label , parallel-group , multicenter study of healthy women ( aged 18–35 years ) over seven treatment cycles . Both combined oral contraceptives were administered once daily for 21 consecutive days followed by a 7-day hormone-free interval . Results : A total of 445 women were r and omized to treatment ; of these , 441 ( ethinylestradiol 20μg/drospirenone 3 mg , n = 220 ; ethinylestradiol 20μg/desogestrel 150μg , n = 221 ) went on to receive study medication . There was a trend towards reduced intracyclic bleeding with continued treatment in both treatment groups , consistent with clinical experience . Intracyclic bleeding was highest during the first treatment cycle in both treatment groups , but was generally much lower in subsequent cycles . More than 90 % of women in each of the groups experienced withdrawal bleeding during the study . The duration of withdrawal bleeding remained fairly constant throughout the study . The maximum intensity was mainly bleeding , rather than spotting . Overall , cycle control , efficacy , and safety profiles were comparable between both groups . Adverse events were generally of mild-to-moderate intensity and were those typical of hormonal contraceptive use . Conclusion : In conclusion , both ethinylestradiol 20μg/drospirenone 3 mg and ethinylestradiol 20μg/desogestrel 150μg are effective and well tolerated contraceptives that provide good cycle control A comparative multicenter clinical trial of two combined oral contraceptives ( OCs ) was conducted at clinics located in the Sudan , Sri Lanka , Chile , the Dominican Republic and Ecuador . The trial was design ed to determine if there were differences in efficacy , safety and acceptability between a triphasic and a low-dose monophasic OC . This report includes analysis of 1088 women . At each center , subjects were r and omly allocated to one of the two OCs . Follow-up visits were scheduled at 1 , 4 , 8 and 12 months after admission . There were two accidental pregnancies attributed to user failure reported during the study period ; one in the triphasic group and one in the monophasic group . Adverse experiences were mainly minor with headaches and dizziness being the most common complaints ; frequency of reports was similar in both groups . Cycle control was good in both groups with women in the triphasic group reporting fewer complaints of intermenstrual bleeding . Both OCs were safe and effective OBJECTIVE : To compare bleeding patterns between a 21/7-day triphasic norgestimate/ethinyl estradiol ( E2 ) 25-microgram oral contraceptive pill ( OCP ) and a 24/4-day drospirenone/ethinyl E2 20-microgram OCP . METHODS : In a three-cycle , open-label , multicenter study , healthy , sexually active women were assigned r and omly to a 21/7-day ( norgestimate/ethinyl E2 ) or 24/4-day ( drospirenone/ethinyl E2 ) OCP regimen . R and omization was stratified to assure a balanced distribution between regimens for “ fresh starts ” and “ switchers . ” Bleeding data were collected daily using an interactive voice-response system . Bleeding was defined according to the 2007 U.S. Food and Drug Administration ’s Reproductive Health Drug Advisory Committee – endorsed criteria . RESULTS : Across the three cycles , the 21/7-day OCP group ( n=165 ) reported fewer unscheduled bleeding days than did the 24/4-day OCP group ( n=167 ) ( mean 4.6 compared with 6.1 days , P=.003 ) . Women using the 21/7-day OCP had significantly fewer episodes of unscheduled bleeding than did those using the 24/4-day OCP ( mean 1.47 compared with 2.01 , P=.001 ) . Moreover , women using the 21/7-day OCP had a significantly lower absence of scheduled bleeding at each cycle ( P<.001 ) . Both regimens were well-tolerated . CONCLUSION : A 21-day norgestimate/ethinyl E2 25-microgram regimen results in less unscheduled bleeding and more scheduled bleeding than does a 24-day drospirenone/ethinyl E2 20-microgram regimen . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . Clinical Trials.gov , NCT00745901 . LEVEL OF EVIDENCE : This study compares the contraceptive reliability , cycle control , and tolerability of two oral contraceptive preparations containing 20 micrograms of ethinyl estradiol combined with either 75 micrograms of gestodene ( EE/GSD ) or 150 micrograms of desogestrel ( EE/DSG ) . Women received the trial preparations daily for 21 days , followed by a 7-day pill-free interval . Contraceptive efficacy , cycle control , and tolerability were evaluated over a period of 12 cycles . Efficacy data of 14,700 treatment cycles ( EE/GSD : 7299 ; EE/DSG : 7401 ) were obtained from 1476 women ( EE/GSD , n = 740 ; EE/DSG , n = 736 ) . Both preparations provided effective contraception and good cycle control with a similarly low incidence of both spotting and breakthrough bleeding . The spotting rates in both treatment groups decreased from 35.1 % ( EE/GSD ) and 37.5 % ( EE/DSG ) in the first treatment cycle to approximately 10 % in the fourth treatment cycle . The spotting incidence as percent of the total number of cycles was 12.7 % for EE/GSD and 14.3 % for EE/DSG . The breakthrough bleeding incidence was 5.2 % of all cycles for EE/GSD and 6.0 % of all cycles for EE/DSG . For 84.7 % of the cycles in the gestodene group and for 82.5 % of the cycles in the desogestrel group , neither spotting nor breakthrough bleeding were recorded . Overall , the spotting and breakthrough bleeding incidence tended to be lower with EE/GSD than with EE/DSG . However , the difference was not statistically significant . Amenorrhea was recorded in 2.7 % of the cycles with EE/GSD and in 2.9 % with EE/DSG . Both preparations were well tolerated and showed a similar pattern of adverse events . More than 83 % of the women in both groups either did not gain weight or lost more than 2 kg . Both preparations had a beneficial effect on dysmenorrhea . Both regimens provided reliable contraception and good cycle control . The incidence of adverse events was relatively low and both preparations were well tolerated BACKGROUND This study compared the bleeding pattern , cycle control and safety of an oral contraceptive ( OC ) comprising estradiol valerate/dienogest ( E2V/DNG ; administered using a dynamic dosing regimen ) with a monophasic OC containing ethinyl estradiol 20 mcg/levonorgestrel 100 mcg ( EE/LNG ) . E2V releases estradiol ( E2 ) , which is identical to endogenously produced 17beta-estradiol . STUDY DESIGN This was a r and omized , multicenter , double-blind , double-dummy trial lasting seven cycles in healthy women aged 18 - 50 years . RESULTS Overall , 798 women were r and omized and received allocated treatment ( 399 per group ) . There were significantly fewer bleeding/spotting days reported by women who received E2V/DNG than those who received EE/LNG [ 17.3+/-10.4 vs. 21.5+/-8.6 , respectively , p<.0001 , Reference Period 1 ( Days 1 - 90 ) ; and 13.4+/-9.vs . 15.9+/-7.1 , respectively , p<.0001 , Reference Period 2 ( Days 91 - 180 ) ] . Through Cycles 1 - 7 , the occurrence of scheduled withdrawal bleeding per cycle was 77.7 - 83.2 % with E2V/DNG and 89.5 - 93.8 % with EE/LNG ( p<.0001 per cycle ) . The duration and intensity of scheduled withdrawal bleeding were reduced with E2V/DNG vs. EE/LNG . The incidence of intracyclic bleeding was similar with E2V/DNG ( 10.5%-18.6 % ) and EE/LNG ( 9.9%-17.1 % ) ( p>.05 per cycle ) . No unintended pregnancies occurred with E2V/DNG , but there was one unintended pregnancy with EE/LNG . Adverse drug reactions occurred in 10.0 % and 8.5 % of women taking E2V/DNG and EE/LNG , respectively . Overall , 79.4 % of women were satisfied with E2V/DNG and 79.9 % with EE/LNG . CONCLUSIONS A novel OC composed of E2V/DNG is associated with an acceptable bleeding profile that is comparable to that of an EE-containing OC As part of an international multicentered investigation a double-blind comparative clinical trial was conducted at the Department of Obstetrics and Gynecology , University Medical School , Szeged , Hungary , in order to study the effect of different combined oral contraceptives on blood pressure . Healthy , normotensive women were r and omly allocated to either of the following oral contraceptives : 250 micrograms levonorgestrel + 50 micrograms ethinyloestradiol ( LN 250 + EE 50 ) , 250 micrograms levonorgestrel + 30 micrograms ethinyloestradiol ( LN 250 + EE 30 ) , 1 mg norethisterone acetate + 50 micrograms ethinyloestradiol ( NA 1 + EE 50 ) . St and ardized blood pressure measurements were carried out at admission and 3 , 6 , 9 , and 12 months after admission . Blood pressure change from admission to subsequent visits was analysed in subjects who were seen by the same observer both at admission and the follow-up under consideration . The systolic blood pressure slightly but not significantly increased in groups LN 250 + EE 50 and NA 1 + EE 50 , whereas the diastolic pressure showed a minimal decrease . In group LN 250 + EE 30 both systolic and diastolic blood pressure increased significantly ( + 5.58 and + 3.20 mm Hg , respectively ) at the 12-month follow-up . The study supports previous findings that combined oral contraceptive use is associated with a moderate rise in blood pressure . The progestogen-to-oestrogen ratio in the pill may be as important in this context as the dose of either component itself OBJECTIVE : To estimate whether progestin type or estrogen dose influences bleeding patterns , adverse effects , or satisfaction with combined oral contraceptives dosed continuously . METHODS : This was a r and omized , double blind , 4-arm active treatment study . Subjects received either 100 & mgr;g levonorgestrel/20 & mgr;g ethinyl estradiol ( E2 ) ( 20LNG group ) , 100 & mgr;g levonorgestrel/30 & mgr;g ethinyl E2 ( 30LNG group ) , 1,000 & mgr;g norethindrone acetate/20 & mgr;g ethinyl E2 ( 20NETA group ) , or 1,000 & mgr;g norethindrone acetate/30 & mgr;g ethinyl E2 ( 30NETA group ) for 180 days . Subjects logged bleeding events and adverse effects on a daily menstrual calendar . An exit survey measured satisfaction with bleeding patterns . RESULTS : One hundred thirty-nine women were enrolled . Patients in the 20NETA and 30NETA arms had significantly more days of amenorrhea than the 30LNG arm in the second 90 days ( P < .008 ) . The 30LNG group reported more spotting days than the 20NETA group over the entire study period ( P < .008 ) and the 30NETA group for the second 90 days ( P < .008 ) . Only a small number of bleeding days were reported with no differences between groups . No differences in adverse effects between groups were found . Women in the 30LNG arm reported lower levels of satisfaction with their bleeding patterns than the other groups ( 30LNG compared with 20NETA , P = .01 ; 30LNG compared with 30NETA , P = .001 ) . CONCLUSION : The addition of 10 & mgr;g of ethinyl E2 to a 20 & mgr;g ethinyl E2 pill containing levonorgestrel or norethindrone acetate did not improve bleeding patterns . During continuous dosing , the use of oral contraceptives containing 1,000 & mgr;g norethindrone acetate result ed in more days of amenorrhea and fewer days of spotting than preparations containing 100 & mgr;g levonorgestrel . LEVEL OF EVIDENCE : Cycle control over 12 months with low-dose oral contraceptives ( OCs ) was analyzed using calendars of bleeding on pill-taking days 1 through 21 ( intermenstrual bleeding ; IMB ) . One preparation contained 0.5 mg norethindrone and 0.035 mg ethinyl estradiol ( NET + EE ) , the other 0.3 mg norgestrel and 0.03 mg ethinyl estradiol ( Ng + EE ) . Half the subjects had previously used OCs containing greater than or equal to 0.05 mg estrogen ( switch-over ) ; the others had not previously used OCs for 2 months or more ( fresh ) . Fresh subjects reported more IMB than switch-over subjects , especially during the first three cycles ; IMB decreased over time for both groups . Ng + EE subjects had fewer IMB episodes during the early cycles than NET + EE subjects . Daily incidence of IMB formed a characteristic W-shaped curve in the NET + EE subjects that was most apparent in early cycles Abstract Background : The combined oral contraceptive Yasmin ® ( drospirenone 3 mg plus ethinylestradiol 30 μg [ DRSP 3 mg/EE 30 μg ] ) has been shown to be a well tolerated and effective combination that provides high contraceptive reliability and good cycle control . Furthermore , DRSP 3 mg/EE 30 μg has been shown to have a positive effect on premenstrual symptoms and well-being/health-related quality of life , and to improve the skin condition of women with acne . To date , however , there have been relatively few studies that have compared the effects of DRSP 3 mg/EE 30 μg on the general well-being of women with those of other oral contraceptives . Objectives : To compare the impact of DRSP 3 mg/EE 30 μg with that of levonorgestrel 150 mg/EE 30 μg ( LNG 150 μg/EE 30 μg ; Microgynon ® 30 ) on various parameters associated with well-being in healthy female subjects . Methods : This was a r and omized , single-blind , parallel-group , multicentre study conducted using 21/7-day regimens of DRSP 3 mg/EE 30 μg and LNG 150 μg/EE 30 μg over seven cycles . Efficacy parameters included : changes in Menstrual Distress Question naire ( MDQ ) normative T scores ; the proportion of subjects with acne ; and menstrual symptoms . Cycle control and subjective well-being parameters were also assessed . Results : Treatment with DRSP 3 mg/EE 30 μg had similar beneficial effects on symptoms of water retention and impaired concentration to LNG 150 μg/EE 30 μg , but was significantly better in alleviating negative affect symptoms during the menstrual phase ( median difference in MDQ T score −3 ; p = 0.027 ; Wilcoxon rank sum test ) . The proportion of subjects with acne decreased from approximately 55 % to approximately 45 % in the DRSP 3 mg/EE 30 μg group , but remained static at approximately 60 % in the LNG 150 μg/EE 30 μg group . Somatic and psychological symptoms occurred at the greatest intensity and for most subjects during the menstrual phase of the cycle in both groups . Both drugs had similar cycle control parameters with a tendency towards reduced bleeding with continued use . More subjects in the DRSP 3 mg/EE 30 μg group reported improved physical well-being ( 60 % vs 46 % ; p = 0.035 ; chi-squared [ χ2 ] test ) . Emotional well-being was reported improved in 61 % and 51 % of DRSP 3 mg/EE 30 μg and LNG 150 μg/EE 30 μg users , respectively ( p = 0.1190 ; χ2 test ) . Adverse events were typical of oral contraceptive use and did not give rise to any safety concerns . Conclusion : Both products had similar beneficial effects on symptoms of water retention and impaired concentration , but DRSP 3 mg/EE 30 μg was significantly better in alleviating negative affect symptoms during the menstrual phase . The proportion of subjects with acne decreased in the DRSP 3 mg/EE 30 μg group but not in the LNG 150 μg/EE 30 μg group . More subjects in the DRSP 3 mg/EE 30 μg group reported improved physical well-being compared with the LNG 150 μg/EE 30 μg group Fifty‐five women using Loestrin‐20 ( 20 μg ethinyl oestradiol and 1 mg norethisterone acetate ) as an oral contraceptive have been compared with a like number using Microgynon‐30 ( 30 μg ethinyl oestradiol and 150 μg levonorgestrel ) in a r and omized , double‐blind trial . Despite the small sample size , the main finding in the trial is clear‐cut ; Loestrin‐20 provides poor cycle control and is thus less acceptable as an oral contraceptive than Microgynon‐30 . Although there is also a suggestion that Loestrin‐20 may be less effective than Microgynon‐30 , the difference in the accidental pregnancy rates is not statistically significant Spotting and bleeding are among the most common side effects associated with oral contraceptive ( OC ) use and their occurrence is a prime determinant of whether a new user will continue to use OCs . Desogestrel and gestodene are two new progestins that were developed in part to minimize the occurrence of these side effects . Assessing the effect of these progestins is difficult , however , in part because their effects may be subtle , requiring a large sample size and possibly being overshadowed by other factors . To address these issues , we analyzed data from two comparative multicenter clinical trials that included 15,421 cycles among 2767 women . One study compared 75 micrograms gestodene + 30 micrograms ethinyl estradiol ( EE ) with 150 micrograms desogestrel + 30 micrograms EE , the other compared the same gestodene preparation with 150 micrograms desogestrel + 20 micrograms EE . Both studies found a higher risk of spotting or bleeding in all cycles among users of the desogestrel-containing preparation , with the differences ranging between 20 % and 70 % higher for the first study and 40 % and 140 % in the second . These differences were statistically significant in four of six cycles in each study and persisted after controlling for consistency and recency of OC use as well as smoking . After pooling the data and controlling for estrogen dose , the desogestrel-containing preparation was significantly associated with more frequent spotting or bleeding in five of six cycles . Smoking and consistency and recency of OC use were also independent predictors of spotting or bleeding Summary : The two types of low dose oral contraceptives one containing levonorgestrel the other containing norethisterone have been compared in a r and omized prospect i ve study . We have found that cycle control was much poorer with the norethisterone pill and would therefore recommend that if the norethisterone‐containing pill needs to be prescribed then either the 1 mg or the ‘ synphasic ’ preparation should be considered 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 Two triphasic oral contraceptives containing gestodene ( GES ) ( a new progestogen ) and levonorgestrel ( LNG ) were compared with respect to contraceptive effect , cycle control , acceptability and side effects . The serum concentrations of ingested hormones were measured together with ovarian , pituitary , and some adrenal hormones , as well as sex hormone binding globulin ( SHBG ) . The contraceptive effect and cycle control were good with both preparations , and there were only a few minor side effects . SHBG was elevated 2-fold in the LNG group and 3-fold in the GES group . The GES concentration in serum varied more than the LNG concentration , but with correction for variations in SHBG binding , less variability in actual GES and LNG concentrations was seen . Serum levels of FSH , LH , estradiol and progesterone were all depressed with both preparations . The depression was more marked in the GES group , despite lower progestogen ingestion and similar serum concentrations . Equal decreases were found in testosterone , and rostenedione and dehydroepi and rosterone sulfate ( DHEA-S ) with both preparations This multicenter study compared the contraceptive efficacy , cycle control , and safety of a new triphasic norgestimate ( 180/215/250 microg)/ethinyl estradiol 25 microg regimen ( Ortho Tri-Cyclen Lo ) ( n = 1,723 ) with that of norethindrone acetate 1 mg/ethinyl estradiol 20 microg ( Loestrin Fe 1/20 ) ( n = 1,171 ) . Healthy women were treated for up to 13 cycles . Demographics were similar between regimens . Contraceptive efficacy was comparable for Ortho Tri-Cyclen Lo and Loestrin Fe 1/20 . The overall and method failure probabilities of pregnancy through 13 cycles were 1.9 % and 1.5 % , respectively , with Ortho Tri-Cyclen Lo and 2.6 % and 2.4 % , respectively , with Loestrin Fe 1/20 . Breakthrough bleeding and spotting was reported by a significantly lower percentage of participants in the Ortho Tri-Cyclen Lo group compared with the Loestrin Fe 1/20 group . At representative Cycles 1 , 3 , 6 , 9 , and 13 , breakthrough bleeding and spotting rates were 16.3 , 11.5 , 10.3 , 7.9 , and 7.7 % , respectively , in the Ortho Tri-Cyclen Lo group and 34.9 , 22.9 , 22.2 , 15.9 , and 13.1 % , respectively , in the Loestrin Fe 1/20 group . Compliance and safety data were similar for the two regimens OBJECTIVE To compare the effect of 2 oral contraceptives ( OCs ) on body weight . STUDY DESIGN A r and omized , parallel-group , multicenter study of 1,723 women taking an OC with norgestimate ( NGM ) 180/215/250 microg/ethinyl estradiol ( EE ) 25 microg vs. 1,171 women taking on OC with norethindrone acetate 1 mg/EE 20 microg for 6 - 13 cycles was performed . Body weight changes between baseline and cycle 6 and baseline and cycle 13 were analyzed . Analysis included not only changes in mean body weight but also the distribution of changes that were within 5 % of baseline weight , 5 - 10 % of baseline weight and > 10 % of baseline weight . Only the 10 % change was felt to be clinical ly significant . RESULTS The distribution of body weight changes did not statistically differ between the 2 OC groups for any parameter measured . The mean weight change after 6 months for the NGM/EE and norethindrone acetate/EE groups was + 0.71 kg and + 0.57 kg , respectively . At 13 cycles for the NGM/EE and norethindrone acetate/ EE groups , the mean body weight change was + 0.93 kg and + 0.62 kg , respectively . Only 0.3 % of subjects in both OC groups experienced a 10 % change in weight . CONCLUSION Use of OCs does not substantially affect body weight for most women The Triphasic R and omized Clinical Trial was a multicenter , open-label , controlled , 6-month study to determine the influence of three currently marketed triphasic oral contraceptives on lipid and carbohydrate metabolism , cyclic bleeding profiles , and other adverse drug experiences . The study protocol m and ated four clinic visits : an initial visit during which study eligibility was determined , a second visit during which baselines were obtained for lipid and carbohydrate parameters , and visits at 3 and 6 months while taking the study drug . The study enrolled healthy women between the ages of 18 and 35 years who were within 20 % of their ideal body weight and who had a history of normal and regular menstrual cycles . Patients were r and omly assigned to one of three treatment groups : 51 patients to Tri-Levlen , 50 patients to Ortho-Novum 7/7/7 , and 56 patients to Tri-Norinyl . The control group consisted of 49 patients using nonhormonal forms of birth control . Eighty-eight percent ( 181/206 ) of the patients completed all four visits and were considered evaluable for subsequent analyses OBJECTIVES Poor cycle control and tolerability can be reasons for irregular pill intake . This study compared the tolerability of two low-dose oral contraceptives and their effect on cycle control . METHODS In this open , group-comparative , r and omized multicenter trial in Germany and the Netherl and s , women received either 20 microg ethinylestradiol plus 150 microg desogestrel ( 20EE/DSG ; n = 500 ) or 20 microg ethinylestradiol plus 100 microg levonorgestrel ( 20EE/LNG ; n = 498 ) for six treatment cycles . Cycle control , dysmenorrhea and premenstrual syndrome ( PMS ) were assessed using diary cards . Tolerability was assessed using the self-administered question naires Psychological General Well-Being Index ( PGWBI ) and the Profile of Mood States ( POMS ) . Acne was assessed by objective ( acne counts ) and subjective ( no , moderate , mild , severe ) acne scoring of the facial area at baseline and treatment cycles 1 , 3 and 6 . RESULTS A total of 404 ( 78.1 % ) and 384 ( 75.3 % ) women in the 20EE/DSG and 20EE/LNG groups , respectively , completed the trial . The occurrence rate of irregular bleeding and spotting was statistically significantly higher with 20EE/LNG than with 20EE/DSG ( 0.18 vs. 0.13 ; p < 0.05 ) . The mean number of bleeding-spotting days per cycle was statistically significantly higher with 20EE/LNG than with 20EE/DSG ( 0.63 vs. 0.48 ; p < 0.05 ) . Early withdrawal bleeding was more frequent with 20EE/LNG ( 0.15 vs. 0.08 ; p < 0.005 ) , whereas continued withdrawal bleeding was more frequent with 20EE/DSG ( 0.32 vs. 0.45 ; p < 0.001 ) ; absence of withdrawal bleeding was comparable ( 0.06 vs. 0.04 , respectively ) . Thirteen subjects in the 20EE/LNG group and three in the 20EE/DSG group discontinued due to unacceptable bleeding ( p < 0.05 ) . Dysmenorrhea and PMS decreased comparably in both groups . There were no differences between groups for the mean total scores of PGWBI or POMS at all time-points . Fewer acne lesions were counted with 20EE/DSG vs. 20EE/LNG after six cycles ( p < 0.05 ) . The subjective acne scores supported this finding . CONCLUSIONS 20EE/DSG provided better cycle control than 20EE/LNG with less treatment discontinuation due to unacceptable bleeding . There were no apparent differences between the two groups regarding tolerability and quality of life . There was less acne with 20EE/DSG Two triphasic oral contraceptives containing either gestodene or norethindrone as the progestogenic compound combined with ethinyl estradiol were compared in a r and omized clinical trial to assess their contraceptive reliability , clinical tolerance and cycle control . Both preparations were effective in preventing pregnancy . The gestodene preparation proved significantly superior regarding cycle control and general tolerance A r and omized controlled clinical trial comparing six combined oral contraceptives with 50 micrograms or less of ethinyl estradiol was undertaken in 10 WHO Collaborating Centres for Clinical Research in Human Reproduction . A total of 2430 women entered the trial and were observed for 28,077 woman-cycles . All low-dose combined oral contraceptives demonstrated equivalent efficiency with one-year pregnancy rates of one to six percent . However , discontinuation rates for medical reasons differed significantly between the treatment groups , with the preparation containing 20 micrograms ethinyl estradiol and that containing 400 micrograms norethisterone acetate being associated with higher discontinuation rates due to bleeding disturbances . Even among the preparations which did not differ in discontinuation rates , the reasons for discontinuation did differ . Women receiving norethisterone preparations tended to discontinue because of bleeding disturbances while those receiving the levonorgestrel-containing preparations tended to discontinue because of complaints of nausea and vomiting A comparative multicenter clinical trial of two low-dose combined oral contraceptives ( OCs ) was conducted in Malaysia , Egypt , Thail and , and Mexico . Efficacy , safety and acceptability were investigated in women taking either a norgestrel-based ( NG ) OC or a norethindrone acetate-based ( NA ) OC . This paper includes analysis of 892 women , all of whom were at least 42 days but within 26 weeks postpartum and r and omly allocated to one of the above OCs . Follow-up visits were scheduled at 1 , 4 , 8 and 12 months after admission . Baseline sociodemographic characteristics were similar for both groups , as well as compliance . There were nine unintended pregnancies reported ; eight of these occurring in the NA group . Adverse experiences were minor with headaches and dizziness being the most common complaints ; frequency of reports was similar in both groups . The group taking the NG-based OC had significantly ( p < .05 ) fewer menstrual-related complaints . Discontinuations due to menstrual problems were significantly more common among NA users ( primarily amenorrhea ) . Discontinuations in the NG group were primarily for other personal reasons , e.g. unable to return to the clinic . There was also a significant difference between the two groups for the 11-month gross cumulative life table discontinuation rates due to menstrual problems ( p < .01 ) ; the NA group had the higher rate Three different low-dose formulations of oral contraceptives were compared to determine the most suitable preparation for Filipino women as reflected in the first year continuation rates , incidence of side effects and failure rates . A total of 1,800 subjects were enrolled in the study from 18 health centers in six provinces in two regions of the Philippines , covering a total of 18,282 women-months of use . Sociodemographic characteristics were comparable . The monophasic levonorgestrel group showed the best performance followed by the triphasic preparation . The norethindrone group consistently showed higher drop-out rates , which may be due to the relatively higher incidence of side effects . For all three preparations , bleeding irregularities were low . There were no major side effects and no pregnancy was reported in one year of use . Noted was a distinct regional and provincial difference in recruitment and follow-up performance , possibly due to clinic , client or program factors A comparative study of two low-dose oral contraceptives , gestodene ( GES ) 75 mcg/ethinyl oestradiol ( EE ) 30 mcg and desogestrel ( DES ) 150 mcg/EE 20 mcg , was conducted in women over 30 years of age . This r and omised , open-label study was organised in Denmark , Italy , New Zeal and and United Kingdom . A total of 505 women received GES/EE and 501 received DES/EE for 6 consecutive menstrual cycles . The two groups were comparable in terms of demographic and gynaecologic characteristics at baseline . However , the menstrual flow length was slightly longer in the GES/EE group before the start of the treatment . The mean age ( + /- SD ) was 35 + /- 4 years in the GES/EE group and 35 + /- 5 years in the DES/EE group . The subjects in the GES/EE group contributed data for a total of 2800 cycles and those in the DES/EE group , data for 2796 cycles . There were no pregnancies on medication with either preparation . The results showed that there were significantly more normal cycles in the GES/EE group for cycles 1 to 6 . Irregular bleeding between withdrawal bleeds occurred in 10 % of GES/EE and 18.5 % of DES/EE cycles . Absence of all bleeding was reported in 29 ( 1 % ) and 63 ( 2 % ) cycles , respectively . The incidence of missed pills was low in both groups ( 11 % of cycles ) . No significant differences were observed in cycle length or withdrawal bleeding episode length . Withdrawal bleeding mean intensity was statistically significantly greater with GES/EE . However , for both preparations , the mean intensity was close to light bleeding . No clinical ly significant differences were noted in weight , blood pressure , Papanicolaou smears or laboratory data . Sixty-eight ( 13.5 % ) subjects in the GES/EE group and 64 ( 12.8 % ) in the DES/EE group discontinued before the end of the study . Among them , 37 ( 7 % ) and 40 ( 8 % ) in the respective groups withdrew because of adverse reactions . There was no difference between groups in terms of primary reasons for withdrawal . The most frequently reported complaints that led to discontinuation in both groups were headache , nausea and metrorrhagia . Breast tenderness led to the discontinuation of 1 subject in the GES/EE group and 3 in the DES/EE group . These results show excellent cycle control , efficacy and very low rate of side effects with both GES/EE and DES/EE . These low-dose oral contraceptives could be well suited to healthy nonsmoking women requiring contraception up to the age of menopause BACKGROUND The study was conducted to investigate whether hormonal contraceptives administered via the oral and vaginal route exert a similar effect on insulin sensitivity ( SI ) . STUDY DESIGN This is a prospect i ve , r and omized study performed in the University Hospital . Subjects were healthy lean young women , needing a hormonal contraceptive , r and omly allocated to receive for 6 months ( a ) an oral contraceptive ( OC ) containing 30 mcg ethinylestradiol (EE)/150 mcg desogestrel ( DSG ) ( high-estrogen group ; n=12 ) , ( b ) an OC containing 20 mcg EE/150 mcg DSG ( low-estrogen group ; n=12 ) and ( c ) a vaginal ring contraceptive releasing , per day , 15 mcg EE/120 mcg etonorgestrel , the active DSG metabolite ( n=12 ) . SI and glucose utilization independent of insulin ( Sg ) were evaluated by the minimal model method . Modifications of total , high-density lipoprotein ( HDL ) and low-density lipoprotein cholesterol and triglycerides were also evaluated . RESULTS Sg did not vary with any treatment . SI decreased during OCs ( 5.74+/-0.49 vs. 3.86+/-0.44 ; p=.0005 ) , independently of the high/low-estrogen dose . SI did not decrease during vaginal ring use ( 4.64+/-1.03 vs. 5.25+/-1.36 ; p=.57 ; p=.019 vs. oral ) . Total cholesterol and HDL cholesterol increased ( p=.02 ) during OCs , independently of the dose . Triglycerides increased during both oral ( p=.01 ) and vaginal ( p=.032 ) contraceptive use . CONCLUSIONS The present data indicate that in contrast to OC use , vaginal contraception with the ring does not deteriorate SI . The vaginal ring may represent an appropriate choice for long-term contraception in women at risk for developing diabetes mellitus or metabolic syndrome |
12,354 | 18,425,950 | No effect was observed on child health , measures of child mental health or emotional state .
Non-significant effects favouring the intervention group were seen for child cognitive development and educational achievement , and a non-significant effect favouring controls in rates of teenage pregnancy .
However , on the basis of current evidence we can not state unequivocally whether financial benefits delivered as an intervention are effective at improving child health or wellbeing in the short term .
We note particular concerns by some authors that sanctions and conditions ( such as working hours ) placed on families may increase family stress | BACKGROUND A strong and consistent relationship has been observed between relative poverty and poor child health and wellbeing even among rich nations .
This review set out to examine evidence that additional monies provided to poor or disadvantaged families may benefit children by reducing relative poverty and thereby improving children 's health , well-being and educational attainment .
AUTHORS ' CONCLUSIONS The review set out to examine the potential of financial support to poor families to improve circumstances for children . | The research design of the r and omised controlled trial is primarily associated today with medicine . It tends either to be ignored or regarded with suspicion by many in such disciplines as health promotion , public policy , social welfare , criminal justice , and education . However , all professional interventions in people 's lives are subject to essentially the same questions about acceptability and effectiveness . As the social reformers Sidney and Beatrice Webb pointed out in 1932 , there is far more experimentation going on in “ the world sociological laboratory in which we all live ” than in any other kind of laboratory , but most of this social experimentation is “ wrapped in secrecy ” and thus yields “ nothing to science.”1 # # # Summary points Many social scientists argue that r and omised controlled trials are inappropriate for evaluating social interventions , but they ignore a considerable history , mainly in the United States , of the use of r and omised controlled trials to assess different approaches to public policy and health promotion A tradition of experimental sociology was well established by the 1930s , built on the early use of controlled experiments in psychology and education From the early 1960s to early 1980s r and omised experiments were considered the optimal design for evaluating public policy interventions in the United States , and major evaluations using this design were carried out This approach became less popular as policy makers reacted negatively to evidence of “ near zero ” effects Lessons to be learnt about implementing r and omised controlled trials in real life setting s include the difficulty of assessing complex multi-level interventions and the challenge of integrating qualitative data The Webbs argued for a more “ scientific ” social policy , with social scientists being trained in experimental methods and evaluations of social interventions being carried out by independent investigators . They were apparently unaware that a strong tradition in experimental sociology had already been established , mainly in the United States . Reductions in the generosity of fee-for-service insurance lower the use of general medical and mental health services , but do they lead to lower mental health status for the covered population ? We addressed this question using data from the R AND Corporation Health Insurance Experiment . Families in six sites in the United States were r and omly assigned to one of 14 insurance plans for three- or five-year periods . On average , there were no significant adverse effects of cost-sharing plans , relative to a free-care plan , on either psychological well-being or psychological distress , when the cost-sharing plans included full catastrophic coverage . Those with high mental health status but low income at baseline had significantly more favorable mental health outcomes on the cost-sharing plans than on the free-care plan . We can not definitively comment on the effects of insurance generosity for the sick poor . Our findings apply in the context of m and ated comprehensive mental and general health coverage for a general nonelderly , nondisabled household population We assess the impact of the New Hope Project , an antipoverty program tested in a r and om assignment experimental design , on family functioning and developmental outcomes for preschool- and school-aged children ( N = 913 ) . New Hope offered wage supplements sufficient to raise family income above the poverty threshold and subsidies for child care and health insurance to adults who worked full-time . New Hope had strong positive effects on boys ' academic achievement , classroom behavior skills , positive social behavior , and problem behaviors , as reported by teachers , and on boys ' own expectations for advanced education and occupational aspirations . There were not corresponding program effects for girls . The child outcomes may have result ed from a combination of the following : Children in New Hope families spent more time in formal child care programs and other structured activities away from home than did children in control families . New Hope parents were employed more , had more material re sources , reported more social support , and expressed less stress and more optimism about achieving their goals than did parents in the control sample . The results suggest that an anti-poverty program that provides support for combining work and family responsibilities can have beneficial effects on the development of school-age children The present study examined the effectiveness and cost efficiency of three different techniques to encourage low-income rural parents to seek dental care for their children . The families of 51 children who needed immediate dental care ( determined by dental screening at a local school ) were placed into three matched groups and r and omly assigned to the treatment conditions : One Prompt ( Note Only ) , Three Prompt ( Note , Telephone Contact , Home Visit ) , and One Prompt plus $ 5 Incentive- The Three Prompt and One Prompt plus $ 5 Incentive were significantly more effective in initiating dental visits than the Note-Only procedure . Not only was the One Prompt plus $ 5 Incentive technique effective in producing a slightly larger percentage of initial dental visits compared to the Three-Prompt technique , it also produced a significantly larger number of followup visits . Furthermore , the cost-effectiveness analysis showed the Incentive condition to be less costly than the Three-Prompt condition in encouraging initial dental visits This study examined the effect of a time-limited welfare program on school-age children using data on almost 3,000 children ( ages 5 - 17 at the four year follow up-point ) from the r and om assignment evaluation of Florida 's Family Transition Program ( FTP ) . FTP was one of the first welfare reform initiatives to impose a time limit on the receipt of cash assistance , and it combined the time limit with a rich array of m and atory services . The effects of FTP on children were moderated by families ' risk of long-term welfare dependency . Contrary to predictions laid out at the outset , there were few effects of FTP on middle childhood and adolescent children for children of parents most likely to be long-term welfare dependent ( those most likely to hit the time limit ) . However , consistent negative effects on this same age group of children were found for children of parents least likely to be long-term welfare dependent -- parents who had the largest employment gains-- and effects of FTP were most strongly negative for the oldest adolescent children . The findings suggest a different theoretical model for movements into employment than the one suggested in the previous literature for job loss . The findings are discussed in terms of their contribution to research and policy This study examined the effectiveness of short-term contingency management for eliminating cocaine use and increasing full day treatment attendance with pregnant methadone-maintained women r and omly assigned to either an escalating voucher incentive schedule ( n=44 ) or non-incentive ( n=36 ) conditions . Full day treatment attendance and urine toxicology for cocaine and heroin were assessed and consequated for 14 days . The escalating voucher incentive schedule significantly increased full day treatment attendance and drug abstinence compared to the non-incentive schedule . These results suggest that reinforcing the co-occurrence of two required behaviors ( treatment attendance and abstinence from illicit drug use ) is effective , and may be an important adjunct to methadone pharmacotherapy for treating pregnant drug dependent women Approximately 4,000 preschool black children from low-income families in South Memphis participated for three years in a supplementary food program sponsored by the US Department of Agriculture . Part of this group received additional benefit from food stamps , day-care centers , and an infant-feeding program . We evaluated the effects of this participation in 250 children selected r and omly from the enrollment list of the supplemetary program . Each child was examined for height , weight , head circumference , and levels of hemoglobin , serum iron , and vitamins A and C. The data were then compared with those from a similar survey in the same area conducted three years before . The results of this comparison indicate considerable improvements in height and weight and a reduction in the incidence of anemia and in the numbers of children with low plasma vitamin A levels . In the absence of other recognizable intervening factors , we conclude that federal food assistance programs were primarily responsible for the observed nutritional improvements Objective : To raise immunization coverage among children at risk for underimmunization , we evaluated the effectiveness and cost-effectiveness of immunization activities in the Special Supplemental Program for Women , Infants and Children ( WIC ) . Method : A controlled intervention trial was conducted in seven WIC sites in Chicago between October 1990 and March 1994 . At intervention sites , staff screened children for vaccination status at every visit , referred vaccine-eligible children to either an on-site WIC nurse , on-site clinic , or off-site community provider , and issued either a 3-month supply of food vouchers to up-to- date children or a 1-month supply to children not up-to- date —a usual practice for high-risk WIC children . Our primary measure of effectiveness was the change in the baseline percentage of up-to- date children at the second birthday ; cost-effectiveness was approximated for each of the three referral interventions . Results : After one year , up-to- date vaccination coverage increased 23 % above baseline for intervention groups and decreased 9 % in the control group . After the second year , up-to- date vaccination further increased to 38 % above baseline in intervention groups and did not change in the control group . The total cost per additional up-to- date child ranged from $ 30 for sites referring children off-site to $ 73 for sites referring children on-site to a nurse . Conclusion : This controlled intervention trial of screening , referral , and a voucher incentive in the WIC program demonstrated a substantial increase in immunization coverage at a low cost . Continuing to design linkages between WIC and immunization programs by building on WIC 's access to at-risk population s is worth the investment Inner-city infants ( n = 565 ) enrolled in the WIC program were r and omly assigned at 6 months of age to either of 2 groups : ( 1 ) voucher incentive ( frequency of issuance of food vouchers based on immunization status ) plus reminder-recall ( calls and /or letters to families of under-vaccinated children ) or ( 2 ) voucher incentive alone . At 12 months , both groups ' immunization levels were high and not significantly different : 80 % + /- 4 % versus 79 % + /- 5 % ( P = .749 ) Data from the Minnesota Family Investment Program and the New Hope demonstration were used to determine whether experimental effects of antipoverty policies differ by parents ' risk for nonemployment . Using propensity score analysis , increases in employment and income were largest in the harder-to-employ halves of both sample s. However , only children in the moderately hard-to-employ quartiles ( 50th to 75th percentile ) consistently showed improvements in school and behavior outcomes . The very-hardest-to-employ 25 % experienced decreases in school engagement , and increases in aggressive behaviors , despite substantial increases in parental employment and income . In this group , increases in maternal depression , reductions in regular family routines , and smaller increases in job stability and center-based child care occurred . These factors may have counteracted the potential benefits of increased income on children Do Conditional Cash Transfers Improve Child Health ? Evidence from PROGRESA 's Control R and omized Experiment Author(s ) : Paul Gertler Source : The American Economic Review , Vol . 94 , No. 2 , Papers and Proceedings of the One Hundred Sixteenth Annual Meeting of the American Economic Association San Diego , CA , January 3 - 5 , 2004 ( May , 2004 ) , pp . 336 - 341 Published by : American Economic Association Stable URL : http://www.jstor.org/stable/3592906 . Accessed : 13/03/2014 This study examined the age-specific pattern of effects of welfare policies on child achievement . Drawing from 7 r and om-assignment welfare and antipoverty evaluations that provided more than 30,000 observations of children 's achievement , this study found that times of developmental transition are the only periods sensitive to the changes in families brought about by these policies . More specifically , small positive effects of welfare and antipoverty policies were found for children making the transition into middle childhood , and small negative effects of these same policies were found for children making the transition out of middle childhood and into early adolescence . Effects were robust across various program groupings and could not be attributed to family characteristics that differ for children of different ages . This research informs the underst and ing of how changes in employment and income for low-income parents affect development across childhood This prospect i ve longitudinal study , using data from the National Longitudinal Survey of Youth ( NLSY ; N = 614 ) , addresses the gap in the research literature regarding the effects of welfare reform on children . Key questions addressed include whether welfare dynamics and support services relevant to welfare reform , both measured across the first 5 years of life , are associated with mothers ' earnings in the 6th year and three child cognitive outcomes in the 7th and 8th years : Peabody Individual Achievement Test ( PIAT ) math and reading scores , and the Peabody Picture Vocabulary Test ( PPVT ) . Welfare dynamics are represented by total time on welfare , degree of cycling on and off welfare , and degree to which welfare and work are combined . Support services measured include three forms of child care ( relative , babysitter , and center-based ) , as well as three forms of human capital supports ( child support , job training , and education ) . Controlling for a range of background factors and for different patterns of welfare use across the first 5 years , small positive associations with mother 's earnings were found for child support , education , and job training . Small positive associations also were found between child support and both math and reading scores . Finally positive associations of medium effect size were found between center care and both mothers ' earnings and child PPVT scores . Although effect sizes are generally small , the results suggest the potential value of welfare reform approaches that emphasize long-term human capital development . Interactions between welfare dynamics and support services suggest subgroup differences . Specifically , positive effects of support services on earnings are strongest among mothers with higher levels of human capital ( higher levels of work while on welfare , lower total time on welfare ) . Babysitter care appears to have negative effects on both reading and math scores of children whose mothers report low levels of work while on welfare . Implication s for welfare reform policy are discussed The goal of current national and state legislation on welfare reform is to decrease the number of people who are dependent on public assistance , most of whom are mothers and their young children . Mothers ' patterns of welfare receipt in the 3 years following the birth of a child were examined vis-à-vis their associations with maternal emotional distress ( General Health Question naire ) , provision of learning experiences ( Home Observation of the Measurement of the Environment ) , parenting behavior , and the child 's cognitive test score ( Stanford-Binet ) in the third year of life . The data set was the Infant Health and Development Program , an eight-site r and omized clinical trial design ed to test the efficacy of educational and family support services in reducing developmental delays in low-birthweight , preterm infants ( N = 833 ) . Strong negative associations were found between receiving welfare and parenting behavior and child outcomes at age 3 years . Outcomes varied depending on when the mother received public assistance ( earlier or later in her child 's first 3 years ) and family poverty status on leaving welfare . The parenting behavior of mothers who had left welfare by their child 's third birthday was more likely to be authoritarian if she had left public assistance without also leaving poverty . Implication s of these findings for the well-being of children in low-income families are discussed Little is known about the effects of the most recent welfare reform initiatives -- which include work m and ates , time limits , and enhanced earnings disregards -- on children 's outcomes . This is partly because the ways in which maternal employment and income affect children more generally are not well understood . This article describes the effects on child development of the Minnesota Family Investment Program ( MFIP ) , a welfare program that began prior to 1996 federal welfare reform legislation . The present study utilized MFIP 's unique , three-group research design to untangle the effects of different components of the program , and , in turn , discover how each component 's effects on parents ' income or employment affected children 's development . This study 's findings showed that MFIP increased employment rates and decreased poverty and , according to reports from mothers , children were less likely to exhibit problem behaviors and more likely to perform better and be more highly engaged in school . These findings , based on a total of 879 participants , bolster the long-st and ing literature that has associated poverty with worse outcomes for children by confirming , in a rigorous experiment , that incremental increases in income for working poor parents bring benefits to children OBJECTIVE We have previously shown that an educational program was not effective in increasing bicycle helmet use in children of low-income families . The objective of this study was to evaluate a combined educational and helmet subsidy program in the same population , while controlling for secular trends . The secondary objective was to complete a third year of surveying children 's bicycle helmet use throughout the study community . DESIGN A prospect i ve , controlled , before- and -after study . SUBJECTS Bicycling children 5 to 14 years of age from areas of low average family income . SETTING A defined geographic community within a large urban Canadian city . INTERVENTION In April 1992 , students in three schools located in the area of lowest average family income were offered $ 10 helmets and an educational program ; three other low-income areas served as control areas . MAIN OUTCOME MEASURE Helmet use was determined by direct observation of more than 1800 bicycling children . RESULTS Nine hundred ten helmets were sold to a school population of 1415 ( 64 % ) . Reported helmet ownership increased from 10 % to 47 % . However , observed helmet use in the low-income intervention area was no different from the rate in the three low-income control areas ( 18 % versus 19 % ) . There was no difference in the trend in helmet use during the period of 1990 through 1992 in the intervention area ( 4 % to 18 % ) compared with the control areas ( 3 % to 19 % ) . Helmet use rates from all income areas have increased from 3.4 % in 1990 , to 16 % in 1991 , to 28 % in 1992 . In 1992 , helmet use in the high-income areas was 48 % and in the low-income areas was 20 % . CONCLUSIONS There has been a trend toward increasing helmet use in all income areas during the 3-year period . Despite encouraging helmet sales and increases in reported helmet ownership , the results of the observational study do not support the efficacy of a helmet subsidy program in increasing helmet use in children residing in areas of low average family income . Strategies to increase helmet use in children of low average family income remain a priority Significant re sources have been directed at underst and ing and alleviating the achievement gap in education . Most programs focused on this aim rely on a top-down approach , including funding for infrastructure improvement , curriculum development , class size , and teacher salaries . This article presents findings from a r and omized field trial that evaluates a bottom-up approach in which high-achieving students of diverse racial and ethnic background s from poor families are given monetary incentives to maintain their academic st and ing . The evaluation was design ed to explore the role of monetary incentives as a mechanism for promoting resiliency in the face of poverty-related challenge . Discussion of what motivates students to learn is framed as a function of normal cognitive and socioemotional development in challenging environments . Evaluation findings indicate that monetary incentives are effective in promoting academic success to different degrees and for different reasons depending on students ’ perception of the meaning of the incentive in relation to their emergent identity |
12,355 | 21,901,711 | When compared to st and ard care or minimal HIV support intervention , meta- analysis showed that behavioral interventions had no effect on increasing condom use among HIV-positive women .
Meta- analysis shows that behavioral interventions have little effect on increasing condom use among HIV-positive women . | BACKGROUND High rates of HIV infection among women of reproductive age have dramatic consequences for personal and public health .
Prophylaxis during sexual intercourse in the form of condoms has been the most effective way to prevent both STI and HIV transmission among people living with HIV .
OBJECTIVES To investigate the effectiveness of behavioral interventions in promoting condom use among women living with HIV . | Objectives : To examine the effect of a 15-session coping group intervention compared with a 15-session therapeutic support group intervention among HIV-positive men and women with a history of childhood sexual abuse ( CSA ) on sexual transmission risk behavior . Design : A r and omized controlled behavioral intervention trial with 12-month follow-up . Methods : A diverse sample of 247 HIV-positive men and women with histories of CSA was r and omized to 1 of 2 time-matched group intervention conditions . Sexual behavior was assessed at baseline ; immediately after the intervention ; and at 4- , 8- , and 12-month follow-up periods ( 5 assessment s ) . Changes in frequency of unprotected anal and vaginal intercourse by intervention condition were examined using generalized linear mixed models for all partners , and specifically for HIV-negative or serostatus unknown partners . Results : Participants in the HIV and trauma coping intervention condition decreased their frequency of unprotected sexual intercourse more than participants in the support intervention condition for all partners ( P < 0.001 ; d = 0.38 , 0.32 , and 0.38 at the 4- , 8- , and 12-month follow-up periods , respectively ) and for HIV-negative and serostatus unknown partners ( P < 0.001 ; d = 0.48 , 0.39 , and 0.04 at the 4- , 8- , and 12-month follow-up periods , respectively ) . Conclusion : A group intervention to address coping with HIV and CSA can be effective in reducing transmission risk behavior among HIV-positive men and women with histories of sexual trauma We investigated prevalence of sexually transmitted infections ( STI ) in a cohort of HIV-1-infected pregnant women and described factors associated with STI diagnosis , as a nested study within the European Collaborative Study ( ECS ) . The ECS is a cohort study in which HIV-infected pregnant women are enrolled and their children followed from birth , according to st and ard clinical and laboratory protocol s. Information on STIs diagnosed during pregnancy was collected retrospectively from the antenatal records of women enrolling between January 1999 and October 2005 ; other variables were obtained from the ECS prospect i ve data base . A total of 1,050 women were included : 530 in Western Europe and 520 in Ukraine . Syphilis was the most common bacterial STI ( 2 % prevalence , 95 % CI 1.2–3.0 ) . Prevalence of HPV-related genital lesions was 8.6 % ( 95%CI 6.9–10.4 ) and prevalence of Trichomonas vaginalis was 12.1 % ( 95%CI 10.2–14.2 ) . Women in Ukraine ( AOR 10.7 , 95%CI 3.7–30.5 ) , single women ( AOR 3.9 , 95%CI 1.2–12.7 ) , sexual partners of injecting drug users ( AOR 3.8 , 95%CI 1.4–10.4 ) and women with CD4 counts < 200 cells/mm3 ( AOR 5.4 , 95%CI 1.0–28.1 ) were at increased risk of diagnosis with Chlamydia trachomatis , syphilis or Trichomonas vaginalis . African origin ( AOR 1.9 , 95%CI 1.1–3.3 ) and CD4 count < 200 cells/mm3 ( AOR 3.4 , 95%CI 1.5–7.8 ) were associated with HSV-2 and /or HPV-related genital lesions . Antenatal screening should be considered an effective tool for diagnosis , treatment and prevention of further transmission of STIs . HIV-infected women should receive adequate screening for STIs during pregnancy together with appropriate counseling and follow-up for treatment and prevention Background : There is a lack of effective behavioral interventions for HIV-positive injection drug users ( IDUs ) . We sought to evaluate the efficacy of an intervention to reduce sexual and injection transmission risk behaviors and to increase utilization of medical care and adherence to HIV medications among this population . Methods : HIV-positive IDUs ( n = 966 ) recruited in 4 US cities were r and omly assigned to a 10-session peer mentoring intervention or to an 8-session video discussion intervention ( control condition ) . Participants completed audio computer-assisted self-interviews and had their blood drawn to measure CD4 cell count and viral load at baseline and at 3-month ( no blood ) , 6-month , and 12-month follow-ups . Results : Overall retention rates for r and omized participants were 87 % , 83 % , and 85 % at 3 , 6 , and 12 months , respectively . Participants in both conditions reported significant reductions from baseline in injection and sexual transmission risk behaviors , but there were no significant differences between conditions . Participants in both conditions reported no change in medical care and adherence , and there were no significant differences between conditions . Conclusions : Both interventions led to decreases in risk behaviors but no changes in medical outcomes . The characteristics of the trial that may have contributed to these results are examined , and directions for future research are identified Background : Most HIV-infected patients attending a consultation-liaison psychiatry service show symptoms of anxiety and depression . The present study sought to evaluate the immediate and long-term efficacy of a structured cognitive-behavioural group therapy reducing anxiety and depression in HIV-infected patients referred to a consultation-liaison psychiatry department , and to identify baseline variables predictive of greater improvement . Methods : Repeated- measures ANOVA was used to analyse changes in the Beck Depression Inventory ( BDI ) and the state subscale of the State/Trait Anxiety Inventory ( STAI ) administered to 39 participants at 4 time points : T1 ( 1 month before beginning the therapy ) , T2 ( during the first session ) , T3 ( during the last session ) and T4 ( 3 months after the last session ) . The therapy consisted of 16 weekly 2-hour sessions following a structured time-limited cognitive-behavioural group psychotherapy programme . Results : During the intervention time ( between T2 and T3 ) an improvement was observed in depression and anxiety , which persisted after the 3-month follow-up period ( between T3 and T4 ) . No changes were observed during baseline ( between T1 and T2 ) . Patients with higher levels of anxiety at baseline showed greater improvement in STAI state subscale scores . Transmission of HIV infection through intravenous drug use was associated with less improvement on the BDI . Conclusions : This is the first report of an ongoing study which suggests long-lasting efficacy of a structured cognitive-behavioural group psychotherapy programme in a heterogeneous sample of HIV-1-infected patients referred to a consultation-liaison psychiatry unit BACKGROUND As many as one in three HIV-positive people continue unprotected sexual practice s after learning that they are HIV infected . This article reports the outcomes of a theory-based intervention to reduce risk of HIV transmission for people living with HIV infection . METHODS Men ( n=233 ) and women ( n=99 ) living with HIV-AIDS were r and omly assigned to receive either ( 1 ) a five-session group intervention focused on strategies for practicing safer sexual behavior , or ( 2 ) a five-session , contact-matched , health-maintenance support group ( st and ard-of-care comparison ) . Participants were followed for 6 months post-intervention . RESULTS The intervention to reduce risk of HIV transmission result ed in significantly less unprotected intercourse and greater condom use at follow-up . Transmission-risk behaviors with non-HIV-positive sexual partners and estimated HIV transmission rates over a 1-year horizon were also significantly lower for the behavioral risk-reduction intervention group . CONCLUSIONS This study is among the first to demonstrate successful HIV-transmission risk reduction result ing from a behavioral intervention tailored for HIV-positive men and women Testing behavioral interventions to increase safer sex practice s of HIV+ individuals has the potential to significantly reduce the number of new infections . This study evaluated a behavioral intervention design ed to reduce the sexual risk behaviors of HIV+ individuals . HIV+ individuals ( N = 387 ) who reported engaging in unprotected sex with HIV- or partners of unknown serostatus were r and omly assigned to ( a ) a single counseling session targeting problem areas identified by the participant in 3 possible intervention domains ( i.e. , condom use , negotiation , disclosure ) ; ( b ) a single-session comprehensive intervention that covered all 3 intervention domains ; ( c ) the same comprehensive intervention , plus 2 monthly booster sessions ; or ( d ) a 3-session diet and exercise attention-control condition . The median number of unprotectedsex acts decreasedfrom 14 at baseline to6 , 6 , and 4 at 4- , 8- , and 12-month follow-ups , respectively . A repeated measures analysis of variance revealed a significant decrease in unprotected sex acts across all groups across time . A significant Group x Time interaction revealed that the comprehensive-with-boosters group had the most unprotected sex at 8-month follow-up as compared to the other 3 groups . These findings suggest that a brief intervention can result in large reductions in HIV transmission risks among HIV+ individuals , but the relative benefit of one intervention approach over another remains unclear Objective : To evaluate the effectiveness of a clinician-delivered intervention , implemented during routine clinical care , in reducing unprotected sexual behavior of HIV-infected patients . Design : A prospect i ve clinical trial comparing the impact of a clinician-delivered intervention arm vs. a st and ard-of-care control arm on unprotected sexual behavior of HIV-infected patients . Setting : The 2 largest HIV clinics in Connecticut . Participants : A total of 497 HIV-infected patients , aged ≥18 years , receiving HIV clinical care . Intervention : HIV clinical care providers conducted brief client-centered interventions at each clinical encounter that were design ed to help HIV-infected patients reduce unprotected sexual behavior . Main Outcome Measures : Unprotected insertive and receptive vaginal and anal intercourse and unprotected insertive oral sex ; unprotected insertive and receptive vaginal and anal intercourse only . Results : HIV-infected patients who received the clinician-delivered intervention showed significantly reduced unprotected insertive and receptive vaginal and anal intercourse and insertive oral sex over a follow-up interval of 18 months ( P < 0.05 ) . These behaviors increased across the study interval for patients in the st and ard-of-care control arm ( P < 0.01 ) . For the measure of unprotected insertive and receptive vaginal and anal sex only , there was a trend toward a reduction in unprotected sex among intervention arm participants over time ( P < 0.09 ) , and a significant increase in unprotected sex in the st and ard-of-care control arm ( P < 0.01 ) . Conclusions : A clinician-delivered HIV prevention intervention targeting HIV-infected patients result ed in reductions in unprotected sex . Interventions of this kind should be integrated into routine HIV clinical care This study examined whether a culturally adapted version of a previously evaluated efficacious HIV prevention program reduced sexual risk behaviors of youth living with HIV ( YLH ) in Ug and a. YLH , 14 to 21 years , were r and omized to intervention ( N = 50 ) or control ( N = 50 ) conditions . Significantly more YLH in the intervention used condoms consistently and decreased their number of sexual partners in comparison to the control condition . Western interventions can be culturally adapted to retain efficacy in reducing the sexual risk behavior of YLH Child sexual abuse ( CSA ) is associated with HIV risk behaviors [ Bensley , L. , Van Eenwyk , J. , and Simmons , K. W. , 2003 . ] and more prevalent among women living with HIV than in the general population [ Koenig , L. J. , and Clark , H. , 2004 ] . This r and omized Phase ~ I clinical trial tested the impact of a culturally congruent psychoeducational intervention design ed to reduce sexual risks and increase HIV medication adherence for HIV-positive women with CSA histories . An ethnically diverse sample of 147 women were r and omized to two conditions : an 11-session Enhanced Sexual Health Intervention ( ESHI ) or an attention control . Results based on “ intent to treat ’ ’ analysesof pre – post changes are reported here . Additional analyses explored whether theobserved effects might depend on “ intervention dose , ’ ’ i.e. , number of sessions attended . Women in the ESHI condition reported greater sexual risk reduction than women in the control condition . Although there were no differences between women in the ESHI and control groups on medication adherence , women in the ESHI condition who attended 8 or more sessions reported greater medication adherence at posttest than control women . The findings provide initial support for this culturally and gender-congruent psychoeducational intervention for HIV-positive women with CSA , and highlight the importance of addressing the effects of CSA on sexual risk reduction and medicationadherence in preventive interventions for women Background : The impact of antiretroviral therapy ( ART ) on sexual risk behavior and HIV transmission among HIV-infected persons in Africa is unknown . Objective : To assess changes in risky sexual behavior and estimated HIV transmission from HIV-infected adults after 6 months of ART . Design and methods : A prospect i ve cohort study was performed in rural Ug and a. Between May 2003 and December 2004 a total of 926 HIV-infected adults were enrolled and followed in a home-based ART program that included prevention counselling , voluntary counseling and testing ( VCT ) for cohabitating partners and condom provision . At baseline and follow-up , participants ’ HIV plasma viral load and partner-specific sexual behaviors were assessed . Risky sex was defined as inconsistent or no condom use with partners of HIV-negative or unknown serostatus in the previous 3 months . The rates of risky sex were compared using a Poisson regression model and transmission risk per partner was estimated , based on established viral load-specific transmission rates . Results : Six months after initiating ART , risky sexual behavior reduced by 70 % [ adjusted risk ratio , 0.3 ; 95 % confidence interval ( CI ) , 0.2–0.7 ; P = 0.0017 ] . Over 85 % of risky sexual acts occurred within married couples . At baseline , median viral load among those reporting risky sex was 122 500 copies/ml , and at follow-up , < 50 copies/ml . Estimated risk of HIV transmission from cohort members declined by 98 % , from 45.7 to 0.9 per 1000 person years . Conclusions : Providing ART , prevention counseling , and partner VCT was associated with reduced sexual risk behavior and estimated risk of HIV transmission among HIV-infected Ug and an adults during the first 6 months of therapy . Integrated ART and prevention programs may reduce HIV transmission in Africa Summary HIV risky behaviors and health practice s were examined among young people living with HIV ( YPLH ) in Los Angeles , San Francisco , and New York over 15 months in response to receiving a preventive intervention . YPLH aged 16 to 29 years ( n = 175 ; 26 % black and 42 % Latino ; 69 % gay men ) were r and omly assigned to a 3-module intervention totaling 18 sessions delivered by telephone , in person , or a delayed-intervention condition . Intention-to-treat analyses found that the in-person intervention result ed in a significantly higher proportion of sexual acts protected by condoms overall and with HIV-seronegative partners . Pre- and postanalyses of YPLH in the delayed-intervention condition alone found that YPLH tended to have fewer sexual partners , used fewer drugs , reported less emotional distress , and decreased their use of antiretroviral therapies . Prevention programs can be delivered in alternative formats while retaining efficacy . When YPLH are using hard drugs , drug treatment may be needed before delivery of preventive interventions This study evaluates the effectiveness of a holistic model for treating people living with AIDS in Africa ; the model aims to improve knowledge about AIDS prevention and care , increase trust in the health centre , impact behaviour , and promote a high level of adherence to HAART . The study took place in the context of the DREAM ( Drug Re source Enhancement against AIDS and Malnutrition ) programme in Mozambique , design ed by the Community of Sant'Egidio to treat HIV patients in Africa . It provides patients with free anti-retroviral drugs , laboratory tests ( including viral load ) , home care and nutritional support . This is a prospect i ve study involving 531 patients over a 12-month period . The patients , predominantly poor and with a low level of education , demonstrated a good level of knowledge about AIDS ( more than 90 % know how it is transmitted ) and trust in the treatment , with a relatively small percentage turning to traditional healers . Overall the patients had a low level of engaging in risky sexual behaviour and a very good level of adherence to HAART ( 69.5 % of the 531 subjects had a pill count higher than 95 % ) . The positive results of the programme 's educational initiatives were confirmed with the patients ' good clinical results OBJECTIVE To examine the maintenance of effects of Motivational Enhancement Therapy ( MET ) shown to improve risk behaviors and viral load in youth living with HIV ( YLH ) immediately posttreatment . METHODS Sixty-five youth ( ages 16 - 25 years ) were r and omized to Healthy Choices or a waitlist control . Frequency of substance use , frequency of unprotected intercourse , and viral load were obtained at baseline , 3 , and 6 months after study entry . The waitlist control then received intervention . An additional data collection was obtained at 9 months for follow-up of the original treatment group . RESULTS One-tailed ANOVA showed that the treatment group had greater reductions in viral load and alcohol use from baseline to 6 months . These reductions appeared to be maintained at 9-month follow-up . Improvements in sexual risk were not evident . CONCLUSIONS MET showed significant promise in reducing substance use and in improving HIV-related health in YLH immediately posttreatment . These effects were maintained after treatment termination Background Reducing substance use and unprotected sex by HIV-positive persons improves individual health status while decreasing the risk of HIV transmission . Despite recommendations that health care providers screen and counsel their HIV-positive patients for ongoing behavioral risks , it is unknown how to best provide “ prevention with positives ” in clinical setting s. Positive Choice , an interactive , patient-tailored computer program , was developed in the United States to improve clinic-based assessment and counseling for risky behaviors . Methodology and Findings We conducted a parallel groups r and omized controlled trial ( December 2003–September 2006 ) at 5 San Francisco area outpatient HIV clinics . Eligible patients ( HIV-positive English-speaking adults ) completed an in-depth computerized risk assessment . Participants reporting substance use or sexual risks ( n = 476 ) were r and omized in stratified blocks . The intervention group received tailored risk-reduction counseling from a “ Video Doctor ” via laptop computer and a printed Educational Worksheet ; providers received a Cueing Sheet on reported risks . Compared with control , fewer intervention participants reported continuing illicit drug use ( RR 0.81 , 95 % CI : 0.689 , 0.957 , p = 0.014 at 3 months ; and RR 0.65 , 95 % CI : 0.540 , 0.785 , p<0.001 at 6 months ) and unprotected sex ( RR 0.88 , 95 % CI : 0.773 , 0.993 , p = 0.039 at 3 months ; and RR 0.80 , 95 % CI : 0.686 , 0.941 , p = 0.007 at 6 months ) . Intervention participants reported fewer mean days of ongoing illicit drug use ( -4.0 days vs. -1.3 days , p = 0.346 , at 3 months ; and -4.7 days vs. -0.7 days , p = 0.130 , at 6 months ) than did controls , and had fewer casual sex partners at ( −2.3 vs. −1.4 , p = 0.461 , at 3 months ; and −2.7 vs. −0.6 , p = 0.042 , at 6 months ) . Conclusions The Positive Choice intervention achieved significant cessation of illicit drug use and unprotected sex at the group-level , and modest individual-level reductions in days of ongoing drug use and number of casual sex partners compared with the control group . Positive Choice , including Video Doctor counseling , is an efficacious and appropriate adjunct to risk-reduction efforts in outpatient setting s , and holds promise as a public health HIV intervention . Trial Registration Clinical trials.gov Context : The US Centers for Disease Control and Prevention ( CDC ) strongly recommend comprehensive risk counceling and services for people living with HIV ( PLH ) ; yet , there are no evidence -based counseling protocol s. Objective : To examine the effect of a 15-session , individually delivered , cognitive behavioral intervention on a diverse sample of PLH at risk of transmitting to others . Design : This was a multisite , 2-group , r and omized , controlled trial . Participants : Nine hundred thirty-six HIV-infected participants considered to be at risk of transmitting HIV of 3818 persons screened were r and omized into the trial . Participants were recruited in Los Angeles , Milwaukee , New York , and San Francisco . Intervention : Fifteen 90-minute individually delivered intervention sessions were divided into 3 modules : stress , coping , and adjustment ; safer behaviors ; and health behaviors . The control group received no intervention until the trial was completed . Both groups completed follow-up assessment s at 5 , 10 , 15 , 20 , and 25 months after r and omization . Main Outcome Measure : Transmission risk , as measured by the number of unprotected sexual risk acts with persons of HIV-negative or unknown status , was the main outcome measure . Results : Overall , a significance difference in mean transmission risk acts was shown between the intervention and control arms over 5 to 25 months ( χ2 = 16.0 , degrees of freedom = 5 ; P = 0.007 ) . The greatest reduction occurred at the 20-month follow-up , with a 36 % reduction in the intervention group compared with the control group . Conclusion : Cognitive behavioral intervention programs can effectively reduce the potential of HIV transmission to others among PLH who report significant transmission risk behavior BACKGROUND Sexually transmitted diseases ( STDs ) enhance human immunodeficiency virus (HIV)-1 susceptibility , but few studies have examined the reciprocal effect of HIV-1 on STD acquisition . METHODS Data from a prospect i ve cohort study conducted among female sex workers in Mombasa , Kenya between 1993 and 2003 were used to determine the effect of HIV-1 infection on STD susceptibility . The cohort included 1215 HIV-1-seronegative women who underwent monthly HIV-1 and STD screening , of whom 238 experienced seroconversion to HIV-1 during follow-up . And ersen-Gill proportional-hazards models were used to compare the incidence rates for genital-tract infections ( syphilis , genital ulcer disease [ GUD ] , Neisseria gonorrhoeae infection , Chlamydia trachomatis infection , Trichomonas vaginalis infection , vulvovaginal c and idiasis , and bacterial vaginosis ) in HIV-1-seropositive versus HIV-1-seronegative women , after controlling for sexual behavior and other potential confounding factors . RESULTS HIV-1 infection was associated with a significantly higher incidence of GUD ( hazard ratio [ HR ] , 2.8 ; 95 % confidence interval [ CI ] , 2.0 - 3.9 ) , gonorrhea ( HR , 1.6 ; 95 % CI , 1.1 - 2.2 ) , and vulvovaginal c and idiasis ( HR , 1.5 ; 95 % CI , 1.3 - 1.8 ) . The risks of GUD and vulvovaginal c and idiasis increased with progressive levels of immunosuppression . CONCLUSIONS The increased incidence of genital-tract infections among HIV-1-seropositive women could promote the spread of both HIV-1 and other STDs , particularly in areas where these conditions are highly prevalent Objective : To examine the effect of a 15-session individually delivered cognitive behavioral intervention on antiretroviral ( ART ) medication adherence . Design : A multisite , 2-group , r and omized controlled trial . Participants : Two hundred four HIV-infected participants with self-reported ART adherence < 85 % from a total of 3818 participants screened were r and omized into the trial . Potential participants were recruited for the main trial based on sexual risk criteria in Los Angeles , Milwaukee , New York , and San Francisco . Intervention : The primary outcome of the intervention was a reduction in HIV transmission risk behaviors . Fifteen 90-minute individually delivered sessions were divided into 3 modules : Stress , Coping , and Adjustment ; Safer Behaviors ; and Health Behaviors , including an emphasis on ART adherence . Controls received no intervention until trial completion . Both groups completed follow-up assessment s at 5 , 10 , 15 , 20 , and 25 months after r and omization . Main Outcome Measure : Self-reported ART adherence as measured by 3-day computerized assessment . Results : A significance difference in rates of reported adherence was observed between intervention and control participants at months 5 and 15 , corresponding to the assessment s after the Stress , Coping , and Adjustment module ( 5-month time point ) and after the Health Behaviors module ( 15-month time point ) . The relative improvements among the intervention group compared with the control group dissipated at follow-up . Conclusions : Cognitive behavioral intervention programs may effectively improve ART adherence , but the effects of intervention may be short-lived OBJECTIVES We examined the efficacy of the Healthy Living Program in reducing risky sexual behavior and substance use among adults with HIV infection who were marginally housed ( i.e. , homeless at some point over a 37-month period ) . METHODS We had previously conducted a r and omized controlled trial with 936 adults living with HIV infection . In that study , 3 intervention modules of 5 sessions each addressed different goals : reducing risky sexual acts and drug use , improving the quality of life , and adhering to healthful behaviors . Participants were interviewed at baseline and at 5 , 10 , 15 , 20 , and 25 months ; 746 completed 4 or more assessment s. In this study , we analyzed sexual behavior and drug use outcomes for the 35 % ( n = 270 of 767 ) of participants who were considered marginally housed . RESULTS Among the marginally housed participants , there were significantly greater reductions in unprotected risky sexual acts , the number of sexual partners of HIV negative or unknown serostatus , alcohol or marijuana use , and hard drug use among the intervention group than among the control group . CONCLUSIONS Intensive , skill-focused intervention programs may improve the lives of marginally housed adults living with HIV infection Objective : To determine the association between maternal syphilis and HIV mother-to-child transmission ( MTCT ) . Design : Prospect i ve cohort study . Methods : Pregnant women admitted at Queen Elizabeth Central Hospital ( Malawi ) in late third trimester were screened for HIV ( by HIV rapid tests ) and syphilis ( by rapid plasma regain test and Treponema pallidum hemagglutination assay ) . HIV-infected women and their infants received nevirapine , according to the HIVNET 012 protocol . They were followed up at 6 and 12 weeks postpartum . Infant HIV infection was diagnosed by DNA PCR . Findings : Of the 1155 HIV-infected women enrolled , 1147 had syphilis test results , of whom 92 ( 8.0 % ) were infected . Only 751 HIV-positive women delivered live singleton infants who were tested for HIV at birth . Of these , 65 ( 8.7 % ) were HIV-infected , suggesting in utero ( IU ) HIV MTCT . Of the 686 infants who were HIV-negative at birth , 507 were successfully followed up . Of these , 89 ( 17.6 % ) became HIV-infected , suggesting intrapartum/postpartum ( IP/PP ) HIV MTCT . Maternal syphilis was associated with IU HIV MTCT , after adjusting for maternal log10 HIV-1 viral load and low birth weight ( LBW ) [ adjusted relative risk ( ARR ) , 2.77 ; 95 % CI , 1.40–5.46 ] . Furthermore , maternal syphilis was associated with IP/PP HIV MTCT ( ARR , 2.74 ; 95 % CI , 1.58–4.74 ) , after adjusting for recent fever , breast infection , LBW and maternal log10 HIV-1 viral load . Conclusion : Maternal syphilis is associated with IU and IP/PP HIV MTCT . Screening and early treatment of maternal syphilis during pregnancy may reduce pediatric HIV infections Care and support should play a critical role in assisting people who are HIV-positive to underst and the need for prevention and to enable them to protect others . Differences in sexual risk reduction among 154 newly diagnosed HIV-positive individuals from semi-urban Tanzania were examined using a r and omized control design , which assigned a control group to regular health services and an experimental group to enhanced care and support . Data were collected at baseline , three months and six months on self-reported sexual risk behaviours , disclosure of serostatus , reproductive health and psychosocial support . Over the six-month period , significant risk reduction occurred among both groups , with most of the behaviour change occurring during the first three months , e.g. 86 respondents ( 56 % ) reported condom use at last intercourse at 3 months compared with 24(16 % ) at baseline ( p = 0.05 ) . Extra care and support did not lead to increased risk reduction among the experimental group . The study population as a whole significantly changed their behaviour , suggesting that in the short term , learning one is HIV-positive has an impact on risk reduction Sexual risk behavior interventions in sub-Saharan Africa focus predominantly on individual and couples counseling . This cognitive-behavioral group intervention was adapted from an urban US context to urban Zambia . Preliminary data analyses assessed the influence of partner participation on sexual risk behavior among HIV-positive Zambian women . Female participants ( n=180 ) attended four group intervention sessions and received sexual behavior skill training and male and female condoms ; male partners ( n=152 ) were r and omly assigned to high-or low-intensity genderconcordant group intervention sessions . Sexual risk behavior , strategies , attitudes , and knowledge were assessed at baseline , 6 , and 12 months . At baseline , 19 % of males reported using alcohol before sex , 10 % reported using alcohol to cope , and negative coping was associated with sexual risk behavior . In contrast , 1 % of women reported using alcohol before sex , and 15 % used alcohol as an HIV-coping strategy . Consistent barrier use was reported by 48 % of women and 74 % of men . After intervention , female high intensity participants reported higher rates of condom use ( F=5.68 , P=.02 ) , more positive condom attitudes , safer sex intentions , and less alcohol use . These findings highlight the influence of male partners in implementation of effective risk reduction interventions There is an urgent need for the development and implementation of effective and feasible behavioral HIV and STD interventions . The purpose of the present r and omized controlled trial was to evaluate the effectiveness of a single-session , skill-based sexual risk reduction intervention for women . Participants were assessed at baseline and at 1 month and 3 months following the intervention on measures of AIDS knowledge , behavioral intentions , self-efficacy , and sexual risk behavior . Compared with women in an AIDS-education-only condition , women receiving the skill-based intervention reported significantly higher rates of condom use at 3-month follow-up . Results suggest that brief sexual risk reduction programs are feasible and effective within a community setting To determine the effects of plasma , genital , and breast milk human immunodeficiency virus type 1 ( HIV-1 ) and breast infections on perinatal HIV-1 transmission , a nested case-control study was conducted within a r and omized clinical trial of breast-feeding and formula feeding among HIV-1-seropositive mothers in Nairobi , Kenya . In analyses comparing 92 infected infants with 187 infants who were uninfected at 2 years , maternal viral RNA levels > 43,000 copies/mL ( cohort median ) were associated with a 4-fold increase in risk of transmission ( 95 % confidence interval [ CI ] , 2.2 - 7.2 ) . Maternal cervical HIV-1 DNA ( odds ratio [ OR ] , 2.4 ; 95 % CI , 1.3 - 4.4 ) , vaginal HIV-1 DNA ( OR , 2.3 ; 95 % CI , 1.1 - 4.7 ) , and cervical or vaginal ulcers ( OR , 2.7 ; 95 % CI , 1.2 - 5.8 ) were significantly associated with infant infection , independent of plasma virus load . Breast-feeding ( OR , 1.7 ; 95 % CI , 1.0 - 2.9 ) and mastitis ( relative risk [ RR ] , 3.9 ; 95 % CI , 1.2 - 12.7 ) were associated with increased transmission overall , and mastitis ( RR , 21.8 ; 95 % CI , 2.3 - 211.0 ) and breast abscess ( RR , 51.6 ; 95 % CI , 4.7 - 571.0 ) were associated with late transmission ( occurring > 2 months postpartum ) . Use of methods that decrease infant exposure to HIV-1 in maternal genital secretions or breast milk may enhance currently recommended perinatal HIV-1 interventions Healthy Relationships is a small-group , social cognitive theory-based HIV prevention intervention design ed for people living with HIV/AIDS . The Healthy Relationships intervention was demonstrated effective in a controlled r and omized clinical trial . The intervention also integrated stress reduction with sexual risk reduction techniques , but the mental health outcomes from the intervention have not yet been reported . This study examined the 6-month follow-up mental health outcomes of the Healthy Relationships intervention among 81 HIV-positive study participants ( 45 in the Healthy Relationships condition and 36 in the health maintenance control condition ) who reported sexual relationships with HIV-negative or unknown HIV status ( nonconcordant ) partners . Compared with the time-matched control condition , the Healthy Relationships intervention demonstrated significant reductions in perceived HIV-related stress . There was also evidence that reductions in perceived HIV-related stress mediated the intervention effects on sexual risk behaviors with nonconcordant partners . Results have implication s for design ing the next generation of HIV prevention interventions targeted to people living with HIV/AIDS The relationship between sexual abuse and sexually transmitted disease ( STD ) represents an important and underinvestigated context of domestic violence . This study examined the association between sexual abuse , sexual risk behaviors , and risk for reinfection and HIV among minority women with STD . Mexican American and African American women ( n = 617 ) with active STD entered a r and omized study of behavioral intervention to reduce STD recurrence . Each underwent question ing at entry regarding sexual abuse and sexual risk behaviors . Comparisons of these behaviors using chi-square , t tests , and logistic regression were made by history of sexual abuse . Sexually abused women were more likely to have lower incomes , earlier coitus , STD history , currently abusive partners , new sex partners , anal sex , and bleeding with sex , placing them at increased risk for STD reinfection and HIV . Due to this association with sexual risk behavior , assessment for sexual abuse is essential in programs focusing on STD/HIV prevention Abstract This study assessed and compared the efficacy of culturally tailored behavioral interventions to increase use and acceptability of sexual barrier products among HIV-positive women in Zambia . It also sought to evaluate cultural preferences as facilitators or impediments to potential use of vaginal chemical barriers for sexual risk reduction within the Zambian context . Women ( N=240 ) , recruited from the University Teaching Hospital HIV Voluntary Counseling and Testing Center , were r and omized into group or individual intervention arms . Participants attended a baseline assessment , three intervention sessions and follow up assessment s at six and 12 months . All participants increased use and acceptability of female condoms and vaginal products and maintained male condom use at six and 12 months . Preliminary data indicated that group participants increased male condom use at six months and trial use and acceptability of female condoms and lubricants predicted their use in the group condition . Results support group interventions to increase sexual barrier use and acceptability in HIV-positive women within the Zambian context . From a public health st and point , groups may represent a cost-effective and culturally congruent intervention This article reports pilot data from a newly developed disclosure intervention and associated measures specifically tailored for disclosure to casual sexual partners . Treatment consisted of a four-session , theoretically driven intervention focusing on the costs and benefits of disclosure . Using a r and omized control , crossover design 77 men were r and omized into one of three conditions ( wait-list control , facilitator only , and computer and facilitator ) . Results of the study suggest that facilitated administration of the pilot intervention was effective in reducing mean scores on the HIV disclosure behavior and attitude scales and that these reductions were both statistically and practically significant The NIMH Healthy Living Project ( HLP ) , a r and omized behavioral intervention trial for people living with HIV , enrolled 943 individuals , including women , heterosexual men , injection drug users , and men who have sex with men from Los Angeles , Milwaukee , New York , and San Francisco . The intervention , which is based on qualitative formative research and Ewart 's Social Action Theory , addresses three interrelated aspects of living with HIV : stress and coping , transmission risk behavior , and medication adherence . Fifteen 90-minute structured sessions , divided into 3 modules of five sessions each , are delivered to individuals . Sessions are tailored to individuals within a structure that uses role-plays , problem solving , and goal setting techniques . A ' Life Project'--or overarching goal related to personal striving-provides continuity throughout sessions . Because this is an ongoing project with efficacy yet to be established , we do not report intervention outcomes . However , the intervention was design ed to be useful for prevention case management , setting s where repeated one-on-one contact is possible , and where a structured but highly individualized intervention approach is desired Questions remain regarding the clinical utility of psychological interventions for HIV-positive persons because r and omized controlled trials have utilized stringent inclusion criteria and focused extensively on gay men . The present r and omized controlled trial examined the efficacy of a 15-session , individually delivered cognitive-behavioral intervention ( n = 467 ) compared to a wait-list control ( n = 469 ) in a diverse sample of HIV-positive persons who reported HIV transmission risk behavior . Five intervention sessions that dealt with executing effective coping responses were delivered between baseline and the 5 months post-r and omization . Additional assessment s were completed through 25 months post-r and omization . Despite previously documented reductions in HIV transmission risk , no intervention-related changes in psychosocial adjustment were observed across the 25-month investigation period . In addition , there were no intervention effects on psychosocial adjustment among individuals who presented with mild to moderate depressive symptoms . More intensive mental health interventions may be necessary to improve psychosocial adjustment among HIV-positive individuals Objective . The authors used data from a larger study to evaluate the long-term effects of a peer advocate intervention on condom and contraceptive use among HIV-infected women and women at high risk for HIV infection . Methods . HIV-infected women in one study and women at high risk for HIV infection in a second study were selected from the Women and Infants Demonstration Project and assigned to a st and ard or an enhanced HIV prevention treatment group . The enhanced intervention included support groups and one-on-one contacts with peer advocates tailored to clients ' needs . The authors interviewed women at baseline and at 6- , 12- and 18-months , and measured changes in consistency of condom and contraceptive use and in self-efficacy and perceived advantages and disadvantages of condom and contraceptive use . Results . Of HIV-infected women , the enhanced group had improved consistency in condom use , increased perceived advantages of condom use , and increased level of self-efficacy compared with the st and ard group . Of women at risk , the enhanced intervention group at six months maintained consistent condom use with a main partner and perceived more benefit of condom use compared with the st and ard group . These differences diminished at 12 months . Conclusions . The enhanced intervention was generally effective in the HIV+ study . In the at-risk study , however , intervention effects were minimal and short-lived . Factors related to the theory , intervention design , and sample characteristics help explain these differences Abstract The prevalence of HIV infection continues to increase among women in South Africa while there are few interventions specifically targeting condom use promotion in this population . We report the results of an experimental pilot study of a health education intervention aim ed at enhancing coping skills and consistent condom use among HIV-positive women attending primary health clinics in the Western Cape province of South Africa . One hundred and twenty women were r and omised into the intervention condition or a control condition . Both groups completed an interviewer administered question naire that included measures of self-esteem , attitude towards condom use , and self-efficacy towards condom use and negotiating condom use , and provided vaginal swab specimen at baseline and three months after the intervention . Tests for intervention effects at three months while controlling for baseline revealed that only self-esteem was significantly higher in the intervention group relative to the control group . No significant differences were found on measures of coping skills and condom use behaviour . Importantly , incidence for Chlamydia Trachomatis , Neisseria Gonorrhea and Trichomona vaginalis during the study period were significantly lower in the intervention group than the control group . These results are strong indications that this intervention could serve as a basis for the development of potentially effective interventions to reduce STI-related sexual risk behaviours among HIV-positive black women in South Africa Abstract The present study evaluated the efficacy of an individualized psycho-education ( PE ) program in reducing psychological distress and risky sexual behavior and enhancing self-disclosure associated with an HIV diagnosis among attendees of a walk-in non-governmental voluntary counseling and testing ( VCT ) center in Nigeria . Ninety-four consecutive individuals were asked to complete a pre-counseling , baseline question naire detailing their sociodemographic characteristics , psychopathology , sexual practice s , self-disclosure intention and coping behaviors . They were screened for HIV and post-test counseled . Sixty-seven individuals ( 72.2 % ) who tested positive were consecutively r and omly assigned to one of two groups : a PE program ( four 60-minute weekly manual driven sessions ) ( N=34 ) and a wait-list ( WL ) control group ( N=33 ) . The major outcome measures used were the Crown Crisp Experiential Index ( CCEI ) , the Beck Depression Inventory ( BDI ) ( Beck et al. , ( 1961 ) , self-report sexual practice s in past three months , self-disclosure intention and the brief COPE . At four weeks post-intervention , significant reductions on all measures as well as reduction in risky sexual practice s were observed in the treatment group compared with the wait-list group . Treatment group members were also significantly more likely to disclose their serostatus and accept their HIV status as a way of coping , compared with the wait-list group . Overall , support was found for the efficacy of a manual-driven PE program for self-disclosure , reduction of depression and improvement in safe sexual practice OBJECTIVE To develop and test an HIV intervention targeting sex workers and madams in the brothels of Bombay . SUBJECTS AND METHODS In a controlled intervention trial , with measurements before and after the intervention , 334 sex workers and 20 madams were recruited from an intervention site , and 207 and 17 , respectively , from a similar control site , both in red-light areas of Bombay . All sex workers were tested for antibodies to HIV and syphilis , and for hepatitis B surface antigen . Information on sexual practice s , condom use and knowledge of HIV was collected by interviewer-administered question naire . All subjects in the intervention group underwent a 6-month program of educational videos , small group discussion s and pictorial educational material s ; free condoms were also distributed . The blood tests and the question naire were readministered to all subjects at both sites immediately after the intervention . Both groups were followed for approximately 1 year . RESULTS The baseline level of knowledge about HIV and experience with condoms was extremely low among both sex workers and madams . The baseline prevalence of HIV antibodies was 47 % in the intervention group and 41 % in the control group ( P = 0.17 ) . The incidence densities for HIV and sexually transmitted diseases were significantly different in the two groups ( all P < 0.005 ) : 0.05 and 0.16 per person-year of follow-up for HIV , 0.08 and 0.22 per person-year for antibodies to syphilis , and 0.04 and 0.12 per person-year for hepatitis B surface antigen in the intervention and control women , respectively . Following the intervention , women reported increased levels of condom use , and some ( 41 % ) said they were willing to refuse clients who would n't use them . However , both the sex workers and the madams were concerned about losing business if condom use was insisted upon . CONCLUSIONS Both HIV prevalence and incidence are alarmingly high among female sex workers in Bombay . Successful interventions can be developed for these women , and even a partial increase in condom use may decrease the transmission of HIV and sexually transmitted diseases . Intervention programs of longer duration that target madams and clients and make condoms easily available are urgently needed at multiple sites in red-light areas Objectives To assess the effectiveness of an intervention for providing information , and support to HIV-positive donors on changes in their sexual behavior , and to assess which donor characteristics are predictive of behavior change . Design Subjects were r and omly assigned to a structured intervention or community referral group . Follow-up assessment s were conducted every 6 months . Setting New York City , New York , USA . Participants A cohort of 271 HIV-infected persons who donated blood to the New York Blood Center . InterventionDonors r and omized to the structured intervention program met individually with a nurse for counseling , and were offered a six-session support group . The program was design ed to provide information , encourage safer sexual behavior , and provide support . Main outcome measures Sexual behavior , psychological distress , and psychological help seeking , and immune function . Results In both groups there was a large decrease over time in reports of unsafe sexual activity . However , more than 30 % of participants in both groups reported unsafe sexual activity at the 1-year follow-up visit . Donors r and omized to the structured intervention program did not report significantly more behavior change at the 1-year follow-up . Conclusions Better programs to promote behavior change in seropositive individuals are needed Objective : To provide an overview of the National Institute of Mental Health Multisite HIV/sexually transmitted disease ( STD ) Prevention Trial for African American Couples conducted in 4 urban areas : Atlanta , Los Angeles , New York , and Philadelphia . The rationale , study design methods , proposed data analyses , and study management are described . Design : This is a 2-arm r and omized trial , implementing a modified r and omized block design , to evaluate the efficacy of a couples-based intervention design ed for HIV-serodiscordant African American couples . Methods : The study phases consisted of formative work , pilot studies , and a r and omized clinical trial . The sample is 535 HIV-serodiscordant heterosexual African American couples . There are 2 theoretically derived behavioral interventions with 8 group and individual sessions : the Eban HIV/STD Risk Reduction Intervention ( treatment ) versus the Eban Health Promotion Intervention ( control ) . The treatment intervention was couples based and focused on HIV/STD risk reduction whereas the control was individual based and focused on health promotion . The 2 study conditions were structurally similar in length and types of activities . At baseline , participants completed an audio computer-assisted self-interview and interviewer-administered question naire and provided biological specimens to assess for STDs . Similar follow-up assessment s were conducted immediately after the intervention , at 6 months , and at 12 months . Results : The trial results will be analyzed across the 4 sites by r and omization assignment . Generalized estimating equations and mixed-effects modeling are planned to test : ( 1 ) the effects of the intervention on STD incidence and condom use and on mediator variables of these outcomes and ( 2 ) whether the effects of the intervention differ depending on key moderator variables ( eg , gender of the HIV-seropositive partners , length of relationship , psychological distress , sexual abuse history , and substance abuse history ) . Conclusions : The lessons learned from the design and conduct of this clinical trial provide guidelines for future couples-based clinical trials in HIV/STD risk reduction and can be generalized to other couples-based behavioral interventions Objective : To evaluate the feasibility , fidelity , and effectiveness of a human immunodeficiency virus ( HIV ) prevention intervention delivered to HIV-infected patients by counselors during routine clinical care in KwaZulu-Natal , South Africa . Methods : A total of 152 HIV-infected patients , aged 18 years and older , receiving clinical care at an urban hospital in South Africa , were r and omly assigned to intervention or st and ard-of-care control counselors . Intervention counselors implemented a brief risk reduction intervention at each clinical encounter to help patients reduce their unprotected sexual behavior . Self-report question naires were administered at baseline and 6 months to assess number of unprotected sex events in previous 3 months . Results : Intervention was delivered in 99 % of routine patient visits and included a modal 8 of 8 intervention steps . Although HIV-infected patients in both conditions reported more vaginal and anal sex events at 6-month follow-up than at baseline , patients who received the counselor-delivered intervention reported a significant decrease over time in number of unprotected sexual events . There was a marginally significant increase in these events among patients in the st and ard-of-care control condition . Conclusions : A counselor-delivered HIV prevention intervention targeting HIV-infected patients seems to be feasible to implement with fidelity in the South African clinical care setting and effective at reducing unprotected sexual behavior Results of a r and omized controlled trial show that a behavioral intervention grounded in social cognitive theory reduces unprotected sexual behaviors among men and women living with HIV infection , with the greatest reductions in HIV transmission risk behaviors occurring with non-HIV-positive sex partners . In this article , the authors describe the intervention development and intervention content of the social cognitive risk reduction intervention for HIV-positive persons . The effective five group session intervention focused on enhancing motivation through self-reflection and developing coping efficacy skills for HIV disclosure decision making , active listening , assertiveness , and problem solving for disclosure and transmission risk reduction behaviors . Intervention components were tailored for gender and sexual orientation and integrated skills practice sessions used role-plays couched within scenes from popular films . This intervention was demonstrated to be effective in a community-service delivery setting and can be adapted for implementation in HIV-related services delivered within support groups Objective To evaluate the efficacy of an intervention to reduce HIV transmission risk behaviors and sexually transmitted diseases ( STDs ) and enhance HIV-preventive psychosocial and structural factors among women living with HIV . Design A r and omized controlled trial of 366 women living with HIV in Alabama and Georgia . InterventionThe intervention emphasized gender pride , maintaining current and identifying new network members , HIV transmission knowledge , communication and condom use skills , and healthy relationships . Primary Outcome Unprotected vaginal intercourse . Other Outcomes Proportion never used condoms , incident STDs , psychosocial factors , and number of supportive network members . Results Over the 12-month follow-up , women in the WiLLOW intervention , relative to the comparison , reported fewer episodes of unprotected vaginal intercourse ( 1.8 vs. 2.5 ; P = 0.022 ) ; were less likely to report never using condoms ( odds ratio [ OR ] = 0.27 ; P = 0.008 ) ; had a lower incidence of bacterial infections ( Chlamydia and gonorrhea ) ( OR = 0.19 ; P = 0.006 ) ; reported greater HIV knowledge and condom use self-efficacy , more network members , fewer beliefs that condoms interfere with sex , and fewer partner-related barriers to condom use ; and demonstrated greater skill in using condoms . Conclusion This is the first trial to demonstrate reductions in risky sexual behavior and incident bacterial STDs and to enhance HIV-preventive psychosocial and structural factors among women living with HIV Abstract The purpose of this study was to evaluate a novel psycho-educational intervention intended to increase patients ’ medication preparedness and treatment adherence skills before initiating highly active antiretroviral therapy ( HAART ) . Sixty-three HIV-positive patients not currently on antiretroviral therapy participated in a r and omized controlled trial of a st and ardized , four-session psycho-educational intervention ( Supportive Therapy for Adherence to Antiretroviral Treatment ; STAART ) . Session topics included learning techniques to increase medication adherence and learning effective strategies to cope with stress and depression . Patients completed psychological question naires assessing psychological readiness to initiate HAART and depressed mood . They completed both measures at study baseline and at four-weeks post-baseline . After controlling for baseline medication readiness scores , intervention patients ( n=30 ) reported significantly higher mean medication readiness following the STAART intervention ( four-weeks post-baseline ) ( 27.3±6.9 ) compared to controls ( n=33 ; 24.6±9.9 ; p<0.05 ) . Among depressed patients ( n=27 ) , those receiving the intervention ( n=15 ) reported significantly lower mean depression scores at four-weeks post-baseline ( 22.5±12.9 ) compared to controls ( n=12 ; 27±9.9 ; p<0.05 ) . The STAART intervention enhanced HIV treatment readiness by better preparing patients prior to initiating HAART . It was also beneficial for reducing depressive symptoms in depressed , HIV-positive patients This study piloted a brief individual motivational intervention targeting multiple health risk behaviors in HIV-positive youth aged 16 - 25 . Interviews about sexual behavior and substance use and viral load testing were obtained from 51 HIV-positive youth at baseline and post intervention . Youth were r and omized to receive a four-session motivational enhancement intervention ( N = 25 ) or to a wait-list control ( N = 26 ) . Of the eligible youth approached , 88 % agreed to participate , and 80 % percent of participants completed at least three of four sessions . The treatment group showed significantly greater reductions in unprotected sex acts and in viral load compared with controls . Although change scores for substance use were not significantly different between the two groups , paired t tests demonstrated that reductions in alcohol use and marijuana use were significant for the treatment group at the trend level . There were no significant differences in substance use from baseline to posttest for the control group . Findings demonstrate the potential of a brief motivational enhancement intervention to improve health risk behaviors in HIV-positive youth . Larger r and omized clinical trials are warranted . Re sources required for retention should not be underestimated Objective : To compare the HIV transmission risk among patients r and omized to episodic versus continuous antiretroviral therapy . Design : This was a sub study of the Strategies of Management of Antiretroviral Therapy study , in which patients were r and omized to continuous versus CD4 + -guided episodic antiretroviral therapy . Participants were surveyed about sexual activity and needle sharing and had laboratory testing for gonorrhea , chlamydia , and syphilis . Results : A total of 883 patients were enrolled in this study , the mean age of the patients was 45 years , 25 % were women , and 78 % were on antiretroviral therapy . At baseline , 136 participants ( 15.4 % ) had high-risk behavior ( vaginal or anal sex without a condom , needle sharing , or incident bacterial sexually transmitted infection ) . After r and omization , the proportion of participants reporting high-risk behavior was stable and did not differ by r and omized arm ( P = 0.39 ) . Among participants off therapy at baseline , high-risk behavior was less common 4 months after r and omization among those who were r and omized to start antiretroviral therapy ( P = 0.03 ) . HIV transmission risk ( high-risk behavior while HIV RNA level > 1500 copies/mL ) with partners perceived to be HIV uninfected was higher in the episodic therapy arm ( P = 0.02 ) . Conclusions : Patients on episodic antiretroviral therapy did not decrease high-risk behavior , and because HIV RNA levels were higher , this strategy may result in increased HIV transmission Background : Although several studies have characterized patterns and predictors of continued risky sexual behavior in HIV-infected rural persons , far less research has evaluated interventions to reduce risky sex in this group . This pilot r and omized clinical trial compared 2 brief telephone-administered interventions design ed to reduce continued risky sexual behaviors in HIV-infected rural persons . Methods : Participants were 79 HIV-infected rural persons who reported 1 or more occasions of unprotected anal , vaginal , or oral sex in the past 2 months . Participants were recruited through AIDS service organizations in rural areas of 27 states and assigned r and omly to either a 2-session , motivational interviewing plus skills-building intervention ( i.e. , integrated intervention ; n = 48 ) or a 2-session , skills-building only comparison intervention ( n = 31 ) . Participants completed self-report measures of sexual behaviors and factors related to risky sex at preintervention and 2-month follow-up . Results : Before enrolling into the intervention , 37 % of participants had 2 or more sexual partners in the past 2 months , 29 % had sex with 1 or more partners without knowing their partners ' HIV serostatus , and almost one-third of participants located sex partners in high-risk environments ( e.g. , public parks , roadside rest areas ) . A 2 × 2 repeated measures multivariate analyses of variance found that integrated intervention participants reported greater increases in risk-reduction motivation and greater increases in condom-protected vaginal and oral intercourse occasions at follow-up compared to skills-building only participants . Conclusions : Brief telephone-administered interventions that integrate motivational interviewing with skills-building show potential to reduce risky sexual behaviors in HIV-infected rural persons . Additional and large-scale evaluations of this intervention approach appear warranted |
12,356 | 27,147,384 | A wide range of outcomes assessing impairments , activities and participation were assessed but the findings were mixed . | OBJECTIVE To establish the current evidence base for the use of orthotics and taping for people with osteoporotic vertebral fracture ( OVF ) . | To comprehend the results of a r and omised controlled trial ( RCT ) , readers must underst and its design , conduct , analysis , and interpretation . That goal can be achieved only through total transparency from authors . Despite several decades of educational efforts , the reporting of RCTs needs improvement . Investigators and editors developed the original CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to help authors improve reporting by use of a checklist and flow diagram . The revised CONSORT statement presented here incorporates new evidence and addresses some criticisms of the original statement . The checklist items pertain to the content of the Title , Abstract , Introduction , Methods , Results , and Discussion . The revised checklist includes 22 items selected because empirical evidence indicates that not reporting this information is associated with biased estimates of treatment effect , or because the information is essential to judge the reliability or relevance of the findings . We intended the flow diagram to depict the passage of participants through an RCT . The revised flow diagram depicts information from four stages of a trial ( enrolment , intervention allocation , follow- up , and analysis ) . The diagram explicitly shows the number of participants , for each intervention group , included in the primary data analysis . Inclusion of these numbers allows the reader to judge whether the authors have done an intention- to-treat analysis . In sum , the CONSORT statement is intended to improve the reporting of an RCT , enabling readers to underst and a trial 's conduct and to assess the validity of its results BACKGROUND Greater thoracic kyphosis is associated with increased biomechanical loading of the spine which is potentially problematic in individuals with osteoporotic vertebral fractures . Conservative interventions that reduce thoracic kyphosis warrant further investigation . This study aim ed to investigate the effects of therapeutic postural taping on thoracic posture . Secondary aims explored the effects of taping on trunk muscle activity and balance . METHODS Fifteen women with osteoporotic vertebral fractures participated in this within-participant design study . Three taping conditions were r and omly applied : therapeutic taping , control taping and no taping . Angle of thoracic kyphosis was measured after each condition . Force plate-derived balance parameters and trunk muscle electromyographic activity ( EMG ) were recorded during three static st and ing tasks of 40s duration . RESULTS There was a significant main effect of postural taping on thoracic kyphosis ( p=0.026 ) , with a greater reduction in thoracic kyphosis after taping compared with both control tape and no tape . There were no effects of taping on EMG or balance parameters . CONCLUSIONS The results of this study demonstrate that the application of postural therapeutic tape in a population with osteoporotic vertebral fractures induced an immediate reduction in thoracic kyphosis . Further research is needed to investigate the underlying mechanisms associated with this decrease in kyphosis Background It is possible that cross-over studies included in current systematic review s are being inadequately assessed , because the current risk of bias tools do not consider possible biases specific to cross-over design . We performed this study to evaluate whether this was being done in cross-over studies included in Cochrane Systematic Review s ( CSRs ) . Methods We search ed the Cochrane Library ( up to 2013 issue 5 ) for CSRs that included at least one cross-over trial . Two authors independently undertook the study selection and data extraction . A r and om sample of the CSRs was selected and we evaluated whether the cross-over trials in these CSRs were assessed according to criteria suggested by the Cochrane h and book . In addition we reassessed the risk of bias of these cross-over trials by a checklist developed form the Cochrane h and book . Results We identified 688 CSRs that included one or more cross-over studies . We chose a r and om sample of 60 CSRs and these included 139 cross-over studies . None of these CSRs undertook a risk of bias assessment specific for cross-over studies . In fact items specific for cross-over studies were seldom considered anywhere in quality assessment of these CSRs . When we reassessed the risk of bias , including the 3 items specific to cross-over trials , of these 139 studies , a low risk of bias was judged for appropriate cross-over design in 110(79 % ) , carry-over effects in 48(34 % ) and for reporting data in all stages of the trial in 114(82 % ) . Assessment of biases in cross-over trials could affect the GRADE assessment of a review ’s findings . Conclusion The current Cochrane risk of bias tool is not adequate to assess cross-over studies . Items specific to cross-over trials leading to potential risk of bias are generally neglected in CSRs . A proposed check list for the evaluation of cross-over trials is provided OBJECT External supports serve as a traditional treatment option for osteoporotic vertebral fractures ( OVFs ) . However , the role of external supports in the treatment of OVF remains inconclusive . The purpose of this study was to determine the role of a rigid external support in the healing of OVFs by prospect ively evaluating union ( fracture settling ) rates and prognostic variables for patients suffering from an incident OVF . METHODS Fifty-five patients with acute back pain were enrolled in this study after being diagnosed with an OVF based on MRI findings . Patients were treated using a plastic thoracolumbosacral orthosis ( TLSO ) and underwent follow-up at 2 , 3 , and 6 months . Vertebrae were referred to as " settled " when there was no dynamic mobility on sitting lateral and supine lateral radiographs . At the time of the 3- and 6-month follow-up visits , the patients were divided into 2 groups , the " settled group " and the " unsettled group . " Patients in these groups were compared with regard to clinical and radiographic features . RESULTS Of the 55 patients enrolled , 53 patients were followed up for 6 months . There were 14 men and 39 women with an average age of 75.3 years . Fracture settling of the affected vertebra was defined in 54.7 % of the patients at 2 months , in 79.2 % at 3 months , and in 88.7 % at 6 months . All 5 components of the Japanese Orthopaedic Association Back Pain Evaluation Question naire improved significantly both at 3 months and 6 months . Patients in the unsettled group exhibited a statistically greater likelihood of having fractures at the thoracolumbar junction , Type A3 fractures , and fractures with a diffuse low-intensity area on T2-weighted MRI studies at 3 months . In contrast , at 6 months , the only statistically significant difference between the groups was patient age . CONCLUSIONS The biomechanical disadvantages of OVFs ( location , type , and size ) adversely influencing the fracture healing were overcome by the treatment using a TLSO within 6 months . The authors ' findings show that a TLSO plays a biomechanical role in the healing of OVFs OBJECTIVE To assess the changes in static and dynamic balance and movement strategies in patients with severe osteoporotic vertebral compression fracture while wearing and not wearing the Knight-Taylor ( K-T ) spinal brace . SUBJECTS 47 patients with severe osteoporotic vertebral compression fracture , which was confirmed on radiographs and with bone density measurements obtained by dual energy X-ray absorption . INTERVENTION Patients were r and omly subjected to computerized dynamic posturography , which contained sensory organization tests , motor control balance test at 75 % limit of stability ( LOS ) in 8 movement directions , and left/right rhythmic weight shift test ( L/R RWS ) , while wearing and not wearing the K-T spinal brace , respectively . RESULTS Patients wearing the spinal brace had significantly increased average stability , significantly increased average maximal stability under the swayed vision with fixed support surface condition and under the eye open with swayed support surface condition , significantly increased ankle strategy and decreased average velocity of COG target sway under the eye open with swayed support surface condition , significantly reduced the frequency of falls under the eye closed with swayed support surface condition and swayed vision with swayed support surface condition , and significantly decreased in the percentage of directional control with no difference of reaction time in the LOS test , and an increase in the on-axis velocity in the L/R RWS test . CONCLUSIONS The K-T spinal brace efficiently enables the subjects to maintain static and dynamic motor balance . Its use decreases the fall frequency but limits the directional control in severe osteoporotic patients with vertebral compression fracture Summary In a prospect i ve cohort study of 395 geriatric out patients , mortality after 3 years was associated with prevalent vertebral fractures at baseline . The mortality risk was independently associated with the presence of three or more vertebral fractures at baseline . In the surviving patients , the risk of incident fractures was noteworthy , occurring in 26 % of these patients . Introduction The purpose of this study is to determine mortality rate and the incidence of vertebral fractures in a geriatric outpatient group , during a 3-year follow-up period , in a teaching hospital in Amsterdam , The Netherl and s. Methods This study includes a prospect i ve cohort study of 395 geriatric patients who had their baseline visit at a diagnostic day hospital in 2007 and 2008 . They were invited for follow-up 3 years later . Lateral X-rays of the lumbar spine and chest were performed at baseline and after 3 years ; vertebral fractures were scored in all patients according to the semi-quantitative method of Genant . Results After 3 years , mortality was 46 % and associated with prevalent vertebral fractures at baseline ( odds ratio ( OR ) , 1.83 ; 95 % CI , 1.23–2.74 ) . The presence of three or more vertebral fractures at baseline was an independent risk factor for mortality ( OR , 3.32 ; 95 % CI , 1.56–7.07 ) . Other independently associated risk factors were greater age , higher co-morbidity score , and having more prescriptions . Higher cognitive capacity protected against mortality after 3 years . In 72 patients , radiography was repeated . Nineteen patients ( 26 % ) had an incident radiographic vertebral fracture : 16 in those with a prevalent fracture , and 3 in those without a prevalent vertebral fracture at baseline . Conclusions In geriatric out patients , mortality after 3 years was associated with prevalent vertebral fractures at baseline , and the mortality risk was independently associated with 3 or more vertebral fractures at baseline . In survivors , the risk of incident fractures was noteworthy , since these occurred in 26 % of the patients , particularly in those with a prevalent vertebral fracture Objectives : We conducted a prospect i ve r and omized study to evaluate the efficacy of two newly developed spinal orthoses in patients with vertebral fractures . Design : We conducted a prospect i ve , r and omized , cross-over study to evaluate the efficacy of two newly developed spinal orthoses in patients with osteoporotic vertebral fractures . Measurements include trunk muscle strength , angle of kyphosis , body height , body sway , and parameters of quality -of-life such as pain , well-being , and limitations of daily living . Results : Wearing the orthosis Spinomed during a 6-mo period ( results of Spinomed active are given in parentheses ) was associated with a 72 % ( 64 % ) increase in back extensor strength ( P < 0.01 ) , a 44 % ( 56 % ) increase in abdominal flexor strength ( P < 0.01 ) , an 11 % ( 11 % ) decrease in the angle of kyphosis ( P < 0.01 ) , a 23 % ( 20 % ) decrease in body sway ( P = 0.03 and P = 0.02 ) , a 19 % ( 18 % ) increase in vital capacity ( P < 0.01 and P = 0.03 ) , a 41 % ( 47 % ) decrease in average pain ( P < 0.01 ) , an 18 % ( 18 % ) increase in well-being ( P < 0.01 ) , and a 49 % ( 54 % ) decrease in limitations of daily living ( P < 0.01 ) , respectively . The overall tolerability of the orthoses was good ; no adverse effects were reported and the dropout rate with 7 % was rather low . Conclusions : The use of an orthosis increases trunk muscle strength and therefore improves posture in patients with vertebral fractures caused by osteoporosis . In addition , a better quality -of-life is achieved by pain reduction , decreased limitations of daily living , and improved well-being . Thereby , the use of an orthosis may represent an efficacious nonpharmacologic treatment option for spinal osteoporosis Pfeifer M , Begerow B , Minne HW : Effects of a new spinal orthosis on posture , trunk strength , and quality of life in women with postmenopausal osteoporosis : A r and omized trial . Am J Phys Med Rehabil 2004;83:177–186 . Objective One fourth of women ≥50 yrs of age in the general population have one or more vertebral fractures . The orthotic treatment modality in the management of vertebral fractures caused by osteoporosis remains subjective because no objective data from clinical trials are available . The objective of this research was to evaluate the efficacy of a newly developed spinal orthosis in patients with osteoporotic vertebral fractures . Design We conducted a study that measured trunk muscle strength , angle of kyphosis , body height , body sway , and variables of quality of life such as pain , well-being , and limitations of daily living . Results Wearing the orthosis for 6-mo period was associated with a 73 % increase in back extensor strength , a 58 % increase in abdominal flexor strength , an 11 % decrease in angle of kyphosis , a 25 % decrease in body sway , a 7 % increase in vital capacity , a 38 % decrease in average pain , a 15 % increase in well-being , and a 27 % decrease in limitations of daily living . The overall tolerability of the orthosis was good , no side-effects were reported , and the drop-out rate of 3 % was rather low . Conclusions The use of an orthosis increases trunk muscle strength and thus improves posture in patients with vertebral fractures caused by osteoporosis . In addition , a better quality of life is achieved by pain reduction , decreased limitations of daily living , and improved well-being . Therefore , the use of an orthosis may represent an efficacious nonpharmacologic treatment option for spinal osteoporosis Background : Osteoporosis is one of the major health problems in aging population and may lead to osteoporotic vertebral fracture that causes severe back pain and reduced functional independency . Objectives : To compare the efficacy of SpinoMed ® and soft lumbar orthosis at the subacute stage ( the second and third weeks of disease onset ) of the patients with osteoporotic vertebral fracture . Study design : Prospect i ve r and omized trial , pilot trial . Methods : A total of 51 female subjects aged 55 years or above with osteoporotic vertebral fracture were r and omly distributed to the soft lumbar orthosis ( control group , n = 24 ) and SpinoMed ® ( test group , n = 27 ) groups after the acute stage ( the first week of disease onset ) . The pain level was assessed by obtaining verbally feedback in 10-point scale scoring , while functional mobility level was estimated with Functional Independence Measure-motor Scores , Elderly Mobility Scale , and Modified Functional Ambulation Category . The thoracic kyphosis angle was measured from st and ing X-ray on 10 out of 51 subjects . Results and Conclusion : Both groups showed significant reduction in the patients ’ pain level and limitations of daily life ( p < 0.05 ) . The effect of the two types of spinal orthoses on the pain level reduction and functional mobility level gain did not show significant difference ( p > 0.05 ) at the subacute stage . Clinical relevance In this study , SpinoMed ® could not provide additional treatment benefits to patients with osteoporotic vertebral fracture regarding pain relief and functional independence improvement at the subacute stage . The effects of SpinoMed ® in muscle-strengthening and thoracic kyphotic angle reduction for patients with osteoporotic vertebral fracture need to be further verified in a more intensive and longer-term training program BACKGROUND The efficacy of brace application for the treatment of osteoporotic compression fractures remains unclear . The purpose of this study was to compare the treatment outcomes in patients with osteoporotic compression fractures with regard to whether the patients had no braces , rigid braces , or soft braces . METHODS We r and omly assigned sixty patients with acute one-level osteoporotic compression fractures within three days of injury to the no-brace , soft-brace , and rigid-brace groups through 1:1:1 allocation . The primary outcome was the baseline adjusted Oswestry Disability Index score at twelve weeks after compression fracture . The non-inferior margin of the Oswestry Disability Index was set at an average of 10 points . RESULTS The baseline adjusted Oswestry Disability Index score at twelve weeks after compression fracture in the no-brace group was not inferior to that in the soft-brace or rigid-brace groups . The mean adjusted Oswestry Disability Index score was 35.95 points ( 95 % confidence interval , 25.42 to 46.47 points ) in the no-brace group and 37.83 points ( 95 % confidence interval , 26.77 to 48.90 points ) in the soft-brace group , with a difference of -1.88 points ( 95 % confidence interval , -7.02 to 9.38 points ) between the groups . Similarly , the mean adjusted Oswestry Disability Index score was 35.95 points ( 95 % confidence interval , 25.42 to 46.47 points ) in the no-brace group and 33.54 points ( 95 % confidence interval , 23.79 to 43.29 points ) in the rigid-brace group , with a difference of 2.41 points ( 95 % confidence interval , -7.86 to 9.27 points ) between the groups . During the follow-up assessment period , there was no significant difference among the groups for the overall Oswestry Disability Index scores ( p = 0.260 ) , visual analog scale for pain scores for back pain ( p = 0.292 ) , and anterior body compression ratios ( p = 0.237 ) . However , the Oswestry Disability Index scores and the visual analog scale scores for back pain significantly improved with time after the fractures ( p < 0.001 ) , and the body compression ratios significantly decreased with time in all three groups ( p < 0.001 ) . CONCLUSIONS The Oswestry Disability Index scores for the treatment of compression fractures without a brace were not inferior to those with soft or rigid braces . Moreover , the improvement in back pain and progression of anterior body compression were similar among the three groups . LEVEL OF EVIDENCE Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence |
12,357 | 25,779,378 | Conclusion The current prospect i ve evidence s are not sufficient to support the positive association between abortion ( including IA and SA ) and breast cancer risk | Objective Although positive association between abortion and breast cancer was frequently reported from case – control studies , results from prospect i ve studies were still unclear .
This study aim ed to evaluate this association based on prospect i ve studies . | Time-related effects of a pregnancy on breast cancer risk were examined in a population -based prospect i ve study of 802,457 parous Norwegian women aged 20 - 56 years . The mean follow-up time was 16.4 years . A total of 4787 women were diagnosed with breast cancer . We observed a short-term increase in risk of breast cancer after a full-term pregnancy , with a maximum 3 - 4 years after delivery , followed by a long-lasting decrease in risk . The maximum risk was about twice the risk for women whose last delivery was 20 or more years previously ( incidence rate ratio = 1.99 , 95 % confidence interval = 1.70 - 2.33 ) . Compared with nulliparous women , those with one or two children were at higher risk in the first decade after the last pregnancy , whereas those with three or more children were at lower risk in most categories of time since the last birth . The positive association between breast cancer risk and age at last birth was markedly reduced after adjustment for time since last birth . We conclude that there is a non-linear relationship between breast cancer incidence and time since last birth . Part of the relation with age at last birth may be attributed to the association with time since last birth Results from case-control studies suggest that induced abortion may be associated with a small increase in risk of breast cancer . While risk estimates from cohort studies have generally not observed such an association , these studies have had limited information regarding abortion and possible confounding variables . Therefore , we conducted a study among a cohort of post-menopausal women from whom detailed information regarding pregnancy outcomes as well as risk factors for breast cancer had been collected . The study sample included 37,247 Iowa Women 's Health Study participants , 55 - 64 years of age at baseline in 1986 , who reported no history of breast , or other , cancer ( except non-melanoma skin cancer ) , and for whom information regarding pregnancy outcomes ( that is , live birth , stillbirth , spontaneous abortion , ectopic pregnancy or induced abortion ) was available . We used linkage with records of the State Health Registry of Iowa , part of the National Cancer Institute 's Surveillance , Epidemiology , and End Results ( SEER ) program , to estimate the incidence of breast cancer among cohort members through 1995 . We calculated age-adjusted relative risks and 95 % confidence intervals using Cox proportional hazards regression . Only 653 women ( 1.8 % ) reported an induced abortion . The age-adjusted relative risk of breast cancer among women with prior induced abortion compared with those without was 1.1 ( 95 % CI = 0.8 - 1.6 ) . Relative risks were higher among women whose age at first abortion was less than 20 or at least 30 years , for those whose abortion took place after their first birth or who never gave birth , and for those with early termination ( 0 - 2 months ) . These estimates varied from 1.3 - 1.7 , but the confidence intervals around each were wide . Since most women in this cohort were beyond their reproductive years when abortion became legal in 1973 , the low prevalence of induced abortion argues for a cautious interpretation We investigated whether induced abortion is associated with breast cancer when lifestyle confounders , including smoking and alcohol consumption , are adjusted for . Design . Prospect i ve cohort study Abstract Objective : Previous studies of induced abortion and breast cancer may have been limited by differential reporting of abortion history . We conducted a population -based case – control study to evaluate abortion ( both induced and spontaneous ) and breast cancer risk . Methods : All study subjects were aged 20–69 years and members of Group Health Cooperative of Puget Sound ( GHC ) . Incident invasive breast cancer cases ( n = 138 ) were identified from the linkage between the GHC enrollment file and the Seattle – Puget Sound SEER Cancer Registry . Controls ( n = 252 ) were r and omly selected from GHC enrollment files and matched to cases on age and enrollment period . All subjects had to have been enrolled at GHC for the 2 years preceding diagnosis ( cases ) or reference ( controls ) date . The unified medical record of each case was abstract ed for pregnancy history , including prior induced and spontaneous abortions , menopause status , height and weight , screening practice s , and other risk factors . Results : Compared to all women who had never had an induced abortion , the multivariate adjusted relative risk of breast cancer in women with an induced abortion was 0.9 ( 95 % confidence interval 0.5–1.6 ) . This risk was similar in parous women , and nulliparous women . There was no association between spontaneous abortion and breast cancer risk . Conclusions : These results do not support a relation between induced abortion and breast cancer incidence The possible influence of induced abortion on breast cancer risk was assessed in a cohort of 267 040 women enrolled in a r and omised trial of breast self-examination in Shanghai , China . Based on answers to a baseline question naire , subsequent breast cancer risk was not significantly associated with ever having an induced abortion . After adjustment for potential confounders , the relative risk estimate was 1.06 ( 95 % C.I. : 0.91 , 1.25 ) , and there was no trend in risk with number of abortions . Analysis of data from more detailed interviews of 652 cases and 694 controls from the cohort yielded similar results . There was also no overall increase in risk in women with induced abortion after first birth . Few women had undergone an abortion after 13 weeks gestation or before their first child . Although increases in risk were observed in such women , they were not statistically significant and could have been due to recall bias . Abortions as they have been performed in China are not an important cause of breast cancer Objective : To examine the relationship between breast cancer risk and the cumulative number of cycles before a first full-term pregnancy ( FTP ) and lifetime , taking age at menarche and at onset of regular cycling , periodicity and regularity of cycles , duration of periods of pregnancy , and lactation , oral contraceptive ( OC ) use , and age at menopause into account . Methods : The data were taken from the E3N prospect i ve cohort study of women aged 40–65 years in 1990 . A total of 1718 breast cancer cases were identified during the 579,525 person-years of follow-up . Results : There was a highly significant linear relationship between breast cancer risk and both the cumulative number of cycles before a first FTP ( p for trend < 0.0001 ) and lifetime ( p for trend < 0.001 ) , with multivariate relative risk ( RR ) of a similar magnitude for both variables . Compared to women with a lifetime number of cycles ≤ 402 ( ≤ 30 years ) , the RR for those with a lifetime total of 403–441 , 442–480 , 481–520 , and ≥ 521 cycles were 0.95 ( 0.75–1.21 ) , 1.21 ( 0.97–1.52 ) , 1.23 ( 0.96–1.58 ) , and 1.60 ( 1.25–2.04 ) , respectively . Results restricted to never OC users were similar . Conclusions : Further investigation is needed to clarify whether the underlying factor is repeated exposure to fluctuating hormones , the number of anovular/ovular cycles , or the relative importance of the follicular and luteal phases BACKGROUND Induced abortion has been inconsistently associated with breast cancer risk in case-control studies . Retrospective cohort studies using registry information in Sc and inavia have not suggested an increase in the incidence of breast cancer , although data on individual reproductive factors were not accounted for . METHODS We examined the association between induced and spontaneous abortion and the incidence of breast cancer in a prospect i ve cohort of young women , the Nurses ' Health Study II . The study included 105 716 women 29 to 46 years old at the start of follow-up in 1993 . Information on induced or spontaneous abortions was collected in 1993 and up date d biennially . During 973 437 person-years of follow-up between 1993 and 2003 , 1458 newly diagnosed cases of invasive breast cancer were ascertained . RESULTS A total of 16 118 participants ( 15 % ) reported a history of induced abortion , and 21 753 ( 21 % ) reported a history of spontaneous abortions . The hazard ratio for breast cancer among women who had 1 or more induced abortions was 1.01 ( 95 % confidence interval , 0.88 - 1.17 ) after adjustment for established breast cancer risk factors ; among women with 1 or more spontaneous abortions , the covariate-adjusted hazard ratio was 0.89 ( 95 % confidence interval , 0.78 - 1.01 ) . The relation between induced abortion and the incidence of breast cancer did not differ material ly by number of abortions ( P for trend = .98 ) , age at abortion ( P for trend = .68 ) , parity ( P for interaction = .54 ) , or timing of abortion with respect to a full-term pregnancy ( P for interaction = .10 ) . CONCLUSION Among this predominantly premenopausal population , neither induced nor spontaneous abortion was associated with the incidence of breast cancer Controversy exists over the possible relationship between induced and spontaneous abortion and risk of breast cancer . Thus , the association of fatal breast cancer and spontaneous abortion was examined in a large prospect i ve study of United States adult women . After seven years of follow-up , 1,247 cases of fatal breast cancer were observed among 579,274 women who were cancer-free at interview in 1982 and who provided complete reproductive histories . Results from Cox proportional hazards models , adjusted for other risk factors , showed no association between a history of spontaneous abortion and risk of fatal breast cancer ( rate ratio [RR]=0.89 , 95 percent confidence interval [CI]=0.78–1.02 ) . The RR did not increase with increasing numbers of abortions . Parous women who had a spontaneous abortion before their first term birth were not at increased risk compared with parous women with no history of spontaneous abortion ( RR=0.76 , CI=0.54–1.05 ) . Women whose only pregnancy ended in a spontaneous abortion were not at increased risk compared with women who were never pregnant ( RR=0.61 , CI=0.27–1.38 ) or whose only pregnancy ended in a livebirth ( RR=0.72 , CI=0.32–1.65 ) . These findings do not support an association between spontaneous abortion and fatal breast cancer We recently provided data from a prospect i ve cohort study of postmenopausal women which suggested that a first livebirth at age 30 or older ( cf before age 20 ) was associated with a twofold increased risk of breast cancer in women without a family history , but a 5.8-fold higher risk in women with a positive family history . To address the question of whether these observations reflect difficulty becoming pregnant or maintaining a pregnancy , we performed additional analyses in which the outcome of each pregnancy was considered . During five years of follow-up , 620 incident cases of breast cancer were identified in the 37,105 women at risk . There was little evidence for an increased risk associated with a history of spontaneous abortion ( relative risk [RR]=1.1 ; 95 percent confidence interval [CI]=0.9–1.4 ) , nor was the risk higher among women who reported two or more spontaneous abortions in consecutive pregnancies ( RR=1.0 , CI=0.7–1.4 ) . Although women who reported that they had tried unsuccessfully to become pregnant had only slightly and nonsignificantly elevated risks of breast cancer ( RR=1.1 , CI=0.9–1.3 ) , a more pronounced and statistically significant association was noted in women with a positive family history ( RR=2.0 , CI=1.4–3.2 ) . There was a strong inverse association between failure to become pregnant and parity ( P<0.0001 ) ; nearly 50 percent of the nulliparous married women reported having tried and failed to become pregnant , whereas the frequency was only 6.8 percent among married women with five or more livebirths . Thus , difficulties in becoming pregnant may characterize a subset of women at increased risk of breast cancer , especially in the presence of a family history Studies suggesting a positive association between pregnancy termination and breast cancer risk have often been of retrospective case-control design , so subject to selection and recall biases . We undertook a registry-based analysis with minimal selection bias and prospect i ve record-based ascertainment of terminations . The source population comprised Massachusetts women with a record of giving birth between 1987 and 1999 in the Massachusetts Vital Statistics Registry . Primary breast cancer cases were 25 - 55 years old at diagnosis between 1988 and 2000 and had a record of the diagnosis in the Massachusetts Cancer Registry . We matched 3 controls to each case on maternal age , year of giving birth and birth facility . Information on terminations ( induced and spontaneous ) before the birth of record , the matched factors and potential confounders were collected from the birth certificate . After adjustment for the matched factors , age , parity and maternal and paternal education , the odds ratio associating any termination history with breast cancer risk equaled 0.91 ( 95 % CI = 0.79 - 1.05 ) . The marginally protective adjusted odds ratio largely derived from a protective effect among women with parity equaled to 1 ( OR for any termination = 0.68 ; 95 % CI = 0.45 - 1.03 ) , suggesting a protective effect of terminated pregnancy among women with one live birth Objective : There continues to be controversy about whether induced abortion influences the risk of breast cancer . Because case – control studies of this relation are subject to recall bias , there is a need for prospect i ve data . Further , there has been little study of abortion and breast cancer in African-American women . We assessed the relation of abortion to risk of breast cancer in a prospect i ve follow-up study of African-American women . Methods : Black Women 's Health Study participants have been followed by mailed question naires every two years since enrollment in 1995 . Participants reported 348 incident breast cancers during 205,983 person-years of follow-up . Women who had an induced abortion were compared with women who had never had one , with nulliparous and parous women analyzed separately . Incidence rate ratios ( IRR ) with two-sided 95 % confidence intervals ( CI ) were derived from Cox regression models that controlled for age , age at first birth , number of births , history of spontaneous abortion , and other factors . Results : Among nulliparous women , the IRR for any induced abortion relative to none was 0.9 ( 95 % CI = 0.5–1.4 ) , and among parous women , the comparable IRR was 1.1 ( 95 % CI = 0.8–1.4 ) . Risk did not vary by number of abortions , age at first abortion , age at diagnosis or a family history of breast cancer in either nulliparous or parous women . Conclusions : Our findings indicate that induced abortion does not increase breast cancer risk in African-American women The role of spontaneous and induced abortion on breast cancer risk is examined among 267,361 women recruited into the European Prospect i ve Investigation into Cancer and nutrition between 1992 and 2000 . The data were collected from 20 centers , across 9 countries , and included information on a total of 4,805 women with breast cancer , of whom 1,657 reported having ever had any type of abortion . Overall , the relative risk of breast cancer in women who reported ever having had a spontaneous abortion was not significantly elevated when compared with women who reported never having had such an abortion ( RR = 1.07 , 95 % CI = 0.99 - 1.14 ) . However , there was some evidence of a slight increase in the risk of breast cancer among women who reported having had 2 or more spontaneous abortions ( 1.20 , 1.07 - 1.35 ) . The relative risk of breast cancer among women who reported ever having had an induced abortion when compared to women who reported never having had an induced abortion was 0.95 ( 0.87 - 1.03 ) . Overall , the findings provide further unbiased evidence of the lack of an adverse effect of induced abortion on breast cancer risk BACKGROUND Early studies of incomplete pregnancy and development of breast cancer suggested that induced abortion might increase risk . Several large prospect i ve studies , which eliminate recall bias , did not detect associations , but this relationship continues to be debated . STUDY DESIGN To further inform this important question , we examined invasive breast cancer as it relates to incomplete pregnancy , including total number of induced abortions , age at first induced abortion and total number of miscarriages among women participating in the ongoing California Teachers Study ( CTS ) cohort . Incomplete pregnancy was self-reported on the CTS baseline question naire in 1995 - 1996 . Incident breast cancers were ascertained in 3324 women through 2004 via linkage with the California Cancer Registry . RESULTS Using Cox multivariable regression , we found no statistically significant association between any measure of incomplete pregnancy and breast cancer risk among nulliparous or parous women . CONCLUSION These results provide strong evidence that there is no relationship between incomplete pregnancy and breast cancer risk |
12,358 | 29,436,954 | The following categories showed evidence of clinical utility and were recommended for use in practice : CA 15 - 3 , CA 27.29 , carcinoembryonic antigen , estrogen receptor , progesterone receptor , human epidermal growth factor receptor 2 , urokinase plasminogen activator , plasminogen activator inhibitor 1 , and certain multiparameter gene expression assays .
Not all applications for these markers were supported , however . | Purpose To up date the recommendations for the use of tumor marker tests in the prevention , screening , treatment , and surveillance of breast cancer . | BACKGROUND The likelihood of distant recurrence in patients with breast cancer who have no involved lymph nodes and estrogen-receptor-positive tumors is poorly defined by clinical and histopathological measures . METHODS We tested whether the results of a reverse-transcriptase-polymerase-chain-reaction ( RT-PCR ) assay of 21 prospect ively selected genes in paraffin-embedded tumor tissue would correlate with the likelihood of distant recurrence in patients with node-negative , tamoxifen-treated breast cancer who were enrolled in the National Surgical Adjuvant Breast and Bowel Project clinical trial B-14 . The levels of expression of 16 cancer-related genes and 5 reference genes were used in a prospect ively defined algorithm to calculate a recurrence score and to determine a risk group ( low , intermediate , or high ) for each patient . RESULTS Adequate RT-PCR profiles were obtained in 668 of 675 tumor blocks . The proportions of patients categorized as having a low , intermediate , or high risk by the RT-PCR assay were 51 , 22 , and 27 percent , respectively . The Kaplan-Meier estimates of the rates of distant recurrence at 10 years in the low-risk , intermediate-risk , and high-risk groups were 6.8 percent ( 95 percent confidence interval , 4.0 to 9.6 ) , 14.3 percent ( 95 percent confidence interval , 8.3 to 20.3 ) , and 30.5 percent ( 95 percent confidence interval , 23.6 to 37.4 ) . The rate in the low-risk group was significantly lower than that in the high-risk group ( P<0.001 ) . In a multivariate Cox model , the recurrence score provided significant predictive power that was independent of age and tumor size ( P<0.001 ) . The recurrence score was also predictive of overall survival ( P<0.001 ) and could be used as a continuous function to predict distant recurrence in individual patients . CONCLUSIONS The recurrence score has been vali date d as quantifying the likelihood of distant recurrence in tamoxifen-treated patients with node-negative , estrogen-receptor-positive breast cancer BACKGROUND Amplification of the human epidermal growth factor receptor type 2 ( HER2 , also called HER2/neu ) gene and overexpression of its product in breast-cancer cells may be associated with responsiveness to anthracycline-containing chemotherapy regimens . METHODS In the r and omized , controlled Mammary.5 trial , we studied 639 formalin-fixed paraffin-embedded specimens obtained from 710 premenopausal women with node-positive breast cancer who had received either cyclophosphamide , epirubicin , and fluorouracil ( CEF ) or cyclophosphamide , methotrexate , and fluorouracil ( CMF ) as adjuvant chemotherapy . HER2 amplification or overexpression was evaluated with the use of fluorescence in situ hybridization , immunohistochemical analysis , and polymerase-chain-reaction analysis . RESULTS Amplification of HER2 was associated with a poor prognosis regardless of the type of treatment . In patients whose tumors showed amplification of HER2 , CEF was superior to CMF when assessed on the basis of relapse-free survival ( hazard ratio , 0.52 ; 95 percent confidence interval , 0.34 to 0.80 ; P=0.003 ) and overall survival ( hazard ratio , 0.65 ; 95 percent confidence interval , 0.42 to 1.02 ; P=0.06 ) . For women whose tumors lacked amplification of HER2 , CEF did not improve relapse-free survival ( hazard ratio for relapse , 0.91 ; 95 percent confidence interval , 0.71 to 1.18 ; P=0.49 ) or overall survival ( hazard ratio for death , 1.06 ; 95 percent confidence interval , 0.83 to 1.44 ; P=0.68 ) . The adjusted hazard ratio for the interaction between treatment and HER2 amplification was 1.96 for relapse-free survival ( 95 percent confidence interval , 1.15 to 3.36 ; P=0.01 ) and 2.04 for overall survival ( 95 percent confidence interval , 1.14 to 3.65 ; P=0.02 ) . CONCLUSIONS Amplification of HER2 in breast-cancer cells is associated with clinical responsiveness to anthracycline-containing chemotherapy . ( cancer.gov number , NCI-V90 - 0027 . ) PURPOSE Histologic grade , Nottingham Prognostic Index ( NPI ) , estrogen receptor ( ER ) and progesterone receptor ( PgR ) status , and tumor size have previously been shown to be important prognostic indicators for distant recurrence of breast cancer . The purpose of this study was to compare the prognostic value of these factors with flow cytometric S-phase fraction ( SPF ) , urokinase plasminogen activator ( uPA ) , and plasminogen activator inhibitor type 1 ( PAI-1 ) in premenopausal patients with lymph node-negative breast cancer . PATIENTS AND METHODS In 237 consecutive premenopausal patients with lymph node-negative breast cancer and freshly frozen tumor material available , SPF , ER and PgR status , uPA and its inhibitor PAI-1 , histologic grade , and NPI were evaluated . RESULTS SPF was univariately the most powerful prognostic factor for distant recurrence , followed by uPA , histologic grade , PgR , age , ER , NPI , and PAI-1 , the latter being nonsignificant . Multivariate analysis revealed that neither NPI nor histologic grade was significant after adjustment for SPF , a fact that may be explained by the strong association between these factors . uPA was , however , an independent prognostic factor in addition to SPF , NPI , or histologic grade . CONCLUSION In this prospect i ve study , SPF and uPA were found to be independent prognostic factors in premenopausal women with lymph node-negative breast cancer . We suggest that SPF , if performed under st and ardized conditions , can replace histologic grade as a selection instrument for adjuvant medical treatment . The value of the combination of SPF and uPA needs to be confirmed in an independent prospect i ve trial BACKGROUND Abnormal expression of the cell cycle regulatory proteins p27(Kip1 ) ( p27 ) and cyclin E may be associated with breast cancer survival and relapse . We studied these markers in a clinical trial setting with patients with breast cancer treated by a uniform drug regimen so that treatment was not associated with variability in outcome . METHODS We used tissue microarrays to evaluate the expression of p27 and cyclin E proteins by immunohistochemistry in tumor tissue from 2123 ( 68 % ) of 3122 patients with moderate-risk primary breast cancer who were enrolled in Southwest Oncology Group-Intergroup Trial S9313 , in which patients were assigned to receive doxorubicin and cyclophosphamide administered concurrently ( n = 1595 ) or sequentially ( n = 1527 ) . Disease-free and overall survival were equivalent in the two arms . Expression of the proteins was rated on a scale of 1 - 7 , and the median value was used as the cut point . Log-rank tests and Cox regression analyses were used to assess associations with survival . Overall survival was defined as time to death from all causes ; disease-free survival was defined as time to recurrence or death . All P values were from two-sided statistical tests . RESULTS Lower p27 expression was associated with worse overall survival ( unadjusted hazard ratio [ HR ] = 1.50 , 95 % confidence interval [ CI ] = 1.21 to 1.86 ) and disease-free survival ( unadjusted HR = 1.31 , 95 % CI = 1.10 to 1.57 ) than higher p27 expression . Among hormone receptor-positive patients , lower p27 expression was associated with worse overall survival ( HR = 1.42 , 95 % CI = 1.05 to 1.94 ) and worse disease-free survival ( HR = 1.27 , 95 % CI = 0.99 to 1.63 ) than higher p27 expression after adjustment for treatment , menopausal status , tumor size , and number of positive lymph nodes . Among these patients , 5-year overall survival associated with higher p27 expression ( 0.91 , 95 % CI = 0.89 to 0.93 ) was similar to that associated with lower p27 expression ( 0.85 , 95 % CI = 0.82 to 0.87 ) . No association between p27 expression and survival was found in hormone receptor-negative patients . Cyclin E expression was not statistically significantly associated with overall survival ( HR = 1.12 , 95 % CI = 0.91 to 1.38 ) or disease-free survival ( HR = 1.09 , 95 % CI = 0.92 to 1.29 ) . CONCLUSIONS Low p27 expression appears to be associated with poor prognosis , especially among patients with steroid receptor-positive tumors Proteomic analysis of body fluids , including breast nipple aspirate fluid ( NAF ) , holds promise to aid in early cancer detection . We conducted a prospect i ve trial that collected NAF from women scheduled for diagnostic breast surgery to determine 1 ) the consistency of proteomic results , 2 ) protein masses associated with breast cancer , 3 ) subsets of women with a unique proteomic profile and 4 ) a breast cancer predictive model . NAF was collected preoperatively in 114 women and analyzed by SELDI-TOF mass spectrometry over a 3 - 50 kDa range using H4 , NP and SAX ProteinChips . For all 3 chips , the same protein peaks were detected over 90 % of the time in duplicate sample s. The overall coefficient of variation was < or = 0.17 % for each chip for the internal st and ard and < or = 0.29 % for the unknown proteins . Seven c and i date protein ion masses frequently expressed in NAF were identified . Three ( 5,200-H4 , p=.04 , 11,880-H4 , p=.07 and 13,880 Da-SAX , p=.03 ) were differentially expressed in women with/without breast cancer . Protein expression differed between women with/without pathologic nipple discharge ( PND ) , but the 5,200 , 11,880 and 13,880 proteins remained associated with breast cancer even if PND sample s were excluded . Subset analysis identified differences in expression between benign disease and DCIS and between DCIS and invasive cancer for the 5,200 and 33,400 Da proteins . The best cancer detection model included age , parity and the 11,880 Da protein , and excluded women with PND . 1 ) NAF proteomic analysis using SELDI-TOF is reproducible with the same sample set across different platforms , 2 ) differential proteomic expression exists between women/without breast cancer and 3 ) combining proteomic and clinical information that are available before surgery optimizes the prediction of which women have breast cancer BACKGROUND Overexpression of the erbB-2 protein by breast cancer cells has been suggested to be a predictor of response to doxorubicin . A retrospective study was design ed to test this hypothesis . METHODS In National Surgical Adjuvant Breast and Bowel Project protocol B-11 , patients with axillary lymph node-positive , hormone receptor-negative breast cancer were r and omly assigned to receive either L-phenylalanine mustard plus 5-fluorouracil ( PF ) or a combination of L-phenylalanine mustard , 5-fluorouracil , and doxorubicin ( PAF ) . Tumor cell expression of erbB-2 was determined by immunohistochemistry for 638 of 682 eligible patients . Statistical analyses were performed to test for interaction between treatment and erbB-2 status ( positive versus negative ) with respect to disease-free survival ( DFS ) , survival , recurrence-free survival ( RFS ) , and distant disease-free survival ( DDFS ) . Reported P values are two-sided . RESULTS Overexpression of erbB-2 ( i.e. , positive immunohistochemical staining ) was observed in 239 ( 37.5 % ) of the 638 tumors studied . Overexpression was associated with tumor size ( P=.02 ) , lack of estrogen receptors ( P=.008 ) , and the number of positive lymph nodes ( P=.0001 ) . After a mean time on study of 13.5 years , the clinical benefit from doxorubicin ( PAF versus PF ) was statistically significant for patients with erbB-2-positive tumors -- DFS : relative risk of failure (RR)=0.60 ( 95 % confidence interval [CI]=0.44 - 0.83 ) , P=.001 ; survival : RR=0.66 ( 95 % CI=0.47 - 0.92 ) , P = .01 ; RFS : RR=0.58 ( 95 % CI=0.42 - 0.82 ) , P=.002 ; DDFS : RR=0.61 ( 95 % CI=0.44 - 0.85 ) , P=.003 . However , it was not significant for patients with erbB-2-negative tumors-DFS : RR=0.96 ( 95 % CI=0.75 - 1.23 ) , P=.74 ; survival : RR = 0.90 ( 95 % CI=0.69 - 1.19 ) , P=.47 ; RFS : RR=0.88 ( 95 % CI=0.67 - 1.16 ) , P=.37 ; DDFS : RR=1.03 ( 95 % CI=0.79 - 1.35 ) , P=.84 . Interaction between doxorubicin treatment and erbB-2 overexpression was statistically significant for DFS ( P=.02 ) and DDFS ( P=.02 ) but not for survival ( P= .15 ) or RFS ( P=.06 ) . CONCLUSIONS These data support the hypothesis of a preferential benefit from doxorubicin in patients with erbB-2-positive breast cancer PURPOSE To investigate the relationships between biomarker changes in breast cancer during neoadjuvant ( preoperative ) endocrine therapy . PATIENTS AND METHODS The IMPACT trial compared the preoperative use of tamoxifen with anastrozole alone or in combination in postmenopausal women ( n = 330 ) with primary breast cancer . Biomarkers were measured in tumor biopsy specimens taken at baseline , and after 2 and 12 weeks of treatment . RESULTS 52 ( 93 % ) of 56 , 46 ( 85 % ) of 54 , and 37 ( 84 % ) of 44 patients in the anastrozole , tamoxifen , and combination groups , respectively . There was a significantly greater suppression of Ki67 in the anastrozole-treated group than in the tamoxifen- or combination-treated groups , which is parallel to the greater efficacy seen for anastrozole over these two treatments in the Arimidex , Tamoxifen , Alone or in Combination adjuvant trial . A positive relationship was noted between estrogen-receptor level and Ki67 suppression in all patients . Ki67 was reduced to a greater extent in progesterone receptor-positive tumors compared with progesterone receptor-negative tumors . HER-2-negative tumors tended to show a greater reduction in Ki67 compared with HER-2-positive tumors , but the difference was only significant in the tamoxifen group after 2 weeks , and in the anastrozole group after 12 weeks . CONCLUSION These results confirm the value of Ki67 as a molecular marker , and provide information regarding the relationships between treatment-induced changes in Ki67 and other important biomarkers . Studies such as this should help integrate agents targeted at growth factor signaling with endocrine agents in breast cancer PURPOSE The independent clinical relevance of invasion factors urokinase-type plasminogen activator (uPA)/PAI-1 and HER2 status was evaluated in lymph node-negative breast cancer patients ( N = 118 ) without adjuvant systemic therapy after long-term follow-up of more than 10 years ( median , 126 months ) . PATIENTS AND METHODS Levels of uPA and its inhibitor PAI-1 were prospect ively measured by enzyme-linked immunosorbent assay in primary tumor tissue extracts . HER2 gene amplification ( HER2_AMP ) was evaluated by fluorescence in situ hybridization ( FISH ; Ventana Medical Systems HER-2/neu probe ; Tucson , AZ ) , and HER2 protein overexpression ( HER2_EXP ) was evaluated by immunohistochemistry ( IHC ; Oncogene Science antibody Ab-3 ; Cambridge , MA ) on parallel-cut formalin-fixed paraffin-embedded tissue sections . RESULTS uPA/PAI-1 was high ( either one or both factors were high ) in 44 % of the tumors . HER2_AMP was detected by FISH in 33 % of the patients , and HER2_EXP was found by IHC in 44 % of the patients . In a multivariate analysis of established and tumor-biologic prognostic factors , uPA/PAI-1 was the only independent prognostic factor for disease-free survival ( [ DFS ] ; P < .001 ; relative risk [ RR ] , 8.3 ; 95 % confidence interval [ CI ] , 3.4 to 20.4 ) . Although HER2_AMP and HER2_EXP did not reach significance for DFS , they were significant for overall survival ( OS ) , even in multivariate analysis ( HER2_AMP : P = .004 ; RR , 3.7 ; 95 % CI , 1.5 to 9.2 ; HER2_EXP : P = .009 ; RR , 3.4 ; 95 % CI , 1.4 to 8.7 ) . CONCLUSION After long-term follow-up , uPA/PAI-1 levels in primary tumor tissue reliably and strongly indicate an aggressive course of disease in lymph node-negative breast cancer independent of HER2 status . The particular prognostic effect of HER2 status on OS may reflect its ability to predict resistance to systemic therapy BACKGROUND We present the combined results of two trials that compared adjuvant chemotherapy with or without concurrent trastuzumab in women with surgically removed HER2-positive breast cancer . METHODS The National Surgical Adjuvant Breast and Bowel Project trial B-31 compared doxorubicin and cyclophosphamide followed by paclitaxel every 3 weeks ( group 1 ) with the same regimen plus 52 weeks of trastuzumab beginning with the first dose of paclitaxel ( group 2 ) . The North Central Cancer Treatment Group trial N9831 compared three regimens : doxorubicin and cyclophosphamide followed by weekly paclitaxel ( group A ) , the same regimen followed by 52 weeks of trastuzumab after paclitaxel ( group B ) , and the same regimen plus 52 weeks of trastuzumab initiated concomitantly with paclitaxel ( group C ) . The studies were amended to include a joint analysis comparing groups 1 and A ( the control group ) with groups 2 and C ( the trastuzumab group ) . Group B was excluded because trastuzumab was not given concurrently with paclitaxel . RESULTS By March 15 , 2005 , 394 events ( recurrent , second primary cancer , or death before recurrence ) had been reported , triggering the first scheduled interim analysis . Of these , 133 were in the trastuzumab group and 261 in the control group ( hazard ratio , 0.48 ; P<0.0001 ) . This result crossed the early stopping boundary . The absolute difference in disease-free survival between the trastuzumab group and the control group was 12 percent at three years . Trastuzumab therapy was associated with a 33 percent reduction in the risk of death ( P=0.015 ) . The three-year cumulative incidence of class III or IV congestive heart failure or death from cardiac causes in the trastuzumab group was 4.1 percent in trial B-31 and 2.9 percent in trial N9831 . CONCLUSIONS Trastuzumab combined with paclitaxel after doxorubicin and cyclophosphamide improves outcomes among women with surgically removed HER2-positive breast cancer . ( Clinical Trials.gov numbers , NCT00004067 and NCT00005970 . PURPOSE To up date the 1999 American Society of Clinical Oncology ( ASCO ) guideline on breast cancer follow-up and management in the adjuvant setting . METHODS An ASCO Expert Panel review ed pertinent information from the literature through March 2006 . More weight was given to studies that tested a hypothesis directly relating testing to one of the primary outcomes in a r and omized design . RESULTS The evidence supports regular history , physical examination , and mammography as the cornerstone of appropriate breast cancer follow-up . All patients should have a careful history and physical examination performed by a physician experienced in the surveillance of cancer patients and in breast examination . Examinations should be performed every 3 to 6 months for the first 3 years , every 6 to 12 months for years 4 and 5 , and annually thereafter . For those who have undergone breast-conserving surgery , a post-treatment mammogram should be obtained 1 year after the initial mammogram and at least 6 months after completion of radiation therapy . Thereafter , unless otherwise indicated , a yearly mammographic evaluation should be performed . Patients at high risk for familial breast cancer syndromes should be referred for genetic counseling . The use of CBCs , chemistry panels , bone scans , chest radiographs , liver ultrasounds , computed tomography scans , [18F]fluorodeoxyglucose-positron emission tomography scanning , magnetic resonance imaging , or tumor markers ( carcinoembryonic antigen , CA 15 - 3 , and CA 27.29 ) is not recommended for routine breast cancer follow-up in an otherwise asymptomatic patient with no specific findings on clinical examination . CONCLUSION Careful history taking , physical examination , and regular mammography are recommended for appropriate detection of breast cancer recurrence Altogether , 243 female breast cancer patients with localised disease diagnosed between 1991 and 1995 in the Tampere University Hospital area were followed prospect ively after primary treatment until the first relapse . In the follow-up period , the serum tumour marker Ca 15 - 3 was analysed every 6 months to ascertain the validity of this marker in detecting the first relapse . The sensitivity and specificity of the test were analysed in different metastatic situations . During the 5 years of follow-up , 59 ( 24 % ) relapses were discovered . Ca 15 - 3 was elevated in 21/59 ( 36 % ) of the relapsed cases at least once . The 59 patients were subjected to 199 tests , of which 25 ( 13 % ) were positive . Among the 184 patients without recurrence , there were 6 ( 3 % ) with a positive Ca 15 - 3 level . The test failed to detect locoregional relapse or contralateral breast cancer . It was elevated in approximately half of bone-only metastases and in all of the liver-only metastases . In the pulmonary-only recurrences , the marker value was not elevated . We conclude that the Ca 15 - 3 tumour marker test is specific , but not sensitive enough to indicate the first relapse earlier than other methods . The positive predictive value especially remained poor in patients with a relatively good prognosis . Our results confirm that the test is not suitable alone for breast cancer follow-up Purpose : In the adjuvant treatment of estrogen receptor (ER)–positive breast cancer , additional markers are needed to identify women at high risk for recurrence . Experimental Design : We examined the association between the ratio of the homeobox 13 ( HOXB13 ) to interleukin-17B receptor ( IL-17BR ) expression and the clinical outcomes of relapse and survival in women with ER-positive breast cancer enrolled onto a North Central Cancer Treatment Group adjuvant tamoxifen trial ( NCCTG 89 - 30 - 52 ) . Results : Tumor blocks were obtained from 211 of 256 eligible patients , and quantitative reverse transcription-PCR profiles for HOXB13 and IL-17BR were obtained from 206 patients . The cut point for the two-gene log 2(expression ratio ) that best discriminated clinical outcome ( recurrence and survival ) was selected and identified women with significantly worse relapse-free survival ( RFS ) , disease-free survival ( DFS ) , and overall survival ( OS ) , independent of st and ard prognostic markers . The cut point differed as a function of nodal status [ node negative ( 59th percentile ) versus node positive ( 90th percentile ) ] . In the node-positive cohort ( n = 86 ) , the HOXB13/IL-17BR ratio was not associated with relapse or survival . In contrast , in the node-negative cohort ( n = 130 ) , a high HOXB13/IL-17BR ratio was associated with significantly worse RFS [ hazard ratio ( HR ) , 1.98 ; P = 0.031 ] , DFS ( HR , 2.03 ; P = 0.015 ) , and OS ( HR , 2.4 ; P = 0.014 ) , independent of st and ard prognostic markers . Conclusion : A high HOXB13/IL-17BR expression ratio is associated with increased relapse and death in patients with resected node-negative , ER-positive breast cancer treated with tamoxifen and may identify patients in whom alternative therapies should be studied PURPOSE Carcinoembryonic antigen ( CEA ) is still a widely used test for monitoring breast cancer , although recent reports discourage its routine use because of low sensitivity . This is a prospect i ve study evaluating the efficacy of CEA and CA 15.3 in monitoring breast cancer . EXPERIMENTAL DESIGN Serum CEA and CA 15.3 were measured in 2191 patients with either benign ( n = 738 ) or malignant ( n = 1453 ) breast diseases . Five hundred and forty-nine patients were monitored during postsurgical follow-up for either a minimum of 5 years or until time of recurrence . Fifty-three patients with metastases were also monitored during chemotherapy . RESULTS Elevated CEA and CA 15.3 levels were found in 16.7 % and 33.0 % of patients , respectively . CEA sensitivity rose to 41.3 % and CA 15.3 sensitivity rose to 80.8 % in metastatic patients . The adjunct of CEA increased the CA 15.3 sensitivity by 6 % in the overall population and by only 2.1 % for patients with metastases . During postsurgical follow-up , CEA was elevated in 38.0 % and CA 15.3 in 70.2 % of patients with recurrence . The combination of CEA and CA 15.3 increased the overall sensitivity by only 1.4 % . Longitudinal monitoring of 53 metastatic patients undergoing chemotherapy demonstrated that , when positive , both CEA and CA 15.3 paralleled response to treatment , although CA 15.3 was a significantly more powerful marker for determining response to treatment . The cost effectiveness ratio of CEA was clearly less favorable than that of CA 15.3 . CONCLUSIONS CEA monitoring should be considered an expensive and inefficient method of follow-up evaluation for breast cancer patients , and it provides no additional value when used in combination with CA 15.3 BACKGROUND Most patients with lymph node-negative breast cancer are cured by locoregional treatment ; however , about 30 % relapse . Because traditional histomorphologic and clinical factors fail to identify the high-risk patients who may benefit from adjuvant chemotherapy , other prognostic factors are needed . In a unicenter study , we have found that levels of urokinase-type plasminogen activator ( uPA ) and plasminogen activator inhibitor type 1 ( PAI-1 ) in the primary tumor are predictive of disease recurrence . Thus , we design ed the Chemo N(0 ) prospect i ve r and omized multicenter therapy trial to investigate further whether uPA and PAI-1 are such prognostic factors and whether high-risk patients identified by these factors benefit from adjuvant chemotherapy . After 4.5 years , we present results of the first interim analysis . METHODS We studied 556 patients with lymph node-negative breast cancer . The median follow-up was 32 months . All patients with low tumor levels of uPA ( < or = 3 ng/mg of protein ) and of PAI-1 ( < or = 14 ng/mg of protein ) were observed . Patients with high tumor levels of uPA ( > 3 ng/mg of protein ) and /or of PAI-1 ( > 14 ng/mg of protein ) were r and omly assigned to combination chemotherapy or subjected to observation only . All statistical tests were two-sided . RESULTS A total of 241 patients had low levels of uPA and PAI-1 , and 315 had elevated levels of uPA and /or PAI-1 . The estimated 3-year recurrence rate for patients with low tumor levels of uPA and PAI-1 ( low-risk group ) was 6.7 % ( 95 % confidence interval [ CI ] = 2.5 % to 10.8 % ) . This rate for patients with high tumor levels of uPA and /or PAI-1 ( high-risk group ) was 14.7 % ( 95 % CI = 8.5 % to 20.9 % ) ( P = 0.006 ) . First interim analysis suggests that high-risk patients in the chemotherapy group benefit , with a 43.8 % lower estimated probability of disease recurrence at 3 years than high-risk patients in the observation group ( intention-to-treat analysis : relative risk = 0.56 ; 95 % CI = 0.25 to 1.28 ) , but further follow-up is needed for confirmation . CONCLUSIONS Using uPA and PAI-1 , we have been able to classify about half of the patients with lymph node-negative breast cancer as low risk , for whom adjuvant chemotherapy may be avoided , and half as high risk , who appear to benefit from adjuvant chemotherapy The purpose of this study was to classify breast carcinomas based on variations in gene expression patterns derived from cDNA microarrays and to correlate tumor characteristics to clinical outcome . A total of 85 cDNA microarray experiments representing 78 cancers , three fibroadenomas , and four normal breast tissues were analyzed by hierarchical clustering . As reported previously , the cancers could be classified into a basal epithelial-like group , an ERBB2-overexpressing group and a normal breast-like group based on variations in gene expression . A novel finding was that the previously characterized luminal epithelial/estrogen receptor-positive group could be divided into at least two subgroups , each with a distinctive expression profile . These subtypes proved to be reasonably robust by clustering using two different gene sets : first , a set of 456 cDNA clones previously selected to reflect intrinsic properties of the tumors and , second , a gene set that highly correlated with patient outcome . Survival analyses on a subcohort of patients with locally advanced breast cancer uniformly treated in a prospect i ve study showed significantly different outcomes for the patients belonging to the various groups , including a poor prognosis for the basal-like subtype and a significant difference in outcome for the two estrogen receptor-positive groups PURPOSE The purpose of this study is to evaluate HER-2 and topoisomerase IIalpha ( topo IIalpha ) as c and i date s for predicting the activity of anthracyclines in the adjuvant treatment of breast cancer patients . EXPERIMENTAL DESIGN In this study , we evaluated HER-2 and topo IIalpha gene aberrations by fluorescence in situ hybridization in a series of 430 primary breast cancer sample s. Sample s came from node-positive breast cancer patients r and omly treated either with one of two anthracycline-based regimens [ full-dose epirubicin-cyclophosphamide ( HEC ) and moderate-dose epirubicin-cyclophosphamide ( EC ) ] or with cyclophosphamide , methotrexate , and 5-fluorouracil ( CMF ) in the context of a Phase III adjuvant therapy trial . Event-free survival comparisons were performed between the three study arms in the subgroups of HER-2-amplified and nonamplified tumors . An explorative analysis was also performed to evaluate the predictive value of topo IIalpha in the cohort of HER-2-amplified patients . RESULTS HER-2 amplification was observed in 73 of the 354 evaluable sample s ( 21 % ) , whereas topo IIalpha amplification was found in 23 of the 61 evaluable HER-2-amplified tumors ( 38 % ) . The three event-free survival comparisons were CMF versus HEC , CMF versus EC , and EC versus HEC . Hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) were as follows : ( a ) CMF versus HEC , HR = 1.42 for HER-2-amplified tumors ( 95 % CI , 0.54 - 3.76 ; P = 0.48 ) and 0.84 for HER-2-nonamplified tumors ( 95 % CI , 0.49 - 1.44 ; P = 0.53 ) ; ( b ) CMF versus EC , HR = 1.65 for HER-2-amplified tumors ( 95 % CI , 0.66 - 4.13 ; P = 0.29 ) and 0.66 for HER-2-nonamplified tumors ( 95 % CI , 0.39 - 1.10 ; P = 0.11 ) ; and ( c ) EC versus HEC , HR = 0.93 for HER-2-amplified tumors ( 95 % CI , 0.31 - 2.77 , P = 0.90 ) and 1.33 for HER-2-nonamplified tumors ( 95 % CI , 0.82 - 2.14 ; P = 0.25 ) . Observed HRs suggest that the anthracycline-based therapy could be more effective than CMF in the subgroup of HER-2-amplified patients , whereas treatments could be equally active in the HER-2-nonamplified cohort . topo IIalpha evaluation suggests that the superiority of anthracyclines over CMF in HER-2-amplified patients could be confined to the subgroup of topo IIalpha-amplified tumors . CONCLUSIONS HER-2 could have a predictive value for the activity of anthracycline-based regimens in the adjuvant therapy of breast cancer patients . The predictive value of HER-2 would most likely be related to the concomitant amplification of the topo IIalpha gene To test the hypothesis of an association between HER2 and chemotherapy resistance , we performed a prospect i ve assessment of the predictive value of the circulating HER2 extracellular domain ( ECD ) in patients with advanced breast carcinoma in the setting of a multicenter Phase II trial using paclitaxel and doxorubicin . Serum sample s were collected from 58 patients with metastatic breast carcinoma before first-line chemotherapy for advanced disease , and the levels of circulating HER2 ECD were measured using an enzyme immunoassay . Immunohistochemistry with anti-HER2 monoclonal antibody CB11 was used to assess the overexpression of HER2 in the primary tumors . When 450 fmol/ml was used as a cutoff , 24 cases ( 41 % ) had elevated HER2 ECD levels . Elevated levels of circulating HER2 ECD were associated with the expression of HER2 in the primary tumor tissue and with the metastatic tumor burden ( evaluated with the marker CA 15 - 3 ; P = 0.032 and P = 0.002 , respectively ) but not with variables such as menopausal status , stage at diagnosis , previous adjuvant therapy , or the number of metastatic sites . The levels of circulating HER2 ECD correlated inversely with the response to treatment . The probability of obtaining a complete response to chemotherapy was significantly lower ( P = 0.021 ) in patients with elevated HER2 ECD levels ( 0 % ; 95 % confidence interval , 0 - 13 % ) compared with patients with nonelevated HER2 ( 26 % ; 95 % confidence interval , 12 - 45 % ) . In addition , the duration of clinical response was significantly shorter in patients with elevated HER2 ECD , compared with the cases with nonelevated HER2 ( 7.5 versus 11 months ; P = 0.035 ) . In conclusion , elevated levels of circulating HER2 ECD in patients with metastatic breast cancer correlate with reduced efficacy of a paclitaxel-doxorubicin chemotherapy combination . We suggest that the poor response rate associated with HER2 expression in advanced breast cancer may not be reversed by aggressive chemotherapy alone PURPOSE Human epidermal growth factor receptor 2 ( HER2 ) overexpression was found to predict a good response in breast carcinoma patients treated with doxorubicin ( Adriamycin [ ADM ] ) . Evidence from our recent study indicates that node-positive patients respond to cyclophosphamide , methotrexate , and fluorouracil ( CMF ) regardless of HER2 status . We address the issue of whether therapy regimens including CMF and ADM versus CMF alone have the same therapeutic effect in patients with HER2 + and HER2- tumors in terms of relapse-free survival ( RFS ) and overall survival ( OS ) . METHODS Archival specimens of the primary tumors from 506 patients in a prospect i ve clinical trial were stained with the anti-HER2 monoclonal antibody CB11 . Originally , patients were r and omly allocated to receive either 12 courses of intravenous CMF or eight courses of the same regimen followed by four cycles of ADM . RFS and OS were analyzed by a Cox model taking into account treatment , HER2 status , and the interaction between treatment and HER2 status , adjusting for the effect of other known clinical and biopathologic factors . RESULTS Analysis of survival rates indicates a possible differential effect of treatment in the patients grouped according to HER2 status . Improved RFS and OS were observed in the HER2 + subgroup after treatment with CMF plus ADM versus CMF alone . With a median follow-up of 15 years , the hazard ratio ( HR ) for RFS was 0.83 in HER2 + tumors and 1.22 in HER2- tumors . The effect of treatment was more evident on OS in HER2 + patients ( HR = 0.61 ; CI , 0.32 to 1.16 ) than in HER2- patients ( HR = 1.26 ) . CONCLUSION Our data indicate that adding ADM to CMF might be beneficial for patients with HER2 + tumors PURPOSE The aim of the study was to evaluate the predictive value of HER2 and topoisomerase IIalpha gene ( TOP2A ) for the efficacy of epirubicin in the adjuvant setting of breast cancer patients . PATIENTS AND METHODS In the Danish Breast Cancer Cooperative Group trial 89D , 980 pre- and postmenopausal primary patients were r and omly allocated to either CMF ( cyclophosphamide , methotrexate , and fluorouracil ; n = 500 ) or CEF ( cyclophosphamide , epirubicin , and fluorouracil ; n = 480 ) times 9 , between January 1990 and November 1999 . Tumor tissue was retrospectively identified from 805 patients and was analyzed for HER2-positivity and for TOP2A-amplifications and deletions . RESULTS HER2-positivity was found in 33 % of the 805 investigated tumors and was not a predictive marker for epirubicin sensitivity . TOP2A changes were identified in 23 % of the 773 investigated tumors : 12 % had TOP2A amplifications and 11 % had TOP2A deletions . We found that patients with TOP2A amplification had an increased recurrence-free ( RFS ; hazard ratio [ HR ] , 0.43 ; 95 % CI , 0.24 to 0.78 ) and overall survival ( OS ; HR , 0.57 ; 95 % CI , 0.29 to 1.13 ) , respectively if treated with CEF compared with CMF , and that patients with TOP2A deletions had an almost identical hazard ratio ( RFS : HR , 0.63 ; 95 % CI , 0.36 to 1.11 ; OS : HR , 0.56 ; 95 % CI , 0.30 to 1.04 ) . This is in contrast to patients with a normal TOP2A genotype for whom similar outcome was observed in both treatment arms ( RFS : HR , 0.90 ; 95 % CI , 0.70 to 1.17 ; OS : HR , 0.88 ; 95 % CI , 0.66 to 1.17 ) . CONCLUSION TOP2A amplification- and possibly deletion-seems to be predictive markers for the effect of adjuvant epirubicin containing therapy in primary breast cancer , but a final conclusion has to await a confirmative study or a meta- analysis PURPOSE There is considerable interest in biologic markers able to predict the response of cancer patients to therapy . HER2 overexpression is a potential indicator of responsiveness to doxorubicin and paclitaxel and of unresponsiveness to tamoxifen in breast carcinoma patients . However , the significance of HER2 overexpression in responsiveness to cyclophosphamide , methotrexate , and fluorouracil ( CMF ) has remained unclear . In this study , we investigated this issue in the 386 breast cancer patients in the first CMF controlled clinical trial with a 20-year follow-up . PATIENTS AND METHODS Node-positive breast carcinoma patients were r and omly assigned to receive either no further treatment after radical mastectomy ( 179 women ) or 12 monthly cycles of adjuvant CMF chemotherapy ( 207 women ) . Overexpression of HER2 and the status of other tumor variables was assessed by immunohistochemistry in at least 324 ( 84 % ) of the 386 patients . Statistical analyses were performed to assess the efficacy of CMF treatment for the subgroups defined by HER2 and the status of other variables using a Bayesian approach . The end points considered were relapse-free survival ( RFS ) and cause-specific survival ( CSS ) . RESULTS Bayesian analysis of the treatment effect for HER2 and other variables indicated a clinical benefit from CMF treatment in all subgroups defined according to variables status . In particular regarding HER2 status , Bayesian estimates of RFS hazard ratios were equal to 0.484 and 0.641 and estimates of CSS hazard ratios were equal to 0.495 and 0.730 for HER2-positive and -negative tumors , respectively . CONCLUSION CMF treatment showed a clinical benefit in the considered subgroups , defined according to HER2 and other tumor variables status . Patients with HER2-positive or HER2-negative tumors benefit from CMF treatment , and the poor prognosis associated with the HER2 overexpression in the untreated group could be completely overcome by the chemotherapy treatment In a prospect i ve study at the University of Erlangen , Dept . Gynaecol , and Obstet . , 228 patients with breast cancer during their primary surgery and 20 patients during their metastatic surgery , underwent bone marrow punctions at six punction sides , which were twice at the sternum and twice at both iliac crest . The control group was 20 patients without an invasive carcinoma . Aim of the study was to detect or exclude tumour cells in the bone marrow via examination of the biopsies with monoclonal antibodies EMA and cytokeratin and consequently to find out the meaning of the results as prognostic criteria by statistical measurements . Tumour cells in the bone marrow were detected in 46.5 % ( 106/228 ) of the patients , who underwent a bone marrow biopsy during primary surgery . 21 % ( 23/106 ) of the patients who were bone marrow positive , but only 5.75 % ( 7/122 ) of the patients , who were bone marrow negative , developed metastases during a median follow-up of 20 months . This difference is statistically significant . 17 of the 30 patients with recurrences developed bone metastases ; 16 of them were EMA-positive . The median recurrence-free interval was 5 months in the bone marrow positive group and therefore noticeably shorter , than in the bone marrow negative patient group with 11 months . Of the nodal negative patients , 2 bone marrow positive patients developed distant metastases . With the knowledge of the nodal status and bone marrow biopsy result , it was possible to predict 28 of the 30 patients correctly in respect of their risk to metastasize . The result of the bone marrow puncture was proved in a multivariate analysis to be an independent prognostic factor . ( ABSTRACT TRUNCATED AT 250 WORDS 510 Background : CALGB 9344 showed 4 cycles of paclitaxel ( T ) after 4 cycles of doxorubicin/cyclophosphamide ( AC ) improved disease-free ( DFS ) and overall survival ( OS ) compared to 4 cycles of AC . Higher dose of A had no benefit ( Henderson JCO ' 03 ) . Prior studies suggest HER2 is associated with benefit from st and ard vs low dose of C&A ( Dressler JCO ' 05 ) . We hypothesized that HER2 might predict benefit from higher dose of A or from T , and that HER2 might refine the observed negative interaction of T with estrogen receptor ( ER ) . METHODS 3121 node + women in CALGB 9344 received 4 q3wk cycles of AC ( A : 60 , 75 , or 90 mg/m2 ) and then 4 cycles of T ( 175 mg/m2 q3wk ) or no T. Blocks were collected from ∼2800 subjects . 2 sets of 750 patients each were r and omly selected from these cases : Set 1 to develop hypotheses ; Set 2 for validation . Tissue specimens were available from 643 ( set1 ) and 679 ( set2 ) cases ( 20 % & 22 % total enrolled in 9344 respectively ) . HER2 was evaluated by FISH and by IHC ( by antibody cb11 and by Herceptest ) . Statistical analyses used Cox proportional hazards models , including interaction terms , and Kaplan-Meier estimates for comparing 5-yr DFS by treatment group . RESULTS In Set 1 , all 3 assays suggested that T improved DFS for HER2 + but not for HER2- . For this single set the interaction was not statistically significant . There appeared to be an interaction of HER2 , T and ER . IHC using cb11 was applied to Set 2 , revealing nearly identical results . In the two sets combined ( n=1322 ) , the interaction between HER2 and T was statistically significant ( p=0.013 ) . The 3-way interaction of HER2 , ER and T was hypothesis-generating and not tested statistically . Differences in 5-yr DFS rates ( 95 % CI ) for T vs. no T by HER2 and ER ( both sets combined ) There was no interaction between HER2 and dose of A. CONCLUSIONS These results suggest that the benefit of adding T to AC is greater for HER2 + tumors , even if ER+ , while T was of no apparent benefit in the ER+ , HER2- group . Further validation is needed from remaining cases in 9344 and from other trials involving T. [ Table : see text ] [ Table : see text ] PURPOSE Overexpression of the HER-2/c-neu/c-erbB2 proto-oncogene is associated with a worse prognosis in patients with breast cancer , perhaps due to an association of the HER-2 proto-oncogene protein with resistance to hormone and /or chemotherapy . Circulating levels of the extracellular domain ( ECD ) of the HER-2/c-neu-related protein ( NRP ) are elevated in 20 % to 40 % of patients with metastatic breast cancer . We investigated whether pretreatment levels of NRP predict response to hormone therapy ( HT ) . MATERIAL S AND METHODS Circulating NRP levels were determined in 94 patients who participated in a r and omized trial of three different doses of the antiestrogen , droloxifene ( DRO ) , as first-line HT for metastatic breast cancer . RESULTS NRP levels were elevated ( > or = 5,000 U/mL ) in 32 of 94 patients ( 34 % ) . Only three of 32 patients ( 9 % ) with elevated NRP levels responded to DRO , compared with 35 of 62 ( 56 % ) with nonelevated NRP levels ( P = .00001 ) . Low pretreatment NRP level was the most powerful predictor of response to DRO ( odds ratio of response , 22.4 ; P = .0001 ) . Elevated pretreatment NRP levels were also associated with a shorter time to progression ( TTP ) and survival duration . CONCLUSION Pretreatment circulating NRP levels predict a low likelihood of benefit from HT , specifically DRO , in patients with estrogen receptor (ER)-positive and /or progesterone receptor (PgR)-positive or receptor-unknown metastatic breast cancer , even when adjusted for other known predictive factors , such as ER and /or PgR levels , site of disease , disease-free interval from primary treatment to recurrence , and prior adjuvant chemotherapy . These data suggest that pretreatment NRP levels may be useful in deciding whether to treat a patient who otherwise appears to be likely to respond to HT PURPOSE Expression of ErbB-1 and ErbB-2 ( epidermal growth factor receptor and HER2/neu ) in breast cancer may cause tamoxifen resistance , but not all studies concur . Additionally , the relationship between ErbB-1 and ErbB-2 expression and response to selective aromatase inhibitors is unknown . A neoadjuvant study for primary breast cancer that r and omized treatment between letrozole and tamoxifen provided a context within which these issues could be addressed prospect ively . PATIENTS AND METHODS Postmenopausal patients with estrogen- and /or progesterone receptor-positive ( ER+ and /or PgR+ ) primary breast cancer ineligible for breast-conserving surgery were r and omly assigned to 4 months of neoadjuvant letrozole 2.5 mg daily or tamoxifen 20 mg daily in a double-blinded study . Immunohistochemistry ( IHC ) for ER and PgR was conducted on pretreatment biopsies and assessed by the Allred score . ErbB-1 and ErbB-2 IHC were assessed by intensity and completeness of membranous staining according to published criteria . RESULTS For study biopsy-confirmed ER+ and /or PgR+ cases that received letrozole , 60 % responded and 48 % underwent successful breast-conserving surgery . The response to tamoxifen was inferior ( 41 % , P = .004 ) , and fewer patients underwent breast conservation ( 36 % , P = .036 ) . Differences in response rates between letrozole and tamoxifen were most marked for tumors that were positive for ErbB-1 and /or ErbB-2 and ER ( 88 % v 21 % , P = .0004 ) . CONCLUSION ER+ , ErbB-1 + , and /or ErbB-2 + primary breast cancer responded well to letrozole , but responses to tamoxifen were infrequent . This suggests that ErbB-1 and ErbB-2 signaling through ER is lig and -dependent and that the growth-promoting effects of these receptor tyrosine kinases on ER+ breast cancer can be inhibited by potent estrogen deprivation therapy BACKGROUND We have shown previously that lumpectomy with radiation therapy was more effective than lumpectomy alone for the treatment of ductal carcinoma in situ ( DCIS ) . We did a double-blind r and omised controlled trial to find out whether lumpectomy , radiation therapy , and tamoxifen was of more benefit than lumpectomy and radiation therapy alone for DCIS . METHODS 1804 women with DCIS , including those whose resected sample margins were involved with tumour , were r and omly assigned lumpectomy , radiation therapy ( 50 Gy ) , and placebo ( n=902 ) , or lumpectomy , radiation therapy , and tamoxifen ( 20 mg daily for 5 years , n=902 ) . Median follow-up was 74 months ( range 57 - 93 ) . We compared annual event rates and cumulative probability of invasive or non-invasive ipsilateral and contralateral tumours over 5 years . FINDINGS Women in the tamoxifen group had fewer breast-cancer events at 5 years than did those on placebo ( 8.2 vs 13.4 % , p=0.0009 ) . The cumulative incidence of all invasive breast-cancer events in the tamoxifen group was 4.1 % at 5 years : 2.1 % in the ipsilateral breast , 1.8 % in the contralateral breast , and 0.2 % at regional or distant sites . The risk of ipsilateral-breast cancer was lower in the tamoxifen group even when sample margins contained tumour and when DCIS was associated with comedonecrosis . INTERPRETATION The combination of lumpectomy , radiation therapy , and tamoxifen was effective in the prevention of invasive cancer PURPOSE Amplification and /or overexpression of the HER-2/neu oncogene have been shown to correlate with poor clinical outcome in patients with axillary node-positive breast cancer . In contrast , the prognostic significance of HER-2/neu in node-negative disease is controversial . This study was undertaken to evaluate further the relationship between HER-2/neu and clinical outcome in node-negative disease . PATIENTS AND METHODS Overexpression of HER-2/neu was evaluated by permanent-section immunohistochemistry in tumors from 613 patients with long-term clinical follow-up enrolled in the Intergroup Study 0011 . Patients were stratified into low-risk ( n = 307 ) and high-risk ( n = 306 ) groups on the basis of tumor size and estrogen-receptor ( ER ) status . Low-risk patients were defined as having small ( less than 3 cm ) , ER-positive tumors and were observed without additional treatment after initial surgery . High-risk patients had either ER-negative or large ( greater than or equal to 3 cm ) , ER-positive tumors and were r and omized to be observed ( n = 146 ) or to receive adjuvant chemotherapy ( n = 160 ) after surgery . RESULTS The rate of HER-2/neu overexpression was 14.3 % in all tumors combined and was higher in invasive carcinomas with ( 21.5 % ) than without ( 11.2 % ) a significant noninvasive or in situ histologic component ( P less than .0001 ) . There was no relationship between overexpression and clinical outcome in the natural history setting of combined low-risk and high-risk patients not receiving adjuvant therapy ( n = 453 ) . Based on the reasoning that the influence of HER-2/neu may have been obscured by high-risk features and /or the presence of noninvasive carcinoma , we also analyzed the subset of patients with low-risk lesions not containing a significant in situ component ( n = 179 ) . Patients of this group with HER-2/neu-positive tumors showed only 40 % disease-free survival ( DFS ) at 5 years , compared with over 80 % in patients with HER-2/neu-negative tumors ( P less than .0001 ) . A similar inverse correlation was observed between overexpression and overall survival in the same group of patients ( P = .0001 ) . In a separate analysis involving patients receiving adjuvant chemotherapy , those with HER-2/neu-negative tumors showed significantly improved DFS in response to therapy compared with patients with HER-2/neu-positive tumors . CONCLUSION Overexpression of HER-2/neu is associated with poor clinical outcome in a subset of node-negative patients with small , ER-positive , predominantly invasive tumors and may play a role in resistance to adjuvant chemotherapy PURPOSE Trastuzumab combined with chemotherapy improves outcomes for women with human epidermal growth factor receptor 2 ( HER2 ) overexpressing advanced breast cancer . We conducted a pilot study of preoperative trastuzumab and paclitaxel , followed by surgery and adjuvant doxorubicin and cyclophosphamide chemotherapy in earlier stage breast cancer . PATIENTS AND METHODS Patients with HER2-positive ( 2 + or 3 + by immunohistochemistry ) stage II or III breast cancer received preoperative trastuzumab ( 4 mg/kg x 1 , then 2 mg/kg/wk x 11 ) in combination with paclitaxel ( 175 mg/m(2 ) every 3 weeks x 4 ) . Patients received adjuvant doxorubicin and cyclophosphamide chemotherapy following definitive breast surgery . Clinical and pathologic response rates were determined after preoperative therapy . Left ventricular ejection fraction and circulating levels of HER2 extracellular domain were measured serially . RESULTS Preoperative trastuzumab and paclitaxel achieved clinical response in 75 % and complete pathologic response in 18 % of the 40 women on study . HER2 3 + tumors were more likely to respond than 2 + tumors ( 84 % v 38 % ) . No unexpected treatment-related noncardiac toxicity was encountered . Four patients developed grade 2 cardiotoxicity ( asymptomatic declines in left ventricular ejection fraction ) . Baseline HER2 extracellular domain was elevated in 24 % of patients and declined with preoperative therapy . Immunohistochemical analyses of posttherapy tumor specimens indicated varying patterns of HER2 expression following trastuzumab-based treatment . CONCLUSION Preoperative trastuzumab and paclitaxel is active against HER2 overexpressing early-stage breast cancer and may be feasible as part of a sequential treatment program including anthracyclines . The observed changes in cardiac function merit further investigation . Correlative analyses of HER2 status may facilitate underst and ing of tumor response and resistance to targeted therapy AIM : To determine the importance of tumour DNA ploidy and cell proliferation , as measured by the S phase fraction ( SPF ) , in relation to other established clinicopathological indicators of prognosis in breast cancer . METHODS : A prospect i ve study of 308 patients . Tumours were staged following the TNM system criteria and were classified according to the histological type and grade . DNA flow cytometry was performed on fresh/frozen sample s stained with propidium iodide . Hormone receptors were analyzed by immunocytochemistry . A Cox proportional hazards regression model was used for statistical evaluation of the prognostic factors . RESULTS : Median follow up time was 39.6 months ( range 3 to 84 ) . A DNA diploid pattern was found in 134 tumours ( 43.5 % ) and aneuploid in 174 ( 56.5 % ) . Median SPF value was 6.1 % ( range 1 % to 27.8 % ) . DNA ploidy and SPF were strongly correlated ( p < 0.001 ) , and both were related to histological type ( p < 0.001 ) , grade of differentiation ( p < 0.001 ) , tumour size ( p = 0.006 and p = 0.002 ) , and hormone receptor activity ( p < 0.001 ) . DNA ploidy was also related to node status ( p = 0.022 ) , but SPF was not . In univariate analysis , there were significant correlations between disease-free survival and age , histological grade , tumour size , node status , DNA ploidy , SPF , and hormone receptor activity ; age , tumour size , node status , DNA ploidy , and hormone receptors were predictors of overall survival . In multivariate analysis , only node status ( p = 0.001 ) and DNA ploidy ( p = 0.006 ) retained independent prognostic significance in relation with overall survival , while node status ( p < 0.001 ) and SPF ( p < 0.001 ) were predictors of disease-free survival . DNA ploidy and SPF continued to predict disease-free and overall survival in lymph node positive ( pN1 ) patients but not in the lymph node negative ( pN0 ) group . CONCLUSIONS : DNA ploidy and SPF are strongly intercorrelated and have independent prognostic value for predicting the short term clinical outcome of breast carcinoma patients BACKGROUND Trastuzumab , a recombinant monoclonal antibody against HER2 , has clinical activity in advanced breast cancer that overexpresses HER2 . We investigated its efficacy and safety after excision of early-stage breast cancer and completion of chemotherapy . METHODS This international , multicenter , r and omized trial compared one or two years of trastuzumab given every three weeks with observation in patients with HER2-positive and either node-negative or node-positive breast cancer who had completed locoregional therapy and at least four cycles of neoadjuvant or adjuvant chemotherapy . RESULTS Data were available for 1694 women r and omly assigned to two years of treatment with trastuzumab , 1694 women assigned to one year of trastuzumab , and 1693 women assigned to observation . We report here the results only of treatment with trastuzumab for one year or observation . At the first planned interim analysis ( median follow-up of one year ) , 347 events ( recurrence of breast cancer , contralateral breast cancer , second nonbreast malignant disease , or death ) were observed : 127 events in the trastuzumab group and 220 in the observation group . The unadjusted hazard ratio for an event in the trastuzumab group , as compared with the observation group , was 0.54 ( 95 percent confidence interval , 0.43 to 0.67 ; P<0.0001 by the log-rank test , crossing the interim analysis boundary ) , representing an absolute benefit in terms of disease-free survival at two years of 8.4 percentage points . Overall survival in the two groups was not significantly different ( 29 deaths with trastuzumab vs. 37 with observation ) . Severe cardiotoxicity developed in 0.5 percent of the women who were treated with trastuzumab . CONCLUSIONS One year of treatment with trastuzumab after adjuvant chemotherapy significantly improves disease-free survival among women with HER2-positive breast cancer . ( Clinical Trials.gov number , NCT00045032 . The purpose of this prospect i ve study was to evaluate the usefulness of tumor marker CA 15.3 determined at the time of primary diagnosis as a prognostic factor in breast cancer . The power of CA 15.3 to predict survival was compared to established prognostic markers , namely stage , grade , receptor status , and histological subtype . CA 15.3 was abnormal ( ≥30 U/ml ) in 31 ( 11 % ) of the 272 patients . During the median follow-up of 9.8 years , 83 ( 31 % ) of the patients died of breast cancer . The disease-specific survival at 5 years were 86 and 45 % with normal and abnormal CA 15.3 values , respectively ( p < 0.00005 ) . When using univariate analysis , tumor size , nodal status , M status , stage , tumor grade , and CA 15.3 were significantly related to patient outcome . In the regression analysis , stage ( p = 0.00023 ) and CA 15.3 ( p = 0.00006 ) were prognostic factors for survival . These results indicate that CA 15.3 can predict survival in primary breast cancer We present a new prognostic classification design ated the Van Nuys classification for ductal carcinoma-in-situ ( DCIS ) . The classification combines high nuclear grade and comedo-type necrosis to predict clinical recurrence . Three groups of DCIS patients were defined by the presence or absence of high nuclear grade and comedo-type necrosis : 1 - -non-high- grade DCIS without comedo-type necrosis , 2 - -non-high- grade DCIS with comedo-type necrosis , 3 - -high- grade DCIS with or without comedo-type necrosis . There were 31 local recurrences in 238 patients after breast-conservation surgery 3.8 % ( 3/80 ) in group 1 , 11.1 % ( 10/90 ) in group 2 , and 26.5 % ( 18/68 ) in group 3 . The 8-year actuarial disease-free survivals were 93 % , 84 % , and 61 % , respectively ( all p < or = 0.05 ) . The Van Nuys classification defines three distinct and easily recognisable groups , each of which has a different likelihood of local recurrence if treated with breast conservation PURPOSE Decisions concerning the use of hormone therapy to treat metastatic breast cancer are made on the basis of the presence of estrogen receptor ( ER ) . Despite the presence of ER , half of patients will not respond to hormone treatment . The purpose of this study was to determine the effect of overexpression of HER-2/neu on the response to hormone therapy . PATIENTS AND METHODS Sera from 300 metastatic breast cancer patients with ER-positive ( ER+ ) , ER status unknown , or ER-/progesterone receptor-positive ( PR+ ) r and omized to receive second-line hormone therapy with either megestrol acetate or fadrozole were evaluated . An enzyme immunoassay ( EIA ) specific for the extracellular domain of the c-erbB-2 ( HER-2/neu ) oncogene product was used to detect serum levels . RESULTS Fifty-eight patients ( 19.3 % ) had elevated serum c-erbB-2 protein levels , using a selected cut-point of 30 U/mL. The response rate ( complete responses [ CRs ] plus partial responses [ PRs ] plus stable disease [ S ] ) to endocrine therapy was 40.9 % in 242 patients with low serum c-erbB-2 levels and only 20.7 % in 58 patients with elevated serum c-erbB-2 levels ( P = .004 ) . The median duration of treatment response was longer in the group with low serum c-erbB-2 levels ( 15.5 months ) compared with the group with elevated serum c-erbB-2 levels ( 11.6 months ) . Survival was also significantly shorter in patients with elevated serum c-erbB-2 levels ( P < .0001 ) . CONCLUSION Patients with ER+/c-erbB-2 + metastatic breast cancer are less likely to respond to hormone treatment than ER+/c-erbB-2- patients . Their survival duration is also shorter PURPOSE The objective of this study was to determine whether the addition of trastuzumab to chemotherapy in the neoadjuvant setting could increase pathologic complete response ( pCR ) rate in patients with human epidermal growth factor receptor 2 ( HER2 ) -positive disease . PATIENTS AND METHODS Forty-two patients with HER2-positive disease with operable breast cancer were r and omly assigned to either four cycles of paclitaxel followed by four cycles of fluorouracil , epirubicin , and cyclophosphamide or to the same chemotherapy with simultaneous weekly trastuzumab for 24 weeks . The primary objective was to demonstrate a 20 % improvement in pCR ( assumed 21 % to 41 % ) with the addition of trastuzumab to chemotherapy . The planned sample size was 164 patients . RESULTS Prognostic factors were similar in the two groups . After 34 patients had completed therapy , the trial 's Data Monitoring Committee stopped the trial because of superiority of trastuzumab plus chemotherapy . pCR rates were 25 % and 66.7 % for chemotherapy ( n = 16 ) and trastuzumab plus chemotherapy ( n = 18 ) , respectively ( P = .02 ) . The decision was based on the calculation that , if study continued to 164 patients , there was a 95 % probability that trastuzumab plus chemotherapy would be superior . Of the 42 r and omized patients , 26 % in the chemotherapy arm achieved pCR compared with 65.2 % in the trastuzumab plus chemotherapy arm ( P = .016 ) . The safety of this approach is not established , although no clinical congestive heart failure was observed . A more than 10 % decrease in the cardiac ejection fraction was observed in five and seven patients in the chemotherapy and trastuzumab plus chemotherapy arms , respectively . CONCLUSION Despite the small sample size , these data indicate that adding trastuzumab to chemotherapy , as used in this trial , significantly increased pCR without clinical congestive heart failure BACKGROUND Increased mammographic density reduces the sensitivity of screening mammography , is associated with increased breast cancer risk , and may be hormone related . We assessed the effect of estrogen-plus-progestin therapy on mammographic density . METHODS In a racially and ethnically diverse ancillary study of the Women 's Health Initiative , we examined data from 413 postmenopausal women who had been r and omly assigned to receive daily combined conjugated equine estrogens ( 0.625 mg ) plus medroxyprogesterone acetate ( i.e. , progestin ; 2.5 mg ) ( n = 202 ) or daily placebo ( n = 211 ) . We assessed the effect of estrogen plus progestin on measured mammographic percent density and abnormal findings over a 1-year and 2-year period . All tests of statistical significance were two-sided and were based on F tests or t tests from mixed-effects models . RESULTS Mean mammographic percent density increased by 6.0 % at year 1 , compared with baseline , in the estrogen-plus-progestin group but decreased by 0.9 % in the placebo group ( difference = 6.9 % , 95 % confidence interval [ CI ] = 5.3 % to 8.5 % ; P < .001 ) . The mean changes in mammographic density persisted but were attenuated slightly after 2 years , with an absolute increase of 4.9 % in the estrogen-plus-progestin group and a decrease of 0.8 % in the placebo group ( difference = 5.7 % , 95 % CI = 4.3 % to 7.3 % ; P < .001 ) . These effects were consistent across racial/ethnic groups but were higher among women aged 70 - 79 years in the estrogen-plus-progestin group ( mean increase at year 1 = 11.6 % ) than in the placebo group ( mean decrease at year 1 = 0.1 % ) ( difference of the means = 11.7 % , 95 % CI = 8.2 % to 15.4 % ; P < .001 , comparing across age groups ) . At year 1 , women who were adherent to treatment in the estrogen-plus-progestin group had a mean increase in density of 7.7 % ( 95 % CI = 5.9 % to 9.5 % ) , and women in the placebo group had a mean decrease in density of 1.1 % ( 95 % CI = 0.3 % to 1.9 % ) . Use of estrogen plus progestin was associated with an increased risk of having an abnormal mammogram at year 1 ( relative risk = 3.9 , 95 % CI = 1.5 to 10.2 ; P = .003 ) , compared with placebo , that was not explained by an increase in density . CONCLUSIONS Use of up to 2 years of estrogen plus progestin was associated with increases in mammographic density The tumor markers , CEA and CA 15.3 , were prospect ively studied in the sera of 1057 untreated patients with locoregional breast cancer diagnosed from 1983 to 2001 . Abnormal CEA and CA 15.3 serum levels were found in 13 % and 18.8 % of the patients , respectively . One tumor marker or another was abnormal in 22.8 % of the patients . Both tumor markers were correlated with tumor size and nodal involvement , with significantly higher concentrations in patients with larger tumors or in patients with nodal involvement . CEA was also related to the histological type and CA 15.3 with the histological grade . Univariate prognostic evaluation showed that tumor size , nodal involvement , histological grade , steroid receptors , adjuvant treatment , CEA , CA 15.3 and treatment before surgery were prognostic factors in both disease-free survival ( DFS ) and overall survival ( OS ) . Similar results were obtained in node-positive patients , with the same factors being prognostic , excluding adjuvant treatment and CA 15.3 , in both DFS and OS . Multivariate analysis showed that tumor size , nodal involvement , histological grade , ER and CEA were independent prognostic factors in both DFS and OS in the whole group as well as in node-positive patients . In contrast , tumor size was the only useful parameter in the prognosis of node-negative patients . CA 15.3 was useful for prognosis ( OS ) in node-negative patients . In summary , tumor markers are useful tools in the prognostic evaluation of patients with breast cancer PURPOSE The 21-gene recurrence score ( RS ) assay quantifies the likelihood of distant recurrence in women with estrogen receptor-positive , lymph node-negative breast cancer treated with adjuvant tamoxifen . The relationship between the RS and chemotherapy benefit is not known . METHODS The RS was measured in tumors from the tamoxifen-treated and tamoxifen plus chemotherapy-treated patients in the National Surgical Adjuvant Breast and Bowel Project ( NSABP ) B20 trial . Cox proportional hazards models were utilized to test for interaction between chemotherapy treatment and the RS . RESULTS A total of 651 patients were assessable ( 227 r and omly assigned to tamoxifen and 424 r and omly assigned to tamoxifen plus chemotherapy ) . The test for interaction between chemotherapy treatment and RS was statistically significant ( P = .038 ) . Patients with high-RS ( > or = 31 ) tumors ( ie , high risk of recurrence ) had a large benefit from chemotherapy ( relative risk , 0.26 ; 95 % CI , 0.13 to 0.53 ; absolute decrease in 10-year distant recurrence rate : mean , 27.6 % ; SE , 8.0 % ) . Patients with low-RS ( < 18 ) tumors derived minimal , if any , benefit from chemotherapy treatment ( relative risk , 1.31 ; 95 % CI , 0.46 to 3.78 ; absolute decrease in distant recurrence rate at 10 years : mean , -1.1 % ; SE , 2.2 % ) . Patients with intermediate-RS tumors did not appear to have a large benefit , but the uncertainty in the estimate can not exclude a clinical ly important benefit . CONCLUSION The RS assay not only quantifies the likelihood of breast cancer recurrence in women with node-negative , estrogen receptor-positive breast cancer , but also predicts the magnitude of chemotherapy benefit PURPOSE An association between the overexpression of proto-oncogene HER-2/neu and resistance to tamoxifen in estrogen receptor (ER)-positive primary and metastatic breast cancer has been suggested . We examine a possible interaction between HER-2/neu or p53 expression and tamoxifen effectiveness in patients with ER-positive , node-positive disease treated with cyclophosphamide , doxorubicin , and fluorouracil in a large adjuvant chemotherapy trial ( Cancer and Leukemia Group B [ CALGB ] 8541 ) . Tamoxifen assignment was not r and omized-physician discretion was used for premenopausal and postmenopausal women . Trial protocol then specified assignment to postmenopausal women with ER-positive tumors , although not all took tamoxifen . PATIENTS AND METHODS CALGB 8541 assessed HER-2/neu expression in patients with ER-positive disease by immunohistochemistry ( IHC ) and fluorescent in situ hybridization ( FISH ) and amplification by differential polymerase chain reaction ( PCR ) . IHC assessed expression of p53 . Univariate and multivariate proportional hazards models assessed tamoxifen-HER-2/neu status interactions and tamoxifen-p53 status interactions . RESULTS HER-2/neu status was available for 651 patients with ER-positive disease ; 650 , 608 , and 353 patients were assessed by IHC , PCR , and FISH , respectively . Approximately one half received tamoxifen . Reduction in risk of disease recurrence or death result ing from tamoxifen was approximately 37 % ( 32 % with overexpression and 39 % with normal expression of HER-2/neu ; n = 155 by IHC ) . The tamoxifen-HER-2/neu status interaction was not significant in multivariate analysis of all three HER-2/neu assessment methods . Tamoxifen-p53 interaction did not significantly predict outcome . CONCLUSION Disease-free and overall survival benefit of tamoxifen in patients with ER-positive , node-positive breast cancer does not depend on HER-2/neu or p53 status . Our data suggest that neither HER-2/neu nor p53 expression should be used to determine assignment of tamoxifen BACKGROUND Ductal carcinoma in situ ( DCIS ) of the breast is a disorder that has become more common since it may manifest as microcalcifications that can be detected by screening mammography . Since selected women with invasive cancer can be treated safely with breast conservation therapy it is paradoxical that total mastectomy has remained the st and ard treatment for DCIS . We did a r and omised phase III clinical trial to investigate the role of radiotherapy after complete local excision of DCIS . METHODS Between 1986 and 1996 , women with clinical ly or mammographically detected DCIS measuring less than or equal to 5 cm were treated by complete local excision of the lesion and then r and omly assigned to either no further treatment ( n=503 ) or to radiotherapy ( n=507 ; 50 Gy in 5 weeks to the whole breast ) . The median duration of follow-up was 4.25 years ( maximum 12.0 years ) . All analyses were by intention to treat . FINDINGS 500 patients were followed up in the no further treatment group and 502 in the radiotherapy group . In the no further treatment group 83 women had local recurrence ( 44 recurrences of DCIS , and 40 invasive breast cancer ) . In the radiotherapy group 53 women had local recurrences ( 29 recurrences of DCIS , and 24 invasive breast cancer ) . The 4-year local relapse-free was 84 % in the group treated with local excision alone compared with 91 % in the women treated by local excision plus radiotherapy ( log rank p=0.005 ; hazard ratio 0.62 ) . Similar reductions in the risk of invasive ( 40 % , p=0.04 ) and non-invasive ( 35 % , p=0.06 ) local recurrence were seen . CONCLUSIONS Radiotherapy after local excision for DCIS , as compared with local excision alone , reduced the overall number of both invasive and non-invasive recurrences in the ipsilateral breast at a median follow-up of 4.25 years PURPOSE It remains a challenge to predict which women with axillary node-negative ( ANN ) breast cancer at greatest risk of relapse may benefit most from adjuvant therapy . Increases in neu/erbB-2 have been implicated in breast cancer prognosis . Although overexpression has been investigated extensively , this study represents the first prospect i ve assessment of the prognostic value of neu/erbB-2 DNA amplification in a cohort of women with newly diagnosed ANN . METHODS A consecutive series of women was monitored for recurrence ( median follow-up duration , 36 months ) and tumors from 580 individuals were analyzed for amplification . The association of amplification with risk of recurrence was examined in survival analyses with traditional and histologic markers as prognostic factors . RESULTS Neu/erbB-2 was amplified in 20 % of cases . We found an increased risk of disease recurrence when neu/erbB-2 was amplified > or = twofold that persisted with adjustment for other prognostic factors ( relative risk , 2.36 ; P = .002 ) . We found some evidence that amplification was more important in patients who received chemotherapy compared with untreated patients . CONCLUSION neu/erbB-2 amplification is an independent prognostic factor for risk of recurrence in ANN breast cancer . Women with tumors without neu/erbB-2 amplification have a good prognosis ; aggressive therapy in this group is therefore difficult to justify . On the other h and , even with adjuvant chemotherapeutic treatment , women whose tumors exhibit neu/erbB-2 amplification have an increased risk of recurrence . We encourage a r and omized trial to compare more aggressive adjuvant chemotherapy versus st and ard chemotherapy for ANN women whose tumors exhibit neu/erbB-2 amplification The clinical relevance of DNA image cytometry ( ICM ) and flow cytometry ( FCM ) remains under investigation in breast carcinoma . The objective of the current work was to study the prognostic value of DNA ICM and FCM in a series of patients r and omized in a control trial . A multivariate analysis has been performed including other factors still under investigation such as Ki‐67 index , mitotic count , microvessel density , and P53 and Bcl‐2 expression PURPOSE To detail the outcome , in terms of local recurrence , local invasive recurrence , distant recurrence , and breast cancer mortality for patients previously treated for ductal carcinoma in situ ( DCIS ) . PATIENTS AND METHODS Clinical , pathologic , and outcome data were collected prospect ively for 707 patients with DCIS accrued from 1972 through June 1997 . RESULTS There were 74 local recurrences ; 39 were noninvasive ( DCIS ) and 35 were invasive . Fifty-one percent of patients with invasive recurrences presented with stage 1 disease ; the remainder presented with more advanced disease . Invasive local recurrence after mastectomy was a rare event that occurred in 0.8 % of patients . Invasive recurrence after breast preservation was more common and occurred in 7.4 % of patients . The 8-year probability of breast cancer mortality after breast preservation was 2.1 % , a number that is likely to increase with longer follow-up . The 8-year breast cancer-specific mortality and distant-disease probability for the subgroup of 74 patients with locally recurrent disease was 8.8 % and 20.8 % , respectively . If only the 35 invasive recurrences are considered as events , the 8-year breast cancer-specific mortality and distant-disease probability was 14.4 % and 27.1 % , respectively . CONCLUSION Invasive local recurrence after breast-preservation treatment for patients with DCIS is a serious event that converts patients with previous stage 0 disease to patients with disease that ranges from stage I to stage IV . These results , however , indicate that most DCIS patients with local recurrence can be salvaged PURPOSE To establish , in patients with breast cancer subjected to primary conventional chemotherapy and enrolled in a prospect i ve study , the mobilizing effect of therapy on potentially neoplastic cells by means of a reverse transcriptase polymerase chain reaction ( RT-PCR ) assay for mRNA of maspin , a protein related to the serpin family of protease inhibitors . PATIENTS AND METHODS Peripheral-blood sample s were collected from 30 patients with histologically proven breast cancer before and 4 and 8 days after conventional chemotherapy for three consecutive courses . A total of 216 sample s were screened for the presence of maspin mRNA by RT-PCR . RESULTS Before therapy , all sample s but one were negative . After chemotherapy , 11 patients ( 38 % ) had positive sample s. No difference in the rate of positivity was observed between groups defined according to initial stage , type of chemotherapy , Ki-67-related proliferative activity , or CA 15.3 expression . CONCLUSION Our results confirm that RT-PCR for maspin mRNA is a sensitive assay for the study of circulating potentially neoplastic mammary cells in patients with breast cancer . Moreover , our findings indicate a marked effect of conventional-dose chemotherapy on the mobilization of these cells in breast tumors . In our series of patients , this phenomenon does not seem to be associated with other known risk factors . Finally , the data suggest , without proving , an association between the presence of circulating maspin positive cells and a higher risk of disease progression . If this association could be confirmed , then the assay could have prognostic significance . However , larger confirmatory studies are necessary CONTEXT DNA flow cytometry of breast cancer is a proposed tumor marker of prognostic significance that is of controversial clinical utility because of lack of st and ardization and confirmatory studies . OBJECTIVE To evaluate the prognostic significance of the more informative technique of multiparametric 2-color DNA flow cytometry as recommended by the 1992 DNA Cytometry Consensus Conference . DESIGN Three hundred thirty-two breast carcinomas with 7 to 12 years of follow-up were prospect ively analyzed as fresh tumors that were mechanically dissociated into whole cell suspensions . These suspensions were dual fluorescence-labeled with propidium iodide ( DNA ) and antibodies to cytokeratin ( epithelium ) and leukocyte common antigen ( internal leukocyte control ) for gated analysis of sub population s. Multicycle software with histogram-dependent algorithms employing background , aggregate , and debris correction were used in DNA and cell-cycle quantitation . Data were analyzed according to the DNA Flow Cytometry Consensus Conference recommendations . RESULTS DNA ploidy and proliferation stratified into 3 categories were not predictive of overall or disease-free survival . Sixty-five percent of tumors were nondiploid , and 35.4 % were diploid . Two hundred six tumors were able to be evaluated for synthesis -phase fraction ( SPF ) analysis , with 74 of 206 cases in the low range ( < 13.4 % ) , 36.4 % in the intermediate range ( > 13.5 to < 25.4 % ) , and 27.6 % in the high SPF ( > 25.5 % ) category . Aneuploid tumors tended to have a higher SPF . Univariate survival analysis showed prognostic significance of the following : tumor size , stage , TNM components , vascular invasion , nuclear grade , and histologic grade . Only T classification , presence of positive axillary lymph nodes , and distant metastases were significant independent predictors of survival in multivariate Cox regression models . Age and hormone receptor status showed no prognostic significance . Synthesis -phase fraction was significantly correlated with tumor size , stage , T classification , nuclear and histologic grade , presence of estrogen or progesterone receptors , and axillary lymph node status . None of the histologic parameters showed any significant association with DNA aneuploidy , except for high nuclear and histologic grade and the absence of estrogen receptors . CONCLUSIONS Despite the use of state-of-the-art processing and flow cytometry analytic techniques , DNA ploidy and proliferation measurements were not predictive of survival in any stage of breast cancer . However , select histopathologic parameters and TNM stage were significant predictors of survival in univariate and multivariate analyses . We conclude that DNA ploidy and proliferation measurements do not provide significant prognostic information for clinicians to integrate into therapeutic decision making for patients with breast cancer New approaches are needed for the early detection of breast cancer . Proteomic profiling technologies , such as surface-enhanced laser desorption ionization mass spectrometry ( SELDI-MS ) , may be able to identify tumor markers in biological fluids . The objective of this study was to determine whether there are differences in protein expression patterns in nipple aspirate fluid ( NAF ) from the cancerous and noncancerous breasts of patients with unilateral breast cancer and the breasts of healthy volunteers . Paired NAF sample s were obtained from 23 women with stage I or II unilateral invasive breast carcinoma and five healthy female volunteers . Aliquots of the sample s were applied to SELDI Protein-chip arrays ( WCX2 and IMAC3-Cu++ ) , and protein expression was analyzed using time-of-flight MS . A total of 463 distinct peaks were detected and analyzed . In breast cancer patients , no differences in protein expression were identified between the breast with the intact primary carcinoma and the contralateral noncancerous breast . Seventeen peaks were overexpressed in cancer-bearing breasts compared to breasts of healthy volunteers ( p < 0.0005 ) . When spectra from the nontumor-bearing breasts of breast cancer patients were compared with spectra from breasts of healthy volunteers , two peaks that were overexpressed in breast cancer patients and one peak that was underexpressed in breast cancer patients were detected ( p < 0.0027 ) . SELDI-MS was able to identify differences in the phenotypic proteomic profile of NAF sample s obtained from patients with early-stage breast cancer and healthy women . Proteomic screening techniques such as SELDI-MS analysis of NAF may be useful for breast cancer screening and diagnosis PURPOSE To evaluate the prognostic importance of immunocytochemically determined c-erbB-2 overexpression in the primary tumors of patients with breast cancer . PATIENTS AND METHODS Primary tumors from 1,506 breast cancer patients ( 760 node-negative and 746 node-positive ) who were treated in the International ( Ludwig ) Breast Cancer Study Group Trial V were studied . Node-negative patients were allocated r and omly to either a single cycle of perioperative chemotherapy ( PeCT ) or no adjuvant treatment , and node-positive patients received either a prolonged chemotherapy ( with tamoxifen for postmenopausal patients ) or a single perioperative cycle . RESULTS Tumors from 16 % of the node-negative patients and 19 % of the node-positive patients were found to be c-erbB-2-positive . In both groups c-erbB-2 positivity correlated with negative progesterone receptors ( PR ) , negative estrogen receptors ( ER ) , and high tumor grade . Lobular carcinomas were all negative , and , thus support the view that such tumors represent a defined subtype of breast carcinoma . The expression of c-erbB-2 was prognostically significant for node-positive but not for node-negative patients . However , in both subgroups , the prognostic significance was greater for patients who had received more adjuvant therapy . For node-positive patients , the effect of prolonged- duration therapy on disease-free survival ( DFS ) was greater for patients without c-erbB-2 overexpression ( hazards ratio [ HR ] , = 0.57 ; 95 % confidence interval [ CI ] , 0.46 to 0.72 ) than for those with c-erbB-2 overexpression ( HR , 0.77 ; 95 % CI , 0.51 to 1.16 ) . Similarly , for node-negative patients , the effect of PeCT on DFS was greater for those without c-erbB-2 overexpression ( HR , 0.82 ; 95 % CI , 0.61 to 1.09 ) than for those with c-erbB-2 overexpression ( HR , 1.22 ; 95 % CI , 0.66 to 2.25 ) . CONCLUSION We conclude that tumors with overexpression of the c-erbB-2 oncogene are less responsive to cyclophosphamide , methotrexate , and fluorouracil (CMF)-containing adjuvant therapy regimens than those with a normal amount of gene product Mammography remains the diagnostic test of choice for breast cancer , but 20 % of cancers still go undetected . Many serum biomarkers have been reported for breast cancer but none have proven to represent effective diagnostic strategies . ProteinChip mass spectrometry is an innovative technology that search es the proteome for differentially expressed proteins , allowing for the creation of a panel or profile of biomarkers . The objective of this study was to construct unique cancer-associated serum profiles that , combined with a classification algorithm , would enhance the detection of breast cancer Pretreatment serum sample s from 134 female patients ( 45 with cancer , 42 with benign disease , 47 normal ) were procured prospect ively following institutional review board-approved protocol s. Proteins were denatured , applied onto ProteinChip affinity surfaces , and subjected to surface enhanced laser desorption/ionization ( SELDI ) time-of-flight mass spectrometry . The SELDI output was analyzed using Biomarker Pattern Software to develop a classification tree based on group-specific protein profiles . The cross-validation analysis of cancer versus normal revealed sensitivity and specificity rates of 80 % and 79 % , and for cancer versus benign disease , 78 % and 83 % , respectively . When 2 different chip surfaces were combined the sensitivity and specificity increased to 90 % and 93 % , respectively . The sensitivity and specificity of this technique are comparable to those of mammography and , if confirmed in a larger study , this technique could provide the means toward development of a simple blood test to aid in the early detection of breast cancer . The combination of SELDI ProteinChip mass spectrometry and a classification- and regression-tree algorithm has the potential to use serum protein expression profiles for detection and diagnosis of breast cancer Various molecular markers have been used for the detection of circulating breast cancer cells in blood by reverse transcriptase-polymerase chain reaction ( RT-PCR ) . Using nested RT-PCR , we compared the specificity and sensitivity of human mammaglobin ( hMAM ) , epidermal-growth-factor receptor ( EGF-R ) , and cytokeratin 19 ( CK-19 ) expression as markers for circulating carcinoma cells in the peripheral blood of patients with breast cancer . Blood sample s from 12 patients with ductal carcinoma in situ , 133 patients with invasive breast cancer , 20 patients with hematological malignancies , 31 healthy volunteers , and tumor tissues from 40 patients with invasive breast cancer were screened for mRNA encoding hMAM , EGF-R , or CK-19 by nested RT-PCR . In all breast cancer tissues , mRNA for hMAM , EGF-R , and CK-19 was detectable . In blood sample s from patients with invasive breast cancer , 11 ( 8 % ) , 13 ( 10 % ) , and 64 ( 48 % ) were positive for mRNA encoding hMAM , EGF-R , or CK-19 , respectively . Blood sample s from none of the healthy volunteers and patients with hematological disorders were positive for hMAM , while CK-19 mRNA was found in the blood of 12 ( 39 % ) healthy volunteers and transcripts for EGF-R and CK-19 were detectable in 5 ( 25 % ) and 2 ( 10 % ) , respectively , of the patients with hematological malignancies . Only hMAM mRNA expression in blood correlated with clinical parameters such as nodal status , metastasis , and CA 15–3 serum levels . In summary , hMAM transcripts detectable in blood by RT-PCR represent the most specific molecular marker for hematogenous spread of breast cancer cells . With the nested RT-PCR method , aberrant EGF-R mRNA expression might occasionally be found in hematological malignancies , whereas CK-19 mRNA expression proved to be rather nonspecific . The prognostic value of hMAM RT-PCR – based tumor cell detection in peripheral blood should be further tested and vali date d in prospect i ve studies The National Surgical Adjuvant Breast and Bowel Project ( NSABP ) conducted two sequential r and omized clinical trials to aid in resolving uncertainty about the treatment of women with small , localized , mammographically detected ductal carcinoma in situ ( DCIS ) . After removal of the tumor and normal breast tissue so that specimen margins were histologically tumor-free ( lumpectomy ) , 818 patients in the B-17 trial were r and omly assigned to receive either radiation therapy to the ipsilateral breast or no radiation therapy . B-24 , the second study , which involved 1,804 women , tested the hypothesis that , in DCIS patients with or without positive tumor specimen margins , lumpectomy , radiation , and tamoxifen ( TAM ) would be more effective than lumpectomy , radiation , and placebo in preventing invasive and noninvasive ipsilateral breast tumor recurrences ( IBTRs ) , contralateral breast tumors ( CBTs ) , and tumors at metastatic sites . The findings in this report continue to demonstrate through 12 years of follow-up that radiation after lumpectomy reduces the incidence rate of all IBTRs by 58 % . They also demonstrate that the administration of TAM after lumpectomy and radiation therapy results in a significant decrease in the rate of all breast cancer events , particularly in invasive cancer . The findings from the B-17 and B-24 studies are related to those from the NSABP prevention ( P-1 ) trial , which demonstrated a 50 % reduction in the risk of invasive cancer in women with a history of atypical ductal hyperplasia ( ADH ) or lobular carcinoma in situ ( LCIS ) and a reduction in the incidence of both DCIS and LCIS in women without a history of those tumors . The B-17 findings demonstrated that patients treated with lumpectomy alone were at greater risk for invasive cancer than were women in P-1 who had a history of ADH or LCIS and who received no radiation therapy or TAM . Although women who received radiation benefited from that therapy , they remained at higher risk for invasive cancer than women in P-1 who had a history of LCIS and who received placebo or TAM . Thus , if it is accepted from the P-1 findings that women at increased risk for invasive cancer are c and i date s for an intervention such as TAM , then it would seem that women with a history of DCIS should also be considered for such therapy in addition to radiation therapy . That statement does not imply that , as a result of the findings presented here , all DCIS patients should receive radiation and TAM . It does suggest , however , that , in the treatment of DCIS , the appropriate use of current and better therapeutic agents that become available could diminish the significance of breast cancer as a public health problem BACKGROUND The role of molecular markers in predicting the response to treatment of breast cancer is poorly defined . The Cancer and Leukemia Group B ( CALGB ) conducted a r and omized adjuvant-chemotherapy trial ( CALGB 8541 ) comparing three doses ( high , moderate , and low ) of cyclophosphamide , doxorubicin , and fluorouracil in 1572 women with node-positive breast cancer . This study ( CALGB 8869 ) was design ed to determine whether the DNA index , the S-phase fraction , c-erbB-2 expression , or p53 accumulation could be used as a marker to identify a subgroup of patients more likely than others to benefit from high doses of chemotherapy . METHODS Tissue blocks were obtained from 442 patients r and omly selected from the larger CALGB trial . Paraffin sections from the primary lesions were analyzed for DNA content , S-phase fraction , c-erbB-2 expression , and p53 accumulation . RESULTS Patients r and omly assigned to the high-dose regimen of adjuvant chemotherapy had significantly longer disease-free and overall survival if their tumors had c-erbB-2 overexpression . No further information was gained by adding the data on S-phase fraction or p53 accumulation to the analysis . There was no clear evidence of a dose-response effect in patients with minimal or no c-erbB-2 expression . CONCLUSIONS There is a significant dose-response effect of adjuvant chemotherapy with cyclophosphamide , doxorubicin , and fluorouracil in patients with overexpression of c-erbB-2 but not in patients with no c-erbB-2 expression or minimal c-erbB-2 expression . Overexpression of c-erbB-2 may be a useful marker to identify the patients who are most likely to benefit from high doses of adjuvant chemotherapy PURPOSE Studies evaluating the relationship of HER-2/neu breast tumor status and response to adjuvant endocrine therapy have reached conflicting conclusions about resistance of HER-2/neu-positive tumors to this treatment . We studied 282 patients participating in a r and omized controlled trial of adjuvant oophorectomy and tamoxifen or observation who had estrogen receptor-positive tumors and whose tumors were evaluated for HER-2/neu overexpression by immunohistochemistry . PATIENTS AND METHODS Univariate and multivariate Cox proportional hazards regression models and Kaplan-Meier disease-free and overall survival estimate methods were used . RESULTS HER-2/neu overexpression was a negative prognostic factor for overall survival . In univariate analyses , in HER-2/neu-positive patients , the hazard ratio ( HR ) for disease-free survival ( DFS ) with adjuvant endocrine therapy was 0.37 ( 95 % confidence interval [ CI ] , 0.26 to 0.89 ) ; for HER-2/neu-negative patients , the corresponding HR for DFS was 0.48 ( 95 % CI , 0.31 to 0.71 ) . The overall survival ( OS ) data were HR=0.26 ( 95 % CI , 0.07 to 0.92 ) and HR=0.68 ( 95 % CI , 0.32 to 1.42 ) for HER-2/neu-positive and HER-2/neu-negative patients , respectively . In multivariate models , the P values for tests of interaction of HER-2/neu status and response to adjuvant endocrine therapy were 0.18 and 0.07 for DFS and OS , respectively . Kaplan-Meier DFS and OS curves and 3-year DFS estimates were consistent in showing greater benefit to the HER-2/neu-positive subgroup given adjuvant treatment . CONCLUSION HER-2/neu overexpression does not adversely and may favorably influence response to adjuvant oophorectomy and tamoxifen treatment in patients with estrogen receptor-positive tumors PURPOSE To determine the effect of elevated serum HER-2/neu on the response of metastatic breast cancer patients to an aromatase inhibitor versus an antiestrogen . PATIENTS AND METHODS Five hundred sixty-two estrogen receptor-positive metastatic breast cancer patients were r and omized to first-line hormone therapy with either letrozole or tamoxifen . An automated enzyme-linked immunosorbent assay was used to detect serum HER-2/neu . RESULTS For patients with normal serum HER-2/neu ( 70.5 % ) , objective response rate ( ORR ; 39 % in letrozole-treated patients v 26 % in tamoxifen-treated patients ; P = .008 ) , clinical benefit ( CB ; 57 % v 45 % ; P = .016 ) , time to progression ( TTP ; median , 12.2 v 8.5 months ; P = .0019 ) , and time to treatment failure ( TTF ; median , 11.6 v 6.2 months ; P = .0066 ) were significantly better in patients treated with letrozole . In the elevated HER-2/neu group ( 29.5 % ) , there was no significant difference in ORR ( 17 % in letrozole-treated patients v 13 % in tamoxifen-treated patients ; P = .45 ) or CB ( 33 % v 26 % ; P = .31 ) , but there was a strong trend in favor of a longer TTP with letrozole ( median , 6.1 v 3.3 months ; P = .0596 ) and a significantly longer TTF with letrozole ( median , 6.0 v 3.2 months ; P = .0418 ) . Multivariate analysis revealed that elevated serum HER-2/neu was a negative predictor for ORR and TTP . CONCLUSION Patients with normal serum HER-2/neu receiving letrozole demonstrated a significantly greater ORR and CB and longer TTP and TTF than patients receiving tamoxifen . Although in patients with elevated serum HER-2/neu there was no significant difference between letrozole and tamoxifen in ORR or CB , there was a strong trend favoring longer TTP and significantly longer TTF with letrozole BACKGROUND Lapatinib , a tyrosine kinase inhibitor of human epidermal growth factor receptor type 2 ( HER2 , also referred to as HER2/neu ) and epidermal growth factor receptor ( EGFR ) , is active in combination with capecitabine in women with HER2-positive metastatic breast cancer that has progressed after trastuzumab-based therapy . In this trial , we compared lapatinib plus capecitabine with capecitabine alone in such patients . METHODS Women with HER2-positive , locally advanced or metastatic breast cancer that had progressed after treatment with regimens that included an anthracycline , a taxane , and trastuzumab were r and omly assigned to receive either combination therapy ( lapatinib at a dose of 1250 mg per day continuously plus capecitabine at a dose of 2000 mg per square meter of body-surface area on days 1 through 14 of a 21-day cycle ) or monotherapy ( capecitabine alone at a dose of 2500 mg per square meter on days 1 through 14 of a 21-day cycle ) . The primary end point was time to progression , based on an evaluation by independent review ers under blinded conditions . RESULTS The interim analysis of time to progression met specified criteria for early reporting on the basis of superiority in the combination-therapy group . The hazard ratio for the independently assessed time to progression was 0.49 ( 95 % confidence interval , 0.34 to 0.71 ; P<0.001 ) , with 49 events in the combination-therapy group and 72 events in the monotherapy group . The median time to progression was 8.4 months in the combination-therapy group as compared with 4.4 months in the monotherapy group . This improvement was achieved without an increase in serious toxic effects or symptomatic cardiac events . CONCLUSIONS Lapatinib plus capecitabine is superior to capecitabine alone in women with HER2-positive advanced breast cancer that has progressed after treatment with regimens that included an anthracycline , a taxane , and trastuzumab . ( Clinical Trials.gov number , NCT00078572 [ Clinical Trials.gov ] . ) Recently , the extracellular domain of the c‐erbB‐2 oncogene product ( HER‐2/neu ) has been reported to be elevated in the serum of one‐fourth of patients with metastatic breast carcinoma . The role of serum c‐erbB‐2 as a tumor marker , however , is still poorly defined . The purpose of this study was to evaluate the utility of serial serum c‐erbB‐2 levels as a tumor marker in patients with metastatic breast carcinoma We have investigated the relationship between c‐erbB2 status , estrogen receptor ( ER ) status and outcome in 274 women with node‐positive breast cancer who , following excision and axillary clearance , were r and omized to receive either 6 cycles of cyclophosphamide/methotrexate/fluorouracil ( CMF ) ( n = 129 ) or no such treatment ( n = 145 ) . Follow‐up data ( median 13.3 years ) were available on all patients . CMF improved relapse‐free and overall survival of all women . The greatest benefit was seen in women with ER‐negative tumors ; the median overall survival of those given CMF was 11.6 years compared with only 2 years for the control group . For the women with ER‐positive tumors the median overall survival of the CMF‐treated women was 11.3 years compared with 7.7 years in the control group . When benefit from CMF was examined in relation to c‐erbB2 status , the women with c‐erbB2‐negative tumors who received CMF had a median overall survival of 12.7 years compared with only 7.3 years for the c‐erbB2‐negative women in the control group . The improvement in survival was less marked in the women with c‐erbB2‐positive tumors ; median overall survival was 6.1 years for those who received CMF compared with 4.4 years for women in the control group . All women benefited from adjuvant CMF chemotherapy , those with ER‐negative tumors benefiting the most . Int . J. Cancer ( Pred . Oncol . ) 84:354–359 , 1999 . © 1999 Wiley‐Liss , |
12,359 | 21,795,405 | Conclusion : Our review of the literature showed a lack of well-described protocol s and studies on orientation and mobility training in identification cane use | Objective : This study aim ed to provide an overview of the development , content , feasibility , and effectiveness of existing orientation and mobility training programmes in the use of the identification cane . | Background Orientation and mobility training ( O&M-training ) in using an identification cane , also called symbol cane , is provided to people with low vision to facilitate independent participation in the community . In The Netherl and s this training is mainly practice -based because a st and ardised and validly evaluated O&M-training in using the identification cane is lacking . Recently a st and ardised O&M-training in using the identification cane was developed . This training consists of two face-to-face sessions and one telephone session during which , in addition to usual care , the client 's needs regarding mobility are prioritised , and cognitive restructuring techniques , action planning and contracting are applied to facilitate the use of the cane . This paper presents the design of a r and omised controlled trial aim ed to evaluate this st and ardised O&M-training in using the identification cane in older adults with low vision . Methods / design A parallel group r and omised controlled trial was design ed to compare the st and ardised O&M-training with usual care , i.e. the O&M-training commonly provided by the mobility trainer . Community-dwelling older people who ask for support at a rehabilitation centre for people with visual impairment and who are likely to receive an O&M-training in using the identification cane are included in the trial ( N = 190 ) . The primary outcomes of the effect evaluation are ADL self care and visual functioning with respect to distance activities and mobility . Secondary outcomes include quality of life , feelings of anxiety , symptoms of depression , fear of falling , and falls history . Data for the effect evaluation are collected by means of telephone interviews at baseline , and at 5 and 17 weeks after the start of the O&M-training . In addition to an effect evaluation , a process evaluation to study the feasibility of the O&M-training is carried out . Discussion The screening procedure for eligible participants started in November 2007 and will continue until October 2009 . Preliminary findings regarding the evaluation are expected in the course of 2010 . If the st and ardised O&M-training is more effective than the current O&M-training or , in case of equal effectiveness , is considered more feasible , the training will be embedded in the Dutch national instruction for mobility trainers . Trial registration Clinical Trials.gov PURPOSE To provide a comprehensive description of vision function beyond acuity in older individuals . METHODS A sample of 900 individuals between the ages of 58 and 102 years ( mean age of 75.5 ) was binocularly tested wearing habitual correction on a battery of psychophysical tests including high and low contrast acuity , low contrast low luminance acuity , disability glare , contrast sensitivity , color vision , stereoacuity , recovery from glare , and attentional visual fields . RESULTS High contrast acuity is reasonably well maintained on average , even into very old ages . Spatial vision measures under conditions of reduced contrast or luminance , or glare reveal significant impairment in a large portion of the aged . Many older individuals also have greatly reduced stereopsis , poor color discrimination , and severely restricted peripheral fields under conditions of divided attention . A single exponential function relating performance to age fits all spatial vision data sets . The function for individual spatial measures lies at different positions along the age scale . The derived aging function with a time constant of approximately 15 years also fits results from other recent aging studies of acuity and contrast sensitivity . CONCLUSIONS St and ard visual acuity underestimates the degree of vision function loss suffered by many older individuals under the nonoptimal viewing conditions encountered in daily life . All spatial vision functions show a similar rate of decline with age of the population , but the age at which decline begins varies among measures This paper reports two experiments about street crossing under conditions of free flowing traffic , with a focus on modern roundabout intersections . Experiment 1 was conducted at three roundabouts varying in size and traffic volume . Six totally blind and six sighted adults judged whether gaps in traffic were long enough to permit crossing to the median ( splitter ) isl and before the next vehicle arrived . Gap distributions and measures of judgment quality are reported . Overall , blind participants were about 2.5 times less likely to make correct judgments than sighted participants , took longer to detect crossable gaps , and were more likely to miss crossable gaps altogether . However , the differences were significant only at the two higher volume roundabouts . In Experiment 2 , we evaluated the response of drivers to pedestrians with and without mobility devices ( i.e. , long canes , dog guides ) . The experiment was conducted at a single-lane roundabout , a midblock crossing , and a two-way-stop-controlled intersection . Site-specific characteristics appeared to have a greater impact on drivers ' yielding than did a mobility device . Actual or potential applications of this research include the development of methods for assessing pedestrian safety and driver behavior as well as identifying intersections that may require modification in order to be accessible to blind pedestrians |
12,360 | 26,323,092 | Age , skin involvement , lower aGVHD grade , and the number of infusions are the main prognostic factors affecting the efficacy of MSC therapy for steroid-refractory aGVHD | BACKGROUND Mesenchymal stem cells ( MSCs ) have been broadly used experimentally in various clinical context s. The addition of MSCs to initial steroid therapy for acute graft-versus-host disease ( aGVHD ) may improve patient outcomes .
However , investigations regarding prognostic factors affecting the efficacy of MSC therapy for steroid-refractory aGVHD remain controversial .
We thus conducted a systematic review and meta- analysis of published clinical trials to determine possible prognostic factors affecting the efficacy of MSCs in treating steroid-refractory aGVHD . | Results of a previous phase I study suggested that a single 3 mg/m2 dose of the humanized non-FcR-binding anti-CD3 monoclonal antibody visilizumab ( Nuvion ) was well tolerated and had efficacy for the treatment of steroid-refractory acute graft-versus-host disease ( GVHD ) . We now report results of a multicenter phase II study in which visilizumab was given to 44 participants with steroid-refractory acute GVHD . Eighty-two percent of the participants had visceral involvement , and 86 % had overall grade III or IV acute GVHD at study entry . The respective complete and overall response rates were 14 % and 32 % at 42 days . Plasma Epstein-Barr virus DNA increased to more than 1000 copies per milliliter in 19 subjects . Seventeen received rituximab , and no fatal lymphoproliferative disorders were observed . Survival at 180 days was 32 % ( 95 % confidence interval , 18%-46 % ) . The administration of visilizumab as used in this study seems to be sufficiently safe and effective to warrant further assessment for treatment or prevention of GVHD Daclizumab , a humanized monoclonal IgG1 directed against the alpha chain of the interleukin-2 receptor ( IL-2R ) , is a competitive inhibitor of IL-2 on activated lymphocytes . To test the hypothesis that specific inhibition of activated lymphocytes in patients with ongoing acute graft-versus-host disease ( GVHD ) might ameliorate the process , we treated 43 patients with advanced or steroid-refractory GVHD with daclizumab . The first cohort of 24 patients was treated with daclizumab 1 mg/kg on days 1 , 8 , 15 , 22 , and 29 . On day 43 , the complete response ( CR ) rate was 29 % ( 95 % confidence interval [ CI ] , 13%-51 % ) . Survival on day 120 was 29 % ( 95 % CI , 13%-51 % ) . A second cohort of 19 patients was treated with daclizumab 1 mg/kg on days 1 , 4 , 8 , 15 , and 22 . For these patients , the CR rate on day 43 was 47 % ( 95 % CI , 24%-71 % ) , and survival on day 120 was 53 % ( 95 % CI , 29%-76 % ) . There were no infusion-related reactions and no serious side effects related to daclizumab . Following treatment , there was a reduction in serum concentrations of soluble IL-2R and peripheral blood CD3 ( + ) 25(+ ) lymphocytes , but these changes were not predictive of response . Daclizumab has substantial activity for the treatment of acute GVHD , and the second regimen evaluated is recommended for a controlled study . ( Blood , 2000 ; 95:83 - 89 BACKGROUND Severe graft-versus-host disease ( GVHD ) is a life-threatening complication after allogeneic transplantation with haemopoietic stem cells . Mesenchymal stem cells modulate immune responses in vitro and in vivo . We aim ed to assess whether mesenchymal stem cells could ameliorate GVHD after haemopoietic-stem-cell transplantation . METHODS Patients with steroid-resistant , severe , acute GVHD were treated with mesenchymal stem cells , derived with the European Group for Blood and Marrow Transplantation ex-vivo expansion procedure , in a multicentre , phase II experimental study . We recorded response , transplantation-related deaths , and other adverse events for up to 60 months ' follow-up from infusion of the cells . FINDINGS Between October , 2001 , and January , 2007 , 55 patients were treated . The median dose of bone-marrow derived mesenchymal stem cells was 1.4x10(6 ) ( min-max range 0.4 - 9x10(6 ) ) cells per kg bodyweight . 27 patients received one dose , 22 received two doses , and six three to five doses of cells obtained from HLA-identical sibling donors ( n=5 ) , haploidentical donors ( n=18 ) , and third-party HLA-mismatched donors ( n=69 ) . 30 patients had a complete response and nine showed improvement . No patients had side-effects during or immediately after infusions of mesenchymal stem cells . Response rate was not related to donor HLA-match . Three patients had recurrent malignant disease and one developed de-novo acute myeloid leukaemia of recipient origin . Complete responders had lower transplantation-related mortality 1 year after infusion than did patients with partial or no response ( 11 [ 37 % ] of 30 vs 18 [ 72 % ] of 25 ; p=0.002 ) and higher overall survival 2 years after haemopoietic-stem-cell transplantation ( 16 [ 53 % ] of 30 vs four [ 16 % ] of 25 ; p=0.018 ) . INTERPRETATION Infusion of mesenchymal stem cells exp and ed in vitro , irrespective of the donor , might be an effective therapy for patients with steroid-resistant , acute GVHD HE EFFICACY and safety of mycophenolate mofetil ( MMF ) in combination with CyA and Prednisolone for the treatment of acute and chronic GVHD ( aGVHD and cGVHD respectively ) after BMT and PBSCT from HLA mismatched and matched donors was evaluated in an open single center trial . Thirty patients , with aGVHD ( n 5 21 ) and cGVHD ( n 5 9 ) were treated with 2 g MMF daily in addition to Cyclosporin A ( CyA ) and Prednisolone . The control group consisted of 21 patients with aGVHD ( n 5 14 ) and cGVHD ( n 5 7 ) treated with Predniosolone and CyA only . Acute GVHD prophylaxis consisted of a combination of MTX , CyA , and Prednisolone . Overall grade improvement of aGVHD was found in 15/21 ( 71 % ) patients treated with MMF and was significantly different compared to the control group . MMF therapy in the treatment of cGVHD lead to moderate improvement in 4 of 8 patients with limited cGVHD . The most common adverse hematologic events of MMF were leukopenia ( n 5 6 ) , anemia ( n 5 4 ) , and thrombocytopenia ( n 5 5 ) . Haematological adverse events were not severe and did not require the discontinuation of MMF . Similar to the study group , leukopenia was found in 4 of the 21 control patients , anemia in 1/21 , and thrombocytopenia in 8/21 patients . In addition , 33 % of the patients in the control group developed severe adverse effects due to Prednisolone therapy , which were not observed in the MMF group . In this preliminary study , we have shown that MMF can be used safely for the treatment of aGVHD . In addition , the MMF therapy result ed in a significant dose reduction of Prednisolone for the treatment of GVHD when compared to a control group of patients . Treatment for GvHD after allogeneic related and unrelated BMT is one of the most critical elements in the reduction of transplant related morbidity and mortality 1 . High incidence of aGVHD indicates that more effective therapy and prevention of this severe complication is needed . MMF is a potent , uncompetitive , reversible inhibitor of eucaryotic inosine monophosphate dehydrogenase and is successfully used in the prevention of acute rejection in renal allograft recipients . 2 However , very little is known about the effect of MMF in prevention or treatment of GVHD in experimental animals . 3 The aim of our study was to evaluate the safety and efficacy of MMF in the treatment of aGVHD and cGVHD in patients after allogeneic BMT . PATIENTS AND METHODS This study included 30 patients given a sibling transplant BM or PBSCT ( n 5 12 ; four of which were HLA mismatched ) as well as allogeneic MUD BM or PBSCT ( n 5 18 ; three of which were HLA mismatched ) . Of these patients , 19 had AML , 7 had CML , and 4 had ALL . The conditioning regimens included TBI and CY in 24/30 patients . A BU/VP16 regimen was used in 3 patients . The control group included 21 patients given allogeneic familiar BM ( n 5 8 , 3 of which were HLA mismatched ) or allogeneic MUD BM ( n 5 13 , 3 of which were HLA mismatched ) . As many variables as possible were matched between the control patients and the patients receiving MMF in the following order of priority : diagnosis , disease phase at transplant , patient age 6 5 years , and type of BMT . Of these patients , 7 had AML , 11 had CML , and 3 had ALL . The conditioning regimens in the control group of patients included TBI and CY in 17/21 patients . A BU/CY regimen was used in 2 patients , and a BU/VP16 regimen was used in 2 patients BACKGROUND AND OBJECTIVES Tumor necrosis factor a is one of the principal cytokines involved in the pathogenesis of acute graft-versus-host-disease ( GVHD ) . Infliximab is an antibody to this cytokine . DESIGN AND METHODS We performed a retrospective analysis to evaluate the activity of infliximab in 32 patients with severe steroid-refractory acute GVHD . The patients received a median of 3 weekly courses of infliximab . The main organs involved in the patients were skin ( n=2 ) liver ( n=1 ) , bowel ( n=19 ) , liver and bowel at the same stage ( n=10 ) . RESULTS Nineteen out 32 patients ( 59 % ) responded to infliximab with 6 ( 19 % ) complete and 13 ( 40 % ) partial responses . Age younger than 35 years , intestinal involvement and a longer time between hematopoietic stem cell transplantation and infliximab administration were factors predicting a favorable response . Infective episodes developed in 23/32 ( 72 % ) patients . All the 13 unresponsive patients died of GVHD shortly after infliximab . Thirteen of 19 responsive patients were alive at a median follow-up of 449 days ( range 155 - 842 ) after infliximab , with no signs of chronic GVHD ( n=5 ) , limited ( n=5 ) or extensive involvement ( n=3 ) . Six patients who responded subsequently died , one of chronic lung GVHD , the others of vascular complications or infections ( 2 fungal diseases ) . INTERPRETATION AND CONCLUSIONS We conclude that infliximab is active in the treatment of severe steroid-refractory acute GVHD , particularly when the intestine is involved . Infections commonly followed its administration . The clinical activity of infliximab and the possibility that it increases the risk of infections are worth investigating in prospect i ve trials Background . Mesenchymal stem cells ( MSC ) have immunomodulatory effects . The aim was to study the effect of MSC infusion on graft-versus-host disease ( GVHD ) . Methods . We gave MSC to eight patients with steroid-refractory grade s III-IV GVHD and one who had extensive chronic GVHD . The MSC dose was median 1.0 ( range 0.7 to 9) × 106/kg . No acute side-effects occurred after the MSC infusions . Six patients were treated once and three patients twice . Two patients received MSC from HLA-identical siblings , six from haplo-identical family donors and four from unrelated mismatched donors . Results . Acute GVHD disappeared completely in six of eight patients . One of these developed cytomegalovirus gastroenteritis . Complete resolution was seen in gut ( 6 ) , liver ( 1 ) and skin ( 1 ) . Two died soon after MSC treatment with no obvious response . One of them had MSC donor DNA in the colon and a lymph node . Five patients are still alive between 2 months and 3 years after the transplantation . Their survival rate was significantly better than that of 16 patients with steroid-resistant biopsy-proven gastrointestinal GVHD , not treated with MSC during the same period ( P=0.03 ) . One patient treated for extensive chronic GVHD showed a transient response in the liver , but not in the skin and he died of Epstein-Barr virus lymphoma . Conclusion . MSC is a very promising treatment for severe steroid-resistant acute GVHD This trial evaluated the feasibility and efficacy of the infusion of mesenchymal stem cells exp and ed using human serum for the treatment of refractory acute or chronic graft-versus-host disease . Twenty-eight expansions were started . In 22 , a minimum of more than 1x106 mesenchymal stem cells/kg were obtained after a median of 26 days ; this threshold was not obtained in the remaining cases . Ten patients received cells for the treatment of refractory or relapsed acute graft-versus-host disease and 8 for chronic disease . One patient treated for acute graft-versus-host disease obtained a complete response , 6 had a partial response and 3 did not respond . One of the chronic patients achieved complete remision , 3 a partial response , and 4 did not respond . The current study supports the use of this approach in less heavily treated patients for both acute and chronic graft-versus-host disease . The trial has been registered at Clinical Trials.gov : identifier NCT00447460 The optimal primary endpoint for acute graft-versus-host disease ( GVHD ) therapeutic trials has not been established . In a retrospective analysis , we examined the response of 864 patients who received prednisone 60 mg/m(2)/d for 14 days , followed by an 8-week taper , as initial therapy for acute GVHD from 1990 - 2007 at the University of Minnesota . Patients received grafts of human leukocyte antigen-matched sibling bone marrow ( BM ) or peripheral blood ( PB ; n = 315 ) , partially matched sibling BM or PB ( n = 24 ) , unrelated donor BM or PB ( n = 313 ) , single ( n = 89 ) or double ( n = 123 ) umbilical cord blood . Day 28 responses were similar to day 56 responses and better than day 14 responses in predicting transplantation-related mortality ( TRM ) . In multiple regression analysis , patients with no response at day 28 were 2.78 times ( 95 % CI , 2.17 - 3.56 times ; P < .001 ) more likely to experience TRM before 2 years than patients with a response . Other factors associated with significantly worse 2-year TRM include older age , high-risk disease , severe GVHD , and partially matched related BM/PB . No other differences in response by donor source were observed . These data suggest that day 28 is the best early endpoint for acute GVHD therapeutic trials in predicting 2-year TRM This phase I multicenter study was aim ed at assessing the feasibility and safety of intravenous administration of third party bone marrow-derived mesenchymal stromal cells ( MSC ) exp and ed in platelet lysate in 40 patients ( 15 children and 25 adults ) , experiencing steroid-resistant grade II to IV graft-versus-host disease ( GVHD ) . Patients received a median of 3 MSC infusions after having failed conventional immunosuppressive therapy . A median cell dose of 1.5 × 10(6)/kg per infusion was administered . No acute toxicity was reported . Overall , 86 adverse events and serious adverse events were reported in the study , most of which ( 72.1 % ) were of infectious nature . Overall response rate , measured at 28 days after the last MSC injection , was 67.5 % , with 27.5 % complete response . The latter was significantly more frequent in patients exhibiting grade II GVHD as compared with higher grade s ( 61.5 % versus 11.1 % , P = .002 ) and was borderline significant in children as compared with adults ( 46.7 versus 16.0 % , P = .065 ) . Overall survival at 1 and 2 years from the first MSC administration was 50.0 % and 38.6 % , with a median survival time of 1.1 years . In conclusion , MSC can be safely administered on top of conventional immunosuppression for steroid resistant GVHD treatment . Eudract Number 2008 - 007869 - 23 , NCT01764100 We evaluated the feasibility , safety , and efficacy of the administration of 4 sequential doses ( intravenously administered on days 1 , 4 , 11 , and 18 ) of cryopreserved bone marrow-derived mesenchymal stromal cells ( MSC ) exp and ed with platelet lysate and obtained from third-party donors as a second-line treatment for steroid-refractory acute graft-versus-host ( aGVHD ) disease in a series of 25 patients . All patients received at least 2 doses of MSC , whereas 21 received 3 doses and 18 received the initially planned 4 doses . Because of the achievement of partial response , 4 patients received additional doses of MSC . Median single cell dose administered was 1.1 × 10(6 ) MSC/kg of recipient body weight . There were no adverse events related to the MSC infusion in the 99 procedures performed , with the exception of a cardiac ischemic event that occurred twice in a patient with prior history of cardiac ischemia . Response to MSC at 60 days after the first dose was evaluable in 24 patients . Seventeen patients ( 71 % ) responded ( 11 complete and 6 partial responses ) , with a median time to response of 28 days after the first MSC dose , whereas 7 patients did not respond . In summary , we can conclude that sequential cryopreserved third-party MSC therapy administered on days 1 , 4 , 11 , and 18 is a safe procedure for patients with steroid-refractory aGVHD . This strategy may provide a high rate of overall responses of aGVHD with a low toxicity profile Etanercept is a recombinant human soluble tumor necrosis factor ( TNF‐α ) receptor fusion protein that inhibits TNF‐α , a major mediator in the pathogenesis of graft‐versus‐host disease ( GVHD ) . The purpose of our study was to evaluate the safety and efficacy of etanercept therapy in 21 patients with steroid‐refractory acute GVHD ( aGVHD ) ( n = 13 ) and chronic GVHD ( cGVHD ) ( n = 8) . Etanercept 25 mg was given subcutaneously twice weekly for 4 weeks followed by 25 mg weekly for 4 weeks . At the time of initiation of etanercept , 14 patients had skin , 13 had gastro‐intestinal , 5 had liver , 5 had pulmonary , and 4 had oral involvement . Twelve patients ( 57 % ) completed 12 doses of therapy . Overall , 11 of 21 patients ( 52 % ) responded to the treatment with etanercept , including 6 patients ( 46 % ) with aGVHD [ n = 4 complete response ( CR ) , n = 2 partial response ( PR ) ] and 5 patients ( 62 % ) with cGVHD ( n = 1 CR , n = 4 PR ) . Clinical responses were most commonly seen in patients with refractory gut aGVHD with 55 % of the patients having a CR and 9 % having a PR . CMV reactivation occurred in 48 % of patients , bacterial infections in 14 % of patients , and fungal infections in 19 % of patients . Fourteen patients ( 67 % ) were alive after a median follow‐up of 429 days ( range 71–1007 days ) since initiation of etanercept . Seven patients died , 3 of infections , 2 of refractory aGVHD , and 2 of disease progression . In conclusion , our preliminary data indicate that etanercept is well tolerated and can induce a high response rate in patients with steroid‐refractory aGVHD and cGVHD , particularly in the setting of GI involvement . Am . J. Hematol . , 2006 . © 2006 Wiley‐Liss , Treatment for steroid-resistant acute graft-versus-host disease ( GVHD ) has had limited success . ABX-CBL is a hybridoma-generated murine IgM monoclonal antibody against the CD147 antigen , weakly expressed on human leukocytes and up-regulated on activated lymphocytes . A prospect i ve , multicenter , open-label , r and omized clinical trial comparing ABX-CBL to antithymocyte globulin ( ATG ) for treatment of steroid-resistant acute GVHD was conducted in 95 patients at 21 centers . Forty-eight patients received ABX-CBL daily for 14 consecutive days followed by up to 6 weeks of ABX-CBL twice weekly . Forty-seven patients received equine ATG , 30 mg/kg every other day for a total of 6 doses with additional courses as needed . By day 180 , overall improvement was similar in the patients receiving ABX-CBL and in those receiving ATG ( 56 % versus 57 % , P = .91 ) . Patient survival at 18 months was less favorable on ABX-CBL than on ATG ( 35 % versus 45 % ) , with the 95 % confidence interval ruling out that ABX-CBL provides at least a 10.4 % improvement . Data from this trial suggest that ABX-CBL does not offer an improvement over ATG in the treatment of acute steroid-resistant GVHD . This prospect i ve , multicenter , r and omized clinical trial for steroid-resistant acute GVHD serves as a model for future evaluation of new agents Steroid-refractory acute graft versus host disease ( AGVHD ) and chronic graft versus host disease ( CGVHD ) after allogeneic haematopoietic stem cell transplantation are major causes of morbidity and mortality . We undertook a phase I trial in patients with steroid-refractory AGVHD and CGVHD utilising bone marrow-derived mesenchymal stromal cells ( MSC ) . Additionally , all refractory patients were treated with etanercept concomitantly . The primary end point was safety , and secondary end points were best response achieved and overall survival . A median of two infusions per patient were administered . The response rate overall for AGVHD was complete in seven , partial in four and no response in one patient . Of the seven patients who achieved a complete response , six are alive . The actuarial survival for the overall group of AGVHD was 55 % at 30 months . Two patients with CGVHD achieved complete response with two partial responses and three with no response . The survival for those with AGVHD who achieved a complete response compared with those who did not was significant ( p = 0.03 ) . We identified no early or late safety issues in the nineteen patients . In view of the poor outlook for steroid-refractory AGVHD , further trials are warranted of MSC with steroid therapy , at the onset of AGVHD before steroid resistance Denileukin diftitox ( Ontak ) , a recombinant protein composed of human interleukin 2 ( IL-2 ) fused to diphtheria toxin , has selective cytotoxicity against activated lymphocytes expressing the high-affinity IL-2 receptor . We conducted a phase 1 study of denileukin diftitox in 30 patients with steroid refractory acute graft-versus-host disease ( GVHD ) . Seven patients received 9 microg/kg intravenously on days 1 and 15 ; 18 received 9 microg/kg intravenously on days 1 , 3 , 5 , 15 , 17 , and 19 ; and 5 received 9 microg/kg intravenously on days 1 to 5 and 15 to 19 . Hepatic transaminase elevation was the dose-limiting toxicity ( DLT ) , and dose level 2 was the maximum tolerated dose ( MTD ) . Overall , 71 % of patients responded with complete resolution ( 12 of 24 ; 50 % ) or partial resolution ( 5 of 24 ; 21 % ) of GVHD . Eight of 24 patients ( 33 % ) are alive at 6.3 to 24.6 months ( median , 7.2 months ) . Denileukin diftitox is tolerable and has promising activity in steroid-refractory acute GVHD We conducted a multicenter phase I/II study using mesenchymal stem cells ( MSCs ) manufactured from the bone marrow of healthy unrelated volunteers to treat steroid-refractory acute graft-versus-host disease ( aGVHD ) . Fourteen patients with hematological malignancies who suffered from grade II ( 9 patients ) or III aGVHD ( 5 ) were treated . Affected organs were gut ( 10 patients ) , skin ( 9 patients ) , and liver ( 3 patients ) . Seven patients had two involved organs . The median age was 52 . No other second-line agents were given . MSCs were given at a dose of 2 × 106 cells/kg for each infusion twice a week for 4 weeks . If needed , patients were continuously given MSCs weekly for an additional 4 weeks . By week 4 , 13 of 14 patients ( 92.9 % ) had responded to MSC therapy with a complete response ( CR ; n = 8) or partial response ( PR ; n = 5 ) . At 24 weeks , 11 patients ( 10 with CR and 1 with PR ) were alive . At 96 weeks , 8 patients were alive in CR . A total of 6 patients died , attributable to the following : underlying disease relapse ( 2 patients ) , breast cancer relapse ( 1 ) , veno-occlusive disease ( 1 ) , ischemic cholangiopathy ( 1 ) , and pneumonia ( 1 ) . No clear adverse effects associated with MSC infusion were observed . Third party-derived bone marrow MSCs may be safe and effective for patients with steroid-refractory aGVHD Preliminary studies using directed-donor ex vivo exp and ed human mesenchymal stem cells ( hMSCs ) have shown promise in the treatment of acute graft-versus-host disease ( aGVHD ) . However , their production is cumbersome and st and ardization is difficult . We describe the first experience of using a premanufactured , universal donor , formulation of hMSCs ( Prochymal ) in children ( n = 12 ; 10 boys ; 9 Caucasian ; age range : 0.4 - 15 years ) with treatment-resistant grade III and IV aGVHD who received therapy on compassionate use basis between July 2005 and June 2007 at 5 transplant centers . All patients had stage III or IV gut ( GI ) symptoms and half had additional liver and /or skin involvement . Disease was refractory to steroids in all cases and additionally to a median of 3 other immunosuppressive therapies . The hMSCs ( 8 × 10(6)cells/kg/dose in 2 patients and 2 × 10(6)cells/kg/dose in the rest ) were infused intravenously over 1 hour twice a week for 4 weeks . Partial and mixed responders received subsequent weekly therapy for 4 weeks . HLA or other matching was not needed . The hMSCs were started at a median of 98 days ( range : 45 - 237 ) posttransplant . A total of 124 doses were administered , with a median of 8 doses ( range : 2 - 21 ) per patient . Overall , 7 ( 58 % ) patients had complete response , 2 ( 17 % ) partial response , and 3 ( 25 % ) mixed response . Complete resolution of GI symptoms occurred in 9 ( 75 % ) patients . Two patients relapsed after initial response and showed partial response to retreatment . The cumulative incidence of survival at 100 days from the initiation of Prochymal therapy was 58 % . Five of 12 patients ( 42 % ) were still alive after a median follow-up of 611 days ( range : 427 - 1111 ) in surviving patients . No infusional or other identifiable acute toxicity was seen in any patient . Multiple infusions of hMSCs were well tolerated and appeared to be safe in children . Clinical responses , particularly in the GI system , were seen in the majority of children with severe refractory aGVHD . Given the favorable results observed in a patient population with an otherwise grave prognosis , we conclude that hMSCs hold potential for the treatment of aGVHD , and should be further studied in phase III trials in pediatric and adult patients PURPOSE Acute graft-versus-host disease ( aGVHD ) is a major complication of allogeneic bone marrow transplantation . In steroid-refractory aGVHD , mortality is very high . Pentostatin , a potent inhibitor of adenosine deaminase , induces lymphocyte apoptosis and may be useful in the treatment of this condition . PATIENTS AND METHODS We have conducted a phase I dose escalation study of pentostatin in patients with steroid-refractory aGVHD . Twenty-three patients were enrolled . Starting dose was 1 mg/m2/d by intravenous injection for 3 days . RESULTS The maximum tolerated dose was found to be 1.5 mg/m2/d . Late infections at the 2-mg/m2/d dose level were believed to be dose limiting toxicities . Lymphopenia was universal , but the neutrophil count was generally not affected . Fevers associated with neutropenia were not observed . Otherwise , the drug was well tolerated , with only modest elevations of liver function tests and thrombocytopenia , each being observed in a single patient . Twenty-two patients were assessable for response , including 14 complete responses ( 63 % ) and three partial responses ( 13 % ) . Median survival after therapy for the group was 85 days ( range , 5 to 1,258 days ) . CONCLUSION The suggested intravenous dose for a phase II study will be 1.5 mg/m2/d for 3 days . Pentostatin has activity in patients with steroid-refractory aGVHD that is worth exploring in future trials |
12,361 | 17,564,547 | CONCLUSIONS Most studies of cultural competence training used self-administered tools that have not been vali date d. The results of cultural competence training could be interpreted more accurately if vali date d tools were used | BACKGROUND Tools that measure knowledge , attitudes , and skills reflecting cultural competence of health professionals have not been comprehensively identified , described , or critiqued . | BACKGROUND This study examined the nurse outcomes of a cancer pain education program for nurses of patients from 11 different ethnic groups . METHODS Four hundred ninety six home , hospital , and hospice nurses participated in a one-day workshop or two half-day workshops on cancer pain assessment and management . Of these , 116 were r and omized to participate in a bedside-precepted visit with an oncology nurse specialist with pain specialization and a focus group to discuss attitudinal issues . Eighty-six nurses served as controls . Pre- , post- and one-year follow-up tests were administered . RESULTS Attitudes , knowledge , and application skills significantly improved for workshop-only and enriched-model nurses relative to controls . CONCLUSION For postgraduate nurses , daylong cancer pain education workshops were , in the group studied , as effective as h and s-on experience in improving cancer pain knowledge and changing attitudes . Both the workshop-only and the enriched-model nurses relative to controls had significantly improved knowledge and changed attitudes towards optimal pain management Abstract The changes in attitudes towards cultural difference of seventeen participants in a three-week community health study abroad program to Nepal were compared with the changes in attitudes of a similar group who did not participate in the tour . Participants in the tour group were surveyed eight weeks prior to departure and in the last week of the tour using a twenty-six item question naire employing a six-point forced-choice response scale . The responses of participants in the lour group showed significant shifts in relation to eight items compared while the responses for the control group showed no significant shifts . Observed student advantages of participation in this study tour included the development of independent behaviour and positive cultural adjustment and adaptation The purpose of this two group intervention study ( N = 94 ) was to determine if RNs who participated in " culture school " improved levels of cultural competence to a greater extent than RNs who attended nursing informatics classes . The Giger and Davidhizar Transcultural Assessment Model/Theory ( GDTAMT ) was the study 's theoretical foundation ( Giger & Davidhizar , 1995 ) . A sample of 94 participants , was identified from a r and omized group of all Jefferson County , Alabama RNs . R and omly assigned participants ( stratified by race ) experienced 8.5 hours of either culture school or nursing informatics classes and completed survey tools in three phases ( pre-intervention , immediate post intervention , three week follow-up ) . The Cultural Self-Efficacy Scale ( CSES ) by Bernal and Froman ( 1987 ) , knowledge base questions by Rooda ( 1990 ) , and demographic profiles were used . Concepts empirically measured using these tools were analyzed by transcultural nursing experts for their congruence with GDTAMT . Using repeated measures analyses of convariance ( race ) , significant differences between groups for both scales were found . Culture school participants demonstrated significantly more cultural self-efficacy and cultural knowledge , and these improvements remained during phase three . Further research is recommended to allow for greater generalizability of findings , an examination of client perceptions , and actual nurse behaviors The objective of the present study was to prepare new doctors with an awareness of cultural and health issues to facilitate positive experiences with indigenous patients . The study incorporated the 1998 intern orientation programs in Queensl and public hospitals . The study method included tier one of the Three Tiered Plan , which was implemented and audited . Indigenous liaison officers , directors of clinical training and medical education officers were surveyed prior to this implementation to determine whether any or similar initiatives had been carried out in previous years and /or were planned . Post-implementation feedback from interns was obtained by using question naires . Follow-up telephone interviews with the directors of clinical training , medical education officers and indigenous hospital liaison officers detailed the format and content of tier one at each hospital . The results indicate that this active intervention improved the implementation rate of tier one from nine of 19 ( 47 % ) Queensl and public hospitals in 1997 to 17 ( 90 % ) in 1998 . The 14 indigenous hospital liaison officers ( 100 % ) involved in the intervention perceived it as beneficial . Forty-three ( 67 % ) of interns who responded to the survey indicated they had encountered an indigenous patient within the last 2 - 4 months . The level of knowledge of indigenous health and culture self-reported by interns was between the categories ' enough to get by ' and ' inadequate ' . In conclusion , it appears that tier one has been successful and is to be a formal component of intern orientations in Queensl and public hospitals . Further initiatives in indigenous health and culture targeting medical staff ( i.e. tier two and tier three ) , are needed |
12,362 | 22,296,867 | Meta- analysis was appropriate for studies examining the immediate effect of SMT on mechanical pressure pain threshold ( PPT ) .
SMT demonstrated a favorable effect over other interventions on increasing PPT .
Subgroup analysis showed a significant effect of SMT on increasing PPT at the remote sites of stimulus application supporting a potential central nervous system mechanism . | Spinal manipulation ( SMT ) is commonly used for treating individuals experiencing musculoskeletal pain .
The mechanisms of SMT remain unclear ; however , pain sensitivity testing may provide insight into these mechanisms .
The purpose of this systematic review is to examine the literature on the hypoalgesic effects of SMT on pain sensitivity measures and to quantify these effects using meta- analysis . | Background The mechanisms thorough which spinal manipulative therapy ( SMT ) exerts clinical effects are not established . A prior study has suggested a dorsal horn modulated effect ; however , the role of subject expectation was not considered . The purpose of the current study was to determine the effect of subject expectation on hypoalgesia associated with SMT . Methods Sixty healthy subjects agreed to participate and underwent quantitative sensory testing ( QST ) to their leg and low back . Next , participants were r and omly assigned to receive a positive , negative , or neutral expectation instructional set regarding the effects of a specific SMT technique on pain perception . Following the instructional set , all subjects received SMT and underwent repeat QST . Results No interaction ( p = 0.38 ) between group assignment and pain response was present in the lower extremity following SMT ; however , a main effect ( p < 0.01 ) for hypoalgesia was present . A significant interaction was present between change in pain perception and group assignment in the low back ( p = 0.01 ) with participants receiving a negative expectation instructional set demonstrating significant hyper algesia ( p < 0.01 ) . Conclusion The current study replicates prior findings of c- fiber mediated hypoalgesia in the lower extremity following SMT and this occurred regardless of expectation . A significant increase in pain perception occurred following SMT in the low back of participants receiving negative expectation suggesting a potential influence of expectation on SMT induced hypoalgesia in the body area to which the expectation is directed INTRODUCTION The aim of the study was to investigate the hypoalgesic effects of a single spinal manipulation treatment on acute inflammatory reactions and pain induced by cutaneous application of capsaicin . METHODS Twenty healthy subjects participated in the experiment , which consisted of 2 sessions . In both sessions , following control measurements , topical capsaicin was applied to the right or left forearm to induce cutaneous inflammatory reactions . The cream was removed after 20 minutes . Then subjects received either spinal manipulation treatment ( SMT ) or " nonspinal manipulation treatment " ( N-SMT ) , respectively . In control as well as pretreatment and posttreatment intervals , the following tests were performed : measurement of the areas of mechanical hyperalgesia and stroking allodynia , assessment of spontaneous pain , and measurement of blood flow . RESULTS The results confirmed that topical capsaicin induced inflammatory reactions based on occurrence of hyperalgesia and allodynia , augmented pain perception , and increased blood flow following capsaicin application compared with the control session . When compared with N-SMT , spontaneous pain was rated significantly lower post-SMT ( P < .014 ) . In addition , areas of both secondary hyperalgesia and allodynia decreased after SMT ( hyperalgesia : P < .007 ; allodynia : P < .003 ) . However , there was no significant treatment effect for local blood flow . CONCLUSION These results suggest hypoalgesic effects following a single SMT . As local vascular parameter was not affected by the single SMT , the hypoalgesic effects appear to be due to central mechanisms The treatment of lateral epicondylalgia , a widely-used model of musculoskeletal pain in the evaluation of many physical therapy treatments , remains somewhat of an enigma . The protagonists of a new treatment technique for lateral epicondylalgia report that it produces substantial and rapid pain relief , despite a lack of experimental evidence . A r and omized , double blind , placebo-controlled repeated- measures study evaluated the initial effect of this new treatment in 24 patients with unilateral , chronic lateral epicondylalgia . Pain-free grip strength was assessed as an outcome measure before , during and after the application of the treatment , placebo and control conditions . Pressure-pain thresholds were also measured before and after the application of treatment , placebo and control conditions . The results demonstrated a significant and substantial increase in pain-free grip strength of 58 % ( of the order of 60 N ) during treatment but not during placebo and control . In contrast , the 10 % change in pressure-pain threshold after treatment , although significantly greater than placebo and control , was substantially smaller than the change demonstrated for pain-free grip strength . This effect was only present in the affected limb . The selective and specific effect of this treatment technique provides a valuable insight into the physical modulation of musculoskeletal pain and requires further investigation Background Current evidence suggests that spinal manipulative therapy ( SMT ) is effective in the treatment of people with low back pain ( LBP ) ; however , the corresponding mechanisms are unknown . Hypoalgesia is associated with SMT and is suggestive of specific mechanisms . Objective The primary purpose of this study was to assess the immediate effects of SMT on thermal pain perception in people with LBP . A secondary purpose was to determine whether the result ing hypoalgesia was a local effect and whether psychological influences were associated with changes in pain perception . Design This study was a r and omized controlled trial . Setting A sample of convenience was recruited from community and outpatient clinics . Participants Thirty-six people ( 10 men , 26 women ) currently experiencing LBP participated in the study . The average age of the participants was 32.39 ( SD=12.63 ) years , and the average duration of LBP was 221.79 ( SD=365.37 ) weeks . Intervention and Measurements Baseline demographic and psychological measurements were obtained , followed by quantitative sensory testing to assess temporal summation and Aδ fiber – mediated pain perception . Next , participants were r and omly assigned to ride a stationary bicycle , perform low back extension exercises , or receive SMT . Finally , the same quantitative sensory testing protocol was reassessed to determine the immediate effects of each intervention on thermal pain sensitivity . Results Hypoalgesia to Aδ fiber – mediated pain perception was not observed . Group-dependent hypoalgesia of temporal summation specific to the lumbar innervated region was observed . Pair-wise comparisons indicated significant hypoalgesia in participants who received SMT , but not in those who rode a stationary bicycle or performed low back extension exercises . Psychological factors did not significantly correlate with changes in temporal summation in participants who received SMT . Limitations Only immediate effects of SMT were measured , so the authors are unable to comment on whether the inhibition of temporal summation is a lasting effect . Furthermore , the authors are unable to comment on the relationship between their findings and changes in clinical pain . Conclusions Inhibition of Aδ fiber – mediated pain perception was similar for all groups . However , inhibition of temporal summation was observed only in participants receiving SMT , suggesting a modulation of dorsal horn excitability that was observed primarily in the lumbar innervated area OBJECTIVE The purpose of this study was to investigate the effects of a spinal thrust manipulation directed to the upper cervical segments ( atlanto-occipital joint ) on active mouth opening and pressure pain sensitivity in a trigeminal nerve innervated region ( sphenoid bone ) in women with mechanical neck pain . METHODS Thirty-seven women , ages 21 to 50 years old ( mean age , 35 + /- 8 years ) with mechanical neck pain were recruited for this study . Participants were r and omly assigned into 1 of 2 groups as follows : an experimental group that received a spinal manipulation of the atlanto-occipital joint and a control group that received a manual contact placebo intervention . Outcomes collected were assessed pretreatment and 5 minutes posttreatment by an assessor blinded to the treatment allocation and included active mouth opening and pressure pain thresholds ( PPTs ) over both sides of the sphenoid bone . A 2-way repeated measures analysis of variance ( ANOVA ) with time ( pre-post ) as the within subjects variable and group ( control , experimental ) as the between subjects variable was used to examine the effects of the intervention . The hypothesis of interest was group-time interaction . RESULTS The ANOVA showed a significant effect for time ( F = 23.1 ; P < .001 ) and an interaction between group and time ( F = 37.7 ; P < .001 ) for active mouth opening as follows : the experimental group showed a greater improvement when compared to the control group . A large positive within-group effect size ( d > 1.5 ) for the experimental group , whereas a negative medium within-group effect size ( d = -0.5 ) for the control group were identified . The ANOVA showed a significant interaction between group and time ( F = 14.4 ; P < .001 ) for PPT levels at the sphenoid bone as follows : the experimental group showed a greater improvement when compared to the control group . A medium positive within-group effect size ( d = -0.5 ) for the experimental group , whereas a negative medium within-group effect size ( d = -0.5 ) for the control group was found . CONCLUSIONS Our findings suggest that the application of an atlantoaxial joint thrust manipulation result ed in an increase in active mouth opening and PPT over a trigeminal nerve distribution area ( sphenoid bone ) in women with mechanical neck pain BACKGROUND CONTEXT Spinal manipulative techniques ( SMT ) have shown clinical effectiveness in some patients with musculoskeletal pain . PURPOSE We performed the current experiment to test whether regional pain modulation is to be expected from thoracic SMT . STUDY DESIGN / SETTING R and omized experimental design performed in a university pain laboratory . OUTCOME MEASURES The primary outcome was experimental pain sensitivity in cervical and lumbar innervated area . METHODS Ninety healthy volunteers were r and omly assigned to receive one of three interventions ( SMT , exercise , or rest ) to the upper thoracic spine . Participants completed question naires about pain-related affect and expectations regarding each of the interventions . We collected experimental pain sensitivity measures of cervical and lumbar innervated areas before and immediately after r and omly assigned intervention . Mixed model analysis of covariance was used to test changes in measures of experimental pain sensitivity . RESULTS No interactions or intervention ( group ) effects were noted for pressure or A-delta-mediated thermal pain responses . Participants receiving SMT had greater reductions in temporal sensory summation ( TSS ) . CONCLUSIONS This present study indicates thoracic SMT that reduces TSS in healthy subjects . These findings extend our previous work in healthy and clinical subjects by indicating change in the nocioceptive afferent system occurred caudal to the region of SMT application . However , the duration of reduction in TSS is unknown , and more work needs to be completed in clinical population s to confirm the relevance of these findings OBJECTIVE The purpose of this study was to evaluate the pain/pressure threshold of selected myofascial points in subjects with chronic mechanical back pain after a single manipulation or mobilization . DESIGN The study design was a r and omized control trial . SETTING Chiropractic College outpatient clinic . PARTICIPANTS Thirty subjects aged 18 - 50 yr ( mean age 31 yr , SD = 7 yr ) with chronic mechanical low back pain ( mean duration of pain 74 months , SD = 83 months ) were r and omized into two groups . One group received a manipulation and the other received a mobilization . OUTCOME MEASURE Pain/pressure threshold of selected myofascial points were measured before , immediately after , and 15 and 30 min postintervention . RESULTS Sixteen patients were allocated to the manipulation group and 14 to the mobilization group . Repeated measured analysis of variance for all locations failed to show clinical or statistical significance ( p > .287 ) . The overall effect between treatments and the interaction between treatment and time was not significant ( p > .268 ) . CONCLUSION The absence of significant changes may be attributed to the selection of myofascial points , the instrument sensitivity to small changes , the differences in baseline measures and the absence of effect from one intervention OBJECTIVE The objective of this study was to determine whether mechanical force , manually-assisted ( MFMA ) spinal manipulative therapy ( SMT ) affects paraspinal muscle strength as assessed through use of surface electromyography ( sEMG ) . DESIGN Prospect i ve clinical trial comparing sEMG output in 1 active treatment group and 2 control groups . SETTING Outpatient chiropractic clinic , Phoenix , AZ . SUBJECTS Forty subjects with low back pain ( LBP ) participated in the study . Twenty patients with LBP ( 9 females and 11 males with a mean age of 35 years and 51 years , respectively ) and 20 age- and sex-matched sham-SMT/control LBP subjects ( 10 females and 10 males with a mean age of 40 years and 52 years , respectively ) were assessed . METHODS Twenty consecutive patients with LBP ( SMT treatment group ) performed maximum voluntary contraction ( MVC ) isometric trunk extensions while lying prone on a treatment table . Surface , linear-enveloped sEMG was recorded from the erector spinae musculature at L3 and L5 during a trunk extension procedure . Patients were then assessed through use of the Activator Methods Chiropractic Technique protocol , during which time they were treated through use of MFMA SMT . The MFMA SMT treatment was followed by a dynamic stiffness and algometry assessment , after which a second or post-MVC isometric trunk extension and sEMG assessment were performed . Another 20 consecutive subjects with LBP were assigned to one of two other groups , a sham-SMT group and a control group . The sham-SMT group underwent the same experimental protocol with the exception that the subjects received a sham-MFMA SMT and dynamic stiffness assessment . The control group subjects received no SMT treatment , stiffness assessment , or algometry assessment intervention . Within-group analysis of MVC sEMG output ( pre-SMT vs post-SMT sEMG output ) and across-group analysis of MVC sEMG output ratio ( post-SMT sEMG/pre-SMT sEMG output ) during MVC was performed through use of a paired observations t test ( POTT ) and a robust analysis of variance ( RANOVA ) , respectively . MAIN OUTCOME MEASURES Surface , linear-enveloped EMG recordings during isometric MVC trunk extension were used as the primary outcome measure . RESULTS Nineteen of the 20 patients in the SMT treatment group showed a positive increase in sEMG output during MVC ( range , -9.7 % to 66.8 % ) after the active MFMA SMT treatment and stiffness assessment . The SMT treatment group showed a significant ( POTT , P < 0.001 ) increase in erector spinae muscle sEMG output ( 21 % increase in comparison with pre-SMT levels ) during MVC isometric trunk extension trials . There were no significant changes in pre-SMT vs post-SMT MVC sEMG output for the sham-SMT ( 5.8 % increase ) and control ( 3.9 % increase ) groups . Moreover , the sEMG output ratio of the SMT treatment group was significantly greater ( robust analysis of variance , P = 0.05 ) than either that of the sham-SMT group or that of the control group . CONCLUSIONS The results of this preliminary clinical trial demonstrated that MFMA SMT results in a significant increase in sEMG erector spinae isometric MVC muscle output . These findings indicate that altered muscle function may be a potential short-term therapeutic effect of MFMA SMT , and they form a basis for a r and omized , controlled clinical trial to further investigate acute and long-term changes in low back function & NA ; Manipulative therapy is frequently used in the management of musculoskeletal pain . A frequently reported clinical feature of this treatment is the immediacy with which it appears to initiate improvement in pain and function . A r and omised , double blind , placebo controlled , repeated measures design was employed to study the initial effects of a cervical spine treatment technique in a group of 15 patients with lateral epicondylalgia . Pressure pain threshold , pain‐free grip strength , upper limb neurodynamics , pain and function were assessed prior to and following application of either a treatment , placebo or control condition . All subjects received all three conditions . Differences between the pre‐post measures were used as indicators of change in subject 's symptom profiles . The treatment condition produced significant improvement in pressure pain threshold , pain‐free grip strength , neurodynamics and pain scores relative to placebo and control conditions ( P < 0.05 ) . In summary , this study demonstrates that manipulative therapy is capable of eliciting a rapid hypoalgesic effect OBJECTIVE To develop a sham manipulation procedure for the cervical spine for use in r and omized clinical trials of cervical disorders . METHODS A single-group , single-intervention study design was used . Adult neck pain subjects underwent a screening examination that included palpation for a site of cervical spine joint dysfunction . Eligible subjects underwent measurements of regional cervical ranges of motion as well as pressure algometry ( tenderness ) at the site of cervical joint dysfunction . Subjects were instructed that they would receive one of several types of manipulative procedures . A newly developed sham manipulation was delivered once . Subjects were then remeasured for ranges of motion and tenderness . They were asked if they had experienced any pain during the procedure , if they had experienced a " cavitation " sound , and if they thought that the procedure they received was a " real " manipulation . Finally , they were debriefed as to the deception involved in this study . A prior level of 65 % was set for endorsement that the procedure was a real manipulation . Changes in pre-post measures of ranges of motion and tenderness were analyzed descriptively for clinical ly important differences . RESULTS Twenty eligible subjects were included ( 12 males , 8 females ) with an average age of 30.4 ( 2.8 ) years . Twelve of the subjects were not students , with 3 of these having no prior experience with chiropractic treatment ; 8 were students . Of the total sample ( N = 19 ) , 8 ( 42.1 % ) indicated that the procedure was a " real adjustment " ; of the 12 nonstudents , 8 ( 58.3 % ) indicated similarly . None of the procedures in the final sample result ed in a cavitation , and none of the subjects registered the procedure as painful . None of the measures for ranges of motion or tenderness showed clinical ly important changes . CONCLUSIONS The sham cervical manipulation studied here appears to approximate the necessary features of a placebo maneuver in that it is perceived by a majority of nonstudent neck pain subjects to be a real manipulation , although it does not produce any important change in cervical status . The small sample size of nonstudent participants precludes a strong recommendation for this procedure at this time OBJECTIVE The purpose of this study is to investigate the immediate effects of a single cervical spine manipulation and a manual contact intervention ( MCI ) on pressure pain thresholds ( PPTs ) and thermal pain thresholds over the elbow region and pain-free grip ( PFG ) force in patients with lateral epicondylalgia ( LE ) . METHODS A repeated measures , crossover , single-blinded r and omized study was done . Ten patients with LE ( 5 female ) aged from 30 to 49 years ( mean , 42 ; SD , 6 years ) participated in this study . Subjects attended 2 experimental sessions on 2 separate days at least 48 hours apart . At each session , participants received either a manipulative intervention or MCI assigned in a r and om fashion . Pressure pain threshold and hot and cold pain thresholds ( HPT and CPT , respectively ) over the lateral epicondyle of both elbows was assessed preintervention and 5 minutes postintervention by an examiner blinded to the treatment allocation of the patients . In addition , PFG on the affected arm and maximum grip force on the unaffected side were also assessed . A 3-way analysis of variance ( ANOVA ) with time ( pre-post ) and side ( ipsilateral , contralateral to the intervention ) as within-subjects variable and intervention ( manipulation or MCI ) as between-subjects variable was used to evaluate changes in PPT , HPT , CPT , or PFG . RESULTS The ANOVA detected a significant effect for time ( F = 37.2 , P < .001 ) and a significant interaction between intervention and time ( F = 25.1 , P < .001 ) for PPT levels . Post hoc revealed that the manipulative intervention produced a greater increase of PPT in both sides when compared with MCI ( P < .001 ) . The ANOVA did not detect significant effects for time ( F = 2.7 , P > .2 ) , intervention ( F = 2.8 , P > .2 ) , or side ( F = 0.9 , P > .4 ) for HPT . Again , no significant effects for time ( F = 0.8 , P > .4 ) , side ( F = 0.6 , P > .4 ) , or intervention ( F = 0.8 , P > .5 ) was found for CPT . Finally , a significant interaction between intervention and time ( F = 9.4 , P = .004 ) and between time * side * intervention ( F = 18.2 , P < .001 ) was found for grip force . Post hoc analysis revealed that the cervical manipulation produced an increase of PFG on the affected side as compared with the MCI ( P < .001 ) . CONCLUSIONS The application of a manipulation at the cervical spine produced an immediate bilateral increase in PPT in patients with LE . No significant changes for HPT and CPT were found . Finally , cervical manipulation increased PFG on the affected side , but not the maximum grip force on the unaffected arm . Future studies with larger sample sizes are required to examine the effects of thrust manipulation on PPT , HPT , CPT , or PFG Background The underlying causes of spinal manipulation hypoalgesia are largely unknown . The beneficial clinical effects were originally theorized to be due to biomechanical changes , but recent research has suggested spinal manipulation may have a direct neurophysiological effect on pain perception through dorsal horn inhibition . This study added to this literature by investigating whether spinal manipulation hypoalgesia was : a ) local to anatomical areas innervated by the lumbar spine ; b ) correlated with psychological variables ; c ) greater than hypoalgesia from physical activity ; and d ) different for A-delta and C-fiber mediated pain perception . Methods Asymptomatic subjects ( n = 60 ) completed baseline psychological question naires and underwent thermal quantitative sensory testing for A-delta and C-fiber mediated pain perception . Subjects were then r and omized to ride a stationary bicycle , perform lumbar extension exercise , or receive spinal manipulation . Quantitative sensory testing was repeated 5 minutes after the intervention period . Data were analyzed with repeated measures ANOVA and post-hoc testing was performed with Bonferroni correction , as appropriate . Results Subjects in the three intervention groups did not differ on baseline characteristics . Hypoalgesia from spinal manipulation was observed in lumbar innervated areas , but not control ( cervical innervated ) areas . Hypoalgesic response was not strongly correlated with psychological variables . Spinal manipulation hypoalgesia for A-delta fiber mediated pain perception did not differ from stationary bicycle and lumbar extension ( p > 0.05 ) . Spinal manipulation hypoalgesia for C-fiber mediated pain perception was greater than stationary bicycle riding ( p = 0.040 ) , but not for lumbar extension ( p = 0.105 ) . Conclusion Local dorsal horn mediated inhibition of C-fiber input is a potential hypoalgesic mechanism of spinal manipulation for asymptomatic subjects , but further study is required to replicate this finding in subjects with low back pain Nine subjects with chronic mechanical neck pain syndromes were evaluated for pressure pain threshold ( PPT ) over st and ardized tender points in the paraspinal area surrounding a manipulable spinal lesion . The subjects were then allocated r and omly to an intervention consisting of either an oscillatory mobilization of the cervical spine ( n = 4 ) , which was design ated as the control procedure , or a rotational manipulation of the cervical spine ( n = 5 ) . An assessor-blinded re-evaluation of the pressure pain threshold levels was conducted after 5 min . In the group receiving a manipulation the mean increases in pressure pain threshold ranged from 40 - 56 % with an average of 45 % . In the control group no change in any of the pressure pain thresholds was found . These results were analyzed using ANOVA and were found to be statistically significant ( p less than 0.0001 ) . This study confirms that manipulation can increase local paraspinal pain threshold levels . The use of the pressure pain threshold meter allows for the determination of such a beneficial effect in the deeper tissues STUDY DESIGN Prospect i ve cohort/predictive validity study . OBJECTIVE To determine the predictive validity of selected clinical exam items and to develop a clinical prediction rule ( CPR ) to determine which patients with patellofemoral pain syndrome ( PFPS ) have a positive immediate response to lumbopelvic manipulation . BACKGROUND Quadriceps muscle function in patients with PFPS was recently shown to improve following treatment with lumbopelvic manipulation . No previous study has determined if individuals with PFPS experience symptomatic relief of activity-related pain immediately following this manipulation technique . METHODS AND MEASURES Fifty subjects ( 26 male , 24 female ; age range , 18 - 45 years ) with PFPS underwent a st and ardized history and physical examination . After the evaluation , each subject performed 3 typically pain-producing functional activities ( squatting , stepping up a 20-cm step , and stepping down a 20-cm step ) . The pain level perceived during each activity was rated on a numerical pain scale ( 0 representing no pain and 10 the worst possible pain ) . Following the assessment , all subjects were treated with a lumbopelvic manipulation , which was immediately followed by retesting the 3 functional activities to determine if there was any change in pain ratings . An immediate overall 50 % or greater reduction in pain , or moderate or greater improvement on a global rating of change question naire , was considered a treatment success . Likelihood ratios ( LRs ) were calculated to determine which examination items were most predictive of treatment outcome . RESULTS Data for 49 subjects were included in the data analysis , of which 22 ( 45 % ) had a successful outcome . Five predictor variables were identified . The most powerful predictor of treatment success was a side-to-side difference in hip internal rotation range of motion greater than 14 masculine ( + LR , 4.9 ) . If this variable was present , the chance of experiencing a successful outcome improved from 45 % to 80 % . CONCLUSION A CPR was developed to predict an immediate successful response to lumbopelvic manipulation in patients with PFPS . However , in light of a limited sample size and omission of potentially meaningful predictor variables , future studies are necessary to vali date the CPR OBJECTIVE To investigate the effect of instrument-delivered compared with traditional manual-delivered thrust chiropractic adjustments in the treatment of sacroiliac joint syndrome . METHODS Prospect i ve , r and omized , comparative clinical trial . Sixty patients with sacroiliac syndrome were r and omized into two groups of 30 subjects . Each subject received 4 chiropractic adjustments over a 2-week period and was evaluated at 1-week follow-up . One group received side-posture , high-velocity , low-amplitude chiropractic adjustments ; the other group received mechanical-force , manually-assisted chiropractic adjustments using an Activator Adjusting Instrument ( Activator Methods International , Ltd , Phoenix , Ariz ) . RESULTS No significant differences between groups were noted at the initial consultation for any of the outcome variables . Statistically significant improvements were observed in both groups from the first to third , third to fifth , and first to fifth consultations for improvements ( P < .001 ) in mean numerical pain rating scale 101 ( group 1 , 49.1 - 23.4 ; group 2 , 48.9 - 22.5 ) , revised Oswestry Low Back Pain Disability Question naire ( group 1 , 37.4 - 18.5 ; group 2 , 36.6 - 15.1 ) , orthopedic rating score ( group 1 , 7.6 - 0.6 ; group 2 , 7.5 - 0.8 ) , and algometry measures ( group 1 , 4.8 - 6.5 ; group 2 , 5.0 - 6.8 ) for first to last visit for both groups . CONCLUSIONS The results indicate that a short regimen of either mechanical-force , manually-assisted or high-velocity , low-amplitude chiropractic adjustments were associated with a beneficial effect of a reduction in pain and disability in patients diagnosed with sacroiliac joint syndrome . Neither mechanical-force , manually-assisted nor high-velocity , low-amplitude adjustments were found to be more effective than the other in the treatment of this patient population DESIGN A placebo , control , repeated- measures , single-blinded r and omized study . OBJECTIVES To compare the immediate effects on pressure pain threshold ( PPT ) tested over the lateral elbow region following a single cervical high-velocity low-amplitude ( HVLA ) thrust manipulation , a sham-manual application ( placebo ) , or a control condition ; and to analyze if a different effect was evident on the side ipsilateral to , compared to the side contralateral to , the intervention . BACKGROUND Previous studies investigating the effects of spinal manual therapy used passive mobilization procedures . There is a lack of studies exploring the effect of cervical manipulative interventions . METHODS Fifteen asymptomatic volunteers ( 7 male , 8 female ; aged 19 - 25 years ) participated in this study . Each subject attended 3 experimental sessions on 3 separate days , at least 48 hours apart . At each session , subjects received either the manipulation , placebo , or control intervention provided by an experienced therapist . The manipulative intervention was directed at the posterior joint of the C5 - 6 vertebral level . PPT over the lateral epicondyle of both elbows was assessed preintervention and 5 minutes postintervention by an examiner blinded to the treatment allocation of the subject . A 3-way analysis of covariance ( ANCOVA ) with intervention , side , and time as factors , and gender as covariate , was used to evaluate changes in PPT . RESULTS The analysis of variance detected a significant effect for intervention ( F = 31.46 , P < .001 ) and for time ( F = 33.81 , P < .001 ) , but not for side ( F = 0.303 , P > .5 ) . A significant interaction between intervention and time ( F = 15.74 , P < .001 ) was also found . Gender did not influence the comparative analysis ( F = 0.252 , P > .6 ) . Post hoc analysis revealed that the application of a HVLA thrust manipulation produced a greater increase of PPT in both elbows , as compared to placebo or control interventions ( P < .001 ) . No significant changes in PPT levels were found after the placebo and control interventions ( P > .6 ) . Within-group effect sizes were large for PPT levels in both elbows after the manipulative procedure ( d > 1.0 ) , but small after placebo or control intervention ( d < 0.1 ) . CONCLUSIONS The application of a manipulative intervention directed at the posterior joint of the C5 - 6 vertebral level produced an immediate increase in PPT over the lateral epicondyle of both elbows in healthy subjects . Effect sizes for the HVLA thrust manipulation were large , suggesting a strong effect of unknown clinical importance at this stage , whereas effect sizes for both placebo and control procedures were small , suggesting no significant effect OBJECTIVE This study examines if C7-T1 manipulation results in changes in pressure pain thresholds ( PPT ) over bilateral C5-C6 zygapophyseal joints in asymptomatic subjects . METHODS Thirty subjects , 13 men and 17 women , without a current history of neck , shoulder , or upper extremity pain participated . Participants were r and omly divided into 3 groups : experimental dominant group , subjects who received the manipulative thrust directed at the right side of the C7-T1 joint ; experimental nondominant group , those who received the thrust on the left side of the C7-T1 joint ; and a placebo group , those who received a sham-manual procedure . The outcome measure was the PPT on both right and left C5-C5 zygapophyseal joints , which was assessed at preintervention and 5 minutes postintervention by an assessor blinded to the treatment allocation of the subject . A 3-way repeated measures analysis of covariance was used to evaluate changes in PPT . RESULTS The analysis of covariance revealed time x group ( F = 32.3 ; P < .001 ) , time x side ( F = 4.9 ; P < .05 ) , time x sex ( F = 7.93 ; P < .01 ) , and time x group x sex ( F = 7.606 ; P < .001 ) interactions . Post hoc analyses found that ( a ) both experimental groups showed greater improvements in PPT than the placebo group ( P < .05 ) , without significant differences between them ( P > .6 ) ; ( b ) the right side had greater increases in PPT in both experimental groups ( P < .05 ) , but not within the placebo group ( P > .8 ) ; ( c ) men experienced greater increases in PPT levels than women , particularly in the experimental nondominant group ( P < .01 ) . Within-group effect sizes were large for both experimental groups ( d > 1 ) , but small for the placebo condition ( d < 0.2 ) . CONCLUSIONS These results suggest that a C7-T1 manipulation induced changes in PPT in both right and left C5-C6 zygapophyseal joints in healthy subjects Glover , J. R. , Morris , Jean G. , and Khosla , T. (1974).British Journal of Industrial Medicine,31 , 59 - 64 . Back pain : a r and omized clinical trial of rotational manipulation of the trunk . A therapeutic trial was conducted in a medium-sized engineering works on patients suffering from back pain with its accompanying tenderness and hyperaesthesia . The patients were r and omly allocated to two treatment groups , ( a ) manipulation , and ( b ) de-tuned ( i.e. , simulated ) short-wave diathermy , the latter acting as a placebo . The manipulated group were given one lumbar rotational manipulation session of 15 minutes or less and this was followed by four daily detuned short-wave diathermy sessions of 15 minutes . The control group were given five 15-minute daily sessions of detuned short-wave diathermy only . The patients ' own subjective assessment of relief from pain was recorded in the range 0 % ( no relief ) to 100 % ( complete relief ) . The responses were measured at three stages , ( 1 ) within 15 minutes , ( 2 ) three days after treatment , and ( 3 ) seven days after treatment . Although each of the two treatment groups showed progressive and marked improvement in the percentage of relief from pain during the seven-day period , there was no demonstrable difference between the two , except that at the 15-minute stage the relief from pain in the manipulated group was always greater than in the controls The response of paraspinal cutaneous pain tolerance levels to spinal manipulation has not been studied in an experimental model . This paper proposes such a model of pain tolerance measurement and describes the results of a controlled study of 50 assymptomatic subjects . The group receiving a spinal manipulation demonstrated a 140 % increase in local cutaneous pain tolerance levels which was statistically significant ( p less than 0.05 ) . This is consistent with previous hypotheses regarding the mode of action of manipulation in the relief of spinal pain The authors carried out a single-blind , r and omized controlled clinical trial of rotational manipulation for low-back pain of recent onset in 81 adults . Control treatments were minimal massage and low-level electrostimulation . Initial status and outcome were measured on scales quantifying symptoms , activities of dally life , mobility , tenderness to palpation , aggravation of pain by coughing or sneezing , limitation of motion on testing , and forward flexion . Both treated and control patients improved rapidly in the 2 - 3-week observation period . On retest there was no statistically significant difference between the improvement scores of the treated or control groups on any of the scales Osteopathic physicians caring for patients with fibromyalgia syndrome ( FM ) often use osteopathic manipulative treatment ( OMT ) in conjunction with other forms of st and ard medical care . Despite a growing body of evidence on the efficacy of manual therapy for the treatment of selected acute musculoskeletal conditions , the role of OMT in treating patients with chronic conditions such as FM remains largely unknown . Twenty-four female patients meeting American College of Rheumatology criteria for FM were r and omly assigned to one of four treatment groups : ( 1 ) manipulation group , ( 2 ) manipulation and teaching group , ( 3 ) moist heat group , and ( 4 ) control group , which received no additional treatment other than current medication . Participants ' pain perceptions were assessed by use of pain thresholds measured at each of 10 bilateral tender points using a 9-kg dolorimeter , the Chronic Pain Experience Inventory , and the Present Pain Intensity Rating Scale . Patients ' affective response to treatment was assessed using the Self-Evaluation Question naire . Activities of daily living were assessed using the Stanford Arthritis Center Disability and Discomfort Scales : Health Assessment Question naire . Depression was assessed using the Center for Epidemiological Studies Depression Scale . Significant findings between the four treatment groups on measures of pain threshold , perceived pain , attitude toward treatment , activities of daily living , and perceived functional ability were found . All of these findings favored use of OMT . This study found OMT combined with st and ard medical care was more efficacious in treating FM than st and ard care alone . These findings need to be replicated to determine if cost savings are incurred when treatments for FM incorporate nonpharmacologic approaches such as OMT OBJECTIVE To investigate a proposed model in which manipulative therapy produces a treatment-specific initial hypoalgesic and sympathoexcitatory effect by activating a descending pain inhibitory system . The a priori hypothesis tested was that manipulative therapy produces mechanical hypoalgesia and sympathoexcitation beyond that produced by placebo or control . Furthermore , these effects would be correlated , thus supporting the proposed model . DESIGN A r and omized , double-blind , placebo-controlled , repeated- measures study of the initial effect of treatment . SETTING Clinical neurophysiology laboratory . SUBJECTS Twenty-four subjects ( 13 women and 11 men ; mean age , 49 yr ) with chronic lateral epicondylalgia ( average duration , 6.2 months ) . INTERVENTION Cervical spine lateral glide oscillatory manipulation , placebo and control . OUTCOME MEASURES Pressure pain threshold , thermal pain threshold , pain-free grip strength test , upper limb tension test 2b , skin conductance , pileous and glabrous skin temperature and blood flux . RESULTS Treatment produced hypoalgesic and sympathoexcitatory changes significantly greater than those of placebo and control ( p < .03 ) . Confirmatory factor- analysis modeling , which was performed on the pain-related measures and the indicators of sympathetic nervous system function , demonstrated a significant correlation ( r = .82 ) between the latencies of manipulation-induced hypoalgesia and sympathoexcitation . The Lagrange Multiplier test and Wald test indicated that the two latent factors parsimoniously and appropriately represented their observed variables . CONCLUSION Manual therapy produces a treatment-specific initial hypoalgesic and sympathoexcitatory effect beyond that of placebo or control . The strong correlation between hypoalgesic and sympathoexcitatory effects suggests that a central control mechanism might be activated by manipulative therapy OBJECTIVE To evaluate the possible effect of the supine cervical rotary manipulation and the supine lateral break manipulation in the treatment of mechanical neck pain , according to subjective and objective clinical findings . BACKGROUND Delivering a supine lateral break manipulation to the ipsilateral side of an inflamed facet joint(s ) that exhibits a lateral flexion fixation may result in pain and /or discomfort to the patient . Thus the proposed alternative is a supine cervical rotary manipulation delivered on the ipsilateral side or a supine lateral break manipulation delivered on the contralateral side of the relevant joint(s ) . DESIGN R and omized , comparative clinical trial . SUBJECTS Two groups of 15 subjects diagnosed with mechanical neck pain . INTERVENTION The diagnosis of mechanical neck pain and the identification of lateral flexion fixations in the cervical spine were made with conventional clinical evaluation , including motion palpation . Group A received a cervical rotary manipulation(s ) on the ipsilateral side of the lateral flexion fixation(s ) , while group B received a supine lateral break manipulation(s ) on the contralateral side of the lateral flexion fixation(s ) . Subjects received a maximum of 10 treatments over a 4-week treatment period . OUTCOME MEASURES Both treatment groups were assessed with subjective ( Numerical Pain Rating Scale 101 , McGill Short-Form Pain Question naire and the Canadian Memorial Chiropractic College Neck Disability Index ) and objective ( cervical range of motion goniometer and algometer ) measurement parameters at the initial consultation ( before any treatment ) , the final consultation , and at a 1-month follow-up consultation . Statistical analysis was conducted at a 95 % confidence level ( alpha = .05 ) with the non-parametric 2-tailed Wilcoxon signed ranks test , the Mann-Whitney U test , and descriptive statistics . Two-tailed power analysis was conducted after the fact , where a confidence level of 80 % ( beta = .20 ) was considered satisfactory . RESULTS Intragroup analysis indicated a significant difference between the initial consultation data and the final consultation data for the subjective data , indicating an effect . Analysis of the objective data did not reveal any significant difference . Intergroup analysis did not reveal any significant difference between the 2 groups when comparing the data of the initial consultation and the final consultation , indicating that both treatments had a similar or equal effect . Power analysis was not satisfactory for most data , indicating the possibility of many Type II errors . CONCLUSION AND RECOMMENDATIONS Statistically , the results suggested that both treatments had an effect but that neither group showed a benefit over the other . However , because of the unsatisfactory power of the study , conclusions are to be drawn with caution . Clinical significance supported the statistical outcomes where it was suggested that both treatments had an effect and that neither treatment had a greater effect . A larger sample size and the inclusion of a placebo group is recommended to reveal true treatment outcomes and trends Twenty-one patients with symptomatic cervical spondylosis or nonspecific neck pain were given an amnesic dose of diazepam before manipulation of the cervical spine . Eighteen patients served as controls and also received diazepam but no manipulation . Results were obtained in a r and omized , double-blind fashion . Statements of outcome by patients and mean visual analog scales for pain and activity showed no significant differences between manipulation and control groups , though both tests favored manipulation . Control subjects subsequently treated by manipulation showed no consistent favorable response . Question naires dealing with personality , life events , social and medical histories , etc . , provided no correlations with outcome , nor did radiographic findings . Diffuse local tenderness correlated with high pain scores after treatment . The authors conclude that the value of a single manipulation of the cervical spine has not been established and that further exploration of indications is needed . The use of intravenous diazepam should be considered because it allows a double-blind experimental design Context In this r and omized , controlled trial , spinal manipulation plus exercise produced outcomes for low back pain similar to those produced by exercise alone . Yet , some patients did respond to spinal manipulation , and it would be helpful for doctors to be able to identify such patients . Contribution Patients were most likely to benefit from spinal manipulation if they met 4 of 5 of the following criteria : symptom duration less than 16 days , no symptoms distal to knee , score less than 19 on a fear-avoidance measure , at least 1 hypomobile lumbar segment , and at least 1 hip with more than 35 degrees of internal rotation . Implication s Clinicians may be able to use these criteria to identify patients with low back pain who are good c and i date s for spinal manipulation . The Editors Next to the common cold , low back pain is the most common reason that individuals visit a physician 's office ( 1 ) . Billions of dollars in medical expenditures and lost labor costs for this condition are incurred each year ( 2 , 3 ) . Attempts to identify effective interventions for individuals with low back pain have been largely unsuccessful ( 4 ) . In particular , conflicting evidence exists about the effectiveness of spinal manipulation ; some r and omized trials have shown a benefit , while other trials have not ( 5 - 7 ) . These conflicting conclusions are reflected in the various recommendations in national clinical practice guidelines , with some recommending manipulation and others not ( 8) . The variety of conclusions in trials of manipulation may be attributable to the failure of research ers to adequately consider the importance of classification . Using broad inclusion criteria results in a heterogeneous sample that may include many patients for whom no benefit is expected , thus masking the intervention 's true value ( 9 , 10 ) . Consequently , developing methods for matching patients with low back pain to treatments that are most likely to benefit them has become an important research priority ( 11 ) . Clinical prediction rules are tools design ed to assist clinicians in decision making when caring for patients ( 12 ) . Several clinical prediction rules have been developed and vali date d to improve clinical decision making for the use of imaging in patients with ankle , knee , cervical spine , or minor head injuries ( 13 - 16 ) . Few studies have attempted to develop rules that establish prognosis on the basis of outcome from a specific intervention , such as spinal manipulation . Recently , Flynn and colleagues ( 17 ) developed a clinical prediction rule for identifying patients with low back pain who are likely to benefit from manipulation . They examined a series of patients with low back pain who received a manipulation intervention . Five factors formed the most parsimonious set of predictors for identifying patients who achieved at least 50 % improvement in disability within 1 week with a maximum of 2 manipulation interventions ( Table 1 ) ( 17 ) . The positive likelihood ratio among patients who met at least 4 of 5 of the criteria was 24.4 ( 95 % CI , 4.6 to 139.4 ) . Table 1 . Five Criteria in the Spinal Manipulation Clinical Prediction Rule Clinical prediction rules must be vali date d in separate population s before being recommended for widespread implementation ( 18 ) . A clinical prediction rule for identifying which patients with low back pain are most likely to respond to manipulation could improve clinical efficiency and re source utilization . Thus , we aim ed to vali date the spinal manipulation clinical prediction rule in a multicenter trial . Methods We considered consecutive patients with a primary symptom of low back pain who were referred to physical therapy for participation . We used 14 physical therapists at 8 clinics in various U.S. regions and setting s ( 2 academic medical centers and smaller outpatient practice setting s ) . Most participating sites were health care facilities within the U.S. Air Force . Each site 's institutional review board approved the study before we began recruitment and data collection . Inclusion criteria were age 18 to 60 years ; a primary symptom of low back pain , with or without referral into the lower extremity ; and an Oswestry Disability Question naire ( ODQ ) score of at least 30 % . We excluded patients who had red flags for a serious spinal condition ( for example , tumor , compression fracture , or infection ) , those who had signs consistent with nerve root compression ( that is , positive straight-leg increase < 45 degrees or diminished reflexes , sensation , or lower-extremity strength ) , those who were pregnant , or those who had previous surgery to the lumbar spine or buttock . These criteria are consistent with those used in Flynn and colleagues ' study ( 17 ) and were design ed to include patients without a contraindication to manipulation . Once patients were admitted to the study , we used intention-to-treat principles , and no patient was removed for nonadherence . History and Physical Examination Before r and omization , patients completed several self-report measures and then received a st and ardized history and physical examination . We collected demographic information , including age and sex ; medical history ; and location and nature of symptoms . Self-report measures included a body diagram to assess the symptom distribution ( 19 ) . We used an 11-point pain-rating scale ranging from 0 ( no pain ) to 10 ( worst imaginable pain ) to assess current pain intensity and the best and worst level of pain during the last 24 hours ( 20 ) . We used the average of the 3 ratings . We used the Fear-Avoidance Beliefs Question naire ( FABQ ) to quantify the patient 's fear of pain and beliefs about avoiding activity ( 21 ) . Previous studies have found a high level of testretest reliability for both the FABQ physical activity and work subscales ( 22 ) . Fearavoidance beliefs have been associated with current and future disability and work loss in patients with acute ( 23 ) and chronic ( 24 ) low back pain . The modified ODQ is a region-specific disability scale for patients with low back pain ( 25 ) that has high levels of reliability , validity , and responsiveness ( 26 ) . Physical examination measures included lumbar active range of motion ( 27 ) and various tests purported to identify dysfunction in the lumbopelvic region ( 28 ) . Complete details of the physical examination are described elsewhere ( 26 ) . Specific components pertinent to validation of the rule were assessment s of segmental mobility and hip internal rotation range of motion , the performance of which is described in Appendix 1 and Appendix 3 video . Each physical therapist received a detailed manual that operationally defined each examination and treatment procedure and was trained in the study procedures by an investigator before data collection began . Supplement . Appendix 3 video : A Clinical Prediction Rule To Identify Patients with Low Back Pain Most Likely To Benefit from Spinal Manipulation Determining Status on the Clinical Prediction Rule A physical therapist who was blinded to the patients ' treatment group assignment assessed the 5 criteria in the rule ( Table 1 , Appendix 1 , and Appendix 3 video ) . To further minimize bias , examiners were not instructed in the rule 's criteria and were unaware of the patient 's status on the rule . After completion of the study , an examiner who was blinded to the patient 's treatment assignment determined the patient 's status on the rule by using the results of the baseline examination . As was done in the initial study ( 17 ) , we classified patients as positive if they met at least 4 of 5 criteria and were therefore likely to respond to manipulation . We classified patients with 3 or fewer criteria as negative . An examiner who was blinded to the patient 's status on the rule repeated the history and physical examination 1 and 4 weeks after r and omization . Patients also completed a 6-month follow-up postal question naire to assess disability , work status , and health care utilization . Treatment Groups We used a r and om-number generator to generate a r and omization list before the study began . We prepared individual , sequentially numbered index cards with the r and omization assignments . We folded the cards and placed them in sealed envelopes . After the baseline examination , the physical therapist who conducted the examination opened the next envelope , indicating the treatment group assignment . We r and omly assigned patients to 1 of 2 groups : 1 ) spinal manipulation plus an exercise program ( manipulation group ) or 2 ) an exervideocise program alone ( exercise group ) . Patients in both groups attended physical therapy twice during the first week and then once a week for the next 3 weeks , for a total of 5 sessions . We initiated treatment immediately after completion of the baseline examination , unless prohibited by time constraints ; in that case the first treatment session took place 24 to 48 hours after the baseline examination . All patients received an exercise instruction booklet that outlined the proper performance and frequency of each exercise and were instructed to perform their assigned exercise program once daily on the days that they did not attend therapy . On the basis of the benefits associated with remaining active ( 29 ) , patients in both groups were given advice to maintain usual activity within the limits of pain . Manipulation Group The treatment received by the manipulation group differed from that of the exercise group during the first 2 physical therapy sessions . During these 2 sessions , patients received high-velocity thrust spinal manipulation and a range-of-motion exercise only . First , the physical therapist performed the manipulation by using the same technique used by Flynn and colleagues ( 17 ) . Appendix 2 describes and Figure 1 and Appendix 3 video illustrate the procedures used to perform the manipulation technique . Figure 1 . Manipulative intervention used in developing and validating the spinal manipulation clinical prediction rule . Exercise Group We treated patients in the exercise group with a low-stress OBJECTIVE The purpose of this study was to identify the immediate effects of a manipulation of C5/C6 level on electromyography ( EMG ) of the deltoid muscle and in pressure pain thresholds ( PPTs ) in patients with mechanical neck pain . METHODS Thirty-seven subjects with mechanical neck pain were r and omly divided into 2 groups : manipulative group , which received a cervical spine manipulation targeted to C5/C6 segment , and a control group , which did not receive any procedure . Outcomes were EMG data of the deltoid muscle ( rest , isometric contraction for 5 or 30 seconds , and isotonic contraction ) and PPT over upper trapezius and deltoid muscles and C5 spinous process . They were assessed before and 5 minutes after treatment by a blinded assessor . A 3-way repeated- measures analysis of variance was used to examine the effects of the manipulation . RESULTS A significant group time interaction for MF at the beginning of isometric contraction for 30 seconds ( F = 7.957 , P = .006 ) was also found : the manipulative group experienced a greater increase in MF at the beginning of the isometric contraction than did the control group . A significant group time interaction was also found for root mean square during isometric contraction for 30 seconds ( P = .003 ) ; however , changes were small . Patients within the manipulative group experienced an increase on PPT over the deltoid ( P = .010 ) and C5 spinous process ( P = .025 ) , but not over upper trapezius ( P = .776 ) . CONCLUSIONS Manipulation at C5/C6 level in the study participants seemed to increase EMG amplitude signal and fatigue resistance in a nonspinal ( deltoid ) muscle innervated by the same segment in patients with mechanical neck pain . However , these changes were relative small . An increase on PPT over those tissues innervated by the manipulated segment was also found after the manipulative procedure DESIGN A r and omized controlled trial . OBJECTIVE To investigate the immediate effects on pressure pain thresholds over latent trigger points ( TrPs ) in the masseter and temporalis muscles and active mouth opening following atlanto-occipital joint thrust manipulation or a soft tissue manual intervention targeted to the suboccipital muscles . BACKGROUND Previous studies have described hypoalgesic effects of neck manipulative interventions over TrPs in the cervical musculature . There is a lack of studies analyzing these mechanisms over TrPs of muscles innervated by the trigeminal nerve . METHODS One hundred twenty-two volunteers , 31 men and 91 women , between the ages of 18 and 30 years , with latent TrPs in the masseter muscle , were r and omly divided into 3 groups : a manipulative group who received an atlanto-occipital joint thrust , a soft tissue group who received an inhibition technique over the suboccipital muscles , and a control group who did not receive an intervention . Pressure pain thresholds over latent TrPs in the masseter and temporalis muscles , and active mouth opening were assessed pretreatment and 2 minutes posttreatment by a blinded assessor . Mixed-model analyses of variance ( ANOVA ) were used to examine the effects of interventions on each outcome , with group as the between-subjects variable and time as the within-subjects variable . The primary analysis was the group-by-time interaction . RESULTS The 2-by-3 mixed-model ANOVA revealed a significant group-by-time interaction for changes in pressure pain thresholds over masseter ( P<.01 ) and temporalis ( P = .003 ) muscle latent TrPs and also for active mouth opening ( P<.001 ) in favor of the manipulative and soft tissue groups . Between-group effect sizes were small . CONCLUSIONS The application of an atlanto-occipital thrust manipulation or soft tissue technique targeted to the suboccipital muscles led to an immediate increase in pressure pain thresholds over latent TrPs in the masseter and temporalis muscles and an increase in maximum active mouth opening . Nevertheless , the effects of both interventions were small and future studies are required to eluci date the clinical relevance of these changes . LEVEL OF EVIDENCE Therapy , level 1b . J Orthop Sports Phys Ther 2010;40(5):310 - 317 , Epub 12 April 2010 . doi:10.2519/jospt.2010.3257 |
12,363 | 28,378,180 | We observed that female generally has a lower the gastric emptying time , gastric PH , lean body mass , and higher plasma volume , BMI , body fat , as well as reduce hepatic clearance , difference in activity of Cytochrome P450 enzyme , and metabolize drugs at different rate compared with male .
However , these differences can lead to adverse effects in female especially for the pregnant , post-menopausal , and elderly women .
Conclusion This systematic review provides an evidence for the effectiveness of dosage difference to ensure safety and efficient treatment . | Purpose In general , male and female are prescribed the same amount of dosage even if most of the cases female required less dosage than male .
Physicians are often facing problem on appropriate drug dosing , efficient treatment , and drug safety for a female in general .
To identify and synthesize evidence about the effectiveness of gender-based therapy ; provide the information to patients , providers , and health system intervention to ensure safety treatment ; and minimize adverse effects .
Methods We performed a systematic review to evaluate the effect of gender difference on pharmacotherapy . | Background Adverse effects of drugs are poorly reported in the literature . The aim of this study was to examine the frequency of the adverse events of antiepileptic drugs ( AEDs ) , in particular carbamazepine ( CBZ ) and oxcarbazepine ( OXC ) in patients with neuralgiform pain using the psychometrically tested Liverpool Adverse Events Profile ( AEP ) and provide clinicians with guidance as to when to change management . Methods The study was conducted as a clinical prospect i ve observational exploratory survey of 161 patients with idiopathic trigeminal neuralgia and its variants of whom 79 were on montherapy who attended a specialist clinic in a London teaching hospital over a period of 2 years . At each consultation they completed the AEP question naire which provides scores of 19–76 with toxic levels being considered as scores > 45 . Results The most common significant side effects were : tiredness 31.3 % , sleepiness 18.2 % , memory problems 22.7 % , disturbed sleep 14.1 % , difficulty concentrating and unsteadiness 11.6 % . Females reported significantly more side effects than males . Potential toxic dose for females is approximately 1200 mg of OXC and 800 mg of CBZ and 1800 mg of OXC and 1200 mg of CBZ for males . Conclusions CBZ and OXC are associated with cognitive impairment . Pharmacokinetic and pharmacodynamic differences are likely to be the reason for gender differences in reporting side effects . Potentially , females need to be prescribed lower dosages in view of their tendency to reach toxic levels at lower dosages . Side effects associated with AED could be a major reason for changing drugs or to consider a referral for surgical management The impact of gender , use of oral contraceptive steroids ( OCS ) , coffee consumption and of smoking on the metabolism of sparteine , caffeine , and paracetamol was studied in 194 r and omly selected subjects ( 98 male and 95 female ) . Thirty-eight of the male volunteers were cigarette smokers , 40 of the female subjects were smokers and /or users of OCS . The metabolic ratio of sparteine oxidation ( MRs ) showed a trimodal distribution . 7.7 % of the subjects had a MRs > 20 and thus were poor metabolizers ( PMs ) . Within the extensive metabolizer ( EM ) subjects , a distinct subgroup accounting for 11 % was observed with 20 > MRs > 1.2 . Six of the 15 phenotypical PMs were heterozygous EMs by genotyping . This indicates the existence of one or several CYP2D6 mutations which can not be identified by the currently employed genotyping methods . In each subgroup , i.e. smokers/OCS and non-smokers/non-OCS , the cumulative frequency distribution of the heterozygous ( wt/B ) phenotype caused a shift to higher MRs compared with the wild-type homozygotes ( wt/wt ) . Thus , for the in vivo activity of CYP2D6 , genetic determinants prevail over environmental factors . Smoking , use of oral contraceptive steroids , caffeine consumption , or gender had no influence on sparteine metabolism . The distribution of the paracetamol glucuronide/paracetamol metabolic ratio appeared to be unimodal although skewed . Glucuronidation capacity was clearly affected by gender , OCS use and smoking . It was higher in male than in female subjects . Male smokers had the highest , and female non-smokers/non-OCS users the lowest metabolic ratio . CYP1A2 activity , as determined by a caffeine metabolic ratio ( ( AFMU + 1X + 1U)/1 , 7U ) , was multimodally distributed and was clearly increased in smokers . It was significantly correlated to paracetamol glucoronidation in male heavy smokers ( r=0.85 ) , suggesting an element of co-regulation of CYP1A2 and of paracetamol conjugating UDP-glucuronosyltransferase isozymes , including UGTI.6 BACKGROUND Amiodarone use was associated with an increased need for pacemaker insertion in a retrospective study of patients with atrial fibrillation ( AF ) and prior myocardial infa rct ion . The aims of this study were to determine prospect ively whether amiodarone increases the need for pacemakers in a general population of patients with AF and whether this effect is modified by sex . METHODS The study included 1005 patients with new-onset AF who were enrolled in the Fibrillation Registry Assessing Costs , Therapies , Adverse events , and Lifestyle ( FRACTAL ) . Multivariable Cox regression models , including time-dependent covariates accounting for medication exposure , were used to evaluate the risk of pacemaker insertion associated with amiodarone use . RESULTS Amiodarone use was associated with an increased risk of pacemaker insertion ( hazard ratio [ HR ] , 2.01 ; 95 % confidence interval [ CI ] , 1.08 - 3.76 ) after adjustment for age , sex , atrial flutter , coronary artery disease , heart failure , and hypertension . The effect of amiodarone use was modified by sex , with a significant risk in women but not in men ( HR , 4.69 ; 95 % CI , 1.99 - 11.05 vs HR , 1.05 ; 95 % CI , 0.42 - 2.58 [ P = .02 ] ) . This interaction remained significant after adjustment for weight , body mass index , weight-adjusted amiodarone dose , and use of other antiarrhythmic or rate control drugs . CONCLUSION The risk of bradyarrhythmia requiring pacemaker insertion associated with amiodarone use for AF is significantly greater in women than in men , independent of weight or body mass index Purpose Data from two clinical studies ( hyperCholesterolaemia in cHildren and Adolescents taking Rosuvastatin OpeN label [ CHARON ; NCT01078675 ] and Study 4522IL/0086 ) were used to describe rosuvastatin pharmacokinetics in patients with heterozygous familial hypercholesterolemia aged ≥6 to < 18 years . Methods Rosuvastatin concentration – time data were analyzed via non-linear mixed-effects modeling ( NONMEM ) , with clearance ( CL/F ) as the pre-defined key pharmacokinetic parameter of interest . In addition , descriptive comparisons between pediatric patients and adults ( healthy and dyslipidemic ) were performed . The data set included 214 pediatric patients , with 2,029 rosuvastatin concentrations . Results A linear two-compartment model with first-order absorption and elimination processes adequately described the combined data set . Weight and gender were significant covariates for CL/F , with moderate between-patient variability remaining ( coefficient of variation ( CV ) 40 % ): CL/F in female children was approximately 30 % lower than in male children , and there was a twofold mean difference in CL/F across the observed weight range . Age was not a significant covariate after accounting for weight and gender differences . However , weight and gender only reduced between-patient variability from 45 ( without covariates ) to 40 % and are considered unlikely to be clinical ly relevant . Conclusions Rosuvastatin pharmacokinetics appeared generally predictable with respect to dose , and time ( study duration ) and the exposure ( dose-normalized area under the plasma concentration – time curve at steady state ( AUCss ) ) in children and adolescents appeared to be similar or lower than adult patients with dyslipidemia PURPOSE Encenicline ( EVP-6124 ) is a selective α7 nicotinic acetylcholine receptor partial agonist being developed for cognitive impairment in Alzheimer 's disease and schizophrenia . We report on 2 single-dose studies to assess the relative bioavailability , pharmacokinetic profile , tolerability , and cognitive effects of encenicline in healthy volunteers . METHODS A single ascending-dose study assessed the safety , tolerability , pharmacokinetic , and pharmacodynamic profiles of encenicline in healthy male volunteers . Subjects received a single 1- , 3.5- , 7- , 20- , 60- , or 180-mg oral solution dose of encenicline or placebo . A second single-dose , r and omized , open-label , 3-period , crossover study in healthy male and female subjects compared the relative bioavailability of a 1-mg oral capsule versus a 1-mg oral solution dose of encenicline and evaluated the effects of food and sex on encenicline pharmacokinetic profile . FINDINGS In the first study , encenicline was well tolerated and dose-proportional increases in C(max ) ( mean range 0.59 - 100 ng/mL ) and AUC0-∞ ( mean range 45.6 - 8890 ng·h/mL ) were observed over a 1- to 180-mg dose range . Procognitive effects on the Digit Symbol Substitution Test were maximal at the 20-mg dose . In the second study , encenicline 1-mg oral capsules and oral solution were bioequivalent and there was no observed food effect on encenicline pharmacokinetic profile with the 90 % confidence intervals of the treatment ratios for both comparisons ( ie , capsule to solution and fed to fasted ) for Cmax and AUC being within 80 % to 125 % . A 30 % to 40 % higher encenicline exposure in female subjects than respective values in male subjects was consistent with a 33 % higher weight of the male subjects . No clinical ly relevant safety profile or tolerability effects of encenicline were observed . IMPLICATION S Encenicline was well tolerated at single doses up to 180 mg , and doses as low as 1 mg had dose- and time-dependent pharmacodynamic effects on the central nervous system . Oral capsule and solution were bioequivalent and were not affected by food . Although a sex effect on pharmacokinetic profile was observed , it was attributable to weight differences . Clinical Trial Registration at EudraCT : 2006 - 005623 - 42 and EudracT : 2008 - 000029 - 20 STUDY OBJECTIVES To compare the steady-state pharmacokinetics and safety of saquinavir soft-gelatin capsules ( SGC ) plus low-dose ritonavir administered once/day in antiretroviral-naive adult patients infected with the human immunodeficiency virus type 1 ( HIV-1 ) and to evaluate any sex-related differences . DESIGN Single-center , open-label , pharmacokinetic study . SETTING University-affiliated outpatient HIV clinic . PATIENTS Six men and seven women with HIV-1 . INTERVENTION Each patient received saquinavir SGC 1600 mg and ritonavir 100 mg for a 14-day course of therapy . Nine serial blood sample s during 24 hours were collected on day 14 of therapy MEASUREMENTS AND MAIN RESULTS Plasma saquinavir and ritonavir concentrations were measured by high-performance liquid chromatography . St and ard noncompartmental methods were used to calculate the pharmacokinetic parameters . The unpaired Student t test was used for the statistical comparison of pharmacokinetic parameters between male and female patients . Once-daily saquinavir SGC plus ritonavir was generally well tolerated . Pharmacokinetic data from five men and five women were evaluable . The median saquinavir area under the concentration-time curve from 0 - 24 hours ( AUC0 - 24 ) in the female patients ( 82,300 ng x hr/ml ) was significantly ( p=0.036 ) higher than that in the male patients ( 47,400 ng x hr/ml ) . This relationship remained significant for weight-adjusted saquinavir AUC0 - 24 values . Ritonavir 's apparent oral clearance in the women was significantly ( p=0.023 ) lower than that in the men . CONCLUSION Significantly higher plasma concentrations of saquinavir were achieved in female compared with male HIV-infected patients receiving once-daily saquinavir SGC 1600 mg plus ritonavir 100 mg STUDY OBJECTIVE To examine the comparative pharmacokinetics of long-term methylprednisolone therapy in black and white renal transplant recipients . DESIGN Comprehensive pharmacokinetic evaluations of patients who participated in our glucocorticoid-monitoring program . SETTING University-based renal transplantation clinic . PATIENTS Six white renal transplant recipients with stable renal function , sex- and ( approximate ) age-matched with six preselected black patients . INTERVENTIONS The daily oral methylprednisolone dose for each patient was administered intravenously , and serial plasma sample s were obtained over 24 hours . MEASUREMENTS AND MAIN RESULTS Methylprednisolone was analyzed by high-performance liquid chromatography . The drug 's pharmacokinetics in black and white patients , respectively , were as follows : mean clearance 234 + /- 124 and 472 + /- 180 ml/hr/kg ( p < 0.05 ) ; volume of distribution 0.3 - 2.0 and 0.8 - 2.0 L/kg ; and elimination rate constant 0.13 - 0.41 and 0.27 - 0.42 hour-1 ( p < 0.06 ) . No statistical difference was noted in the last two parameters . The mean half-life of 3.4 + /- 1.4 hours in black patients compared with 2.1 + /- 0.3 hours in white patients approached statistical significance ( p < 0.08 ) . CONCLUSIONS These preliminary observations suggest that the disposition of methylprednisolone differs between black and white renal transplant recipients . The current method of prescribing glucocorticoids employs a fixed-dose regimen that does not take these possible interracial differences into consideration . Incorporating the differences may allow for more individualized dosing and more efficacious use of the agent in this patient population AIDS Clinical Trials Group study 359 was a controlled study of saquinavir with either ritonavir or nelfinavir , together with delavirdine , adefovir , or both , in indinavir-experienced persons . Saquinavir was common in all study arms , and the study investigated relationships among characteristics of patients , saquinavir area under the curve ( AUC ) and trough concentrations ( C(min ) ) , and virologic response . Concentrations of saquinavir were higher when it was combined with ritonavir than when it was combined with nelfinavir and were lower with adefovir-containing regimens . Females had higher AUC and C(min ) values than did males . Higher saquinavir AUC and C(min ) values were associated with a greater likelihood of human immunodeficiency virus ( HIV ) RNA levels < /=500 copies/mL ( P=.008 ) and were better predictors of response than was the saquinavir inhibitory quotient . Males had a lower probability of having HIV RNA levels < /=500 copies/mL at week 16 than did females ( 28 % vs. 42 % ; adjusted odds ratio , 0.43 ) . In this study , a greater proportion of females had HIV RNA levels < /=500 copies/mL than did males , which can be attributed to higher concentrations of saquinavir in females than in males Abstract Purpose Many studies have demonstrated the effectiveness of isoflavones on menopausal symptoms ; however , these mostly used high dosages . Because high-dose isoflavone may result in endometrial hyperplasia , we investigated whether low-dose isoflavone aglycone alleviates menopausal symptoms similarly to high dosages . Methods We conducted a r and omized , double-blind , placebo-controlled study in 90 healthy women aged 40–60 years who had at least one menopausal symptom on the Menopausal Symptom Scale ( MSS ) . The participants were r and omized to receive active tablets containing ultralow-dose ( 12.5 mg/day ; n = 30 ) or low-dose ( 25 mg/day ; n = 30 ) isoflavone aglycone , or placebo ( n = 30 ) tablets , for 8 weeks . Their menopausal symptoms were evaluated using MSS , Hospital Anxiety and Depression Scale ( HADS ) , and Athens Insomnia Scale ( AIS ) before , and 4 and 8 weeks after treatment . Results Eighty-seven women ( 97 % ) completed the 8-week treatment . In the low-dose group , significant improvement was observed from baseline , in the following parameters : ( 1 ) HADS-depression subscale score , ( 2 ) AIS score , ( 3 ) MSS-somatic symptom score after 4 and 8 weeks of treatment , and ( 4 ) MSS-vasomotor symptom score after 8 weeks of treatment . The changes in scores on HADS-depression subscale and AIS from baseline to 8 weeks were significantly higher in the low-dose group than in the placebo group . Conclusions Low-dose ( 25 mg/day ) isoflavone aglycone significantly alleviated symptoms of depression and insomnia in Japanese middle-aged women . Clinical Trial Registration UMIN-CTR UMIN000011876 ABSTRACT Indinavir is currently used at a fixed dose of 800 mg either three times a day or twice a day in combination with 100 mg of ritonavir . Dosage individualization based on plasma concentration monitoring might , however , be indicated . This study aim ed to assess the pharmacokinetic profile of indinavir in patients infected with human immunodeficiency virus to characterize interpatient and intrapatient variability and to build up a Bayesian approach for dosage adaptation . A population analysis was performed with the NONMEM computer program with 569 plasma sample s from a cohort of 239 unselected patients receiving indinavir . A one-compartment model with first-order absorption was adapted , and the influences of clinical characteristics on oral clearance ( CL ) and distribution volume ( V ) were examined . Predicted average drug exposure and trough and peak concentrations were derived for each patient and correlated with efficacy and toxicity markers . The population estimates of CL were 32.4 liters/h for female and 42.0 liters/h for male patients ; oral V was 65.7 liters ; and the rate constant of absorption ( Ka ) was 1.0 h−1 . CL decreased by 63 % with ritonavir intake and was moderately correlated to body weight . Both interpatient variability , best assigned to oral CL ( coefficient of variation [ CV ] , 39 % ) and Ka ( CV , 67 % ) , and intrapatient variability were large ( CV , 41 % ; st and ard deviation , 670 μg/liter ) . In conclusion , initial indinavir dosage should be decided according to ritonavir intake and sex , prior to plasma concentration measurements . The high interpatient pharmacokinetic variability represents an argument for therapeutic drug monitoring OBJECTIVE Gender differences in antidepressant treatment response , side effects , dropout rates , and plasma concentrations were examined in patients with major and predominantly melancholic depression . METHOD The study included a subgroup of 292 in patients ( 96 men , 196 women ) from three Danish double-blind , r and omized , controlled trials . All patients completed a 5-week treatment period and fulfilled the DSM-III or DSM-III-R criteria for major depression . Clomipramine ( 150 mg/day ) was the reference treatment , and comparable treatments were citalopram ( 40 mg/day ) , paroxetine ( 30 mg/day ) , and moclobemide ( 400 mg/day ) . Assessment s were performed by using the 17-item Hamilton Depression Rating Scale and the Udvalg for Kliniske Undersøgelser Side Effect Rating Scale . In a subgroup of 110 patients , weekly measurements of clomipramine plasma concentrations were obtained . Nonparametric statistical tests and multiple linear and logistic regression models were used for statistical evaluations . RESULTS Both genders had similar remission rates ( Hamilton depression scale score < 8) when treated with clomipramine and had significantly higher remission rates with clomipramine than with the comparable treatments . The plasma concentrations of clomipramine were significantly higher for female than for male patients . No gender differences were found in posttreatment Hamilton depression scale scores , nor did the therapeutic effects of treatment depend on gender . Rates of dropout and side effects were similar for men and women . No relationship between plasma concentrations , gender , and therapeutic outcome was found . CONCLUSIONS In a group of patients with major and predominantly melancholic depression , differentiation according to gender was not important in treatment with common antidepressants . Women appeared to have higher plasma concentrations of tricyclic antidepressants than men . The consequences of this difference for clinical effects are unclear . Gender-specific recommendations for dosing of tricyclic antidepressants may be considered To investigate the sex‐based PK of gatifloxacin ( GATI ) following oral administration ABSTRACT Management of treatment-experienced human immunodeficiency virus patients has become complex , and therapy may need to include two protease inhibitors at therapeutic doses . The objective of this study was to characterize the pharmacokinetics in serum of saquinavir ( 1,000 mg twice daily [ b.i.d . ] ) , lopinavir ( 400 mg b.i.d . ) , and ritonavir ( 100 mg b.i.d . ) in a multidrug rescue therapy study and to investigate whether steady-state pharmacokinetics of lopinavir-ritonavir are affected by coadministration of saquinavir . Forty patients were included ( 25 given ritonavir , lopinavir , and saquinavir and 15 given ritonavir and lopinavir ) . The median pharmacokinetic parameters of lopinavir were as follows : area under the concentration-time curve from 0 to 12 h ( AUC0 - 12 ) , 85.1 μg/ml · h ; maximum concentration of drug in serum ( Cmax ) , 10.0 μg/ml ; trough concentration of drug in serum ( Ctrough ) , 7.3 μg/ml ; and minimum concentration of drug in serum ( Cmin ) , 5.5 μg/ml . Lopinavir concentrations were similar in patients with and without saquinavir . The median pharmacokinetic parameters for saquinavir were as follows : AUC0 - 12 , 22.9 μg/ml · h ; Cmax , 2.9 μg/ml ; Ctrough , 1.6 μg/ml ; and Cmin , 1.4 μg/ml . There was a strong linear correlation between lopinavir and ritonavir and between saquinavir and ritonavir concentrations in plasma . The correlation between lopinavir and saquinavir levels was weaker . We found higher saquinavir concentrations in women than in men , with no difference in lopinavir levels . Only patients with very high body weight presented lopinavir and saquinavir concentrations lower than the overall group . Ritonavir has a double-boosting function for both lopinavir and saquinavir , and in terms of pharmacokinetics , the drug doses selected seemed appropriate for combining these agents in a dual protease inhibitor-based antiretroviral regimen for patients with several prior virologic failures Purpose Animal and human studies suggest that vitamin D regulates functions of the reproductive system . Vitamin D deficiency is prevalent in women of reproductive age . Vitamin D status has been associated with in vitro fertilisation outcome , features of polycystic ovarian syndrome ( PCOS ) and endometriosis . The aims of our study were to investigate the prevalence of vitamin D deficiency of infertile women living in central Germany , to identify risk factors for vitamin D deficiency and to specify seasonal variations of vitamin D status . Methods This was a retrospective cohort study at an academic tertiary care centre ( N = 113 ) and an Outpatient Centre for Reproductive Medicine ( N = 193 ) of women presenting for infertility treatment . The statistical evaluation was descriptive and explorative . Possible risk factors associated with an increased risk for vitamin D deficiency were assessed using multiple logistic regression models . Variables with p value less than 0.05 were further assessed in a multivariable logistic regression model . Results Overall , 98.2 % of patients at centre 1 and 81.3 % of women with impaired fertility at centre 2 had deficient or insufficient vitamin D levels . Overweight BMI and limited exposure to sun ( winter , spring and autumn trimester ) were associated with an increased risk of vitamin D deficiency . Vitamin D levels did not vary according to age or infertility associated disorders ( e.g. endometriosis , PCOS ) . Conclusion The rate of vitamin D deficiency among women with impaired fertility is alarming . Prospect i ve studies are pressingly needed to confirm a causal relationship and to investigate the potential therapeutic benefits of vitamin D supplementation in this population We used electrically induced pain in healthy young subjects to study gender differences in nociception and the analgesic efficacy of ibuprofen . Cutaneous stimulation of the earlobe allowed measurement of pain detection thresholds and maximal pain tolerance . Drug and placebo were each administered twice using a double-blind , r and omized , multiple cross-over design . Male subjects had greater stimulus thresholds ( lower nociception ) compared with female subjects ( 18 + /- 0.3 vs 15 + /- 0.3 volts , mean + /- SEM ; n = 10 in each group ) and a greater pain tolerance ( 24 + /- 0.4 vs 21 + /- 0.4 volts ) . Response variability was also greater in the male subjects , yet only the men exhibited a statistically significant analgesic response to ibuprofen ( Delta volts ; ibuprofen versus placebo : 2.80 + /- 0.33 vs -0.18 + /- 0.34 ; P < 0.05 , n = 10 ) . None of these results could be attributed to pharmacokinetic differences . The finding that ibuprofen was less effective in women than in men has potential clinical significance , especially as a factor in the response variability to nonsteroidal antiinflammatory drugs . Implication s : In this study , we examined ibuprofen , a widely used nonsteroidal antiinflammatory drug , for its ability to reduce experimental pain . We found that it had such properties in healthy young male subjects but not in young female subjects . This is a paradox because many of the painful conditions for which nonsteroidal antiinflammatory drugs are used ( e.g. , rheumatoid arthritis ) occur more often in women . ( Anesth Analg 1998;86:1257 - 62 Single 25 mg intravenous and 50 mg oral doses of trazodone were given to 43 healthy subjects , divided into young men and women ( aged 18 to 40 years ) and elderly men and women ( aged 60 to 76 years ) . Among men , trazodone volume of distribution ( Varea ) was increased in elderly vs. young subjects ( 1.15 vs. 0.89 L/kg ; P < 0.05 ) , and clearance decreased ( 1.65 vs. 2.31 ml/min/kg ; P < 0.05 ) , thereby increasing elimination half‐life ( t½ ) in elderly men ( 8.2 vs. 4.7 hours ; P < 0.001 ) . Varea in women was also increased in the elderly ( 1.5 vs. 1.27 L/kg ; P < 0.02 ) , causing increased t½ ( 7.6 vs. 5.9 hours ; P < 0.05 ) , but clearance was unrelated to age . Absolute bioavailability of oral trazodone averaged 70 % to 90 % and was unrelated to age or sex . In 23 obese subjects ( mean weight 112 kg ) vs. 23 matched control subjects of normal weight ( mean 65 kg ) , Varea was greatly increased ( 162 vs. 67 L ; 1.43 vs. 1.04 L/kg ; P < 0.001 ) and was highly correlated with body weight ( r = 0.91 ) . Clearance was unchanged between groups ( 146 vs. 136 ml/min ) , but the increased Varea caused prolonged t½ in obese subjects ( 13.3 vs. 5.9 hours ; P < 0.001 ) . Reduced clearance of trazodone among elderly men may indicate a need for dosage reduction during chronic therapy . In obese individuals , choice of dosage during chronic treatment should be based on ideal rather than total body weight The influence of age and gender on the pharmacokinetics of levofloxacin in healthy subjects receiving a single oral 500-mg dose of levofloxacin was investigated in this parallel design study . Six young males ( aged 18 to 40 years ) , six elderly males ( aged > or = 65 years ) , six young females ( aged 18 to 40 years ) , and six elderly females ( aged > or = 65 years ) were enrolled and completed the study . The study reveals that the bioavailability ( rate and extent ) of levofloxacin was not affected by either age or gender . In both age ( young and elderly ) and gender ( male and female ) groups of subjects , peak concentrations in plasma were reached at approximately 1.5 h after dosing ; renal clearance of levofloxacin accounted for approximately 77 % of total body clearance , and approximately 76 % of the administered dose was recovered unchanged in urine over the 36 h of collection . The apparent differences in the calculated pharmacokinetic parameters for levofloxacin between the age groups ( young versus elderly ) and between the gender groups ( males versus females ) could be explained by differences in renal function among the subjects . A single dose of 500 mg of levofloxacin administered orally to both young and old , male and female healthy subjects was found to be safe and well tolerated . As the differences in levofloxacin kinetics between the young and the elderly or the males and the females are limited and are mainly related to the renal function of the subjects , dose adjustment based on age or gender alone is not necessary Objective Delavirdine is a non-nucleoside reverse transcriptase inhibitor used in combination regimens for the treatment of HIV-1 infection . Our objective was to characterise the population pharmacokinetics of delavirdine in HIV-infected patients who participated in the adult AIDS Clinical Trials Group ( ACTG ) 260 and 261 studies . Methods ACTG 261 was a r and omised , double-blind study of delavirdine 400 mg three times daily , in various combination regimens ; ACTG 260 was a concentration-targeted monotherapy study . Two hundred and thirty-four patients , and 1254 and 1251 plasma concentrations for delavirdine and N-delavirdine , respectively , were available for population pharmacokinetic analysis . The pharmacokinetic model ( and initial parameters ) , based on previous studies , included two compartments for delavirdine ( peripheral and central ) and parallel clearance pathways ( nonlinear conversion to N-delavirdine and first order clearance from the body ) . The model was one compartment for N-delavirdine with first order clearance . Diurnal variation of delavirdine and N-delavirdine oral clearance was modelled as a cosine function , with amplitude variation a fitted parameter . Pharmacokinetic parameter estimates were derived from iterative two-stage analysis ; observed delavirdine and N-delavirdine concentrations fit with weighting by the inverse observation variance . Covariates were analysed by multiple general linear modelling . Results The mean ( percent coefficient of variation [ % CV ] ) CD4 count was 315 ( 109 ) cells/mm3 , weight 76.9 ( 14.7 ) kg , age 37 ( 8.5 ) years , and 15 % of the population were women . Mean ( % CV ) population pharmacokinetic parameter estimates for delavirdine were : volume of distribution at steady state 67.6 ( 100 ) L , intrinsic oral clearance 19.8 ( 64 ) L/h , concentration at half the maximum velocity of metabolism ( Vmax ) 6.3 ( 69 ) μmol/L and first order oral clearance 0.57 ( 86 ) L/h . For N-delavirdine , the mean ( % CV ) apparent volume of distribution was 24.7 ( 75 ) L and apparent clearance 29.7 ( 42 ) L/h . The mean Vmax was 1376 ( 68 ) mg/day . The final model for average intrinsic clearance of delavirdine included race , sex , weight and age as significant covariates ( p < 0.05 ) ; however , these covariates do not explain a significant proportion of the overall variability in the population . Conclusions Delavirdine disposition exhibits nonlinear pharmacokinetics and large interpatient variability , and is significantly altered by time of day ( impacting potential therapeutic drug monitoring and future pharmacokinetic study design s ) . Although race and sex appear to influence delavirdine pharmacokinetics , men and women and patients of different races should receive similar mg/kg dosage regimens . The presence of large interpatient variability supports the further investigation of the utility of therapeutic drug monitoring for delavirdine , if target drug concentrations can be better defined AIMS To investigate the distribution characteristics of CYP1A2 in a Chinese population , and to examine gender-related differences in CYP1A2 activity . METHODS Two hundred and twenty-nine healthy subjects , 120 men and 109 women , were enrolled in this study . CYP1A2 activity was measured by plasma paraxanthine/caffeine ( 1,7X/1,3,7X ) ratio 6 h after administration of 300 mg caffeine . The concentrations of paraxanthine and caffeine in plasma were detected by h.p.l.c . RESULTS A 16-fold variation of CYP1A2 activity ( range 0 . 09 to 1.46 ) was shown in this study . The coefficient of variation ( CV % ) of CYP1A2 activity was 62.9 % . Non-normal distribution of CYP1A2 activity was indicated by the Shapiro-Wilk test ( P<0.001 ) . Probit plots of CYP1A2 activity revealed a bimodal distribution with breakpoint of 1,7X/1,3,7X ratio of 0.12 . The percentage of poor metabolizers ( PMs ) was 5.24 % ( 95 % CI : 2.35 % approximately 8.13 % ) in this Chinese population . Residual analysis of the data also supported bimodality ( P<0.01 ) . The CYP1A2 activity of men was higher than that of women ( median : 0.33 vs 0.23 , P<0.001 ) . A probit plot of CYP1A2 activity in men was shifted to the left compared with that in women . Based on phenotype , the gender-related difference was observed in extensive metabolizers ( EMs ) ( P<0.001 ) , but not in PMs ( P > 0.1 ) . In addition , there was no sex-related difference in the incidence of PMs ( P > 0.1 ) . CONCLUSIONS There is a phenotypic polymorphism in CYP1A2 activity in this Chinese population , and CYP1A2 activity is higher in men than that in women Bidirectional drug interactions between fluvoxamine and classical antidepressants were studied in depressed patients . A column switching technique combined with high performance liquid chromatography ( HPLC ) enabled automated analyses of plasma for simultaneous determination of fluvoxamine , tricyclic and tetracyclic antidepressants and demethylated and major hydroxylated metabolites in a single HPLC run . The measurements revealed that fluvoxamine inhibited N-demethylation of imipramine , clomipramine , amitriptyline and maprotiline whereas interferences with hydroxylation reactions were restricted to aromatic 8-hydroxylation of clomipramine . In patients under fluvoxamine monotherapy before comedication , plasma concentrations of fluvoxamine increased after administration of a tricyclic antidepressant , thus indicating bidirectional drug interactions . The inhibitory effects of fluvoxamine on the metabolism of classical antidepressants disappeared after discontinuation of concomitant fluvoxamine treatment within at least 1–2 weeks . The reported alterations in drug metabolism observed in depressed patients who were under fluvoxamine/tricyclic antidepressant comedication suggested that careful supervision and regular drug monitoring are necessary in such patients The antiepileptic drug ( AED ) perampanel is approved in ≥40 countries as adjunctive therapy for drug‐resistant partial seizures in patients with epilepsy . This post hoc analysis of pooled data from three phase III , double‐blind , r and omized studies of perampanel examines between‐gender differences in perampanel efficacy and safety . Of the 1,478 subjects in the pooled analysis ( 719 male , 759 female ) , 1,109 were included in the pharmacokinetic/pharmacodynamic analysis . Perampanel oral clearance was 17 % lower in female than in male patients not receiving enzyme‐inducing AEDs . Pooled efficacy analysis revealed that seizure frequency was reduced with perampanel treatment regardless of gender ; a greater numerical reduction in seizure frequency and increased responder rates occurred in female participants at perampanel doses of 4 , 8 , and 12 mg . Tolerability was similar between groups , although common adverse events such as dizziness and headache occurred more frequently in female subjects . Modest elevations in perampanel exposure in female patients may result in meaningful between‐gender differences in efficacy and safety ; therefore , dosing should be individualized and clinical response monitored STUDY OBJECTIVE To evaluate the impact of gender on labetalol kinetics . DESIGN Part of a r and omized , crossover study . SETTING Academic medical center . PATIENTS Nineteen hypertensive patients ( 14 men , 5 women ; 6 blacks , 13 whites ) . INTERVENTIONS Participants had labetalol dosages titrated to a specific antihypertensive response , then underwent ambulatory blood pressure monitoring ( ABPM ) and a pharmacokinetic study . Labetalol plasma concentrations were measured by high-performance liquid chromatography ( HPLC ) and labetalol stereoisomer ratios were determined in a single plasma sample by chiral HPLC , both with fluorescence detection . MEASUREMENTS AND MAIN RESULTS Labetalol concentrations were 80 % higher in women ( area under the concentration-time curve [AUC]/dose x 1000 : 6.79 + /- 2.11 in women vs 3.82 + /- 1.37 hr/L in men , p<0.05 ) , yet both genders had a similar antihypertensive response by 24-hour ABPM . Dose-corrected AUC ( AUC/dose x 1000 ) for labetalol 's stereoisomers in women and men , respectively , were S , R-labetalol 7.55 + /- 1.47 and 4.83 + /- 1.54 hr/L ( p<0.05 ) , S , S-labetalol 8.23 + /- 2.93 and 4.65 + /- 1.78 hr/L ( p<0.05 ) , R , S-labetalol 6.99 + /- 3.30 and 4.25 + /- 2.35 hr/L ( p=0.11 ) , and R , R-labetalol 3.91 + /- 2.57 and 3.55 + /- 3.08 hr/L ( NS ) . CONCLUSION The higher labetalol concentration in women than in men was explained largely by differences in inactive and alpha1-blocking stereoisomers . However , concentrations were similar between genders for the beta-blocking stereoisomer ( R , R-labetalol ) , possibly explaining the similarity in antihypertensive response to the drug . This study highlights the importance of determining stereoisomer kinetics for agents administered as racemates , particularly when relating concentrations to pharmacologic response In 1972 , 171 ( 18 , 7 % ) of 914 patients showed evidence of an adverse drug reaction ( ADR ) in a prospect i ve study of the division of internal medicine in a regional teaching hospital ( Zieglerspital , Bern ) . The following factors correlated positively with frequency of ADR : 1 . The duration of hospital stay . 2 . The age between 60 and 80 years . 3 . Female sex . 4 . Previous ADR . The fact that most of the ADR occur within the first three weeks of a hospital stay , combined with point 1 , suggests early ADR having some predictive value for duration of hospital stay . Statistical data of type , severity , duration and pathogenesis of ADR are given . The drugs involved are mentioned Sex-related variations in the clinical effects of drugs may be observed . In an intensive prospect i ve drug surveillance study of 1920 patients hospitalized at the Department of Medicine of the J. J. Aguirre Hospital in Santiago , Chile , the frequency of adverse drug reactions ( ADR ) was significantly higher in females than in males ( p < 0.0005 ) . Women presented more commonly gastrointestinal and cutaneous allergic reactions . In males electrolyte disturbances were more frequent . Drugs inducing ADR were very similar in both sexes . Eighty-three per cent of ADR in males and 93 % in females were dose-related effects . Hospitalization was lengthened by a significantly higher proportion of ADR in men than in women . Other ADR 's risk fators such as age , number of drugs administered and duration of hospitalization did not account for the differences observed . In males with ADR there was a higher proportion of patients with cirrhosis and renal insufficiency . These findings suggest that sex is a determinant of the frequency and characteristics of ADR The purpose of this study was to determine the pharmacokinetics and safety of eletriptan in different phases of the menstrual cycle . Female volunteers ( n = 16 ) with a regular menstrual cycle ( 28 + /- 4 days ) received a single oral dose of 80 mg eletriptan during each of the four cycle phases : phase 1 ( menses ) , days 1 to 4 ; phase 2 ( follicular ) , days 6 to 10 ; phase 3 ( ovulatory ) , days 11 to 13 ; and phase 4 ( luteal ) , days 21 to 24 . Eletriptan plasma concentrations were determined from serial plasma sample s taken during a 24-hourperiod after dosing . Blood pressure , pulse rate , and ECG measurements were performed at baseline , 1 and 24 hours after dosing . No significant differences between phases were observed for maximum plasma concentration ( cmax , range of means = 188 - 234 ng/ml ) , time to maximum concentration ( tmax , range of means = 1.8 - 2.5 h ) , or systemic exposure ( area under the curve [ AUC ] , range of means = 1194 - 1514 ng x h/ml ) . Although there was a statistically significant difference in the terminal phase elimination rate constant ( kel ) between phases 1 and 2 ( 0.175/h vs. 0.158/h , p = 0.044 ) , the corresponding difference in terminal phase half-life ( t 1/2 ) ( 4.0 h vs. 4.4 h ) was not considered to be clinical lyrelevant . No clinical ly relevant differences in blood pressure , pulse rate , or ECG were observed , and the incidence , nature , and severity of adverse events were similar in all phases . The different phases of the menstrual cycle had no clinical ly significant effect on the pharmacokinetics , safety , or tolerability of oral 80 mg eletriptan in healthy females To determine whether there are gender‐specific differences in the pharmacokinetics and pharmacodynamics of metoprolol enantiomers Prednisolone pharmacokinetics ( PK ) and pharmacodynamics ( PD ) were investigated in relation to sex and race in white males , black males , white females , and black females ( n = 8/group ) after a single oral dose ( 0.27 mg/kg ) of prednisone . The study consisted of baseline and prednisone phases with 32-hour sampling in each phase . Women were studied during the luteal phase of their menstrual cycle . Total and free plasma prednisolone concentrations were assayed by HPLC and ultrafiltration , and pharmacokinetic data were analyzed by compartmental fitting using WinNonlin . Plasma cortisol concentrations were assayed by HPLC ; T-helper , T-suppressor lymphocyte , and neutrophil cell counts were determined by FACS and hemocytometry , and these pharmacodynamic data were evaluated by basic and extended indirect response models using ADAPT II . Total body weight-normalized free prednisolone oral clearance and apparent volume of distribution were higher in men compared with women , regardless of race ( by 22 % in whites and 40 % in blacks for oral clearance , p < 0.01 ; by32 % in whites and 38 % in blacks for apparent volume of distribution , p < 0.01 ) . The 50 % inhibitory concentration ( IC50 ) values for T-suppressor cell-trafficking inhibition were higher in whites than in blacks , regardless of sex ( by 125 % in men and 208 % in women , p < 0.01 ) . The IC50 or SC50 values for effects of prednisolone on cortisol secretion and T-helper lymphocyte or neutrophil trafficking were not statistically different between men and women , blacks and whites . The findings of this study suggest that there are some prednisolone PK/PD differences related to sex and race . However , these differences do not suggest the need for dosage adjustments , and additional experiments with repeat dosing are needed to fully evaluate the clinical implication of these findings The incidence of adverse reactions to drugs has been assessed with prospect i ve epidemiological studies conducted within single units , departments , or hospitals.1–3 Because of the variability of the results and a lack of representativeness , it is difficult to confidently extrapolate these results to a national level . To calculate the incidence of admissions caused by adverse drug reactions we conducted a prospect i ve cross sectional study of a representative nationwide sample of medical wards in public hospitals . Between 2 March and 20 April 1998 , the study was conducted for 14 days in each of a representative sample of medical departments in French teaching hospitals and general hospitals . The sample size required was calculated from the results of a pilot study .4 All patients admitted to the departments sample d were included in the study . Each patient was assessed by a team of local clinicians and pharmacologists to determine whether the admission was the result of an adverse |
12,364 | 15,466,943 | There is convincing evidence that a higher protein intake increases thermogenesis and satiety compared to diets of lower protein content .
The weight of evidence also suggests that high protein meals lead to a reduced subsequent energy intake .
Some evidence suggests that diets higher in protein result in an increased weight loss and fat loss as compared to diets lower in protein , but findings have not been consistent . | For years , proponents of some fad diets have cl aim ed that higher amounts of protein facilitate weight loss .
Only in recent years have studies begun to examine the effects of high protein diets on energy expenditure , subsequent energy intake and weight loss as compared to lower protein diets . | OBJECTIVE To test whether overfeeding isoenergetic doses protein , carbohydrate and fat would differentially influence appetite on the same day , and the subsequent day 's food intake . DESIGN Six men were each studied three times on a 5-day protocol . On days 1 and 2 they were fed a medium fat ( MF ) maintenance diet ( comprising 40:47:13 % fat , CHO and protein by energy ) calculated at 1.6 x RMR . Subjects entered the calorimeter at 08.00 on day 3 for 48 h. On day 3 ( manipulation day ) , they ate a MF diet at 1.5 x RMR with an additional 0.6 x RMR as protein ( HP ) , carbohydrate ( HC ) or fat ( HF ) . On days 4 and 5 , ( outcome days ) , subjects had ad libitum access to isoenergetically dense MF ( 40:47:13 ) foods ( 550kJ/100 g ) . Subjective hunger and satiety were tracked hourly during waking hours throughout days 1 - 5 . RESULTS Throughout day 3 subjects felt significantly more full and less hungry on the high protein diet relative to the other two diets ( P = 0.002 ) . Also by the end of day 3 each overfed nutrient led to a significant increase in its own balance of the other two diets ( P < 0.01 ) . These effects did not influence the subsequent day 's energy intake . The alterations in nutrient balance by the end of day 3 were partially buffered by increases in the oxidative disposal of each overfed macronutrient throughout day 4 ( which was proportionately greater for protein ( P < 0.001 ) than carbohydrate ( P = 0.07 ) or fat ( P = 0.1 ) ) . CONCLUSIONS HP diets were more satiating that isoenergetically-dense HC or HF diets on the day they are eaten . The HC diet was transiently more satiating than the HF diet after each meal . This study supports previous work which suggests that relatively large changes in nutrient balance produced on one day appear to be poorly compensated by changes in energy intake on a subsequent day in men OBJECTIVE To investigate whether protein intake influences the decline in energy expenditure during energy restriction . DESIGN Cross-over study of three diets of 4.2 MJ/d for 7 days : one diet with 36 % energy as protein and two with 15 % energy as protein , one high in carbohydrate and the other high in fat . SUBJECTS Two men and six women aged 31 - 57 y. BMI 27.B-34.1 kg/m2 . MEASUREMENTS 24-h energy expenditure ( 24-h EE ) , sleeping metabolic rate ( SMR ) and body weight on days 0 and 7 of each diet ; 24-h urinary nitrogen excretion ( 24-h UN ) on days 0 - 7 of each diet . RESULTS 24-h EE and SMR declined on all three diets but the decrease was significantly less on the high protein diet than on the two low protein diets . Weight loss was similar on all three diets . 24-h UN was less than N intake on the high protein diet but greater than N intake on the two low protein diets . CONCLUSIONS Maintaining protein intake reduces the decrease in energy expenditure during energy restriction BACKGROUND The effects of a carbohydrate-restricted diet on weight loss and risk factors for atherosclerosis have been incompletely assessed . METHODS We r and omly assigned 132 severely obese subjects ( including 77 blacks and 23 women ) with a mean body-mass index of 43 and a high prevalence of diabetes ( 39 percent ) or the metabolic syndrome ( 43 percent ) to a carbohydrate-restricted ( low-carbohydrate ) diet or a calorie- and fat-restricted ( low-fat ) diet . RESULTS Seventy-nine subjects completed the six-month study . An analysis including all subjects , with the last observation carried forward for those who dropped out , showed that subjects on the low-carbohydrate diet lost more weight than those on the low-fat diet ( mean [ + /-SD ] , -5.8+/-8.6 kg vs. -1.9+/-4.2 kg ; P=0.002 ) and had greater decreases in triglyceride levels ( mean , -20+/-43 percent vs. -4+/-31 percent ; P=0.001 ) , irrespective of the use or nonuse of hypoglycemic or lipid-lowering medications . Insulin sensitivity , measured only in subjects without diabetes , also improved more among subjects on the low-carbohydrate diet ( 6+/-9 percent vs. -3+/-8 percent , P=0.01 ) . The amount of weight lost ( P<0.001 ) and assignment to the low-carbohydrate diet ( P=0.01 ) were independent predictors of improvement in triglyceride levels and insulin sensitivity . CONCLUSIONS Severely obese subjects with a high prevalence of diabetes or the metabolic syndrome lost more weight during six months on a carbohydrate-restricted diet than on a calorie- and fat-restricted diet , with a relative improvement in insulin sensitivity and triglyceride levels , even after adjustment for the amount of weight lost . This finding should be interpreted with caution , given the small magnitude of overall and between-group differences in weight loss in these markedly obese subjects and the short duration of the study . Future studies evaluating long-term cardiovascular outcomes are needed before a carbohydrate-restricted diet can be endorsed BACKGROUND : A relatively high percentage of energy intake as protein has been shown to increase satiety and decrease energy efficiency during overfeeding . AIM : To investigate whether addition of protein may improve weight maintenance by preventing or limiting weight regain after weight loss of 5–10 % in moderately obese subjects . DESIGN OF THE STUDY : In a r and omized parallel design , 148 male and female subjects ( age 44.2±10.1 y ; body mass index ( BMI ) 29.5±2.5 kg/m2 ; body fat 37.2±5.0 % ) followed a very low-energy diet ( 2.1 MJ/day ) during 4 weeks . For subsequent 3 months weight-maintenance assessment , they were stratified according to age , BMI , body weight , restrained eating , and resting energy expenditure ( REE ) , and r and omized over two groups . Both groups visited the University with the same frequency , receiving the same counseling on dem and by the dietitian . One group ( n=73 ) received 48.2 g/day additional protein to their diet . Measurements at baseline , after weight loss , and after 3 months weight maintenance were body weight , body composition , metabolic measurements , appetite profile , eating attitude , and relevant blood parameters . RESULTS : Changes in body mass , waist circumference , REE , respiratory quotient ( RQ ) , total energy expenditure ( TEE ) , dietary restraint , fasting blood-glucose , insulin , triacylglycerol , leptin , β-hydroxybutyrate , glycerol , and free fatty acids were significant during weight loss and did not differ between groups . During weight maintenance , the ‘ additional-protein group ’ showed in comparison to the nonadditional-protein group 18 vs 15 en% protein intake , a 50 % lower body weight regain only consisting of fat-free mass , a 50 % decreased energy efficiency , increased satiety while energy intake did not differ , and a lower increase in triacylglycerol and in leptin ; REE , RQ , TEE , and increases in other blood parameters measured did not differ . CONCLUSION : A 20 % higher protein intake , that is , 18 % of energy vs 15 % of energy during weight maintenance after weight loss , result ed in a 50 % lower body weight regain , only consisting of fat-free mass , and related to increased satiety and decreased energy efficiency OBJECTIVE To compare the effect of isoenergetically-dense , high-protein ( HP ) , high-fat ( HF ) or high-carbohydrate ( HC ) breakfasts ( at 08.30 ) on subjective hunger , fullness and appetite ( measured hourly on a 100 mm visual analogue scale ) , macronutrient balance and ad libitum energy intake ( EI ) , at a test meal ( 13.30 ) and throughout the rest of the day ( until 23.00 ) . DESIGN Six men each spent 24 h in a whole-body indirect calorimeter on three separate occasions during which they received breakfasts design ed to match 75 % of BMR and that comprised , on average 3.1 MJ of protein ( HP ) , carbohydrate ( HC ) or fat ( HF ) , respectively , the remainder being split between the other two macronutrients . Every item of the ad libitum diet comprised 13 % protein , 40 % fat and 47 % carbohydrate by energy , with an energy density of 550 kJ/100 g. RESULTS Subjectively-rated pleasantness did not differ between the breakfasts , or any of the subsequent ad libitum meals . Subjective hunger was significantly greater during the hours between breakfast and lunch after the HF ( 26 ) treatment relative to the HP ( 18 ) or HC ( 18 mm ) meals ( P < 0.001 ) , although the HP treatment suppressed hunger to a greater extent than the other two treatments over 24 h. However , mean ad libitum lunch intakes were similar at 5.38 , 5.30 and 5.18 MJ ( NS ) on the HP , HC and HF treatments , respectively . After-lunch intakes were also very similar at 6.14 , 6.18 and 5.83 MJ ( NS ) . Mean 24-h energy expenditure amounted to 11.12 , 11.14 and 10.93 MJ , respectively , producing energy balances of 5.71 , 5.83 and 5.04 MJ ( NS ) , respectively . The HP , HF and HC breakfasts led to enhanced P , F and C oxidation , respectively ( P < 0.003 ) . CONCLUSIONS Large HP , HC or HF breakfasts led to detectable changes in hunger that were not of sufficient magnitude to influence lunch-time intake 5 h later , or EI for the rest of the day . A single positive balance of each macronutrient can be buffered by oxidation and storage capacity , without leading to changes in meal-to-meal EI , when subjects feed ad libitum on unfamiliar diets of fixed composition The aim of this study was to investigate whether a high protein meal has a different effect on short-term satiety in preschool children than a high carbohydrate meal by measuring their intake of a subsequent meal . Subjects were 35 normal preschool children of both genders aged 5 to 6 years . All children were healthy and r and omly chosen from those who were attending to a day-care center where they received feeding at three meal times : breakfast , lunch and teatime . Children were weighed with light clothes following st and ard recommendations . They were normal according to the weight for height index , using the NCHS st and ards . Two meals with different levels of protein and carbohydrate and equal energy contents were assayed at lunch . The lunches were cooked dishes made from common ingredients . The high carbohydrate meal was consumed in greater amount than the high protein meal ( P < 0.01 ) and a significantly greater energy intake was observed ( P < 0.01 ) . Food and energy intakes at teatime were greater with the high carbohydrate meal , but only the energy intake was significant ( P < 0.05 ) . When subjects consumed the high protein meal during lunch , they ate a significantly lower amount of protein in the subsequent meal , but the carbohydrate intake was similar . The long-term effects of a high protein diet remain to be investigated before recommending of a high protein for obese children The purpose of this investigation was to learn whether the thermogenic effect in man of sucrose and glucose was similar and whether normal weight and overweight subjects responded in a similar manner . Dietary-induced thermogenesis was calculated for the period 15 to 180 min after ingestion of sucrose or glucose in six normal weight and five obese subjects . The metabolic rate was calculated from the oxygen consumption and carbon dioxide output utilizing the ventilated hood technique . In normal weight subjects , the total dietary-induced thermogenesis was significantly greater after sucrose than after glucose ( p less than 0.005 ) but the difference was much less marked in the obese subjects The rates of energy expenditure and wholebody protein turnover were determined during a 9-h period in a group of seven men while they received hourly isocaloric meals of high-protein ( HP ) or high-carbohydrate ( HC ) content . Their responses to feeding were compared with those to a short period of fasting ( 15 - 24 h ) . The 9-h thermic response to the repeated feeding of HP meals was found to be greater than that to the HC meals ( 9.6 + /- 0.6 % vs 5.7 + /- 0.4 % of the energy intake , respectively , means + /- SEM , p less than 0.01 ) . The rate of whole-body nitrogen turnover over 9 h increased from 17.6 + /- 2.2 g on the fasting day to 27.4 + /- 1.4 g during HC feeding ( NS ) and there was a further increase to 58.2 + /- 5.3 g result ing from HP feeding ( p less than 0.001 ) . By using theoretical estimates ( based upon ATP requirements ) of the metabolic cost of protein synthesis , 36 + /- 9 % of the thermic response to HC feeding and 68 + /- 3 % of the response to HP feeding could be accounted for by the increases in protein synthesis compared with the fasting state Cl aims about the merits or risks of carbohydrate ( CHO ) vs. protein for weight loss diets are extensive , yet the ideal ratio of dietary carbohydrate to protein for adult health and weight management remains unknown . This study examined the efficacy of two weight loss diets with modified CHO/protein ratios to change body composition and blood lipids in adult women . Women ( n = 24 ; 45 to 56 y old ) with body mass indices > 26 kg/m(2 ) were assigned to either a CHO Group consuming a diet with a CHO/protein ratio of 3.5 ( 68 g protein/d ) or a Protein Group with a ratio of 1.4 ( 125 g protein/d ) . Diets were isoenergetic , providing 7100 kJ/d , and similar amounts of fat ( approximately 50 g/d ) . After consuming the diets for 10 wk , the CHO Group lost 6.96 + /- 1.36 kg body weight and the Protein Group lost 7.53 + /- 1.44 kg . Weight loss in the Protein Group was partitioned to a significantly higher loss of fat/lean ( 6.3 + /- 1.2 g/g ) compared with the CHO Group ( 3.8 + /- 0.9 ) . Both groups had significant reductions in serum cholesterol ( approximately 10 % ) , whereas the Protein Group also had significant reductions in triacylglycerols ( TAG ) ( 21 % ) and the ratio of TAG/HDL cholesterol ( 23 % ) . Women in the CHO Group had higher insulin responses to meals and postpr and ial hypoglycemia , whereas women in the Protein Group reported greater satiety . This study demonstrates that increasing the proportion of protein to carbohydrate in the diet of adult women has positive effects on body composition , blood lipids , glucose homeostasis and satiety during weight loss BACKGROUND The metabolic effects of diets high in vegetable protein have not been assessed despite much recent interest in the effect of soy proteins in reducing serum cholesterol . OBJECTIVE We assessed the metabolic effects of diets high in vegetable protein ( specifically , wheat gluten ) on serum lipids , uric acid concentrations , and renal function . DESIGN Twenty hyperlipidemic men and women consumed isoenergetic test ( high-protein ) and control metabolic diets for 1 mo in a r and omized crossover design . In the high-protein diet , 11 % of the total dietary energy from starch in the control bread was replaced by vegetable protein ( wheat gluten ) , result ing in 27 % of total energy from protein compared with 16 % in the control diet . In other respects , the 2 diets were identical . RESULTS Compared with the control , the high-protein diet result ed in lower serum concentrations of triacylglycerol ( by 19.2 + /- 5.6 % ; P = 0.003 ) , uric acid ( by 12.7 + /- 2.0 % ; P < 0.001 ) , and creatinine ( by 2.5 + /- 1.1 % ; P = 0.035 ) and higher serum concentrations of urea ( by 42.2 + /- 5.8 % ; P < 0.001 ) and a higher 24-h urinary urea output ( by 99.2 + /- 17.2 % ; P < 0.001 ) . No significant differences were detected in total or HDL cholesterol or in the renal clearance of creatinine . LDL oxidation , assessed as the ratio of conjugated dienes to LDL cholesterol in the LDL fraction , was lower with the high-protein diet ( by 10.6 + /- 3.6 % ; P = 0.009 ) . CONCLUSIONS High intakes of vegetable protein from gluten may have beneficial effects on cardiovascular disease risk by reducing oxidized LDL , serum triacylglycerol , and uric acid . Further studies are required to assess the longer-term effects on renal function BACKGROUND Single-meal tests have shown that protein has greater thermogenic and satiating effects than does carbohydrate , which may be relevant for the prevention and treatment of obesity if these effects can be maintained over 24 h. OBJECTIVE The effects of pork-meat protein , soy protein , and carbohydrate on 24-h energy expenditure were compared . DESIGN Twelve young , healthy , overweight and mildly obese [ body mass index ( in kg/m(2 ) ) : 26 - 32 ] nonsmoking men participated in a r and omized , single-blind , 3-way crossover study lasting 4 d. The intervention had a 1 - 10-wk washout period . The 3 isoenergetic intervention diets were as follows : pork diet ( 29 % of energy as fat and 29 % as protein , mainly from pork meat ) , soy diet ( 29 % of energy as fat and 28 % as protein , mainly from soy ) , and carbohydrate diet ( 28 % of energy as fat and 11 % as protein ) . Twenty-four-hour energy expenditure was measured in a respiratory chamber at baseline and on day 4 of each intervention period . RESULTS Twenty-four-hour energy expenditure was higher with the pork than with the soy ( 248 kJ/d , 1.9 % ; P : = 0.05 ) or carbohydrate ( 492 kJ/d , 3.9 % ; P : < 0.0001 ) diet and higher with the soy than with the carbohydrate ( 244 kJ/d , 1.9 % ; P : < 0.05 ) diet . However , because of a higher satiating effect , energy intake was 10 - 15 % lower during the chamber stay than at baseline ( P : > 0.05 ) with all 3 diets . The differences in energy expenditure remained unchanged after adjustment for differences in 24-h energy balance . CONCLUSIONS Substitution of carbohydrate with 17 - 18 % of energy as either pork-meat or soy protein produced a 3 % higher 24-h energy expenditure . The animal protein in pork meat produced a 2 % higher 24-h energy expenditure than did the vegetable protein in soy BACKGROUND It is not clear whether varying the protein-to-carbohydrate ratio of weight-loss diets benefits body composition or metabolism . OBJECTIVE The objective was to compare the effects of 2 weight-loss diets differing in protein-to-carbohydrate ratio on body composition , glucose and lipid metabolism , and markers of bone turnover . DESIGN A parallel design included either a high-protein diet of meat , poultry , and dairy foods ( HP diet : 27 % of energy as protein , 44 % as carbohydrate , and 29 % as fat ) or a st and ard-protein diet low in those foods ( SP diet : 16 % of energy as protein , 57 % as carbohydrate , and 27 % as fat ) during 12 wk of energy restriction ( 6 - 6.3 MJ/d ) and 4 wk of energy balance ( approximately 8.2 MJ/d ) . Fifty-seven overweight volunteers with fasting insulin concentrations > 12 mU/L completed the study . RESULTS Weight loss ( 7.9 + /- 0.5 kg ) and total fat loss ( 6.9 + /- 0.4 kg ) did not differ between diet groups . In women , total lean mass was significantly ( P = 0.02 ) better preserved with the HP diet ( -0.1 + /- 0.3 kg ) than with the SP diet ( -1.5 + /- 0.3 kg ) . Those fed the HP diet had significantly ( P < 0.03 ) less glycemic response at weeks 0 and 16 than did those fed the SP diet . After weight loss , the glycemic response decreased significantly ( P < 0.05 ) more in the HP diet group . The reduction in serum triacylglycerol concentrations was significantly ( P < 0.05 ) greater in the HP diet group ( 23 % ) than in the SP diet group ( 10 % ) . Markers of bone turnover , calcium excretion , and systolic blood pressure were unchanged . CONCLUSION Replacing carbohydrate with protein from meat , poultry , and dairy foods has beneficial metabolic effects and no adverse effects on markers of bone turnover or calcium excretion BACKGROUND : Due to the high satiating effect of protein , a high-protein diet may be desirable in the treatment of obesity . However the long-term effect of different levels of protein intake on renal function is unclear . OBJECTIVE : To assess the renal effects of high vs low protein contents in fat-reduced diets . DESIGN : R and omized 6 months dietary intervention study comparing two controlled ad libitum diets with 30 energy ( E% ) fat content : high-protein ( HP ; 25 E% ) or low-protein , ( LP , 12 E% protein ) . All food was provided by self- selection in a shop at the department , and high compliance to the diet composition was confirmed by measurements of urinary nitrogen excretion . SUBJECTS : 65 healthy , overweight and obese ( 25<body mass index ( BMI ) < 34 kg/m2 ) . RESULTS : Dietary protein intake changed from 91.1 g/d to a 6 months intervention average of 70.4 g/d ( P<0.05 ) in the LP group and from 91.4 g/d to 107.8 g/d ( P<0.05 ) in the HP group , producing changes in glomular filtration rate ( GFR ) of −7.1 ml/min in the LP group and + 5.2 ml/min in the HP group ( group effect : P<0.05 ) . Kidney volume decreased by −6.2 cm3 in the LP group and increased by + 9.1 cm3 in the HP group ( P<0.05 ) , whereas albuminuria remained unchanged in all groups . CONCLUSION : Moderate changes in dietary protein intake cause adaptive alterations in renal size and function without indications of adverse effects OBJECTIVE : To study the effect on weight loss in obese subjects by replacement of carbohydrate by protein in ad libitum consumed fat-reduced diets . DESIGN : R and omized dietary intervention study over six months comparing two ad libitum fat reduced diets ( 30 % of total energy ) strictly controlled in composition : High-carbohydrate ( HC , protein 12 % of total energy ) or high-protein ( HP , protein 25 % of total energy ) . SETTING AND PARTICIPANTS : Subjects were 65 healthy , overweight and obese subjects ( 50 women , 15 men , aged 18–55 y ) r and omly assigned to HC ( n=25 ) , HP ( n=25 ) or a control group ( C , n=15 ) . All food was provided by self- selection in a shop at the department , and compliance to the diet composition was evaluated by urinary nitrogen excretion . MAIN OUTCOME MEASURE : Change in body weight , body composition and blood lipids . RESULTS : More than 90 % completed the trial . Weight loss after six months was 5.1 kg in the HC group and 8.9 kg in the HP group ( difference 3.7 kg , 95 % confidence interval (CI)(1.3–6.2 kg ) P<0.001 ) , and fat loss was 4.3 kg and 7.6 kg , respectively ( difference 3.3 kg ( 1.1–5.5 kg ) P<0.0001 ) , whereas no changes occurred in the control group . More subjects lost > 10 kg in the HP group ( 35 % ) than in the HC group ( 9 % ) . The HP diet only decreased fasting plasma triglycerides and free fatty acids significantly . CONCLUSIONS : Replacement of some dietary carbohydrate by protein in an ad libitum fat-reduced diet , improves weight loss and increases the proportion of subjects achieving a clinical ly relevant weight loss . More freedom to choose between protein-rich and complex carbohydrate-rich foods may allow obese subjects to choose more lean meat and dairy products , and hence improve adherence to low-fat diets in weight reduction programs OBJECTIVE : To determine the effect of replacing some dietary carbohydrate with protein , during energy restriction , on weight loss , total energy expenditure ( TEE ) , resting energy expenditure ( REE ) , respiratory quotient ( RQ ) , and the thermic effect of feeding ( TEF ) in subjects with hyperinsulinemia . DESIGN : Parallel , clinical intervention study of 12 weeks energy restriction ( 6.5 MJ/day ) and 4 weeks energy balance ( 8.2 MJ/day ) in two groups of subjects r and omly assigned to either a high-protein ( HP ) diet ( 27 % of energy ( % E ) as protein , 45%E as carbohydrate ) or a lower-protein ( LP ) diet ( 16%E as protein , 57%E as carbohydrate).SUBJECTS : A total of 36 obese nondiabetic volunteers with hyperinsulinemia ( 10 males/26 females , aged 34–65 y , BMI 28–43 kg/m2 , fasting insulin 12–45 mU/l ) . MEASUREMENTS : Body weight and composition , TEE , REE , and RQ were measured at baseline and at week 16 . In addition , the TEF to an HP or LP meal was determined for 3 h , at baseline and at week 16 . RESULTS : After 16 weeks , weight loss was similar in response to each diet ; the overall decrease was 7.9±0.6 kg ( P<0.001 ) , of which 6.8±0.5 kg was fat ( P<0.001 ) . REE fell similarly with each diet ; the overall decrease was 719±106 kJ/day ( P<0.001 ) . The TEF was 2 % greater after the HP than after the LP meal at baseline ( P<0.01 ) and 0.8 % greater at week 16 ( P=0.35 ) . After 16 weeks , the TEF was not reduced in either dietary group . There was no change in TEE after 16 weeks . CONCLUSION : In subjects with hyperinsulinemia an energy-restrictive diet containing an increased protein-to-carbohydrate ratio does not enhance weight loss or significantly affect energy expenditure . Caloric restriction , rather than the macronutrient composition of the diet , is the most important determinant of weight loss This study investigated the relative satiating hierarchy of the four energy-providing macronutrients ( fat , carbohydrate ( CHO ) , protein , and alcohol ) in lean women . On four separate occasions , the composition of an iso-energetic lunch preload was manipulated in 12 lean ( BMI < 25 kg/m2 ) women . The four treatments comprised a 1-MJ baseline meal and drink ( 40 % fat , 48 % CHO , 12 % protein ) to which was covertly added : 1 ) + 1MJ protein ; 2 ) + 1MJ alcohol ; 3 ) + 1MJ CHO ; and 4 ) + 1MJ fat . Prior to and at 30-min intervals , subjects completed 100-mm visual analogue scales rating subjective hunger and satiety . Ninety min following the preload , an ad lib . lunch meal was given ( 40 % fat , 48 % CHO , and 12 % protein ) and energy intake ( EI ) measured . Energy intake at the lunch meal was 2195 ( 880 , SD ) kJ , 2772 ( 1191 , SD ) kJ , 2502 ( 681 , SD ) , kJ and 2558 ( 1050 , SD ) kJ for the protein , alcohol , CHO , and fat preloads , respectively . There was no significant difference between the pleasantness of the preloads ( p > 0.05 ) . Macronutrient composition had a significant effect on short-term hunger ( F = 3.19 ; p < 0.05 ) , subjects being less hungry after the protein preload . Subjects also had a lower energy intake after the protein preload ( F = 3.11 ; p < 0.05 ) . We conclude that only protein has a differential short-term satiating effect when incorporated iso-energetically and at a similar energy density into the diet Context Low-carbohydrate weight reduction diets are popular despite a dearth of data on long-term efficacy and adverse effects . Contribution Community-dwelling hyperlipidemic persons were r and omly assigned to either a low-carbohydrate , ketogenic diet or a low-fat , low-cholesterol , reduced-calorie diet for 24 weeks . Compared to the low-fat group , patients in the low-carbohydrate group lost more weight , had a greater decrease in triglyceride levels , and had higher high-density lipoprotein cholesterol levels . Levels of low-density lipoprotein cholesterol remained stable in both groups . Side effects were more common in the low-cholesterol group but were generally mild . Caution s While the study suggests the efficacy and relative safety of the low-cholesterol diet , the high dropout rate , self-directed adherence to the diet , and relatively short observation period challenge the generalizability of the findings . The Editors As the prevalence of obesity has increased over the past 20 years ( 1 ) , the difficulties faced by overweight patients and their health care practitioners have become apparent . Fewer than 25 % of Americans who attempt to lose weight actually reduce caloric intake and increase exercise as currently recommended ( 2 ) . Persons who successfully lose weight have difficulty maintaining their weight loss ( 3 ) . Therefore , it is not surprising that consumers spend $ 33 billion yearly on weight loss products and services in search of effective therapies ( 2 ) . Because many weight loss interventions are unproven and untested , practitioners often lack information with which to recommend a certain therapy or to monitor a patient once a therapy is chosen . One approach to weight loss that has gained recognition in the face of modest supportive scientific evidence is the low-carbohydrate diet . A popular version of this diet recommends extreme restriction of carbohydrate intake to less than 20 g/d initially ( 4 ) . This level of carbohydrate restriction can induce serum and urinary ketones and weight loss ( 5 , 6 ) . However , until recently , available data on low-carbohydrate diets came from small studies of short duration , most of which were uncontrolled ( 5 , 7 - 10 ) . We examined body weight , body composition , serum lipid levels , and adverse effects over 24 weeks in hyperlipidemic persons who were r and omly assigned to follow a low-carbohydrate , ketogenic diet or a low-fat , low-cholesterol , reduced-calorie diet commonly used to induce weight loss and decrease serum lipid levels . Methods Participants Generally healthy persons were recruited from the community . Inclusion criteria were age 18 to 65 years , body mass index of 30 to 60 kg/m2 , desire to lose weight , elevated lipid levels ( total cholesterol level > 5.17 mmol/L [ > 200 mg/dL ] , low-density lipoprotein [ LDL ] cholesterol level > 3.36 mmol/L [ > 130 mg/dL ] , or triglyceride level > 2.26 mmol/L [ 200 mg/dL ] ) , and no serious medical condition . Exclusion criteria were use of any prescription medication in the previous 2 months ( except for oral contraceptives , estrogen therapy , and stable thyroid medication ) , pregnancy or breastfeeding , use of any weight loss diet or diet pills in the previous 6 months , and baseline ketonuria . All participants provided written informed consent , and the institutional review board of Duke University Health System approved the study . Participants received no monetary incentive . Interventions By using a computer-generated simple r and omization list , participants were allocated to receive the low-carbohydrate diet or low-fat diet . The intervention for both groups included group meetings , diet instruction , and an exercise recommendation . Group meetings took place at an outpatient research clinic twice monthly for 3 months , then monthly for 3 months . These meetings typically lasted 1 hour and consisted of diet instruction , supportive counseling , question naires , and biomedical measurements . During the study , participants selected their own menus and prepared or bought their own meals according to the guidelines presented to them . Participants were encouraged to exercise for 30 minutes at least 3 times weekly , but no formal exercise program or incentives were provided . Low-Carbohydrate Diet Using a popular diet book published by a lay press and additional h and outs , trained research staff instructed participants to restrict intake of carbohydrates to less than 20 g/d ( 4 ) . Participants were permitted unlimited amounts of animal foods ( meat , fowl , fish , and shellfish ) , unlimited eggs , 4 oz of hard cheese , 2 cups of salad vegetables ( such as lettuce , spinach , or celery ) , and 1 cup of low-carbohydrate vegetables ( such as broccoli , cauliflower , or squash ) daily . Participants were encouraged to drink 6 to 8 glasses of water daily . When participants were halfway to their goal body weight ( determined at the week 10 visit with assistance from research personnel ) , they were advised to add approximately 5 g of carbohydrates to their daily intake each week until they reached a level at which body weight was maintained . To simulate the practice of the study sponsor , the low-carbohydrate diet group also received daily nutritional supplements ( multivitamin , essential oils , diet formulation , and chromium picolinate ; for a list of the composition of these supplements , see the Appendix ) ( 6 ) . Low-Fat Diet Using a commonly available booklet and additional h and outs , a registered dietitian instructed participants in a diet consisting of less than 30 % of daily energy intake from fat , less than 10 % of daily energy intake from saturated fat , and less than 300 mg of cholesterol daily ( 11 , 12 ) . The recommended energy intake was 2.1 to 4.2 MJ ( 500 to 1000 kcal ) less than the participant 's calculated energy intake for weight maintenance ( body weight in pounds 10 ) ( 13 ) . Primary Outcome Measure Body weight and body mass index were the primary outcome measures . At each visit , participants were weighed on the same calibrated scale while wearing lightweight clothing and no shoes . Body mass index was calculated as body weight in kilograms divided by height in meters squared . Secondary Outcome Measures Adherence Adherence to the diet was measured by self-report , food records , and , for the low-carbohydrate diet group , urinary ketone assessment . Diet Composition All participants completed a 24-hour recall of food intake at baseline and take-home food records ( 5 consecutive days , including a weekend ) that were collected at each meeting during the study . Participants were instructed on how to document food intake and were given h and outs with examples of how to complete the records . A sample of participants ( 13 in the low-carbohydrate diet group and 7 in the low-fat diet group ) who completed the study was selected for food record analysis by the research staff on the basis of adequacy of detail in their records . A registered dietitian analyzed the food records by using a nutrition software program ( Nutritionist Five , version 1.6 [ First Data Bank , Inc. , San Bruno , California ] ) . Ketonuria Restriction of dietary intake of carbohydrates to less than 40 g/d typically results in ketonuria that is detectable by dipstick analysis , which can be used to monitor adherence to the low-carbohydrate diet ( 14 , 15 ) . At each return visit , participants provided a fresh urine specimen for analysis . The following semi-quantitative scale was used to categorize ketone content : none , trace ( up to 0.9 mmol/L [ 5 mg/dL ] ) , small ( 0.9 to 6.9 mmol/L [ 5 to 40 mg/dL ] ) , moderate ( 6.9 to 13.8 mmol/L [ 40 to 80 mg/dL ] ) , large80 ( 13.8 to 27.5 mmol/L [ 80 to 160 mg/dL ] ) , and large160 ( > 27.5 mmol/L [ > 160 mg/dL ] ) . Body Composition Body composition was estimated by using bioelectric impedance ( model TBF-300A [ Tanita Corp. , Arlington Heights , Illinois ] ) at approximately the same time of day ( afternoon or evening ) at each return visit . In a subset of 33 participants , the percentage of body fat as measured by bioelectric impedance had excellent correlation with the percentage as measured by dual-energy x-ray absorptiometry ( r = 0.93 [ 95 % CI , 0.87 to 0.97 ] ) . Vital Signs Blood pressure and pulse rate were measured in the nondominant arm by using an automated digital cuff ( model HEM-725C [ Omron Corp. , Vernon Hills , Illinois ] ) after the participant had been sitting for 3 minutes . Two measurements were taken at each visit and averaged for the analysis . Serum Lipids and Lipoproteins Serum specimens for lipid measurement were obtained in the morning after at least 8 hours of fasting at the screening visit and at 8 , 16 , and 24 weeks . Other Metabolic Effects Serum tests for sodium , potassium , chloride , urea nitrogen , creatinine , calcium , phosphorus , total protein , albumin , uric acid , total bilirubin , alanine aminotransferase , aspartate aminotransferase , alkaline phosphatase , thyroid-stimulating hormone , iron , hemoglobin , leukocyte count , and platelet count were obtained at the screening visit and at 8 , 16 , and 24 weeks . The glomerular filtration rate was estimated by using an equation that included age ; sex ; race ; and serum levels of albumin , creatinine , and urea nitrogen ( Modification of Diet in Renal Disease Study equation ) ( 16 ) . Adverse Effects At all return visits , participants completed an open-ended question naire on side effects . At the 20- and 24-week visits , participants completed a checklist of the side effects that were most often mentioned during the study . Statistical Analysis Analyses were performed by using S-PLUS software , version 6.1 ( Insightful Corp. , Seattle , Washington ) , or SAS software , version 8.02 ( SAS Institute , Inc. , Cary , North Carolina ) . For categorical outcomes , groups were compared by using the chi-square test or Fisher exact test , as appropriate . For all primary and secondary continuous outcomes , linear mixed-effects models ( PROC MIXED procedure in SAS software ) that included fixed and r and om effects were used to determine expected mean values at each time point and to test hypotheses of group differences . In most body weight and Objectives : To evaluate energy expenditure after three isoenergetic meals of different nutrient composition and to establish the relationship between the thermic effect of food ( TEF ) , subsequent energy intake from a test meal and satiety sensations related to consumption . Design : The study employed a repeated measures design . Ten subjects received , in a r and omized order , three meals of 2331±36 kJ ( 557±9 kcal ) . About 68 % of energy from protein in the high protein meal ( HP ) , 69 % from carbohydrate in the high carbohydrate meal ( HC ) and 70 % from fat in the high fat meal ( HF ) . Setting : The experiments were performed at the University of Milan . Subjects : Ten normal body-weight healthy women . Methods : Energy expenditure was measured by indirect calorimetric measurements , using an open-circuit ventilated-hood system ; intake was assessed 7 h later by weighing the food consumed from a test meal and satiety sensations were rated by means of a satiety rating question naire . Results : TEF was 261±59 , 92±67 and 97±71 kJ over 7 h after the HP , HC and HF meals , respectively . The HP meal was the most thermogenic ( P<0.001 ) and it determined the highest sensation of fullness ( P=0.002 ) . There were no differences in the sensations and thermic effect between fat and carbohydrate meals . A significant relationship linked TEF to fullness sensation ( r=0.41 , P=0.025 ) . Energy intake from the test meal was comparable after HP , HC and HF meals . Conclusions : Our results suggest that TEF contributes to the satiating power of foods . Sponsorship : This work was supported by the National Research Council , targeted project ‘ Prevention and Control of Disease Factors ’ , subproject ‘ Nutrition ’ , grant no. 94.00365.PF41 Objective : To develop and test an experimental model design ed to detect changes in selection between foods individually enriched in protein , carbohydrate and fat in human subjects . Design : R and omised counterbalanced ( Latin square ) design . Setting : The metabolic suite at the Rowett Research Institute ’s Human Nutrition Unit . Subjects : 16 normal-weight men ( mean BMI = 23.5 ) . Interventions : Subjects were each studied 4 times in a 2-day protocol . On day 1 subjects received a fixed maintenance diet ; on day 2 they received a m and atory intake as breakfast ( 08.30 ) plus a drink at 10.30 . This comprised 80 % of resting energy requirements as high-protein ( HP ) , high-carbohydrate ( HC ) or high-fat ( HF ) foods ( 60 % of energy in each case ) or an equal mixture ( M ) of macronutrients , 33 % by energy . All m and atory treatments contained the same energy content and density . From 12.30 onwards , subjects had ad libitum access to a counter-balanced selection of three groups of familiar foods ( 10 HP , 10 HC and 10 HF ; 30 foods in total ) . Most energy in each food was derived from one macronutrient ( ∼60 % ) , the remainder being equally split between the other two macronutrients . Results : Subjects were significantly less hungry before lunch on the HP and M ( 33 % protein ) treatments ( F3,44=7.35 ; P<0.001 ) . At lunch , they ate more energy after the HF treatment than after any of the other treatment ( F1,38=9.00 ; P=0.005 ) . This was largely in the form of fat and protein , and to a lesser extent carbohydrate . Subsequent energy intake ( EI ) were lower on the HF treatment , largely through selection of less fat in the afternoon ( F1,42=6.90 ; P=0.012 ) . Daily EIs were similar across treatments . Conclusion : This design appears sensitive meal-to-meal to changes in both nutrient and EIs . Sponsorship : This work was supported by the Scottish Office , Agriculture , Environment and Fisheries Department Objective : The recent literature suggests that high-protein , low-fat diets promote a greater degree of weight loss compared to high-carbohydrate , low-fat diets , but the mechanism of this enhanced weight loss is unclear . This study compared the acute , energy-cost of meal-induced thermogenesis on a high-protein , low-fat diet versus a high-carbohydrate , low-fat diet . Methods : Ten healthy , normal weight , non-smoking female volunteers aged 19 - 22 years were recruited from a campus population . Using a r and omized , cross-over design , subjects consumed the high-protein and the high-carbohydrate diets for one day each , and testing was separated by a 28- or 56-day interval . Control diets were consumed for two days prior to each test day . On test day , the resting energy expenditure , the non-protein respiratory quotient and body temperature were measured following a 10-hour fast and at 2.5-hour post breakfast , lunch and dinner . Fasting blood sample s were collected test day and the next morning , and complete 24-hour urine sample s were collected the day of testing . Results : Postpr and ial thermogenesis at 2.5 hours post-meal averaged about twofold higher on the high protein diet versus the high carbohydrate diet , and differences were significant after the breakfast and the dinner meals ( p < 0.05 ) . Body temperature was slightly higher on the high protein diet ( p = 0.08 after the dinner meal ) . Changes in the respiratory quotient post-meals did not differ by diet , and there was no difference in 24-hour glomerular filtration rates by diet . Nitrogen balance was significantly greater on the high-protein diet compared to the high-carbohydrate diet ( 7.6 ± 0.9 and −0.4 ± 0.5 gN/day , p < 0.05 ) , and at 24-hour post-intervention , fasting plasma urea nitrogen concentrations were raised on the high protein diet versus the high-carbohydrate diet ( 13.9 ± 0.9 and 11.2 ± 1.0 mg/dL respectively , p < 0.05 ) . Conclusions : These data indicate an added energy-cost associated with high-protein , low-fat diets and may help explain the efficacy of such diets for weight loss BACKGROUND Despite the popularity of the low-carbohydrate , high-protein , high-fat ( Atkins ) diet , no r and omized , controlled trials have evaluated its efficacy . METHODS We conducted a one-year , multicenter , controlled trial involving 63 obese men and women who were r and omly assigned to either a low-carbohydrate , high-protein , high-fat diet or a low-calorie , high-carbohydrate , low-fat ( conventional ) diet . Professional contact was minimal to replicate the approach used by most dieters . RESULTS Subjects on the low-carbohydrate diet had lost more weight than subjects on the conventional diet at 3 months ( mean [ + /-SD ] , -6.8+/-5.0 vs. -2.7+/-3.7 percent of body weight ; P=0.001 ) and 6 months ( -7.0+/-6.5 vs. -3.2+/-5.6 percent of body weight , P=0.02 ) , but the difference at 12 months was not significant ( -4.4+/-6.7 vs. -2.5+/-6.3 percent of body weight , P=0.26 ) . After three months , no significant differences were found between the groups in total or low-density lipoprotein cholesterol concentrations . The increase in high-density lipoprotein cholesterol concentrations and the decrease in triglyceride concentrations were greater among subjects on the low-carbohydrate diet than among those on the conventional diet throughout most of the study . Both diets significantly decreased diastolic blood pressure and the insulin response to an oral glucose load . CONCLUSIONS The low-carbohydrate diet produced a greater weight loss ( absolute difference , approximately 4 percent ) than did the conventional diet for the first six months , but the differences were not significant at one year . The low-carbohydrate diet was associated with a greater improvement in some risk factors for coronary heart disease . Adherence was poor and attrition was high in both groups . Longer and larger studies are required to determine the long-term safety and efficacy of low-carbohydrate , high-protein , high-fat diets Normal subjects were fed protein or carbohydrate breakfasts . Both meals were in the form of a chocolate pudding and had similar sensory qualities . At lunchtime subjects were allowed to select from a buffet . The protein breakfast had a greater satiating power than the carbohydrate breakfast , but there was no difference in overall selection of protein or carbohydrate at lunchtime . However , the carbohydrate breakfast did decrease selection of apple , the only pure carbohydrate food available at lunchtime . In a second experiment changes in plasma amino acid levels were studied after subjects received carbohydrate breakfasts containing 0 , 4 , 8 or 12 % protein , or a danish pastry . Only the 0 % protein breakfast increased tryptophan availability to the brain . These experiments were performed to test the hypothesis that alterations in brain 5-hydroxytryptamine , brought about by dietary alterations in brain tryptophan , regulate selection of protein and carbohydrate . The results suggest that this mechanism was not operating in our experiments The objectives of this study were to determine if high-protein versions of the same food systems show more sensory-specific satiety than lower-protein versions , and to determine the effect of these protein differences on hunger levels following a meal . Subjects ate a high-protein and a low-protein version of a food system ( either strawberry yogurt or a s and wich ) as test meals . The high-protein strawberry yogurt test meal consisted of a serving of strawberry yogurt that contained whey protein isolate ; the low-protein yogurt test meal consisted of a close-to-commercial strawberry yogurt . The high-protein s and wich meal consisted of a ham s and wich ; the low-protein s and wich meal consisted of a bacon s and wich . Subjects tasted small portions of a set of foods ( which included a sample of the test meal ) , and rated their liking of these foods before and after eating a test meal . Sensory-specific satiety occurred for all test meals . The decreases in liking when the high-protein versions of the test meals were eaten were significantly greater than the decreases in liking for the paired low-protein test meals . Higher-protein versions of the test meals also decreased hunger more than the lower-protein versions BACKGROUND A high dietary calcium intake is strongly suspected of increasing the risk of kidney stones . However , a high intake of calcium can reduce the urinary excretion of oxalate , which is thought to lower the risk . The concept that a higher dietary calcium intake increases the risk of kidney stones therefore requires examination . METHODS We conducted a prospect i ve study of the relation between dietary calcium intake and the risk of symptomatic kidney stones in a cohort of 45,619 men , 40 to 75 years of age , who had no history of kidney stones . Dietary calcium was measured by means of a semiquantitative food-frequency question naire in 1986 . During four years of follow-up , 505 cases of kidney stones were documented . RESULTS After adjustment for age , dietary calcium intake was inversely associated with the risk of kidney stones ; the relative risk of kidney stones for men in the highest as compared with the lowest quintile group for calcium intake was 0.56 ( 95 percent confidence interval , 0.43 to 0.73 ; P for trend , < 0.001 ) . This reduction in risk decreased only slightly ( relative risk , 0.66 ; 95 percent confidence interval , 0.49 to 0.90 ) after further adjustment for other potential risk factors , including alcohol consumption and dietary intake of animal protein , potassium , and fluid . Intake of animal protein was directly associated with the risk of stone formation ( relative risk for men with the highest intake as compared with those with the lowest , 1.33 ; 95 percent confidence interval , 1.00 to 1.77 ) ; potassium intake ( relative risk , 0.49 ; 95 percent confidence interval , 0.35 to 0.68 ) and fluid intake ( relative risk , 0.71 ; 95 percent confidence interval , 0.52 to 0.97 ) were inversely related to the risk of kidney stones . CONCLUSIONS A high dietary calcium intake decreases the risk of symptomatic kidney stones OBJECTIVE To determine the effect of a high-protein ( HP ) weight loss diet compared with a lower-protein ( LP ) diet on fat and lean tissue and fasting and postpr and ial glucose and insulin concentrations . RESEARCH DESIGN AND METHODS Replacing dietary protein for carbohydrate ( CHO ) during energy restriction and weight loss has been effective in sparing lean mass and improving insulin sensitivity in obese subjects but has not been tested in subjects with type 2 diabetes . We compared an HP diet ( 28 % protein , 42 % CHO , 28 % fat [ 8 % saturated fatty acids , 12 % monounsaturated fatty acids , 5 % polyunsaturated fatty acids ] ) with an LP diet ( 16 % protein , 55 % CHO , 26 % fat [ 8 % saturated fatty acids , 11 % monounsaturated fatty acids , 5 % polyunsaturated fatty acids ] ) in 54 obese men and women with type 2 diabetes during 8 weeks of energy restriction ( 1,600 kcal ) and 4 weeks of energy balance . Body composition was determined by dual-energy X-ray absorptiometry at weeks 0 and 12 . RESULTS Overall , weight loss of 5.2 + /- 1.8 kg was achieved independently of diet composition . However , women on the HP diet lost significantly more total ( 5.3 vs. 2.8 kg , P=0.009 ) and abdominal ( 1.3 vs. 0.7 kg , P=0.006 ) fat compared with the women on the LP diet , whereas , in men , there was no difference in fat loss between diets ( 3.9 vs. 5.1 kg ) . Total lean mass decreased in all subjects independently of diet composition . LDL cholesterol reduction was significantly greater on the HP diet ( 5.7 % ) than on the LP diet ( 2.7 % ) ( P < 0.01 ) . CONCLUSIONS Both dietary patterns result ed in improvements in the cardiovascular disease ( CVD ) risk profile as a consequence of weight loss . However , the greater reductions in total and abdominal fat mass in women and greater LDL cholesterol reduction observed in both sexes on the HP diet suggest that it is a valid diet choice for reducing CVD risk in type 2 diabetes Low protein diets are commonly prescribed for patients with idiopathic calcium nephrolithiasis , who account for > 80 % of new diagnoses of kidney stones . This dietary advice is supported by metabolic studies and epidemiologic observational studies but has not been evaluated in a controlled trial . Using 1983 - 1985 data from three Northern California Kaiser Permanente Medical Centers , the authors r and omly assigned 99 persons who had calcium oxalate stones for the first time to a low animal protein , high fiber diet that contained approximately 56 - 64 g daily of protein , 75 mg daily of purine ( primarily from animal protein and legumes ) , one-fourth cup of wheat bran supplement , and fruits and vegetables . Intervention subjects were also instructed to drink six to eight glasses of liquid daily and to maintain adequate calcium intake from dairy products or calcium supplements . Control subjects were instructed only on fluid intake and adequate calcium intake . Both groups were followed regularly for up to 4.5 years with food frequency question naires , serum and urine chemistry analysis , and abdominal radiography ; and they were urged to comply with dietary instructions . In the intervention group of 50 subjects , stones recurred in 12 ( 7.1 per 100 person-years ) compared with two ( 1.2 per 100 person-years ) in the control group ; both groups received a mean of 3.4 person-years of follow-up ( p = 0.006 ) . After adjustment for possible confounding effects of age , sex , education , and baseline protein and fluid intake , the relative risk of a recurrent stone in the intervention group was 5.6 ( 95 % confidence interval 1.2 - 26.1 ) compared with the control group . The authors conclude that advice to follow a low animal protein , high fiber , high fluid diet has no advantage over advice to increase fluid intake alone OBJECTIVE : To test the hypothesis that hyperinsulinemic obese subjects would respond differently to changes in the composition of hypoenergetic diets . DESIGN : A 4-week r and omized dietary intervention trial . SUBJECTS : Thirteen male obese hyperinsulinemic normoglycemic subjects were divided into two groups and fed hypoenergetic diets providing 80 % of their resting energy expenditure ( REE ) . One group received a high-protein diet ( HP ; 45 % protein , 25 % carbohydrates , and 30 % fat as percent of dietary energy ) and the other a high-carbohydrate diet ( HC ; 12 % protein , 58 % carbohydrates and 30 % fat ) . MEASUREMENTS : Anthropometry , body composition , fasting serum insulin and lipids , and REE were performed before and after the feeding period . RESULTS : Weight loss was higher in the HP than HC group ( 8.3±0.7 vs 6.0±0.6 kg , P<0.05 ) . There was a decrease in body fat in both groups , whereas body water decreased significantly more in the HP group . REE decreased more in the HC than the HP group ( −384.3±84.6 vs −132.3±51.0 kcal , P<0.05 ) . Serum total cholesterol , triglycerides and LDL cholesterol decreased significantly to a similar extent in both diet groups , while HDL cholesterol was decreased significantly only in the HP group . Mean fasting insulin decreased significantly in both diet groups and reached the normal range only in the HP group . CONCLUSION : A low-carbohydrate ( LC ) , HP hypoenergetic diet could be the diet composition of choice for a weight-reducing regimen in obese hyperinsulinemic subjects Objective : Assessment of a possible relationship between perception of satiety and diet-induced thermogenesis , with different macronutrient compositions , in a controlled situation over 24 h. Design : Two diets with different macronutrient compositions were offered to all subjects in r and omized order . Setting : The study was executed in the respiration chambers at the department of Human Biology , Maastricht University . Subjects : Subjects were eight females , ages 23–33 y , BMI 23±3 kg/m2 , recruited from University staff and students . Interventions : Subjects were fed in energy balance , with protein/carbohydrate/fat : 29/61/10 and 9/30/61 percentage of energy , with fixed meal sizes and meal intervals , and a fixed activity protocol , during 36 h experiments in a respiration chamber . The appetite profile was assessed by question naires during the day and during meals . Diet induced thermogenesis was determined as part of the energy expenditure . Results : Energy balance was almost complete , with non-significant deviations . Diet-Induced-Thermogenesis ( DIT ) was 14.6±2.9 % , on the high protein/carbohydrate diet , and 10.5±3.8 % on the high fat diet ( P<0.01 ) . With the high protein/high carbohydrate diet , satiety was higher during meals ( P<0.001 ; P<0.05 ) , as well as over 24 h ( P<0.001 ) , than with the high fat diet . Within one diet , 24 h DIT and satiety were correlated ( r=0.6 ; P<0.05 ) . The difference in DIT between the diets correlated with the differences in satiety ( r=0.8 ; P<0.01 ) . Conclusion : In lean women , satiety and DIT were synchronously higher with a high protein/high carbohydrate diet than with a high fat diet . Differences ( due to the different macronutrient compositions ) in DIT correlated with differences in satiety over 24 Untested alternative weight loss diets , such as very low carbohydrate diets , have unsubstantiated efficacy and the potential to adversely affect cardiovascular risk factors . Therefore , we design ed a r and omized , controlled trial to determine the effects of a very low carbohydrate diet on body composition and cardiovascular risk factors . Subjects were r and omized to 6 months of either an ad libitum very low carbohydrate diet or a calorie-restricted diet with 30 % of the calories as fat . Anthropometric and metabolic measures were assessed at baseline , 3 months , and 6 months . Fifty-three healthy , obese female volunteers ( mean body mass index , 33.6 + /- 0.3 kg/m(2 ) ) were r and omized ; 42 ( 79 % ) completed the trial . Women on both diets reduced calorie consumption by comparable amounts at 3 and 6 months . The very low carbohydrate diet group lost more weight ( 8.5 + /- 1.0 vs. 3.9 + /- 1.0 kg ; P < 0.001 ) and more body fat ( 4.8 + /- 0.67 vs. 2.0 + /- 0.75 kg ; P < 0.01 ) than the low fat diet group . Mean levels of blood pressure , lipids , fasting glucose , and insulin were within normal ranges in both groups at baseline . Although all of these parameters improved over the course of the study , there were no differences observed between the two diet groups at 3 or 6 months . beta- Hydroxybutyrate increased significantly in the very low carbohydrate group at 3 months ( P = 0.001 ) . Based on these data , a very low carbohydrate diet is more effective than a low fat diet for short-term weight loss and , over 6 months , is not associated with deleterious effects on important cardiovascular risk factors in healthy women The influence of the nutrient composition of food on energy expenditure during a 24 h period was investigated in adult volunteers . The maximum probable effect was determined using iso-energetic diets high in either protein or in glucose . Two men and four women took part in the study . Their body-weights and body composition were within the normal range . Each subject lived for 28 h in a whole-body calorimeter set at 26 degrees , on two separate occasions . During each session they ate one of the following iso-energetic diets : high-protein-low-carbohydrate or high-glucose-low-protein . Energy expenditure was determined while the subject followed a pre-set pattern of activity . A 24 h collection of urine was made and total nitrogen , creatinine and urea excretions were determined , so that heat production could be corrected for protein metabolism . Two independent measures of energy expenditure were made : direct calorimetry was used to obtain heat loss partitioned into its sensible and evaporative components , while indirect calorimetry was used to estimate heat production from oxygen consumption , carbon dioxide production and N excretion . There was good agreement between the two estimates of 24 h energy expenditure : for the twelve sessions in the calorimeter the mean difference between heat production and heat loss was only 0.4 ( SEM 0.39)% . The results showed that nutrient composition can have a marked influence on 24 h energy expenditure in adult humans . Mean values of 8659 ( SEM 230 ) kJ and 7735 ( SEM 250 ) kJ were obtained for the high-protein and high-glucose diets respectively . This 12 % increase in energy expenditure on the high-protein intake was significant ( P less than 0.001 ) . On the high-glucose intake , total heat loss comprised 22 and 78 % evaporative and sensible heat losses respectively . The increase in heat loss on the high-protein intake was accounted for by a 39 % increase in evaporative heat loss and a 7 % increase in sensible heat loss . It is concluded that the composition of the nutrient intake has a greater influence on the metabolic rate of adult humans than has been suggested by some groups of workers in recent years OBJECTIVE : To study the effect of diet composition on diet-induced thermogenesis ( DIT ) over 24 h in a respiration chamber . SUBJECTS : Eight healthy female volunteers ( age 27±3 y ; body mass index , BMI 23±3 kg/m2).DIETS : A high protein and carbohydrate ( HP/C ) ( 60:10:30 ; percentage energy (E%)carbohydrate , fat and protein , respectively ) and high fat ( HF ) ( 30:60:10 respectively ) diet , both isoenergetic , isovolumetric , composed of normal food items and matched for organoleptic properties ( taste , smell , appearance ) . DESIGN : Subjects spent two 36 h periods each in a respiration chamber consuming both test diets in r and om order . Components of 24 h energy expenditure ( 24 h EE ) : sleeping metabolic rate , DIT and activity induced energy expenditure were measured . RESULTS : DIT was higher in all subjects while on the HP/C diet ( 1295 kJ/d vs 931 kJ/d ; 14.6 % vs 10.5 % of energy intake ; P<0.02 ) . There was no significant difference in other components or total 24 h EE , although there was a trend towards higher EE on the HP/C diet . CONCLUSION : A high protein and carbohydrate diet induces a greater thermic response in healthy individuals when compared to a high fat diet OBJECTIVE The prevalence of obesity has increased dramatically in recent years . However , the role of dietary composition in body weight regulation remains unclear . The purpose of this work was to investigate the acute effects of dietary glycemic index ( GI ) on energy metabolism and voluntary food intake in obese subjects . METHODS Twelve obese teenage boys were evaluated on three separate occasions using a crossover study protocol . During each evaluation , subjects consumed identical test meals at breakfast and lunch that had a low , medium , or high GI . The high- and medium-GI meals were design ed to have similar macronutrient composition , fiber content , and palatability , and all meals for each subject had equal energy content . After breakfast , plasma and serum concentrations of metabolic fuels and hormones were measured . Ad libitum food intake was determined in the 5-hour period after lunch . RESULTS Voluntary energy intake after the high-GI meal ( 5.8 megajoule [ mJ ] ) was 53 % greater than after the medium-GI meal ( 3.8 mJ ) , and 81 % greater than after the low-GI meal ( 3.2 mJ ) . In addition , compared with the low-GI meal , the high-GI meal result ed in higher serum insulin levels , lower plasma glucagon levels , lower postabsorptive plasma glucose and serum fatty acids levels , and elevation in plasma epinephrine . The area under the glycemic response curve for each test meal accounted for 53 % of the variance in food intake within subjects . CONCLUSIONS The rapid absorption of glucose after consumption of high-GI meals induces a sequence of hormonal and metabolic changes that promote excessive food intake in obese subjects . Additional studies are needed to examine the relationship between dietary GI and long-term body weight regulation OBJECTIVE To describe the sources of protein intake in a sample of the US adult population and among subgroups defined by race-ethnicity , age , and gender . DESIGN The Third National Health and Nutrition Examination Survey , 1988 - 1991 , is a stratified r and om sample of the total civilian noninstitutionalized population , drawn from the 50 United States and the District of Columbia . For all foods consumed by the participants , based on a 24-hour dietary recall , protein sources and the contribution of each protein type to the total protein intake were determined . SUBJECTS Adult participants in the third National Health and Nutrition Examination Survey ( n = 7,924 ) . STATISTICAL ANALYSES Weighted total , age-specific , and age-adjusted mean protein intakes were calculated using SAS and WesVarPC . Statistical differences were determined by 2-tailed t tests . RESULTS The main protein source in the American diet is animal protein ( 69 % ) . Meat , fish , and poultry protein combined contributed the most to animal protein ( 42 % ) , followed by dairy protein ( 20 % ) . Grains ( 18 % ) contributed the most to plant protein consumption . Women consumed a lower percentage of beef ( 14 % ) and pork ( 7 % ) protein than did men ( 18 % and 9 % , respectively ) . Women also consumed a higher percentage of poultry ( 13 % ) , dairy ( 22 % ) , and fruit and vegetable ( 11 % ) protein than did men ( 11 % , 19 % , and 9 % , respectively ) . Blacks reported eating a higher percentage of poultry ( 18 % ) and pork ( 11 % ) protein and a lower percent of dairy protein ( 14 % ) than did whites ( 12 % , 7 % , and 22 % , respectively ) and Mexican-Americans ( 11 % , 8 % , and 17 % , respectively ) . Mexican-Americans consumed a higher percentage of legume ( 7 % ) and egg ( 7 % ) protein than did whites ( 4 % and 4 % , respectively ) and blacks ( 4 % and 5 % , respectively ) . Whites consumed a higher percentage of grain protein ( 19 % ) than did blacks ( 16 % ) and Mexican-Americans ( 15 % ) . CONCLUSIONS These results show that , although the percentage of total energy from protein may be similar among race-ethnicities and between men and women , their sources of protein are different . These differences should be taken into account when providing nutrition education for specific population OBJECTIVE To determine the effect of a high-protein ( HP ) diet compared with a low-protein ( LP ) diet on weight loss , resting energy expenditure ( REE ) , and the thermic effect of food ( TEF ) in subjects with type 2 diabetes during moderate energy restriction . RESEARCH DESIGN AND METHODS In this study , 26 obese subjects with type 2 diabetes consumed a HP ( 28 % protein , 42 % carbohydrate ) or LP diet ( 16 % protein , 55 % carbohydrate ) during 8 weeks of energy restriction ( 1,600 kcal/day ) and 4 weeks of energy balance . Body weight and composition and REE were measured , and the TEF in response to a HP or LP meal was determined for 2 h , at weeks 0 and 12 . RESULTS The mean weight loss was 4.6 + /- 0.4 kg ( P < 0.001 ) , of which 4.5 + /- 0.4 kg was fat ( P < 0.001 ) , with no effect of diet ( P = 0.6 ) . At both weeks 0 and 12 , TEF was greater after the HP than after the LP meal ( 0.064 vs. 0.050 kcal x kcal(-1 ) energy consumed x 2 h(-1 ) , respectively ; overall diet effect , P = 0.003 ) . REE and TEF were reduced similarly with each of the diets ( time effects , P = 0.02 and P < 0.001 , respectively ) . CONCLUSIONS In patients with type 2 diabetes , a low-fat diet with an increased protein-to-carbohydrate ratio does not significantly increase weight loss or blunt the fall in REE 1 . We studied the relationship between changes in glomerular filtration rate ( GFR ) determined as inulin clearance ( CIn ) , and changes in renal blood flow ( RBF ) , determined as p-aminohippurate clearance ( CPAH ) , after the ingestion of a large ( 1.35 + /- SEM 0.04 g/kg , n = 9 ) , moderate ( 1.08 + /- 0.03 g/kg , n = 10 ) or mild ( 0.55 + /- 0.02 g/kg , n = 8) protein load given as a meat meal . Control subjects ( n = 10 ) received a carbohydrate meal . 2 . CIn and CPAH increased after a protein meal . Two hours after eating the test meal , GFR levels were ( mean + /- SEM ) 160.0 + /- 13.8 ( P less than 0.05 ) , 141 + /- 7.69 and 127.8 + /- 9.07 ml/min in the groups that received a large , moderate and mild protein load , respectively . Peak CIn values after the meal were 211.6 + /- SEM 14.92 ( P less than 0.001 ) , 177.5 + /- 10.88 ( P less than 0.01 ) and 129.0 + /- 8.72 ml/min after a large , moderate and mild protein load , respectively . 3 . At peak GFR levels after the meal , filtration fraction ( FF ) ( CIn X 100/CPAH ) increased significantly ( P less than 0.02 ) with the large and with the moderate protein load , but not with the mild protein load . 4 . There was a significant ( P less than 0.001 ) positive relationship between increments of FF and increments of CIn , but not CPAH , whether the values were expressed as post-meal/pre-meal ratios or as absolute changes . ( ABSTRACT TRUNCATED AT 250 WORDS The aim of the study was to investigate the effects of two hypocaloric ( 800-kcal ) diets on body weight reduction and composition , insulin sensitivity , and proteolysis in 25 normal glucose-tolerant obese women . The two diets had the following composition : 45 % protein , 35 % carbohydrate ( CHO ) , and 20 % fat ( HP diet , 10 subjects ) , and 60 % CHO , 20 % protein , and 20 % fat ( HC diet , 15 subjects ) ; both lasted 21 days . A euglycemic hyperinsulinemic ( 25 mU/kg/h ) clamp lasting 150 minutes combined with indirect calorimetry was performed before and after the diet . Both diets induced a similar decrease in body weight and fat mass ( FM ) , whereas fat-free mass ( FFM ) decreased only after the HC diet . 3-Methylhistidine ( 3-CH3-HIS ) excretion was reduced by 48 % after the HP diet and remained unchanged after the HC diet ( P < .05 ) . A significant correlation was found between the changes in FFM and in 3-CH3-HIS excretion after the diet ( rs = .50 , P < .02 ) . Blood glucose remained unchanged , while insulin decreased in both diets . Free fatty acids ( FFA ) significantly increased only after the HC diet ( P < .05 ) . During the clamp period , glucose disposal and glucose oxidation significantly increased after the HP diet and significantly decreased after the HC diet . Opposite results were found when measuring lipid oxidation . In conclusion , our experience suggests that ( 1 ) a hypocaloric diet providing a high percentage of natural protein can improve insulin sensitivity ; and ( 2 ) conversely , a hypocaloric high-polysaccharide-CHO diet decreases insulin sensitivity and is unable to spare muscle tissue |
12,365 | 28,518,283 | We found no beneficial or detrimental effects of BCAA on nausea or vomiting in a r and om-effects meta- analysis or on quality of life or nutritional parameters . | BACKGROUND Hepatic encephalopathy is a brain dysfunction with neurological and psychiatric changes associated with liver insufficiency or portal-systemic shunting .
The severity ranges from minor symptoms to coma .
A Cochrane systematic review including 11 r and omised clinical trials on branched-chain amino acids ( BCAA ) versus control interventions has evaluated if BCAA may benefit people with hepatic encephalopathy .
OBJECTIVES To evaluate the beneficial and harmful effects of BCAA versus any control intervention for people with hepatic encephalopathy . | Acute hepatic encephalopathy in 70 cirrhotic patients was monitored during parenteral administration of amino acids between January 1979 and January 1984 . The diagnosis of cirrhosis was confirmed by needle biopsy , and HE by conventional clinical and EEG parameters . The infusion of AA solutions was initiated 48 h after admission and during a 5-day period : 34 patients received a control aminoacid solution , a commercially available AA mixture ( Azonutril ) , and 36 patients a modified solution enriched in BAA prepared from crystallized AA dissolved in distilled water . The calorie intake for both groups was 1600 calories per day from glucose and lipid emulsion . No significant difference was noted based on clinical evolution , even though the plasma AAA/BAA ratio was corrected using the modified AA solution . Of the 34 patients in Group 1 : 10 improved , 14 were unchanged , 10 deteriorated and 7 died . Of the 36 patients in Group 2 : 12 improved , 14 were unchanged , 10 deteriorated and 7 died . EEG tracing evolved in parallel fashion . The authors conclude that modified AA solutions are ineffective in the treatment of acute hepatic encephalopathy in cirrhotic patients The influence of intravenous infusion of branched-chain amino acids ( BCAAs ) on brain function in patients with liver cirrhosis and acute hepatic encephalopathy was examined using a double-blind , r and omized study design . Five medical centers in France and Sweden participated , and 50 patients were studied . The patients received either BCAAs ( 40 gm per day ) in 5 % glucose or 5 % glucose alone ( placebo ) for 5 days or until " wake up " . Nutritional support was provided with equal proportions of carbohydrate and fat . During BCAA administration , plasma concentrations of aromatic amino acids and methionine fell ( 20 to 40 % , p less than 0.05 to 0.01 ) , and the ratio of BCAAs to aromatic amino acid concentrations increased significantly . Clinical improvement was seen in 14 of 25 BCAA-treated patients and in 12 of 25 patients receiving placebo ( N.S. ) . EEG responses were similar in the two groups during treatment . In the BCAA group , 10 of 25 patients died in the course of the study , compared to 5 of 25 in the placebo group ( N.S. ) ; six patients died from encephalopathy in the BCAA group as compared to three among placebo-treated patients . It is concluded that BCAA administration , in the dose and composition employed in the present study , reduces the concentrations of aromatic amino acids but neither improves cerebral function nor decreases mortality in patients with hepatic encephalopathy In a double blind r and omized study , branched-chain amino acids and placebo ( casein ) were compared as a treatment for chronic hepatic encephalopathy in cirrhosis . After a 15-day run-in period with controlled diet ( 45 - 65 g protein ) , the patients were administered , in addition to their diet , branched-chain amino acids ( 0.24 g/kg , 30 patients ) or an equinitrogenous amount of casein ( 34 patients ) . One patient on branched-chain amino acids and two on casein were lost to the study . After 3 months , the index of portal-systemic encephalopathy significantly improved in patients on active treatment ( from 40 [ S.D. 14]% to 21 [ 17 ] ) , but was not in subjects receiving casein ( from 37 [13]% to 36 [ 12 ] ) . Two or more parameters of the index improved in 24 patients treated with amino acids ( 80 % ; confidence limits , 61 - 92 % ) , and only in 12 receiving casein ( 35 % ; confidence limits , 20 - 54 % ; p less than 0.001 ) . Patients who did not improve were given an alternative treatment for 3 more months . Casein-treated patients given branched-chain amino acids rapidly improved . The changes in neuropsychologic function were associated with an improvement in semiquantitative nitrogen balance , which became consistently positive in amino acid-treated subjects ; there was also a mild improvement in nutritional parameters and in liver function tests . The supplementation of oral branched-chain amino acids to the diet is superior to casein as a treatment for providing adequate nitrogen supply and improving the mental state of cirrhotic patients with chronic encephalopathy This trial was undertaken to assess the safety and efficacy of long-term oral supplementation with branched-chain amino acids as an adjunct to conventional therapy in patients with stable cirrhosis and latent encephalopathy . Latent encephalopathy was diagnosed by psychometric testing , used to assess automobile driving capacity . Seventeen patients with impaired driving capacity received either branched-chain amino acids or placebo for 8 weeks before being crossed over to the other regimen for an equal period . Branched-chain amino acids but not placebo significantly improved psychomotor disturbances ( p < 0.01 ) and driving capacity ( p < 0.002 ) . No adverse reactions were observed . We conclude that long-term branched-chain amino acid supplementation is well tolerated and effective in the treatment of impaired automobile driving capacity associated with latent portosystemic encephalopathy We studied the effects of infusion of a branched chain enriched amino acid mixture versus glucose on acute hepatic encephalopathy in patients with cirrhosis . Sixty-five patients were r and omly treated with 1 g/kg per day of an amino acid mixture with 40 % branched chain contents ( 32 patients ) , or isocaloric glucose ( 33 patients ) for a maximum of 16 days . The regimens further included glucose infusion to a total of 26.5 kcal/kg per day and lactulose . The patients took part in the study for 5 - 6 days . In each group 17 patients woke up . In the amino acid group eleven died and four developed renal failure . In the glucose group ten died , three developed renal and two respiratory failure , and one remained encephalopathic . The coma score worsened in three of the patients who died in the amino acid group , but in all patients who died in the glucose group . The negative nitrogen balance on entry reversed in the amino acid group , but not in the glucose group . Thus , the branched chain enriched amino acid supplement did not change the prognosis for wake-up , but had other effects on the cerebral state and on nitrogen homeostasis BACKGROUND & AIMS The role of oral supplementation with branched-chain amino acids ( BCAA ) in advanced cirrhosis is far from settled . A nutritional approach might prevent progressive liver failure and improve nutritional parameters and quality of life . METHODS A multicenter , r and omized study comparing 1-year nutritional supplementation with BCAA against lactoalbumin or maltodextrins was performed in 174 patients with advanced cirrhosis . Primary outcomes were the prevention of a combined end point ( death and deterioration to exclusion criteria ) , the need for hospital admission , and the duration of hospital stay . Secondary outcomes were nutritional parameters , laboratory data and Child-Pugh score , anorexia , health-related quality of life , and need for therapy . RESULTS Treatment with BCAA significantly reduced the combined event rates compared with lactoalbumin ( odds ratio , 0.43 ; 95 % confidence interval , 0.19 - 0.96 ; P = 0.039 ) and nonsignificantly compared with maltodextrins ( odds ratio , 0.51 ; 95 % confidence interval , 0.23 - 1.17 ; P = 0.108 ) . The average hospital admission rate was lower in the BCAA arm compared with control treatments ( P = 0.006 and P = 0.003 , respectively ) . In patients who remained in the study , nutritional parameters and liver function tests were , on average , stable or improved during treatment with BCAA and the Child-Pugh score decreased ( P = 0.013 ) . Also , anorexia and health-related quality of life ( SF-36 question naire ) improved . Long-term compliance with BCAA was poor . CONCLUSIONS In advanced cirrhosis , long-term nutritional supplementation with oral BCAA is useful to prevent progressive hepatic failure and to improve surrogate markers and perceived health status . New formulas are needed to increase compliance BACKGROUND / AIMS The value of paper-pencil tests and West-Haven- criteria for assessment of low- grade hepatic encephalopathy under conditions of a r and omized , double-blind , placebo-controlled , clinical trial was evaluated in a cohort of 217 cirrhotics . METHODS Patients were grade d at least twice clinical ly for severity of hepatic encephalopathy and tested concomitantly with a recommended psychometric test battery . RESULTS Re-evaluation of the study documentation showed that at study entry 33 % and during the study even 50 % of the patients were wrongly allocated to minimal or overt hepatic encephalopathy . Despite the participating physicians ' training , 31 % of the number-connection-tests-A , 20 % of the number-connection-tests-B and 28 % of the line-tracing-test were in retrospect considered invalid by an independent psychologist . Neither the Portosystemic-Encephalopathy-Syndrome ( PSE ) test nor the Psychometric-Hepatic-Encephalopathy-Sum (PHES)-score reliably picked up clinical improvement in the individual patient . Although these test scores could statistically differentiate between patients with minimal and overt hepatic encephalopathy , the clinical classification of individual patients into one of the groups will have a high rate of error . The PHES-Score was less balanced than the score derived from the PSE-Syndrome-Test . CONCLUSIONS Inaccuracies in conducting paper-pencil tests together with the subjectivity and incorrectness of clinical HE-grading question the usefulness of West-Haven- criteria and paper-pencil tests including related scores for quantification of low- grade HE at least in multicenter approaches OBJECTIVES To analyze sources search ed in Cochrane review s , to determine the proportion of trials included in review s that are indexed in major data bases , and to compare the quality of these trials with those from other sources . METHODS All new systematic review s in the Cochrane Library , Issue1 2001 , that were restricted to r and omized controlled trials ( RCTs ) or quasi- RCTs were selected . The sources search ed in the review s were recorded , and the trials included were checked to see whether they were indexed in four major data bases . Trials not indexed were checked to determine how they could be identified . The quality of trials found in major data bases was compared with those found from other sources . RESULTS The range in the number of data bases search ed per review ranged between one and twenty-seven . The proportion of the trials in the four data bases were Cochrane Controlled Trials Register = 78.5 % , MEDLINE = 68.8 % , Embase = 65.0 % , and Science/Social Sciences Citation Index = 60.7 % . Search ing another twenty-six data bases after Cochrane Controlled Trials Register ( CCTR ) , MEDLINE , and Embase only found 2.4 % additional trials . There was no significant difference between trials found in the CCTR , MEDLINE , and Embase compared with other trials , with respect to adequate allocation concealment or sample size . CONCLUSIONS There was a large variation between review s in the exhaustiveness of the literature search es . CCTR was the single best source of RCTs . Additional data base search ing retrieved only a small percentage of extra trials . Contacting authors and manufacturers to find unpublished trials appeared to be a more effective method of obtaining the additional better quality trials This multicenter study compared the effects of branched-chain amino acid granules ( Livact((R ) ) Granules , LIV ) and an enteral nutrient for chronic hepatic failure ( Aminoleban((R ) ) EN , EN ) on serum albumin in patients with decompensated liver cirrhosis . This study enrolled " patients with decompensated liver cirrhosis associated with hepatic encephalopathy who were suffering from hypoalbuminemia in spite of adequate food intake , " a condition for which both drugs are indicated . Enrolled patients were r and omized to the two groups according to the central registration method . This study continued for 24 weeks . Selected foods were supplied to each patient in principle so that caloric and protein intakes were st and ardized between the two groups . A total of 281 patients were enrolled . LIV was not inferior to EN concerning the primary efficacy endpoint changes in serum albumin OBJECTIVES : Protein intake impacts on nutritional status and may determine the recurrence of hepatic encephalopathy ( HE ) . A low-protein diet has been considered the st and ard treatment after an episode of HE , while branched-chain amino acids ( BCAA ) have been shown to improve minimal HE . We performed a study to investigate the long-term effects of supplementing a protein-controlled diet with BCAA . METHODS : A r and omized , double-blind , multicenter study that included 116 patients with cirrhosis and a previous episode of HE was conducted in four tertiary care hospitals . All patients received a st and ard diet of 35 kcal/kg per day and 0.7 g of proteins/kg per day and a supplement of 30 g of BCAA ( BCAA group ) or maltodextrin ( MDX group ) during 56 weeks . RESULTS : The actuarial risk of remaining free of HE did not differ between groups ( BCAA=47 % , MDX=34 % , P=0.274 ) , but patients in the BCAA group exhibited a better outcome on two neuropsychological tests and an increase in the mid-arm muscle circumference . Recurrence was associated with low plasma albumin at baseline and a decrease in sodium and an increase in creatinine during follow-up . Patients with recurrence of HE exhibited a lack of improvement in global cognitive function . CONCLUSIONS : Diet supplementation with BCAA after an episode of HE does not decrease recurrence of HE . However , supplementation with BCAA improves minimal HE and muscle mass . Identification of risk factors for recurrence of HE may allow the development of new preventive therapies that could decrease the neuropsychological sequelae of repeated episodes of HE Background Physical exercise could improve functional limitations , muscle mass , and health-related quality of life ( HRQoL ) in patients with cirrhosis . Aim The purpose of this study was to evaluate the efficacy and safety of an exercise programme and leucine supplementation to increase exercise capacity , muscle mass , and HRQoL in patients with cirrhosis . Patients and Methods Seventeen out patients with cirrhosis were r and omized to an exercise group ( n = 8) or a control group ( n = 9 ) in a pilot study . The programme of moderate exercise was performed for 12 weeks under supervision of a physiotherapist . All patients received oral leucine ( 10 g/day ) during the study . At baseline and at the end of the study , we determined exercise capacity ( 6-min walk and 2-min step tests ) , anthropometric measurements , and HRQoL by Short Form-36 ( SF-36 ) question naire . We also analyzed safety regarding complications of cirrhosis , liver and renal function , inflammatory response and oxidative stress . Results In the exercise group , exercise capacity improved , as shown by the increase in the 6-min walk test from 365 ( 160–420 ) to 445 m ( 250–500 ) ( p = 0.01 ) , and in the 2-min step test ( p = 0.02 ) . Lower thigh circumference also increased , from 41 ( 34–53 ) to 46 cm ( 36–56 ) ( p = 0.02 ) , and the domains of SF-36 general health ( p = 0.03 ) , vitality ( p = 0.01 ) and social function ( p = 0.04 ) improved significantly . In the control group , no statistically significant changes were observed in any of the parameters . We did not observe complications of cirrhosis in either group during the study . Conclusions A programme of moderate physical exercise together with leucine supplements in patients with cirrhosis is safe and improves exercise capacity , leg muscle mass and UNLABELLED Prevalence of cirrhosis among older adults is expected to increase ; therefore , we studied the health status , functional disability , and need for supportive care in a large national sample of individuals with cirrhosis . A prospect i ve cohort of individuals with cirrhosis was identified within the longitudinal , nationally representative Health and Retirement Study . Cirrhosis cases were identified in linked Medicare data via ICD-9-CM ( International Classification of Diseases , Ninth Revision , Clinical Modification ) codes and compared to an age-matched cohort without cirrhosis . Two primary outcome domains were assessed : ( 1 ) patients ' health status ( perceived health status , comorbidities , health care utilization , and functional disability as determined by activities of daily living and instrumental activities of daily living ) , and ( 2 ) informal caregiving ( hours of caregiving provided by a primary informal caregiver and associated cost ) . Adjusted negative binomial regression was used to assess the association between cirrhosis and functional disability . A total of 317 individuals with cirrhosis and 951 age-matched comparators were identified . Relative to the comparison group , individuals with cirrhosis had worse self-reported health status , more comorbidities , and used significantly more health care services ( hospitalizations , nursing home stays , physician visits ; P < 0.001 for all bivariable comparisons ) . They also had greater functional disability ( P < 0.001 for activities of daily living and instrumental activities of daily living ) , despite adjustment for covariates such as comorbidities and health care utilization . Individuals with cirrhosis received more than twice the number of informal caregiving hours per week ( P < 0.001 ) , at an annual cost of US $ 4700 per person . CONCLUSION Older Americans with cirrhosis have high rates of disability , health care utilization , and need for informal caregiving . Improved care coordination and caregiver support is necessary to optimize management of this frail population The therapeutic efficacy of orally administered branched-chain amino acids in patients with liver cirrhosis and chronic encephalopathy was examined in a double blind , r and omised crossover study . Seven patients with manifest hepatic cirrhosis and encephalopathy of six months ' duration or longer ingested 30 g branched-chain amino acids or placebo during two 14-day periods . Psychometric tests and electroencephalograms were used to evaluate cerebral function . Neither clinical observations nor psychometric testing or electroencephalogram indicated a significant difference in the patients ' response to branched-chain amino acids as compared with placebo . In four patients given branched-chain amino acids for longer periods ( five to 22 weeks ) , psychometric tests also remained unchanged . The plasma concentrations of these acids after oral intake increased significantly , demonstrating adequate absorption . Basal plasma amino acid concentrations were unchanged , however , after branched-chain amino acid therapy . No side-effects were seen , which indicates that these amino acids are well tolerated as an extra protein supply in patients with chronic hepatic encephalopathy . As compared with placebo , however , no effect of branched-chain amino acids on the encephalopathy could be detected A r and omized study was conducted in 37 hospitalized patients at six cooperating hospitals in which protein‐intolerant cirrhotic patients were fed increasing amounts of either dietary protein or a branched‐chain enriched amino acid solution ( BCAA ) until they attained an intake of 80 gm protein per day or equivalent or until they developed stage 2 encephalopathy . All patients initially received 20 gm of dietary protein for 1 week , after which 20 gm of protein or BCAA were added weekly . Nitrogen balance improved from negative to positive in all patients in whom it was measured and increased equally in both groups . Seven of the 20 patients in the protein group and 1 of 17 in the BCAA group developed encephalopathy of stage 2 or greater ( p < 0.05 ) . Changes in each component of the portal‐systemic encephalopathy syndrome were compared , and differences were statistically significant for mental status grade ( p < 0.01 ) , asterixis ( p < 0.05 ) , Portal‐systemic encephalopathy index ( p < 0.01 ) , but insignificant for Number Connection Test , EEG or ammonia . Plasma amino acid profiles showed an increase in BCAA in the study group . Thus , oral BCAA supplements appear to induce positive nitrogen balance to approximately the same degree as an equivalent amount of dietary protein without inducing encephalopathy as frequently A controlled study was carried out in two groups of 20 patients with cirrhosis of the liver and deep coma in order to compare the efficacy of intravenous branched-chain amino acid solutions in 20 % glucose ( group A ) vs lactulose plus glucose in isocaloric amount ( group B ) . There were 3 drop-outs from each group . Plasma amino acids and ammonia were assayed at fixed intervals throughout the 10-day observation period . Routine tests were assayed daily . Complete mental recovery was obtained in 70 % of patients in group A and in 47 % in group B. The difference was not significant , likely due to the lack of placebo group . With the exception of free tryptophan/all competing amino acids ratio , the modifications in plasma amino acid levels showed no correlation with the clinical course under either treatment . Ammonia , like free tryptophan , decreased significantly upon mental recovery , paralleling the clinical course throughout the study . In conclusion , branched-chain amino acids are at least as effective as lactulose in deep hepatic coma . It is suggested that branched-chain amino acids may reverse coma either by competing with brain entry of the aromatic amino acid or by metabolically decreasing free tryptophan and ammonia Branched chain amino acids have been recommended for the treatment of portosystemic encephalopathy based on the false neurotransmitter hypothesis . This hypothesis implies that by correction of the deranged amino acid pattern in the blood of cirrhotics , false neurotransmission and then portosystemic encephalopathy is improved . We conducted a double-blind crossover placebo-controlled trial in 22 in patients with liver cirrhosis and obtained evidence of latent ( sub clinical ) portosystemic encephalopathy using an extensive psychometric test program . Patients received a defined diet of 35 cal/kg X day containing 1 g of protein . In addition , branched chain amino acids or casein in a dosage of 0.25 g/kg X day was administered in a crossover fashion , each for 1 wk . Semiquantitative nitrogen balance increased during both treatments , with a tendency of a larger increase during branched chain amino acid treatment . At the same time ammonia concentration tended to decrease during branched chain amino acid treatment . Taking into account the crossover design , significant improvements attributable to branched chain amino acid treatment could be demonstrated in psychomotor functions ( line tracing , tapping , steadiness , auditory reaction time ) , attention ( digit table ) , and practical intelligence ( digit symbol , number connection test ) Seventy-five patients with acute hepatic decompensation superimposed on chronic alcoholic cirrhosis were prospect ively r and omized for a blinded trial of the treatment of hepatic encephalopathy . The control group received 4 g of enteral neomycin daily along with 25 % dextrose by a central venous catheter . The experimental group received a placebo resembling neomycin and isocaloric dextrose plus a modified amino acid mixture enriched with branched-chain amino acids to 36 % and deficient in aromatic amino acids and methionine . Thirty patients in the F080 group and 29 in the control group completed the trial . The group receiving the modified amino acid mixture demonstrated a statistically significant improvement in encephalopathy as compared to the neomycin group , while maintaining nitrogen equilibrium . Survival and discharge from the hospital were statistically greater in the group treated with the modified amino acid solution and hypertonic dextrose . Treatment of hepatic encephalopathy in the presence of hepatic decompensation with an amino acid solution formulated for its treatment seems to produce faster , more complete recovery with improved capacity for nutritional support BACKGROUND & AIMS Nutritional intervention with branched-chain amino acid ( BCAA ) is reported to increase serum albumin concentration in patients with decompensated cirrhosis . However , a definite conclusion on whether it can improve patients ' survival has not yet been reached . The present study aim ed to test possibilities of improving survival of patients with decompensated cirrhosis by using a BCAA preparation that is suitable for long-term oral administration . METHODS A multicenter , r and omized , and nutrient intake-controlled trial on the comparative effects of BCAA orally administered at 12 g/day for 2 years versus diet therapy with defined daily food intake ( 1.0 - 1.4 g protein kg(-1 ) day(-1 ) including BCAA preparation and 25 - 35 kcal kg(-1 ) day(-1 ) ) was conducted in 646 patients with decompensated cirrhosis . The primary end point was a composite of death by any cause , development of liver cancer , rupture of esophageal varices , or progress of hepatic failure ( event-free survival ) . The secondary end points were serum albumin concentration and health-related quality of life ( QOL ) measured by Short Form-36 question naire . RESULTS The incidence of events comprising the primary end point significantly decreased in the BCAA group as compared with the diet group ( hazard ratio , 0.67 ; 95 % confidence interval , 0.49 - 0.93 ; P = .015 ; median observation period , 445 days ) . Serum albumin concentration increased significantly in the BCAA group as compared with the diet group ( P = .018 ) . The " general health perception " domain in Short Form-36 measures was also improved ( P = .003 ) . Patients ' adherence to the prescription was favorable . CONCLUSIONS Oral supplementation with a BCAA preparation that can be administered for a long period improves event-free survival , serum albumin concentration , and QOL in patients with decompensated cirrhosis with an adequate daily food intake Objective Our earlier study has demonstrated that the administration of L-acetylcarnitine ( LAC ) improves neurological symptoms and serum parameters in hepatic coma . The aim of this work has been to evaluate the efficacy of the LAC and branched chain amino acids ( BCAA ) versus BCAA , administered in intravenous infusion , in patients with cirrhotic hepatic coma . Methods Forty-eight highly selected patients were enrolled in the study and , after r and omization , received blindly LAC+BCAA ( n=24 ) versus BCAA ( n=24 ) . The two groups were similar in age , sex , pathogenesis of cirrhosis , and severity of liver disease . The comparison between values before and after LAC planned treatment showed statistical significant differences in neurological findings , evaluated by the Glasgow Scale , ammonia serum levels , blood urea nitrogen , and EEG . Results After 60 min of the study period , the LAC+BCAA treated patients compared with BCCA treated showed a significant decrease of ammonia serum levels : 41.20 versus 10.40 μmol P<0.05 . After 1 day of the study period , the LAC+BCAA treated patients compared with BCCA treated patients showed a significant increase of Glasgow 's score : 3.60 versus 1.50 score P<0.05 ; a significant decrease of ammonia serum levels : 63.30 versus 27.00 μmol P<0.01 ; a significant improvement of EEG cps/s : 2.70 versus 0.6 P<0.001 . No side-effects were observed in our study series . Conclusion Our study demonstrated that the administration of BCAA supplemented with LAC might improve neurological symptoms and serum ammonium levels in selected cirrhotic patients with hepatic coma It has been suggested that the ability to drive a car is impaired in patients with cirrhosis of the liver and minimal hepatic encephalopathy ( MHE ) . However , the only study using an on‐road driving test did not reveal such an impairment . In a prospect i ve controlled study , we evaluated patients with cirrhosis of the liver for MHE and the ability to drive a car . MHE was diagnosed using three psychometric tests : Number Connection Test Part A , Digit Symbol Test , and a Complex Choice Reaction Test . In a st and ardized on‐road driving test ( 22 miles , 90 minutes ) , design ed for patients with brain impairment , a professional driving instructor blind to the subjects ' diagnosis and test results assessed the driving performance . Four global driving categories ( car h and ling , adaptation to traffic situation , cautiousness , maneuvering ) , 17 specific driving actions ( e.g. , changing lanes , overtaking , etc . ) , and a total score of driving performance were rated using a 6‐point scale . Of 274 consecutive patients with liver cirrhosis , 48 fulfilled the medical and driving inclusion criteria , 14 of them with and 34 without MHE . Forty‐nine subjects in a stable phase of chronic gastroenterological diseases and with normal liver findings served as controls . The total driving score of patients with MHE was significantly reduced in comparison to either cirrhotic patients without MHE or to controls ( P < .05 ) . Significant differences in ratings were found in the following driving categories : car h and ling , adaptation , and cautiousness . Significant differences were also found in specific driving actions . The instructor had to intervene in the driving of 5 of the 14 MHE patients to avoid an accident , significantly more than in cirrhotic patients without MHE and in controls . There was no significant difference in any driving category or specific driving action in cirrhotic patients without MHE compared to controls . In conclusion , fitness to drive a car can be impaired in patients with MHE . Therefore , patients with liver cirrhosis should be tested for MHE and informed in the case of abnormal test results . Therapy known to improve psychometric test results should be initiated . ( HEPATOLOGY 2004;39:739 –745 . The effects of oral BCAA supplementation on fasting levels of prolactin and estradiol were retrospectively analyzed in frozen plasma sample s of patients with cirrhosis and chronic hepatic encephalopathy , taking part in a 3-month r and omized , double-blind trial . Twenty-five patients had received 0.24 g of BCAA per kg body weight , 24 had received an equinitrogenous amount of casein , in addition to a diet providing 0.7 - 1.0 g/kg of protein . Thirty-eight were males , 11 post-menopausal women . Fasting prolactin did not show any change in the BCAA group , where mental state significantly improved . In the casein group plasma prolactin increased by nearly 50 % during the 3-month period . Similarly , estradiol concentrations were unchanged during BCAA supplementation , and increased during casein treatment . The analysis of variance demonstrated significant differences between the 2 treatments . Liver function tests and nutritional parameters ( albumin , transferrin , urinary creatinine ) supported a superiority of BCAA over casein . These data suggest that the favorable effects of BCAA on mental state are not mediated by changes in cerebral neurotransmission , but are due mainly to maintained liver function , possibly related to improved nutrition The effects of branched chain amino acid (BCAA)-enriched diets ( fed for 7 days ) on encephalopathy , plasma amino acid concentrations , aromatic amino acid turnover , and protein synthesis rates were determined in eight patients with alcoholic liver failure . Four patients were given the diet intravenously ( iv group ) ( total amino acids , 60 - 80 g/day , BCAA content 51 % , energy 2000 kcal/day ) and four patients ( NG group ) were given a semi-elemental formulation via constant nasogastric ( NG ) infusion ( amino acids 58 g , BCAA 43 % , oligopeptides 19.5 g , energy 2000 kcal/day ) . The enteral diet was given at one-half strength for the first 3 days . A 10-hr constant infusion of [U-14C]phenylalanine tracer was used in four patients to measure aromatic amino acid ( AA ) turnover and rates of incorporation into various body proteins . Seven of the eight patients made a good clinical recovery , with reversal of encephalopathy within 3 days of dietary intervention . One became septicemic and deteriorated . While plasma bilirubin concentrations dropped , liver enzymes remained elevated . Mean nitrogen balance was negative at the beginning and positive at the end of the study , in both groups . Initial amino acid profiles demonstrated low plasma BCAA content and BCAA : AA ratios . Significant improvements occurred in the iv group by day 2 and in both groups by day 7 . Isotope studies showed that , whereas aromatic amino acid oxidation remained unchanged , greater quantities were incorporated in whole body protein , albumin , transferrin , fibrinogen , and immunoglobulins Sixty-four patients admitted with acute alcoholic hepatitis , with or without underlying cirrhosis , were r and omized regardless of encephalopathy to receive a controlled diet either alone , or supplemented orally , nasogastrically , or intravenously as necessary , with 2000 kCal and 10 g nitrogen daily . Whether this came from a conventional protein source or a branched chain amino acid enriched formulation was also r and omly determined . In the absence of renal failure , nitrogen intakes of 10 g or more daily were invariably associated with positive nitrogen balance , but complications of liver dysfunction prevented the attainment of significantly more positive balance in the supplemented groups than in controls . Neither in the series as a whole , nor in any identifiable subgroup of patients , was mortality affected by treatment . Changes in prothrombin time and in measured nutritional parameters during the study did not differ between supplemented and control groups , and the observed changes in midarm muscle circumference appeared to reflect changes in degree of fluid retention . Neither enteral nor parenteral branched chain amino acids showed any consistent effect upon encephalopathy Forty-seven patients with alcoholic hepatitis and /or cirrhosis were r and omised to receive nutritional supplementation by oral sip feeding or by nasogastric infusion administered via either an East Grinstead or a Viomedex nasoenteric tube . The three groups were well matched for severity and complications of liver disease . Patients fed by the nasogastric route attained their daily target dietary intake significantly more often than did those supplemented orally , but the consequent improvement in their nitrogen balance was not significant . There were no significant differences between nasogastric and sip feeding , or between the types of tube studied , in the frequency with which vomiting , diarrhoea or variceal bleeding occurred , but Viomedex tubes required reinsertion significantly less frequently than did the East Grinstead type BACKGROUND / AIMS Protein-restricted diets are usually prescribed for cirrhotic patients with hepatic encephalopathy . However , protein restriction may worsen the nutritional status without result ing in an improvement of hepatic encephalopathy . We design ed a study to assess the effects of the amount of protein in the diet on the evolution of episodic hepatic encephalopathy . METHODS Cirrhotics admitted to the hospital because of an episode of encephalopathy ( n=30 ) were r and omized to receive a low-protein diet with progressive increments or a normal protein diet for 14 days , in addition to st and ard measures to treat hepatic encephalopathy . Protein synthesis and breakdown were studied at day 2 and day 14 with the glycine-N(15 ) infusion method . RESULTS The outcome of hepatic encephalopathy was not significantly different between both groups of treatment . Protein synthesis was similar for low and normal protein diet , but those of the low-protein diet group showed higher protein breakdown . CONCLUSIONS Diets with a normal content of protein , which are metabolically more adequate , can be administered safely to cirrhotic patients with episodic hepatic encephalopathy . Restriction of the content of protein of the diet does not appear to have any beneficial effect for cirrhotic patients during an episode of encephalopathy Previous uncontrolled studies indicated a positive effect of keto analogs of amino acids on plasma ammonia in patients with cirrhosis of the liver and on portal-systemic encephalopathy . In the present double-blind study the influence of keto analogs of the branched chain amino acids valine , leucine and isoleucine on plasma ammonia and encephalopathy was investigated in 12 patients with cirrhosis of the liver and surgical portal systemic shunts . In addition to the usual therapy with lactulose and protein restriction ( 40 g protein/day ) all patients received 15.24 g keto analogs and placebo orally over 4 weeks in a crossover regimen . In contrast to uncontrolled studies , plasma ammonia , which was elevated in all patients before the beginning of the study , was not significantly changed . In addition plasma amino acids , electroencephalogram , number connection test , clinical state and laboratory tests were not influenced by the therapy with keto analogs Published evidence suggests that aspects of trial design lead to biased intervention effect estimates , but findings from different studies are inconsistent . This study combined data from 7 meta-epidemiologic studies and removed overlaps to derive a final data set of 234 unique meta-analyses containing 1973 trials . Outcome measures were classified as " mortality , " " other objective , " " or subjective , " and Bayesian hierarchical models were used to estimate associations of trial characteristics with average bias and between-trial heterogeneity . Intervention effect estimates seemed to be exaggerated in trials with inadequate or unclear ( vs. adequate ) r and om-sequence generation ( ratio of odds ratios , 0.89 [ 95 % credible interval { CrI } , 0.82 to 0.96 ] ) and with inadequate or unclear ( vs. adequate ) allocation concealment ( ratio of odds ratios , 0.93 [ CrI , 0.87 to 0.99 ] ) . Lack of or unclear double-blinding ( vs. double-blinding ) was associated with an average of 13 % exaggeration of intervention effects ( ratio of odds ratios , 0.87 [ CrI , 0.79 to 0.96 ] ) , and between-trial heterogeneity was increased for such studies ( SD increase in heterogeneity , 0.14 [ CrI , 0.02 to 0.30 ] ) . For each characteristic , average bias and increases in between-trial heterogeneity were driven primarily by trials with subjective outcomes , with little evidence of bias in trials with objective and mortality outcomes . This study is limited by incomplete trial reporting , and findings may be confounded by other study design characteristics . Bias associated with study design characteristics may lead to exaggeration of intervention effect estimates and increases in between-trial heterogeneity in trials reporting subjectively assessed outcomes |
12,366 | 29,954,105 | Based on the results of this study , ETS might be an important risk factor of female lung cancer in non-smokers | More than 50 % of women worldwide are exposed to Environmental Tobacco Smoke ( ETS ) .
The impact of ETS on lung cancer remains unclear .
Cohort studies since the late 1990s have provided new evidence of female lung cancer risk due to ETS .
The objective of this meta- analysis and systematic review was to analyze the association of ETS with female lung cancer risk from 1997 to 2017 , organised based on research design . | Introduction : The incidence of lung cancer in women living in China is among the highest in the world but it does not appear that tobacco smoking is a major risk factor for lung cancer . As tobacco smoking is highly prevalent in Chinese men , exposure to environmental tobacco smoke ( ETS ) may play an important role in the development of lung cancer in Chinese women who never smoked . We conducted the present investigation because previous studies did not account for dietary habits or indoor air pollution from Chinese-style cooking and they did not assess the effect of occupational exposure to ETS . Methods : A population -based , case – control study was conducted to evaluate the relationship between lung cancer and exposure to ETS among nonsmoking women living in Shanghai , China . Five-hundred and four women diagnosed with incident , primary lung cancer between February 1992 and January 1994 were identified through the population -based Shanghai Cancer Registry . A control group of 601 nonsmoking women was selected r and omly from the Shanghai Residential Registry , and was approximately frequency-matched to the age distribution of the lung cancer cases . Information on lifetime domestic and occupational exposure to ETS was obtained through face-to-face interviews . Adjusted odds ratios ( OR ) and 95 % confidence intervals ( CI ) were estimated by unconditional logistic regression . Results : The OR for ever exposed to ETS from spouses was 1.1 ( 95 % CI : 0.8–1.5 ) , and the OR for ever exposed to ETS at work was 1.7 ( 95 % CI : 1.3–2.3 ) . Furthermore , the OR increased with increasing number of hours of daily exposure to ETS in the workplace and with increasing number of smoking co-workers . No associations were found for exposure to ETS during childhood . Conclusions : The main findings of the present study are that long-term occupational exposure to ETS , both alone or in combination with exposures at home , conferred an increased risk of lung cancer among women who never smoked . The inconsistency of the results regarding exposure to ETS at home and at work may have been due to lower exposures at home Objective : To investigate whether the Irish smoking ban has had an impact on secondh and smoke ( SHS ) exposures for hospitality workers . Design , setting , and participants : Before and after the smoking ban a cohort of workers ( n = 35 ) from a sample of city hotels ( n = 15 ) were tested for saliva cotinine concentrations and completed question naires . Additionally , a r and om sample ( n = 20 ) of city centre bars stratified by size ( range 400–5000 square feet ) , were tested for air nicotine concentrations using passive sample rs before and after the ban . Main outcome measures : Salivary cotinine concentrations ( ng/ml ) , duration of self reported exposures to secondh and smoke , air nicotine ( μg/cubic metre ) . Results : Cotinine concentrations reduced by 69 % , from 1.6 ng/ml to 0.5 ng/ml median ( SD 1.29 ; p < 0.005 ) . Overall 74 % of subjects experienced decreases ( range 16–99 % ) , with 60 % showing a halving of exposure levels at follow up . Self reported exposure to SHS at work showed a significant reduction from a median 30 hours a week to zero ( p < 0.001 ) . There was an 83 % reduction in air nicotine concentrations from median 35.5 µg/m3 to 5.95 µg/m3 ( p < 0.001 ) . At baseline , three bars ( 16 % ) were below the 6.8 μg/m3 air nicotine significant risk level for lung cancer alone ; at follow up this increased to 10 ( 53 % ) . Conclusions : Passive smoking and associated risks were significantly reduced but not totally eliminated . Exposure to SHS is still possible for those working where smoking is still allowed and those working where smoke may migrate from outdoor areas . Further research is required to assess the true extent and magnitude of these exposures Background Profile regression is a Bayesian statistical approach design ed for investigating the joint effect of multiple risk factors . It reduces dimensionality by using as its main unit of inference the exposure profiles of the subjects that is , the sequence of covariate values that correspond to each subject . Objectives We applied profile regression to a case – control study of lung cancer in nonsmokers , nested within the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) cohort , to estimate the combined effect of environmental carcinogens and to explore possible gene – environment interactions . Methods We tailored and extended the profile regression approach to the analysis of case – control studies , allowing for the analysis of ordinal data and the computation of posterior odds ratios . We compared and contrasted our results with those obtained using st and ard logistic regression and classification tree methods , including multifactor dimensionality reduction . Results Profile regression strengthened previous observations in other study population s on the role of air pollutants , particularly particulate matter ≤ 10 μm in aerodynamic diameter ( PM10 ) , in lung cancer for nonsmokers . Covariates including living on a main road , exposure to PM10 and nitrogen dioxide , and carrying out manual work characterized high-risk subject profiles . Such combinations of risk factors were consistent with a priori expectations . In contrast , other methods gave less interpretable results . Conclusions We conclude that profile regression is a powerful tool for identifying risk profiles that express the joint effect of etiologically relevant variables in multifactorial diseases Biomass is widely used for fuel in developing countries . Particles and gases of biomass burning may cause changes in the lung . In this prospect i ve study we investigated histopathological changes in the lungs of 42 non-smoking women [ mean age ( 59±10 ) years ] caused by biomass smoke . We valuated exposure to biomass smoke , case histories , and the fi ndings of physical examination , radiology , bronchoscopy , and lung histopathology . Mean exposure to biomass smoke was ( 28±9 ) hour-year ( 1 hour-year equals 365 hours of exposure per year with average exposure of 1 hour a day ) . The radiological fi ndings were mass ( 42 % ) , reticulonodular opacities ( 31 % ) , mediastinal lymphadenopathy ( 26 % ) , pleuro-parenchymal fi brotic b and ing ( 19 % ) , widening of the pulmonary artery ( 14 % ) , ground glass ( 11 % ) , mosaic perfusion ( 9 % ) , consolidation ( 9 % ) , segmental or subsegmental atelectasis ( 7 % ) , and bronchiectasis ( 7 % ) . The patients were diagnosed with lung cancer ( 35 % ) , interstitial lung disease ( 31 % ) , sarcoidosis ( 9 % ) , tuberculosis ( 9 % ) , chronic obstructive pulmonary disease ( 4 % ) , chronic bronchitis ( 9 % ) , and metastasis ( 4 % ) . Bronchoscopy showed pilies , oedema , erythema , bronchus narrowing , endobronchial tumour , mucosal irregularity , increased vascularisation , blue-black anthracotic plaques , mucosal oedema , and purulent secretion . Transbronchial biopsies revealed neutrophil and lymphocyte leucocytes in the perivascular , peribronchiolar , and interalveolar septa , slightly enlarged connective tissue , thickening of the basal membrane , thickening of interalveolar septa , intimal and medial thickening of the vascular wall and vascular lumen narrowing , anthracosis between the cells and in the bronchiole epithelium . These fi ndings confi rm that biomass smoke has important toxic effects on the lung parenchyma , interstitium , and pulmonary vessels that may result in malignancies The aim of this study was to estimate the effect of exposure to secondh and tobacco smoke on the incidence of lung adenocarcinoma in situ/minimally invasive adenocarcinoma ( AIS/MIA ) . Data from seven case – control studies participating in the International Lung Cancer Consortium ( ILCCO ) were pooled , result ing in 625 cases of AIS/MIA and 7,403 controls , of whom 170 cases and 3,035 controls were never smokers . Unconditional logistic regression was used to estimate adjusted ORs ( ORadj ) and 95 % confidence intervals ( CI ) , controlling for age , sex , race , smoking status ( ever/never ) , and pack-years of smoking . Study center was included in the models as a r and om-effects intercept term . Ever versus never exposure to secondh and tobacco smoke was positively associated with AIS/MIA incidence in all subjects ( ORadj = 1.48 ; 95 % CI , 1.14–1.93 ) and in never smokers ( ORadj = 1.45 ; 95 % CI , 1.00–2.12 ) . There was , however , appreciable heterogeneity of ORadj across studies ( P = 0.01 ) , and the pooled estimates were largely influenced by one large study ( 40 % of all cases and 30 % of all controls ) . These findings provide weak evidence for an effect of secondh and tobacco smoke exposure on AIS/MIA incidence . Further studies are needed to assess the impact of secondh and tobacco smoke exposure using the newly recommended classification of subtypes of lung adenocarcinoma . Cancer Epidemiol Biomarkers Prev ; 24(12 ) ; 1902–6 . © 2015 AACR Background : Several countries are discussing new legislation regarding the ban on smoking in public places , based on the growing evidence of the hazards of secondh and smoke ( SHS ) exposure . The objective of the present study is to quantitatively assess the relationship between smoking , SHS , and serum cotinine levels in the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) cohort . Methods : From a study on lung cancer in the EPIC cohort , question naire information on smoking was collected at enrolment , and cotinine was measured in serum . Three statistical models were applied by using sample s available in a cross-section design : ( i ) cotinine levels by categories combining smoking and SHS ( n = 859 ) ; ( ii ) the effect of hours of passive smoking exposure in nonsmokers only ( n = 107 ) ; ( iii ) the effect of the number of cigarettes consumed per day in current smokers only ( n = 832 ) . All models were adjusted for country , sex , age , and body mass index . Results : Among nonsmokers , passive smokers presented significant differences in cotinine compared with nonexposed , with a marked ( but not significant ) difference among former-smokers . A one hour per day increment of SHS gave rise to a significant 2.58 nmol/L ( 0.45 ng/mL ) increase in mean serum cotinine ( P < 0.001 ) . In current smokers , a one cigarette per day increment gave rise to a significant 22.44 nmol/L ( 3.95 ng/mL ) increase in cotinine mean ( P < 0.001 ) . Conclusions : There is clear evidence that not only tobacco smoking but also involuntary exposure increases cotinine levels . Impact : This study strengthens the evidence for the benefits of a smoking ban in public places . Cancer Epidemiol Biomarkers Prev ; 20(5 ) ; 869–75 . © 2011 AACR Abstract Objectives To investigate the association between environmental tobacco smoke , plasma cotinine concentration , and respiratory cancer or death . Design Nested case-control study within the European prospect i ve investigation into cancer and nutrition ( EPIC ) . Participants 303 020 people from the EPIC cohort ( total 500 000 ) who had never smoked or who had stopped smoking for at least 10 years , 123 479 of whom provided information on exposure to environmental tobacco smoke . Cases were people who developed respiratory cancers or died from respiratory conditions . Controls were matched for sex , age ( plus or minus 5 years ) , smoking status , country of recruitment , and time elapsed since recruitment . Main outcome measures Newly diagnosed cancer of lung , pharynx , and larynx ; deaths from chronic obstructive pulmonary disease or emphysema . Plasma cotinine concentration was measured in 1574 people . Results Over seven years of follow up , 97 people had newly diagnosed lung cancer , 20 had upper respiratory cancers ( pharynx , larynx ) , and 14 died from chronic obstructive pulmonary disease or emphysema . In the whole cohort exposure to environmental tobacco smoke was associated with increased risks ( hazard ratio 1.30 , 95 % confidence interval 0.87 to 1.95 , for all respiratory diseases ; 1.34 , 0.85 to 2.13 , for lung cancer alone ) . Higher results were found in the nested case-control study ( odds ratio 1.70 , 1.02 to 2.82 , for respiratory diseases ; 1.76 , 0.96 to 3.23 , for lung cancer alone ) . Odds ratios were consistently higher in former smokers than in those who had never smoked ; the association was limited to exposure related to work . Cotinine concentration was clearly associated with self reported exposure ( 3.30 , 2.07 to 5.23 , for detectable/non-detectable cotinine ) , but it was not associated with the risk of respiratory diseases or lung cancer . Frequent exposure to environmental tobacco smoke during childhood was associated with lung cancer in adulthood ( hazard ratio 3.63 , 1.19 to 11.11 , for daily exposure for many hours ) . Conclusions This large prospect i ve study , in which the smoking status was supported by cotinine measurements , confirms that environmental tobacco smoke is a risk factor for lung cancer and other respiratory diseases , particularly in ex-smokers Based on several severe air pollution episodes , a temporal correlation between high concentrations of particulate matter ( PM ) and SO2 pollution and acute increases in respiratory and cardiopulmonary mortality had been established in Vienna for the 1970 's . After air pollution had decreased in Austria in the 1980's -- as documented by data on SO2 , and total suspended particles (TSP)--no such associations between day-to-day changes of SO2 and TSP and mortality have been documented any more , however , traffic related pollutants like fine particles and NO2 remained a problem . Therefore , short term effects of PM on lung function , morbidity and mortality were investigated in Vienna , Linz , Graz and a rural control area . Long-term exposure and chronic disease -- even more important for public health -- were studied in repeated cross-sectional , a mixed longitudinal and a birth cohort study on school children in the city of Linz . Lung function growth was found impaired from long-term exposure to air pollutants and improved in districts where ambient air pollution had decreased . Where only TSP and SO2 had decreased , no continuous improvement of small airway function was found and end-expiratory flow rates stayed impaired where NO2-reduction from technical improvements of cars and industry was counterbalanced by increase of motorized ( diesel ) traffic . Remaining acute effects of ambient air pollution in 2001 from PM , NO2 and co-pollutants found in a time series study also show that continuing efforts are necessary . Active surface of particles inhaled several hours to days before spirometry was found related to short-term reductions in forced vital capacity-FVC ( p<0.01 ) , forced expiratory volume in one second-FEV1 ( p<0.01 ) and maximal expiratory flow rate at 50 % of vital capacity-MEF50 ( p<0.05 ) . In pupils with asthma or previous airway obstruction 4-week-diaries proved that the following symptoms increased with acute exposure to higher active surface of particles : wheezing ( p<0.01 ) , dyspnea , cough when going to sleep , cough at night ( p<0.05 ) . Efforts to reduce exposure to fine particles from motor traffic and passive smoking have to be increased if we want to achieve full recovery of children from air pollution effects and best respiratory performance in adulthood . Surveillance seems to be necessary not only for particle mass but also for particle number and surface . Little is known on the mechanisms of irreversible long-term effects of PM such as myocardial infa rct ion and cancer . In a prospect i ve cohort study on 1630 dust-exposed and 1630 non dust-exposed workers matched for smoking we found an increase of lung cancer related to nonfibrous insoluble PM . Other studies were able to relate lung cancer to specific particles like those from diesel engines , and a large prospect i ve study of the American Cancer Society was able to link lung cancer in the general population with long-term exposure to fine particles from combustion processes . All these recent epidemiological findings will have consequences for occupational and ambient air PM st and ards Lung cancer mortality rates were computed for nonsmokers in the American Cancer Society 's prospect i ve study for three 4-year periods from 1960 to 1972 and in the Dorn study of veterans for three 5-year periods from 1954 to 1969 . There was no evidence of any trend in these rates by 5-year age groups or for the total groups . No time trend was observed in nonsmokers for cancers of other selected sites except for a decrease in cancer of the uterus . Compared to nonsmoking women married to nonsmoking husb and s , nonsmokers married to smoking husb and s showed very little , if any , increased risk of lung cancer OBJECTIVE -To assess the risk of cardiorespiratory symptoms and mortality in non-smokers who were passively exposed to environmental smoke . DESIGN -- Prospect i ve study of cohort from general population first screened between 1972 and 1976 and followed up for an average of 11.5 years , with linkage of data from participants in the same household . SETTING --Renfrew and Paisely , adjacent burghs in urban west Scotl and . SUBJECTS--15,399 Men and women ( 80 % of all those aged 45 - 64 resident in Renfrew or Paisley ) comprised the original cohort ; 7997 attended for multiphasic screening with a cohabitee . Passive smoking and control groups were defined on the basis of a lifelong non-smoking index case and whether the cohabitee had ever smoked or never smoked . MAIN OUTCOME MEASURE -- Cardiorespiratory signs and symptoms and mortality . RESULTS --Each of the cardiorespiratory symptoms examined produced relative risks greater than 1.0 ( though none were significant ) for passive smokers compared with controls . Adjusted forced expiratory volume in one second was significantly lower in passive smokers than controls . All cause mortality was higher in passive smokers than controls ( rate ratio 1.27 ( 95 % confidence interval 0.95 to 1.70 ) ) , as were all causes of death related to smoking ( rate ratio 1.30 ( 0.91 to 1.85 ] and mortality from lung cancer ( rate ratio 2.41 ( 0.45 to 12.83 ) ) and ischaemic heart disease ( rate ratio 2.01 ( 1.21 to 3.35 ) ) . When passive smokers were divided into high and low exposure groups on the basis of the amount smoked by their cohabitees those highly exposed had higher rates of symptoms and death . CONCLUSION --Exposure to environmental tobacco smoke can not be regarded as a safe involuntary habit Cigarette smoking is irrefutably the strongest risk factor for lung cancer ; however , approximately 25 % of cases worldwide occur among nonsmokers . The age-adjusted annual incidence rate of lung cancer in Shanghai , a region where relatively few women smoke cigarettes , is one of the highest in the world . To help further eluci date the etiology of lung cancer among nonsmokers , the authors examined hormonal factors among women who were lifetime nonsmokers . They analyzed data from the prospect i ve Shanghai Women 's Health Study , which recruited Chinese women aged 40 - 70 years between 1996 and 2000 from selected urban communities . The current analysis included 71,314 women ( n = 220 cases ) who were lifetime nonsmokers and had no history of cancer at baseline . Later age at menopause ( > or = 51 vs. < 46 years ; hazard ratio ( HR ) = 0.63 , 95 % confidence interval ( CI ) : 0.40 , 1.00 ) , longer reproductive period ( > or = 36 vs. < 31 years ; HR = 0.60 , 95 % CI : 0.39 , 0.93 ) , higher parity ( > or = 4 vs. 0 children ; HR = 0.42 , 95 % CI : 0.19 , 0.90 ) , and intrauterine device use ( HR = 0.59 , 95 % CI : 0.41 , 0.86 ) were associated with decreased risks of lung cancer . This large prospect i ve study suggests a potential role for hormonal factors in the etiology of lung cancer among nonsmoking women Background : There is uncertainty regarding the association of occupational exposures with lung cancer . We have studied the association between 52 high-risk job titles and lung cancer incidence in a large prospect i ve study , with more than 200,000 participants followed for more than 6 years and 809 incident cases of lung cancer . Methods : Hazard ratios and 95 % confidence intervals were computed by the Cox proportional-hazard regression model , adjusting for country , age , sex , social class , diet , physical activity , and smoking habits . We used a CAREX-based job-exposure matrix to infer exposure to lung carcinogens . False-positive report probability was calculated as a measure of potentially false-positive results . Results : Eighteen occupations , mainly related with agriculture , constructions , and metal processing , were associated with increased risk . In addition , incidence tended to increase with the number of hazardous jobs reported . When the occupations were classified according to the presumed exposure to specific carcinogenic agents , the hazard ratios were 1.5 ( 95 % confidence interval = 1.2–1.9 ) for asbestos , 1.4 ( 1.1–1.8 ) for heavy metals , 1.4 ( 1.1–1.8 ) for polycyclic aromatic hydrocarbons , and 1.6 ( 1.2–2.1 ) for work-related environmental tobacco smoke . The estimated population attributable risk for employment in at least 1 at-risk job was 16 % in men and 12 % in women . Conclusions : This large prospect i ve study suggests that exposure to occupational lung carcinogens is still a problem , with such exposures producing moderate to large increases in risk The high incidence of lung cancer among Chinese females , despite a low smoking prevalence , remains poorly explained . Cooking fume exposure during frying could be an important risk factor . We carried out a population -based case-control study in Hong Kong . Cases were Chinese female nonsmokers with newly diagnosed primary lung cancer . Controls were female nonsmokers r and omly sample d from the community , frequency matched by age groups . Face-to-face interviews were conducted using a st and ardized question naire . The " total cooking dish-years , " categorized by increments of 50 , was used as a surrogate of cooking fumes exposure . Multiple unconditional logistic regression was used to estimate the odds ratios ( OR ) for different levels of exposure after adjusting for various potential confounding factors . We interviewed 200 cases and 285 controls . The ORs of lung cancer across increasing levels of cooking dish-years were 1 , 1.17 , 1.92 , 2.26 , and 6.15 . After adjusting for age and other potential confounding factors , the increasing trend of ORs with increasing exposure categories became clearer , being 1 , 1.31 , 4.12 , 4.68 , and 34 . The OR of lung cancer was highest for deep-frying ( 2.56 per 10 dish-years ) followed by that of frying ( 1.47 ) , and stir-frying had the lowest OR ( 1.12 ) among the three methods . Cumulative exposure to cooking by means of any form of frying could increase the risk of lung cancer in Hong Kong nonsmoking women . Practical means to reduce exposures to cooking fumes should be given top priority in future research BACKGROUND Lung cancer is the leading cause of worldwide cancer deaths . While smoking is its leading risk factor , few prospect i ve cohort studies have reported on the association of lung cancer with both active and passive smoking . This study aim ed to determine the relationship between lung cancer incidence with both active and passive smoking ( childhood , adult at home , and at work ) . PATIENTS AND METHODS The Women 's Health Initiative Observational Study ( WHI-OS ) was a prospect i ve cohort study conducted at 40 US centers that enrolled postmenopausal women from 1993 to 1999 . Among 93 676 multiethnic participants aged 50 - 79 , 76 304 women with complete smoking and covariate data comprised the analytic cohort . Lung cancer incidence was calculated by Cox proportional hazards models , stratified by smoking status . RESULTS Over 10.5 mean follow-up years , 901 lung cancer cases were identified . Compared with never smokers ( NS ) , lung cancer incidence was much higher in current [ hazard ratio ( HR ) 13.44 , 95 % confidence interval ( CI ) 10.80 - 16.75 ] and former smokers ( FS ; HR 4.20 , 95 % CI 3.48 - 5.08 ) in a dose-dependent manner . Current and FS had significantly increased risk for all lung cancer subtypes , particularly small-cell and squamous cell carcinoma . Among NS , any passive smoking exposure did not significantly increase lung cancer risk ( HR 0.88 , 95 % CI 0.52 - 1.49 ) . However , risk tended to be increased in NS with adult home passive smoking exposure ≥30 years , compared with NS with no adult home exposure ( HR 1.61 , 95 % CI 1.00 - 2.58 ) . CONCLUSIONS In this prospect i ve cohort of postmenopausal women , active smoking significantly increased risk of all lung cancer subtypes ; current smokers had significantly increased risk compared with FS . Among NS , prolonged passive adult home exposure tended to increase lung cancer risk . These data support continued need for smoking prevention and cessation interventions , passive smoking research , and further study of lung cancer risk factors in addition to smoking . CLINICAL TRIALS.GOV : NCT00000611 The available epidemiological studies of lung cancer and exposure to other people 's tobacco smoke , in which exposure was assessed by whether or not a person classified as a non-smoker lived with a smoker , were identified and the results combined . There were 10 case-control studies and three prospect i ve studies . Overall , there was a highly significant 35 % increase in the risk of lung cancer among non-smokers living with smokers compared with non-smokers living with non-smokers ( relative risk 1.35 , 95 % confidence interval 1.19 to 1.54 ) . Part of this increase was almost certainly caused by the misclassification of some smokers as non-smokers . As smokers , who are more likely to get lung cancer than non-smokers , tend to live with smokers this misclassification probably exaggerated the estimated increase in risk . Adjustment for this error reduced the estimate to 30 % ( relative risk 1.30 ) , but as people who live with non-smokers may still be exposed to other people 's smoke this estimate was revised again to allow for the fact that a truly unexposed reference group was not used . The increase in risk among non-smokers living with smokers compared with a completely unexposed group was thus estimated as 53 % ( relative risk of 1.53 ) . This analysis , and the fact that non-smokers breathe environmental tobacco smoke , which contains carcinogens , into their lungs and that the generally accepted view is that there is no safe threshold for the effect of carcinogens , leads to the conclusion that breathing other people 's tobacco smoke is a cause of lung cancer . About a third of the cases of lung cancer in non-smokers who live with smokers , and about a quarter of the cases in non-smokers in general , may be attributed to such exposure Vitamin E includes several tocopherol isoforms , which may reduce lung cancer risk , but past studies evaluating the association between vitamin E intake and lung cancer risk were inconsistent . We prospect ively investigated the associations between tocopherol intake from diet and from supplements with lung cancer risk among 72,829 Chinese female nonsmokers aged 40–70 years and participating in the Shanghai Women 's Health Study ( SWHS ) . Dietary and supplement tocopherol exposure was assessed by a vali date d food‐frequency question naire at baseline and reassessed for change in intake during follow‐up . Cox proportional hazards models with time‐dependent covariates were used to calculate multivariate‐adjusted hazard ratios ( HRs ) and 95 % confidence interval ( CIs ) for lung cancer . After 12.02 years of follow‐up , 481 women were diagnosed with lung cancer . Total dietary tocopherol was inversely associated with lung cancer risk among women meeting dietary guidelines for adequate intake ( AI ) of tocopherol ( 14 mg/day or more : HR : 0.78 ; 95 % CI 0.60–0.99 ; compared with the category less than AI ) . The protective association between dietary tocopherol intake and lung cancer was restricted to women exposed to side‐stream smoke in the home and workplace [ HR = 0.53 ( 0.29–0.97 ) , p‐trend = 0.04 ] . In contrast , vitamin E supplement use was associated with increased lung cancer risk ( HR : 1.33 ; 95 % CI : 1.01–1.73 ) , more so for lung adenocarcinoma risk ( HR : 1.79 ; 95 % CI : 1.23–2.60 ) . In summary , dietary tocopherol intake may reduce the risk of lung cancer among female nonsmokers ; however , supplements may increase lung adenocarcinoma risk and requires further investigation A number of studies suggest a role of dietary factors as risk predictors of lung cancer in never smokers . However , it is difficult to interpret the observed associations of lung cancer risk with any particular dietary item due to high correlation among different dietary items . In this study , we derived uncorrelated patterns of dietary items in the never smokers and evaluated the association of these patterns with lung cancer risk , using food frequency data from 299 never-smoker lung cancer patients and 317 controls enrolled in an ongoing case – control lung cancer study . We identified 2 major dietary patterns in never smokers : a “ healthy eating ” pattern including vegetables , fruits , and low-fat food items , and a “ mixed dishes ” pattern including most foods with positive loadings . Using multivariable regression analysis , we show that the healthy eating pattern is associated with a significant reduction of lung cancer risk among never smokers . The effect of the healthy eating pattern remained significant after adjustment for age , gender , education , caloric intake , secondh and smoke exposure , and family history of cancer . This finding , if confirmed in a prospect i ve study , has a clear preventive significance , by promoting interventions encouraging healthier diets Factors that affect the risk of lung adenocarcinoma among females were investigated in Shenyang , China , using a population -based case-control study design . A total of 72 new cases , ages 35 - 69 , diagnosed with incident , primary pulmonary adenocarnoma , were collected between April 1991 and December 1995 , and were 1:1 age-matched with healthy females r and omly selected from the general population . A question naire covering demographics , diet/nutritional preferences and cooking habits , living conditions , family history of cancer , sources of indoor/outdoor/occupational pollution , exposure to ETS from spousal smoking , workplace exposure , and exposure during childhood , history of menstruation and pregnancy , was given to each subject in a structured in-person interview given by trained field workers . Univariate analysis was performed on the data collected . The results showed that cooking fumes , family history of lung cancer , economic status , and number of live births and intake of vitamin E were risk factors significantly associated with adenocarcinoma of the lung . In particular , exposure to different levels of cooking fumes , an indoor air pollutant , increased the odds ratio of lung adenocarcinoma by 1.33 , 7.33 and 1.67 , respectively ( trend p=0.006 ) . Another important risk factor was family history of lung cancer , which gave an OR of 7.65 ( 95 % CI , 0.90 - 169.84 ) . Intake of beta-carotene from vegetables and fruit offered protection against lung adenocarcinoma , giving an OR of 0.28 ( 95 % CI , 0.12 - 0.69 ) . These results were confirmed by multivariable logistic regression analysis BACKGROUND Lung cancer continues to remain as one of the leading causes of morbidity and mortality worldwide , despite the decreasing trends in smoking prevalence worldwide . An earlier study from the authors ' institute reported the increasing trends of " Nonsmoking associated lung cancers . " MATERIAL S AND METHODS All consecutive histologically confirmed patients with lung cancer who presented to the outpatient department over a year ( November 2014-October 2015 ) were included in this current prospect i ve study . RESULTS Seven hundred and thirteen patients presented with clinicoradiologically suspicious findings of lung cancer in the said period . A pathological confirmation of lung cancer could be ascertained in 495 patients , and this cohort was further analyzed . The mean age of presentation was 57.76 years ; the male to female ratio was approximately 2.5:1 . Interestingly , 55.35 % of the patients were nonsmokers . Adenocarcinoma ( 63 % ) was the predominant histology . Never smokers , both among men ( P = 0.02 ) and women ( P = 0.001 ) , presented more frequently with adenocarcinoma histology . Further , 84.9 % ( 45/53 ) of rural and 76.1 % ( 19/25 ) of urban women who were never smokers reported exposure to indoor air pollution ( secondh and smoke/fuel used for cooking purpose s ) which was significantly associated with adenocarcinoma histology . CONCLUSION Our study confirmed our initial observation of the changing epidemiology of lung cancer in the Indian subcontinent , paralleling the global trends of rise in adenocarcinoma . Lung cancer in never smokers outnumbering that among smokers was another interesting observation . The take-home message for both the clinicians as well as the policymakers is to study factors beyond tobacco exposure to underst and the direction of the current lung cancer epidemic Although smoking is a major cause of lung cancer , the proportion of lung cancer cases among Japanese women who never smoked is high . As the prevalence of smoking in Japan is relatively high in men but low in women , the development of lung cancer in non-smoking Japanese women may be significantly impacted by passive smoking . We conducted a population -based prospect i ve study established in 1990 for Cohort I and in 1993 for Cohort II . The study population was defined as all residents aged 40 - 69 years at the baseline survey . 28,414 lifelong non-smoking women provided baseline information on exposure to tobacco smoke from their husb and , at the workplace and during childhood . Over 13 years of follow-up , 109 women were newly diagnosed with lung cancer , of whom 82 developed adenocarcinoma . Compared with women married to never smokers , hazard ratio ( HR ) [ 95 % confidence interval ( CI ) ] for all lung cancer incidence in women who lived with a smoking husb and was 1.34 ( 95 % CI 0.81 - 2.21 ) . An association was clearly identified for adenocarcinoma ( HR 2.03 , 95 % CI 1.07 - 3.86 ) , for which dose-response relationships were seen for both the intensity ( p for trend = 0.02 ) and amount ( p for trend = 0.03 ) of the husb and 's smoking . Passive smoking at the workplace also increased the risk of lung cancer ( HR 1.32 , 95 % CI 0.85 - 2.04 ) . Moreover , a higher risk of adenocarcinoma was seen for combined husb and and workplace exposure ( HR 1.93 , 95 % CI 0.88 - 4.23 ) . These findings confirm that passive smoking is a risk factor for lung cancer , especially for adenocarcinoma among Japanese women Background : Although substantial evidence suggests that higher intake of fruits and vegetables can reduce the adverse impact of smoking on lung cancer risk , great uncertainty exists regarding the specific foods and their constituents that are protective . We therefore examine prospect ively the relation between cigarette smoking and lung cancer incidence among women , and quantify the associations between dietary antioxidants , other nutrients , and lung cancer risk . Methods : In a 16-year prospect i ve cohort study ( the Nurses'2 Health Study ) , 593 cases of lung cancer were confirmed during 1,793,327 person-years of follow-up . Dietary data , including vitamin supplement use and food intake , were collected in 1980 using a vali date d semiquantitative food frequency question naire . Results : The risk of lung cancer increased with the number of cigarettes smoked and with early onset of cigarette smoking . The risk decreased rapidly with the discontinuation of smoking but took 15 years to fall to about the level of risk for women who had never smoked . Dietary intake of fat was not related to the risk of lung cancer . Although β-carotene intake was not related to risk , intake of carrots showed a strong inverse relation : women who reported consuming five or more carrots per week had a relative risk of 0.4 ( 95 % CI = 0.2–0.8 ) compared with the risk for women who never ate carrots . Conclusions : Smoking is the most important risk factor for lung cancer in women , as it is in men . Higher vegetable consumption , particularly of carrots , may significantly reduce the risk of lung cancer , but dietary modification can not be considered a substitute for smoking prevention and cessation Epidemiological evidence suggests that airway obstruction is an independent risk factor for lung cancer and that this can not be explained by active or passive smoking alone . Chlamydia pneumoniae infection has been associated with chronic bronchitis and its exacerbates . Our aim was to evaluate the association between chronic C. pneumoniae infection and risk of lung cancer among male smokers . Smoking males with lung cancer ( n = 230 ) and their age- and locality-matched controls were selected among participants of the Alpha-Tocopherol , Beta-Carotene Cancer Prevention Study . The presence of C. pneumoniae infection was assessed by analyzing specific antibodies and immune complexes in 2 serum sample s collected with a 3-year interval before the lung cancer diagnosis . The diagnosis of chronic infection was based on stable levels of positive specific IgA antibody ( titer > or = 16 ) and immune complex ( titer > or = 4 ) . Relative risks were estimated by odds ratios ( OR ) adjusted for age , locality and smoking history by a conditional logistic regression model . Markers suggesting chronic C. pneumoniae infection were present in 52 % of cases and 45 % of controls and hence were positively associated with the incidence of lung cancer ( OR 1.6 ; 95 % confidence interval [ CI ] 1.0 - 2.3 ) . The incidence was especially increased in men younger than 60 years ( OR 2.9 ; 95 % CI 1.5 - 5.4 ) but not in the older age group ( OR 0.9 ; 95 % CI 0.5 - 1.6 ) . Before concluding that C. pneumoniae infection is a new independent risk factor for lung cancer , corroboration from other studies with larger number of cases and longer follow-up is needed CONTEXT The dominant role of tobacco smoke as a causative factor in lung carcinoma is well established ; however , an inherited predisposition may also be an important factor in the susceptibility to lung carcinoma . OBJECTIVE To investigate the contribution of genetic factors to the risk of developing lung carcinoma in the Icel and ic population . DESIGN , SETTING , AND PARTICIPANTS Risk ratios ( RRs ) of lung carcinoma for first- , second- , and third-degree relatives of patients with lung carcinoma were estimated by linking records from the Icel and ic Cancer Registry ( ICR ) of all 2756 patients diagnosed with lung carcinoma within the Icel and ic population from January 1 , 1955 , to February 28 , 2002 , with an extensive genealogical data base containing all living Icel and ers and most of their ancestors since the settlement of Icel and . The RR for smoking was similarly estimated using a r and om population -based cohort of 10,541 smokers from the Reykjavik Heart Study who had smoked for more than 10 years . Of these smokers , 562 developed lung cancer based on the patients with lung cancer list from the ICR . MAIN OUTCOME MEASURES Estimation of RRs of close and distant relatives of patients with lung carcinoma and comparison with RRs for close and distant relatives of smokers . RESULTS A familial factor for lung carcinoma was shown to extend beyond the nuclear family , as evidence d by significantly increased RR for first-degree relatives ( for parents : RR , 2.69 ; 95 % confidence interval [ CI ] , 2.20 - 3.23 ; for siblings : RR , 2.02 ; 95 % CI , 1.77 - 2.23 ; and for children : RR , 1.96 ; 95 % CI , 1.53 - 2.39 ) , second-degree relatives ( for uncles/aunts : RR , 1.34 ; 95 % CI , 1.15 - 1.49 ; and for nephews/nieces : RR , 1.28 ; 95 % CI , 1.10 - 1.43 ) , and third-degree relatives ( for cousins : RR , 1.14 ; 95 % CI , 1.05 - 1.22 ) of patients with lung carcinoma . This effect was stronger for relatives of patients with early-onset disease ( age at onset < or = 60 years ) ( for parents : RR , 3.48 ; 95 % CI , 1.83 - 8.21 ; for siblings : RR , 3.30 ; 95 % CI , 2.19 - 4.58 ; and for children : RR , 2.84 ; 95 % CI , 1.34 - 7.21 ) . The hypothesis that this increased risk is solely due to the effects of smoking was rejected for all relationships , except cousins and spouses , with a single-sided test of the RRs for lung carcinoma vs RRs for smoking . CONCLUSIONS These results underscore the importance of genetic predisposition in the development of lung carcinoma , with its strongest effect in patients with early-onset disease . However , tobacco smoke plays a dominant role in the pathogenesis of this disease , even among those individuals who are genetically predisposed to lung carcinoma Abstract Objectives : To investigate the relationship between passive smoking at home and the incidence of various cancers in a population -based prospect i ve study . Methods : The subjects were 9675 Japanese lifelong nonsmoking women aged over 40 years who lived in three municipalities of Miyagi Prefecture , and completed a self-administration question naire in 1984 . During 9 years of follow-up , 426 cancers were identified by record linkage to the population -based cancer registry . The data were analyzed using the Cox proportional hazards model . Results : The age-adjusted relative risks ( RR ) and 95 % confidence intervals ( CI ) of smoking-related cancers and lung cancer for women who had smoking husb and s , compared with women whose husb and s did not smoke , were 1.7 ( 0.94–2.9 , p = 0.079 ) and 1.9 ( 0.81–4.4 , p = 0.14 ) , respectively . In contrast , a significant inverse association was observed for breast cancer ; the RR ( 95 % CI ) was 0.58 ( 0.34–0.99 , p = 0.047 ) . After multivariate adjustment for confounding factors , the risks of smoking-related cancers and breast cancer were material ly unchanged . Conclusions : These results show that passive smoking may affect the risk of cancers other than lung cancer Lung cancer risk estimates for exposure to environmental tobacco smoke remain controversial , a major unresolved issue being misclassification of smokers . We studied misclassification rates in two large cohorts using information on smoking obtained several years apart . Cohort I included Swedish twins born between 1886 and 1925 who answered question naires in 1961 and again in 1967 or 1970 . Cohort II was a r and om stratified population sample of individuals born between 1894 and 1945 who responded to postal smoking surveys in 1963 and 1969 . We considered those who stated that they had never smoked in the second question naire , but who reported smoking or former smoking in the first question naire , to be misclassified . In cohort I , 4.9 % of male and 4.5 % of female ever‐smokers were misclassified , corresponding to 11.1 % and 1.3 % of reported never‐smokers , respectively . Cohort II yielded similar results . A follow‐up through 1992 of cohort I showed a relative risk for lung cancer among misclassified men of 1.9 [ 95 % confidence interval ( CI ) = 0.4–9.1 ] , as compared with 4.5 ( 95 % CI = 2.0–9.9 ) and 13.3 ( 95 % CI = 6.5–27.0 ) for former and current smokers , respectively . No case occurred among misclassified women . Although misclassification of smokers exists , our results indicate that it mainly concerns light smokers or long‐time ex‐smokers , who have only a very moderately elevated risk of lung cancer . It therefore appears unlikely that confounding by smoking explains the increased risk for lung cancer related to environmental tobacco smoke exposure Abstract Objective To measure the relation between environmental tobacco smoke , as estimated by smoking in spouses , and long term mortality from tobacco related disease . Design Prospect i ve cohort study covering 39 years . Setting Adult population of California , United States . Participants 118 094 adults enrolled in late 1959 in the American Cancer Society cancer prevention study ( CPS I ) , who were followed until 1998 . Particular focus is on the 35 561 never smokers who had a spouse in the study with known smoking habits . Main outcome measures Relative risks and 95 % confidence intervals for deaths from coronary heart disease , lung cancer , and chronic obstructive pulmonary disease related to smoking in spouses and active cigarette smoking . Results For participants followed from 1960 until 1998 the age adjusted relative risk ( 95 % confidence interval ) for never smokers married to ever smokers compared with never smokers married to never smokers was 0.94 ( 0.85 to 1.05 ) for coronary heart disease , 0.75 ( 0.42 to 1.35 ) for lung cancer , and 1.27 ( 0.78 to 2.08 ) for chronic obstructive pulmonary disease among 9619 men , and 1.01 ( 0.94 to 1.08 ) , 0.99 ( 0.72 to 1.37 ) , and 1.13 ( 0.80 to 1.58 ) , respectively , among 25 942 women . No significant associations were found for current or former exposure to environmental tobacco smoke before or after adjusting for seven confounders and before or after excluding participants with pre-existing disease . No significant associations were found during the shorter follow up periods of 1960 - 5 , 1966 - 72 , 1973 - 85 , and 1973 - 98 . Conclusions The results do not support a causal relation between environmental tobacco smoke and tobacco related mortality , although they do not rule out a small effect . The association between exposure to environmental tobacco smoke and coronary heart disease and lung cancer may be considerably weaker than generally believed BACKGROUND To investigate the risk factors of lung cancer in female nonsmokers . METHODS An 1:1 matched case-control study was carried out in Shenyang , P.R.China . A question naire covering demographics , family history of cancer , previous disease history , living conditions , passive smoking history , occupational exposure , diet/nutritional preferences and cooking habits , sources of indoor pollution and so on was used to ask each subject . A total of 126 new cases diagnozed as primary lung cancer and 126 controls matched for age and sex were r and omly selected from the female nonsmokers . RESULTS Adenocarcinoma was the main type of female lung cancer , accounting for 62.7 % . The higher number of deliveries was , the more risk of lung cancer was ( OR=1.466 , 95%CI=1.06 - 2.01 ) . The lower the body mass index ( BMI ) , the higher the risk of lung cancer ( OR=2.082 , 95%CI=1.2 - 3.60 ) . With the increase of BMI , the risk of lung cancer decreased . Eating too much viscera ( OR=1.891 , 95%CI=1.45 - 2.46 ) , maize and sorghum ( OR=1.538 , 95%CI= 1.22 -1.93 ) could increase the risk of lung cancer . Using petroleum gas as fuel ( OR=1.741 , 95%CI=1.29 - 2.34 ) and indoor coal burning ( OR=1.785 , 95%CI=1.33 - 2.38 ) were lung cancer 's risk factors , too . The OR value of family cancer history of first-class relatives was 3.18 ( 95%CI=2.43 - 4.15 ) . CONCLUSIONS The results suggest that low value of BMI , high number of child deliveries , eating too much viscera , maize and sorghum , indoor coal burning and using petroleum gas as fuel can increase the risk of lung cancer in female nonsmokers BACKGROUND Molecular studies have demonstrated actionable driver oncogene alterations are more frequent in never-smokers with non-small-cell lung cancer ( NSCLC ) . The etiology of these driver oncogenes in patients with NSCLC remains unknown , and environmental tobacco smoke ( ETS ) is a potential cause in these cases . MATERIAL S AND METHODS We assembled clinical and genetic information for never-smoker patients with NSCLC accrued in Japan , Korea , Singapore , and the United States . To determine an association between cumulative ETS and activating EGFR mutations or ALK rearrangements , the Mantel extension test was used . Multivariate analysis on activating EGFR and ALK gene rearrangements was performed using the generalized linear mixed model with nations as a r and om effect . RESULTS From July 2007 to December 2012 , 498 never-smokers with pathologically proven NSCLC were registered and tested for the association between ETS and EGFR and ALK status . EGFR mutations were more frequent in the ever-ETS cohort ( 58.4 % ) compared with the never-ETS cohort ( 39.6 % ) , and the incidence of EGFR mutations was significantly associated with the increment of cumulative ETS ( cETS ) in female never-smokers ( P = .033 ) , whereas the incidence of ALK rearrangements was not significantly different between the ever-ETS and never-ETS cohorts . Odds ratio for EGFR mutations for each 10-year increment in cETS was 1.091 and 0.89 for female and male never-smokers ( P = .031 and P = .263 , respectively ) . CONCLUSION Increased ETS exposure was closely associated with EGFR mutations in female never-smokers with NSCLC in the exp and ed multinational cohort . However , the association of ETS and ALK rearrangements in never-smokers with NSCLC was not significant |
12,367 | 30,076,616 | The most common OxS biomarkers used were 8-hydroxydeoxiguanosine ( 8-OHdG ) , total oxidant status ( TOS ) , and total antioxidant status ( TAS ) .
After treatment , most of the studies reported a decrease in 8-OHdG concentration in the gingival crevicular fluid ( GCF ) and saliva .
In addition , the salivary concentration of this biomarker was similar to periodontally healthy patients .
Periodontal therapy was effective in reducing TOS in GCF , saliva , and serum in most studies .
TAS , however , responded inconsistently to the periodontal intervention .
Periodontal therapy reduces the levels of OxS biomarkers , even to values similar to those found in periodontally healthy individuals . | AIM To systematic ally review the literature about the effect of periodontal treatment on oxidative stress ( OxS ) biomarkers . | Objective : Chronic periodontitis ( CP ) is associated with increased levels of blood reactive oxygen species ( ROS ) . So , treatment of CP may lead to decrease in blood ROS . However , not much literature is available comparing the effect of surgical and non-surgical periodontal treatment on blood ROS levels . Reactive oxygen metabolites ( ROMs ) are a useful measure of blood ROS . The aim of this study was to investigate the effect of periodontal treatment on plasma ROM levels in CP patients . Material s and Methods : Thirty CP patients and 15 controls were monitored . Plasma sample s were collected at baseline and the clinical parameters were recorded . The CP patients were r and omly divided into two groups : Scaling and root planing ( Group II ) and periodontal flap surgery ( Group III ) . Both groups were re-evaluated 1 and 2 months after therapy . Clinical parameters were review ed , plasma sample s collected , and ROM levels were determined using a spectrophotometric technique . Results : At baseline , the ROM levels for Group II and Group III were 519.8 ± 62.4 and 513.4 ± 74.7 CARR U , respectively , which were higher than Group I value ( 282.9 ± 23.9 , P < 0.001 ) . Periodontal treatment in CP patients result ed in improvement of clinical parameters and a highly significant reduction in plasma ROM level ( P < 0.001 ) after 2 months . Also , there was a more significant reduction in plasma ROM levels in Group III as compared to Group II ( P < 0.05 ) . Conclusions : In CP patients , surgical periodontal treatment was more effective in lowering the plasma ROM levels than when non-surgical periodontal treatment was performed alone and , therefore , may be more beneficial in reducing systemic oxidative stress 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 : Plasma glutathione peroxidase ( eGPx ) is an important selenium containing antioxidant in human defense against oxidative stress . While crevicular fluid ( GCF ) eGPx levels and its association with periodontal disease is well documented , there is no data on correlation of GCF and serum eGPx levels in chronic periodontitis . Hence this study was undertaken to further probe into the role of oxidative stress in periodontal diseases and effect of nonsurgical periodontal therapy ( NSPT ) by correlating GCF and serum levels of eGPx . Material s and methods : Thirty subjects ( 16-Males and 14-Females ; age : 30–38 years ) participated in the study . The subjects were divided , based on gingival index , probing pocket depth and clinical attachment level into : Healthy ( group-1 , n=10 ) , Gingivitis ( group-2 , n=10 ) and Periodontitis ( group-3 , n=10 ) . Chronic periodontitis patients after NSPT constituted group 4 . GCF and serum sample s collected from each subject were quantified for eGPx levels using Enzyme linked Immunosorbent Assay . Results : The mean eGPx concentrations increased from health ( 14.01 ng/μl and 78.26 ng/ml ) to gingivitis ( 22.86 ng/μl and 90.44 ng/ml ) and then to periodontitis ( 29.89 ng/μl and 103.43 ng/ml ) , in GCF and serum respectively . After NSPT , there was statistically significant reduction in eGPx concentration in GCF and serum ( 19.41 ng/μl and 85.21 ng/ml ) . Further , all the GCF eGPx values showed a positive correlation to that of serum eGPx level . Conclusion : Thus , increased eGPx concentration in GCF can be considered as an indicator of local increase in oxidative stress . While , increase in serum eGPx levels indicates that periodontal disease can also lead to increased oxidative stress at the systemic level Aim The purpose of this study was to investigate the effects of non-surgical periodontal treatment on hemoglobinA1c ( HbA1c ) levels , oxidative stress balance and quality of life ( QOL ) in patients with type 2 diabetes mellitus ( T2DM ) compared to no periodontal treatment ( simple oral hygiene instructions only ) . Methods The design was a 6-month , single-masked , single center , r and omized clinical trial . Patients had both T2DM and chronic periodontitis . Forty participants were enrolled between April 2014 and March 2016 at the Nephrology , Diabetology and Endocrinology Department of Okayama University Hospital . The periodontal treatment group ( n = 20 ) received non-surgical periodontal therapy , including scaling and root planing plus oral hygiene instructions , and consecutive supportive periodontal therapy at 3 and 6 months . The control group ( n = 17 ) received only oral hygiene instructions without treatment during the experimental period . The primary study outcome was the change in HbA1c levels from baseline to 3 months . Secondary outcomes included changes in oxidative stress balance ( Oxidative-INDEX ) , the Diabetes Therapy-Related QOL and clinical periodontal parameters from baseline to 3 months and baseline to 6 months . Results Changes in HbA1c in the periodontal treatment group were not significantly different with those in the control group at 3 and 6 months . Systemic oxidative stress balance and QOL significantly improved in the periodontal treatment group compared to the control group at 3 months . In the subgroup analysis ( moderately poor control of diabetes ) , the decrease in HbA1c levels in the periodontal treatment group was greater than that in the control group at 3 months but not significant . Conclusions In T2DM patients , non-surgical periodontal treatment improved systemic oxidative stress balance and QOL , but did not decrease HbA1c levels at 3 months follow-up . Trial registration Current Controlled Trials UMIN-ICDR UMIN 000013278 ( Registered April 1 , 2014 ) BACKGROUND This study investigates the levels of superoxide dismutase ( SOD ) activity in serum and saliva of patients with chronic periodontitis ( CP ) . In addition , the outcome of scaling and root planing ( SRP ) with and without vitamin E supplementation is evaluated in terms of changes in periodontal parameters and SOD activity in patients with CP . METHODS Serum and salivary SOD activity in 38 patients with CP were compared with those of 22 systemically and periodontally healthy individuals ( control group ) . At periodontal examination , serum and saliva sample s were obtained . Patients with CP were r and omly divided into treatment groups 1 ( TG-1 ) and 2 ( TG-2 ) . SRP was performed for both groups , and TG-2 also received 200 mg ( 300 IU ) vitamin E every other day . Periodontal parameters and SOD activity were evaluated after 3 months . SOD activity was determined using an SOD assay and enzyme-linked immunosorbent assay reader at 450 nm . RESULTS SOD activity in both serum ( P < 0.05 ) and saliva ( P < 0.001 ) was lower in patients with CP compared with controls . After 3 months of follow-up , SOD activity improved in both treatment groups ; however , the improvement in TG-2 was higher than in TG-1 , along with more improvement in periodontal parameters . Serum SOD levels in TG-2 increased even above the level of the control group . CONCLUSIONS Systemic and local SOD levels are lowered in CP . Adjunctive vitamin E supplementation improves periodontal healing as well as antioxidant defense |
12,368 | 30,693,409 | Conclusion The Fisher scale , modified Fisher scale , and Hijdra sum score are all associated with clinical DCI .
The risk of DCI , however , does not increase with increasing Fisher grade as opposed to the modified Fisher scale . | Purpose Delayed cerebral ischemia ( DCI ) is a severe complication of aneurysmal subarachnoid hemorrhage ( aSAH ) .
The extent of subarachnoid blood is a strong predictor of DCI and is frequently estimated with the Fisher scale , modified Fisher scale , or Hijdra sum score .
It is unclear which scale has the strongest association with clinical DCI .
To evaluate this , we performed a systematic review of the literature . | Background and Purpose — Patients are classically at risk of delayed cerebral ischemia ( DCI ) after aneurysmal subarachnoid hemorrhage . We vali date d a grading scale — the VASO GRADE —for prediction of DCI . Methods — We used data of 3 phase II r and omized clinical trials and a single hospital series to assess the relationship between the VASO GRADE and DCI . The VASO GRADE derived from previously published risk charts and consists of 3 categories : VASO GRADE -Green ( modified Fisher scale 1 or 2 and World Federation of Neurosurgical Societies scale [ WFNS ] 1 or 2 ) ; VASO GRADE -Yellow ( modified Fisher 3 or 4 and WFNS 1–3 ) ; and VASO GRADE -Red ( WFNS 4 or 5 , irrespective of modified Fisher grade ) . The relation between the VASO GRADE and DCI was assessed by logistic regression models . The predictive accuracy of the VASO GRADE was assessed by receiver operating characteristics curve and calibration plots . Results — In a cohort of 746 patients , the VASO GRADE significantly predicted DCI ( P<0.001 ) . The VASO GRADE -Yellow had a tendency for increased risk for DCI ( odds ratio [ OR ] , 1.31 ; 95 % CI , 0.77–2.23 ) when compared with VASO GRADE -Green ; those with VASO GRADE -Red had a 3-fold higher risk of DCI ( OR , 3.19 ; 95 % CI , 2.07–4.50 ) . Studies were not a significant confounding factor between the VASO GRADE and DCI . The VASO GRADE had an adequate discrimination for prediction of DCI ( area under the receiver operating characteristics curve=0.63 ) and good calibration . Conclusions — The VASO GRADE results vali date d previously published risk charts in a large and diverse sample of subarachnoid hemorrhage patients , which allows DCI risk stratification on presentation after subarachnoid hemorrhage . It could help to select patients at high risk of DCI , as well as st and ardize treatment protocol s and research studies Using logistic regression , we analyzed the predictive value of a number of entry variables with respect to the outcome variables delayed cerebral ischemia , rebleeding , and poor outcome ( death or severe disability ) in patients with aneurysmal subarachnoid hemorrhage . The entry variables were clinical condition on admission ( grade s on the Glasgow Coma Scale , Hunt and Hess system ) , the amount of subarachnoid and intraventricular blood and the presence of hydrocephalus on the admission computed tomogram , and antifibrinolytic treatment with tranexamic acid . We used data from a prospect ively studied population of 176 patients admitted within 72 hours after subarachnoid hemorrhage . The risk of delayed cerebral ischemia was best predicted by the amount of subarachnoid blood , intraventricular blood , and antifibrinolytic treatment irrespective of clinical condition and hydrocephalus . The site of delayed cerebral ischemia was not related to the location of the subarachnoid hemorrhage . Antifibrinolytic treatment was the only entry variable ( negatively ) predicting the risk of rebleeding . Death or severe disability after 3 months was best predicted by the amount of subarachnoid blood and the initial clinical condition reflected by the grade on the Glasgow Coma Scale Introduction Subarachnoid hemorrhage ( SAH ) can trigger immune activation sufficient to induce the systemic inflammatory response syndrome ( SIRS ) . This may promote both extra-cerebral organ dysfunction and delayed cerebral ischemia , contributing to worse outcome . We ascertained the frequency and predictors of SIRS after spontaneous SAH , and determined whether degree of early systemic inflammation predicted the occurrence of vasospasm and clinical outcome . Methods Retrospective analysis of prospect ively collected data on 276 consecutive patients admitted to a neurosciences intensive care unit with acute , non-traumatic SAH between 2002 and 2005 . A daily SIRS score was derived by summing the number of variables meeting st and ard criteria ( HR > 90 , RR > 20 , Temperature > 38 ° C , or < 36 ° C , WBC count < 4,000 or > 12,000 ) . SIRS was considered present if two or more criteria were met , while SIRS burden over the first four days was calculated by averaging daily scores . Regression modeling was used to determine the relationship among SIRS burden ( after controlling for confounders including infection , surgery , and corticosteroid use ) , symptomatic vasospasm , and outcome , determined by hospital disposition . Results SIRS was present in over half the patients on admission and developed in 85 % within the first four days . Factors associated with SIRS included poor clinical grade , thick cisternal blood , larger aneurysm size , higher admission blood pressure , and surgery for aneurysm clipping . Higher SIRS burden was independently associated with death or discharge to nursing home ( OR 2.20/point , 95 % CI 1.27–3.81 ) . All of those developing clinical vasospasm had evidence of SIRS , with greater SIRS burden predicting increased risk for delayed ischemic neurological deficits ( OR 1.77/point , 95 % CI 1.12–2.80 ) . Conclusions Systemic inflammatory activation is common after SAH even in the absence of infection ; it is more frequent in those with more severe hemorrhage and in those who undergo surgical clipping . Higher burden of SIRS in the initial four days independently predicts symptomatic vasospasm and is associated with worse outcome OBJECTIVE The aim of this study was to investigate prospect ively in an unselected series of patients with an aneurysmal subarachnoid haemorrhage what at present the complications are , what the outcome is , how many of these patients have “ modern treatment”—that is , early obliteration of the aneurysm and treatment with calcium antagonists — what factors cause a delay in surgical or endovascular treatment , and what the estimated effect on outcome will be of improved treatment . METHODS A prospect i ve , observational cohort study of all patients with aneurysmal subarachnoid haemorrhage in the hospitals of a specified region in The Netherl and s. The condition on admission , diagnostic procedures , and treatments were recorded . If a patient had a clinical deterioration , the change in Glasgow coma score ( GCS ) , the presence of focal neurological signs , the results of additional investigations , and the final diagnosed cause of the deterioration were recorded . Clinical outcome was assessed with the Glasgow outcome scale ( GOS ) at 3 month follow up . In patients with poor outcome at follow up , the cause was diagnosed . RESULTS Of the 110 patients , 47 ( 43 % ) had a poor outcome . Cerebral ischaemia , 31 patients ( 28 % ) , was the most often occurring complication . Major causes of poor outcome were the effects of the initial haemorrhage and rebleeding in 34 % and 30 % of the patients with poor outcome respectively . Of all patients 102 ( 93 % ) were treated with calcium antagonists and 45 ( 41 % ) patients had early treatment to obliterate the aneurysm . The major causes of delay of treatment were a poor condition on admission or deterioration shortly after admission , in 31 % and 23 % respectively . CONCLUSIONS In two thirds of the patients with poor outcome the causes of poor outcome are the effects of the initial bleeding and rebleeding . Improved treatment of delayed or postoperative ischaemia will have only minor effects on the outcome of patients with subarachnoid haemorrhage Background The risk of delayed cerebral ischemia ( DCI ) after subarachnoid hemorrhage ( SAH ) is associated with large cerebral artery vasospasm , but vasospasm is not a strong predictor for DCI . Assessment of cerebral autoregulation with transcranial Doppler ( TCD ) may improve the prediction of DCI . The aim of this prospect i ve study was to assess the value of TCD-derived variables to be used alone or in combination for prediction of DCI . Methods We included consecutive patients with low- grade aneurysmal SAH within 4 days of aneurysm rupture . Cerebral autoregulation was evaluated using the moving correlation coefficient Mx calculated from spontaneous fluctuations of cerebral blood flow velocities and arterial blood pressure . Transcranial color-coded sonography was performed to assess large artery vasospasm . Results Thirty patients ( 19 women and 11 men ; mean age ± SD 44.7 ± 12.1 years ) were included . Twenty ( 66.7 % ) patients had vasospasm . DCI occurred in six ( 20 % ) patients after a median delay of 10 days ( range 8–13 days ) . Cerebral autoregulation was impaired at baseline and at day 7 and then returned to normal at day 14 . Neither cerebral autoregulation impairment nor large artery vasospasm alone was associated with DCI . In contrast , the combination of large artery vasospasm with worsening impairment of cerebral autoregulation from baseline to day 7 was significantly correlated to subsequent DCI ( p = 0.007 ) . Conclusions Early deterioration of cerebral autoregulation was strongly predictive of DCI in patients with large artery vasospasm after low- grade SAH . Our results suggest that consideration to both cerebral blood flow velocities and cerebral autoregulation may improve the prediction of DCI UNLABELLED The Fisher revised scale ( FRS ) presents an alternative for evaluating patients with subarachnoid hemorrhage ( SAH ) . In this study , we compared the prognosis of patients with SAH and vasospasms ( VSP ) . METHOD This was a prospect i ve study on patients with a diagnosis of aneurysmal SAH , 72 hours after the initial event . Sequential neurological examinations and Hunt and Hess ( HaH ) score were performed on the 1(st ) , 7(th ) and 14(th ) days . Transcranial Doppler was used to assess vasospasms . RESULTS Out of the 24 patients studied , ten ( 41.66 % ) presented a delayed neurological deficit , such as diminished consciousness , decreased HaH score or death . The single patient classified as FS-1 did not have any delayed neurological deficit , while such deficits evolved in one patient out of five with FS-2 ( 20 % ) ; two out of seven with FS-3 ( 28.57 % ) and seven out of 11 with FS-4 ( 63.63 % ) . CONCLUSION Level three of the FS and FRS seemed to be compatible with regard to predicting the likelihood of progression to severe VSP Background and Purpose — A single-center prospect i ve r and omized controlled trial has been conducted to determine if lumbar drainage of cerebrospinal fluid after aneurysmal subarachnoid hemorrhage reduces the prevalence of delayed ischemic neurological deficit and improves clinical outcome . Methods — Patients with World Federation of Neurological Surgeons Grade 1 to 3 aneurysmal subarachnoid hemorrhage and modified Fisher Grade s 2 , 3 , 4 , and 3 + 4 were r and omized to either the study group of st and ard therapy plus insertion of a lumbar drain or the control group of st and ard therapy alone . The primary outcome measure was the prevalence of delayed ischemic neurological deficit . Results — Two hundred ten patients with aneurysmal subarachnoid hemorrhage ( 166 female , 44 male ; median age , 54 years ; interquartile range , 45–62 years ) were recruited into the control ( n=105 ) and study ( n=105 ) groups of the trial . World Federation of Neurological Surgeons grade was : 1 ( n=139 ) , 2 ( n=60 ) , and 3 ( n=11 ) ; Fisher grade was : 2 ( n=87 ) , 3 ( n=85 ) , and 4 ( n=38 ) . The prevalence of delayed ischemic neurological deficit was 35.2 % and 21.0 % in the control and study groups , respectively ( P=0.021 ) . The prevalence of a modified Rankin Scale score of 4 , 5 , or 6 at Day 10 and 6 months , respectively , was 62.5 % and 18.6 % in the control group and 44.8 % and 19.8 % in the study group ( P=0.009 and 0.83 , respectively ) . Conclusions — Lumbar drainage of cerebrospinal fluid after aneurysmal subarachnoid hemorrhage has been shown to reduce the prevalence of delayed ischemic neurological deficit and improve early clinical outcome but failed to improve outcome at 6 months after aneurysmal subarachnoid hemorrhage . Clinical Trial Registration — URL : www . clinical trials.gov . Unique identifier : NCT00842049 OBJECTIVE We developed a modification of the Fisher computed tomographic rating scale and compared it with the original Fisher scale to determine which scale best predicts symptomatic vasospasm after subarachnoid hemorrhage . METHODS We analyzed data from 1355 subarachnoid hemorrhage patients in the placebo arm of four r and omized , double-blind , placebo-controlled studies of tirilazad . Modified Fisher computed tomographic grade s were calculated on the basis of the presence of cisternal blood and intraventricular hemorrhage . Crude odds ratios ( OR ) reflecting the risk of developing symptomatic vasospasm were calculated for each scale level , and adjusted ORs expressing the incremental risk were calculated after controlling for known predictors of vasospasm . RESULTS Of 1355 patients , 451 ( 33 % ) developed symptomatic vasospasm . For the modified Fisher scale , compared with Grade 0 to 1 patients , the crude OR for vasospasm was 1.6 ( 95 % confidence interval [ CI ] , 1.0 - 2.5 ) for Grade 2 , 1.6 ( 95 % CI , 1.1 - 2.2 ) for Grade 3 , and 2.2 ( 95 % CI , 1.6 - 3.1 ) for Grade 4 . For the original Fisher scale , referenced to Grade 1 , the OR for vasospasm was 1.3 ( 95 % CI , 0.7 - 2.2 ) for Grade 2 , 2.2 ( 95 % CI , 1.4 - 3.5 ) for Grade 3 , and 1.7 ( 95 % CI , 1.0 - 3.0 ) for Grade 4 . Early angiographic vasospasm , history of hypertension , neurological grade , and elevated admission mean arterial pressure were identified as risk factors for symptomatic vasospasm . After adjusting for these variables , the modified Fisher scale remained a significant predictor of vasospasm ( adjusted OR , 1.28 ; 95 % CI , 1.06 - 1.54 ) , whereas the original Fisher scale was not . CONCLUSION The modified Fisher scale , which accounts for thick cisternal and ventricular blood , predicts symptomatic vasospasm after subarachnoid hemorrhage more accurately than original Fisher scale OBJECTIVE Endothelin-1 , a potent vasoconstrictor , and its receptors may be involved in the pathogenesis of aneurysmal subarachnoid hemorrhage ( aSAH ) , clinical vasospasm , delayed cerebral ischemia ( DCI ) , and functional outcome following aSAH . In the present study , common endothelin single nucleotide polymorphisms ( SNPs ) and their relation to aSAH were evaluated . METHODS Blood sample s from all patients enrolled in the Cerebral Aneurysm Renin Angiotensin System ( CARAS ) study were used for genetic evaluation . The CARAS study prospect ively enrolled patients with aSAH at 2 academic institutions in the US from 2012 to 2015 . Common endothelin SNPs were detected using 5 ' exonnuclease ( TaqMan ) genotyping assays . Analysis of associations between endothelin SNPs and aSAH and its clinical sequelae was performed . RESULTS Sample s from 149 patients with aSAH and 50 controls were available for analysis . In multivariate logistic regression analysis , the TG ( odds ratio [ OR ] 2.102 , 95 % confidence interval [ CI ] 1.048 - 4.218 , p = 0.036 ) and TT genotypes ( OR 7.884 , 95 % CI 1.003 - 61.995 , p = 0.05 ) of the endothelin-1 T/G SNP ( rs1800541 ) were significantly associated with aSAH . There was a dominant effect of the G allele ( CG/GG genotypes ; OR 4.617 , 95 % CI 1.311 - 16.262 , p = 0.017 ) of the endothelin receptor A G/C SNP ( rs5335 ) on clinical vasospasm . Endothelin SNPs were not associated with DCI or functional outcome . CONCLUSIONS Common endothelin SNPs were found to be associated with presentation with aSAH and clinical vasospasm . Further studies are required to eluci date the relevant pathophysiology and its potential implication s in the treatment of patients with aSAH Background : Serum lipid abnormalities are known to be important risk factors for vascular disorders . However , their role in delayed cerebral ischemia ( DCI ) , the major cause of morbidity after subarachnoid hemorrhage ( SAH ) remains unclear . This study was an attempt to evaluate the spectrum of lipid profile changes in SAH compared to matched controls , and their relation with the occurrence of DCI . Methods : Admission serum lipid profile levels were measured in patients of SAH and prospect ively studied in relation to various factors and clinical development of DCI . Results : Serum triglyceride ( TG ) levels were significantly lower among SAH patients compared to matched controls ( mean [ ±st and ard deviation ( SD ) ] mg/dL : 117.3 [ ±50.4 ] vs. 172.8 [ ±89.1 ] , P = 0.002 ) , probably because of energy consumption due to hypermetabolic response . Patients who developed DCI had significantly higher TG levels compared to those who did not develop DCI ( mean [ ±SD ] mg/dL : 142.1 [ ±56 ] vs. 111.9 [ ±54 ] , P = 0.05 ) . DCI was noted in 62 % of patients with TG > 150 mg/dL , compared to 22 % among the rest ( P = 0.01 ) . Total cholesterol , low-density lipoprotein cholesterol , high-density lipoprotein cholesterol and lipoprotein ( a ) neither showed a significant difference between SAH and controls and nor any significant association with DCI . Multivariate analysis using binary logistic regression adjusting for the effects of age , sex , systemic disease , World Federation of Neurosurgical Societies grade , Fisher grade , and clipping/coiling , revealed higher TG levels to have significant independent association with DCI ( P = 0.01 ) . Conclusions : Higher serum TG levels appear to be significantly associated with DCI while other lipid parameters did not show any significant association . This may be due to their association with remnant cholesterol or free fatty acid-induced lipid peroxidation Background and Purpose — Thick cisternal clot on CT is a well-recognized risk factor for delayed cerebral ischemia ( DCI ) after subarachnoid hemorrhage ( SAH ) . Whether intraventricular hemorrhage ( IVH ) or intracerebral hemorrhage ( ICH ) predisposes to DCI is unclear . The Fisher CT grading scale identifies thick SAH but does not separately account for IVH or ICH . Methods — We studied 276 consecutively admitted patients with an available admission CT scan performed within 72 hours of onset . Demographic , clinical , laboratory , and neuroimaging data were recorded , and the amount and location of SAH , IVH , and ICH on admission CT scans were quantified . The relationship between these variables and DCI was analyzed separately and in combination with multiple logistic regression . Results — DCI developed in 20 % of patients ( 54 of 276 ) . Among SAH variables , thick clot completely filling any cistern or fissure was the best predictor of DCI ( P = 0.008 ) , and among IVH variables , blood in both lateral ventricles was most predictive ( P = 0.001 ) . These variables had independent predictive value for DCI in a multivariate analysis of CT findings , and both were included in a final multivariate model when evaluated in conjunction with other clinical risk factors : IVH ( OR 4.1 , 95 % CI 1.7 to 9.8 ) , SAH ( OR 2.3 , 95 % CI 1.5 to 9.5 ) , mean arterial pressure > 112 mm Hg ( OR 4.9 , 95 % CI 2.1 to 11.4 ) , and transcranial Doppler mean velocity > 140 cm/s within 5 days of hemorrhage ( OR 3.8 , 95 % CI 1.5 to 9.5 ) . Similar results were obtained in a repeat analysis with infa rct ion due to vasospasm as the dependent variable . Conclusions — SAH completely filling any cistern or fissure and IVH in the lateral ventricles are both risk factors for DCI , and their risk is additive . We propose a new SAH rating scale that accounts for the independent predictive value of subarachnoid and ventricular blood for DCI We enrolled 125 neurologically normal patients with intracranial aneurysms in a multi-institution , prospect i ve , double-blind , r and omized , placebo-controlled trial within 96 hours of their subarachnoid hemorrhage , to determine whether treatment with the calcium blocker nimodipine would prevent or reduce the severity of ischemic neurologic deficits from arterial spasm . A deficit from cerebral arterial spasm that persisted and was severe or caused death by the end of the 21-day treatment period occurred in 8 of 60 patients given placebo and in 1 of 56 given nimodipine ( P = 0.03 , Fisher 's exact test ) . Analysis of the amount of basal subarachnoid blood on pre-entry CAT scans in patients with deficits from spasm showed that an increase in subarachnoid blood was not associated with a worse neurologic outcome among patients who received nimodipine , unlike the situation in patients given a placebo . There were no side effects from nimodipine . We conclude that nimodipine should be given to patients who are neurologically normal after subarachnoid hemorrhage in order to reduce the occurrence of severe neurologic deficits due to cerebral arterial spasm OBJECT Cerebral vasospasm after subarachnoid hemorrhage ( SAH ) continues to be a major source of morbidity in patients despite significant clinical and basic science research . Efforts to prevent vasospasm by removing spasmogens from the subarachnoid space have produced mixed results . The authors hypothesize that lumbar cisternal drainage can remove blood from the basal subarachnoid spaces more effectively than an external ventricular drain ( EVD ) . This non-r and omized , controlled-cohort study was undertaken to evaluate the effectiveness of a lumbar drain in patients with SAH compared with those in whom an EVD or no form of cerebrospinal fluid ( CSF ) drainage was used to prevent the development of clinical vasospasm and its sequelae . METHODS The authors collected data on 266 patients with nontraumatic SAH who were admitted to the University of Utah Health Sciences Center between January 1994 and January 2003 . Of these , 167 met the study entry criteria . The treatment group consisted of 81 patients in whom a lumbar drain had been placed for CSF shunting , whereas the control group was composed of 86 patients who received no form of CSF drainage or who were treated solely with an EVD . Primary outcome measures were as follows : 1 ) clinical ly evident vasospasm ; 2 ) the need for endovascular intervention ; 3 ) vasospasm-induced infa rct ion ; 4 ) disposition at time of discharge ; and 5 ) Glasgow Outcome Scale ( GOS ) score at 1 to 3 months postdischarge . Secondary outcomes included length of stay and the need for CSF shunting . The presence of a lumbar drain conferred a statistically significant protective and beneficial effect across all outcome measures , reducing the incidence of clinical vasospasm from 51 to 17 % , the need for angioplasty from 45 to 17 % , and the occurrence of vasospastic infa rct ion from 27 to 7 % ( all p < or = 0.001 - 0.008 ) . Patients in the treatment group were more likely to be discharged home ( 54 % compared with 25 % , p = 0.002 ) and to have a GOS score of 5 at follow up ( 71 % compared with 35 % , p < 0.001 ) . The mean number of days spent in the intensive care unit and in the hospital overall was also fewer in the treatment group . A similar degree of benefit was found in patients with different Fisher grade s and regardless of whether an EVD was needed on presentation , both by subgroup analysis and multivariate logistic regression modeling . There was no statistical difference between the groups in terms of patients requiring a shunt . Complications with lumbar drains were rare and yielded no permanent sequelae . CONCLUSIONS Shunting of CSF through a lumbar drain after an SAH markedly reduces the risk of clinical ly evident vasospasm and its sequelae , shortens hospital stay , and improves outcome . Its beneficial effects are probably mediated through the removal of spasmogens that exist in the CSF . The results of this study warrant a r and omized clinical trial , which is currently under way AIM We set forth to identify predictors of symptomatic vasospasm in patients with subarachnoid hemorrhage ( SAH ) . MATERIAL AND METHODS We used multivariate logistic regression analysis of the prospect i ve , hospital based , single center register of the Department of Neurosurgery , University of Debrecen , Hungary . Evaluated patients ' characteristics were : sex , age , Hunt-Hess grade on admission , location of aneurysm , thickness of blood clot on initial CT scan ( Fisher grade ) , hypertension . RESULTS Between 1987 and 2004 , 567 SAH cases were registered , 457 were included in this study . Symptomatic vasospasm developed in 22.5 % of the cases . In univariate analysis , Hunt-Hess grade s 2 and 3 and female sex were predictive for symptomatic vasospasm . In multivariate analysis , female sex remained a significant predictor : OR : 1.8 ( 1.005 - 3.2 ) . CONCLUSION Women are at more danger of developing symptomatic vasospasm after subarachnoid hemorrhage BACKGROUND AND PURPOSE The role of type of treatment on cerebral vasospasm occurrence after aneurysmal subarachnoid hemorrhage ( SAH ) has not been studied . Through multivariate analysis we determined the independent prognostic factors of the occurrence of symptomatic vasospasm following aneurysmal SAH in a study cohort of 244 patients undergoing either surgical or endovascular treatment . The prognostic factors of sequelae after aneurysmal SAH were studied as well . METHODS Symptomatic vasospasm was defined as the association of deterioration in a patient 's neurological condition between 3 and 14 days after SAH with no other explanation and an increase in mean transcranial Doppler velocities of > 120 cm/s . The prognostic factors were registered on admission and during the intensive care stay . RESULTS Symptomatic vasospasm occurred in 22.2 % surgical patients compared with 17.2 % endovascular treatment patients ( P=0.37 ) . Multivariate analysis revealed that the probability of occurrence of symptomatic vasospasm decreased with age > 50 years ( relative risk [ RR ] , 0.47 [ 0.25 to 0.88 ] ) and severe World Federation of Neurological Surgeons ( WFNS ) grade measured on admission ( RR , 0.43 [ 0.20 to 0.90 ] ) and increased with hyperglycemia occurring during the intensive care stay ( RR , 1.94 [ 1.04 to 3.63 ] ) . No difference in risk of symptomatic vasospasm could be identified between surgical and endovascular treatment . Symptomatic vasospasm ( OR , 4.73 [ CI , 1 . 77 to 12.6 ] ) as well as WFNS grade of > 2 ( OR , 8.95 [ 3.46 to 23.2 ] ) , treatment complications ( OR , 8.39 [ 3.16 to 22.3 ] ) , and secondary brain insults were associated with an increased risk of 6-month sequelae . CONCLUSIONS Age < 50 years , good neurological grade , and hyperglycemia were all associated with an increased risk of cerebral vasospasm whereas treatment was not . This provides a basis for future clinical prospect i ve r and omized trials comparing both treatments OBJECT Delayed cerebral ischemia is a major cause of morbidity and death following aneurysmal subarachnoid hemorrhage and requires timely intervention for a successful outcome to be achieved . In this study the investigators compared the commonly used Fisher scale with 2 newer radiographic scales for the prediction of vasospasm , delayed infa rct ion , and poor outcome . METHODS This was a single-center , retrospective cohort study involving 271 consecutive patients with a ruptured cerebral aneurysm . Without knowledge of subsequent events , admission CT scans were each assigned scores by using 3 different grading schemes : the Fisher , modified Fisher , and Claassen scales . For each of the scales , the relationship between an increasing score and the risk of later complications was assessed in univariate and multiple logistic regression analyses . RESULTS With the Fisher scale , the risk of complications was relatively high when the score was 3 , but not for other scores . In contrast , using the other scales , there was a more linear relationship between a rising score and the frequency of complications . This was particularly true for the modified Fisher scale , in which each stepwise increase was associated with an escalating risk of vasospasm , delayed infa rct ion , and poor prognosis . Kappa scores measuring interobserver variability among 4 CT readers were also slightly better with the newer scales . CONCLUSIONS Although the modified Fisher and Claassen scales have yet to be prospect ively vali date d , the authors ' findings suggest that the clinical performance of these systems is superior to that of the Fisher scale Background : Cerebral vasospasm is the most common cause of morbidity and mortality after aneurysmal subarachnoid hemorrhage ( SAH ) . This study is design ed to determine whether the incidence of symptomatic vasospasm and the overall clinical outcome differ between patients treated with surgical clipping compared with endovascular obliteration of aneurysms . Methods : In this prospect i ve study , 98 patients with aneurysmal SAH were treated . Seventy-two patients underwent surgery and clipping and 26 had coil embolization . The incidence of symptomatic vasospasm , permanent neurologic deficit due to vasospasm and clinical outcome were analyzed . Patients with better clinical and radiological grade s ( World Federation of Neurological Surgeons grade s I – III and Fisher grade s I – III ) were analyzed separately . Results : Symptomatic vasospasm occurred in 22 % of the patients ; 25 % in the surgical group and 15 % in the endovascular group . Nine percent of the patients in the surgical group and 7 % in the endovascular group suffered ischemic infa rct ion with permanent neurological deficit . These differences did not reach statistical significance ( p = 0.42 ) . For patients with better clinical and radiological grade s , no significant difference was found for the rate of symptomatic vasospasm ; 23 % in the surgical and 12 % in the endovascular group ( p = 0.49 ) . The overall clinical outcome was comparable in both groups , with no difference in the likelihood of a Glasgow Outcome Scale score of 3 or less ( 15 % in the surgical and 16 % in the endovascular group ; p = 0.87 ) . The same results for outcome were obtained for the subgroup of patients with better clinical grade s on admission . Conclusion : Symptomatic vasospasm and ischemic infa rct ion rate seem comparable in both groups , even for patients with better clinical and radiological admission grade s. There is no significant difference in the overall clinical outcome at the long-term follow-up between both groups Objectives To prospect ively evaluate the predictive value of cerebral perfusion – computerized tomography ( CTP ) parameters variation between day0 and day4 after aneurysmal subarachnoid haemorrhage ( aSAH ) . Methods Mean transit time ( MTT ) and cerebral blood flow ( CBF ) values were compared between patients with delayed cerebral ischemia ( DCI+ group ) and patients without DCI ( DCI- group ) for previously published optimal cutoff values and for variations of MTT ( ΔMTT ) and of CBF ( ΔCBF ) values between day0 and day4 . DCI+ was defined as a cerebral infa rct ion on 3-months follow-up MRI . Results Among 47 included patients , 10 suffered DCI+ . Published optimal cutoff values did not predict DCI , either at day0 or at day4 . Conversely , ΔMTT and ΔCBF significantly differed between the DCI+ and DCI- groups , with optimal ΔMTT and ΔCBF values of 0.91 seconds ( 83.9 % sensitivity , 79.5 % specificity , AUC 0.84 ) and -7.6 mL/100 g/min ( 100 % sensitivity , 71.4 % specificity , AUC 0.86 ) , respectively . In multivariate analysis , ΔCBF ( OR = 1.91 , IC95 % 1.13–3.23 per each 20 % decrease of ΔCBF ) and ΔMTT values ( OR = 14.70 , IC95 % 4.85–44.52 per each 20 % increase of ΔMTT ) were independent predictors of DCI . Conclusions Assessment of MTT and CBF value variations between day0 and day4 may serve as an early imaging surrogate for prediction of DCI in aSAH.Key points• CT perfusion values are an imaging surrogate for prediction of DCI.• Early variations ( day0–day4 ) after aneurysmal subarachnoid haemorrhage predicted DCI.• A CBF decrease of 7.6 mL/min/100 g predicted DCI with 100 % sensitivity.• An MTT increase of 0.91 seconds predicted DCI with 83.9 % sensitivity.• DCI risk multiplied by 2 per 20 % ΔCBF decrease and by 15 per 20 % ΔMTT increase Vasospasm following aneurysmal subarachnoid hemorrhage ( SAH ) is correlated with the thickness of blood within the basal cisterns on the initial computerized tomography ( CT ) scan . To identify additional risk factors for symptomatic vasospasm , the authors performed a prospect i ve analysis of 75 consecutively admitted patients who were treated for aneurysmal SAH . Five patients who died before treatment or were comatose postoperatively were excluded from the study . Of the remaining 70 patients , demographic ( age , gender , and race ) and clinical ( hypertension , diabetes , coronary artery disease , smoking , alcohol abuse , illicit drug use , sentinel headache , Fisher grade , Hunt and Hess grade , World Federation of Neurological Surgeons grade , and ruptured aneurysm location ) parameters were evaluated using multivariate logistic regression to determine factors independently associated with cerebral vasospasm . All patients were treated with hypervolemic therapy and administration of nimodipine as prophylaxis for vasospasm . Cerebral vasospasm was suspected in cases that exhibited ( by elevation of transcranial Doppler velocities ) neurological deterioration 3 to 14 days after SAH with no other explanation and was confirmed either by clinical improvement in response to induced hypertension or by cerebral angiography . The mean age of the patients was 50 years . Sixty-three percent of the patients were women , 74 % were white , 64 % were cigarette smokers , and 46 % were hypertensive . Ten percent of the patients suffered from alcohol abuse , 19 % from sentinel bleed , and 49 % had a Fisher Grade 3 SAH . Twenty-nine percent of the patients developed symptomatic vasospasm . Multivariate analysis demonstrated that cigarette smoking ( p = 0.033 ; odds ratio 4.7 , 95 % confidence interval [ CI ] 2.4 - 8.9 ) and Fisher Grade 3 , that is , thick subarachnoid clot ( p = 0.008 ; odds ratio 5.1 , 95 % CI 2 - 13.1 ) , were independent predictors of symptomatic vasospasm . The authors make the novel observation that cigarette smoking increases the risk of symptomatic vasospasm after aneurysmal SAH , independent of Fisher grade Vasospasm is a major cause of morbidity and mortality after aneurysmal subarachnoid hemorrhage ( aSAH ) . Studies have shown a link between single-nucleotide polymorphisms ( SNPs ) in the endothelial nitric oxide synthase ( eNOS ) gene and the incidence of coronary spasm and aneurysms . Alterations in the eNOS T-786 SNP may lead to an increased risk of post-aSAH cerebral vasospasm . In this prospect i ve clinical study , 77 aSAH patients provided genetic material and were followed for the occurrence of vasospasm . In multivariate logistic regression analysis , genotype was the only factor predictive of vasospasm . The odds ratio ( OR ) for symptomatic vasospasm in patients with one T allele was 3.3 ( 95 % confidence interval ( CI ) : 1.1 to 10.0 , P=0.034 ) and 10.9 for TT . Patients with angiographic spasm were 3.6 times more likely to have a T allele ( 95 % CI : 1.3 to 9.6 , P=0.013 ; for TT : OR 12.6 ) . Patients with severe vasospasm requiring endovascular therapy were more likely to have a T allele ( OR 3.5 , 95 % CI : 1.3 to 9.5 , P=0.016 ; for TT : OR 12.0 ) . Patients with the T allele of the eNOS gene are more likely to have severe vasospasm . Presence of this genotype may allow the identification of individuals at high risk for post-aSAH vasospasm and lead to early treatment and improved outcome OBJECTIVES To examine the relationship between regional cerebral oxygen saturation ( rSO2 ) , delayed cerebral ischaemia ( DCI ) , and outcomes after aneurysmal subarachnoid haemorrhage ( aSAH ) . RESEARCH METHODOLOGY Subjects ( n = 163 ) with aSAH , age 21 - 75 years , and Fisher grade > 1 were included in the study . Continuous rSO2 monitoring was performed for 5 - 10 days after injury using near-infrared spectroscopy with sensors over the frontal/temporal cortex . rSO2<50 indicated desaturation . DCI was defined as neurological deterioration due to impaired cerebral blood flow . Three- and 12-month functional outcomes were assessed by the modified Rankin scale ( MRS ) as good ( 0 - 3 ) and poor ( 4 - 6 ) . RESULTS DCI occurred in 57 % of patients ; of these 66 % had rSO2<50 . Overall , 56 % had rSO2<50 on either side , 21 % and 16 % had poor MRS at 3 and 12 months . Subjects with rSO2 < 50 were 3.25 times more likely to have DCI compared to those with rSO2 > 50 ( OR 3.25 , 95%CI 1.58 - 6.69 ) , positive predictive value ( PPV ) = 70 % . Subjects with rSO2 < 50 were 2.7 times more likely to have poor 3-month MRS compared to those with rSO2 > 50 ( OR 2.7 , 95%CI 1.1 - 7.2 ) , PPV = 70 % . CONCLUSIONS These results suggest that NIRS has the potential for detecting DCI after aSAH . This potential needs to be further explored in a larger prospect i ve study OBJECTIVE : Although several recent studies have suggested that the incidence of vasospasm after aneurysmal subarachnoid hemorrhage is lower in patients undergoing aneurysmal coiling as compared with clipping , other studies have had conflicting results . We review ed our experience over 8 years and assessed whether clipping , craniotomy , or coiling affects patient outcomes or the risk for vasospasm . METHODS : We included 515 patients with aneurysmal subarachnoid hemorrhage , identified prospect ively from November 2000 to February 2003 ( 243 patients ) and retrospectively from November 1995 to October 2000 ( 272 patients ) , by using International Classification of Diseases , 9th Revision , codes for subarachnoid hemorrhage . We classified patients as follows : clipping ( 413 patients ) , coiling ( 79 patients ) , and craniotomy ( 436 patients , including all 413 patients who underwent clipping plus 23 who underwent coiling as well as craniotomy for various reasons ) . We studied four outcome measures : total vasospasm , symptomatic vasospasm , poor outcome ( modified Rankin score 3–6 ) , and in-hospital mortality . To assess the risk of total vasospasm and symptomatic vasospasm , we performed multivariate regression analyses adjusting for age , Fisher grade , Hunt and Hess grade , aneurysm location ( anterior versus posterior circulation ) , and aneurysm treatment modality . To assess the risk for poor outcome and in-hospital mortality , we adjusted for all the above variables as well as for total and symptomatic vasospasm . RESULTS : In the clipping group there was 63 % total vasospasm and 28 % symptomatic vasospasm ; in the coiling group there was 54 % total vasospasm and 33 % symptomatic vasospasm ; and in the craniotomy group there was 64 % total vasospasm and 28 % symptomatic vasospasm . In the multivariate analysis , age < 50 years ( P = 0.0099 ) and Fisher Grade 3 ( P < 0.00001 ) predicted total vasospasm , and Fisher Grade 3 ( P < 0.000001 ) and Hunt and Hess Grade IV or V ( P = 0.018 ) predicted symptomatic vasospasm . Predictors of poor outcome were age ≥50 years ( P < 0.0001 ) , Fisher Grade 3 ( P = 0.0072 ) , Hunt and Hess Grade IV or V ( P < 0.00001 ) , symptomatic vasospasm ( P < 0.0001 ) , and coiling ( P = 0.0314 versus clipping and P = 0.045 versus craniotomy ) . Predictors of in-hospital mortality were age ≥ 50 years ( P = 0.0030 ) , Hunt and Hess Grade IV or V ( P = 0.0001 ) , symptomatic vasospasm ( P < 0.00001 ) , and coiling ( P = 0.008 versus clipping and P = 0.0013 versus craniotomy ) . There was no significant difference in total vasospasm or symptomatic vasospasm when patients who underwent clipping or craniotomy were compared with patients who underwent coiling . In patients with Hunt and Hess Grade I to III ( “ good grade ” ) , clipping and craniotomy were associated with better outcome and less in-hospital mortality , but there was no difference in total vasospasm or symptomatic vasospasm versus coiling . In patients with Hunt and Hess Grade IV or V ( “ poor grade ” ) , there was no difference in any outcome measure among the treatment groups . CONCLUSION : In a single-center , retrospective , nonr and omized study , performance of clipping and /or craniotomy had significantly better outcome and lower mortality at discharge than coiling in good- grade patients but had no effect on total vasospasm or symptomatic vasospasm in good- or poor- grade patients BACKGROUND Patients undergoing neurosurgical clipping or endovascular coiling of a ruptured aneurysm may differ in their risk of vasospasm . OBJECTIVE Because clot clearance affects vasospasm , we tested the hypothesis that clot clearance differs in patients depending on method of aneurysm treatment . METHODS Exploratory analysis was performed on 413 patients from CONSCIOUS-1 , a prospect i ve r and omized trial of clazosentan for the prevention of angiographic vasospasm in patients with aneurysmal subarachnoid hemorrhage ( SAH ) . Clot clearance was measured by change in Hijdra score between baseline computed tomography and one performed 24 to 48 hours after aneurysm treatment . Angiographic vasospasm was assessed by the use of catheter angiography 7 to 11 days after SAH , and delayed ischemic neurological deficit ( DIND ) was determined clinical ly . Extended Glasgow Outcome Score ( GOSE ) was assessed 3 months after SAH , and poor outcome was defined as death , vegetative state , or severe disability . Multivariable ordinal and binary logistic regression were used . RESULTS There was no significant difference in the rate of clot clearance between patients undergoing clipping or coiling ( P = .56 ) . Coiling was independently associated with decreased severity of angiographic vasospasm ( odds ratio [ OR ] 0.53 , 95 % confidence interval [ CI ] 0.33 - 0.86 ) , but not with DIND or GOSE . Greater clot clearance decreased the risk of severe angiographic vasospasm ( OR 0.86 , 95 % CI 0.81 - 0.91 ) , whereas higher baseline Hijdra score predicted increased angiographic vasospasm ( OR 1.17 , 95 % CI 1.11 - 1.23 ) and poor GOSE ( OR 1.09 , 95 % CI 1.04 - 1.14 ) . CONCLUSION Aneurysm coiling and increased clot clearance were independently associated with decreased severity of angiographic vasospasm in multivariate analysis , although no differences in clot clearance were seen between coiled and clipped patients |
12,369 | 29,852,054 | There is high- quality evidence that all of the licensed forms of NRT ( gum , transdermal patch , nasal spray , inhalator and sublingual tablets/lozenges ) can help people who make a quit attempt to increase their chances of successfully stopping smoking .
NRTs increase the rate of quitting by 50 % to 60 % , regardless of setting , and further research is very unlikely to change our confidence in the estimate of the effect .
The relative effectiveness of NRT appears to be largely independent of the intensity of additional support provided to the individual .
Provision of more intense levels of support , although beneficial in facilitating the likelihood of quitting , is not essential to the success of NRT .
NRT often causes minor irritation of the site through which it is administered , and in rare cases can cause non-ischaemic chest pain and palpitations | BACKGROUND Nicotine replacement therapy ( NRT ) aims to temporarily replace much of the nicotine from cigarettes to reduce motivation to smoke and nicotine withdrawal symptoms , thus easing the transition from cigarette smoking to complete abstinence .
OBJECTIVES To determine the effectiveness and safety of nicotine replacement therapy ( NRT ) , including gum , transdermal patch , intranasal spray and inhaled and oral preparations , for achieving long-term smoking cessation , compared to placebo or ' no NRT ' interventions .
Adverse events from using NRT were related to the type of product , and include skin irritation from patches and irritation to the inside of the mouth from gum and tablets . | Subjects ( N = 139 ) were assigned to intensive behavioral or to low-contact smoking treatment and to 2-mg nicotine gum or to placebo gum in a 2 X 2 factorial design . The 2-mg gum produced higher abstinence rates than did the placebo . Subjects receiving the low-contact condition plus the 2-mg nicotine gum had excellent abstinence rates at both 26 weeks ( 56 % abstainers ) and 52 weeks ( 50 % abstainers ) . Smokers who scored at the median on a measure of physical dependence to nicotine were more likely to benefit by nicotine gum treatment than subjects who scored either higher or lower , but this relation was nonsignificant . The results of this study are compared with an earlier nonblind trial While sex differences in the nicotine withdrawal ( NW ) symptoms and craving ( NC ) have been extensively described in adult cigarette smokers , few studies have investigated these phenomena in adolescents . We investigated the effect of gender and hormonal contraception ( HC ) on NW and NC during the first 14 days of cessation in adolescent smokers using data from a r and omized , placebo-controlled , double-blind trial of the transdermal nicotine replacement therapy for smoking cessation . Analyses showed similar levels of NW severity in males and females , regardless of HC use . However , significantly higher NC was observed in females compared to males , ( 2.22+/-0.12 vs. 1.65+/-1.14 ; p=0.003 ) . Further , females not using HC reported the highest level of NC ( 2.38+/-0.16 ) followed by females using HC ( 2.08+/-0.25 ) and males ( 1.71+/-0.16 ; p=0.007 ) . The current findings suggest that adolescent females experience similar NW severity to males , but have stronger NC . Further , the use of hormonal contraceptives may impact the severity of craving . Addressing these different symptoms in adolescents may be useful in increasing smoking cessation rates in this special population of smokers BACKGROUND This study was conducted to determine the efficacy of the nicotine patch in smoking cessation when combined with self-help material s , three brief visits , and telephone counseling . METHODS One hundred fifty-nine healthy volunteers who smoked at least one pack of cigarettes per day and desired to quit smoking were enrolled in a double-blind trial with 6-week treatment and 6-month follow-up periods . After review of self-help material s , subjects were r and omly assigned to regimens of nicotine or placebo patches . Subjects wore two patches per day for 4 weeks ( 25 mg of nicotine per 24 hours ) , then one patch per day for 2 weeks . Return visits were at the ends of weeks 4 and 6 . Telephone counseling was given during weeks 1 , 2 , 3 , and 5 . Abstinence at 6 weeks was defined as zero cigarettes smoked for the previous 28 days , verified by exhaled carbon monoxide less than 8 ppm at 4 weeks and 6 weeks . Abstinence at 3 and 6 months was defined as self-report of zero cigarettes since the previous contact , verified by carbon monoxide value at 6 months . RESULTS Abstinence rates at 6 weeks , 3 months , and 6 months were 29.5 % , 21.8 % , and 20.5 % in the active group , and 8.8 % , 3.8 % , and 2.5 % in the placebo group ( P < or = .001 for each comparison ) , respectively . Skin irritation was the main side effect , causing 1.3 % to drop out . CONCLUSION The nicotine patch is efficacious in smoking cessation over a 6-month period , when combined with only self-help material s , three brief visits , and telephone counseling The use of nicotine chewing gum combined with psychological support improves the success rate in stopping smoking . We studied the safety and efficacy of a transdermal nicotine patch in stopping smoking . We conducted a double-blind r and omized study comparing the effect of a 16-hour nicotine patch ( 15 + /- 3.5 mg of nicotine in 16 hours ) with those of a placebo patch . Of the 289 smokers ( 207 women and 82 men ) enrolled in the study , 145 were treated with nicotine patches and 144 with placebo patches for 16 weeks . The rates of sustained abstinence were significantly better with active treatment than with the placebo : 53 , 41 , 24 and 17 % of those in the nicotine-patch group were abstinent after 6 , 12 , 26 , and 52 weeks , respectively , as compared with 17 , 10 , 5 and 4 % of those in the placebo-patch group ( p less than 0.0001 ) . Only two subjects with the nicotine patch and one with the placebo patch withdrew from the study because of side effects . The nicotine skin patch proved to be safe and effective , as demonstrated by a higher rate of abstinence than with the placebo AIMS Of six established nicotine replacement therapy ( NRT ) formulations , only the gum and patch have been tested without specialist clinic support in placebo-controlled trials . We aim ed to broaden the evidence base by examining if the nicotine nasal spray ( NNS ) could be effective with only brief support in general practice . DESIGN R and omized placebo-controlled trial . SETTING Twenty-seven English general practice s. PARTICIPANTS A total of 761 heavy smokers received brief support and 12 weeks of treatment with NNS ( 506 ) or placebo ( 255 ) . MEASUREMENTS The primary outcome was biochemically verified complete abstinence from smoking throughout weeks 3 - 12 . FINDINGS NNS compared with placebo more than doubled the number who successfully stopped smoking [ 15.4 % versus 6.7 % , odds ratio ( OR ) = 2.6 , 95 % confidence interval ( CI ) = 1.5 - 4.4 ] . Many participants reported minor irritant adverse symptoms . NNS was particularly effective among those who were more highly dependent on nicotine ( OR = 6.17 , 95 % CI = 2.13 - 17.9 ) . Of those who failed to stop during the first week ( 417 , 54.8 % ) , only one ( 0.2 % ) achieved later success . CONCLUSIONS NNS is effective when given in primary care . The benefit was lower than in a specialist clinic but similar to that with the nicotine patch in primary care . Unlike most other NRT formulations , bupropion or varenicline , NNS was especially helpful for more dependent smokers . Continuing treatment of those initially failing was not beneficial . An initial 1-week prescription to those more dependent on nicotine is likely to be the most cost-effective NNS treatment protocol . These results should offer support to the effectiveness of the other NRT formulations untested in this setting In a r and omized smoking cessation study 211 , 203 and 82 persons were supported with nicotine , silver acetate and ordinary chewing gum , respectively . After 26 weeks there was no overall difference in number of abstainers between treatments . Participants were divided into subsets with low and high weighted packyears consumption ( WPY ) which modifies tobacco consumption by nicotine content . Abstainer rates in the total population controlled for treatment decreased with increasing WPY ( P<0.005 ) . In participants with low WPY abstainer rate was higher in the silver acetate group compared to the nicotine ( P<0.0005 ) and ordinary ( P<0.05 ) chewing gum groups . Nicotine chewing gum was more effective than silver acetate ( P<0.05 ) and ordinary ( P<0.05 ) chewing gum in smokers with high WPY . Ratings on some inconveniences experienced during earlier attempts to quit smoking influenced the ability to break the habit but had no influence on chewing gum effects . This study indicated that through consideration of smoking history it should be possible to individualize pharmacological support to smokers wanting to quit , with silver acetate chewing gum most effective for smokers with a low WPY and nicotine chewing gum most effective for smokers with a high WPY BACKGROUND Substantial concerns have been raised about the neuropsychiatric safety of the smoking cessation medications varenicline and bupropion . Their efficacy relative to nicotine patch largely relies on indirect comparisons , and there is limited information on safety and efficacy in smokers with psychiatric disorders . We compared the relative neuropsychiatric safety risk and efficacy of varenicline and bupropion with nicotine patch and placebo in smokers with and without psychiatric disorders . METHODS We did a r and omised , double-blind , triple-dummy , placebo-controlled and active-controlled ( nicotine patch ; 21 mg per day with taper ) trial of varenicline ( 1 mg twice a day ) and bupropion ( 150 mg twice a day ) for 12 weeks with 12-week non-treatment follow-up done at 140 centres ( clinical trial centres , academic centres , and outpatient clinics ) in 16 countries between Nov 30 , 2011 , and Jan 13 , 2015 . Participants were motivated-to-quit smokers with and without psychiatric disorders who received brief cessation counselling at each visit . R and omisation was computer generated ( 1:1:1:1 ratio ) . Participants , investigators , and research personnel were masked to treatment assignments . The primary endpoint was the incidence of a composite measure of moderate and severe neuropsychiatric adverse events . The main efficacy endpoint was biochemically confirmed continuous abstinence for weeks 9 - 12 . All participants r and omly assigned were included in the efficacy analysis and those who received treatment were included in the safety analysis . The trial is registered at Clinical Trials.gov ( number NCT01456936 ) and is now closed . FINDINGS 8144 participants were r and omly assigned , 4116 to the psychiatric cohort ( 4074 included in the safety analysis ) and 4028 to the non-psychiatric cohort ( 3984 included in the safety analysis ) . In the non-psychiatric cohort , 13 ( 1·3 % ) of 990 participants reported moderate and severe neuropsychiatric adverse events in the varenicline group , 22 ( 2·2 % ) of 989 in the bupropion group , 25 ( 2·5 % ) of 1006 in the nicotine patch group , and 24 ( 2·4 % ) of 999 in the placebo group . The varenicline-placebo and bupropion-placebo risk differences ( RDs ) for moderate and severe neuropsychiatric adverse events were -1·28 ( 95 % CI -2·40 to -0·15 ) and -0·08 ( -1·37 to 1·21 ) , respectively ; the RDs for comparisons with nicotine patch were -1·07 ( -2·21 to 0·08 ) and 0·13 ( -1·19 to 1·45 ) , respectively . In the psychiatric cohort , moderate and severe neuropsychiatric adverse events were reported in 67 ( 6·5 % ) of 1026 participants in the varenicline group , 68 ( 6·7 % ) of 1017 in the bupropion group , 53 ( 5·2 % ) of 1016 in the nicotine patch group , and 50 ( 4·9 % ) of 1015 in the placebo group . The varenicline-placebo and bupropion-placebo RDs were 1·59 ( 95 % CI -0·42 to 3·59 ) and 1·78 ( -0·24 to 3·81 ) , respectively ; the RDs versus nicotine patch were 1·22 ( -0·81 to 3·25 ) and 1·42 ( -0·63 to 3·46 ) , respectively . Varenicline-treated participants achieved higher abstinence rates than those on placebo ( odds ratio [ OR ] 3·61 , 95 % CI 3·07 to 4·24 ) , nicotine patch ( 1·68 , 1·46 to 1·93 ) , and bupropion ( 1·75 , 1·52 to 2·01 ) . Those on bupropion and nicotine patch achieved higher abstinence rates than those on placebo ( OR 2·07 [ 1·75 to 2·45 ] and 2·15 [ 1·82 to 2·54 ] , respectively ) . Across cohorts , the most frequent adverse events by treatment group were nausea ( varenicline , 25 % [ 511 of 2016 participants ] ) , insomnia ( bupropion , 12 % [ 245 of 2006 participants ] ) , abnormal dreams ( nicotine patch , 12 % [ 251 of 2022 participants ] ) , and headache ( placebo , 10 % [ 199 of 2014 participants ] ) . Efficacy treatment comparison did not differ by cohort . INTERPRETATION The study did not show a significant increase in neuropsychiatric adverse events attributable to varenicline or bupropion relative to nicotine patch or placebo . Varenicline was more effective than placebo , nicotine patch , and bupropion in helping smokers achieve abstinence , whereas bupropion and nicotine patch were more effective than placebo . FUNDING Pfizer and GlaxoSmithKline Sixty subjects were run in a study comparing the use of nicotine gum with placebo gum during cessation from smoking . Subjects were given clinic support and chewed the gum ad libitum . A survival analysis showed the two groups differed significantly in successful abstinence over time ( p less than .03 ) . Differences between groups appeared early ( within weeks ) and , at six months , a 28 % superiority of nicotine over placebo gum was demonstrated with mean success rates of 48 % and 20 % , respectively . Between six months and one year , relapse in the nicotine group accounted for the 30 % vs. 20 % success rates for nicotine and placebo observed at one year . In a pilot study ( " dispensary " ) testing the efficacy of the two gums when intervention was minimal , subjects in both groups resumed smoking within the first two weeks . The enhanced short-term success rates with nicotine gum in the clinic study are attributed to an effective interaction between use of the active preparation and clinic support . Long-term cessation may require extended maintenance procedures and /or an identification of optimal gum use A non-combustible nicotine inhaler , administered orally , has been developed for treatment of smokers . The inhaler allows weaning from nicotine while maintaining partial reinforcement of the ritual/sensory phenomena of smoking . Subjects were r and omly assigned to active ( n = 112 ) and placebo ( n = 111 ) groups . Some behavioral intervention occurred as a function of participation . Strict abstinence ( primary outcome criterion ) was defined by CO < or = 8 ppm with no slips allowed at any time and cotinine values < or = 14 at 1 year . Survival analysis showed active inhaler was superior to placebo ( p < 0.01 ) . Active vs. placebo success rates were : 63 % vs. 47 % ( day 3 ) , 46 % vs. 28 % ( week 1 ) , 36 % vs. 19 % ( week 2 ) , 33 % vs. 16 % ( week 3 ) , 29 % vs. 14 % ( week 6 ) , 24 % vs. 10 % ( 3 months ) , 17 % vs. 9 % ( 6 months ) and 13 % vs. 8 % ( 1 year ) . chi 2 analyses were significant through 3 months but not at 6 months ( p < 0.08 ) or 1 year . Craving was relieved with active inhalers at day 3 and week 1 . Subjects averaged six inhalers/day . Cotinine levels were 57 - 61 % of smoking levels . Common side effects included throat/mouth irritation and coughing . Failure was predicted by early slips . The inhaler is clearly useful for short-term smoking cessation with potential for long-term efficacy . Extended access to the inhaler and relapse prevention training could improve success rates . Another promising approach would be to combine the inhaler with a nicotine patch IMPORTANCE The US Food and Drug Administration adopted labeling for nicotine patches to allow use beyond the st and ard 8 weeks . This decision was based in part on data showing increased efficacy for 24 weeks of treatment . Few studies have examined whether the use of nicotine patches beyond 24 weeks provides additional therapeutic benefit . OBJECTIVE To compare 8 ( st and ard ) , 24 ( extended ) , and 52 ( maintenance ) weeks of nicotine patch treatment for promoting tobacco abstinence . DESIGN , SETTING , AND PARTICIPANTS We recruited 525 treatment-seeking smokers for a r and omized clinical trial conducted from June 22 , 2009 , through April 15 , 2014 , through 2 universities . INTERVENTIONS Smokers received 12 smoking cessation behavioral counseling sessions and were r and omized to 8 , 24 , or 52 weeks of nicotine patch treatment . MAIN OUTCOMES AND MEASURES The primary outcome was 7-day point prevalence abstinence , confirmed with breath levels of carbon monoxide at 6 and 12 months ( intention to treat ) . RESULTS At 24 weeks , 21.7 % of participants in the st and ard treatment arm were abstinent , compared with 27.2 % of participants in the extended and maintenance treatment arms ( χ(2)(1 ) = 1.98 ; P = .17 ) . In a multivariate model controlled for covariates , participants in the extended and maintenance treatment arms reported significantly greater abstinence rates at 24 weeks compared with participants in the st and ard treatment arm ( odds ratio [ OR ] , 1.70 [ 95 % CI , 1.03 - 2.81 ] ; P = .04 ) , had a longer duration of abstinence until relapse ( β = 21.30 [ 95 % CI , 10.30 - 32.25 ] ; P < .001 ) , reported smoking fewer cigarettes per day if not abstinent ( mean [ SD ] , 5.8 [ 5.3 ] vs 6.4 [ 5.1 ] cigarettes per day ; β = 0.43 [ 95 % CI , 0.06 - 0.82 ] ; P = .02 ) , and reported more abstinent days ( mean [ SD ] , 80.5 [ 38.1 ] vs 68.2 [ 43.7 ] days ; OR , 1.55 [ 95 % CI , 1.06 - 2.26 ] ; P = .02 ) . At 52 weeks , participants in the maintenance treatment arm did not report significantly greater abstinence rates compared with participants in the st and ard and extended treatment arms ( 20.3 % vs 23.8 % ; OR , 1.17 [ 95 % CI , 0.69 - 1.98 ] ; P = .57 ) . Similarly , we found no difference in week 52 abstinence rates between participants in the extended and st and ard treatment arms ( 26.0 % vs 21.7 % ; OR , 1.33 [ 95 % CI , 0.72 - 2.45 ] ; P = .36 ) . Treatment duration was not associated with any adverse effects or adherence to the counseling regimen , but participants in the maintenance treatment arm reported lower adherence to the nicotine patch regimen compared with those in the st and ard and extended treatment arms ( mean [ SD ] , 3.94 [ 2.5 ] , 4.61 [ 2.0 ] , and 4.7 [ 2.4 ] patches/wk , respectively ; F2,522 = 6.03 ; P = .003 ) . CONCLUSIONS AND RELEVANCE The findings support the safety of long-term use of nicotine patch treatment , although they do not support efficacy beyond 24 weeks of treatment in a broad group of smokers . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01047527 Background : Nicotine replacement therapy ( NRT ) helps smokers quit smoking , but trials indicate that there is no evidence that it is effective during pregnancy . As metabolism increases during pregnancy , NRT may deliver insufficient nicotine to alleviate withdrawal symptoms . There is mixed evidence as to what levels of cotinine are reached from nicotine exposure during pregnancy while using NRT compared with smoking . Methods : We analyzed data on 33 pregnant participants from the NRT arm of a r and omized control trial who had stopped smoking and were still using 15mg/16hr nicotine patches 1 month after quitting . Salivary cotinine levels when smoking at baseline were compared with levels on NRT at 1 month using the Wilcoxon test . Results : Cotinine levels were a median of 98.5ng/ml while smoking and 62.8ng/ml while using NRT and remaining abstinent ( p = .045 ) . Participants with the highest cotinine measurements when smoking also tended to have the steepest reduction in cotinine levels while using NRT . This was most noticeable among participants with baseline cotinine levels more than 150ng/ml ( n = 9 ) who had a greater reduction in median cotinine levels ( median difference −134.8ng /ml [ 95 % CI = −144.5 to −125.9 ] ) than those with a baseline cotinine level under 150ng/ml ( n = 24 ; median difference −27.9ng/ml [ 95 % CI = −49.35 to −1.75 ] ) . Conclusions : In a pragmatic trial that replicated clinical practice , cotinine levels generated using NRT during pregnancy were lower than levels achieved from smoking . Although the sample size of this study was small , our findings are significant and are consistent with the hypothesis that NRT patches deliver an inadequate dose of nicotine to aid smoking cessation during pregnancy BACKGROUND Smoking is considered as an addiction to nicotine for most subjects consuming 10 cigarettes or more per day . Hence , nicotine replacement therapy by way of gum , patch , or spray has been advocated . The rationale of this study is to evaluate the possible beneficial effects of adding nicotine gum to the routine of subjects using the nicotine patch . The effect of the nicotine patch against the placebo , both groups receiving placebo nicotine gum , has also been assessed . METHODS Healthy subjects ( 374 ) were r and omized at their work- setting in a 1-year double-blind placebo-controlled trial : 149 subjects to active nicotine patch + active gum ( group 1 ) , 150 to active nicotine patch + placebo gum ( group 2 ) , and 75 to placebo patch + gum ( group 3 ) . Treatment duration was 12 weeks with a 16-hr transdermal patch of 15 mg , followed by a 6 + 6-weeks weaning period on respectively 10 and 5 mg patches . Gum use was not restricted during the first 6 months , with recommendations to use at least four pieces a day . A strict definition of smoking abstinence was used in this study , which did not allow smoking any cigarette after Week 1 . Nonsmoking status at each visit , as reported by the subjects , was verified by CO below 10 ppm in expired air . RESULTS Abstinence rates in group 1 against group 2 were 34.2 and 22.7 % ( P = 0.027 ) at 12 weeks , 27.5 and 15.3 % ( P = 0.010 ) at 24 weeks , and 18.1 and 12.7 % ( P = 0.191 ) at 52 weeks . In group 3 , abstinence rates were 17.3 , 14.7 , and 13.3 % respectively at 12 , 24 , and 52 weeks . Using logistic regression with adjustment for six baseline covariates , odds ratios for abstinence ( with 95 % CI ) were computed . For group 1/group 2 , OR at 12 , 24 , and 52 weeks were 1.72 ( 1.03 - 2.94 ) ( P = 0.039 ) , 2.04 ( 1.14 - 3.57 ) ( P = 0.018 ) , and 1.47 ( 0.76 - 2.76 ) ( P = 0.125 ) . No significant differences in OR were observed when comparing groups 2 and 3 . Time to relapse is significantly longer in group 1 as compared to that of group 2 ( P = 0.041 ) , whereas no significant differences between groups 2 and 3 were observed . No significant differences between the three groups in systemic and local adverse drug events were observed . CONCLUSION Adding active gum use to active patch use in subjects smoking 10 cigarettes or more a day increased abstinence rates , which are statistically significant up to 24 weeks BACKGROUND To determine the effectiveness of a 16-hour transdermal nicotine patch in assisting smokers to stop smoking , when used in a primary medical practice model . METHODS A single-site , r and omized , double-blind , out-patient , parallel-group , placebo-controlled trial consisting of 220 regular , otherwise healthy cigarette smokers . Patients participated in a 12-week patch treatment phase plus a 6-week tapering phase . A st and ard medical office model of physician intervention , such as could easily be employed by any primary care physician , without need for any special psychological services , training , or skills , was the behavioral intervention . RESULTS Sustained abstinence , determined at each visit by absolutely no cigarette use , carbon monoxide level of 9 ppm or less , and serum cotinine level of 15 ng/mL or less ( after week 18 ) , was significantly greater for those patients receiving the active nicotine patch than for those receiving the placebo patch : the percent of patients not smoking at 6 , 12 , 18 , 26 , and 52 weeks was 61 % vs 35 % , 45 % vs 26 % , 41 % vs 16 % , 34 % vs 12 % , and 25 % vs 9 % , respectively ( P < .001 ) . This 16-hour nicotine patch produced no systemic side effects and minimal skin irritation . CONCLUSIONS Nicotine replacement therapy via a 16-hour transdermal nicotine patch provided safe and effective treatment for tobacco-dependent patients . One-year sustained nonsmoking rates were nearly three times higher in the active than in the placebo condition , when the patch was used in an easily applicable st and ard medical practice setting , without the need for psychological interventions . This outcome was as good as or better than results achieved by nicotine patches using behavior modification or group counseling Background : Guidelines recommend that smoking cessation interventions are offered in all clinical setting s to all smokers willing to make a quit attempt . Since the effectiveness of routine provision of behavioural counselling and nicotine replacement therapy ( NRT ) to smokers admitted to hospital has not been established , a r and omised controlled trial of these interventions given together compared with counselling alone or minimal intervention was performed in hospital in patients . Methods : Medical and surgical in patients who were current smokers at the time of admission were r and omised to receive either usual care ( no additional advice at admission ) , counselling alone ( 20 minute intervention with written material s ) , or NRT plus counselling ( counselling intervention with a 6 week course of NRT ) . Continuous and point prevalence abstinence from smoking ( vali date d by exhaled carbon monoxide < 10 ppm ) was measured at discharge from hospital and at 3 and 12 months , and self-reported reduction in cigarette consumption in smokers was assessed at 3 and 12 months . Results : 274 inpatient smokers were enrolled . Abstinence was higher in the NRT plus counselling group ( n=91 ) than in the counselling alone ( n=91 ) or usual care ( n=92 ) groups . The difference between the groups was significant for vali date d point prevalence abstinence at discharge ( 55 % , 43 % , 37 % respectively , p=0.045 ) and at 12 months ( 17 % , 6 % , 8 % , p=0.03 ) . The respective differences in continuous vali date d abstinence at 12 months were 11 % , 4 % , 8 % ( p=0.25 ) . There was no significant difference between counselling alone and usual care , or in reduction in cigarette consumption between the treatment groups . Conclusions : NRT given with brief counselling to hospital in patients is an effective routine smoking cessation intervention Smokeless tobacco ( ST ) is associated with adverse health consequences yet treatment re sources for ST are not widely available . Cost-effective behavioral interventions incorporating self-help material s and counseling calls have been demonstrated to reduce ST use rates and can be easily disseminated , but the feasibility and effectiveness of incorporating pharmacotherapy into this approach have not been evaluated . We conducted a clinical pilot study r and omizing 60 patients to 12 weeks of the 4-mg nicotine lozenge or placebo delivered through the mail . All subjects received an assisted self-help intervention ( ASH ) with telephone support . At the end of the medication phase , lozenges were being used by 63 % of subjects in the 4-mg nicotine lozenge group and 43 % in placebo . The nicotine lozenge decreased composite withdrawal symptoms and adverse events were minimal . No significant differences were observed in abstinence rates between the two groups at 3 or 6 months . We conclude that the mailing of nicotine lozenges to ST users is a feasible and safe strategy the efficacy of which needs to be evaluated Medication noncompliance with smoking cessation pharmacotherapies is a significant problem in both research and clinical setting s. This r and omized , controlled , single-blind study compared three single-session psychological interventions to increase use of nicotine gum during a 15-day treatment period . A total of 97 adult smokers were r and omized to receive st and ard treatment ( ST , n = 31 ) , brief feedback ( BF , n = 32 ) plus ST , or contingency management ( CM ; i.e. , payment for chewing at least 12 pieces/day on 10 of 15 intervention days , n = 34 ) plus ST and BF . Only the CM condition led to significantly greater average daily gum use ( pieces/day : ST , 6.17 ; BF , 7.81 ; CM , 10.17 [ p values < .05 ] ) and higher rates of compliance ( ST , 13.6 % ; BF , 25.2 % ; CM , 65.6 % [ p values < .001 ] ) . No differences were observed in smoking abstinence , nicotine withdrawal , or urinary cotinine as a function of treatment . Implication s of the present findings are discussed , including application to clinical trials and extension to real-world use of nicotine gum Purpose . This study describes the design , recruitment , and baseline data of the first smoking-cessation clinical trial for African-American light smokers , Kick It at Swope II ( KIS-II ) . Design . KIS-II was a r and omized trial testing the efficacy of nicotine gum ( vs. placebo gum ) in combination with counseling ( motivational interviewing or health education ) . Setting . This study was conducted at an urban community-based clinic serving predominantly lower-income African-Americans . Subjects . African-Americans who smoked 1 to 10 cigarettes per day were eligible . Of 1933 individuals screened , 1012 ( 52 % ) were eligible and 755 ( 75 % ) were enrolled in the study . Measures . Baseline assessment included smoking history and psychometric measures . Analysis . The majority of participants were women ( 67 % ) with a mean age of 45.1 years ( SD = 10.7 ) . Participants smoked on average 7.6 cigarettes ( SD = 3.21 ) per day , had a mean exhaled carbon monoxide level of 13.9 ppm ( SD = 8.9 ) and a mean serum cotinine level of 244.2 ng/mL ( SD = 154.4 ) , and reported high levels of motivation and confidence to quit smoking . Conclusion . African-American light smokers were motivated to stop smoking and to enroll in a smoking-cessation program . Characteristics of our sample suggest African-American light smokers are an appropriate group for inclusion in smoking-cessation interventions Objective To assess the impact of instructional guidance in the regular use of use nicotine nasal spray ( NNS ) on the true use of NNS during the first three weeks of smoking cessation for heavy smokers who are willing to quit . Methods This r and omized , open , controlled trial included 50 patients who were heavy smokers , were willing to quit , and attending an academic outpatient clinic in Western Switzerl and . Patients were r and omised to instruction on NNS use as " ad libitum " ( administration whenever cravings appear ; control group ) or to use NNS when craving appears and at least every hour when awake ( intervention group ) . Intakes were monitored using an electronic device fixed in the spray unit ( MDILog ™ ) during the first three weeks of use . Self reported abstinence from smoking at six months was confirmed by expired-air carbon monoxide . Using intention-to-treat analysis , r and om-effect GLS regression was used to calculate the mean difference of daily doses between groups controlling for lack of independence between measures from the same individual . Results One patient was lost to follow-up . At baseline r and omization , the group receiving instruction to use NNS hourly included more women , patients with previous desires to quit , and patients with more psychiatric comorbidities and less somatic complaints compared to the group instructed to use NNS with cravings ( group imbalance ) . Both groups self-administered more than the daily recommended dosage of 8 uses . Mean daily usage was 13.6 dose/day and 11.1 dose/day for the group instructed to use NNS hourly and with cravings , respectively . Adjusting for baseline imbalance , the increased daily doses in the intervention group ( hourly use ) remained nonsignificant compared to ad libitum use ( -0.5 dose/day ; CI 95 % -6.2 ; 5.3 , from day 1 to day 7 ; and 2.3 dose/day ; CI 95 % -5.4 ; 10.0 , from day 8 to day 21 ) . Instructing patients to use the NNS daily had no effect on smoking cessation at six months ( RR = 0.69 ; CI 95 % 0.34 ; 1.39 ) . Conclusion Heavy smokers willing to quit use NNS frequently , regardless of the instructions given . Recommending the use of NNS only when craving appears for heavy smokers willing to quit seems acceptable compared to prescribing hourly administration . Trial registration - Clinical Trials.gov : IMPORTANCE The efficacy of nicotine replacement therapy ( NRT ) is well demonstrated in clinical trials in which NRT is accompanied by behavioral support . Epidemiologic data , however , indicate that people using NRT are no more likely to successfully quit smoking than those who do not use NRT . OBJECTIVE To evaluate the effect of mailing nicotine patches to smokers without behavioral support on quit success rates . DESIGN , SETTING , AND PARTICIPANTS A single-blinded , 2-group r and omized clinical trial of adult smokers recruited across Canada by r and om-digit dialing of home and cell telephone numbers from June 4 , 2012 , through June 26 , 2014 . Follow-up was completed on January 5 , 2015 , and data were analyzed from May 24 , 2015 , through July 6 , 2015 . A total of 2093 individuals who smoked more than 10 cigarettes per day were interviewed at baseline and asked if they would be hypothetically interested in receiving nicotine patches by mail to quit smoking . Those who were interested and deemed eligible to participate ( no contraindications to NRT ) were r and omized to the experimental group to be mailed a 5-week supply of nicotine patches or to a control group . Telephone follow-ups were conducted at 8 weeks and 6 months . INTERVENTIONS Participants in the experimental group were sent a 5-week course of nicotine patches by expedited postal mail ( 3 weeks of step 1 [ 21 mg of nicotine ] , 1 week of step 2 [ 14 mg of nicotine ] , 1 week of step 3 [ 7 mg of nicotine ] , no behavioral support provided ) . Participants r and omized to the control group were not offered the nicotine patches or any other intervention . MAIN OUTCOMES AND MEASURES The primary outcome was 30-day smoking abstinence at 6 months . RESULTS Of the 2093 participants who were interviewed as part of the baseline survey ( 76.5 % response rate ) , 1000 were found eligible for the trial and r and omized to a group . Analyses were conducted on 500 participants in the experimental group ( mean [ SD ] age , 48.0 [ 12.8 ] years ; 255 female [ 51.0 % ] ) and 499 in the control group ( mean [ SD ] age , 49.7 [ 12.7 ] years ; 256 female [ 51.3 % ] ) . Self-reported abstinence rates were significantly higher among participants who were sent nicotine patches compared with the control group ( 30-day abstinence : 38 [ 7.6 % ] of 500 vs 15 [ 3.0 % ] of 499 ; odds ratio , 2.65 ; 95 % CI , 1.44 - 4.89 ; P = .002 ) . Usable saliva sample s were returned by only 50.9 % of the participants . Biochemically vali date d abstinence at 6 months was found in 14 ( 2.8 % ) of 500 participants in the experimental group vs 5 ( 1.0 % ) of 499 in the control group ( odds ratio , 2.85 ; 95 % CI , 1.02 - 7.96 ; P = .046 ) . CONCLUSIONS AND RELEVANCE The trial provides evidence of the effectiveness of mailed nicotine patches without behavioral support to promote tobacco cessation . The strength of these findings is tempered by the lack of biochemical validation for all participants . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01429129 Background Web-based smoking cessation interventions can deliver evidence -based treatments to a wide swath of the population , but effectiveness is often limited by insufficient adherence to proven treatment components . This study evaluated the impact of a social network ( SN ) intervention and free nicotine replacement therapy ( NRT ) on adherence to evidence -based components of smoking cessation treatment in the context of a Web-based intervention . Methods A sample of adult U.S. smokers ( N = 5290 ) was recruited via BecomeAnEX.org , a free smoking cessation Web site . Smokers were r and omized to one of four arms : ( 1 ) an interactive , evidence -based smoking cessation Web site ( WEB ) alone ; ( 2 ) WEB in conjunction with an SN intervention design ed to integrate participants into the online community ( WEB+SN ) ; ( 3 ) WEB plus free NRT ( WEB+NRT ) ; and ( 4 ) the combination of all treatments ( WEB+SN+NRT ) . Adherence outcomes assessed at 3-month follow-up were as follows : Web site utilization metrics , use of skills training components , intratreatment social support , and pharmacotherapy use . Results WEB+SN+NRT outperformed all others on Web site utilization metrics , use of practical counseling tools , intratreatment social support , and NRT use . It was the only intervention to promote the sending of private messages and the viewing of community pages over WEB alone . Both social network arms outperformed WEB on most metrics of online community engagement . Both NRT arms showed higher medication use compared to WEB alone . Conclusions This study demonstrated the effectiveness of two approaches for improving adherence to evidence -based components of smoking cessation treatment . Integrated approaches to medication provision and social network engagement can enhance adherence to components known to improve cessation . Implication s This study demonstrated that an integrated approach to medication provision and social network integration , when delivered through an online program , can enhance adherence across all three recommended components of an evidence -based smoking cessation program ( skills training , social support , and pharmacotherapy use ) . Nicotine replacement therapy-when provided as part of an integrated program-increases adherence to other program elements , which in turn augment its own therapeutic effects . An explicit focus on approaches to improve treatment adherence is an important first step to identifying leverage points for optimizing intervention effectiveness Background In high-income countries , quitting cigarette smoking is associated with weight gain , which can reduce motivation to abstain . Whether smoking cessation is associated with weight gain in a low-income country context has never been investigated . We aim ed to determine the post-cessation changes in body mass index ( BMI ) and its predictors among smokers who received a smoking cessation intervention in a low-income country setting . Methods We performed post hoc analyses of data from 269 smokers who participated in a two-group , parallel-arm , double-blind , placebo-controlled r and omized trial of combined nicotine replacement therapy ( NRT ) and behavioral counseling in primary care clinics in Aleppo , Syria . We used generalized estimating equation modeling to identify predictors of changes in BMI at 6 weeks and 6- and 12-month follow-ups after quit date . Results The mean pre-cessation BMI of the sample was 27.9kg/m2 ( SD = 5.2 ) . Over 12 months of follow-up , BMI of smoking abstainers averaged 1.8 BMI units ( approximately 4.8 kg ) greater than non-abstainers ( p = .012 ) . Throughout the study , greater BMI was associated with being female ( p = .048 ) , reporting smoking to control weight ( p < .001 ) and having previously failed to quit due to weight gain ( p = .036 ) . Conclusion Similar to findings from high-income countries , smoking cessation in Syria is associated with weight gain , particularly among women and those who have weight concerns prior to quitting . This group of smokers may benefit from tailored cessation interventions with integrated body weight management elements that take into consideration the prevailing local and cultural influences on diet and levels of physical activity . Implication s This study provides the first evidence regarding post-cessation changes in BMI among smokers who attempt to quit in a low-income country setting . Our findings advance knowledge regarding post-cessation weight gain and offers insight for research ers and clinicians to identify smokers at higher risk of post-cessation weight gain . This information will help in delivering interventions that take into account the prevailing cultural influence on diet and physical activity and will ultimately help in design ing future tailored cessation programs in Syria and other low-income countries with similar cultural background and level of development Background Large-scale public health initiatives providing free nicotine replacement therapy have been shown to increase smoking cessation rates ; however , their effectiveness among the highly prevalent population of smokers with depression and anxiety disorders has not been explored . The aim of this study was to investigate the influence of lifetime history of depression or anxiety on smoking cessation success following the free distribution of nicotine patches . Method In the context of a r and omised controlled trial , a secondary analysis was conducted on 1000 adult regular smokers r and omised to be mailed a 5-week supply of nicotine patches or to a no intervention control group . Participants were divided into subgroups based on the presence of self-reported lifetime diagnosis of depression and anxiety . Results Irrespective of self-reported lifetime history of depression or anxiety , odds of self-reported cessation at 6 months were significantly greater among groups receiving nicotine patches compared to no intervention control ( no history of depression or anxiety : OR 2.20 ; 95 % CI 1.05 to 4.63 ; history of depression or anxiety present : OR 3.90 ; 95 % CI 1.28 to 11.88 ) . Among nicotine patch recipients only , quit outcomes did not differ between those with and without self-reported lifetime depression or anxiety in models unadjusted and adjusted for differences in demographic and smoking characteristics . Conclusions The mass distribution of free nicotine patches ( without behavioural support ) is effective among smokers with or without lifetime history of depression or anxiety alike , providing further support for the adoption of similar initiatives as a means of promoting tobacco cessation on a population level . Trial registration number NCT01429129 , Post- results BACKGROUND Cessation rates in smokers attending special clinics or their General Practitioners can be increased by transdermal nicotine ( TNS ) . This study assesses the efficacy of TNS as an adjunct to advice and support in helping patients attending hospital with smoking-related diseases to stop smoking . METHODS In a double-blind , placebo-controlled , r and omized manner , 234 in patients and out patients with smoking-related respiratory or cardiovascular disease , aged 18 - 75 years , who were willing to try to stop smoking , were advised by their hospital doctor to stop smoking . This was reinforced by repeated advice and encouragement from the Smoking Cessation Counsellor initially and at 2 , 4 , 8 and 12 weeks , supplemented by a 24 h patch in adjusted doses over that period . Those not smoking at 12 weeks were followed up at 26 and 52 weeks . Self-reported complete abstinence from 12 to 52 weeks was vali date d by expired air carbon monoxide measurement at 12 , 26 and 52 weeks . RESULTS Twenty-four ( 21 % ) of 115 TNS patients were verified as non-smokers at 12 , 26 and 52 weeks and cl aim ed continued abstinence , compared with 17 ( 14 % ) of 119 in the placebo ( P ) group ( P = 0 center dot 15 ) -5 % confidence limits for odds ratio of abstinence on TNS compared to P : 0 center dot 83 , 3 center dot 37 . Cessation was related to increasing age ( P = 0 center dot 02 ) and lower Fagerstrom score ( P = 0 center dot 05 ) . Minor skin reactions were more frequent in the TNS group ( 47 % TNS ; 34 % P ) , as was nausea ( 12 % TNS ; 3 % P ) . Severe skin reactions were rare ( 5 % TNS ; 4 % P ) . CONCLUSION The suggestion that TNS produces an increase of 50 % in relative terms ( 7 % absolute increase ) in smoking cessation over placebo in this population of hospital patients is sufficiently strong to warrant a further study large enough to answer whether or not this result was due to chance This study evaluated the effectiveness of nicotine chewing gum in smoking cessation , when incorporated into a behaviorally oriented self-help program . One hundred ninety-seven patients were r and omly assigned to nicotine gum with a self-help manual , a self-help manual without gum , or a control condition , but received no further treatment from the prescribing physician . At six weeks , the nicotine gum group was superior to both the self-help and control conditions . By one year , many gum patients had relapsed , and the treatment effect was no longer significant . Patients who were able to quit initially were most likely to remain ex-smokers in the self-help condition . The clinical importance of these findings is discussed The efficacy of physician anti-smoking intervention with 289 patients in a family practice setting was assessed . The design included two treatment conditions , physician advice and physician advice plus the offer of nicotine chewing gum ( NCG ) prescription . A no-advice group permitted assessment of the effects of repeated testing . The NCG group had higher rates of abstinence at all follow-up points , but the difference approached statistical significance at 3 months only ( p less than .10 ) . Comparison of those who actually used NCG to all other groups revealed significantly more users were abstinent at 1- and 3-month follow-up . A similar pattern occurred for proportion attempting cessation and smoking reduction . A dose-response relationship of gum use to outcome was identified . Long-term users ( greater than 20 days ) had 86 % abstinence at 3 months versus 18 % for short-term users . Thus , NCG does appear to have a role in family practice for promoting short-term cessation Three smoking cessation interventions design ed for use by general practitioners ( GPs ) within the routine consultation were evaluated in a field setting using 26 GPs throughout metropolitan Sydney . A total of 450 smoking patients were allocated to either Structured Behavioral Change with nicotine gum ( Group SBCN ) , Structured Behavioral Change without nicotine gum ( Group SBC ) , or GP advice with nicotine gum ( Group AN ) . Although significant differences in the percentage of abstainers were observed between Groups SBCN and SBC three weeks after treatment ( 39 % vs. 26 % ) , the point prevalence abstinence rate for patients at 12 months declined to 19 , 18 , and 12 % for Groups SBCN , SBC , and AN , respectively . Continuous abstinence to the end of the 12-month period was 9 % for Groups SBCN and SBC , and 6 % for Group AN . Forty-eight percent of the 450 patients made an attempt to stop smoking , and 89 % reduced their cigarette consumption at some point during the study . Examination of 132 self- selecting patients who fully participated in the three interventions and attended all scheduled visits , revealed significantly larger proportions of abstainers within Groups SBCN ( 34 % ) and SBC ( 33 % ) than in Group AN ( 15 % ) at the 12-month follow-up OBJECTIVES . Nicotine nasal spray has been 1 of the most successful forms of nicotine-replacement therapy in adult population s. The nasal sprayer has not been studied in adolescent smokers . The objective of this pilot study was to determine the feasibility and utility of using nicotine nasal spray for adolescent smokers who wanted to quit smoking . METHODS . Forty adolescent smokers who were between 15 and 18 years of age and smoked ≥5 cigarettes daily for at least 6 months were recruited from several San Francisco Bay area schools from 2005 to 2007 . Using a r and omized , open-label , 12-week trial , adolescent smokers were assigned to receive either weekly counseling alone ( control ) for 8 weeks or 8 weeks of counseling along with 6 weeks of nicotine nasal spray . Self-reported smoking abstinence was verified by both expired-air carbon monoxide and salivary cotinine . RESULTS . There was no difference in cessation rates , the numbers of cigarettes smoked per day , or cotinine levels at 12 weeks . Fifty-seven percent of participants stopped using their spray after only 1 week . The most commonly reported adverse effect was nasal irritation and burning ( 34.8 % ) followed by complaints about the taste and smell ( 13 % ) . CONCLUSIONS . The unpleasant adverse effects , poor adherence , and consequent lack of efficacy observed in our pilot study do not support the use of nicotine nasal spray as an adjunct to counseling for adolescent smokers who wish to quit OBJECTIVES To determine if community subjective social status ( SSS ) predicted smoking abstinence through 26 weeks postr and omization among 755 African American light smokers of low SES ( socioeconomic status ) . METHODS Participants were enrolled in a double-blind , placebo-controlled , r and omized clinical trial , which examined the efficacy of nicotine gum and counseling for smoking cessation . RESULTS Results indicated that SSS predicted smoking abstinence over time [ P=.046 ; odds ratio ( OR ) = 1.075 ( 1.001 - 1.155 ) ] after adjusting for covariates . CONCLUSIONS Further research is needed to underst and the effects of community SSS on smoking cessation among heavy smokers and other ethnic groups AIMS In an additive design , test the efficacy of cue exposure treatment for smoking relapse prevention as an adjunct to current st and ard cognitive behavioral and pharmacological treatments . DESIGN R and omized , controlled clinical trial . SETTING Outpatient behavioral medicine clinic . PARTICIPANTS One hundred and twenty-nine cigarette smokers recruited through newspaper advertisements . INTERVENTION After receiving an initial counseling session for cessation and setting a quit day , 129 smokers were r and omly assigned to one of four relapse prevention treatment conditions : ( 1 ) brief cognitive behavioral ; ( 2 ) cognitive behavioral and nicorette gum ; ( 3 ) cognitive behavioral and cue exposure ; and ( 4 ) cognitive behavioral and cue exposure with nicorette gum . All smokers met individually with their counselor for six RP sessions . MEASURES Seven-day , point-prevalence abstinence rates ( CO verified ) taken at 1 , 3 , 6 and 12-months post-treatment and time to first slip . FINDINGS All manipulation checks and process measures suggested that the treatments were delivered as intended . There were no significant differences between conditions in point-prevalence abstinence rates or in time to first slip . CONCLUSIONS These results call into question the utility of cue exposure treatment for smoking relapse prevention BACKGROUND Nicotine-replacement therapy is effective for smoking cessation outside pregnancy and its use is widely recommended during pregnancy . We investigated the efficacy and safety of nicotine patches during pregnancy . METHODS We recruited participants from seven hospitals in Engl and who were 16 to 50 years of age with pregnancies of 12 to 24 weeks ' gestation and who smoked five or more cigarettes per day . Participants received behavioral cessation support and were r and omly assigned to 8 weeks of treatment with active nicotine patches ( 15 mg per 16 hours ) or matched placebo patches . The primary outcome was abstinence from the date of smoking cessation until delivery , as vali date d by measurement of exhaled carbon monoxide or salivary cotinine . Safety was assessed by monitoring for adverse pregnancy and birth outcomes . RESULTS Of 1050 participants , 521 were r and omly assigned to nicotine-replacement therapy and 529 to placebo . There was no significant difference in the rate of abstinence from the quit date until delivery between the nicotine-replacement and placebo groups ( 9.4 % and 7.6 % , respectively ; unadjusted odds ratio with nicotine-replacement therapy , 1.26 ; 95 % confidence interval , 0.82 to 1.96 ) , although the rate was higher at 1 month in the nicotine-replacement group than in the placebo group ( 21.3 % vs. 11.7 % ) . Compliance was low ; only 7.2 % of women assigned to nicotine-replacement therapy and 2.8 % assigned to placebo used patches for more than 1 month . Rates of adverse pregnancy and birth outcomes were similar in the two groups . CONCLUSIONS Adding a nicotine patch ( 15 mg per 16 hours ) to behavioral cessation support for women who smoked during pregnancy did not significantly increase the rate of abstinence from smoking until delivery or the risk of adverse pregnancy or birth outcomes . However , low compliance rates substantially limited the assessment of safety . ( Funded by the National Institute for Health Research Health Technology Assessment Programme ; Current Controlled Trials number , IS RCT N07249128 . ) This pilot study suggests that changes in prescribing policy for nicotine replacement patches should be made only when evidence of cost-effectiveness can be adduced from a r and omized controlled trial Cigarette smoking remains the single most preventable cause of death in the United States . Nurses can be Instrumental in assisting patients in quitting . A prospect i ve quasi-experimental design was employed to investigate the differences in quit rates , adverse drug reactions , time to relapse , and secondary factors that contribute to smoking cessation in two groups of patients who attended a group program and used either a nicotine patch or nicotine gum . Although there were no significant differences in quit rates at one year , the patch group showed a significant increase in shortterm quit rates and a decrease in adverse reactions as well as a longer time to relapse . Older patients demonstrated a longer time to relapse while a high degree of nicotine dependency was correlated with a shorter time to relapse OBJECTIVE To identify predictors of smoking cessation success or failure with and without transdermal nicotine patch treatment . DESIGN Two independent r and omized , double-blind , placebo-controlled studies using the nicotine patch assessing outcome at the end of treatment and at 6-month follow-up ; each study used a different mode of adjuvant counseling . PATIENTS Subjects were daily smokers ( > or = 15 cigarettes per day ) , aged 21 to 65 years with expired air carbon monoxide levels of at least 10 ppm , and motivated to quit . Eighty-eight subjects participated in study 1 , and 112 subjects participated in study 2 . INTERVENTION Study 1 consisted of 8 weeks of 22-mg nicotine patch therapy with intensive group counseling . Study 2 consisted of 4 weeks of 22-mg nicotine patch therapy and 2 weeks of 11-mg nicotine patch therapy with brief individual counseling . MAIN OUTCOME MEASURES The prediction of smoking cessation ( at end of treatment and after 6 months ) based on pretreatment and intratreatment measures in smokers using active or placebo nicotine patches . RESULTS Pretreatment markers , such as the Fagerstrom Tolerance Question naire score , number of cigarettes smoked per day , years smoked , expired air carbon monoxide level , or baseline blood nicotine and cotinine levels , showed no consistent relationship with successful smoking cessation across both studies . Of the intratreatment markers examined , withdrawal severity and nicotine replacement levels also were not consistently predictive of cessation success . However , any smoking during the second week of treatment was a consistent and powerful predictor of failure at the end of treatment and after 6 months . Among active nicotine patch patients who smoked at all during week 2 after quitting , 83 % and 97 % ( studies 1 and 2 , respectively ) were smoking at 6-month follow-up . Conversely , abstinence during the second week of treatment predicted successful smoking cessation . Among active nicotine patch patients who were totally abstinent during week 2 after quitting , 46 % and 41 % ( studies 1 and 2 , respectively ) were abstinent at 6-month follow-up . Of all nicotine patch patients in both studies who were smoking at 6-month follow-up , 74 % began smoking during week 1 or 2 . Among all placebo patch patients who were smoking at 6-month follow-up , 86 % began smoking during week 1 or 2 . CONCLUSIONS Smoking status ( abstinent or smoking ) during the first 2 weeks of nicotine patch therapy , particularly week 2 , was highly correlated with clinical outcome and can serve as a powerful predictor of smoking cessation . Early smoking behavior also predicted outcome among placebo patch users . Traditional measures of dependence are not consistently predictive of cessation success . Clinicians are advised to emphasize the importance of total abstinence after a quit attempt and to follow-up with patients within the first 2 weeks of quitting ; smoking during this critical time should be assessed and treatment may be altered as appropriate AIMS To determine effects on craving , user satisfaction , and consumption patterns of two new nicotine replacement therapies ( NRT ) used for eight hours after overnight tobacco abstinence . DESIGN In a within-subject , cross-over trial participants were r and omly assigned Zonnic nicotine mouth spray ( 1 mg/spray ) , Zonnic nicotine lozenge ( 2.5 mg ) , Nicorette gum ( 4 mg ) and placebo lozenge on each of four study days . SETTING University research unit . PARTICIPANTS Forty-seven dependent adult smokers . MEASUREMENTS Participants rated their urges to smoke , irritability , concentration and restlessness before and during the first hour of product use on a 100-point scale . A sub sample of 11 participants provided blood sample s for nicotine analysis . FINDINGS All active products reduced craving significantly more than placebo ( mean reductions of 28.6 , 25.8 , 24.7 and 8.9 points for mouth spray , gum , lozenge and placebo ) . Mouth spray relieved craving faster than placebo and gum with significant reductions within five minutes of use ( mean differences of -14.5 ( 95 % CI : -23.0 to -6.0 ) and -10.6 ( 95 % CI : -19.1 to -2.1 ) with placebo and gum respectively . Mouth spray produced a faster time to maximum plasma nicotine concentration ( 14.5 minutes , 95 % CI : 8.0 to 21.0 ) compared to the lozenge ( 30.3 minutes , 95 % CI : 21.1 to 39.5 ) and gum ( 45.8 minutes , 95 % CI : 36.2 to 55.4 ) . Maximum concentrations of blood nicotine were higher with mouth spray ( 10.0 ng/ml ) and lozenge ( 10.8 ng/ml ) compared to gum ( 7.8 ng/ml ) . Both lozenge and mouth spray were well tolerated . CONCLUSIONS The mouth spray and lozenge are at least as effective as 4 mg nicotine gum in relieving craving suggesting that they are likely to be effective in aiding smoking cessation . The mouth spray may be particularly useful for acute craving relief The enrollment process determines the study sample and external validity of clinical trial results ; however , few reports describe the process and outcome of screening efforts for smoking cessation studies among adolescents . We describe and evaluate a screening protocol to enroll adolescent smokers for a r and omized clinical trial of nicotine replacement therapy . Adolescent smokers obtained the recruitment call-in number ( 1 - 800-NO-SMOKE ) via media and other advertisements . Trained recruitment staff collected information using an internally developed , targeted telephone screening interview , which was used to determine pre- eligibility for the clinical trial . Correlates of qualification and of study enrollment were determined . Among 1,347 adolescents screened , 329 ( 24.4 % ) were eligible to participate in the trial . Light smoking ( 39.1 % ) and lack of parental support ( 14.8 % ) were the biggest contributors to in eligibility . Eligible adolescents were more likely to be female ( 66.9 % vs. 58.2 % , p = .0052 ) and more likely to be European American ( 63.5 % vs. 52.2 % , p = .0003 ) . The higher rates of in eligibility for African Americans and boys were partly explained by lower scores on the Fagerström Test for Nicotine Dependence . Of those eligible to participate in the trial , 159 ( 48.3 % ) enrolled . Results underscore the need for screening instruments that are measurement-invariant across ethnicities and gender , and for enrollment strategies that maximize inclusion of eligible participants BACKGROUND AND OBJECTIVES Pregnant women face considerable barriers to smoking cessation . The purpose of this study was to determine the prevalence of major depressive disorder ( MDD ) and post-traumatic stress disorder ( PTSD ) and response to smoking cessation treatment in pregnant smokers participating in a r and omized , placebo-controlled trial of nicotine gum . METHODS Participants were 194 low-income , ethnically diverse pregnant smokers . RESULTS Utilizing a structured interview , 45 % and 18 % of the subjects met criteria for a lifetime diagnosis of MDD and PTSD , respectively . There was no difference in response to treatment , based on the presence of either of these psychiatric disorders . CONCLUSIONS Cumulatively , these findings provide evidence of the high degree of unmet mental health needs in pregnant smokers . SCIENTIFIC SIGNIFICANCE Pregnant women with a history of MDD and PTSD appear to be as likely to benefit from smoking cessation treatment as those without such a history Four hundred and ninety six smokers participated in a r and omised comparison of the effect of silver acetate , nicotine , and ordinary chewing gum on smoking cessation . All were motivated to stop smoking abruptly and all had smoked at least 10 cigarettes a day for at least five years . Side effects and taste acceptability were related to outcome after six months . The participants attended nine meetings over a year , at which lectures , support , and advice about stopping smoking were given . Tobacco abstinence was confirmed by measurement of carbon monoxide in expired air . The chewing gums were used for 12 weeks . After 12 weeks there was a trend towards more abstainers in the nicotine group ( 59 % ) than in the silver acetate ( 50 % ) and ordinary ( 45 % ) chewing gum groups that was not quite significant ( p = 0.07 ) . At 26 and 52 weeks the number of cigarette abstainers was similar in the three treatment groups . Subjects in the nicotine chewing gum group had a longer mean time before relapse than those in the silver acetate and ordinary chewing gum groups . Mean success rates for all subjects combined at 12 , 26 , and 52 weeks were 52.8 % , 39.7 % , and 23.3 % . The side effects of nicotine and silver acetate chewing gum were generally mild and transient , and unimportant except for mouth irritation from silver acetate , which had a negative effect on outcome , and the low taste acceptability of nicotine , which had a strong negative influence on the success rate . The results suggest a short term effect on nicotine chewing gum on smoking cessation , but the abstinence rates after one year were generally disappointing Nicotine patches are commonly used by people who try to quit smoking . Because high doses of nicotine may increase heart rate and potentiate cardiac arrhythmia or ischemia , its use in patients with coronary artery disease was investigated . The objective was to assess the cardiovascular safety of nicotine patches in patients with coronary artery disease ( CAD ) who try to quit smoking . The study was conducted in a double-blind , placebo-controlled , r and omized fashion over a 2-week period . One hundred and six patients with CAD who wished to stop smoking and were taking part in a smoking cessation program were included . Fifty-two patients received nicotine patches ( Nicotinell ® ) and 54 received placebo patches . The cardiovascular effects of nicotine patches were assessed by repeated ambulatory ECG monitoring ( AEM ) and exercise testing . There were no changes in the resting heart rate and in the systolic or diastolic blood pressure between the screening and the two phases of the study in both the Nicotinell and placebo groups . Repeated 48-hour AEM revealed that there were no significant changes in the number and duration of ischemic episodes in both groups . There was no change in the frequency of atrial or ventricular arrhythmias . Exercise duration and time to 1-mm ST-segment depression increased in both groups during the double-blind treatment phase . More patients in the Nicotinell group cl aim ed tobacco abstinence compared with the placebo group ( 27 % vs. 13 % ) . The use of nicotine patches did not cause aggravation of myocardial ischemia or arrhythmia in coronary patients and therefore can be used as a method to promote smoking cessation in this high-risk group The efficacy of a transdermal nicotine patch in facilitation of smoking cessation was evaluated in a r and omized double‐blind trial . Sixty‐five smokers who were highly dependent on cigarettes participated in the study , which included a behavioral smoking‐cessation program . The rates of continuous abstinence were significantly higher in the nicotine group both initially ( 55 % versus 34 % ) and at 3 weeks ( 18 % versus 6 % ) . Certain smoking withdrawal symptoms , including negative affect and hypoarousal , were effectively relieved by the nicotine patch . There was a trend toward a reduction in cigarette craving , whereas hunger and habit withdrawal symptoms were not affected . The main side effect associated with the nicotine patch was skin irritation . These findings suggest that a nicotine skin patch may be a useful aid to smoking cessation ; however , the combination of other techniques with nicotine replacement may provide a more effective treatment for symptoms such as craving for cigarettes BACKGROUND This study was undertaken to evaluate the long-term smoking cessation efficacy of varying doses of transdermal nicotine delivery systems 4 to 5 years post-quit day . METHODS A follow-up study was conducted 48 to 62 months after quit day among patients who were enrolled in the Transdermal Nicotine Study Group investigation . The latter study included group smoking cessation counseling and r and omized assignment to 21 , 14 , or 7 mg nicotine patches or placebo patches . Seven of nine smoking cessation research centers participated in the long term follow-up investigation . RESULTS The self-reported continuous quit rate among patients originally assigned 21 mg ( 20.2 % ) was significantly higher than rates for patients assigned 14 mg ( 10.4 % ) , 7 mg ( 11.8 % ) , or placebo patches ( 7.4 % ) . Log rank survival analysis found no difference in relapse rates after 1 year postcessation . Smokers under age 30 years were significantly less likely to be abstinent at long term follow-up compared to smokers > or = 30 years of age ( 3 vs 13 % , respectively ) . Mean weight gain in confirmed continuous quitters was 10.1 kg in men and 8.0 kg in women . Of the 63 continuous abstainers surveyed , 30 respondents ( 48 % ) reported that they no longer craved cigarettes , and no individual reported daily craving for cigarettes . CONCLUSIONS Nicotine patch therapy with 21 mg/day patches result ed in a significantly higher long-term continuous abstinence rate compared to lower dose patches and placebo . Relapse rates among the various treatment conditions were similar after 1 year postcessation OBJECTIVE : To estimate the safety and efficacy of treatment with 2-mg nicotine gum for smoking cessation during pregnancy . METHODS : Pregnant women who smoked daily received individualized behavioral counseling and r and om assignment to a 6-week treatment with 2-mg nicotine gum or placebo followed by a 6-week taper period . Women who did not quit smoking were instructed to reduce the number of cigarettes smoked by substituting with gum . Measures of tobacco exposure were obtained throughout the study . RESULTS : Participants in the nicotine ( nequals;100 ) and placebo ( nequals;94 ) groups were comparable in age , race/ethnicity , and smoking history . Biochemically vali date d smoking-cessation rates were not significantly higher with nicotine gum compared with placebo ( after 6 weeks of treatment : 13 % compared with 9.6 % , P=.45 ; at 32–34 weeks of gestation : 18 % compared with 14.9 % , P=.56 ) . Using a completer analysis , nicotine gum significantly reduced the number of cigarettes smoked per day ( nicotine gum : −5.7 [ st and ard deviation (SD)=6.0 ] ; placebo : −3.5 [ SD=5.7 ] , P=.035 ) , and cotinine concentration ( nicotine gum : −249 ng/mL [ SD=397 ] ; placebo : −112 ng/mL [ SD=333 ] ; P=.04 ) . Birth weights were significantly greater with nicotine gum compared with placebo ( 3,287 g [ SD=566 ] and 2,950 g [ SD=653 ] , respectively , P<.001 ) . Gestational age was also greater with nicotine-replacement therapy than with placebo ( 38.9 weeks [ SD=1.7 ] and 38.0 weeks [ SD=3.3 ] , respectively ; P=.014 ) . CONCLUSION : Although nicotine gum did not increase quit rates , use of nicotine gum increased birth weight and gestational age , two key parameters in predicting neonatal wellbeing . CLINICAL TRIAL REGISTRATION : Clinical trials.gov , www . clinical trials.gov , NCT00115687 LEVEL OF EVIDENCE : OBJECTIVE --To assess the effectiveness of 12 weeks ' treatment with a 24 hour transdermal nicotine patch in helping heavy smokers to stop smoking ; also to assess the value of a specially written support booklet about smoking cessation and patch use compared with a simple advice pamphlet . DESIGN --Double blind placebo controlled r and omised trial with a 2 x 2 factorial design . SETTING --19 general practice s in Oxfordshire . SUBJECTS--1686 heavy smokers aged 25 - 64 ( mean cigarette consumption 24/day ; mean duration of smoking 25 years ) . MAIN OUTCOME MEASURE -- Sustained cessation for the last four weeks of the 12 week treatment period , confirmed by saliva cotinine estimation ( 226/262 cases ; 86.3 % ) or expired carbon monoxide concentration ( 36/262 ; 13.7 % ) . Patients lost to follow up ( 155/1686 ; 9 % ) were assumed to have continued to smoke . RESULTS --Cessation was confirmed in 163 patients ( 19.4 % ) using the nicotine patch and 99 patients ( 11.7 % ) using the placebo patch ( difference 7.6 % ( 95 % confidence interval 4.2 % to 11.1 % ) ; p < 0.0001 ) . There was no significant advantage in using the more detailed written support material . The most important adverse effect of the patch was local skin irritation , which occurred in 15.8 % ( 133/842 ) and 5.1 % ( 43/844 ) of patients using the nicotine and placebo patches respectively , was grade d as severe in 4.8 % ( 40 ) and 1.1 % ( nine ) , and was stated as a reason for withdrawal from the trial in 9.5 % ( 80 ) and 2.8 % ( 24 ) . CONCLUSION --Nicotine patches are effective in a general practice setting with nursing support , but the extent to which this effect is sustained can not be assessed until the results of longer term follow up are known Two hundred cigarette smokers in Thail and were r and omly assigned to receive a chewing gum containing nicotine or placebo . After six months , significantly more of the group receiving the active gum than those receiving the placebo had given up smoking . The results suggested that this treatment was more effective in highly dependent smokers than in those who were less dependent . Few side effects were reported BACKGROUND A high proportion of African-American smokers are light smokers , and they experience low smoking cessation rates and disproportionately high tobacco-related morbidity ; yet no studies have examined tobacco treatment adherence in this group . OBJECTIVES To determine the predictors of adherence to nicotine gum and counseling among African-American light smokers ( defined as smoking ≤10 cigarettes/day ) , and the effects of adherence on smoking cessation . DESIGN Data were from a 2 × 2 r and omized , placebo-controlled smoking cessation trial of nicotine gum ( 2 mg versus placebo ) and counseling ( motivational interviewing versus health education ) . PARTICIPANTS Seven hundred fifty-five African-American light smokers at a community-based clinic . MEASUREMENTS Demographic and health-related information , smoking behaviors , psychosocial variables , adherence to nicotine gum and counseling , and cotinine-verified 7-day abstinence from smoking at week-26 follow-up . RESULTS A logistic regression model showed that having a higher body mass index ( OR = 1.03 , 95 % CI = 1.01 to 1.05 ) , more quit attempts in the past year ( OR = 1.04 , 95 % CI = 1.01 to 1.07 ) , higher baseline exhaled carbon monoxide ( OR = 1.22 , 95 % CI = 1.01 to 1.48 ) , and higher perceived stress ( OR = 1.12 , 95 % CI = 1.03 to 1.22 ) increased the likelihood of adherence to nicotine gum . Being a high school graduate was a predictor of adherence to counseling ( OR = 1.58 , 95 % CI = 1.02 to 2.44 ) . Surprisingly , being adherent to nicotine gum significantly reduced the odds of smoking cessation ( OR = 0.50 , CI = 0.28 to 0.87 ) . On the other h and , adherence to counseling dramatically increased the likelihood of smoking cessation ( OR = 3.32 , CI = 1.36 to 8.08 ) . CONCLUSIONS Individual risk factors may influence adherence to nicotine gum and counseling . Improving psychological interventions and promoting adherence to counseling may increase overall smoking cessation success among African-American light smokers The Collaborative European Anti-Smoking Evaluation ( CEASE ) was a European multicentre , r and omized , double-blind placebo controlled smoking cessation study . The objectives were to determine whether higher dosage and longer duration of nicotine patch therapy would increase the success rate . Thirty-six chest clinics enrolled a total of 3,575 smokers . Subjects were allocated to one of five treatment arms : placebo and either st and ard or higher dose nicotine patches ( 15 mg and 25 mg daily ) each given for 8 or 22 weeks with adjunctive moderately intensive support . The 12 month sustained success rates were : 25 mg patch for 22 weeks ( L-25 ) , 15.4 % ; 25 mg patch for 8 weeks ( S-25 ) , 15.9 % ; 15 mg patch for 22 weeks ( L-15 ) , 13.7 % ; 15 mg patch for 8 weeks ( S-15 ) , 11.7 % ; and placebo ( P-0 ) 9.9 % ( placebo versus 15 mg , p<0.05 ; 25 mg versus 15 mg , p<0.03 ; 25 mg versus placebo , p<0.001 , Chi-squared test ) . There was no significant difference in success rate between the two active treatment duration s. Of the first week abstainers ( n=1,698 ) , 25.1 % achieved success at 12 months as opposed to first week smokers , 2.7 % of 1,877 subjects ( p < 0.001 ) . In summary , a higher than st and ard dose of nicotine patch was associated with an increase in the long-term success in smoking cessation but continuation of treatment beyond 8 - 12 weeks did not increase the success rates Nicotine gum has been shown to be effective in improving abstinence rates , and in reducing post-cessation withdrawal distress and weight gain . However , the dose effects of nicotine gum on these outcomes is not known . In the present study , we varied the amount of 2 mg nicotine gum prescribed to motivated quitters to explore the hypotheses ( a ) that motivated quitters would use more pieces of gum when coached and counseled to do so and ( b ) that there would be a dose-related effect of gum use on abstinence , withdrawal symptoms , and weight gain . One hundred seventy-seven volunteers were assigned to chew either 0 , 7 , 15 , or 30 , pieces per day of 2 mg nicotine gum . Biological verification of gum use and smoking abstinence were assessed in community volunteers who attended an intensive behavioral counseling program for smoking cessation while using nicotine gum for 3 months . In the survival analysis at 12 weeks , gum-group assignment was not related to successful abstinence . In the subset of 42 abstinent subjects , there was a strong positive relationship between pieces per day of nicotine gum used and saliva cotinine . However , there was substantial variability in groups of subjects reporting similar amounts of gum use . Withdrawal symptom reporting was not related to either gum use or cotinine levels . Weight gain was significantly related in a dose-dependent manner to salivary cotinine levels , but not to gum group assignment , with high and low cotinine subjects gaining on average , 4.0 and 6.6 pounds , respectively . Discussion of the use of high levels of nicotine gum is addressed . Consistent with earlier work , the study provided further support for the relationship between nicotine replacement level and post-cessation weight gain Abstract : The objective of this study was to assess the postintervention effect of nicotine replacement therapy on reduction of cigarette consumption 1.5 years after the end of a 6-month treatment . Heavy smokers who had no intention of quitting smoking were recruited from the general population and were r and omly assigned to a treatment of nicotine ( choice of a 15-mg nicotine patch , a 4-mg nicotine gum , and /or a 10-mg nicotine inhaler , n = 265 ) , matching placebo products ( n = 269 ) , or no intervention ( n = 389 ) . Products were sent to participants by mail . Education was limited to a booklet . Of 923 participants , 879 ( 95 % ) were followed 6 months after r and omization and 846 ( 92 % ) were followed after 26 months . Mean baseline consumption was 30 cigarettes/day in all groups . After 6 months , cigarette consumption had decreased by a mean of 10.9 cigarettes/day in the nicotine group , 8.7 in the placebo group , and 4.9 among controls ( P ≤ 0.02 for all pairwise comparisons ) . After 26 months , compared with baseline , cigarette consumption had decreased by a mean of 9.8 cigarettes/day in the nicotine group , 7.7 in the placebo group , and 7.7 among controls ( nicotine vs. placebo or control : P ≤ 0.03 ) . After 2 years , smoking cessation rates did not differ significantly among groups ( nicotine 11.7 % , placebo 9.3 % , control , 10.0 % ; P = 0.6 ) . Thus , a slight effect of nicotine replacement therapy on reduction of cigarette consumption was maintained 1.5 years after the end of the 6-month treatment , but the initially observed placebo effect was not maintained . Nicotine replacement therapy for smoking reduction had no deleterious impact on smoking cessation 1,218 smokers able to quit smoking for 48 hr were r and omly assigned to one of 12 cells in a 4 x 3 fully crossed factorial experiment . A pharmacologic factor contained four levels : nicotine polacrilex ( gum ) delivered ad lib or on a fixed regimen , placebo gum , and no gum . A self-guided behavioral treatment factor contained three levels : self-selected relapse prevention modules , r and omly administered modules , and no modules . Those receiving nicotine gum were more likely to be abstinent at the 2- and 6-month follow-ups . The fixed regimen accounted for most of the effect for gum . There was no effect for the relapse prevention module factor . Men and women showed a differential treatment response . Men who received nicotine gum were more likely to be abstinent at each follow-up ( 2 , 6 , and 12 months ) . No treatment was significantly better among women . We conclude that research on different gum chewing regimens is warranted and that further examination of possible gender differences in response to replacement therapy is needed Objectives . To determine the safety and efficacy of the nicotine patch and gum for adolescents who want to quit smoking . Design . Double-blind , double-dummy , r and omized , 3-arm trial with a nicotine patch ( 21 mg ) , nicotine gum ( 2 and 4 mg ) , or a placebo patch and gum ; all participants received cognitive-behavioral group therapy . Setting . Inner-city , outpatient clinic on the East Coast . Subjects . Thirteen- to 17-year-old adolescents who smoked ≥10 cigarettes per day ( CPD ) , scored ≥5 on the Fagerström Test of Nicotine Dependence , and were motivated to quit smoking . Intervention . Twelve weeks of nicotine patch or gum therapy with cognitive-behavioral therapy , with a follow-up visit at 6 months ( 3 months after the end of treatment ) . Main Outcome Measures . Safety assessed on the basis of adverse event reports for all 3 groups , prolonged abstinence , assessed through self-report and verified with exhaled carbon monoxide ( CO ) levels of ≤6 ppm , in intent-to-treat analyses , and smoking reduction ( CPD and thiocyanate concentrations ) among trial completers . Results . A total of 120 participants were r and omized ( 72 % white , 70 % female ; age : 15.2 ± 1.33 years ; smoking : 18.8 ± 8.56 CPD ; Fagerström Test of Nicotine Dependence score : 7.04 ± 1.29 ) from 1999 to 2003 . Participants started smoking at 11.2 ± 1.98 years of age and had been smoking daily for 2.66 ± 1.56 years ; 75 % had at least 1 current psychiatric diagnosis . Mean compliance across groups was higher for the patch ( mean : 78.4–82.8 % ) than for the gum ( mean : 38.5–50.7 % ) . Both the patch and gum were well tolerated , and adverse events were similar to those reported in adult trials . Changes in mean saliva cotinine concentrations throughout treatment were not statistically significant . Intent-to-treat analyses of all r and omized participants showed CO-confirmed prolonged abstinence rates of 18 % for the active-patch group , 6.5 % for the active-gum group , and 2.5 % for the placebo group ; the difference between the active-patch and placebo arms was statistically significant . There was no significant effect of patch versus gum or gum versus placebo on cessation outcomes . Abstinence rates at the 3-month follow-up assessment were sustained but were not significantly associated with treatment group . Mean smoking rates , but not CO or thiocyanate concentrations , decreased significantly in all 3 arms but not as a function of treatment group . Conclusions . Nicotine patch therapy combined with cognitive-behavioral intervention was effective , compared with placebo , for treatment of tobacco dependence among adolescent smokers . Decreases in the numbers of cigarettes smoked appeared to be offset by compensatory smoking . Additional study of nicotine gum , with enhanced instructional support , is needed to assess its efficacy among adolescent smokers Objectives To identify predictors of nicotine withdrawal symptoms among smokers who participated in a r and omized cessation trial in a low-income country . Methods We analyzed data from 269 smokers who participated in a r and omized , placebo-controlled smoking cessation trial conducted in primary healthcare in Aleppo , Syria . All participants received behavioral counseling and were r and omized to receive either 6 weeks of nicotine or placebo patch and were followed for one year . Results Throughout the study , lower total withdrawal score was associated with greater education ( p = 0.044 ) , older age of smoking initiation ( p = 0.017 ) , lower nicotine dependence ( p = 0.024 ) , higher confidence in ability to quit ( p = 0.020 ) , lower reported depression ( p < 0.001 ) , higher adherence to patch ( p = 0.026 ) , belief of receiving nicotine patches rather than placebo ( p = 0.011 ) , and waterpipe use ( p = 0.047 ) . Conclusions Lower nicotine dependence , greater educational attainment , higher confidence in ability to quit and waterpipe use predict lower withdrawal severity . Waterpipe smoking may serve as a barrier to smoking cessation efforts in countries where its use is highly prevalent . Further , expectancies about the effects of pharmacotherapy appear to mediate the experience of nicotine withdrawal Effects of a transdermal nicotine substitution on psychological smoking cessation were investigated in a double-blind prospect i ve study . 131 smokers were r and omly assigned to three treatment conditions : All smokers underwent nine weeks of self-controlled smoking cessation . During six weeks one group was additionally treated with nicotine patches continuously releasing nicotine through the skin into the blood circuit . The second group received placebo patches ; while the third group was treated with behavioral training alone . Treatment effects were measured by daily cigarette consumption . Nicotine-treated subjects reached significantly higher abstinence rates during and at the end of treatment than both placebo- and control-subjects : 69 % in the nicotine condition , 51.2 % and 44.4 % under placebo and control conditions respectively . Effects are influenced by initial cigarette consumption , with the light smokers benefitting most from the nicotine patch . Self- assessment s suggest an aversive effect of transdermal nicotine on cigarette taste . Our results , although not yet verified by long-term observations , demonstrate that transdermal nicotine substitution significantly enhances the effectiveness of behavioral smoking cessation methods To assess the smoking cessation efficacy of transdermal nicotine patches as an adjunct to low-intervention therapy , we conducted a double-blind , placebo-controlled trial in 158 smokers . Participants were r and omly assigned to one of the following three study regimens that required daily application of two 15-cm2 patches : ( 1 ) 24-hour nicotine delivery , ( 2 ) nicotine delivery during wakeful hours only , and ( 3 ) placebo . The impact of the three regimens on smoking cessation rates and tobacco withdrawal symptoms was examined . During the last 2 weeks of the trial , 39 % of the 24-hour nicotine regimen delivery group , 35 % of those on wakeful hour nicotine regimens , and 13.5 % of the placebo treatment group achieved abstinence . Self-reported quit rates for the two nicotine patch-wearing regimens , as compared with that for the placebo group , continued to be significantly higher at 6 months . Moreover , compared with placebo , the transdermal nicotine patches significantly reduced tobacco withdrawal symptoms during the first few weeks of quitting . The differences in quit rates and tobacco withdrawal symptoms between the two active groups were not statistically significant . The patches were well tolerated both topically and systemically . We concluded that transdermal nicotine , when used as an adjunct to low-intervention therapy , significantly reduced tobacco withdrawal symptoms and enhanced smoking cessation rates BACKGROUND Smoking cessation outcomes are calculated as the probability of abstinence at follow-up among all enrolled smokers , but it is also useful to estimate the probability of success for those who experienced success or failure at earlier time points . OBJECTIVES The primary aims were to estimate the probability of maintaining abstinence through week 10 among subjects who were abstinent at week 2 , and to assess the effect of active treatment with a nicotine patch . We also examined outcomes at week 6 and , among subjects who smoked during the first 2 weeks of treatment , the probability of reestablishing abstinence later , as well as the effect of active treatment on this outcome . METHODS We analyzed pooled data from 2 previously published , parallel , double-blind studies in which subjects were initially r and omized to receive an active nicotine patch ( starting at 21 mg ) or a placebo patch . Subjects r and omized to active treatment followed a double-blind step-down dosing regimen : 24-h/21-mg patches for the first 6 weeks of treatment , followed by 14- and 7-mg patches for successive 2-week periods . Biochemically verified abstinence ( exhaled carbon monoxide < or=8 ppm ) was assessed during laboratory visits . RESULTS Most subjects were white ( 94.8 % ) and female ( 61.6 % ) , with a mean ( SD ) age of 43.1 ( 10.2 ) years . Subjects had been smoking for a mean of 24.5 ( 10.2 ) years and smoked a mean of 30.6 ( 10.4 ) cigarettes per day . In both the nicotine ( n = 249 ) and placebo ( n = 253 ) groups , all subjects who were abstinent during the first 2 weeks had a high probability of maintaining abstinence through week 10 , but subjects treated with the active patch were significantly more likely to remain abstinent ( active : 79.8 % [ 67/84 ] , placebo : 52.6 % [ 20/38 ] ; relative risk [ RR ] = 1.52 [ 95 % CI , 1.10 - 2.09 ] ) . Also , at week 6 , subjects receiving active treatment had a greater chance of remaining abstinent ( active : 94.3 % [ 82/87 ] , placebo : 78.0 % [ 32/41 ] ; RR = 1.21 [ 95 % CI , 1.02 - 1.43 ] ) . To assess the effect of treatment on recovery from smoking lapses , we examined the probability of abstinence during week 10 among subjects who smoked during the first 2 weeks of treatment . Among them , treatment was associated with a greater probability of later success : 31.4 % ( 50/159 ) of those treated with the active patch and 12.5 % ( 26/208 ) of those receiving placebo were abstinent at week 10 ( RR = 2.52 [ 95 % CI , 1.64 - 3.85 ] ) . Similar results were observed at week 6 ( 49.4 % [ 80/162 ] vs 21.2 % [ 45/212 ] ; RR = 2.33 [ 95 % CI , 1.72 - 3.15 ] ) . CONCLUSIONS More than two thirds ( 71.3 % ) of subjects who were abstinent 2 weeks into a quit attempt maintained that abstinence through the end of 10 weeks of treatment . Use of a nicotine patch was significantly associated with maintaining abstinence and with recovering abstinence after an early lapse A double-blind trial of a smoking-withdrawal chewing gum containing 2 mg nicotine was conducted with 100 consecutive patients in a smoking cessation clinic . All patients received the usual psychological treatment given at the clinic . In addition , the patients were r and omly assigned to a nicotine gum ( the experimental group ) or a placebo chewing gum ( control group ) . The abstinence rates for the experimental group at 1 , 3 , and 6 months after quitting were 90 , 76 , and 63 % , respectively . The comparable abstinence rates for the control group were 60 , 52 , and 45 % . The differences were significant at the 5 % level at all three follow-up periods . When nicotine dependence , as measured by a st and ard question naire , was taken into consideration , it was found that 71 % of the high-nicotine-dependent smokers in the experimental group were abstinent after 6 months , as compared to 39 % in the placebo group . In contrast , low-nicotine-dependent patients achieved 75 and 65 % , respectively , for the same time interval . The gum was well accepted by patients and gave no serious side effects OBJECTIVE To assess the appearance of craving and withdrawal among four combination nicotine replacement treatments ( NRTs ) . METHODS In a crossover trial of NRT preferences , 27 smokers tested 4 combinations of nicotine treatments : 2 mg/4 mg gums + 15 mg patch , 2 mg/4 mg lozenges + 15 mg patch , inhalers + 15 mg patch , and 10 + 15 mg double patch ( approximately 25 mg ) . Overnight abstinence was required prior to ( 1/2 ) day testing of each combination . Combination NRTs were used for approximately 6 h/day . Subjects resumed smoking each afternoon . For this report , we used the Smoker Anchored Withdrawal Grid to look at craving and withdrawal scores over 5 days of testing ( smoking baseline + four treatment days ) . RESULTS " Urge to smoke " and " total withdrawal " showed a rise from baseline to NRT use for the double patch but not for the three acute + patch conditions . Lozenge/patch scores did not rise from baseline for " craving " and " miss a cigarette " but did for gum/patch , inhaler/patch , and double patch . The best relief occurred for NRTs of choice . CONCLUSION This was a small but suggestive finding regarding the potential of patch plus adjunct ad lib NRT . With little data on relief with NRT combinations , more systematic tests are needed This study of 94 postmenopausal female smokers evaluated the effect of nicotine replacement therapy ( NRT ) and hormone therapy ( HT ) on change in weight , energy intake , and physical activity during 2 weeks of smoking abstinence . Women , stratified by current use of HT , were r and omized to nicotine or placebo patch . After 2 weeks of abstinence , women on nicotine patch had significantly larger increases in total caloric and fat intake than women on placebo patch and a trend toward larger increases in carbohydrates ( total and sweet ) . Conversely , the nicotine group had less weight gain , 0.47 kg , than the placebo group , 1.02 kg ( F=10.31 , p=0.002 ) . No effects were observed for hormone therapy . It appears that in short-term smoking abstinence , postmenopausal women on NRT gain less weight than do women on placebo , in spite of consuming more calories . This may be beneficial in the critical first 1 - 2 weeks of tobacco cessation , especially in light of postmenopausal weight gain PURPOSE To determine the effectiveness of the 4-mg and 2-mg dosages of nicotine polacrilex vs placebo through the first 6 weeks of treatment ( during which 75 % of relapse occurs when there is no treatment ) in assisting high-dependent smokers to stop smoking when instructed to use a fixed number ( 12 pieces ) of medication daily . SUBJECTS AND METHODS Ninety high-dependent ( Fagerström Tolerance Question naire score > or = 7 plus baseline carbon monoxide level > 15 ppm ) healthy male and female smokers , highly motivated to quit smoking , were enrolled in a 6-week , r and omized , double-blind , placebo-controlled trial in which they were instructed to use 12 pieces per day of their assigned dosage formulation : 4 mg , 2 mg , or 0.5 mg ( placebo ) of nicotine polacrilex . The behavioral intervention did not depend on providing any special psychological training , skills , or services but rather employed a st and ard medical practice model that could easily be implemented by any primary care physician . RESULTS Sustained abstinence from weeks 2 through 6 , determined at each visit by absolutely no cigarette use plus a carbon monoxide level of 8 ppm or lower was 59 % ( 4-mg group ) , 30 % ( 2-mg group ) , and 39 % ( placebo group ) ( P < .02 ) . For the 55 of the 90 smokers who met the originally planned definition of high dependence ( Fagerström Tolerance Question naire score > or = 7 plus baseline smoking serum cotinine level > 250 ng/mL plus baseline carbon monoxide level > 15 ppm ) , results were 63 % ( 4-mg group ) , 25 % ( 2-mg group ) , and 25 % ( placebo group ) ( P < .02 ) . In addition , the 4-mg dose produced statistically significantly higher abstinence rates in compliant subjects ( P < .02 ) and also in subjects with high baseline serum continine levels who were compliant ( P < .01 ) than did either the 2-mg dose or placebo . CONCLUSIONS It appears that the 4-mg dose of nicotine polacrilex is the drug and dose of choice for the initial phase of tobacco dependence treatment in high-dependent smokers ; the 2-mg dose of nicotine polacrilex is not better than placebo during the first 6 weeks of treatment for high-dependent cigarette smokers , and thus should not be used for these patients during the initial treatment phase Background : Many surgical patients are dependent on nicotine . Smoke-free policies in healthcare facilities m and ate abstinence from smoking , which could contribute to psychological stress in the perioperative period . The authors tested the hypothesis that nicotine replacement therapy decreases psychological stress in cigarette smokers scheduled to undergo elective surgery and determined whether nicotine replacement therapy affects postoperative smoking behavior , even when not specifically prescribed to promote abstinence . Methods : In this double-blind , placebo-controlled trial , 121 smokers , of whom 116 received a study intervention , were r and omly assigned to receive either active ( nicotine-containing ) or placebo patches , beginning on the morning of surgery and continuing for up to 30 days after discharge from the hospital . Outcomes included the Perceived Stress Score , the Nicotine Withdrawal Score , and subject self-report of smoking behavior . Results : The Perceived Stress Score and the Nicotine Withdrawal Score did not change significantly from baseline over the immediate perioperative period and did not differ between active or placebo patch groups ( all P > 0.19 ) . The percentage of placebo versus active patch subjects reporting 7-day abstinence at 30 days postoperatively ( 30 % vs. 39 % ; P = 0.29 ) did not differ significantly between groups . At 30 days postoperatively , subjects in both groups significantly reduced their cigarettes smoked per day from baseline , but those receiving active patches reported a greater decrease ( a mean decrease of 11 ± 11 vs. 15 ± 7 cigarettes/day in placebo and active groups ; P = 0.045 ) . Conclusion : Routine nicotine replacement therapy is not indicated in smokers undergoing surgery for the purpose s of managing nicotine withdrawal and stress but can modify some aspects of postoperative smoking behavior The aim of the study was to examine the effect of 24-hour nicotine patches in smoking cessation among over-the-counter customers in Denmark based on a r and omized , double-blind , placebo-controlled trial . Participants were consecutive customers to whom nicotine patches were offered free of charge and as the only treatment . Forty-two pharmacies in the areas of Aarhus and Copenhagen in Denmark participated in the trial , and 522 customers who smoked 10 or more cigarettes per day were r and omized to either nicotine or placebo patches from January to March 1994 . Twenty-four-hour patches were offered for a three-month period . Those smoking 20 or more cigarettes per day started on 21 mg/day patches . Customers who smoked less started on 14 mg/day patches and all the participants were gradually reduced to 7 mg/day patches during the study period . Smoking behaviour and compliance were recorded by means of self-administered question -naires and telephone interviews . Smoking status was recorded following each four-week treatment period , and 26 weeks after inclusion . There was a significant increase in smoking cessations rates , but only among smokers who started on 21 mg/day patches after eight weeks of follow-up . No significant differences in smoking cessation rates were seen among smokers who started with the low dose nicotine or placebo patches Smoking cessation is an arduous process because nicotine withdrawal syndrome , which occurs following sudden interruption of nicotine use in long-term smokers , frequently prevents them from giving up the habit . Nicotine supplement systems may relieve smokers ' nicotine withdrawal symptoms and , thus , help in the process of abstinence from smoking . The purpose of the present study was to investigate the effectiveness and safety of a 30-mg transdermal nicotine patch in a smoking cessation program for Chinese smokers . In this r and omized , double-blind , placebo-controlled study , 30 heavy smokers , who had smoked more than 20 cigarettes per day for more than a year , were treated with 30-mg transdermal nicotine patches , and 32 heavy smokers were given placebo patches during a 6-week smoking cessation program . The clinical characteristics of the two groups were similar . After 6 weeks , the use of the transdermal nicotine patch was associated with markedly reduced nicotine dependence and severity of withdrawal symptoms . Nineteen ( 63 % , 95 % confidence interval , CI , 46%-80 % ) of the smokers treated with the transdermal nicotine patch had successfully quit smoking at the end of the program ( 6 weeks ) and nine ( 30 % , 95 % CI 14%-46 % ) remained abstinent 1 year later . In contrast , only 11 ( 34 % , 95 % CI 18%-50 % ) of the smokers in the placebo group had successfully stopped smoking after 6 weeks , and three remained abstinent 1 year later ( 9 % , 95 % CI 0%-19 % ) . However , there was no statistically significant difference between the two groups of smokers after 1 year of follow-up ( p = 0.08 ) . Side-effects were minimal and did not affect the efficacy of the skin patch . The results indicate that the transdermal nicotine patch is an effective aid in smoking cessation programs Background : Smoking is a major public health issue , estimated as causing 120 000 deaths in the UK per year . Smoking cessation is an important aspect of the treatment of many diseases . Nicotine replacement therapy ( NRT ) has been shown to increase cessation rates among healthy volunteers and in general practice , but it is not clear whether it has an effect in hospital patients . Methods : Patients referred by their hospital doctor to the smoking cessation counsellor and who agreed to participate in the study were r and omised to receive either NRT given as a nicotine patch daily and a nicotine inhalator on an as needed basis plus advice and support ( AS+NRT ) , or to receive just advice and support ( AS ) . Cl aims of smoking cessation were vali date d at 1 week , 3 months , 6 months , and 1 year by carbon monoxide ( CO ) breath testing . Results : A total of 245 patients were r and omised , 136 AS+NRT and 109 AS . There were no significant demographic differences between the two groups at baseline . At 1 year 35 ( 14 % ) had sustained cessation confirmed by a CO breath test , 20/136 ( 15 % ) AS+NRT and 15/109 ( 14 % ) AS , p=0.857 . One hundred and ten patients gave up smoking for at least 1 week , 54 % AS+NRT and 33 % AS ( p<0.001 ) . By 6 months there was no significant difference between the two groups ( 22/136 ( 16 % ) AS+NRT and 15/109 ( 14 % ) AS ) . Conclusion : In hospital patients NRT , given as regular daily patches plus an inhalator to be used as needed , did not add to the smoking cessation rate achieved at 1 year by regular advice and support , despite significantly increasing the cessation rate at 1 week The objective of this study was to test the efficacy of the nicotine patch for relief of craving and withdrawal beyond 6 weeks ( during weeks 7 - 10 ) , among heavy , dependent smokers , using a multicenter , r and omized , double-blind , placebo-controlled trial . The subjects were 421 nicotine-dependent smokers who had quit smoking with the NicoDerm CQ nicotine patch , recruited from among enrollees in the NicoDerm CQ Committed Quitters behavioral program . Following 6 weeks of 21-mg active patch use , participants who had not relapsed were r and omized to receive either active or placebo patches for an additional 4 weeks with tapering ( 14-mg patch in weeks 7 - 8 and 7-mg patch in weeks 9 - 10 ) . Craving and withdrawal symptoms were assessed daily by phone interview during weeks 7 - 10 following cessation . The active patch group reported significantly lower craving and withdrawal , and higher positive mood scores in weeks 7 - 8 ( p < 0.001 , 0.001 , and 0.03 , respectively ) and weeks 9 - 10 ( p < 0.02 , 0.01 , and 0.02 , respectively ) compared to the placebo group . It was concluded that some smokers may be best served by 10 weeks of patch treatment . This study demonstrated the utility of continuing patch treatment for symptom relief in weeks 7 - 10 of abstinence . Future research should examine the optimal duration of treatment , which may vary across different classes of smokers Smoking cessation is a key intervention for prevention of several lung diseases . The aim of the present study was to compare the effect of smoking cessation with nicotine replacement in a lung clinic in a low re source set-up suitable for implementation in other lung clinics . This was an open , r and omized trial with 4 different nicotine replacement regimes combined with minimal behavioural support in daily routine . A total of 446 smokers ( > 9 cigarettes x day(-1 ) ) were allocated to a nurse-conducted smoking cessation programme with 4 treatment arms : a 5-mg nicotine patch ( " placebo " ) , a 15-mg nicotine patch , nicotine inhaler , and a 15-mg nicotine patch plus nicotine inhaler . Recommended use of the nicotine products were 3 months with the possibility of continuing use up to 9 months on an individual basis . Individual follow-up studies were scheduled after 2 and 6 weeks , 3 , 6 , 9 and 12 months . The 12-month point prevalence was 6 % ( 5-mg patch ( placebo ) ) , 16 % ( 15-mg patch ) ( p<0.05 ) , 9 % ( inhaler ) and 11 % ( 15-mg patch plus inhaler ) , respectively . To conclude , the set-up investigated in this study which included minimal behavioural support with nicotine patches should be evaluated in other lung clinics , as it doubled success rate when compared to a placebo with a 1-yr point prevalence of 16 % and also the re sources used are limited PURPOSE To examine the individual effects of supervised and intensive exercise as well as the combined effects of exercise and nicotine replacement therapy ( NRT ) on ( a ) smoking cessation and reduction rates and ( b ) psychological and physiological processes during withdrawal . METHODS One-hundred and forty-two inactive female smokers were r and omised into the following four groups : exercise+nicotine patch ; exercise+no nicotine patch ; cognitive behavior therapy (CBT)+nicotine patch and CBT+no nicotine patch . Smoking abstinence ( verified by saliva cotinine and expired carbon monoxide ) , cessation self-efficacy , and physical fitness and body weight were assessed at baseline ( week 1 ) , quit date ( week 6 ) , program termination ( week 12 ) , and 3- and 12-month follow-up . RESULTS There were significant differences in a 7-day point prevalence but not continuous abstinence rates between treatment groups across targeted end points . Consistently higher cessation rates were seen when NRT was added to both treatment programs . Compared with CBT participants , exercise participants had significantly increased functional exercise capacity and had gained significantly less weight during program end points but these differences did not hold at a 12-month follow-up . Compared with exercise participants , CBT participants felt greater cessation efficacy and reported greater knowledge , coping and support re sources across all end points . CONCLUSIONS Exercise combined with NRT facilitates smoking cessation , improves functional exercise capacity , and delays weight gain in women smokers . We recommend that physicians and health care professionals recommend exercise and NRT together for highly motivated women interested in quitting smoking Objectives : To trial an intervention in a real-life setting to motivate low-income smokers to try to quit . The intervention under trial was the addition of subsidised nicotine replacement therapy ( NRT ) to a st and ard population quitline service . Design : Participants were low-income smokers , recruited “ cold ” via either a letter in the mail or a flyer inserted in a local newspaper . The intervention group received the usual service of multisession counselling from the quitline plus access to heavily subsidised NRT . A comparison group received the usual quitline service only . Participants were followed up at 3 , 6 , and 12 months . Trial participants were also compared with a sample of general callers to the quitline . Results : The offer of subsidised NRT recruited more than twice as many low-income smokers than the offer of the cessation service alone ( intervention group n = 1000 ; comparison group n = 377 ) . 63 % were first-time callers to the quitline . Intervention respondents showed higher levels of nicotine dependence than comparison group respondents . Comparisons of quitting data were confounded by the differences in the respondents at baseline . 73.5 % of smokers in the intervention group tried to quit compared to 61.0 % in the comparison group . Unadjusted quit rates were higher in the intervention group than in the comparison group at 3 months and 6 months but not at 12 months . Conclusions : Disadvantaged smokers were easily engaged to call the quitline , particularly when offered subsidised NRT . Disadvantaged smokers using the quitline , with and without subsidised NRT , achieved cessation outcomes comparable to other studies of “ mainstream ” smokers OBJECTIVES The purpose of this study was to determine whether smoking cessation improves flow-mediated dilation ( FMD ) of the brachial artery . BACKGROUND The long-term effects of continued smoking and smoking cessation on endothelial function have not been described previously . METHODS This was a 1-year , prospect i ve , double-blind , r and omized , placebo-controlled clinical trial of the effects of 5 smoking cessation pharmacotherapies . FMD was measured by B-mode ultrasonography before and 1 year after the target smoking cessation date . Cessation was verified by exhaled carbon monoxide levels . DeltaFMD was compared among study arms and between subjects who successfully quit smoking and those who continued to smoke . Predictors of baseline FMD and DeltaFMD were identified by multivariable regression . RESULTS The 1,504 current smokers ( 58 % female , 84 % white ) were 44.7 + /- 11.1 years of age and smoked 21.4 + /- 8.9 cigarettes/day . Baseline FMD was similar in each treatment arm ( p = 0.499 ) and was predicted by BA diameter ( p < 0.001 ) , reactive hyperemia blood flow ( p < 0.001 ) , high-density lipoprotein cholesterol ( p = 0.001 ) , and carbon monoxide ( p = 0.012 ) levels . After 1 year , 36.2 % quit smoking . FMD increased by 1 % ( 6.2 + /- 4.4 % to 7.2 + /- 4.2 % ) after 1 year ( p = 0.005 ) in those who quit , but did not change ( p = 0.643 ) in those who continued to smoke . Improved FMD among quitters remained significant ( p = 0.010 ) after controlling for changes in brachial artery diameter , reactive hyperemia , low-density lipoprotein cholesterol , and the presence of a home smoking ban . CONCLUSIONS Despite weight gain , smoking cessation leads to prolonged improvements in endothelial function , which may mediate part of the reduced cardiovascular disease risk observed after smoking cessation . ( Smoking Cessation Medications : Efficacy , Mechanisms and Algorithms ; NCT00332644 ) Rationale Existing nicotine replacement therapies ( NRT ) improve the chances of smoking cessation but are limited by either relatively slow nicotine absorption rates or unpleasant side effects , leaving scope for the development of more effective and acceptable products . Objectives This study aim ed to test the acceptability and effectiveness for withdrawal symptom relief of a novel nicotine delivery device , the ‘ Nicotine Cannon ’ ( NC ) , compared with three existing , equivalent products : the nicotine lozenge , mini-lozenge and nicotine inhalator . Methods A repeated- measures crossover trial where participants were r and omised to one of two conditions ( 1- or 10-h abstinence ) and in each condition to one of 24 possible sequence permutations to test each product for 10 min was carried out . St and ard sociodemographic and smoking characteristics were assessed as well as withdrawal and NRT use symptoms before , during and after NRT use and product satisfaction after use . Results The results were similar across both duration s of abstinence . The NC was significantly more effective than the inhalator in reducing withdrawal symptoms ( F(3 , 196 ) = 3.5 , p = 0.015 ) and together with the mini-lozenge performed better than other NRT in alleviating urges to smoke ( F(3 , 563 ) = 9.6 , p < 0.001 ) and desire for cigarettes within 10 min of use ( F(3 , 727 ) = 26.1 , p < 0.001 ) . The NC induced fewer adverse side effects than other NRT and was judged to be more enjoyable ( F(3 , 87 ) = 13.56 , p < 0.001 ) and satisfying to use ( F(3 , 92 ) = 12.35 , p < 0.001 ) . Conclusions The ‘ Nicotine Cannon ’ is at least as effective as equivalent NRT in reducing withdrawal symptoms and more acceptable to users , suggesting that it would be a useful addition to existing NRT . The acceptability profile could make it particularly useful as a ‘ harm reduction ’ tool To determine the effectiveness of nicotine polacrilex combined with self-administered relapse prevention material s in maintaining smoking cessation , we conducted a r and omized , double-blind , placebo controlled trial . Volunteers aged 18 to 65 years responding to media announcements were required to quit smoking for 48 hours without assistance . Of 1844 potential participants , 136 were medically excluded , 535 declined to make a quit attempt , and 573 were unable to quit , leaving 600 participants ( 35 % ) who were r and omized . Eight self-help relapse prevention modules were mailed weekly . Gum was used either ad lib for smoking urges or on a fixed , hourly schedule ( 12 pieces per day ) . Only 15 % of the subjects in each gum group stopped using the gum altogether because of side effects , but only 20 % of the ad lib groups and 40 % of the fixed-dosage group used at least eight pieces of gum per day during the first week . The abstinence rates ( for at least seven days ) at the six-month follow-up were 31 % in both active gum groups and 22 % in the placebo and no gum groups . Relapse rates in the two active gum groups were about half those in the placebo and no gum groups . Nicotine polacrilex may be a useful adjunct to minimal contact smoking cessation formats , which have broad appeal . Also , minimal contact relapse prevention programs may assist physicians in helping patients to maintain smoking cessation using nicotine polacrilex OBJECTIVE To evaluate the smoking cessation efficacy of nicotine patch therapy as an adjunct to low-intensity , primary care intervention . DESIGN R and omized , placebo-controlled , double-blind , multisite trial . SETTING S Twenty-one primary care sites in Nebraska . PATIENTS A total of 369 smokers of 20 or more cigarettes per day . INTERVENTION Two brief primary care visits for smoking intervention with 10 weeks of active or placebo-patch therapy . MAIN OUTCOME MEASURES Confirmed self-reported abstinence 3 , 6 , and 12 months after the quit day . RESULTS Compared with placebo control subjects , participants assigned nicotine patches had higher 3-month ( 23.4 % vs 11.4 % ; P < .01 ) and 6-month ( 18.5 % vs 10.3 % ; P < .05 ) abstinence rates . The 1-year abstinence rates for the active and placebo patch groups were 14.7 % and 8.7 % , respectively ( P = .07 ) . Of smokers aged 45 years and older , 9 ( 18.8 % ) of 48 using active patches compared with 0 of 31 using placebo patches achieved 12-month abstinence ( chi 2 = 6.56 ; P < .05 ) . Among those with high nicotine dependency scores ( Fagerstrom score > or = 7 ) , 1-year abstinence rates were significantly higher in the nicotine patch group ( 19.1 % ) compared with the placebo group ( 5.0 % ) ( chi 2 = 10.7 ; P = .001 ) . However , there was no significant difference in 1-year quit rates for participants with low Fagerstrom scores ( < 7 ) . CONCLUSIONS Nicotine patch therapy enhanced 6 month quit rates as an adjunct to brief primary care intervention . The highest quit rates were achieved by participants who specifically contacted the site to enroll in the study or to obtain a prescription for nicotine patches . Differences in participant selection factors may account , in part , for the lower smoking cessation rates associated with primary care intervention . Duration of counseling , patient age , and Fagerstrom scores may be important factors related to the long-term smoking cessation success of nicotine patch therapy Hospital patients with smoking-related diseases rarely heed medical advice to stop smoking even when this advice is reinforced with nicotine gum and written material ( 1,2 ) , the exception being those with acute myocardial infa rct ion ( 3,4 ) . In contrast , success rates with advice , nicotine gum and specialized support sessions in smoking cessation clinics range from 38 % in healthy clients ( 5 ) to 29 % in a mixed group of clients and patients ( 6 ) . In our study the ' stop smoking ' advice of the physician was reinforced by advice/support from a research assistant ( SB ) and by nicotine ( N ) or placebo ( P ) chewing gum BACKGROUND Weight gain after smoking cessation is often cited by women smokers as a primary reason for not attempting to quit smoking or for relapsing after a cessation attempt . METHODS A r and omized trial of 417 women smokers was conducted to test the addition of two weight control strategies to a smoking cessation program . Participants received the st and ard smoking cessation program , the program plus nicotine gum , the program plus behavioral weight control , or the program plus both nicotine gum and behavioral weight control . Weight and smoking status were measured at the end of treatment and at 6 and 12 months posttreatment . RESULTS Smoking cessation rates were highest in the group receiving the smoking cessation program plus nicotine gum . Weight gain did not vary by treatment condition , so its effect on relapse could not be examined by group . There was no significant relationship between weight gained and relapse in individuals . CONCLUSIONS The added behavioral weight control program was attractive to the participants and did not reduce smoking cessation rates . However , it did not produce the expected effect on weight , thereby restricting our ability to examine the effect of weight control on smoking cessation and relapse OBJECTIVE To evaluate the efficacy of a new nicotine inhaler system for smoking cessation . DESIGN A 1-year , r and omized , double-blind , placebo-controlled study . SETTING Medical outpatient clinic with physicians experienced in smoking cessation assistance . SUBJECTS A total of 286 volunteers who smoked at least 10 cigarettes daily recruited through a local newspaper . INTERVENTION Subjects were r and omly allocated to nicotine inhalers ( n = 145 ) or placebo ( n = 141 ) to be used for 3 months followed by tapering for 3 months in the context of minimal levels of advice and support . MAIN OUTCOME MEASURE Continuous smoking abstinence at weeks 6 , 12 , 24 , and 52 , verified by measurements of carbon monoxide in expired air . RESULTS Continuous smoking abstinence was significantly higher for the active nicotine inhaler group compared with the placebo inhaler group . The respective success rates were 28 % and 12 % after 6 weeks , 21 % and 9 % after 12 weeks , 17 % and 8 % after 6 months , and 15 % and 5 % after 1 year ( P = .02 to .001 ) . The mean nicotine substitution based on cotinine determinations after 2 weeks was 43 % ( SD , 45 % ) of smoking levels . The treatment was well tolerated , and no serious adverse events were reported . CONCLUSIONS In this setting the nicotine inhaler appeared safe to use and increased success rates of smoking cessation attempts In this report , the authors explore the relationships of perceived treatment to outcome in a large , placebo-controlled trial of nicotine replacement treatment for smoking reduction . In the original study ( J. F. Etter , E. Laszlo , J. P. Zellweger , C. Perrot , & T. V. Perneger , 2002 ) , which was conducted in French-speaking Switzerl and , smokers were r and omly assigned to receive nicotine , matching placebo products , or no intervention . At the end of the 6-month study , participants were asked to guess whether they had received nicotine or placebo . In the present analysis , the authors examined the difference in smoking reduction between those who believed they had received nicotine and those who believed they had received placebo . Regardless of actual treatment , smokers who believed they had received nicotine had significantly better outcome than those who believed they had received placebo BACKGROUND Rates of smoking cessation have not changed in a decade , accentuating the need for novel approaches to prompt quit attempts . METHODS Within a nationwide r and omized clinical trial ( N = 849 ) to induce further quit attempts and cessation , smokers currently unmotivated to quit were r and omized to a practice quit attempt ( PQA ) alone or to nicotine replacement therapy ( hereafter referred to as nicotine therapy ) , sampling within the context of a PQA . Following a 6-week intervention period , participants were followed up for 6 months to assess outcomes . The PQA intervention was design ed to increase motivation , confidence , and coping skills . The combination of a PQA plus nicotine therapy sampling added sample s of nicotine lozenges to enhance attitudes toward pharmacotherapy and to promote the use of additional cessation re sources . Primary outcomes included the incidence of any ever occurring self-defined quit attempt and 24-hour quit attempt . Secondary measures included 7-day point prevalence abstinence at any time during the study ( ie , floating abstinence ) and at the final follow-up assessment . RESULTS Compared with PQA intervention , nicotine therapy sampling was associated with a significantly higher incidence of any quit attempt ( 49 % vs 40 % ; relative risk [ RR ] , 1.2 ; 95 % CI , 1.1 - 1.4 ) and any 24-hour quit attempt ( 43 % vs 34 % ; 1.3 ; 1.1 - 1.5 ) . Nicotine therapy sampling was marginally more likely to promote floating abstinence ( 19 % vs 15 % ; RR , 1.3 ; 95 % CI , 1.0 - 1.7 ) ; 6-month point prevalence abstinence rates were no different between groups ( 16 % vs 14 % ; 1.2 ; 0.9 - 1.6 ) . CONCLUSION Nicotine therapy sampling during a PQA represents a novel strategy to motivate smokers to make a quit attempt . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00706979 Smoking cessation usually results in weight gain . Nicotine gum therapy has been found to reduce weight gain in the first months after cessation , but its long-term effects are not fully known . The present study r and omly assigned 608 smokers to receive placebo , 2 or 4 mg nicotine gum . In a follow-up analysis to the short-term weight change results reported in a previous paper [ Doherty , Militello , Kinnunen , & Garvey ( 1996 ) , Journal of Consulting and Clinical Psychology 64:799 - 807 ] , we examined the effects of the nicotine gum on weight change for 1 year after cessation among the 92 1-year abstainers . We found that weight change showed some variation with gum dose ( active vs. placebo ) , but that weight change appeared to depend more strongly on the percentage of pre-cessation cotinine levels replaced by the nicotine gum . Participants who replaced higher proportions of their pre-cessation cotinine during the gum therapy period gained less weight during the first year post-cessation than those who replaced less cotinine , with those who replaced greater than 90 % of their cotinine gaining only 1.7 kg by 1 year post-cessation . These findings suggest that future research is warranted to determine whether sufficiently high levels of nicotine replacement can help to permanently reduce cessation-related weight gain AIMS To examine the effectiveness of smoking reduction counselling plus free nicotine replacement therapy ( NRT ) for smokers not willing to quit . DESIGN , SETTING AND PARTICIPANTS A total of 1154 Chinese adult smokers not willing to quit but who were interested in reducing smoking were allocated r and omly to three arms . Intervention group A1 ( n=479 ) received face-to-face counselling on smoking reduction and adherence to NRT at baseline , 1 week and 4 weeks with 4 weeks of free NRT . Group A2 ( n=449 ) received the same intervention , but without the adherence intervention . Control group B ( n=226 ) received simple cessation advice at baseline . MEASUREMENTS Self-reported 7-day point prevalence of tobacco abstinence and reduction of cigarette consumption ( ≥50 % ) at 6 months and continuous use of NRT for 4 weeks at 3 months . FINDINGS Using intention-to-treat analysis , compared to control group B , the intervention groups ( A1+A2 ) had achieved higher 6-month tobacco abstinence ( 17.0 % versus 10.2 % , P=0.01 ) and reduction rates ( 50.9 % versus 25.7 % , P<0.001 ) . There was no significant difference in the 4-week NRT adherence rate at 3 months , but group A1 achieved a higher abstinence rate than group A2 at 6 months ( 20.9 % versus 12.9 % ; P=0.001 ) . CONCLUSIONS In smokers with no immediate plans to quit , smoking reduction programmes with behavioural support and nicotine replacement therapy are more effective than brief advice to quit . Current guidelines recommend advice to quit on medical grounds as the best clinical intervention in this group of smokers , but smoking reduction programmes offer an alternative and effective option Background : Smoking is common in young people , particularly in disadvantaged groups , and continued smoking has a major impact on quality and quantity of life . Although many young smokers want to stop smoking , little is known about the design and effectiveness of cessation services for them . Objective : To determine whether nicotine replacement therapy ( NRT ) when combined with counselling is effective in young smokers in a deprived area of Nottingham , UK Methods and subjects : We surveyed smoking prevalence and attitudes to smoking and quitting in young people accessing an open access youth project in a deprived area of Nottingham , and used the information gained to design a community based smoking cessation service incorporating a r and omised controlled trial of nicotine patches against placebo given in association with individual behavioural support . We resurveyed smoking prevalence among project attendees after completing the pilot study . Results : Of 264 young people surveyed ( median age 14 years , range 11–21 ) , 49 % were regular smokers . A total of 98 young people were recruited and r and omised to receive either active nicotine patches on a six week reducing dose regimen ( 49 participants ) , or placebo ( 49 participants ) . Adherence to therapy was low , the median duration being one week , and 63 participants did not attend any follow up . At four weeks , five subjects receiving active NRT and two receiving placebo were abstinent , and at 13 weeks none were . Adverse effects were more common in the active group but none were serious . Smoking prevalence among 246 youth project attendees surveyed after the trial was 44 % . Conclusions : This study suggests that NRT in this context is unlikely to be effective in young smokers , not least because of low adherence to therapy . It also suggests that young smokers want help with smoking cessation , but that establishing the efficacy of smoking cessation services for young people who need them most will be very difficult The results are reported from a multicentered , r and omized clinical trial of a physician-delivered smoking cessation intervention package . All physicians attended a four-hour training session during which the rationale s for the different aspects of the intervention were discussed , including a detailed description of the proper use of nicotine-bearing chewing gum . Patients were r and omized to receive an offer of a prescription of 2 mg of nicotine chewing gum in addition to the basic intervention ( n = 111 ) or the basic intervention alone ( n = 112 ) . The basic intervention included advice , setting a date for quitting , self-help material s , and the offer of supportive follow-up visits . Receptionists were instructed to recruit the first two smokers attending the practice each day . One-year smoking cessation was vali date d by cotinine saliva analysis . The vali date d three-month sustained abstinence rates at one year were 8.1 percent and 9.8 percent in the gum and no-gum groups , respectively . The 95 percent confidence interval about this difference was -9.3 percent to 6.4 percent . There is no evidence from this study that the offer of 2 mg of nicotine-bearing gum enhances smoking cessation rates when added to a comprehensive intervention offered to all smokers in primary care . Until larger trials are completed , however , the possibility that this dose of nicotine gum may produce small beneficial effects can not be excluded Three hundred fifteen smokers who attended a family practice clinic and wished to quit smoking were assigned in a r and om , double-blind manner to receive either nicotine ( 2 mg ) or placebo gum . Smokers initially received brief advice from a physician and nurse , a slide presentation and written material s ( 29 to 35 minutes ) , and a single follow-up visit ( 12 to 20 minutes ) one week after cessation . After corrections for marital status and income , 10 % of those who received nicotine gum and 7 % of those who received placebo gum reported continuous abstinence for 11 months and passed observer and biochemical verification ( this difference was not statistically significant ) . We conclude that , when used in a nonselected group of smokers along with a brief intervention in a general medical practice , the pharmacologic effects of nicotine gum to increase cessation are either small or nonexistent The effectiveness of 2 mg nicotine chewing-gum as an aid to stopping smoking was compared with a placebo containing 1 mg nicotine , but unbuffered , in a double-blind r and omised trial . Of 58 subjects given the active gum , 27 ( 47 % ) were not smoking at one-year follow-up compared with 12 ( 21 % ) of the 58 subjects treated with placebo ( p less than 0.025 ) . By the most stringent criterion of outcome , 18 ( 31 % ) subjects in the active treatment group and eight ( 14 % ) in the placebo group had not smoked at all from the start of treatment to follow-up at one year ( p less than 0.05 ) . Subjects receiving the active gum experienced less severe withdrawal symptoms and rated their gum as more helpful than did the placebo group . Minor side effects were common but only gastric symptoms were more frequent with the active gum . Subjects receiving active gum used it for longer than those receiving placebo but most stopped using it within six months and only four ( 7 % ) developed longer-term dependence . The number of gums used daily correlated significantly with pretreatment blood nicotine concentrations in the active treatment group and with pretreatment cigarette consumption in the placebo group . A lower pretreatment blood nicotine value was the best predictor of success at one year ( p less than 0.001 ) but there was no significant relation to cigarette consumption , sex , and social class . The results clearly confirm the usefulness of nicotine chewing-gum as an aid to stopping smoking and imply a definite role for nicotine in cigarette dependence and withdrawal . Successful use of the gum requires careful attention to subjects ' expectations and clear instructions on how to use it Pharmacological interventions for smoking cessation are typically evaluated using volunteer sample s ( efficacy trials ) but should also be evaluated in population -based trials ( effectiveness trials ) . Nicotine replacement therapy ( NRT ) alone and in combination with behavioral interventions was evaluated on a population of smokers from a New Engl and Veterans Affairs Medical Center . Telephone interviews were completed with 3,239 smokers , and 2,054 agreed to participate ( 64 % ) . Participants were r and omly assigned to one of four conditions : stage-matched manuals ( MAN ) ; NRT plus manuals ( NRT + MAN ) ; expert system plus NRT and manuals ( EXP + NRT + MAN ) ; and automated counseling plus NRT , manuals , and expert system ( TEL + EXP + NRT + MAN ) . Assessment s were completed at baseline , 10 , 20 , and 30 months . The point prevalence cessation rates at final follow-up ( 30 months ) were MAN , 20.3 % ; NRT + MAN , 19.3 % ; EXP + NRT + MAN , 17.6 % ; and TEL + EXP + NRT + MAN , 19.9 % . Stage-matched manuals provided cessation rates comparable with previous studies . The addition of NRT , expert system interventions , and automated telephone counseling failed to produce a further increase in intervention effectiveness Smokers ( N = 126 ) were r and omly assigned to 6-session smoking cessation treatments consisting of 1 of 2 counseling strategies ( skills training or support ) and 1 of 2 nicotine exposure strategies ( nicotine gum or rapid smoking ) . Counseling and nicotine strategies were completely crossed ; all four combinations result ed in equivalent 1-year abstinence rates . Skills training produced higher initial cessation and more coping responses posttreatment than did support . Rapid smoking , but not nicotine gum , produced tachycardia to the taste of cigarettes posttreatment , consistent with cigarette aversion . The treatments were differentially effective among sub population s of smokers : Subjects high in pretreatment negative affect responded best to support counseling ; those low in pretreatment negative affect responded best to skills training . Self-reports of pretreatment craving predicted response to the nicotine exposure treatments OBJECTIVE To monitor the effect of a novel nicotine delivery device that may produce fewer carcinogens ( Eclipse ) on cigarette smoking , carbon monoxide and nicotine concentrations , and motivation to give up smoking . The smoker 's own br and of cigarette and a nicotine replacement product ( Nicotrol inhaler ) were used as comparisons . DESIGN After baseline data were recorded , smokers were r and omised to either Eclipse or inhaler for two weeks and then switched to the other product for another two weeks . Thereafter a second baseline was obtained . SETTING AND PARTICIPANTS Fifty smokers were included and data are reported for the 40 with complete data sets . The smokers were not trying to quit but were interested in trying a new product to reduce their risk . They visited a smoking clinic 10 times during the six week period of the trial . INTERVENTION No counselling to aid reduction by Eclipse or inhaler was given . MAIN OUTCOME MEASURES At each visit smoking status and carbon monoxide concentrations were recorded . In half of the visits withdrawal symptoms , attitudes towards smoking , heart rate , and blood nicotine concentrations were also recorded . RESULTS Eclipse use decreased the number of cigarettes smoked per day ( cpd ) from 19.1 cpd at baseline to 2.1 cpd ( p < 0.001 ) , but increased carbon monoxide concentrations in parts per million ( ppm ) from 21.0 ppm to 33.0 ppm ( p < 0.001 ) . A similar decrease in cigarettes smoked per day was seen with the Nicotrol inhaler , from 19.1 cpd to 4.8 cpd ( p < 0.001 ) , but carbon monoxide decreased from 21.0 ppm to 12.7 ppm ( p < 0.001 ) . The blood nicotine concentration remained fairly stable with Eclipse , increasing slightly from 16.8 ng/ml to 18.0 ng/ml , while for the inhaler a significant drop was noted , from 16.8 ng/ml to 12.2 ng/ml ( p < 0.002 ) . Craving and withdrawal did not increase with Eclipse . Few significant adverse events occurred with Eclipse . CONCLUSIONS Eclipse can dramatically decrease cigarette consumption without causing withdrawal symptoms or decreases in nicotine concentrations or motivation to quit altogether . Unlike the inhaler , Eclipse produces an increase in carbon monoxide concentration . Thus Eclipse may not be a safer cigarette This study examined the efficacy of transdermal nicotine in postmenopausal smokers , and whether a history of depression or hormone replacement therapy ( HRT ) moderated smoking cessation outcomes . Postmenopausal smokers ( N=152 ) received intensive smoking cessation counseling and were r and omly assigned to use either a 21-mg nicotine patch for 3 months , with a 1-month taper , or a placebo patch . The primary outcome was biochemically vali date d 7-day point prevalence smoking abstinence during treatment ( i.e. , 1 , 2 , 6 , and 12 weeks after the quit date ) and 1 year after study medication was discontinued . Subjects who received transdermal nicotine were significantly more likely than placebo-treated subjects to remain abstinent from smoking during treatment , but not at the 1-year follow-up . The majority of subjects ( > 50 % ) in both groups accurately identified their treatment assignment . History of depression was associated with a decreased likelihood to abstain from smoking throughout the study . HRT did not moderate smoking outcomes . These data indicate that transdermal nicotine may provide short-term benefits for smoking cessation in postmenopausal women . However , efforts are needed to improve long-term abstinence rates and smoking outcomes among women with a history of depression The primary aim of this smoking cessation study was to evaluate the effect of long-term treatment with nicotine nasal spray in a group of hard-core smokers . A further aim was to compare the effect of ad libitum with fixed dosage of nasal nicotine spray . Eighty nine smokers , failures from two earlier studies with nicotine patches , were enrolled in an open smoking cessation study with nicotine nasal sprays , to be used ad libitum ( n=45 ) or on a fixed schedule of 1 mg x h-1 during the day ( n= 44 ) . Carbon monoxide-verified continuous abstinence from smoking beyond Week 2 , was 39 % at 3 weeks , 12 % at 3 months , 10 % at 6 months and 6 % after 1 yr , with no significant difference in success rate between ad libitum and fixed dosing . Mean daily nicotine dose was 15 - 16 mg during the first 3 months ( range 2 - 65 mg ) . Tolerance to local irritating side-effects of nicotine developed during the first weeks of use . Although short-term outcome was promising , the long-term success rate in this group of hardcore smokers was low . Other recycling set-ups are warranted , which might include more aggressive nicotine dosing Background : The purpose of this study is to assess social support and demographic factors that influence the success of smoking cessation aided with sublingual nicotine tablets in a Han Chinese population . Methods : We r and omly allocated 211 Beijing residents who smoked ≥ 10 cigarettes a day for at least 1 year into a double-blind , placebo-controlled 3-month r and omized smoking cessation trial using sublingual nicotine replacement therapy ( NRT ) . Self-reports of sustained smoking cessation were verified during the study by expired carbon monoxide concentrations and urine-cotinine concentrations . Logistic regression analysis used an intent to treat sample for sociodemographic associations with abstinence and reduction in smoking . Results : The abstinence rates at the end of treatment for NRT vs. placebo were 52 % vs .19 % , and smoking reduction ( reduced to at least 50 % of baseline ) rates for NRT vs. placebo were 43 % vs .15 % for a total response rate with NRT of 95 % for either stopping completely or reducing smoking by 50 % . The only factor strongly associatedwith successful smoking cessation after 3 months of sublingual NRT was being married ( adjusted odds ratio 2.18 ; 95%confidence interval 1.10–4.33 ) . Smoking association , on the other h and , was associated with being married and with employment as a white collar worker ( 2.24 ; 1.03 to 4.86 ) . Conclusions : These findings suggest the need for a more in-depth examination of the impact of being married and employment as a white collar worker ( rather than manual laborer ) in order to develop better targeted interventions for improving smoking cessation interventions A transdermal nicotine patch , which delivers 0.7 mg/cm2 per 24 h and is available in sizes of 10 , 20 , and 30 cm2 was tested in subjects from 21 general medical practice s in a 3-month , placebo-controlled r and omised double-blind study . The nicotine group ( n = 100 ) and the placebo group ( n = 99 ) were similar at entry . Participants who smoked more than 20 cigarettes a day were treated with the 30 cm2 patch and the others with the 20 cm2 patch . When abstinence , defined as smoking 0 - 3 cigarettes per week and verified by CO measurement , was achieved , the next smallest patch was applied . After 1 , 2 , and 3 months of treatment 41 , 36 , and 36 % , respectively , in the nicotine group were abstinent . The corresponding figures in the placebo group were 19 , 20 , and 23 % . The differences were significant for all 3 months . Body weight did not increase in the nicotine group , but in the placebo group the mean increase was 4.4 kg . Craving and withdrawal symptoms decreased more with nicotine substitution for cigarettes . The patches were generally well tolerated , although 25 % of subjects in the nicotine group and 13 % in the placebo group had transient local erythema after application of the patch ; 5 members of the nicotine group withdrew because of poor cutaneous tolerance This study compares the nicotine patch to placebo in young adult light smokers , and the nicotine patch to varenicline in heavy smokers . Volunteer daily smokers were recruited into a r and omized , placebo‐controlled study via community media , colleges and the army ( aged 18–26 years ) . Those subjects with light tobacco dependence were r and omized to ( i ) placebo patch ( n = 86 ) and ( ii ) nicotine patch 10 mg/16 hr for 8 weeks ( n = 94 ) , and those with stronger dependence to ( iii ) nicotine patch 15 mg/16 hr for 8 weeks ( n = 51 ) and ( iv ) varenicline for 12 weeks ( n = 60 ) . The primary outcome variable was self‐reported smoking abstinence at week 12 . Secondary outcome variables were self‐reported smoking abstinence at weeks 4 and 26 , and self‐reported abstinence verified by saliva cotinine level at week 12 . The prevalence of self‐reported smoking abstinence did not differ statistically significantly in light smokers during the follow‐up ( week 4 : 19.8 % for placebo patch and 26.6 % for nicotine patch 10 mg/16 hr ; week 12 : 17.4 % versus 23.4 % ; week 26 : 15.1 % versus 20.2 % ) , but the groups of heavy smokers differed significantly for 12 weeks ( week 4 : 19.6 % for nicotine patch 15 mg/16 hr and 73.3 % for varenicline , p < 0.001 ; week 12 : 15.7 % versus 36.7 % , p = 0.018 ) . This statistically significant difference did not endure for the entire follow‐up ( week 26 : 9.8 % versus 18.3 % , p = 0.280 ) . However , saliva cotinine verified abstinence at week 12 did not support self‐reported abstinence . Varenicline may be more effective than the nicotine patch as a smoking cessation pharmacotherapy among young adult heavy smokers in the short‐term Background This study evaluates differences in smoking abstinence between white and minority smokers using pharmaceutical aids . Methods This is an analysis of data from a multi-center , r and omized , clinical trial conducted in the United States . Of the 1,684 subjects r and omized to one of three medications ( nicotine inhaler , bupropion , or a combination of both ) , 60 % were women and 10 % were minority races . Results Factors associated with a decreased likelihood of smoking at 12 weeks were older age ( OR = 0.971 , p < 0.0001 ) , being married ( OR = 0.678 , p = 0.0029 ) , using bupropion SR ( OR = 0.480 , p < 0.0001 ) , and using combination therapy ( OR = 0.328 , p < 0.0001 ) . Factors associated with an increased likelihood of smoking were higher tobacco dependence scores ( OR = 1.244 , p < 0.0001 ) , prior quit attempts ( OR = 1.812 , p = 0.004 ) , and being a minority ( OR = 1.849 , p = 0.0083 ) . Compared to white smokers , minority smokers were significantly older at time of study entry ( 46 vs. 42 years , p < 0.0001 ) , less likely to be married ( 35 % vs. 59 % , p < 0.0001 ) , older at smoking initiation ( 21 vs. 19 years of age , p < 0.0001 ) , and had a lower abstinence rate ( 16 % vs. 26 % , p = 0.0065 ) . Conclusion Regardless of the treatment used , minority smokers in the US have lower smoking abstinence after treatment for tobacco dependence . Future research should focus on the improvement in treatment strategies for minority smokers AIMS To identify promising intervention components intended to help smokers to attain and maintain abstinence in their quit smoking attempts . DESIGN A fully crossed , six-factor r and omized fractional factorial experiment . SETTING Eleven primary care clinics in southern Wisconsin , USA . PARTICIPANTS A total of 637 adult smokers ( 55 % women , 88 % white ) motivated to quit smoking who visited primary care clinics . INTERVENTIONS Six intervention components design ed to prepare smokers to quit , and achieve and maintain abstinence ( i.e. for the preparation , cessation and maintenance phases of smoking treatment ) : ( 1 ) preparation nicotine patch versus none ; ( 2 ) preparation nicotine gum versus none ; ( 3 ) preparation counseling versus none ; ( 4 ) intensive cessation in-person counseling versus minimal ; ( 5 ) intensive cessation telephone counseling versus minimal ; and ( 6 ) 16 versus 8 weeks of combination nicotine replacement therapy ( nicotine patch + nicotine gum ) . MEASUREMENTS Seven-day self-reported point-prevalence abstinence at 16 weeks . FINDINGS Preparation counseling significantly improved week 16 abstinence rates ( P = .04 ) , while both forms of preparation nicotine replacement therapy interacted synergistically with intensive cessation in-person counseling ( P < 0.05 ) . Conversely , intensive cessation phone counseling and intensive cessation in-person counseling interacted antagonistically ( P < 0.05)-these components produced higher abstinence rates by themselves than in combination . CONCLUSIONS Preparation counseling and the combination of intensive cessation in-person counseling with preparation nicotine gum or patch are promising intervention components for smoking and should be evaluated as an integrated treatment package Rationale Previous research has shown limited efficacy of nicotine replacement therapy ( NRT ) among adolescents and generally low compliance rates . As higher compliance rates are associated with improved abstinence rates , the present study examined predictors of NRT compliance . Objectives This study aims to test whether different NRT compliance trajectories can be distinguished among adolescents , to test whether these trajectories can be predicted by demographic , smoking-related , and personality factors , and to examine abstinence rates for each trajectory . Methods Data were used from a r and omized controlled trial that tested the efficacy of nicotine patches versus placebo patches among 265 Dutch adolescents . During NRT treatment , adolescents filled out six online question naires in which they reported on the number of days they used the patches . Predictors ( i.e. , demographic and smoking-related factors and personality characteristics ) and end-of-treatment abstinence were also administered through these self-reports . Latent class growth analysis ( LCGA ) was used to analyze compliance data by classifying individuals into similar growth trajectories . Results Three compliance trajectories were found ( i.e. , “ compliers ” ( n = 89 ) , “ moderate decreasers ” ( n = 41 ) , and “ strong decreasers ” ( n = 127 ) ) . The compliers can be characterized by higher levels of conscientiousness and agreeableness and lower levels of extraversion compared with the strong decreasers , and by higher levels of conscientiousness and education compared with the moderate decreasers . Among the compliers , a substantially higher percentage of adolescents achieved abstinence at end-of-treatment ( 10 % ) compared with the moderate decreasers ( 3 % ) and the strong decreasers ( 6 % ) . Conclusions These findings could be the starting point for person-tailored interventions that aim to enhance NRT compliance rates among adolescents Background Hospitalized smokers often quit smoking , voluntarily or involuntarily ; most relapse soon after discharge . Extended follow-up counseling can help prevent relapse . However , it is difficult for hospitals to provide follow-up and smokers rarely leave the hospital with quitting aids ( for example , nicotine patches ) . This study aims to test a practical model in which hospitals work with a state cessation quitline . Hospital staff briefly intervene with smokers at bedside and refer them to the quitline . Depending on assigned condition , smokers may receive nicotine patches at discharge or extended quitline telephone counseling post-discharge . This project establishes a practical model that lends itself to broader dissemination , while testing the effectiveness of the interventions in a rigorous r and omized trial . Methods / design This r and omized clinical trial ( N = 1,640 ) tests the effect of two interventions on long-term quit rates of hospitalized smokers in a 2 x 2 factorial design . The interventions are ( 1 ) nicotine patches ( eight-week , step down program ) dispensed at discharge and ( 2 ) proactive telephone counseling provided by the state quitline after discharge . Subjects are r and omly assigned into : usual care , nicotine patches , telephone counseling , or both patches and counseling . It is hypothesized that patches and counseling have independent effects and their combined effect is greater than either alone . The primary outcome measure is thirty-day abstinence at six months ; a secondary outcome is biochemically vali date d smoking status . Cost-effectiveness analysis is conducted to compare each intervention condition ( patch alone , counseling alone , and combined interventions ) against the usual care condition . Further , this study examines whether smokers ’ medical diagnosis is a moderator of treatment effect . Generalized linear ( binomial ) mixed models will be used to study the effect of treatment on abstinence rates . Clustering is accounted for with hospital-specific r and om effects . Discussion If this model is effective , quitlines across the U.S. could work with interested hospitals to set up similar systems . Hospital accreditation st and ards related to tobacco cessation performance measures require follow-up after discharge and provide additional incentive for hospitals to work with quitlines . The ubiquity of quitlines , combined with the consistency of quitline counseling delivery as central ized state operations , make this partnership attractive . Trial registration Smoking cessation in hospitalized smokers NCT01289275 . Date of registration February 1 , 2011 ; date of first patient August 3 , 2011 OBJECTIVES --(a ) To evaluate the efficacy of transdermal nicotine patches as an aid to stopping smoking when used as an adjunct to brief advice and support in a general practice setting ; ( b ) to see whether an increase in nicotine patch dosage enhances the rate of initial cessation . DESIGN --R and omised double blind placebo controlled parallel group study with one year of follow up . SETTING --30 general practice s in 15 English counties . SUBJECTS--600 dependent heavy smokers ( > or = 15 cigarettes daily ) who were well motivated to give up . INTERVENTIONS --Brief general practitioner advice , booklet , and 16 hours per day patch treatment for 18 weeks with brief support and follow up at one , three , six , 12 , 26 , and 52 weeks . MAIN OUTCOME MEASURES --Self reported complete abstinence for up to one year with biochemical validation at all follow up points . RESULTS --Nicotine patches reduced the severity of craving and adverse mood changes in the first weeks of withdrawal and doubled the rate of initial cessation at week 3 ( nicotine group 36 % of patients ( 144/400 ) , placebo group 16.5 % of patients ( 33/200 ) ) and of continuous abstinence throughout one year ( nicotine group 9.3 % ( 37 ) , placebo group 5.0 % ( 10 ) ) . A dose increase at week 1 among patients experiencing difficulty in quitting increased the proportion who achieved abstinence at week 3 . There were no adverse systemic effects attributable to nicotine , but the incidence of moderate or severe local irritation or itching at the patch site was 16.4 % ( 63 patients ) , compared with 3.8 % ( seven ) with placebo . CONCLUSION --Transdermal nicotine patches used as an adjunct to brief advice and support in a general practice setting are an effective aid to long term cessation of smoking in highly dependent smokers A nicotine mouth spray has advantages over other acute forms of nicotine replacement therapy , such as a faster uptake of nicotine and faster relief of craving . This multicentre , r and omised ( 2:1 ) , double-blind , placebo-controlled efficacy and safety study evaluated self-reported , carbon monoxide-verified continuous abstinence from smoking from week 2 until weeks 6 , 24 , and 52 in 479 smokers ( ≥1 cigarette per day ) who were treated with either active ( n=318 ) or placebo ( n=161 ) spray for 12 weeks and low-intensity counselling at three smoking cessation clinics in Denmark and Germany . Active treatment yielded significantly higher continuous abstinence rates than placebo from week 2 until week 6 ( 26.1 % versus 16.1 % ; relative success rate ( RR ) 1.62 , 95 % CI 1.09–2.41 ) , week 24 ( 15.7 % versus 6.8 % ; RR 2.30 , 95 % CI 1.23–4.30 ) , and week 52 ( 13.8 % versus 5.6 % ; RR 2.48 , 95 % CI 1.24–4.94 ) . Most adverse events were mild to moderate , and 9.1 % of subjects on active spray withdrew due to adverse events , compared to 7.5 % on placebo . The overall rate of treatment-related adverse events was 87.4 % with active spray versus 71.4 % with placebo spray . Nicotine mouth spray delivered significantly higher 6- , 24- and 52-week continuous abstinence rates than placebo Nicotine replacement by transdermal patches is more effective than placebo in smoking cessation , but has a low success rate after one year ( 9 - 18 % ) . We tested whether this was attributed to insufficient nicotine replacement . We conducted a r and omized trial to investigate the effect on outcome of different doses of transdermal nicotine replacement after stratification according to baseline plasma cotinine values . Two hundred and ninety seven adult smokers were enrolled . Those with baseline cotinine < or = 250 ng.ml-1 ( low cotinine ) were r and omly assigned to placebo ( LC-P ) or to 15 mg 16 h nicotine patches ( LC-15 ) , and those with baseline cotinine > 250 ng.mL-1 ( high cotinine ) were r and omly assigned to 15 mg ( HC-15 ) or 25 mg ( HC-25 ) 16 h nicotine patches . Plasma nicotine and cotinine values , expired carbon monoxide and withdrawal symptoms were measured at scheduled intervals during treatment . Smokers in the LC-15 group had a significantly higher success rate than placebo ( 28 vs 9 % ) . Smokers with high baseline cotinine had lower success rates , and a high dose of nicotine did not increase success rate ( HC-25 9 % vs HC-15 11 % ) . Subjects in the HC-15 group had the lowest percentage of nicotine replacement and a higher prevalence of withdrawal symptoms than the HC-25 group . Replacement was similar in groups LC-15 and HC-25 , but the success rate was significantly lower in HC-25 group , despite similar levels of withdrawal symptoms . We conclude that a higher success rate was obtained after one year in smokers with low baseline plasma cotinine values . Determination of plasma cotinine values may be , thus , helpful in identifying smokers who could benefit from transdermal nicotine replacement Background Even with effective smoking cessation medications , many smokers are unable to abruptly stop using tobacco . This finding has increased interest in smoking reduction as an interim step towards complete cessation . Methods This multi-center , double-blind placebo-controlled study evaluated the efficacy and safety of nicotine 4 mg gum or nicotine 10 mg inhaler in helping smokers ( N = 314 ) to reduce or quit smoking . It included smokers willing to control their smoking , and participants could set individual goals , to reduce or quit . The study was placebo-controlled , r and omized in a ratio of 2:1 ( Active : Placebo ) , and subjects could choose inhaler or gum after r and omization . Outcome was short-term ( from Week 6 to Month 4 ) and long-term ( from Month 6 to Month 12 ) abstinence or reduction . Abstinence was defined as not a single cigarette smoked and expired CO readings of < 10 ppm . Smoking reduction was defined as a reduction in number of cigarettes per day by 50 % or more versus baseline , verified by a lower-than-baseline CO reading at each visit during the same periods . Results Significantly more smokers managed to quit in the Active group than in the Placebo group . Sustained abstinence rates at 4 months were 42/209 ( 20.1 % ) subjects in the Active group and 9/105 ( 8.6 % ) subjects in the Placebo group ( p = 0.009 ) . Sustained abstinence rates at 12 months were 39/209 ( 18.7 % ) and 9/105 ( 8.6 % ) , respectively ( p = 0.019 ) . Smoking reduction did not differ between the groups , either at short-term or long-term . Twelve-month reduction results were 17.2 % vs. 18.1 % , respectively . No serious adverse events were reported . Conclusion In conclusion , treatment with 10 mg nicotine inhaler or 4 mg nicotine chewing gum result ed in a significantly higher abstinence rate than placebo . In addition a large number of smokers managed to reduce their cigarette consumption by more than 50 % compared to baseline Background Reducing smoking prevalence is a public health priority that can save more lives and money than almost any other known preventive intervention . Internet interventions have the potential for enormous public health impact given their broad reach and effectiveness . However , most users engage only minimally with even the best design ed websites , diminishing their impact due to an insufficient ‘ dose ’ . Two approaches to improve adherence to Internet cessation programs are integrating smokers into an online social network and providing free nicotine replacement therapy ( NRT ) . Active participation in online communities is associated with higher rates of cessation . Integrating smokers into an online social network can increase support and may also increase utilization of cessation tools and NRT . Removing barriers to NRT may increase uptake and adherence , and may also increase use of online cessation tools as smokers look for information and support while quitting . The combination of both strategies may exert the most powerful effects on adherence compared to either strategy alone . Methods / Design This study compares the efficacy of a smoking cessation website ( WEB ) alone and in conjunction with free NRT and a social network ( SN ) protocol design ed to integrate participants into the online community . Using a 2 ( SN , no SN ) x 2 ( NRT , no NRT ) r and omized , controlled factorial design with repeated measures at baseline , 3 months , and 9 months , this study will recruit N = 4,000 new members of an internet cessation program and r and omize them to : 1 ) WEB , 2 ) WEB + SN , 3 ) WEB + NRT , or 4 ) WEB + SN + NRT . Hypotheses are that all interventions will outperform WEB and that WEB + SN + NRT will outperform WEB + NRT and WEB + SN on 30-day point prevalence abstinence at 9 months . Exploratory analyses will examine theory-driven hypotheses about the mediators and moderators of outcome . Discussion Addressing adherence in internet cessation programs is critical and timely to leverage their potential public health impact . This study is innovative in its use of a social network approach to improve behavioral and pharmacological treatment utilization to improve cessation . This approach is significant for reducing tobacco ’s devastating disease burden and for optimizing behavior change in other arenas where adherence is just as critical . Trial registration IS RCT N : IS RCT AIMS To identify promising intervention components that help smokers attain and maintain abstinence during a quit attempt . DESIGN A 2 × 2 × 2 × 2 × 2 r and omized factorial experiment . SETTING Eleven primary care clinics in Wisconsin , USA . PARTICIPANTS A total of 544 smokers ( 59 % women , 86 % white ) recruited during primary care visits and motivated to quit . INTERVENTIONS Five intervention components design ed to help smokers attain and maintain abstinence : ( 1 ) extended medication ( 26 versus 8 weeks of nicotine patch + nicotine gum ) ; ( 2 ) maintenance ( phone ) counseling versus none ; ( 3 ) medication adherence counseling versus none ; ( 4 ) automated ( medication ) adherence calls versus none ; and ( 5 ) electronic medication monitoring with feedback and counseling versus electronic medication monitoring alone . MEASUREMENTS The primary outcome was 7-day self-reported point-prevalence abstinence 1 year after the target quit day . FINDINGS Only extended medication produced a main effect . Twenty-six versus 8 weeks of medication improved point-prevalence abstinence rates ( 43 versus 34 % at 6 months ; 34 versus 27 % at 1 year ; P = 0.01 for both ) . There were four interaction effects at 1 year , showing that an intervention component 's effectiveness depended upon the components with which it was combined . CONCLUSIONS Twenty-six weeks of nicotine patch + nicotine gum ( versus 8 weeks ) and maintenance counseling provided by phone are promising intervention components for the cessation and maintenance phases of smoking treatment Objective To assess the effect of nicotine patches on continine-vali date d smoking cessation in pregnant women and the effect of nicotine on birth weight and preterm delivery . Methods Pregnant women who smoked ten or more cigarettes after the first trimester ( N = 250 ) were r and omly assigned to receive nicotine patches ( n = 124 ) or placebo patches ( n = 126 ) . Women r and omized to nicotine were treated with 15-mg patches ( 16 hours/day ) for 8 weeks , and 10-mg patches ( 16 hours/day ) for 3 weeks . Results Overall , 26 % stopped smoking and 14 % were nonsmokers 1 year after delivery . There was no difference between nicotine and placebo groups . At the end of the intervention , the mean value of cotinine in saliva in women assigned to nicotine was 120 ng/mL and placebo 153 ng/mL ( mean difference −33 ; 95 % CI −72 , 6 ng/mL ) . Mean birth weight difference was 186 g ( 95 % CI 35 , 336 g ) higher in the nicotine than placebo group , and there was an insignificantly lower rate of low birth weight ( under 2500 g ) in the former group . There was no difference in the rate of preterm delivery between the two groups . Conclusion Nicotine patches had no influence on smoking cessation during pregnancy , although they might increase birth weight in comparison with placebo The purpose of this study was to examine the effectiveness of different practice -based approaches to assist patients of primary care physicians to quit smoking and sustain cessation . Forty-four nonsmoking general practitioners volunteered for the study . After a period of training , they r and omized 923 smoking clients , unselected for motivation toward quitting , to four different intervention groups : ( i ) minimal intervention , consisting of one single counselling session and a brief h and out on quitting techniques ; ( ii ) repeated counselling including reinforcing sessions at Months 1 , 3 , 6 , and 9 ; ( iii ) repeated counselling and use of nicotine gum ; and ( iv ) repeated counselling and spirometry . Biochemically vali date d smoking status was assessed at six and 12 months after recruitment . The proportion of verified quitters at 12 months was 4.8 percent among subjects r and omized to the minimal intervention group , compared to 5.5 percent , 7.5 percent , and 6.5 percent among those r and omized to the three repeated-counselling groups . In no treatment group was the outcome significantly different from that for one-time counselling at the ( P<0.05 ) level . Lack of power , contamination , and low attendance at reinforcing sessions should be taken into account in interpreting the results Cue exposure paradigms have been used to examine reactivity to smoking cues . However , it is not known whether cue-provoked craving is associated with smoking cessation outcomes or whether cue reactivity can be attenuated by nicotine replacement therapy ( NRT ) in clinical sample s. Cue-provoked craving ratings and reaction time responses were measured on the 1st day of abstinence among 158 smokers who had been r and omized to high-dose nicotine ( 35 mg ) or placebo patch . The nicotine patch reduced overall levels of craving but did not attenuate cue-provoked craving increases or reaction time responses . Cue-provoked craving predicted relapse among participants on the nicotine patch but not among those on placebo . In summary , NRT users could benefit from treatment that attenuates cue-provoked craving Objective To compare the effects of free nicotine replacement therapy or proactive telephone counselling in addition to st and ard smoking cessation support offered through a telephone quitline . Design Parallel group , 2 × 2 factorial , r and omised controlled trial . Setting National quitline , Engl and . Participants 2591 non-pregnant smokers aged 16 or more residing in Engl and who called the quitline between February 2009 and February 2010 and agreed to set a quit date : 648 were each r and omised to st and ard support , proactive support , or proactive support with nicotine replacement therapy , and 647 were r and omised to st and ard support with nicotine replacement therapy . Interventions Two interventions were offered in addition to st and ard support : six weeks ’ nicotine replacement therapy , provided free , and proactive counselling sessions ( repeat telephone calls from , and interaction with , cessation advisors ) . Main outcome measures The primary outcome was self reported smoking cessation for six or more months after the quit date . The secondary outcome was cessation vali date d by exhaled carbon monoxide measured at six or more months . Results At six months , 17.7 % ( n=229 ) of those offered nicotine replacement therapy reported smoking cessation compared with 20.1 % ( n=261 ) not offered such therapy ( odds ratio 0.85 , 95 % confidence interval 0.70 to 1.04 ) , and 18.2 % ( n=236 ) offered proactive counselling reported smoking cessation compared with 19.6 % ( n=254 ) offered st and ard support ( 0.91 , 0.75 to 1.11 ) . Data vali date d by carbon monoxide readings changed the findings for nicotine replacement therapy only , with smoking cessation vali date d in 6.6 % ( 85/1295 ) of those offered nicotine replacement therapy compared with 9.4 % ( 122/1296 ) not offered such therapy ( 0.67 , 0.50 to 0.90 ) . Conclusions Offering free nicotine replacement therapy or additional ( proactive ) counselling to st and ard helpline support had no additional effect on smoking cessation . Trial registration Clinical Trials.gov NCT00775944 BACKGROUND Smoking cessation programmes were first introduced in Iran in 1997 . To date a number of types of nicotine replacement therapy have been prescribed . OBJECTIVE To evaluate the effectiveness of varenicline for tobacco cessation . METHODS This was a r and omised parallel clinical study conducted in 2010 . Participants were smokers willing to quit who were visiting a smoking cessation clinic for the first time and were r and omly divided into three groups : all three groups received brief counselling on cessation , Group 2 received nicotine patches and Group 3 was prescribed varenicline for 8 weeks . RESULTS There were 272 participants in the study : 91 in Group 1 , 92 in Group 2 and 89 in Group 3 . At the end of the first month , 128 of the 272 subjects ( 47.1 % ) succeeded in quitting : 17 ( 18.7 % ) in Group 1 , 60 ( 65.2 % ) in Group 2 and 51 ( 57.3 % ) in Group 3 ( P = 0.000 ) . At follow-up after 12 months , 58 subjects ( 21.3 % ) remained smoke-free , of whom 6 ( 6.6 % ) were in Group 1 , 23 ( 25 % ) in Group 2 and 29 ( 32.6 % ) in Group 3 ( P = 0.000 ) . CONCLUSION In the study , varenicline treatment was slightly more effective than but not significantly different from nicotine replacement therapy Many smokers are unable to use gum as a cessation aid due to fillings , bridgework and dyspepsia or they reject it for esthetic reasons . The nicotine sublingual tablet is a new alternative to the nicotine polacrilex chewing gum that does not necessitate chewing . Twenty subjects used 2-mg sublingual nicotine tablets and placebo in a double-blind r and omized crossover study of 2-day smoke-free periods . Craving and other withdrawal symptoms were rated on 100-mm visual analog scales ( VAS ) nine times over each 2-day period . Plasma nicotine concentrations in the afternoon of each study day were determined . A blood sample was also taken in the afternoon of a 2-day period with normal smoking . The mean number of nicotine tablets was 10 and seven on days 1 and 2 , respectively . The corresponding number for placebo tablets was six and five . No subject used less than five tablets on any study day . The degree of nicotine substitution , defined as the quotient between the plasma levels achieved with the sublingual tablet and smoking , was 43 , 30 and 23 % for smokers with FTQ < or = 6 , FTQ = 7 and FTQ > or = 8 ( Fagerström Tolerance Question naire ) , respectively . Active treatment was significantly superior in decreasing craving and other withdrawal symptom scores compared to placebo treatment . Mean total scores were reduced by approximately 50 % . Adverse events were mainly symptoms of local irritation such as a burning sensation in the throat or under the tongue , a lump in the throat and heartburn . These results demonstrate partial relief of the tobacco withdrawal syndrome with use of the sublingual tablet similar to that achieved from other forms of nicotine replacement OBJECTIVE : To determine the efficacy of the transdermal nicotine patch for smoking cessation in inner-city African Americans . DESIGN : Double-blind , placebo-controlled , r and omized trial . SETTING : Outpatient in an inner-city hospital . PATIENTS AND PARTICIPANTS : A computer-generated r and om numbers table with a block size set at 20 was used to r and omize 410 patients to one of two study arms . INTERVENTIONS : The transdermal nicotine patch for 10 weeks as an adjunct to brief counseling . MEASUREMENTS AND MAIN RESULTS : Of the 410 patients r and omized , mean age was 48 years , 65 % were female , 41 % had less than a high school education , 51 % had an annual household income of less than $ 8,000 , and the average number of cigarettes smoked per day was 20 . Quit rates at 10 weeks were 21.5 % ( 44/205 ) with the nicotine patch , and 13.7 % ( 28/205 ) with the placebo patch ( p=.03 ) . At 6 months , quit rates were 17.1 % ( 35/205 ) with the nicotine patch , and 11.7 % ( 24/205 ) with the placebo patch ( p=.08 ) . After adjusting for baseline differences in age and educational attainment , differences remained significant at 10 weeks ( p=.04 ) , but were not significant at 6 months ( p=.14 ) . Compliance rates for return visits were 83 % , 78 % , 55 % , and 52 % , at 1 , 2 , 6 , and 10 weeks , respectively . CONCLUSIONS : The nicotine patch significantly improves short-term quit rates in inner-city African Americans who are interested in trying to quit smoking . Efforts should be made to reach underserved population s through smoking cessation programs , and to assist in maintaining abstinence The transdermal administration of nicotine by means of a transdermal nicotine system ( TNS ) affords a novel way of nicotine replacement to alleviate smoking cessation . The plasma levels of nicotine maintained with the TNS are in the range of the footpoint concentrations observed in smokers . The efficacy of the TNS was investigated in two placebo-controlled double-blind smoking cessation programs with minimal contact and minimal psychological support . A total of 311 smokers were treated for 3 months or 9 weeks . The abstinence rates at the end of the treatment and weaning periods were almost doubled in the TNS groups ( 36 % and 39 % ) as compared to the placebo groups ( 23 % and 20 % ) with a significant difference for both studies ( p<0.05 ) . These data suggest that the TNS can also improve the smoking cessation rates under the conditions of general medical advice , making it suitable for use outside of specialized smoking cessation centers Chewing gum containing nicotine or placebo was given to smokers attending an anti-smoking clinic . During a one week double-blind study subjects receiving nicotine smoked less and chewed less gum than those receiving placebo . The difference in tobacco consumption between the two treatment groups was most apparent among previous heavy smokers . During a 6 month follow-up phase all subjects were offered nicotine-containing chewing gum ; the number of nonsmokers then remained fairly constant in the “ initial-nicotine group ” while it increased in the “ initial-placebo group ” INTRODUCTION There is growing evidence that the mailed distribution of free nicotine replacement therapy ( NRT ) , usually as part of smokers ' helplines , can been effective in increasing the odds of cessation on a population level . However , limited information is available on the utilization of NRT when it is provided for free , and factors associated with regimen adherence have remained largely unexplored . METHODS In the context of a r and omized controlled trial , 500 adult smokers across Canada hypothetically interested in free NRT were mailed a 5week supply of nicotine patches , but no other support was offered . Analyses evaluated which a priori-defined demographic and smoking characteristics predicted nicotine patch use at 8week follow-up of 421 patch recipients , as well as examined the association between patch use and smoking cessation at 6months . RESULTS At 8weeks , 10.9 % had used all , 47.5 % had used some but not all , and 41.6 % had not used any of the provided nicotine patches . Lower age , unemployment , past NRT use and intent to quit in the next 30days at baseline ( preparation stage of change ) were all identified as independent predictors of some nicotine patch use . Only use of all patches was associated with greater odds of smoking cessation , compared to non-users ( Adj . OR=2.96 ; 95%CI=1.06 - 8.27 ) . CONCLUSIONS The mailed distribution of free nicotine patches to smokers at large can be effective at promoting cessation , particularly among financially disadvantaged groups , those with previous NRT experience and among individuals with already advanced intent to quit Seventy-seven smokers quit smoking and were r and omly assigned to a 3 × 2 design contrasting instructions ( told received nicotine gum versus told received placebo gum versus not told which gum received ) and receipt of nicotine ( received nicotine gum versus received placebo gum ) . Both being told one received nicotine and actual recept of nicotine increased the number of days abstinent and decreased the number of cigarettes smoked ( P<0.05 ) . Receipt of nicotine but not instructions appeared to influence withdrawal ( P=0.06 ) . Instructions but not recept of nicotine appeared to influence craving ( P=0.08 ) , gum selfadministration ( P=0.06 ) and reported helpfulness of the gum ( P=0.02 ) . Neither nicotine nor instructions influenced side-effects . Instructions and nicotine interacted in several ways . For example , nicotine appeared to increase abstinence in the blind and told placebo conditions more than in the told nicotine condition ( P<0.05 ) . Our results suggest the effects of instructions and nicotine 1 ) are not mutually exclusive , 2 ) vary across dependent variables and 3 ) can interact such that instructions modify the therapeutic and subjective effects of nicotine Nicotine gum and transdermal nicotine have been shown to relieve withdrawal and double success rates over placebo in trials of smoking cessation . This study tested whether combining the two methods would relieve withdrawal more effectively compared to either treatment alone . Twenty-eight smokers served as their own controls in each of four conditions : active gum + active patch ( double active ) , active gum + placebo patch ( gum only active ) , placebo gum + active patch ( patch active ) and placebo gum+placebo patch ( double placebo ) . This “ double placebo ” design controls sensory , psychological and ritual variables associated with each drug form . Withdrawal symptoms were rated four times daily for 3 days in each condition . Total baseline ( smoking ) withdrawal scores using visual analogue scales ( VAS ) averaged 101.1 . During cessation , total withdrawal increased to 187.0 for the double placebo condition , 142.2 for the active gum/placebo patch treatment and 128.3 for the active patch/placebo gum treatment . The double active condition equalled smoking with score 99.2 . All pairwise comparisons were significant ( P<0.001 ) except between the two single active conditions and between smoking versus the double active condition . Significant time-of-day effects by treatment on withdrawal were observed for the double placebo condition ( P<0.05 ) with less withdrawal in the morning . The findings suggest : 1 ) combining nicotine gum with transdermal nicotine may be superior to either treatment alone , 2 ) more symptoms may be nicotine specific ( relieved by replacement ) than previously thought BACKGROUND Cigarette smoking has been associated with increases in C-reactive protein ( CRP ) and leukocyte counts ( white blood cell [ WBC ] ) ; however , the effects of smoking intensity and smoking cessation on inflammatory markers have not been evaluated prospect ively in a large , modern cohort of current smokers . METHODS White blood cell count and high-sensitivity CRP were measured in current smokers enrolled in a r and omized , prospect i ve clinical trial of 5 smoking cessation pharmacotherapies . Smoking intensity parameters included cigarettes per day , pack-years , Fagerström Test of Nicotine Dependence score , and carbon monoxide levels . C-reactive protein also was measured after 1 year with assessment of abstinence status . RESULTS The 1,504 current smokers ( 58 % female ) were ( mean [ SD ] ) 44.7 ( 11.1 ) years old , smoked 21.4 ( 8.9 ) cigarettes per day , and had a smoking burden of 29.4 ( 20.4 ) pack-years . Log(CRP ) was not associated with any marker of smoking intensity , except for a weak correlation with pack-years ( r = 0.05 , P = .047 ) . In contrast , statistically significant correlations were observed between all 4 markers of smoking intensity and WBC count ( all P ≤ .011 ) . In multivariable models , waist circumference ( P < .001 ) and triglycerides ( P < .05 ) , but no markers of smoking intensity , were associated with log(CRP ) . However , pack-years ( P = .002 ) , cigarettes per day ( P = .013 ) , carbon monoxide ( P < .001 ) , and Fagerström Test of Nicotine Dependence ( P < .001 ) were independently associated with WBC count . After 1 year , log(CRP ) ( P = .296 ) and changes in log(CRP ) ( P = .455 ) did not differ between abstainers and continuing smokers . CONCLUSIONS Smoking intensity is associated with increased WBC count , but not CRP levels . Smoking cessation does not reduce CRP . The relationship between CRP and smoking intensity may be masked by CRP 's stronger relationship with adiposity We compared acceptability , adherence and efficacy of trans-dermal nicotine patches and cognitive behavioral therapy ( Group 1 ) to cognitive behavioral therapy alone ( Group 2 ) in minority pregnant smokers . This is a r and omized controlled trial . 52 women were recruited during pregnancy with a mean gestational age 18.5 ± 5.0 weeks and followed through delivery . R and omization was by site and initial cotinine levels . Interventionists and interviewers were blinded to group assignment . Two different nicotine replacement therapy dosing regiments were administered according to the baseline salivary cotinine level . A process evaluation model summarized patient adherence . The main outcome measure was self-report of cessation since last visit , confirmed by exhaled carbon monoxide . Analyses of categorical and continuous measures were conducted as well as linear trend tests of salivary cotinine levels . Women lost to follow-up were considered treatment failures . Participants were on average 27.5 ± 5.4 years old , 81 % were single , 69 % unemployed and 96 % were Medicaid eligible . A process evaluation indicated patients in both groups were adherent to scheduled program procedures through Visit 4 , but not for Visits 5 and 6 . Confirmed quit rates were : at visit 3 , 23 ( Group 1 ) and 0 % ( Group 2 ) ( p = 0.02 ) ; at visits 4 and 5 , no difference ; at visit 6 , 19 ( Group 1 ) and 0 % ( Group 2 ) ( p = 0.05 ) . Group 1 delivered infants with a mean gestational age of 39.4 weeks versus 38.4 weeks in Group 2 ( p = 0.02 ) . 73 % ( 52/71 ) of the eligible smokers agreed to participate and 65 % ( 17/26 ) of Group 1 completed the protocol ( i.e. attended 6 visits ) . A comparison of Group 1 and 2 quit rates confirmed a non-significant difference Medical advice and use of nicotine gum have recently received increased attention as effective tools to encourage smokers to quit , yet the relative value of nurse vs physician counseling has not been explored in depth . In this study , 425 smokers attending three urban primary care centers in Barcelona were systematic ally allocated to one of three groups : group A patients received a brief counseling session to quit from their family physician ; group B patients were given the same brief counseling along with a free supply of nicotine gum ; group C received a brief health-education session from the primary care nurse . Three hundred forty-nine patients ( 82 % ) could be reached by telephone at the two-month follow up . By that time , after correcting for the estimated validity of the phone report of smoking status , the proportion declaring themselves to be nonsmokers was 10.9 % , 11.1 % , and 10.8 % , respectively , without significant differences between them . At one-year follow up the proportions were 4.4 % , 5.3 % , and 6.0 % . In the logistic regression analysis , only the expected difficulty of quitting was predictive of one-year abstention , OR = 3.1 ( 95 % CI : 1.3 - 7.3 ) . The present study shows no difference between physician versus nurse counseling and no improvement in the proportion of quitters with the addition of nicotine gum in the physician-counseled group Stopping smoking in pregnancy is a public health priority and a clinical imperative . However , many women who have not been able to ' quit ' in early pregnancy find it very difficult to do so . This r and omised-controlled pilot study examined feasibility issues in offering free nicotine patches with counselling to a group of 20 mid-trimester pregnant women at the Women 's and Children 's Hospital , Adelaide . A further 20 were offered counselling only . Smoking status at each visit was measured by self-report , carbon monoxide monitoring , and salivary cotinine . The most common pattern ( eleven of the twenty women ) was intermittent patch use . Only five women used patches continuously up to the 12 week maximum available . Three women in the patch group were abstinent at delivery compared with none in the control group . Notable features of the study were the low interest in participation and the high withdrawal rate . Nicotine patches may not be highly useful for pregnant women . Continuing tobacco control measures and customized support for women and their partners , often smokers , may prove more fruitful BACKGROUND The reasons for relapse to smoking are not fully understood but several factors are of importance . Addiction to nicotine seems to play a prominent role but there are several other contributing factors . METHODS To determine predictors of outcome in smoking cessation , we performed univariate and multivariate analyses in a large smoking cessation trial comprising 289 subjects . Weight gain and withdrawal symptoms were analyzed separately as predictors . To determine self-perceived reasons for relapse we created a question naire , which was answered by 132 relapsers . RESULTS Previous attempts to quit smoking and a low saliva cotinine concentration were significantly associated with abstinence in the nicotine-treated group . A trend toward higher abstinence rates was found among males and among subjects with a low nicotine dependency score . Logistic regression analysis showed higher success rates in subjects with the largest weight gain during the first weeks of quitting in contrast to higher relapse rates in subjects who had the greatest weight gain after 3 months . A high score on withdrawal symptoms was not predictive of relapse . Subjects with " slips " had a markedly increased relapse rate . Craving for cigarettes was the most often self-reported ( 48 % ) reason for relapse . CONCLUSIONS The relation between weight gain , withdrawal scoring , and outcome seems rather complex . Craving for cigarettes was the most reported reason for relapse This study was design ed to see whether the offer and prescription of nicotine chewing gum would enhance the efficacy of general practitioners ' advice to stop smoking . A sample of 1938 cigarette smokers who attended the surgeries of 34 general practitioners in six group practice s were assigned by week of attendance ( in a balanced design ) to one of three groups : ( a ) non-intervention controls , ( b ) advice plus booklet , and ( c ) advice plus booklet plus the offer of nicotine gum . Follow up was done after four months and one year . The results show a clear advantage for those offered the nicotine gum ( p less than 0.001 ) . After correction for those who refused or failed chemical validation and those who switched from cigarettes to a pipe or cigars , the proportions who were abstinent at four months and still abstinent at one year were 3.9 % , 4.1 % , and 8.8 % in the three groups , respectively . These percentages are based on all cigarette smokers who attended the surgeries including those who did not wish to stop and those in the gum group who did not try the gum ( 47 % ) . The effect of the offer and prescription of gum was to motivate more smokers to try to stop , to increase the success rate among those who tried , and to reduce the relapse rate of those who stopped . The self selected subgroup of 8 % who used more than one box of 105 pieces of gum achieved a success rate of 24 % . It would be feasible and effective for general practitioners to include the offer of nicotine gum and brief instructions on its use as part of a minimal intervention routine with all cigarette smokers . A general practitioner who adopts such a routine with similar success could expect to achieve about 35 - 40 long term ex-smokers a year and so save the lives of about 10 of them . If replicated by all general practitioners throughout the country the yield of ex-smokers would be about one million a year The aim of this r and omized , double-blind placebo-controlled clinical trial is to test the efficacy and safety of nicotine replacement therapy ( NRT ) in promoting end-of-treatment abstinence among adolescents and whether this relation is moderated by medication compliance . Participants ( N=257 , age : 16.7±1.13 years ) attended an information meeting followed by a 6- or 9-week treatment . Self-reported smoking cessation , compliance , and side effects were measured by means of online question naires . Intent-to-treat analyses showed that independent of compliance , NRT is effective in promoting abstinence rates after 2 weeks ( OR=2.02 , 95 % CI=1.11 - 3.69 ) , but not end-of-treatment abstinence . However , end-of-treatment abstinence rates significantly increased in high-compliant ( OR=1.09 , 95 % CI=1.01 - 1.17 ) and not in low-compliant participants . No serious adverse events were found . Future research is warranted to disentangle the process involving the decrease in abstinence rates and compliance rates from the third week after the quit date onwards AIMS To determine whether African American light smokers who smoked menthol cigarettes had lower cessation when treated with nicotine replacement therapy and counseling . DESIGN Data were derived from a clinical trial that assessed the efficacy of 2 mg nicotine gum ( versus placebo ) and counseling ( motivational interviewing counseling versus Health Education ) for smoking cessation among African American light smokers ( smoked < or = 10 cigarettes per day ) . PARTICIPANTS The sample consisted of 755 African American light smokers . MEASUREMENTS The primary outcome variable was verified 7-day point-prevalence smoking cessation at 26 weeks follow-up . Verification was by salivary cotinine . FINDINGS Compared to non-menthol smokers , menthol smokers were younger and less confident to quit smoking ( P = 0.023 ) . At 26 weeks post-r and omization , 7-day verified abstinence rate was significantly lower for menthol smokers ( 11.2 % versus 18.8 % for non-menthol , P = 0.015 ) . CONCLUSIONS Among African American light smokers , use of menthol cigarettes is associated with lower smoking cessation rates . Because the majority of African American smokers use menthol cigarettes , a better underst and ing of the mechanism for this lower quit rate is needed AIM To assess the smoking prevalence and efficacy of nicotine replacement therapy on the quitting rate after 3 weeks of therapy and after 1- and 5-year follow-up among health care workers with a smoking habit in Split , Croatia . METHODS Among 311 hospital health professionals included in the study , there were 112 ( 36 % ) smokers ; 44 ( 39 % ) of them were physicians and 68 ( 61 % ) nurses . In a r and omized double-blind study , 112 smokers were divided in 2 groups , applying daily either a transdermal nicotine system ( TNS ) or placebo patch over 3 weeks . Abstinence was evaluated via question naire and on the basis of carbon monoxide concentration measured in the exhaled breath . RESULTS The abstinence rates after the 3-week intervention period were 39 % in the TNS group and almost 20 % in the control group ( chi-square test , p=0.038 ) . After one year , these rates declined to 23 % and 16 % , respectively ( p=0.476 ) , and converged to 18 % and 14 % ( p=0.797 ) , respectively , at 5-year follow-up . CONCLUSIONS Short-term TNS treatment is effective in smoking cessation , although the effects steadily wane over time and the relapse rate is high . Continuous , structured , and composite efforts are needed for the maintenance of the non-smoking behavior BACKGROUND It has been suggested that anti-smoking therapy gives encouraging results , but this has not been verified by well-r and omized study protocol s. The present study was a r and omized controlled trial of varenicline vs nicotine patch in adult smokers for comparison of efficacy , safety and withdrawal symptoms . METHODS AND RESULTS The 32 adult smokers were r and omly divided into a varenicline group ( VG , n=16 ) and a nicotine patch group ( NG , n=16 ) . The primary endpoints were the 12- and 24-week smoking-abstinence rates , safety and withdrawal symptoms including stress . No significant difference in abstinence rates was observed between the 2 groups over weeks 9 - 12 ( 71.4 % vs 78.6 % in the VG and NG , respectively ) , and weeks 9 - 24 ( 64.3 % vs 71.4 % , respectively ) . The frequencies of inability to concentrate at 2 , 4 , and 8 weeks , and wakeful nights at 2 weeks were higher in the VG than in the NG . Adverse side-effects associated with a gastrointestinal disorder occurred in 14 cases and 1 case in the VG and NG , respectively , and skin allergy was seen in 0 and 9 cases , respectively . CONCLUSIONS The selection of treatment depends on the balance of desired acuteness of cessation of smoking and side-effects , such as psychiatric and gastrointestinal problems or skin allergy Smokers aged 18 to 65 years ( N = 1,044 ) who were able to quit for 24 hr were r and omized using a 2 x 2 factorial design to compare nicotine gum to no gum use and self-help material s to no use of material s. All participants were offered a $ 100 incentive to quit and stay quit for 6 months . Six-month abstinence was 27 % in the gum groups , compared with 19 % in the no-gum group ( p = .002 ) . Compared with the no-gum group , relapse occurred at a significantly lower rate in the gum group for the entire 12 months of follow-up ( odds of relapse in the gum group was 0.72 , 95 % confidence interval , 0.62 to 0.83 ) . There was no significant main effect for the self-help material s , no interaction between gum and material s , and no evidence that the effectiveness of gum differed between the sexes or between heavy and light smokers . Nicotine gum is an effective adjunct to minimal-contact smoking cessation material s plus monetary incentive in a population -based sample of smokers Abstract Rationale : Nicotine replacement therapy ( NRT ) in varying forms is becoming widely used . Clinicians , therapists and regulatory authorities are interested in the abuse liability and dependence potential of the different forms . Objectives : To compare the abuse liability and dependence potential of nicotine gum , transdermal patch , spray and inhaler . Methods : 504 male and female smokers seeking help with stopping smoking were r and omly allocated to the four products . Measures were taken at the design ated quit date , then 1 week , 4 weeks , 12 weeks and 15 weeks later . Smokers were advised to use the product for up to 12 weeks . Those still using the product at the 12-week visit were advised to cease use by week 14 . Measures included : pleasantness and satisfaction ratings at weeks 1 and 4 ( used as a marker of abuse liability ) ; ratings of feeling dependent on NRT at weeks 1 , 4 , 12 and 15 ( used as a marker of subjective dependence ) ; mood and physical symptoms ratings at weeks 12 and 15 ( the change being used to assess physical dependence on NRT ) , continued usage of NRT at week 15 ( used as an marker of behavioural dependence ) . Results : Average ratings of pleasantness were low . The nicotine patch was rated as less unpleasant to use than all other products . There were no significant differences between the products in terms of satisfaction or subjective dependence except at week 15 when no patch users rated themselves as dependent . Continued use of NRT at week 15 was related to rate of delivery of nicotine from the products – 2 % for patch , 7 % for gum and inhaler , 10 % for spray ( P<0.05 for linear association ) . Among those abstinent for 15 weeks , the figures were : 8 % , 25 % and 37 % , respectively . Stopping NRT use between weeks 12 and 15 was not accompanied by withdrawal discomfort or increased frequency of urges to smoke although subjects stopping inhaler use experienced a mild increase in strength of urges to smoke . We conclude that abuse liability from all four NRT products was low . Subjective dependence was moderate and did not differ across products . Behavioural dependence was modest and was positively related to rate of nicotine delivery . Physicians can reassure their patients that most are able to come off NRT as recommended without discomfort AIMS To underst and the relations among anxiety disorders and tobacco dependence , withdrawal symptoms , response to smoking cessation pharmacotherapy and ability to quit smoking . DESIGN R and omized placebo-controlled clinical trial . Participants received six 10-minute individual counseling sessions and either : placebo , bupropion SR , nicotine patch , nicotine lozenge , bupropion SR + nicotine lozenge or nicotine patch + nicotine lozenge . SETTING Two urban research sites . PARTICIPANTS Data were collected from 1504 daily smokers ( > 9 cigarettes per day ) who were motivated to quit smoking and did not report current diagnoses of schizophrenia or psychosis or bupropion use . MEASUREMENTS Participants completed baseline assessment s , the Composite International Diagnostic Interview and ecological momentary assessment s for 2 weeks . FINDINGS A structured clinical interview identified participants who ever met criteria for a panic attack ( n = 455 ) , social anxiety ( n = 199 ) or generalized anxiety disorder ( n = 99 ) , and those who qualified for no anxiety diagnosis ( n = 891 ) . Smokers with anxiety disorders reported higher levels of nicotine dependence and pre-quit withdrawal symptoms . Those ever meeting criteria for panic attacks or social anxiety disorder showed greater quit-day negative affect . Smokers ever meeting criteria for anxiety disorders were less likely to be abstinent at 8 weeks and 6 months post-quit and showed no benefit from single-agent or combination-agent pharmacotherapies . CONCLUSIONS Anxiety diagnoses were common among treatment-seeking smokers and were related to increased motivation to smoke , elevated withdrawal , lack of response to pharmacotherapy and impaired ability to quit smoking . These findings could guide treatment assignment algorithms and treatment development for smokers with anxiety diagnoses Objective : To assess the relative impacts of three physician-delivered smoking interventions in combination with follow-up contact from behavioral counselors . Design : R and omized controlled trial with pre-post measures of smoking rates . This paper reports six-month outcome data . Setting : Participants were recruited from among patients seen by 196 medical and family practice residents in five primary care clinics . Participants : Participants were 1,286 patients out of 1,946 eligible smokers approached . The patient group was 57 % female and 91 % white , had an average age of 35 years , and smoked , on average , slightly over one pack per day . Intervention : Physicians were trained to provide each of three interventions : advice only , brief patient-centered counseling , and counseling plus prescription of nicotine-containing gum ( Nicorette ™ ) . Half the patients received follow-up in the form of telephone counseling at three-monthly intervals from behavioral counselors . Measurements and main results : Changes in smoking behaviors were assessed by telephone interview six months after physician intervention . The differences in one-week point prevalence cessation rates among the physician interventions were significant ( p<0.01 ) : advice only , 9.1 % ; counseling , 11.9 % ; counseling plus gum , 17.4 % ; with no effect for telephone counseling . The time elapsed from physician encounter to initial quitting and the length of that period of abstinence also showed significant benefit of the counseling interventions . Patients receiving physician counseling were much more likely than those not receiving counseling to rate their physician as very helpful ( p<0.001 ) . Multiple regression analyses are also reported . Conclusion : Smoking intervention counseling provided by physicians is well received by patients and significantly increases the likelihood of cessation at six months , an effect that is augmented by the prescription of nicotine-containing gum , when compared with physician-delivered advice . Follow-up telephone counseling does not contribute significantly to smoking behavior changes In a placebo-controlled , double-blind , 2-year prospect i ve study , 182 smokers were given either nicotine polacrilex gum containing 4 mg of nicotine ( n = 92 ) or a placebo ( n = 90 ) . The number of participants abstinent at 2-year follow-up was 41 ( 44.6 % ) of 92 in the nicotine group vs 28 ( 31.1 % ) of 90 in the placebo group . Abstinence rates for daily nicotine gum users ( n = 64 ) at 12 months and again at 24 months remained 48.4 % , as compared with 26.1 % and 31.9 % for the daily placebo gum users ( n = 69 ) . Of participants with a high nicotine-dependence score , those allotted to the nicotine group rather than to the placebo group were 13 times more likely to be abstaining at the 2-year follow-up . Use of nicotine polacrilex gum , therefore , can substantially aid in stopping smoking , particularly among highly dependent smokers AIMS To compare a transdermal nicotine patch design ed for 24-hour wear with one design ed for 16-hour wear for relief of craving and withdrawal , particularly in the morning hours . DESIGN Smokers were r and omly assigned to use one of two common patch regimens : NicoDerm/NiQuitin ( 24-hour wear , 21 mg nicotine ) or Nicotrol/Nicorette ( 16-hour wear , 15 mg ) . In a double-dummy design , participants wore two patches during the day , one active , one placebo and one patch while sleeping . SETTING A smoking cessation research clinic . PARTICIPANTS Two hundred and forty-four smokers who suffered morning cravings . INTERVENTION Two patch formulations approved and marketed for over-the-counter use in the US -- NicoDerm CQ ( labeled as 21 mg over 24 hours ) and Nicotrol ( labeled as 15 mg over 16 hours)--were each used according to its instructions . Smokers also received behavioral counseling . MEASUREMENTS For a week of baseline and 2 weeks after quitting , smokers used palm-top computers to assess craving and withdrawal symptoms several times each day . FINDINGS The 21 mg/24-hour patch yielded consistently better control of craving , not only during the morning hours , but throughout the day , and over the 2-week period of abstinence . Additionally , the 21 mg/24-hour patch yielded greater reductions in anxiety , irritability and restlessness . Smokers using the 21 mg/24-hour dosing regimen also experienced longer abstinence than those using the 15 mg/16-hour patch . CONCLUSIONS These findings demonstrate that 24-hour dosing with a 21 mg patch affords superior relief of craving and withdrawal during the first 2 weeks of abstinence , when symptoms are at their peak , and when relapse is most likely . They confirm the importance of dosing parameters in nicotine replacement products OBJECTIVE The purpose of this study was to evaluate the efficacy of long-term use of bupropion sustained release ( SR ) , the nicotine patch , and the combination of these 2 treatments in patients who initially failed treatment . METHODS This was a post hoc analysis of a multicenter , double-blind , r and omized , placebo-controlled clinical trial in 893 smokers . Patients were r and omly assigned to 9 weeks of treatment with placebo ( n = 160 ) , bupropion SR ( n = 244 ) , nicotine patch ( n = 244 ) , or a combination of nicotine patch and bupropion SR ( n = 245 ) . The study was originally design ed with a follow-up period of 52 weeks . In this analysis , short-term success was defined as smoking cessation after 14 or 21 days of therapy and long-term success was defined as smoking cessation after > 21 days of therapy . Patients who did not achieve short-term success were evaluated for long-term success at week 9 ( end of treatment ) , 6 months , and 1 year after the start of the study . RESULTS The mean age of the smokers was 44 years . The majority ( 93 % ) of patients were white , and 52 % were female . The study subjects smoked an average of 27 cigarettes per day . Among the 467 patients who initially failed treatment in the first 3 weeks , treatment with bupropion SR alone and in combination with the nicotine patch produced significant increases in successful smoking cessation rates from weeks 4 to 9 ( 19 % bupropion SR or combination , 7 % nicotine patch , 7 % placebo ) , at month 6 ( 11 % bupropion SR , 13 % combination , 2 % nicotine patch , 3 % placebo ) , and at month 12 ( 10 % bupropion SR , 7 % combination , 2 % nicotine patch , 1 % placebo ) ( P < 0.05 for bupropion SR and combination vs nicotine patch or placebo ) . CONCLUSION Among patients who initially failed treatment , continued therapy with bupropion SR , either alone or in combination with the nicotine patch , result ed in significantly higher short- and long-term smoking cessation rates than treatment with the nicotine patch alone or placebo AIMS Evaluation of the clinical efficacy and safety of a nicotine 2-mg sublingual tablet in smoking cessation . DESIGN A r and omized , double-blind , placebo-controlled study of smokers using the 2-mg tablet for 3 - 6 months with follow-up to 12 months . Dosing was established according to baseline nicotine dependence , scored on the Fagerström Tolerance Question naire ( FTQ ) : FTQ > or = 7 , two tablets/hour ( maximum 40/day ) ; FTQ < 7 , one tablet/hour ( maximum 20/day ) . SETTING Smoking cessation programme in a department of oral and maxillofacial surgery . PARTICIPANTS A total of 247 adult smokers , smoking > or = 10 cigarettes/day for > or = 3 years , of whom 123 received active and 124 placebo treatment . The study was powered to detect difference at 6 months . MEASUREMENTS Efficacy and safety were evaluated at 6 weeks and 3 , 6 and 12 months . Self-reported abstinence was verified by exhaled CO < 10 p.p.m . FINDINGS Success rates for complete abstinence ( no slips after 2 weeks ) for active vs. placebo were 50 % vs. 29 % at 6 weeks , 42 % vs. 23 % at 3 months , 33 % vs. 18 % at 6 months and 23 % vs. 15 % at 12 months ( p < 0.001 , 0.001 , 0.005 and p = 0.14 ) , respectively . Craving during the first 8 days was significantly reduced among highly dependent smokers on active treatment compared to placebo . Baseline mucosal lesions among abstinent subjects were reduced during the treatment period and at the non-treatment follow-up . Adverse events were mild and tolerable , the most common being irritation and soreness in the mouth and throat . CONCLUSION The nicotine sublingual tablet increased the smoking cessation rate compared to placebo , reduced craving in highly dependent smokers and was well tolerated This study of postmenopausal female smokers ( N = 94 ) asked : During short-term smoking abstinence , do the beneficial effects of transdermal nicotine replacement therapy ( NRT ) on acute symptomatology ( i.e. , withdrawal , cigarette craving , smoking urges , mood , depressive symptoms , motor speed , and reaction time ) differ in women who use and do not use hormone replacement therapy ( HRT ) ? Participants were recruited according to HRT and non-HRT use ( self- selecting ) , then r and omized within strata to active nicotine or placebo nicotine patch . After 1 baseline week of smoking , participants quit smoking for 2 weeks . Women received cessation counseling and were monitored for abstinence . Dependent measures were collected during five clinic visits . Two-way analysis of covariance ( ANCOVA ) were run on change scores for dependent variables , with nicotine patch group ( active/placebo ) and HRT group ( HRT/non-HRT ) as independent variables and age as a covariate . No interactions were found between HRT and patch condition , but both showed specific effects . During the first abstinent week , women on active nicotine patch ( compared with placebo ) experienced less severe withdrawal , greater reductions in cigarette cravings , and lower ( more favorable ) Factor 1 scores on the Question naire of Smoking Urges . During the second abstinent week , women using HRT ( compared with the non-HRT group ) exhibited better mood ( Profile of Mood States scores ) and less depression ( Beck Depression Inventory scores ) . These results suggest the following : First , the efficacy of transdermal nicotine replacement is not adversely modified by women 's HRT use ; second , ovarian hormones might influence women 's responses to smoking cessation , and thus should be considered in developing effective strategies for women to quit smoking The effects of nicotine ( NI ) , silver acetate ( SA ) , and ordinary ( PL ) chewing gum on the cessation of smoking were compared through ratings on six smoking types and physiological nicotine dependence ( F-score ) in a placebo-controlled and r and omized study that included 496 smokers in a group-support setting . Results were evaluated after 26 weeks . Ratings on smoking types 1 , 3 , 4 , 5 , and 6 and F-score were related to success rates . The effect of NI was superior to SA in smokers with high type 1 ratings , the effects of NI and SA were almost equal and superior to PL in smokers with high type 4 and 6 ratings , and the effect was independent of the F-score . Treatment of smokers with NI and SA should be restricted to smoking types in which an effect superior to PL is documented , and research should be performed to find support for smoking types where SA and NI have a clear effect Abstract OBJECTIVE : To examine the predictors of quitting among African American ( AA ) light smokers ( < 10 cigarettes per day ) enrolled in a smoking cessation trial . METHODS : Baseline variables were analyzed as potential predictors from a 2 × 2 cessation trial in which participants were r and omly assigned to 1 of 4 treatment groups : nicotine gum plus health education ( HE ) counseling , nicotine gum plus motivational interviewing ( MI ) counseling , placebo gum plus HE counseling , or placebo gum plus MI counseling . Chi-square tests , 2 sample t-tests , and multiple logistic regression analyses were used to identify predictors of cotinine ( COT ) verified abstinence at month 6 . RESULTS : In the final regression model , HE rather than MI counseling ( odds ratio [OR]=2.26 % , 95 % confidence interval [CI]=1.36 to 3.74 ) , older age ( OR=1.03 % , 95 % CI=1.01 to 1.06 ) , and higher body mass index ( OR=1.04 % , 95 % CI=1.01 to 1.07 ) significantly increased the likelihood of quitting , while female gender ( OR=0.46 % , 95 % CI=0.28 to 0.76 ) , ≤$1,800/month income ( OR=0.60 % , 95 % CI=0.37 to 0.97 ) , higher baseline COT ( OR=0.948 % , 95 % CI=0.946 to 0.950 ) , and not completing all counseling sessions ( OR=0.48 % , 95 % CI=0.27 to 0.84 ) reduced the odds of quitting . CONCLUSIONS : Individual characteristics may decrease the likelihood of quitting ; however , the provision of directive , advice-oriented counseling focused on the addictive nature of nicotine , health consequences of smoking , benefits of quitting , and development of a concrete quit plan may be an important and effective facilitator of quitting among AA light smokers BACKGROUND Many telephone quit lines provide free nicotine replacement therapy ( NRT ) to smokers who are trying to stop smoking . However , providing free NRT to smokers can be costly . OBJECTIVE To compare NRT usage patterns , quit rate , and costs of giving smokers calling a telephone quit line different amounts of free NRT . DESIGN A 3-group r and omized trial was conducted . SETTING AND PARTICIPANTS A total of 2806 adult smokers of 10 + cigarettes per day who called the New York State Smokers ' Quit Line ( NYSSQL ) were sent different amounts of nicotine patches for free as follows : ( 1 ) a 2-week supply of nicotine patches , ( 2 ) a 4-week supply , and ( 3 ) a 6-week supply . In addition , all study participants received a free stop smoking guide plus 1 proactive follow-up call attempt conducted 2 weeks after initially contacting the NYSSQL . Of the 2806 enrolled participants , 1682 completed the 7-month follow-up to assess their use of the NRT sent to them and smoking status . MAIN OUTCOME MEASURES Nicotine patch usage , quit rates , reductions in cigarette consumption , and cost-effectiveness measures . RESULTS Most respondents ( 85 % ) reported using the nicotine patches sent to them , although the amount used varied in direct proportion to the amount sent . The 7- and 30-day nonsmoker prevalence rates measured at 7-month follow-up did not differ significantly between the 3 groups . The cost per attributable quit was also not significantly different between the 3 groups . CONCLUSION Sending out more than a free 2-week supply of patches to smokers who contact a quit line is no more effective in achieving smoking cessation than sending just 2 weeks of patches The effectiveness of different nicotine dosages on abstinence rates was investigated in a smoking cessation study . One hundred smokers underwent nine weeks of self-controlled treatment based on behavioral principles . The overall group was divided into two subgroups r and omized according to sex , cigarette consumption and age . The first group ( n = 51 ) was given a nicotine dose adapted to daily cigarette consumption . The second group ( n = 49 ) was given a st and ardized dose . There was , unexpectedly , no difference between the two groups in respect to short-term abstinence rates . These results suggest that st and ardized dosage is preferred to individually adapted dosage The effect of different follow-up programs reinforced or not reinforced with the nicotine chewing gum Nicorette was tested by 13 physicians working in the open health care system . A total of 151 patients were advised to stop smoking , and were asked to participate in the program if judged sufficiently motivated by the physicians . After inclusion they were r and omized into short or long follow-up , and nicotine gum vs no gum . The physicians conducted the follow-up therapy in their own personal way . Short follow-up was comprised of one appointment 14 days after cessation , while long follow-up consisted of a telephone call ( 1 week ) , an appointment ( 2 weeks ) , a second appointment ( 1 month ) , and a letter ( 3 months ) . The results at 12 months were that long follow-up showed a trend ( P less than 0.12 toward being better than short follow-up , while nicotine gum was significantly better than no gum ( P less than 0.05 ) in maintaining abstinence . The group with the best outcome was the one receiving long follow-up and nicotine gum , which yielded an expired air carbon monoxide-controlled , 12-month abstinence rate of 27 % . The abstinence outcomes at 12 months for the other groups were short follow-up and nicotine gum , 22 % ; long follow-up and no gum , 15 % ; and short follow-up and no gum , 3 % . The physicians ' reactions to the smoking cessation treatment were largely positive . The nicotine gum seems to be a relatively simple , cost-effective , and practical tool for physicians to enhance and reinforce their antismoking advice . With a longer active follow-up period than was used here ( 1 month ) , even better results may be possible INTRODUCTION Alcohol and nicotine are commonly used substances in the U.S. , with significant impacts on health . Using both substances concurrently impacts quit attempts . While studies have sought to examine changes in alcohol use co-occurring with tobacco cessation , results have not been consistent . Underst and ing these changes has clinical implication s. The objective of this study is to identify changes in alcohol consumption that occur following tobacco cessation , as well as predictors of alcohol use patterns following a smoking cessation attempt . METHODS A secondary analysis of a r and omized , placebo-controlled trial evaluating the efficacy of five tobacco cessation pharmacotherapies . Participants ( N=1301 ) reported their smoking and alcohol consumption daily for two weeks prior to , and two weeks after , the target quit date ( TQD ) . RESULTS Generally , alcohol use decreased post-TQD . Smokers who reported less pre-quit alcohol use , as well as smokers who were female , non-white , and had a history of alcohol dependence tended to use less alcohol post-quit . Pre- and post-quit alcohol use were more strongly related among men and among those without a history of alcohol dependence . CONCLUSIONS For most smokers alcohol use decreased following smoking cessation . These results suggest that the expectation should be of decreased alcohol use post cessation . However , attention may be warranted for those who drink higher amounts of alcohol pre-cessation because they may be more likely to drink more in the post-quit period which may influence smoking cessation success BACKGROUND the effects of smoking and smoking cessation on lipoproteins have not been studied in a large contemporary group of smokers . This study was design ed to determine the effects of smoking cessation on lipoproteins . METHODS this was a 1-year , prospect i ve , double-blind , r and omized , placebo-controlled clinical trial of the effects of 5 smoking cessation pharmacotherapies . Fasting nuclear magnetic resonance spectroscopy lipoprotein profiles were obtained before and 1 year after the target smoking cessation date . The effects of smoking cessation and predictors of changes in lipoproteins after 1 year were identified by multivariable regression . RESULTS the 1,504 current smokers were ( mean [ SD ] ) 45.4 ( 11.3 ) years old and smoked 21.4 ( 8.9 ) cigarettes per day at baseline . Of the 923 adult smokers who returned at 1 year , 334 ( 36.2 % ) had quit smoking . Despite gaining more weight ( 4.6 kg [ 5.7 ] vs 0.7 kg [ 5.1 ] , P < .001 ] , abstainers had increases in high-density lipoprotein cholesterol ( HDL-C ) ( 2.4 [ 8.3 ] vs 0.1 [ 8.8 ] mg/dL , P < .001 ) , total HDL ( 1.0 [ 4.6 ] vs -0.3 micromol/L [ 5.0 ] , P < .001 ) , and large HDL ( 0.6 [ 2.2 ] vs 0.1 [ 2.1 ] micromol/L , P = .003 ) particles compared with continuing smokers . Significant changes in low-density lipoprotein ( LDL ) cholesterol and particles were not observed . After adjustment , abstinence from smoking ( P < .001 ) was independently associated with increases in HDL-C and total HDL particles . These effects were stronger in women . CONCLUSIONS despite weight gain , smoking cessation improved HDL-C , total HDL , and large HDL particles , especially in women . Smoking cessation did not affect LDL or LDL size . Increases in HDL may mediate part of the reduced cardiovascular disease risk observed after smoking cessation AIM To evaluate the population effectiveness of stop-smoking medications while accounting for potential recall bias by controlling for quit attempt recency . DESIGN Prospect i ve cohort survey . SETTING United Kingdom , Canada , Australia and the United States . PARTICIPANTS A total of 7436 adult smokers ( 18 + years ) selected via r and om digit dialling and interviewed as part of the International Tobacco Control Four Country Survey ( ITC-4 ) between 2002 and 2009 . Primary analyses utilized the subset of respondents who participated in 2006 or later ( n = 2550 ) . MEASUREMENTS Continuous abstinence from smoking for 1 month/6 months . FINDINGS Among participants who recalled making a quit attempt within 1 month of interview , those who reported using varenicline , bupropion or nicotine patch were more likely to maintain 6-month continuous abstinence from smoking compared to those who attempted to quit without medication [ adjusted odds ratio ( OR ) 5.84 , 95 % confidence interval ( CI ) ( 2.12 - 16.12 ) , 3.94 ( 0.87 - 17.80 ) , 4.09 ( 1.72 - 9.74 ) , respectively ] ; there were no clear effects for oral NRT use . Those who did not use any medication when attempting to quit tended to be younger , to be racial/ethnic minorities , to have lower incomes and to believe that medications do not make quitting easier . CONCLUSIONS Consistent with evidence from r and omized controlled trials , smokers in the United Kingdom , Canada , Australia and the United States are more likely to succeed in quit attempts if they use varenicline , bupropion or nicotine patch . Previous population studies that failed to find an effect failed to control adequately for important sources of bias BACKGROUND Nicotine replacement therapies have proved to be of value in smoking cessation . However , not all smokers can use the nicotine gum or nicotine patch owing to side effects . In addition , the absorption of nicotine from these formulas is slow compared with smoking . A nicotine nasal spray delivers nicotine more rapidly . The objective of this study was to evaluate the efficacy and safety of the nicotine nasal spray for smoking cessation . METHODS Subjects were recruited through advertisements in newspapers and among patients referred to the smoking cessation clinic at Sahlgren 's Hospital , Göteborg , Sweden . Two hundred forty-eight smokers were treated in small groups with eight counseling sessions over 6 weeks . At their first group session , subjects were r and omized to a group receiving nicotine spray ( n = 125 ) , 0.5 mg of nicotine per single spray , or to a placebo group ( n = 123 ) . The procedure was double blind . Success rates were measured up to 12 months . The nonsmoking status was verified by expired carbon monoxide less than 10 ppm . RESULTS Significantly more subjects in the nicotine group were continuously abstinent for 12 months than in the placebo group ( 27 % vs 15 % ; odds ratio , 2.16 ; 95 % confidence interval , 1.15 to 4.12 ) . Ten of the 34 abstinent subjects in the nicotine group used the spray for 1 year . Mild or moderate side effects were rather frequent for both sprays , but they were significantly more for the nicotine spray . Subjects with high scores ( > 7 ) on Fagerström 's tolerance question naire had a significantly lower success rate with placebo than with the nicotine spray . For subjects with low scores , there was no difference . CONCLUSION Nicotine nasal spray in combination with group treatment is an effective aid to smoking cessation Etude sur 651 fumeurs , non hospitalises , volontaires . Sur 224 sujets traites par acupunture , 43 ont cesse de fumer au bout d'un mois et 17 ont persevere au bout de 13 mois . Pour 205 sujets traites par chewing gum a la nicotine , ces nombres sont 22 et 12 ; pour 222 « temoins » ( controle psychologique ) , 8 et AIMS Although nicotine replacement therapy ( NRT ) has been used to aid smoking cessation for the last 20 years , little information exists on the effect of nicotine products on the oral mucosa , particularly with regard to the direct effect at the site of application . This study aim ed to assess the oral safety of a new sublingual tablet containing 2 mg nicotine with regard to lesions at the site of application . DESIGN Prospect i ve follow-up to 12 months of smokers using the 2-mg sublingual tablet over a period of 3 - 6 months . SETTING A smoking cessation programme . PARTICIPANTS Thirty smokers . MEASUREMENTS Oral mucosa was inspected and photographed at each visit . At 6 months , subjects were asked for consent to take a biopsy from the site of application . FINDINGS Spontaneous smoking cessation outcome at 12 months was 27 % allowing for lapses . At baseline 21 mucosal lesions were diagnosed in 15 subjects . After 6 months eight lesions were observed in six subjects . The predominant diagnosis at all visits was melanin pigmentation . Eight subjects had lesions in the floor of the mouth during the 6-month medication period , all of which appeared in the first 1 - 6 weeks of treatment . By the 6-month visit all such lesions had resolved . The local symptoms were all mild and tolerable . CONCLUSION The sublingual tablet appears to be a safe form of administration of nicotine with mild and transient effects on the floor of the mouth AIMS To assess smoking cessation rates achieved with nicotine gum and patch in simulated over-the-counter ( OTC ) and actual prescription ( Rx ) setting s. DESIGN Separate open-label studies with gum and patch in OTC and Rx setting s. PARTICIPANTS There were multiple sample s : OTC gum : 2981 smokers ; OTC patch : 2367 ; Rx gum : 324 ; Rx patch : 669 . INTERVENTIONS All smokers received active nicotine replacement . In the OTC setting , smokers self-selected doses of nicotine gum ( 2 or 4 mg Nicorette ) or patch ( 21 , 14 or 7 mg NicoDerm CQ ) . No intervention was provided . In the Rx setting , smokers were prescribed gum or patch by their physician . MEASUREMENTS Biochemically verified continuous smoking abstinence was assessed at 6 weeks ( 28-day abstinence ) and 6 months . FINDINGS OTC success rates were consistently higher than Rx rates : differences were significant at 6 weeks for both patch [ OR = 1.45 ( 1.05 - 1.98 ) ] and gum [ OR 2.92 ( 1.58 - 5.40 ) ] , and remained significant at 6 months for patch [ OR = 3.63 : ( 1.74 - 7.61 ) ] but not gum [ OR = 1.37 : ( 0.73 - 2.58 ) ] . Among OTC gum users . 16.1 % were abstinent at 6 weeks and 8.4 % at 6 months . For Rx gum users , abstinence rates were 7.7 % at 6 weeks and 7.7 % at 6 months . With OTC patch , 19.0 % were abstinent at 6 weeks and 9.2 % at 6 months . With Rx patch . abstinence rates were 16.0 % at 6 weeks and 3.0 % at 6 months . CONCLUSIONS Smoking cessation rates achieved with nicotine gum and patch under OTC conditions were as good as those under real-world prescribing conditions The process and outcome of a smoking cessation program using behavior therapy alone ( BT ) or behavior therapy plus the nicotine patch ( BTP ) was studied in 64 participants . Participants quit smoking on a target date after a period of ad libitum smoking , cognitive-behavior therapy preparing them for cessation , and behavioral rehearsal for high-risk situations , including stress management , and coping with negative affect . Abstinence was significantly higher for the BTP group versus the BT group from the end of behavioral treatment ( 79 % vs. 63 % ) through the 3-month follow-up ( p < .01 ) , with the effects weakening at the 6- ( p = .06 ) and 12-month marks ( p = 38 % vs. 22 % ) . More general distress was observed among BT versus BTP participants ( i.e. , increased withdrawal , tension , fatigue , and coping frequency with decreased coping effort ; coping-to-urge ratio ) . The coping behavior of the BTP group may have been more effective than that of the BT group , as indicated by their significantly higher level of self-efficacy Of 2110 adult cigarette smokers originally recruited to a study of the effect of antismoking advice in general practice , 429 who reported at follow up after one year that they had tried unsuccessfully to stop smoking were offered " a special antismoking chewing gum , " either nicotine gum or a placebo gum , in a double blind study . Of 200 who were willing to try the gum , 101 were r and omly allocated to the nicotine gum and 99 to the placebo gum . They were followed up at six months by an unannounced home visit , at which they were interviewed and asked to provide a breath sample for analysis of carbon monoxide . Twenty five cl aim ed that they had stopped smoking , but , of them , seven exhaled levels of carbon monoxide indicative of continued smoking . Of the 18 in whom giving up smoking was vali date d , 10 had received active gum and eight placebo gum , a difference which was not significant ( odds in favour of nicotine gum = 1.25 , 95 % confidence limits 0.47 - 3.31 ) . The value of nicotine chewing gum , if any , can be quite small when it is used in general practice The objective of the study was to evaluate the therapeutic efficacy of nicotine nasal solution ( NNS ) for smoking cessation from the stopping day up to 3 months . We also followed the participants for 2 yrs after ceasing smoking to assess what happens after stopping using NNS . In a placebo-controlled , double-blind , 2 yr prospect i ve study , 157 smokers were given either NNS , one dose containing 1 mg of nicotine per 100 microL ( n=79 ) , or placebo ( n=78 ) . Treatment was continued for up to 1 yr . One day after quitting smoking , the average number of daily doses was 11 in the group assigned NNS and 14 in the group assigned the placebo , and after 6 weeks , 14 and 6 doses , respectively , among abstinent participants still using spray . After 3 months , 65 % of the abstainers in the nicotine group were still using the NNS . The abstinence rates were 51 , 39 and 29 % after 6 weeks , 3 and 6 months , respectively , as compared to 24 , 19 and 18 % in the placebo group ( p=0.0003 ; p=0.003 ; p=0.050 ) . The proportion abstinent at the 1 yr ( 25 vs 17 % ) and 2 yr follow-ups ( 19 vs 14 % ) was higher among those assigned to the nicotine than to the placebo group , but not significantly so for the numbers used in the study . In conclusion , the use of nicotine nasal spray significantly increased the abstinence rate during the first 6 months following the quitting day OBJECTIVE The purpose of this study was to determine the contribution of r and omization to nicotine replacement therapy ( NRT ) , sociodemographic and psychosocial factors , and pregnancy and medical history to serious perinatal adverse events among pregnant smokers . STUDY DESIGN We performed a retrospective review of all medical records for participants in the Baby Steps Trial . Data that were abstract ed from 157 records were combined with baseline characteristics for logistic regression modeling of serious adverse events and adjusted for covariates . RESULTS Serious adverse events occurred in 17 % ( 9/52 pregnancies ) and 31 % ( 33/105 pregnancies ) of participants in the control and NRT arms , respectively . Black race , adverse pregnancy history , and use of analgesic medication during pregnancy were significant predictors ( P = .02 , .04 , and .01 , respectively ) . Remaining covariates , which included r and omization to NRT , were not statistically significant . CONCLUSION Although race , poor pregnancy history , and use of analgesics were associated with serious adverse events , r and omization to NRT during pregnancy was not a significant factor . Further research is needed to examine the safety of analgesic medications during pregnancy The rate of smoking was significantly reduced in volunteer subjects by providing effective nicotine replacement , self-help material , and weekly visits with a nurse for 6 weeks . Nicotine-replacement therapy with a transdermal nicotine patch ( Nicolan ) almost doubled the 6-week smoking-cessation rate in comparison with that in a placebo group ( 77 % versus 39 % ; P = 0.002 ) among subjects who were smoking at least 20 cigarettes per day at baseline . Although most subjects who used the active nicotine patches had skin reactions , the reactions were primarily mild . For use of both active and placebo patches , the level of patient compliance was high . Among subjects who continued to smoke , the use of cigarettes was decreased to less than 50 % of the baseline smoking level in 7 of 7 with active nicotine patches and in 15 of 19 with placebo patches . Outcomes beyond 6 weeks showed a substantial relapse rate in both groups . Thus , when nicotine-replacement therapy is provided , a need exists for concurrent behavioral intervention and training for prevention of a relapse , neither of which was part of this protocol To test the efficacy of sustained nicotine patch use among at-risk smokers , 55 smokers with a history of abstinence-induced depressed mood were r and omly assigned to either Nicotine Maintenance or St and ard Treatment following preliminary high-dose patch treatment . The Nicotine Maintenance group received 21 mg transdermal nicotine for 8 additional weeks ; the St and ard Treatment group followed a tapered dosing regimen . Significant differences favoring the Nicotine Maintenance group were found in self-reported craving but not withdrawal . No difference was observed in continuous abstinence or in relapse rates . When dropouts who did not relapse during patch use were classified as successful , however , the Nicotine Maintenance group had significantly lower relapse rates . Rate of lapse in the Nicotine Maintenance group during post-trial tapering did not differ significantly from that in the St and ard Treatment group during tapering in the trial , suggesting that the benefits of sustained dosing may persist only as long as dosing continues OBJECTIVE To test initial reactions to 5 nicotine treatments ( NRTs : 2 and 4 mg gum , inhaler , nasal spray , tablet ) in a crossover study ( n=41 ) . METHODS Subjects used each medication on arising ( 1/2 day ) and resumed smoking each afternoon . Subjects rated ( individually ) and ranked ( comparatively ) treatments on use , reinforcement , withdrawal , craving , and preferences . RESULTS Overall preferences : inhaler ( 49 % ) , 4 mg gum ( 24 % ) , 2 mg gum ( 10 % ) , 2 mg tablet ( 10 % ) , nasal spray ( 7 % ) . Overall results were consistent with ratings and rankings of individual characteristics of drugs . CONCLUSION Subjects had varied reactions to NRTs that may affect initiation of cessation INTRODUCTION Post-cessation weight gain is a commonly cited barrier to smoking cessation . Some evidence suggests that nicotine replacement therapy may limit post-cessation weight gain by reducing energy intake . This project aims to assess differential changes in energy intake and body weight during smoking cessation in a sample of postmenopausal women r and omized to receive 21 mg nicotine or placebo patch for 12 weeks . METHODS Postmenopausal women who smoked ≥10 cigarettes/day were enrolled in this double-blind r and omized placebo-controlled study . Total energy intake ( via four-day food diaries ) , body mass index ( BMI ; kg/m(2 ) ) , cigarettes/day and smoking status ( self-report verified by exhaled carbon monoxide ) were assessed at three time points : 2 weeks prior to quit date , 12 weeks after quit date , and 12 months after smoking cessation treatment . RESULTS Participants ( n = 119 ) were , on average , 55.8 ± 6.7 years old with a baseline BMI of 27.0 ± 5.2 and average cigarette/day was 21.1 ± 8.6 . At Week 12 , participants r and omized to nicotine patch increased their mean caloric intake by 146.4 ± 547.7 kcal/day whereas those on placebo patch decreased their caloric intake by 175.3 ± 463.2 ( f-value = 10.1 , p-value = 0.002 ) . Despite the differences in caloric intake , body weight remained similar between groups . CONCLUSIONS The results of this study indicate that nicotine patch may increase energy intake during treatment , and does not prevent post-cessation weight gain in postmenopausal smokers . Additional research is needed to replicate these findings and assess whether different forms of nicotine replacement therapy influence caloric intake and post-cessation weight gain in postmenopausal smokers This study examined the effects of the nicotine patch on craving and withdrawal symptoms , safety , and compliance among adolescents . The secondary goal was to conduct a preliminary investigation of the effectiveness of the nicotine patch in helping adolescents quit smoking . The study design was a double-blind , placebo-controlled , r and omized trial of the nicotine patch . The intervention also provided intensive cognitive-behavioral therapy and a contingency-management procedure . Participants ( n=100 ) attended 10 treatment visits over 13 weeks . Compared with the placebo patch group , the active nicotine patch group experienced a significantly lower craving score and overall withdrawal symptom score ( p=.011 and p=.025 , respectively ) , as well as a time trend toward lower scores ( p<.001 ) in craving only . Moreover , the nicotine patch appeared safe for adolescents to use . No differences by treatment group were found in experiencing adverse events , except that the participants in the placebo patch group reported more headaches than those in the active nicotine patch group . As another measure of safety , the overall mean salivary cotinine levels were significantly lower at 1 , 6 , 8 , and 10 weeks postquit ( all p<.05 ) compared with baseline levels , although these results were confounded by dropouts . Additionally , a significant number of participants were compliant with using the nicotine patch daily . Finally , point prevalence ( 7-day and 30-day abstinence rates ) and survival analysis of participant abstinence indicated no significant differences between treatment groups . The results of this study suggest that the nicotine patch is a promising medication and a larger clinical trial of the nicotine patch among adolescents is warranted AIMS Because smoking cessation rates might be improved by combining drugs and by reducing post-cessation weight gain , we tested the smoking cessation efficacy , safety and effect on body weight of adding the nicotine patch to rimonabant , a cannabanoid type-1 receptor antagonist that reduces body weight . DESIGN R and omized double-blind placebo-controlled trial . SETTING Fifteen US research centers . PARTICIPANTS A total of 755 smokers ( > OR = 15 cigarettes/day ) . Intervention Rimonabant ( 20 mg daily ) was given open-label for 9 weeks . The 735 participants completing week 1 were r and omized at day 8 ( target quit day ) to add a nicotine patch ( n = 369 ) or placebo patch ( n = 366 ) for 10 weeks ( 21 mg daily for 8 weeks plus a 2-week taper ) . Participants received weekly smoking counseling and were followed for 24 weeks . MEASUREMENTS Biochemically vali date d 4-week continuous abstinence at end-of-treatment ( weeks 6 - 9 ; primary end-point ) ; 7-day point prevalence abstinence at weeks 9 and 24 ; sustained abstinence ( weeks 6 - 24 ) ; change in body weight ; and adverse events . FINDINGS Rimonabant plus nicotine patch was superior to rimonabant plus placebo in vali date d continuous abstinence at weeks 6 - 9 ( 39.0 % versus 21.3 % ; odds ratio 2.36 , 95 % confidence interval : 1.71 - 2.37 ; P < 0.01 ) and in all other efficacy measures . Mean end-of-treatment weight gain among quitters did not differ between groups ( 0.04 kg for combination versus 0.49 kg for rimonabant only , P = 0.15 ) and was similar in weight-concerned smokers . Serious adverse event rates did not differ between groups . Depression- and anxiety-related adverse events occurred in 32 ( 4.2 % ) and 44 ( 5.8 % ) subjects , respectively ; eight ( 1.1 % ) and nine ( 1.2 % ) subjects stopped the drug due to depression and anxiety , respectively . CONCLUSIONS Adding a nicotine patch to rimonabant was well tolerated and increased smoking cessation rates over rimonabant alone . There was little post-cessation weight gain in either group , even among weight-concerned smokers , during drug treatment AIM Approximately 50 % of African American smokers are light smokers ( smoke < or = 10 cigarettes a day ) . The prevalence of light smoking in the United States is increasing , yet there has not been a single smoking cessation clinical trial targeting light smokers . The purpose of this 2 x 2 factorial , r and omized clinical trial was to evaluate the efficacy of nicotine gum ( 2 mg versus placebo ) and counseling ( motivational interviewing versus health education ) for African American light smokers . DESIGN Participants were assigned r and omly to one of four study arms : 2 mg nicotine gum plus health education ( HE ) ; 2 mg nicotine gum plus motivational interviewing ( MI ) ; placebo gum plus HE ; and placebo gum plus MI . PARTICIPANTS AND SETTING A total of 755 African American light smokers ( 66 % female , mean age = 45 ) were enrolled at a community health center over a 16-month period . INTERVENTION AND MEASUREMENTS Participants received an 8-week supply of nicotine gum and six counseling sessions during the course of the 26-week study . Biochemical measures included expired carbon monoxide ( CO ) and serum and salivary cotinine . FINDINGS Seven-day quit rates for nicotine gum were no better than for the placebo group ( 14.2 % versus 11.1 % , P = 0.232 ) at 6 months . However , a counseling effect emerged , with HE performing significantly better than MI ( 16.7 % versus 8.5 % , P < 0.001 ) . These results were consistent across outcome time-points ( weeks 1 , 8 , and 26 ) . CONCLUSIONS Results highlight the potential positive impact of directive information and advice-oriented counseling on smoking cessation . Studies are needed to assess other interventions that may further improve quit rates among African American light smokers who are motivated to quit Many smokers are not ready to quit but are interested in changing their smoking behavior , particularly if such a change is associated with a reduction in health risk . The present study evaluated the efficacy of the nicotine inhaler in reducing smoking . Exploratory studies assessed whether reduction in smoking was associated with reduction in markers of disease risk . A total of 429 healthy smokers ( smoking at least 20 cigarettes/day ) were r and omly assigned to either nicotine-containing or placebo inhalers , which subjects were allowed to use ad libitum for up to 1 year . The nicotine inhaler was significantly superior to placebo in achieving reduction in daily cigarette consumption by at least 50 % after 4 months , compared with baseline ( 18 % vs. 8 % , p = .004 ) . Active treatment promoted smoking cessation : 8 % of subjects in the nicotine group and 1 % in the placebo group were abstinent at month 15 . Throughout the study , smoking reduction , per se , independent of treatment group , was associated with a statistically significant decrease in exhaled carbon monoxide and serum cotinine and thiocyanate . Smoking reduction also improved established risk markers for cardiovascular disease over 4 months . The incidence of adverse events did not differ significantly between the active and placebo groups . The most common treatment-related adverse events were throat irritation and cough . In conclusion , the nicotine inhaler can help smokers who are unable or unwilling to quit to reduce daily cigarette consumption , which may be a health benefit on its own and may further promote quitting With smoking prevalence rates beginning to decline , studies design ed to promote cessation in more challenging population s , like weight-concerned smokers , warrant attention . This study assessed the efficacy of two forms of pharmacotherapy [ nicotine and phenylpropanolamine ( PPA ) gums ] in addition to a 13-week cognitive behavioral smoking cessation program targeted for women . Participants were 439 females who met rigorous screening criteria and were r and omized to one of the three treatment intervention groups ( PPA gum , nicotine gum , or placebo gum ) . All participants attended a 13-week cognitive behavioral smoking cessation program and were given specific instructions on gum chewing . At posttest ( 13 weeks ) , and 6- and 12-month follow-ups , body weight and point prevalence abstinence were assessed . Analyses to determine potential differences between treatment groups on weight change and cessation rates were performed . Results indicated that neither change in body weight nor cessation rates significantly differed between groups . Attendance to sessions did appear to consistently increase the likelihood of quitting smoking at posttest and at each of the follow-ups . These results suggest that although the pharmacological interventions had no effect on cessation rates and postcessation weight gain , the behavioral component of the intervention was effective in increasing the odds of quitting smoking in weight-concerned women . Future efforts should focus on increasing adherence to behavioral program components , particularly session attendance BACKGROUND With smoking rates far exceeding the general population , methadone-maintained ( MMT ) opiate-dependent smokers experience high rates of tobacco-related health consequences . Previous treatment studies have used nicotine replacement and produced low quit rates . METHODS We test , using a three-group r and omized design , the efficacy of varenicline versus placebo , in comparison with nicotine replacement therapy ( NRT ) that combines nicotine patch prescription plus ad libitum nicotine rescue , for smoking cessation . We recruited methadone-maintained smokers from nine treatment centers in southern New Engl and and provided six months of treatment , and a minimal behavioral intervention at baseline ( NCI 's 5A 's ) . Outcomes included carbon monoxide ( CO ) confirmed 7-day point smoking cessation prevalence at 6 months and self-reported change in mean cigarettes per day . RESULTS The 315 participants had a mean age of 40 , with 50 % male and 79 % non-Hispanic White , smoked an average of 19.6 ( ± 10.4 ) cigarettes/day , and had a mean daily methadone dose of 109 mg . Intent-to-treat analyses , with missing considered to be smoking , showed the rate of CO-confirmed 7-day abstinence at 6-months was 5.4 % overall , with varenicline 3.7 % compared to placebo 2.2 % , and NRT 8.3 % ( p>.05 ) . Adherence rates during the 7-days immediately prior to 6-month assessment were 34.2 % in varenicline , 34.4 % in placebo , and 48.8 % in NRT . Between baseline and 6-months there was an overall self-reported mean reduction of 8.3 cigarettes/day . CONCLUSION Varenicline did not increase quit rates over placebo . Smoking cessation rates in methadone-maintained smokers are low and novel treatment strategies are required INTRODUCTION Methadone maintenance treatment ( MMT ) patients have an exceedingly high prevalence of tobacco use , and interventions that have been specifically developed for this vulnerable sub population have struggled to attain even modest rates of cessation . A significant barrier has been an inability to initiate a quit attempt early in the treatment process and adherence to treatment . METHODS This study examined the extent to which self-efficacy , medication adherence , and other demographic and smoking variables predicted an early quit day in a sample of MMT smokers ( n = 315 ) enrolled in a smoking cessation pharmacotherapy trial . Using logistic regression , we estimated the association of having an early quit day-24hr without smoking during the first month of treatment . RESULTS Only 35.2 % of participants reported a successful early quit day . The likelihood of an early quit day increased significantly ( odds ratio [ OR ] = 1.39 , 95 % CI = 1.04 - 1.86 , p < .05 ) with education level and if a quit attempt was made in the past year ( OR = 2.27 , 95 % CI = 1.33 - 3.87 , p < .01 ) . Compared to the placebo arm , those r and omized to either nicotine replacement therapy ( OR = 3.25 , 95 % CI = 1.30 - 8.10 , p < .01 ) or varenicline ( OR = 3.16 , 95 % CI = 1.26 - 7.92 ) were significantly more likely to have an early quit day . The likelihood of an early quit day was also positively associated with adherence to the medication protocol ( OR = 2.05 , 95 % CI = 1.52 - 2.76 ) . CONCLUSIONS Difficulty in achieving an early quit attempt may help explain the very low cessation rates found in studies of MMT smokers This study assessed the efficacy and safety of a nicotine sublingual tablet in smoking cessation in a r and omized , double-blind , placebo-controlled outpatient trial conducted between January 1996 and May 1997 . Two hundred and forty-one adult smokers ( > or = 10 cigarettes/day for at least 3 years ) used nicotine 2-mg sublingual tablet ( n = 120 ) or placebo ( n = 121 ) for up to 6 months ( a 3-month treatment period followed by a 3-month tapering period ) . Subjects who scored < 7 on the Fagerström Tolerance Question naire used 1 tablet/h ( up to maximum of 20/day ) , whereas subjects who scored ( 7 used 2 tablets/h ( up to maximum of 40/day ) . Brief counseling was provided at baseline and at all visits . Self-reported abstinence was measured from week 2 onwards , confirmed by expired carbon monoxide ( CO ) levels < 10 ppm at each visit ( 1 , 2 , 3 and 6 weeks and 3 , 6 and 12 months ) . After 6 weeks of treatment , CO-vali date d abstinence rates were 48 % in the active group and 23 % in the placebo group ( p < 0.0001 ) . At the 3- , 6- and 12-month visits , abstinence rates ( active vs. placebo ) were 33 % vs. 17 % ( p = 0.0046 ) , 21 % vs. 11 % ( p = 0.0304 ) and 18 % vs. 10 % ( p = 0.0606 ) . Adverse events were mild and transient and reflected those reported with existing nicotine replacement formulations . We concluded that the nicotine 2-mg sublingual tablet was effective as a smoking cessation aid AIMS To assess the influence of unsuccessful past quit attempts using pharmacological treatment on smoking cessation when using a new nicotine lozenge . DESIGN A double-blind , r and omized , placebo-controlled trial . SETTING Fifteen sites in the United Kingdom and the United States . PARTICIPANTS A total of 1818 smokers seeking smoking cessation treatment ; 1145 had had previous pharmacological treatment for smoking cessation . INTERVENTION Lozenge , 2 mg or 4 mg ( or matched placebo ) ; a higher dose was assigned to smokers who smoked their first cigarette of the day within 30 minutes , a sign of dependence . Smokers received minimal instruction and counseling . MEASUREMENT Outcome was 28-day , CO-verified continuous abstinence at 6 weeks . Past use of medications was ascertained by self-report . FINDINGS Lozenge was efficacious among smokers with prior pharmacotherapy as well as among those without such history . The effect of lozenge ( versus placebo ) was significantly greater among those with previous treatment experience , because previous treatment was associated with significantly poorer outcome on placebo , and active lozenge treatment corrected this imbalance . Lozenge efficacy was similar whether smokers had previously tried patch or acute forms of nicotine replacement therapy ( gum , inhaler and spray ) , and also similar for past use of Zyban ( bupriopion ) . CONCLUSIONS Smokers with a history of past failure of pharmacological treatment have lower success rates without pharmacological treatment , but equally good outcomes with active lozenge treatment . Smokers who previously tried pharmacological treatments but resumed smoking should be encouraged to try quitting again with the new nicotine lozenge AIM Nicotine replacement therapy ( NRT ) is an effective treatment for smokers who want to quit , however , the rates of successful quitting can be improved even more . In this context , nicotine dependence ( assessed via the Fagerström Tolerance Question naire , FTQ ) , psychological distress ( measured via the Symptom Rating Test , SRT ) , and personality traits ( evaluated via the Adult Eysenck Personality Inventory , AEPI ) were evaluated as possible predictors of smoking cessation . RESULTS A total of 297 cigarette smokers were followed for one year as part of a NRT double-blind , parallel group , r and omized trial . Baseline nicotine dependence ( weeks 12 and 26 : p<0.05 ) , AEPI neuroticism ( weeks 12 and 52 : p<0.05 ) , and AEPI psychoticism ( weeks 12 and 52 : p<0.05 ) scores significantly influenced the outcome of smoking cessation during one-year of follow-up . An increase in psychological distress during follow-up was associated with a lower probability of quitting smoking ( p=0.000 ) . CONCLUSIONS Nicotine dependence , neuroticism , psychoticism and , over time , psychological distress were the main factors influencing the long-term outcome ( i.e. , up to 12 months ) of smoking cessation under NRT Rationale Decreasing withdrawal and craving during smoking cessation is a major aim of cessation medications . Prior studies have shown that Nicotine Replacement Therapy ( NRT ) decreases withdrawal symptom severity but have relied on retrospective reports and lacked robust measures of baseline symptoms or symptoms during unmedicated abstinence . Objectives and methods We tested the effect of high-dose ( 35 mg ) nicotine patch on withdrawal and craving during abstinence using real-time assessment with electronic diaries during ad libitum smoking , a brief period of experimentally directed trial abstinence , and the first 3 days of cessation . Subjects were 324 smokers r and omized to high-dose nicotine patches or placebo . Results Treatment with active patches reduced withdrawal and craving during cessation and completely eliminated deprivation-related changes in affect or concentration . Conclusion High-dose NRT reduces withdrawal symptoms and craving and can eliminate some symptoms entirely The objective of this study was to assess whether nicotine replacement therapy , administered in a real-life situation , could reduce cigarette consumption in smokers who were not prepared to quit smoking . Daily smokers of more than 20 cigarettes per day who had no intention to quit smoking in the next 6 months were recruited from the general population and r and omly assigned to either a 6-month treatment of nicotine ( choice among a 15-mg nicotine patch , a 4-mg nicotine gum , a 10-mg nicotine inhaler , or a combination of these , N = 265 ) , matching placebo products ( N = 269 ) , or no intervention ( N = 389 ) . Products were sent to participants by mail . Education was limited to a booklet . Of 923 participants , 879 ( 95 % ) were followed up after 6 months . Mean baseline consumption was 30 cigarettes per day in all groups . At 6 months , cigarette consumption decreased by a median of 10 cigarettes per day in the nicotine group , 7.5 in the placebo group , and 2.5 among controls ( p < 0.04 for all pair-wise comparisons ) . Smoking cessation rates were low ( 2%–4 % ) and did not differ significantly between groups . Quit attempts were less frequent among controls ( 21 % ) than among the nicotine ( 28 % , p = 0.04 ) and placebo ( 27 % , p = 0.08 ) subjects . In conclusion , nicotine replacement therapy helped smokers reduce their cigarette consumption and maintain this reduction over 6 months , but a large part of this reduction was attributable to a placebo effect . Nicotine treatment for smoking reduction had no detectable impact on smoking cessation Objective To estimate the “ real-world ” effectiveness of commonly used aids to smoking cessation in Engl and by using longitudinal data . Patients and Methods We conducted a prospect i ve cohort study in 1560 adult smokers who participated in an English national household survey in the period from November 2006 to March 2012 , responded to a 6-month follow-up survey , and made at least 1 quit attempt between the 2 measurements . The quitting method was classified as follows : ( 1 ) prescription medication ( nicotine replacement therapy [ NRT ] , bupropion , or varenicline ) in combination with specialist behavioral support delivered by a National Health Service Stop Smoking Service ; ( 2 ) prescription medication with brief advice ; ( 3 ) NRT bought over the counter ; ( 4 ) none of these . The primary outcome measure was self-reported abstinence up to the time of the 6-month follow-up survey , adjusted for key potential confounders including cigarette dependence . Results Compared with smokers using none of the cessation aids , the adjusted odds of remaining abstinent up to the time of the 6-month follow-up survey were 2.58 ( 95 % CI , 1.48 - 4.52 ) times higher in users of prescription medication in combination with specialist behavioral support and 1.55 ( 95 % CI , 1.11 - 2.16 ) times higher in users of prescription medication with brief advice . The use of NRT bought over the counter was associated with a lower odds of abstinence ( odds ratio , 0.68 ; 95 % CI , 0.49 - 0.94 ) . Conclusion Prescription medication offered with specialist behavioral support and that offered with minimal behavioral support are successful methods of stopping cigarette smoking in Engl and Background Many smokers remain unwilling or unable to make a quit attempt . For these smokers , novel strategies to induce quit attempts are necessary to achieve further reductions in smoking prevalence . Purpose This article describes the design and methods of an ongoing nationwide telephone-based clinical trial for cessation induction , the principal aim of which is to test the hypothesis that sample s of nicotine replacement therapy ( NRT ) , can induce quit attempts among smokers otherwise unmotivated to quit . Methods Smokers are recruited proactively through online channels . A ‘ behavioral filter ’ is used to identify and separate motivated versus unmotivated smokers , the latter of whom ( N = 750 ) are formally entered into the clinical trial . Participants are r and omized to one of two treatment conditions design ed to promote self-efficacy and motivation to quit : ( 1 ) practice quit attempt ( PQA ) or ( 2 ) PQA plus NRT sampling . The primary outcome measure tested over a 6-month follow-up is the incidence of additional quit attempts as well as hypothesized mediators of treatment effects . Results This study details the challenges of identifying and treating smokers who are unmotivated to quit . Strengths include a novel treatment approach , tested among a group of proactively recruited smokers nationwide , with a unique method of identifying cessation-resistant smokers . Limitations The omission of a true control group , testing the effect of the PQA itself , is an inherent limitation to the study design . Online recruitment presents additional study challenges , all of which are discussed in detail . Conclusions The study has translational potential to guide both clinical and policy recommendations for cessation induction . Further , while the focus is on smoking , this trial may serve as an example to research ers and clinicians who focus on other health behaviors , and who themselves are challenged with motivating people who are unmotivated for change . Clinical Trials 2010 ; 7 : 157—166 . BACKGROUND Since nicotine gum was introduced in the 1980s , nicotine replacement therapy has become the most widely used pharmacological smoking cessation treatment . Some smokers prefer acute oral forms , but many smokers reject chewing gum . We tested the safety and efficacy of a new nicotine polacrilex lozenge for smoking cessation . METHODS Double-blind , placebo-controlled , r and omized clinical trial with parallel arms testing 2- and 4-mg nicotine lozenges . Smokers ( n = 1818 ) were assigned to a lozenge dose on the basis of nicotine dependence , assessed by time to the first cigarette of the day . Low-dependence smokers were r and omized to receive the 2-mg nicotine ( n = 459 ) or placebo ( n = 458 ) lozenge ; high-dependence smokers , the 4-mg nicotine ( n = 450 ) or placebo ( n = 451 ) lozenge . We assessed abstinence at 6 , 12 , 24 , and 52 weeks and analyzed craving and withdrawal symptoms . RESULTS Treatment with the nicotine lozenge result ed in significantly greater 28-day abstinence at 6 weeks , for the 2-mg ( 46.0 % vs. 29.7 % ; odds ratio [ OR ] , 2.10 ; 95 % confidence interval [ CI ] , 1.59 - 2.79 ; P<.001 ) and the 4-mg ( 48.7 % vs. 20.8 % ; OR , 3.69 ; 95 % CI , 2.74 - 4.96 ; P<.001 ) lozenges , compared with placebo . Significant treatment effects were maintained for a full year . Smokers who used more lozenges achieved significantly better treatment effects . Use of the active lozenge also result ed in reduced craving and withdrawal . Most adverse events were moderate and resembled those seen with nicotine gum . CONCLUSION The nicotine lozenge is a safe and effective new treatment for smoking cessation in low- and high-dependence smokers In a controlled trial of brief treatment for smoking using nicotine chewing gum in a workplace setting , 270 of 334 cigarette smokers who expressed interest were invited to take part in the program , which consisted of two individual consultations ; 172 attended . The remaining 64 smokers constituted a no-intervention control group . Using a criterion of sustained one-year abstinence with biochemical validation , success rates were 12 per cent among participants , 1 per cent among those who were invited but did not attend , and 2 per cent in the control group A variety of studies have shown that nicotine skin patches are effective in promoting smoking cessation . This study replicated this effect , in addition , nicotine skin patches were found to decrease a variety of withdrawal effects , including craving for cigarettes , negative affect , hypoarousal , and increased appetite . This study also assessed the depressive symptoms shown by smokers before and after they quit smoking . Control subjects showed a significant increase in depressive symptoms after smoking cessation , whereas the subjects given the nicotine skin patch were not as affected . If the subjects slipped and smoked a cigarette during the time they were wearing the patch , they were asked to rate the effects of that cigarette . These " slip " cigarettes were rated significantly lower in satisfaction and good taste by subjects in the nicotine patch group than by controls . The nicotine skin patch may improve smoking cessation rates both by reducing nicotine withdrawal effects and by reducing the reward of slips back to smoking . This latter effect may prove to be effective in preventing slips from turning into relapses Background Smoking in pregnancy remains a public health challenge . Nicotine replacement therapy ( NRT ) is effective for smoking cessation in non-pregnant people , but because women metabolise nicotine and cotinine much faster in pregnancy , it is unclear whether this will be effective for smoking cessation in pregnancy . The NHS Health Technology Assessment Programme (HTA)-funded smoking , nicotine and pregnancy ( SNAP ) trial will investigate whether or not nicotine replacement therapy ( NRT ) is effective , cost-effective and safe when used for smoking cessation by pregnant women . Methods / Design Over two years , in 5 trial centres , 1050 pregnant women who are between 12 and 24 weeks pregnant will be r and omised as they attend hospital for ante-natal ultrasound scans . Women will receive either nicotine or placebo transdermal patches with behavioural support . The primary outcome measure is biochemically-vali date d , self-reported , prolonged and total abstinence from smoking between a quit date ( defined before r and omisation and set within two weeks of this ) and delivery . At six months after childbirth self-reported maternal smoking status will be ascertained and two years after childbirth , self-reported maternal smoking status and the behaviour , cognitive development and respiratory symptoms of children born in the trial will be compared in both groups . Discussion This trial is design ed to ascertain whether or not st and ard doses of NRT ( as transdermal patches ) are effective and safe when used for smoking cessation during pregnancy BACKGROUND This study was undertaken to assess the safety and efficacy of a treatment involving brief counseling and the nicotine patch among hospital in patients and to identify variables associated with long-term smoking cessation following hospitalization . METHODS One hundred eighty-five patients were r and omly assigned to one of three smoking cessation interventions : ( 1 ) A Minimal Care ( MC ) condition , consisting of a brief physician-delivered motivational message to stop smoking , ( 2 ) a Counseling + Active Nicotine Patch ( CAP ) condition in which patients received the motivational message , a 6-week supply of nicotine patches , and extended bedside and telephone counseling , and ( 3 ) a Counseling + Placebo Patch ( CPP ) condition identical to the CAP condition except the supplied patches contained no nicotine . RESULTS At 6-month follow-up , abstinence rates for the three treatments were 4.9 , 6.5 , and 9.7 % for the MC , CPP , and CAP treatments , respectively . These differences were not statistically significant . Patients admitted for respiratory disease were more likely to quit than patients with any other diagnosis . The nicotine patch was well tolerated by hospital in patients . CONCLUSIONS The initiation of nicotine patch therapy during hospitalization appears to be safe when used among patients carrying a wide range of diagnoses . Our study provided no evidence of the superiority of nicotine patches versus placebo , but this does not preclude the possibility that future research using larger sample s might detect differences between patch groups . Hospital interventions for smoking cessation may be most effective among patients hospitalized for a smoking-related illness such as respiratory disease BACKGROUND This study examines whether adding nicotine replacement therapy ( NRT ) to cognitive-behavioral therapy ( CBT ) for pregnant smokers increases rates of smoking cessation . METHODS An open-label r and omized trial ( Baby Steps , n=181 ) of CBT-only versus CBT+NRT ( choice of patch , gum , or lozenge ; 1:2 r and omization ) was used . Data were collected from 2003 through 2005 ; analyses were conducted in 2006 and 2007 . Outcomes were biochemically vali date d self-reported smoking status at 7 weeks post-r and omization , 38 weeks gestation , and 3 months postpartum . RESULTS Women in the CBT+NRT arm were almost three times more likely than women in the CBT-only arm to have biochemically vali date d cessation at both pregnancy time points ( after 7 weeks : 24 % vs 8 % , p=0.02 ; at 38 weeks gestation : 18 % vs 7 % , p=0.04 ) , but not at 3 months postpartum ( 20 % vs 14 % , p=0.55 ) . Recruitment was suspended early by an Independent Data and Safety Monitoring Board when an interim analysis found a higher rate of negative birth outcomes in the CBT+NRT arm than in the CBT-only arm . In the final analysis , the difference between the arms in rate of negative birth outcomes was 0.09 ( p=0.26 ) , when adjusted for previous history of preterm birth . CONCLUSIONS The addition of NRT to CBT promoted smoking cessation in pregnant women . This effect did not persist postpartum . More data are needed to determine safety parameters and to confirm the efficacy of NRT use during pregnancy OBJECTIVES To evaluate the efficacy of the transdermal nicotine patch as an aid to smoking cessation when used as an adjunct to a cognitive-behavioural group intervention and to assess the effectiveness of the patch in ameliorating withdrawal symptoms . DESIGN AND SETTING Double-blind placebo-controlled r and omised trial with six months ' follow-up of those who returned to the hospital-based out patients smoking cessation clinic . SUBJECTS Three hundred and thirteen smokers recruited from the local community . Mean age was 42 years , 48 % were male , mean cigarette consumption was 29 per day and mean duration of smoking was 24 years . INTERVENTION Cognitive-behavioural intervention delivered in a group context , two hours once a week over five weeks , self-help manual , and 24-hour daily nicotine patch treatment for 10 weeks . MAIN OUTCOME MEASURES Point prevalence abstinence at three and six months , and sustained cessation from end of treatment to six months , with biochemical validation ( expired carbon monoxide ) . We examined the effectiveness of the nicotine patch in ameliorating specific withdrawal symptoms by self-report of degree of severity . RESULTS The active nicotine patch result ed in significantly higher biochemically confirmed abstinence rates when compared with placebo at three months ( 48 % v. 21 % ) and at six months ( 33 % v. 14 % ) . Six-months ' continuous abstinence rates were also significantly higher among the active nicotine group ( 25 % ) compared with placebo ( 12 % ) . The most common adverse events among active patch users were sleep disturbance and local skin irritation . The nicotine patch reduced the severity of some withdrawal symptoms . A low level of dependence was the strongest predictor of three and six months ' abstinence . CONCLUSIONS The transdermal nicotine patch is effective when used as an adjunct to a group cognitive-behavioural intervention and it provides relief from withdrawal symptoms associated with nicotine dependence We have recently published efficacy and safety data of a study using an oral nicotine inhaler in smoking reduction . The current analysis was undertaken to assess the secondary objectives of the trial : the influence of long-term smoking reduction on health risk markers . Four hundred healthy volunteers , unable or unwilling to stop smoking immediately , were enrolled in a double-blind , r and omized , placebo-controlled trial in smoking reduction ; 310 were evaluable up to 2 years . Participants were r and omized to active or placebo inhalers as needed for up to 18 months , with subjects encouraged to reduce their smoking as much as possible ; counseling took place over a 2-year period . For the current prospect i ve cohort study , the number of daily cigarettes , carbon monoxide ( CO ) , cotinine , cardiovascular risk factors , pulmonary function tests , and quality of life were compared between successful reducers ( n = 25 ) and unsuccessful reducers ( control group , n = 285 ) . Success was defined as a reduction of daily cigarettes of at least 50 % from week 6 to 2 years , verified by a decrease in exhaled CO at all visits compared with baseline . At 2 years , successful reducers showed a significantly greater decrease in cotinine levels ( 60 % vs. 1 % , p < 0.001 ) , cholesterol/high-density lipoprotein ( HDL ) ratios ( -2.42 vs. -1.67 , p = 0.025 ) , hemoglobin concentrations ( -5.67 vs. -1.34 g/l , p = 0.023 ) , pulse rate ( -3.7 vs. + 1.0 bpm , p = 0.043 ) , and significantly improved general health score ( 9.40 vs. 2.34 , p = 0.049 ) ; whereas no difference was found in forced expiratory volume during 1 s ( FEV1 ) and forced vital capacity ( FVC ) compared with controls . The benefits of long-term smoking reduction of at least 50 % of daily cigarettes were not offset by compensatory smoking , and the marked decrease in markers of smoke exposure had a positive influence on several cardiovascular risk markers and quality of life assessment BACKGROUND Nicotine replacement therapy has been shown to improve success rates in smoking cessation treatment . However , the available products cause adverse effects , which prevent some smokers from using them . A new method of delivering nicotine via inhaler supplies nicotine orally through inhalation from a plastic tube . This mode of delivering nicotine resembles smoking , as it includes h and ling and active inhalation . OBJECTIVES To assess the efficacy and safety of the nicotine inhaler as an aid in smoking cessation . METHODS A 1-year , r and omized , double-blind , placebo-controlled study was conducted in a smoking cessation clinic . Two hundred forty-seven smokers who smoked at least 10 cigarettes per day and who had previously made a serious attempt to stop smoking using nicotine chewing gum were recruited through advertisements . R and omization to treatment or control conditions were made at the first group session , with 123 participants receiving nicotine inhalers and 124 receiving placebo inhalers . The inhalers were distributed at the second session and participants were allowed to use the inhalers for 6 months . MAIN OUTCOME MEASURE Biochemically verified continuous abstinence from smoking after 2 and 6 weeks and at 3 , 6 , and 12 months . RESULTS Significantly more participants who had used the nicotine inhalers were continuously abstinent compared with those who had used the placebo inhalers . The respective success rates after 12 months were 28 % and 18 % ( P = .046 ) . At 6 months , 20 participants ( 16 % ) in the nicotine group were still using the inhaler , compared with 4 ( 3 % ) in the control group ( P < .001 ) . CONCLUSION The nicotine inhaler was an effective smoking cessation aid that produced a few mild and transient adverse effects This study examines the effects of transdermal nicotine patches for smoking cessation on depressive and withdrawal symptoms among 38 non-medicated subjects with Major Depressive Disorder . The study was conducted over a 29-day period , which included a 7 day baseline phase , a 14 day treatment phase , and an 8 day placebo phase . During the treatment phase subjects received either active nicotine patches ( N = 18 ) or placebo patches ( N = 20 ) that were administered in a r and omized , double-blind fashion . The target quit date ( TQD ) was day 8 . Significantly , more subjects in the placebo group than in the nicotine group resumed smoking following the TQD ( 50 % vs. 22 % ) . There was little evidence for effects of active nicotine patches on measures of mood ( HRSD , BDI , POMS ) or withdrawal symptoms among subjects that remained abstinent throughout the study ( N = 24 ) . Those who resumed smoking had more severe withdrawal symptoms than those who remained abstinent . One patient in the placebo group ( n = 20 ) became more depressed after 2 weeks of abstinence . None of the patients in the nicotine group ( n = 18 ) became more depressed Earlier research indicated that a 10-session mood management ( MM ) intervention was more effective than a 5-session st and ard intervention for smokers with a history of major depressive disorder ( MDD ) . In a 2 x 2 factorial design , the present study compared MM intervention to a contact-equivalent health education intervention ( HE ) and 2 mg to 0 mg of nicotine gum for smokers with a history of MDD . Participants were 201 smokers , 22 % with a history of MDD . Contrary to the earlier findings , the MM and HE interventions produced similar abstinence rates : 2 mg gum was no more effective than placebo . History-positive participants had a greater increase in mood disturbance after the quit attempt . Independent of depression diagnosis , increases in negative mood immediately after quitting predicted smoking . No treatment differences were found in trends over time for measures of mood , withdrawal symptoms , pleasant activities and events , self-efficacy , and optimism and pessimism . History-positive smokers may be best treated by interventions providing additional support and contact , independent of therapeutic content BACKGROUND Nicotine polacrilex lozenges deliver 25 % to 27 % more nicotine compared with equivalent doses of nicotine polacrilex gum . The increased nicotine exposure from the lozenge has raised questions about the relative safety of the lozenge and gum . OBJECTIVE The objective of this study was to compare the safety profiles of the 4-mg nicotine lozenge and 4-mg nicotine gum in smokers with selected label-restricted diseases . METHODS This was a multicenter , r and omized , open-label study in adult smokers with heart disease , hypertension not controlled by medication , and /or diabetes mellitus . Patients were r and omized in a 1:1 ratio to receive the 4-mg nicotine lozenge or 4-mg nicotine gum . Safety assessment s were made at baseline and at 2 , 4 , 6 , and 12 weeks after the start of product use . RESULTS Nine hundred one patients were r and omized to treatment , 447 who received the lozenge and 454 who received the gum ( safety population ) . The majority were women ( 52.7 % ) . Patients ' mean age was 53.9 years , their mean weight was 193.9 pounds , and they smoked a mean of 25.2 cigarettes per day at baseline . Five hundred fifty-three patients , 264 taking the lozenge and 289 taking the gum , used the study product for > or = 4 days per week during the first 2 weeks ( evaluable population ) . The nicotine lozenge and nicotine gum were equally well tolerated , despite increased nicotine exposure from the lozenge . The incidence of adverse events in the 2 groups was similar during the first 2 weeks of product use ( evaluation population : 55.3 % lozenge , 54.7 % gum ) , as well as during the entire study ( safety population : 63.8 % and 58.6 % , respectively ) . Stratification of patients by sex , age , extent of concurrent smoking , extent of product use , and severity of adverse events revealed no clinical ly significant differences between the lozenge and gum . The most common adverse events were nausea ( 17.2 % and 16.1 % ; 95 % CI , -3.7 to 6.0 ) , hiccups ( 10.7 % and 6.6 % ; 95 % CI , 0.5 to 7.8 ) , and headache ( 8.7 % and 9.9 % ; 95 % Cl , -5.0 to 2.6 ) . Serious adverse events were reported in 11 and 13 patients in the respective groups . Fewer than 6 % of patients in either group were considered by the investigator to have a worsening of their overall disease condition during the study . The majority of patients ( > 60 % ) experienced no change in their disease status from baseline . CONCLUSION The 4-mg nicotine lozenge and 4-mg nicotine gum had comparable safety profiles in these patients with label-restricted medical conditions INTRODUCTION Nicotine gum , a proven effective aid to cessation , comes in two doses : 2-mg and 4-mg . Assignment to the higher dose has traditionally been based on daily cigarette consumption . This paper evaluates efficacy of the gum when the 4-mg dose is assigned based on time to first cigarette ( TTFC ) being ≤ 30 min . METHODS In a secondary analysis of a r and omized , double-blind , placebo-controlled trial that allocated smokers r and omly to placebo , 2-mg , or 4-mg gum ( Garvey , A. J. , Kinnunen , T. , Nordstrom , B. L. , Utman , C. H. , Doherty , K. , Rosner , B. , et al. ( 2000 ) . Effects of nicotine gum dose by level of nicotine dependence . Nicotine & Tobacco Research , 2 , 53 - 63 . doi:10.1080/14622200050011303 ) , we evaluated outcomes when 4-mg gum was given to subjects with TTFC ≤ 30 ( n = 158 , placebo n = 159 ) . RESULTS Active treatment doubled or tripled abstinence rates versus placebo . This also held among smokers with a history of treatment failure . The effect of 4-mg gum was significant among light smokers ( < 25 CPD ) with TTFC ≤ 30 ; 2-mg gum was not . CONCLUSION This analysis suggests that assigning dose of nicotine gum based on TTFC is an effective and appropriate means of dose allocation It is unclear whether reducing the number of cigarettes in smokers not trying to quit increases or decreases the likelihood of future quitting . In a pilot study , smokers not currently interested in quitting ( n=67 ) were r and omized to two groups . Experimental participants received behavioral treatment and nicotine replacement therapy ( choice of gum , patch , or inhaler ) to reduce smoking by 50 % over 4 weeks , followed by brief advice to quit . Usual-care participants received only brief advice to quit and nicotine replacement if they decided to quit . During the 4-week treatment period , nonabstaining reduction participants decreased from 23 to 14 cigarettes per day ( p<.01 ) and maintained their reduction over the 6-month follow-up period . At the 6-month follow-up , 35 % of usual-care and 41 % of reduction participants ( nonsignificant [ ns ] ) moved forward in their stage of change . Over the 6 months , 34 % of usual-care participants had at least one 24-h quit attempt , compared with 25 % of reduction participants ( ns ) . A total of 9 % of usual-care participants remained quit at 6 months vs. 13 % in the reduction group ( ns ) . These preliminary results suggest that adding a reduction option neither increases nor undermines interest in cessation . Higher than expected rates of attempted cessation and quitting in the usual-care group suggest that we recruited smokers whose motivation to quit was above average . Thus , a replication test in a less-motivated group of smokers is needed OBJECTIVE Nicotine patch improves treatment outcomes , but lapses are still common . To underst and the process of relapse on patch , we investigated differences in the antecedents ( withdrawal , setting , triggers ) of lapse episodes experienced on high-dose ( 35 mg ) nicotine patches versus placebo . DESIGN Participants were smokers who lapsed during a r and omized , double-blind trial of active patches ( n = 100 ) versus placebo ( n = 85 ) . Participants used electronic diaries to monitor their smoking , affect , and activities in real time for 5 weeks during their cessation attempt . RESULTS We analyzed 490 lapse episodes ( active : 266 ; placebo : 224 ) . Lapses on nicotine patch were characterized by significantly lower positive affect and higher negative affect than placebo lapses . Participants treated with high-dose patch were also significantly more likely to lapse in situations involving little or no craving . Situational antecedents of lapses on patch resembled those on placebo . CONCLUSION The results suggest that treatment with patch may set a higher threshold for affective stimuli to provoke lapses , but does not change the proximal cues that trigger lapses . This suggests that behavioral relapse-prevention strategies developed for unmedicated smokers should also apply to those treated with nicotine patch This study assessed the relationship between treatment outcome and perceived drug assignment in smokers ( nicotine patch [ NP ] or placebo ) using abstinence and relapse status . Smokers ( N = 424 ) were r and omly assigned to receive either NP or placebo as part of a study that examined the effects of combining NP with self-help programs . Beliefs about drug assignment , assessed at the 12-month follow-up , were obtained from 384 participants . Beliefs were related to abstinence at the 2-month , p < .05 , and 6-month follow-ups , p < .05 , for the NP group , but not the placebo . Beliefs were not related to abstinence at 12 months for either group . Survival analysis assessing relapse revealed that beliefs were related to relapse status , regardless of actual group assignment . Our results suggest that there is a relationship between perceived drug assignment and treatment outcome . Future studies using multiple treatment outcome measures and assessment s of beliefs over time are warranted OBJECTIVE : To assess the effect of the various nicotine replacement therapies ( NRT ) on smoking reduction . DESIGN : During an initial sampling week , the subjects familiarised themselves with nicotine gum , patch , nasal spray , vaporiser ( vapour inhaler ) and sublingual tablet . A crossover design was used during the next four study weeks ; during two of these weeks the subjects could select one nicotine replacement product of their choice to use , whereas during the other two they were r and omly assigned a product to use . SUBJECTS : 143 men and women smoking an average of 22.6 ( SD 7.0 ) cigarettes per day and exhibiting a Fagerström Tolerance Question naire ( FTQ ) score of 7.0 ( SD 1.9 ) . INTERVENTIONS : Subjects were asked to use as much NRT as they wished , yet to smoke enough to feel comfortable . MAIN OUTCOME MEASURES : Self-reported cigarette consumption , exhaled carbon monoxide ( CO ) , withdrawal symptom score , cotinine plasma levels and motivation to quit were monitored over a period of five weeks . RESULTS : Self-reported smoking declined steadily over the five weeks , from 22.6 ( SD 7.0 ) to 10.4 ( SD 1.0 ) ( P<0.001 ) cigarettes daily ( 54 % decrease ) , with the biggest drop ( 37 % ) during the first product-sampling week . Smoking reduction was greater on average during the weeks when the subjects could choose their nicotine product than when products were assigned . CO readings decreased from 22.7 ( SD 8.5 ) to 14.8 ( SD 8.4 ) ppm ( P<0.001 ) confirming a reduction in smoking ( 35 % decrease ) , although cotinine levels remained steady , suggesting that subjects were titrating nicotine to their original levels . Withdrawal scores decreased over time ( 32 % decrease , P<0.001 ) , showing that there was no discomfort associated with the smoking reduction , and motivation to quit was enhanced by the treatment in most subjects ( 93 % ) . CONCLUSIONS : NRT for aiding smoking reduction appeared to be safe , was associated with a clinical ly significant reduction in smoke exposure over a five-week follow up , and increased motivation to stop smoking . A smoking reduction procedure may help the very recalcitrant smoker gain confidence and increase the control over his/her smoking behaviour . More controlled research is needed to follow up these promising results The transdermal nicotine patch has proved an effective aid to smoking cessation . The ease of securing good compliance gives it a potential advantage over nicotine gum as an adjunct to brief advice and support in primary care setting s where the major public health impact is obtained . In a preliminary report of half the sample of a r and omized placebo controlled trial , we showed the patch to be effective in a general practice setting . We report here the definitive results of the full sample , including dose effects , predictors of outcome and other issues of theoretical and practical interest . A total of 1200 heavy smokers ( > or = 15 per day ) , attending 30 general practice s in 15 English counties received brief GP advice , a booklet and 16 hours per day patch treatment for 18 weeks . Dose increase and abrupt vs. gradual reduction of patch dosage were also r and omized and follow-ups conducted at 1 , 3 , 6 , 12 , 26 and 52 weeks . Outcome was measured by self-reported complete abstinence from week 3 to 52 with biochemical validation at all follow-up points . Nicotine patch treatment doubled the rate of continuous abstinence up to 1 year ( nicotine 9.6 % , placebo 4.8 % , p < 0.01 ) ; it most likely worked by reducing withdrawal symptoms . It enhanced cessation during the first week and reduced relapse during the second week . The dose increase after week 1 produced no sustained increase in cessation . Gradual reduction was no better at preventing relapse than abrupt withdrawal of patches after week 12 . Whether relapse would have increased by ending treatment at some point between weeks 3 and 12 was not tested . Although pre-treatment dependence on cigarettes was prognostic of failure , the patches were equally helpful to both highly and less dependent smokers . Patches were particularly helpful to smokers with pre-treatment sub clinical dysthymic symptoms . All but one of the 96 subjects eventually achieving long-term abstinence in the study quit during the first week of cessation Medical patients ( n = 315 ) who wished to quit smoking were r and omly assigned in a double-blind manner to receive either nicotine or placebo gum . Subjects were advised to stop gum use by 4 months . Among abstinent smokers , 46 % of those receiving nicotine gum and 17 % of those receiving placebo gum used the gum beyond the recommended 4-month period . By 10 months after cessation 17 % of quitters receiving nicotine gum and 6 % receiving placebo gum were still using gum . Gradual reduction of nicotine gum did not result in withdrawal and cessation of nicotine gum did not increase the probability of relapse to smoking or weight gain . We conclude that use of nicotine gum is due , in part , to the effects of nicotine ; however , long-term use is uncommon STUDY OBJECTIVE To increase the effect that primary care physicians have on their patients who smoke . DESIGN R and omized , controlled trial with 112 general internists and their patients who smoke . PATIENTS Sample of 1420 patients from a general medicine clinic of a city-county teaching hospital , who smoke at least one cigarette a day and were recruited regardless of their interest in quitting smoking . INTERVENTIONS Physicians were r and omly assigned to one of four groups : participants who received a protocol for smoking management and a lecture on the consequences and management of smoking ( control ) ; in addition , had nicotine gum freely available to patients ( gum ) ; had stickers attached to their smokers ' charts ( reminder ) ; or had both gum and reminders ( both ) . MEASUREMENTS AND MAIN RESULTS The percentage of patients with a return visit at 6 months who quit smoking ( alveolar carbon monoxide of less than nine parts per million ) was 1.3 % ( control ) , 7.7 % ( gum ) , 7.0 % ( reminders ) , and 6.3 % ( both ) . At 1 year the percentages were 2.7 % , 8.8 % , 15.0 % , and 9.6 % , respectively . Subsequent pairwise comparisons showed that the three intervention groups were not significantly different , but that each was significantly different from the control group ( P less than 0.05 ) . Physicians in all three intervention groups spent significantly more time than did the physicians in the control group counseling their patients about smoking . CONCLUSIONS The availability of nicotine gum or labeling the charts of smokers can help primary care physicians increase their success rates two- to six-fold in helping patients quit smoking . If all primary care physicians used these procedures , they could help an additional 2 million smokers quit CONTEXT Little direct evidence exists on the relative efficacies of different smoking cessation pharmacotherapies , yet such evidence is needed to make informed decisions about their clinical use . OBJECTIVE To assess the relative efficacies of 5 smoking cessation pharmacotherapy interventions using placebo-controlled , head-to-head comparisons . DESIGN A r and omized , double-blind , placebo-controlled clinical trial . SETTING Two urban research sites . PATIENTS One thous and five hundred four adults who smoked at least 10 cigarettes per day during the past 6 months and reported being motivated to quit smoking . Participants were excluded if they reported using any form of tobacco other than cigarettes ; current use of bupropion ; having a current psychosis or schizophrenia diagnosis ; or having medical contraindications for any of the study medications . INTERVENTIONS Participants were r and omized to 1 of 6 treatment conditions : nicotine lozenge , nicotine patch , sustained-release bupropion , nicotine patch plus nicotine lozenge , bupropion plus nicotine lozenge , or placebo . In addition , all participants received 6 individual counseling sessions . MAIN OUTCOME MEASURES Biochemically confirmed 7-day point-prevalence abstinence assessed at 1 week after the quit date ( postquit ) , end of treatment ( 8 weeks postquit ) , and 6 months postquit . Other outcomes were initial cessation , number of days to lapse , number of days to relapse , and latency to relapse after the first lapse . RESULTS All pharmacotherapies differed from placebo when examined without protection for multiple comparisons ( odds ratios , 1.63 - 2.34 ) . With such protection , only the nicotine patch plus nicotine lozenge ( odds ratio , 2.34 , P < .001 ) produced significantly higher abstinence rates at 6-month postquit than did placebo . CONCLUSION While the nicotine lozenge , bupropion , and bupropion plus lozenge produced effects that were comparable with those reported in previous research , the nicotine patch plus lozenge produced the greatest benefit relative to placebo for smoking cessation Hospital-based out patients participating in a cognitive-behavioural group programme ( 2 hours/week over 5 weeks ) were studied to evaluate the effectiveness of a 24-hour transdermal nicotine patch in assisting smokers to stop smoking when used as an adjunct to a cognitive-behavioural group programme , and to assess weight gain following cessation , using a r and omized , double-blind , placebo-controlled trial with 12 months ' follow-up . The main outcome measure was a comparison between point prevalence abstinence , continuous abstinence and 12-months sustained , biochemically vali date d abstinence . The vali date d abstinence rates at 12 months for point prevalence , sustained and continuous abstinence for subjects in the active and placebo groups were all statistically significant : 28 vs. 12 % ; 24 vs. 11 % ; and 19 vs. 9 % , respectively . Moderately dependent smokers using the nicotine patch were more successful than highly dependent smokers at 3 and 6 months ( p < 0.05 ) . Weight gain was greater among sustained abstainers at 12 months compared to continuing smokers ( p < 0.001 ) . When the active nicotine patch was used in combination with cognitive-behavioural therapy in an outpatient hospital clinic , 12-months sustained abstinence rates were more than double those of a placebo patch To investigate the effectiveness and tolerability of a transdermal nicotine system ( TNS ) as an aid towards easing smoking cessation , two double-blind placebo-controlled r and omized field studies were performed . The TNS was available in sizes of 10 , 20 and 30 cm2 , delivering 7 , 14 and 21 mg of nicotine per 24 h. A first study was undertaken in general medical practice by a group of 21 doctors ( Practitioner Study ) . This study involved 199 nicotine-dependent cigarette smokers of whom 100 were allocated to the nicotine group and 99 to the placebo group . The second trial was performed in 112 young people , 56 in each treatment group , at the Universities of Basle and Zurich ( University Study ) . The placebo and the nicotine groups were comparable in both studies . Participants smoking more than 20 cigarettes a day were treated with the 30-cm2 system and the others with the 20-cm2 system . When abstinence , as verified by CO measurements , was achieved , the next smaller system was applied . In the Practitioner Study , the double-blind treatment phase lasted for 12 weeks with consultations every month and in the University Study the consultations during the 9-weeks ' treatment period took place every 3 weeks . Abstainers in both studies will be followed up until 12 months after treatment was begun . After 1 , 2 and 3 months of treatment 41 % , 36 % and 36 % of the participants in the nicotine group of the Practitioner Study were abstinent . The corresponding figures in the placebo group were 19.4 % , 20.4 % and 22.5 % . The differences were statistically significant for all three months ( p = 0.001 ; p = 0.018 and p = 0.043 ) . Body weight did not increase in the TNS group , but did in the placebo group ( + 4.4 kg ) . The craving for cigarettes and withdrawal symptoms decreased more under nicotine substitution . Abstinence rates in the University Study were initially higher with 51.8 % in the nicotine group and 28.6 % in the placebo group after 3 weeks of treatment , but then declined to 42.9 % after 6 weeks and 39.3 % after 9 weeks in the nicotine group and to 25 % and 19.6 % , respectively , in the placebo group . The differences between the groups were statistically significant on all 3 occasions , with p = 0.012 , p = 0.046 and p = 0.023 . ( ABSTRACT TRUNCATED AT 250 WORDS Abstract Objectives : To determine whether use of an oral nicotine inhaler can result in long term reduction in smoking and whether concomitant use of nicotine replacement and smoking is safe . Design : Double blind , r and omised , placebo controlled trial . Four month trial with a two year follow up . Setting : Two university hospital pulmonary clinics in Switzerl and . Participants : 400 healthy volunteers , recruited through newspaper advertisements , willing to reduce their smoking but unable or unwilling to stop smoking immediately . Intervention : Active or placebo inhaler as needed for up to 18 months , with participants encouraged to limit their smoking as much as possible . Main outcome measures : Number of cigarettes smoked per day from week six to end point . Decrease verified by a measurement of exhaled carbon monoxide at each time point compared with measurement at baseline . Results : At four months sustained reduction of smoking was achieved in 52 ( 26 % ) participants in the active group and 18 ( 9 % ) in the placebo group ( P<0.001 ; Fisher 's test ) . Corresponding figures after two years were 19 ( 9.5 % ) and 6 ( 3.0 % ) ( P=0.012 ) . Conclusion : Nicotine inhalers effectively and safely achieved sustained reduction in smoking over 24 months . Reduction with or without nicotine substitution may be a feasible first step towards smoking cessation in people not able or not willing to stop abruptly BACKGROUND AND OBJECTIVE Tobacco and cannabis are frequently used in combination and cannabis co-use may lead to poor tobacco cessation outcomes . Therefore , it is important to explore if cannabis co-use is associated with a reduced likelihood of achieving successful tobacco abstinence among treatment-seeking tobacco smokers . The present study examined whether current cannabis use moderated tobacco cessation outcomes after 12 weeks of pharmacological treatment ( varenicline vs. nicotine patch vs. placebo ) with adjunctive behavioral counseling . METHODS Treatment-seeking tobacco smokers ( N = 1,246 ) were enrolled in an intent-to-treat study , of which 220 were current cannabis users . Individuals were r and omly assigned to 12 weeks of placebo ( placebo pill plus placebo patch ) , nicotine patch ( active patch plus placebo pill ) , or varenicline ( active pill plus placebo patch ) , plus behavioral counseling . The primary endpoint was biochemically verified 7-day point prevalence abstinence at the end of treatment . RESULTS Controlling for rate of nicotine metabolism , treatment arm , age , sex , alcohol , and level of nicotine dependence , cannabis users were as successful at achieving biochemically verified 7-day point prevalence abstinence compared to tobacco-only smokers . CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE Findings suggest that cannabis use does not hinder the ability to quit tobacco smoking . Future tobacco cessation studies should employ prospect i ve , longitudinal design s investigating cannabis co-use over time and at different severity levels . ( Am J Addict 2016;25:291 - 296 ) The authors examined weight gain in 79 abstinent cigarette smokers during treatment with placebo or with 2 mg or 4 mg of nicotine gum . Results indicated that nicotine gum suppressed weight gain in a linear fashion with increasing nicotine dose . At 90 days postcessation , placebo gum users gained 3.7 kg , 2-mg gum users gained 2.1 kg , and 4-mg gum users gained 1.7 kg . Assessment of nicotine replacement by means of pre- and postcessation salivary continue levels revealed that smokers who replaced a greater percentage of their baseline continue levels during treatment gained less weight . Percentage of baseline cotinine replaced remained related to weight gain after the number of pieces of gum used was controlled . Implication s for smokers hoping to minimize postcessation weight gain are discussed OBJECTIVE To evaluate the efficacy and safety of a transdermal nicotine patch as an aid for smoking cessation in an over-the-counter setting . DESIGN Multicenter , double-blind , r and omized , placebo-controlled trial of 6-week duration with 18 weeks of follow-up . SETTING Four shopping mall precincts . PARTICIPANTS The r and omized sample consisted of 802 adults ( mean age , 39 years ) and was 89 % white and 54 % female . A smoking history of at least 20 cigarettes per day for 1 year and a score of 5 ( on a 10-point scale ) on a motivational assessment question naire were required for enrollment . Post study follow-up was limited to those who had quit smoking at the end of 6 weeks . INTERVENTION Nicotine patches were provided at the shopping mall . Guidance consisted only of package instructions and a smoking cessation self-help booklet . MAIN OUTCOME MEASURES Quit rates were defined as total abstinence from smoking for 4 consecutive weeks ( treatment weeks 3 - 6 ) , point prevalence smoking status at week 6 , or nonsmoker at week 6 and week 24 ( 6-month postquit date ) . Smoking status was assessed by diaries , and verification for the first 2 quit rates was obtained by confirmation of carbon monoxide of 8 ppm or less in expired breath . Safety was evaluated by self-reported adverse events . RESULTS Quit rate was 12 % for the active treatment group and 5.5 % for the placebo group , based on total abstinence for 4 consecutive weeks ( P = .001 ) compared with quit rates of 19.5 % and 7.5 % for active treatment and placebo groups , respectively , based on point prevalence data at week 6 . At 24 weeks , 8.2 % of nonsmokers in the active treatment group and 4.0 % in the placebo group remained nonsmokers . At least 1 adverse event was reported by 57 % receiving the nicotine patch and 39 % receiving placebo ( P<.001 ) . CONCLUSIONS When the nicotine patch was used in an over-the-counter setting , quit rates were comparable to those reported for medical setting s. A 2:1 quit rate advantage was achieved at week 6 and was maintained at 24 weeks Two hundred and ten subjects entered a trial to test the use of a chewing gum containing nicotine as an aid to stopping smoking . They were divided into three groups : nicotine chewing gum , placebo chewing gum , and control . The trial was double blind between the two chewing gum groups . After 1 month the percentage of confirmed non-smokers in the nicotine gum group was 34 % , in placebo chewing gum group 37 % and the control group 24 % . By 6 months most of the non-smokers had relapsed , but the nicotine gum group ( 23 % ) was more successful than the placebo ( 5 % or the control group ( 14 % ) INTRODUCTION Smokeless tobacco ( ST ) use is associated with adverse health consequences , and effective treatments are needed . Pilot data suggest that 4-mg nicotine lozenge decreases tobacco craving and nicotine withdrawal symptoms among ST users . METHODS We conducted a r and omized , placebo-controlled multicenter clinical trial to evaluate the efficacy of 12 weeks of 4-mg nicotine lozenge for ST use . RESULTS We r and omized 270 participants ( 136 active lozenge , 134 placebo ) . No significant differences were observed between the groups in biochemically confirmed all tobacco abstinence rates at Week 12 ( 36 % lozenge vs. 27.6 % placebo ; odds ratio [ OR ] 1.5 , 95 % CI 0.7 - 2.1 ; p = .138 ) . However , the 4-mg nicotine lozenge increased self-reported all tobacco abstinence ( 44.1 % vs. 29.1 % ; OR 1.9 , 95 % CI 1.2 - 3.2 ; p = .011 ) and self-reported ST abstinence ( 50.7 % vs. 34.3 % ; OR 2.0 , 95 % CI 1.2 - 3.2 ; p = .013 ) compared with placebo at the end of treatment ( Week 12 ) . Following target quit date ( TQD ) , nicotine withdrawal symptoms decreased significantly with time ( time effect = -.022 per day , SE = .003 ; p < .001 ) and was significantly lower for the active lozenge ( treatment effect = -.213 , SE = .071 ; p = .003 ) . Tobacco craving also decreased significantly following TQD ( time effect = -.071 , SE = .006 ; p < .001 ) and was lower for the active nicotine lozenge ( treatment effect = -.452 , SE = .164 ; p = .006 ) . DISCUSSION The 4-mg nicotine lozenge increased self-reported but not biochemically confirmed tobacco abstinence rates at 3 months . The use of the 4-mg nicotine lozenge is associated with decreased nicotine withdrawal symptoms and tobacco craving BACKGROUND Tobacco dependence is a chronic , relapsing condition that may require extended treatment . OBJECTIVE To assess whether extended- duration transdermal nicotine therapy increases abstinence from tobacco more than st and ard- duration therapy in adult smokers . DESIGN Parallel r and omized , placebo-controlled trial from September 2004 to February 2008 . Participants and all research personnel except the data base manager were blinded to r and omization . ( Clinical Trials.gov registration number : NCT00364156 ) SETTING Academic center . PARTICIPANTS 568 adult smokers . INTERVENTION In an unstratified small block-r and omization scheme , participants were r and omly assigned to st and ard therapy ( Nicoderm CQ [ GlaxoSmithKline , Research Triangle Park , North Carolina ] , 21 mg , for 8 weeks and placebo for 16 weeks ) or extended therapy ( Nicoderm CQ , 21 mg , for 24 weeks ) . MEASUREMENTS The primary outcome was biochemically confirmed point-prevalence abstinence at weeks 24 and 52 . Secondary outcomes were continuous and prolonged abstinence , lapse and recovery events , cost per additional quitter , and side effects and adherence . RESULTS At week 24 , extended therapy produced higher rates of point-prevalence abstinence ( 31.6 % vs. 20.3 % ; odds ratio , 1.81 [ 95 % CI , 1.23 to 2.66 ] ; P = 0.002 ) , prolonged abstinence ( 41.5 % vs. 26.9 % ; odds ratio , 1.97 [ CI , 1.38 to 2.82 ] ; P = 0.001 ) , and continuous abstinence ( 19.2 % vs. 12.6 % ; odds ratio , 1.64 [ CI , 1.04 to 2.60 ] ; P = 0.032 ) versus st and ard therapy . Extended therapy reduced the risk for lapse ( hazard ratio , 0.77 [ CI , 0.63 to 0.95 ] ; P = 0.013 ) and increased the chances of recovery from lapses ( hazard ratio , 1.47 [ CI , 1.17 to 1.84 ] ; P = 0.001 ) . Time to relapse was slower with extended versus st and ard therapy ( hazard ratio , 0.50 [ CI , 0.35 to 0.73 ] ; P < 0.001 ) . At week 52 , extended therapy produced higher quit rates for prolonged abstinence only ( P = 0.027 ) . No differences in side effects and adverse events between groups were found at the extended-treatment assessment . LIMITATION The generalizability of the findings may be limited because participants were smokers without medical comorbid conditions who were seeking treatment , and differences in adherence across treatment groups were detected . CONCLUSION Transdermal nicotine for 24 weeks increased biochemically confirmed point-prevalence abstinence and continuous abstinence at week 24 , reduced the risk for smoking lapses , and increased the likelihood of recovery to abstinence after a lapse compared with 8 weeks of transdermal nicotine therapy . PRIMARY FUNDING SOURCE National Institutes of Health BACKGROUND Smokers with a history of alcohol dependence may have more difficulty quitting , might relapse to alcohol use , and might especially benefit from nicotine replacement therapy for smoking cessation . METHODS One hundred fifteen smokers with a history of alcohol dependence ( median of 5 years previously ) were r and omly assigned to either a 21-mg nicotine patch or placebo in a trial design ed to be as similar as possible to a prior study that examined smokers with no history of alcoholism . Both studies were of heavy smokers with similar levels of nicotine dependence ; thus , any differences in trials would be due to a history of alcohol problems per se . RESULTS In the current trial , adjusted prolonged smoking abstinence in those with a history of alcohol dependence was higher in the active than the placebo group at end-of-treatment ( 28 % vs. 11 % ; odds ratio , 3.2 ; p = 0.04 ) and at 6-month follow-up ( 24 % vs. 6 % ; odds ratio , 4.9 ; p = 0.02 ) . Among subjects not lost to follow-up , none reported drinking problems or increases in craving for alcohol . Smoking abstinence was not lower and the odds ratio for nicotine patch therapy was not greater in smokers with a history of alcohol dependence than in smokers with no such history . CONCLUSIONS Heavy smokers with a history of alcoholism benefit from nicotine patch treatment . A history of alcohol problems after a period of stable sobriety does not appear to influence smoking outcomes or response to nicotine replacement . Although no smokers relapsed to alcohol use , a trial that follows up all subjects is needed to verify this INTRODUCTION This secondary analysis examined the association between adherence to nicotine replacement therapy ( NRT ) and smoking cessation among pregnant smokers enrolled in Baby Steps , an open-label r and omized controlled trial testing cognitive-behavioral therapy ( CBT ) versus CBT plus NRT . METHOD The analysis included only women who received NRT for whom we had complete data ( N = 104 ) . Data came from daily calendars created from recordings of counseling sessions and from telephone surveys at baseline and 38 weeks gestation . RESULTS Overall , 29 % of the 104 women used NRT for the recommended 6 weeks and 41 % used NRT as directed in the first 48 hr after a quit attempt . Ordinal logistic regression modeling indicated that using NRT as directed in the first 48 hr and having made a previous quit attempt were the strongest predictors of longer NRT use . Univariate analyses suggested that primigravid women and women who used NRT longer were more likely to report quitting at 38 weeks gestation . DISCUSSION Findings indicated that adherence to NRT is low among pregnant smokers , but adherence was a predictor of cessation . Future trials should emphasize adherence , particularly more days on NRT , to promote cessation during pregnancy INTRODUCTION To determine the smoking reduction patterns of light smokers ( ≤ 10 CPD ) and whether reduction predicts future cessation . METHODS Study is a secondary analysis of data that were derived from a 2 × 2 r and omized study that assessed the efficacy of nicotine gum ( vs. placebo ) and counseling ( motivational interviewing vs. health education ) for smoking cessation among 755 light smokers . Participants were categorized into three groups based on self-reported CPD smoked at time of study enrollment compared with CPD smoked a year prior to enrollment . That is , ( a ) those who reduced number of cigarettes per day ( CPD ) , ( b ) those who smoked the same number of CPD , and ( c ) those who increased their number of CPD . Sociodemographic and smoking characteristics were assessed at enrollment as well as cotinine-verified 7-day smoking abstinence rates at the Week 26 follow-up assessment . A stepwise logistic regression model to predict the probability abstinence at 26-week follow-up was also performed . RESULTS Compared with a year prior to enrollment , 43.7 % of participants reduced , 35.2 % smoked the same , and 21.2 % increased their CPD . Compared with those who smoked the same or increased their CPD , those who had reduced their CPD were older , more likely to be males , smoked fewer CPD at enrollment , initiated smoking at a younger age , and less likely to be nicotine dependent . Adjusted logistic regression showed that those who had reduced their smoking prior to enrollment were more likely to quit at Week 26 ( odds ratio [ OR ] = 1.77 ; 95 % CI = 1.062 - 2.957 ; p = .029 ) . DISCUSSION Findings suggest that reducing number of CPD smoked prior to enrolling in a clinical trial is a positive predictor of abstinence . Therefore , encouraging smoking reduction prior to attempting cessation may enhance cessation outcomes for light smokers Tests of addiction treatments seldom reveal where treatment exercises its effect ( i.e. , promoting initial abstinence , preventing lapses , and /or impeding progression from lapse to relapse ) . The authors illustrate analyses distinguishing effects on these milestones in a r and omized trial of high-dose nicotine patch ( 35 mg ; n = 188 ) versus placebo ( n = 136 ) in adult smokers , who used electronic diaries to monitor smoking in real time during 5 weeks of treatment . High-dose patch promoted initial abstinence ( hazard ratio [ HR ] = 1.3 ) and decreased the risk of lapsing among those who achieved abstinence ( HR = 1.6 ) . The biggest effect of treatment was to prevent progression to relapse among those who had lapsed ( HR = 7.1 ) . Analysis of effects by milestones may enhance underst and ing of cessation treatments and their mechanisms of action INTRODUCTION In order to replicate the rewarding effects of smoking , nicotine replacement therapies must deliver nicotine via the pulmonary route . We aim ed to measure the efficacy of a simple pressurized metered dose inhaler containing nicotine combined with a nicotine patch for smoking cessation . METHODS Double-blind r and omized placebo-controlled , parallel group trial conducted at the University of Otago , Wellington , New Zeal and . Five-hundred two adults ( ≥18 years ) who smoked at least nine cigarettes per day , with a Fagerström Test for Nicotine Dependence ≥3 who wanted to quit , were r and omized ( 1:1 ) . INTERVENTIONS active nicotine pressurized metered dose inhaler ( pMDI ) plus active nicotine patch , versus placebo pMDI plus active nicotine patch . Subjects were instructed to use the aerosols for 6 months when they felt an urge to smoke and the patches daily for 5 months , reduce their smoking and quit by the end of the fourth week . Subjects were followed for 7 months . The primary outcome was prolonged 6 month not smoked on 7 consecutive days , analyzed by intention-to-treat . RESULTS For the primary outcome , 78/246 ( 31.71 % ) in the active group versus 46/256 ( 17.97 % ) in the control group were abstinent ( odds ratio 2.12 , 95 % confidence interval 1.40 to 3.23 ) . Adverse events were reported by 245/246 ( 99.6 % ) and 247/256 ( 96.5 % ) subjects in the active and control groups , respectively . Mild coughing which decreased with regular use was common with the nicotine aerosols . CONCLUSION Inhaled nicotine from a metered dose inhaler combined with a nicotine patch substantially improves abstinence for 6 months amongst adult nicotine dependant smokers wanting to quit . IMPLICATION S In 2012 , we published a systematic review of the use nicotine by inhalation in this journal . At that time we were unable to find any studies that had measured the effects of nicotine delivery by pMDI on smoking cessation , and we are not aware of any since 2012 . Our study is the first to look at nicotine by pMDI in smoking cessation . The present trial demonstrates that a simple nonproprietary nicotine inhaler , using relatively inexpensive st and ard technology , increases smoking cessation rates over and above nicotine patch therapy , and could usefully enhance nicotine replacement in smoking cessation treatment Background : Various formulations of nicotine replacement therapy are commercially available . Objectives : It was the aim of this study to test preference , safety and efficacy of a new nicotine mouth spray ( 1 mg/actuation ; NicoNovum ) . Methods : One hundred healthy smokers wanting to quit ( mean age 43.1 ± 11.2 years ) were included . They were given the mouth spray , as well as 2-mg nicotine gums and nicotine oral inhalers to try out for 1 week . Subsequently , all participants were r and omized into 3 groups – mouth spray ( n = 50 ) , gum ( n = 25 ) and inhaler ( n = 25 ) – and treated for 3 months . Results : Fifty-four of the hundred smokers preferred the spray , compared with 28 and 18 who preferred the gum and inhaler , respectively ( p < 0.01 for spray vs. both the gum and inhaler ) . At 6 months , the sustained abstinence rates were 8 ( 16 % ) , 5 ( 20 % ) and 2 ( 8 % ) for the mouth spray , gum and inhaler , respectively ( p values = n.s . ) . Adverse effects ( AEs ) were mostly drug-related local symptoms , most frequently reported at the end of the tryout period : out of 106 drug-related AEs , 90 were due to the spray , 11 and 5 to the inhaler and gum , respectively . The three most frequent AEs were almost exclusively caused by the spray : burning of the tongue/throat reported by 35 , nausea by 18 , and hiccup by 16 participants . Conclusions : Participants preferred the mouth spray over the gum and inhaler , but its use was coupled with a high rate of local AEs . The efficacy of the mouth spray seemed comparable with the one obtained by the gum and inhaler . Further studies are necessary to show whether a reduction in the dose per actuation to about 0.5 mg would result in less side effects , which in turn might yield higher long-term drug compliance and possibly higher success rates than the ones achieved with other forms of nicotine replacement therapy The purpose of this study was to determine the effectiveness of nicotine-patch therapy for smoking cessation in patients with schizophrenia . This was a longitudinal study and sixty-eight schizophrenic patients were assigned to 8 weeks of a nicotine-patch therapy program or a control group . The generalized estimating equation analysis revealed that there were significant reductions in the subjects ' nicotine dependence ( Fagerstrom Tolerance Question naire ) , the number of cigarettes per day , and CO levels over an 8-week period of nicotine-patch therapy and 3-month follow-up . The point-prevalence rates of abstinence from smoking were an abstinence of 26.9 % at 8 weeks and 26.9 % at a 3-month follow-up . At the 3-month follow-up , the rate of continuous smoking abstinence in the nicotine-patch group was 23.1 % This article describes a multidimensional , multivariate , and multilevel approach to the assessment of nicotine withdrawal . In this prospect i ve study , 70 adult smokers assigned to an active or placebo nicotine patch condition completed multiple daily assessment s using an electronic diary . Average and individual growth curves were estimated for affective and nonaffective withdrawal symptoms . All symptoms but hunger increased significantly on the quit day and remained elevated for three weeks . Variability in symptom experiences across individuals increased from pre- to post-quit . Relations between symptom reports ( e.g. , negative affect or craving ) and episodic events ( e.g. , stressful events or seeing someone smoke ) changed from pre-quit to post-quit . Pre-quit increases in negative affect and quit-day increases in craving were inversely related to abstinence three months after the quit day , suggesting that anticipatory and immediate reactions to quitting influence success An analysis of smokers admitted with acute coronary syndrome who received transdermal nicotine therapy and those who did not was performed . Propensity analysis was used to match patients . Transdermal nicotine therapy appears safe and does not have an effect on the mortality of patients with acute coronary syndromes factor and terminal transverse defect . It would be necessary to test this finding in a study with the measurement of cigarette related markers , such as maternal serum or urine cotinine concentrations . The low relative risk ( about 1 5 ) for such a common exposure as smoking has important public health implication s for congenital limb deficiency in the population ( the attributable risk is about 14 % ) . This risk is obviously more important than the association of congenital limb deficiency with chorionic villus sampling.2"28 The confirmed teratogenic effect of maternal smoking may be a further strong indication for public health interventions aim ed at preventing smoking during pregnancy OBJECTIVE To compare the combination of a nicotine inhaler and bupropion to either treatment alone for initiating smoking abstinence and relapse prevention . METHODS Smokers were r and omized to receive a nicotine inhaler , bupropion , or both for 3 months . At 3 months , smoking-abstinent study participants were r and omized to their initial medications or placebo . Participants who were smoking at 3 months were r and omized to an alternative treatment regimen or placebo . This study was conducted from July 2001 to January 2003 . RESULTS A total of 1700 smokers were r and omized to treatment ( phase 1 ) for 3 months . Among the 941 study participants eligible for r and omization to the phase 2 trial , 837 continued in the study . For the phase 2 trial , 405 smoking-abstinent participants were r and omized to relapse prevention for 9 additional months , and 432 smokers were r and omized to re-treatment for an additional 3 months . At the end of the initial 3 months of treatment ( phase 1 ) , 82 ( 14 % ) of 566 , 145 ( 26 % ) of 567 , and 194 ( 34 % ) of 567 study participants receiving a nicotine inhaler , bupropion , or both , respectively , were abstinent from smoking . Of the 405 smoking-abstinent participants at the end of 3 months , the bupropion group had more smokers than the placebo group ( mean No. of smokers , 1.5 vs 1.1 ; P < .001 ) , and the nicotine inhaler group had higher smoking abstinence rates at 12 months than the placebo group . Those receiving combination therapy had reduced rates of relapse to smoking for the first 3 months of relapse prevention , but this difference disappeared after the initial 3 months . Of the 432 study participants who were smoking at the end of 3 months and who received an alternative treatment regimen , the 223 smokers initially assigned to a nicotine inhaler were more likely to stop smoking at 6 months if they were re-treated with bupropion instead of placebo ( 8 [ 7 % ] of 111 vs 0 [ 0 % ] of 112 ; P = .003 ) , and the 209 smokers initially treated with bupropion and re-treated with a nicotine inhaler did not have significantly higher smoking abstinence rates ( 6 [ 6 % ] of 104 vs 3 [ 3 % ] of 105 ; P = -.50 ) . CONCLUSION Combined therapy with a nicotine inhaler and bupropion increased smoking abstinence rates . Continuation of the initial combination therapy does not appear to prevent relapse to smoking . Timing of re-treatment and alternative approaches to relapse prevention should be further examined AIM To test the effect of nicotine gum and placebo in smokers not motivated or not able to quit smoking with regard to smoking reduction and smoking cessation . DESIGN This r and omized study evaluated nicotine gum versus placebo for up to 1 year in 411 healthy smokers highly motivated to reduce cigarette use . Smoking reduction was defined as self-reported daily smoking less than 50 % of baseline and any decrease ( 1 p.p.m . or more ) in carbon monoxide . SETTING Pulmonary department , Copenhagen , Denmark . FINDINGS The overall success rate for sustained smoking reduction was significantly higher at all time-points for active versus placebo gum ( 6.3 % versus 0.5 % after 24 months ) . Nicotine gum achieved significantly higher point prevalence cessation rates than placebo at 12 and 24 months [ 11.2 % versus 3.9 % ( odds ratio = 3.1 ; 95 % CI , 1.4 - 7.2 and 9.3 % versus 3.4 % ( odds ratio = 2.9 ; 95 % CI , 1.2 - 7.1 ) , respectively ] . There was a linear relationship between decrease in number of daily cigarettes and decrease in plasma cotinine , exhaled carbon monoxide and plasma thiocyanate , with significantly greater reduction in the nicotine gum group after 4 and 12 months ( maximum treatment duration ) but not after 24 months . The decrease in toxin intake was smaller than the decline in daily cigarette consumption , suggesting that compensatory smoking occurred . CONCLUSIONS Nicotine gum promoted cessation in this population of smokers unwilling to quit . Among reducers , the toxin intake correlated with reduced cigarette consumption although some compensatory smoking occurred Sensorimotor smoking stimuli are important determinants of cigarette use . The present study aim ed to determine whether denicotinized cigarettes lose their reinforcing and /or subjective effects over a 9-day outpatient period when they are smoked with or without concurrent transdermal nicotine . After a preferred br and baseline , 68 participants were r and omized into one of four conditions based on the dose ( mg ) of transdermal nicotine and the type of cigarettes ( dose/cigarette ) : 0/nicotine , 0/denicotinized , 7/denicotinized , and 21/denicotinized . Under placebo patch conditions , participants smoked a similar number of nicotine and denicotinized cigarettes and no group differences emerged over repeated testing . The total volume of smoke inhaled was lower in the denicotinized group , although this decrease dissipated over time . Denicotinized cigarettes were rated as having low positive and high negative subjective effects . Compared to placebo , transdermal nicotine decreased the number of denicotinized cigarette smoked , produced a lasting decrease in the total volume of denicotinized cigarette smoke inhaled , but had little effect on the subjective effects of denicotinized cigarettes . Transdermal nicotine attenuated withdrawal during initial smoking abstinence ; however , once participants were allowed to smoke withdrawal symptoms were relatively low regardless of patch condition . The persistent use of denicotinized cigarettes may result from the presence of nicotine withdrawal and /or the degree to which smoking becomes somewhat independent of the outcome of the behavior ( i.e. , habit learning ) . Additional studies would be useful to determine what factors drive continued use of denicotinized cigarettes , whether their use subsides as withdrawal dissipates , and whether they address motives for smoking distinct from current pharmacotherapy In a double-blind trial , 48 smokers completed a nicotine tolerance question naire and then received nicotine gum or placebo during smoking cessation . Subjects given active gum were more likely to remain abstinent if their question naire responses indicated high nicotine dependence BACKGROUND The efficacy of pharmacotherapy for smoking cessation is well documented . However , due to relapse rates and side effects , hypnotherapy is gaining attention as an alternative treatment option . The aim of this one-center r and omized study was to compare the efficacy of hypnotherapy alone , as well as hypnotherapy with nicotine replacement therapy ( NRT ) , to conventional NRT in patients hospitalized with a cardiac or pulmonary illness . METHODS We evaluated self-reported and biochemically verified 7-day prevalence smoking abstinence rates at 12 and 26 weeks post-hospitalization . Patients ( n=164 ) were r and omized into one of three counseling-based treatment groups : NRT for 30 days ( NRT ; n=41 ) , a 90-min hypnotherapy session ( H ; n=39 ) , and NRT with hypnotherapy ( HNRT ; n=37 ) . Treatment groups were compared to a " self-quit " group of 35 patients who refused intervention . RESULTS Hypnotherapy patients were more likely than NRT patients to be nonsmokers at 12 weeks ( 43.9 % vs. 28.2 % ; p=0.14 ) and 26 weeks after hospitalization ( 36.6 % vs. 18.0 % ; p=0.06 ) . Smoking abstinence rates in the HNRT group were similar to the H group . There was no difference in smoking abstinence rates at 26 weeks between " self quit " and participants in any of the treatment groups . In multivariable regression analysis adjusting for diagnosis and demographic characteristics , H and HNRT were over three times more likely than NRT participants to abstain at 26-weeks post-discharge ( RR=3.6 ; p=0.03 and RR=3.2 ; p=0.04 , respectively ) . CONCLUSION Hypnotherapy is more effective than NRT in improving smoking abstinence in patients hospitalized for a smoking-related illness , and could be an asset to post-discharge smoking cessation programs Fifty private practitioners and their office staff members were r and omly assigned to one of four groups : participants received a protocol for smoking management and a lecture on the consequences and management of smoking , or in addition , had nicotine gum freely available to patients , had stickers attached to their charts , or had gum and reminders . The percentage of patients in each group who had quit smoking a year later was 7.7 , 16.3 , 8.6 , and 16.9 , respectively , indicating a significant main effect for the gum conditions . The availability of nicotine gum also significantly increased the amount of time that patients reported they received smoking cessation counseling from the dentists and office staff To assess efficacy and tolerance of a transdermal nicotine system ( TNS ) as adjuvant to tobacco withdrawal , 112 young , nicotine-dependent cigarette smokers were treated for nine weeks with TNS ( n = 56 ) or placebo ( n = 56 ) . Initial doses of nicotine ( 21 or 14 mg/24 h ) were based on previous smoking habits and stepwise reduced to 7 mg/24 h if abstinence was achieved during medication . After treatment , 39.3 % of the TNS users were abstinent versus 19.6 % on placebo ( p less than 0.05 ) . The craving for cigarettes diminished steadily , but not more significantly on TNS medication . Tenseness , difficulty in concentration and feelings of hunger were consistently and in part significantly lessened in the TNS group . The other withdrawal symptoms were not influenced by TNS treatment . Nine-month follow-up cotinine-verified abstinence rates were 12.5 % in the TNS and 3.6 % in the placebo group ( n. s. ) . Transient mild or moderate erythema at the application site appeared in 20 % of the TNS and 6.3 % of the placebo group , and 7.1 % of the TNS users dropped out because of severe localized erythema . Other mild , transient , systemic side effects reported by 33.9 % of the TNS and 26.8 % of the placebo users ( n. s. ) did not lead to drop-outs INTRODUCTION Pharmacists are uniquely positioned within the community to provide smoking cessation counseling to their patients . However , pharmacists experience significant barriers to providing counseling , including limited time , reimbursement , and training in counseling techniques . We tested a computer-driven software system , " Exper_Quit " ( EQ ) , that provided individually tailored interventions to patients who smoke and matching tailored reports for pharmacists to help guide cessation counseling . METHODS A two-phase design was used to recruit an observation-only group ( OBS ; n = 100 ) , followed by participants ( n = 200 ) r and omly assigned to receive either EQ-assisted pharmacist counseling or EQ plus 8 weeks of nicotine transdermal patch ( EQ+ ) . Both treatment groups were scheduled to receive two follow-up counseling calls from pharmacists . RESULTS Most participants in the EQ and EQ+ groups reported receiving counseling from a pharmacist , including follow-up calls , while none of the OBS participants reported speaking with the pharmacist about cessation . At 6 months , fewer OBS participants reported a quit attempt ( 42 % ) compared with EQ ( 76 % ) or EQ+ ( 65 % ) participants ( p < .02 ) . At 6 months , 7-day point-prevalence abstinence was 28 % and 15 % among the EQ+ and EQ groups , respectively , compared with 8 % among OBS participants ( p < .01 ) , and EQ+ participants were twice as likely to be quit than were EQ participants ( p < .01 ) . DISCUSSION A tailored software system can facilitate the delivery of smoking cessation counseling to pharmacy patients . Results suggest that EQ was successful in increasing ( a ) the delivery of cessation counseling , ( b ) quit attempts , and ( c ) quit rates . Pharmacists can play an important role in the effective delivery of smoking cessation counseling This study aim ed to assess the efficacy of the nicotine patch for smoking cessation , under simulated conditions of over-the-counter sale , absent any direct instruction or behavioral treatment . In a r and omized , double-blind , placebo-controlled , multicenter study , 567 smokers were r and omized to an active nicotine patch ( n = 283 ) or placebo ( n = 284 ) . Treatment followed a three-step program of 21 mg/day for 6 weeks , 14 mg/day for 2 weeks and 7 mg/day for 2 weeks . Participants received brief written instructions , an audiotape and a written User 's Guide . There was no other intervention and no contact with participants between enrollment and the primary outcome assessment at 6 weeks . Analyses were based on intent to treat , with lost subjects counted as failures , and cl aim ed abstinence was verified by carbon monoxide measures . Use of active patch produced significantly higher abstinence rates . Continuous abstinence rates ( subject to a 2-week grace period ) for nicotine and placebo were 19.4 % and 7.0 % at 6 weeks ( OR = 3.2 ; 95 % CI 1.8 - 5.4 ) and 15.2 % and 5.3 % at 10 weeks ( OR = 3.2 ; 95 % CI 1.7 - 5.9 ) , respectively . Seven-day point-prevalence rates for nicotine and placebo patches were 26.1 % and 7.7 % at 6 weeks ( OR = 4.2 ; 95 % CI 2.5 - 7.0 ) and 23.3 % and 7.7 % at 10 weeks ( OR = 3.6 ; 95 % CI 2.2 - 6.1 ) , respectively . Reported adverse events were mild and consistent with prior observations of nicotine patch use . The nicotine patch was safe and effective for smoking cessation at least during 10 weeks of treatment under open-sale conditions , without face-to-face instruction or counseling OBJECTIVE To examine previous use of nicotine replacement therapy ( NRT ) on the smoking-cessation efficacy of bupropion sustained release ( SR ) . METHODS Secondary analysis of a parallel-group , r and omized , double-blind , placebo-controlled study . Smokers who had , based on self-report , no previous history of NRT ( N = 453 ) or who had used NRT at least once ( N = 440 ) were r and omized to receive placebo , bupropion SR , nicotine transdermal system ( NTS ) , or a combination of bupropion SR and NTS . RESULTS Bupropion SR showed similar efficacy in participants with or without previous use of NRT . CONCLUSION Bupropion SR is effective in promoting smoking abstinence regardless of prior NRT use ABSTRACT Little is known about the relative , additive , and interactive effects of different population -based treatments for smoking cessation . The goal of this study was to evaluate the main and interactive effects of five different smoking interventions . Using the multiphase optimization strategy ( MOST ) , 1,034 smokers who entered a Web site for smokers ( smokefree.gov ) were r and omly assigned to the “ on ” and “ off ” conditions of five smoking cessation interventions : the National Cancer Institute ’s ( NCI ) Web site ( www.smokefree.gov vs a “ lite ” Web site ) , telephone quitline counseling ( vs none ) , a smoking cessation brochure ( vs a lite brochure ) , motivational e-mail messages ( vs none ) , and mini-lozenge nicotine replacement therapy ( NRT vs none ) . Analyses showed that the NCI Web site and NRT both increased abstinence ; however , the former increased abstinence significantly only when it was not used with the e-mail messaging intervention ( messaging decreased Web site use ) . The other interventions showed little evidence of effectiveness . There was evidence that mailed nicotine mini-lozenges and the NCI Web site ( www.smokefree.gov ) provide benefit as population -based smoking interventions Effects of a transdermal nicotine substitution on psychological smoking cessation were investigated in a double-blind prospect i ve study . 131 smokers have been r and omly assigned to three treatment conditions : All smokers underwent nine weeks of self-controlled smoking cessation . During 6 weeks one group was additionally treated with nicotine patches continuously releasing nicotine through the skin into the blood circuit . The second group received placebo patches ; while the third group was treated with behavioral training alone . Treatment effects were measured by daily cigarette consumption . Follow-up investigations were performed 3 , 6 and 12 months after therapy . Nicotine-treated subjects reached significantly higher abstinence rates during and at the end of treatment as well as during the follow-up period , than both placebo- and control-subjects . No severe side effects of plasters have been reported . The results thus indicate good therapeutic effectiveness of transdermal nicotine substitution We examined associations of weight concerns and weight gain with adolescent tobacco cessation treatment and whether these effects differed by gender or ethnoracial group . Participants were 115 urban adolescents recruited for a r and omized clinical trial of nicotine replacement therapy . Baseline weight gain concerns were assessed using the Eating Disorders module from the Diagnostic Interview for the Child and Adolescent ( DICA-IV ) . The average weight gain during the trial was 0.59 + /- 2.85 kg among the 43.5 % of participants who completed the treatment study . As indicated by the DICA , baseline weight gain concerns were not associated with weight gain during treatment , study completion , or abstinence from smoking at 3-month posttreatment follow-up ; these results did not vary by gender or ethnoracial group . Adolescents who quit smoking gained no more weight during the trial than those who smoked BACKGROUND A double-blind RCT on the short-term efficacy of nicotine patches compared to placebo patches among Dutch adolescents was conducted . The findings demonstrated that nicotine patches are efficacious for smoking cessation at end-of-treatment ; however , only in highly compliant participants . We tested whether the effects of NRT also held in 6- ( T7 ) and 12-month ( T8 ) follow-up assessment s. METHODS Adolescents aged 12 - 18 years , who smoked at least seven cigarettes a day and who were motivated to quit smoking were recruited at school yards and r and omly assigned to either a nicotine patch ( n=182 ) or a placebo patch ( n=180 ) condition according to a computer generated list . Participants ( N=257 , age : 16.7 ± 1.13 years ) attended an information meeting followed by a 6- or 9-week treatment . Smoking cessation , compliance , and potential covariates were measured by means of online question naires . Smoking cessation at T8 was biochemically vali date d by saliva cotinine . RESULTS At T7 , 8.1 % and 5.7 % of participants were abstinent in the nicotine and placebo patch groups , respectively . At T8 , abstinence was 4.4 % and 6.6 % , respectively . Intention-to-treat analyses showed no significant effects of NRT on abstinence rates at T7 ( OR=1.54 , 95 % CI=0.57 , 4.16 ) and vali date d abstinence rates at T8 ( OR=0.64 , 95 % CI=0.21 , 1.93 ) neither after considering compliance nor after adjusting for covariates . CONCLUSIONS NRT fails in helping adolescents quit smoking at 6- and 12-month follow-ups . This finding suggests that a more intensive approach is needed to assist youngsters in their quit attempts The effect of 2-mg nicotine chewing gum as an adjunct to group therapy for smoking cessation was studied in a placebo-controlled , double-blind , r and omized trial . After one year , 29 % of the 106 subjects treated with nicotine chewing gum had remained abstinent throughout the year compared with 16 % of the 99 subjects treated with placebo . The results were confirmed by measurement of levels of expired CO . More subjects in the nicotine group ( 70/94 v 45/93 ) reported that the gum reduced the craving for smoking . The adverse effects were few and not serious . In the nicotine group , 3 % were still using the nicotine gum after two years . No subjects in the placebo group used the chewing gum beyond six months . Nicotine chewing gum is effective in improving the success rates in smoking cessation based on group therapy OBJECTIVE To determine the efficacy of a 22-mg nicotine patch combined with the National Cancer Institute program for physician advice and nurse follow-up in providing withdrawal symptom relief , 1-year smoking cessation outcome , and percentage of nicotine replacement . DESIGN R and omized , double-blind , placebo-controlled trial . SUBJECTS Two-hundred forty healthy volunteers who were smoking at least 20 cigarettes per day . INTERVENTIONS Based on the National Cancer Institute program , subjects received smoking cessation advice from a physician . Follow-up and relapse prevention were provided by a study nurse during individual counseling sessions . Subjects were r and omly assigned to 8 weeks of a 22-mg nicotine or placebo patch . MAIN OUTCOME MEASURES Abstinence from smoking was verified by expired air carbon monoxide levels . Withdrawal symptoms were recorded during patch therapy , and the percentage of nicotine replacement was calculated by dividing serum nicotine and cotinine levels at week 8 of patch therapy by levels obtained while smoking . RESULTS Higher smoking cessation rates were observed in the active nicotine patch group at 8 weeks ( 46.7 % vs 20 % ) ( P < .001 ) and at 1 year ( 27.5 % vs 14.2 % ) ( P = .011 ) . Higher smoking cessation rates were also observed in subjects assigned to the active patch who had lower serum levels of nicotine and cotinine at baseline , and withdrawal symptom relief was better in the active patch group compared with placebo . CONCLUSIONS Clinical ly significant smoking cessation can be achieved using nicotine patch therapy combined with physician intervention , nurse counseling , follow-up , and relapse prevention . Smokers with lower baseline nicotine and cotinine levels had better cessation rates , which provides indirect evidence that they had more adequate nicotine replacement with this fixed dose of transdermal nicotine than those smokers with higher baseline levels The use of a chewing gum containing nicotine as an adjunct to a behavior modification smoking-cessation program increased the number of smokers who successfully discontinued smoking Helping patients to quit smoking is in the interest of all health professionals , including dentists . This chewing gum may be able to help INTRODUCTION Most smokers abstain from smoking during hospitalization but relapse upon discharge . This study tests the effectiveness of two proven treatments ( i.e. , nicotine patches and telephone counseling ) in helping these patients stay quit after discharge from the hospital , and assesses a model of hospital-quitline partnership . STUDY DESIGN This study had a 2 × 2 factorial design in which participants were stratified by recruitment site and smoking rate and r and omly assigned to usual care , nicotine patches only , counseling only , or patches plus counseling . They were evaluated at 2 and 6 months post-r and omization . SETTING / PARTICIPANTS A total of 1,270 hospitalized adult smokers were recruited from August 2011 to November 2013 from five hospitals within three healthcare systems . INTERVENTION Participants in the patch condition were provided 8 weeks of nicotine patches at discharge ( or were mailed them post-discharge ) . Quitline staff started proactively calling participants in the counseling condition 3 days post-discharge to provide st and ard quitline counseling . MAIN OUTCOME MEASURES The primary outcome measure was self-reported 30-day abstinence at 6 months using an intention-to-treat analysis . Data were analyzed from September 2015 to May 2016 . RESULTS The 30-day abstinence rate at 6 months was 22.8 % for the nicotine patch condition and 18.3 % for the no-patch condition ( p=0.051 ) . Nearly all participants ( 99 % ) in the patch condition were provided nicotine patches , although 36 % were sent post-discharge . The abstinence rates were 20.0 % and 21.1 % for counseling and no counseling conditions , respectively ( p=0.651 ) . Fewer than half of the participants in the counseling condition ( 47 % ) received counseling ( mean follow-up sessions , 3.6 ) . CONCLUSIONS Provision of nicotine patches proved feasible , although their effectiveness in helping discharged patients stay quit was not significant . Telephone counseling was not effective , in large part because of low rates of engagement . Future interventions will need to be more immediate to be effective . TRIAL REGISTRATION This study is registered at www . clinical trials.gov NCT01289275 We studied the effectiveness of chewing gum containing nicotine , in combination with group counseling , for subjects who were attempting to stop smoking . We used the Horn-Russell scale , based on a smoking question naire , to measure dependence on cigarettes ; 173 smokers were grouped as highly dependent on nicotine or as having medium to low degrees of dependence . In a r and omized double-blind study , the 60 highly dependent smokers were given gum containing 4 mg of nicotine ( n = 27 ) or 2 mg of nicotine ( n = 33 ) , and the 113 smokers with medium or low dependence were given gum containing 2 mg of nicotine ( n = 60 ) or a placebo gum ( n = 53 ) . All smokers took part in group counseling . In the highly dependent group , abstinence from cigarettes was chemically verified after six weeks , one year , and two years ; 81.5 percent , 44.4 percent , and 33.3 percent of the subjects given gum containing 4 mg of nicotine were abstinent after those follow-up periods ; the rates of abstinence were 54.5 percent , 12.1 percent , and 6.1 percent , respectively , for the subjects given gum containing 2 mg of nicotine . In the group with medium or low dependence , the rates of abstinence after the same periods were 73.3 percent , 38.3 percent , and 28.3 percent for the subjects given gum containing 2 mg of nicotine and 41.5 percent , 22.6 percent , and 9.4 percent for those given placebo gum . The differences in outcomes were significant at the 5 percent level for all comparisons , with the exception of the 2-mg nicotine gum versus the placebo gum at one year . This study indicates that the effectiveness of nicotine gum is not due to a placebo effect and that it is related to dose . The use of nicotine gum in appropriate doses should be helpful to persons who are attempting to stop smoking Tobacco use is a major cause of cardiovascular , respiratory and oncological disease . Quitting smoking significantly benefits health , but for highly dependent smokers , unable to overcome their nicotine dependence , the concept of smoking reduction as a method of harm reduction is gaining ground . The University Hospital of Basle , Switzerl and , has run double-blind , placebo-controlled smoking cessation and smoking reduction studies : the CEASE trial evaluated the efficacy of the nicotine patch in achieving abstinence , and the Rosette study is evaluating the efficacy and tolerability of the nicotine oral inhaler in smokers who do not wish to quit . Smokers were instructed either to quit smoking ( CEASE ) or to reduce cigarette consumption by > 50 % ( Rosette ) . In both studies , success rates for active treatment versus placebo at 4 months demonstrated that nicotine replacement therapy ( NRT ) is effective in achieving both smoking cessation and reduction . Current approaches to smoking cessation and reduction at our clinic are discussed . Combination NRT rather than monotherapy is commonly used to achieve both smoking reduction and cessation . Treatment appears to be most effective if subjects are allowed to select their preferred NRT product . There are clear differences in patient population s aim ing to quit or reduce , the cessation population being more motivated . Smoking cessation remains the ultimate aim but , if unfeasible , a significant reduction in cigarette consumption is a valid goal A comparative study aim ed at evaluating the effectiveness of different methods of detoxication for dependent smokers is currently in progress . In this study , the percentage of subjects who gave up smoking after 1 month and changes in this percentage over a 12-month period are determined in 3 groups of subjects : one group treated with acupuncture , one group treated with a chewing-gum containing nicotine , and a control group . The intermediate analysis results include 45 % of the total number of subjects required . They show no statistically significant difference between the control group and the two treated groups . Volunteers are still being recruited Most attempts to quit smoking end in failure , with many quitters relapsing in the first few days . Responses to smoking-related cues may precipitate relapse . A modified emotional Stroop task-which measures the extent to which smoking-related words disrupt performance on a reaction time ( RT ) task-was used to index the distracting effects of smoking-related cues . Smokers ( N = 158 ) r and omized to a high-dose nicotine patch ( 35 mg ) or placebo patch completed the Stroop task on the 1st day of a quit attempt . Smokers using an active patch exhibited less attentional bias , making fewer errors on smoking-related words . Smokers who showed greater attentional bias ( slowed RT on the first block of smoking words ) were significantly more likely to lapse in the short-term , even when controlling for self-reported urges at the test session . Attentional bias measures may tap an important component of dependence Polymorphisms in the dopamine D2 receptor ( DRD2 C/T and DRD2 A/G ) and in dopamine beta hydroxylase ( DBH A/G ) have been implicated in modulation of smoking and other reward-seeking behaviours . We hypothesized that these alleles would predict the outcome of nicotine patch therapy for smoking cessation . In 1991 - 93 , we performed a r and omized controlled trial of the nicotine patch on 1686 heavy smokers ( > or = 15 cigarettes/day ) . In 1999 - 2000 , we contacted 1532 of the 1612 subjects still available ; 767 ( 50 % ) completed a question naire and gave a blood sample . In the 755 cases in which DNA was successfully genotyped , we examined associations between the polymorphisms in DRD2 and DBH , and smoking cessation . At 1 week , the patch was more effective for smokers with DRD2 CT/TT genotype [ patch/placebo odds ratio ( OR ) 2.8 , 95 % confidence interval ( CI ) 1.7 - 4.6 ] than with CC ( OR 1.4 , 0.9 - 2.1 ; P for difference in ORs 0.04 ) . Smokers with both DRD2 CT/TT and DBH GA/AA genotypes had an OR of 3.6 ( 2.0 - 6.5 ) compared to 1.4 ( 1.0 - 2.1 ) for others ( P = 0.01 ) . At 12 weeks , the ORs for these genotypic groups were 3.6 ( 1.7 - 7.8 ) and 1.4 ( 0.9 - 2.3 ) , respectively ( P = 0.04 ) . There was no association between patch effectiveness and DRD2 exon 8 . Short-term effectiveness of the nicotine patch may be related to dopamine beta-hydroxylase and dopamine D2 receptor genotype . Our results support the need for further investigation into personalized therapies for smoking cessation based on individual genotype Studies with nicotine chewing gum and nicotine skin patches indicate that nicotine replacement can help people to give up smoking . The rapidity with which nicotine is absorbed when given as a nasal spray suggests that it might be effective for those for whom the other means of replacement are too slow . The efficacy and safety of a nasal nicotine spray as an adjunct to group treatment for stopping smoking were assessed in a r and omised , double-blind , placebo-controlled trial in which 227 cigarette smokers attending the Maudsley Hospital Smokers Clinic received 4 weeks of supportive group treatment plus active nicotine ( 0.5 mg per shot ) or placebo nasal spray . The main end-point was biochemically vali date d complete abstinence from smoking from the third week of group treatment until the 12-month follow-up . Side-effects were assessed by self-reports and , where necessary , by physical examination . Of subjects assigned to active treatment 26 % ( n = 30 ) were vali date d abstinent throughout the year , compared with 10 % ( n = 11 ) of those assigned to placebo ( relative abstinence rate 2.6 , 95 % CI 1.5 - 4.5 , p less than 0.001 ) . The advantage of the active spray was greatest in the heaviest smokers . Plasma nicotine concentrations from the spray were typically between one-half and three-quarters of baseline smoking levels . Tobacco-withdrawal symptoms , craving for cigarettes , and weight gain in abstinent subjects were reduced by the active spray . Minor irritant side-effects were frequent in both active and placebo sprays , but only 2 subjects had the spray discontinued as a result . No serious adverse effects were encountered . Nasal nicotine spray combined with supportive group treatment is an effective aid to smoking cessation Patterns of smoking cessation using 6- and 12-month follow-up data are reported for 1,261 primary care patients r and omized to 3 physician-delivered smoking interventions : advice only ( AO ) , counseling ( CI ) , and counseling plus availability of nicotine-containing gum ( CI + NCG ) . One-week-point-prevalence cessation rates at 12 months did not differ among the interventions : AO ( 15.2 % ) , CI ( 12.9 % ) and CI + NCG ( 16.7 % ) . However , maintained cessation rates ( abstinent at both 6 and 12 months ) increased with intervention intensity : AO ( 6.0 % ) , CI ( 7.8 % ) and CI + NCG ( 10.0 % ) : Test of trend chi 2 = 5.06 , p = .02 . CI + NCG was significantly higher than AO ( p = .02 ) . The findings support the following conclusions : Brief physician-delivered intervention with availability of nicotine-containing gum can have a beneficial long-term effect on smoking cessation , and cohort data as well as point-prevalence rates are important when assessing the long-term impact of lifestyle interventions Seventy-eight smokers trying to quit were r and omly assigned to 0- , 0.5- , 2- and 4-mg doses of nicotine gum and tracked for 9 months . In the 1st week of abstinence , self-administration of gum did not differ by dose ( 4 mg = 2 mg = 0.5 mg = 0 mg ) . Higher doses did not more effectively suppress withdrawal than lower doses nor induce more accurate nicotine identification ( 4 mg = 2 mg = 0.5 mg greater than 0 mg ) . Higher doses slightly increased ratings of adverse effects in the 1st week ( 4 mg greater than 2 mg greater than 0.5 mg greater than 0 mg ) . Over the next 6 months , the two higher doses appeared to support more gum self-administration than the two lower doses ( 4 mg = 2 mg greater than 0.5 mg = 0 mg ) in the sub sample of long-term quitters ( n = 20 ) . Our results suggest the dose-response curves differ for nicotine gum 's reinforcing , withdrawal-suppression and self-reported effects Introduction : In nonpregnant “ quitters , ” adherence to nicotine replacement therapy ( NRT ) increases smoking cessation . We investigated relationships between adherence to placebo or NRT patches and cessation in pregnancy , including an assessment of reverse causation and whether any adherence : cessation relationship is moderated when using nicotine or placebo patches . Methods : Using data from 1050 pregnant trial participants , regression models investigated associations between maternal characteristics , adherence and smoking cessation . Results : Adherence during the first month was associated with lower baseline cotinine concentrations ( β −0.08 , 95 % confidence interval [ CI ] −0.15 to −0.01 ) and r and omization to NRT ( β 2.59 , 95 % CI 1.50 to 3.68 ) . Adherence during both treatment months was associated with being r and omized to NRT ( β 0.51 , 95 % CI 0.29 to 0.72 ) and inversely associated with higher nicotine dependence . Adherence with either NRT or placebo was associated with cessation at 1 month ( odds ratio [ OR ] 1.11 , 95 % CI 1.08 to 1.13 ) and delivery ( OR 1.06 , 95 % CI 1.03 to 1.09 ) , but no such association was observed in the subgroup where reverse causation was not possible . Amongst all women , greater adherence to nicotine patches was associated with increased cessation ( OR 2.47 , 95 % CI 1.32 to 4.63 ) but greater adherence to placebo was not ( OR 0.98 , 95 % CI : 0.44 to 2.18 ) . Conclusion : Women who were more adherent to NRT were more likely to achieve abstinence ; more nicotine dependent women probably showed lower adherence to NRT because they relapsed to smoking more quickly . The interaction between nicotine-containing patches and adherence for cessation suggests that the association between adherence with nicotine patches and cessation may be partly causal . Implication s : This study used placebo r and omized controlled trial data to investigate both associations between women ’s characteristics and adherence to NRT patch treatment , and the relationship between adherence to NRT patch treatment and odds of cessation in pregnant quitters . Greater adherence was seen with NRT patches , and greater adherence with NRT patches increased the odds of smoking cessation . A likely explanation for findings is that NRT patches , if used sufficiently , may be effective for at least some pregnant women who try to stop smoking . Trials testing interventions which encourage women ’s adherence to higher dose NRT are indicated OBJECTIVE To assess the effectiveness of transdermal nicotine therapy for smoking cessation and suppression of withdrawal severity in conjunction with two different adjuvant counseling treatments . DESIGN Two independent r and omized placebo-controlled double-blind trials . SETTING Smoking cessation clinic . SUBJECTS Eighty-eight ( study 1 ) and 112 ( study 2 ) adult volunteers motivated to quit smoking . INTERVENTIONS Eight weeks of 22-mg transdermal nicotine therapy with group counseling ( study 1 ) ; 4 weeks of 22 mg followed by 2 weeks of 11-mg transdermal nicotine therapy with brief individual counseling ( study 2 ) . MAIN OUTCOME MEASURES Modified point prevalence ( 7 consecutive days of nonsmoking ) at the end of patch treatment and 6 months after treatment initiation was assessed by self-report and biochemically confirmed ; survival analyses were also conducted for both studies to compare treatment efficacy . Also , we examined the impact of the nicotine patch on specific withdrawal symptoms ( anger , anxiety , awakening , difficulty concentrating , depression , hunger , impatience , and craving ) . RESULTS Transdermal nicotine treatment produced higher cessation rates at the end of treatment than did placebo with both adjuvant counseling interventions : 59 percent vs 40 percent ( p < 0.05 in study 1 ) and 37 percent vs 20 percent ( p < 0.05 in study 2 ) , respectively . Smoking cessation efficacy was maintained 6 months after initiation of treatment : 34 percent vs 21 percent ( p = 0.08 in study 1 ) and 18 percent vs 7 percent ( p = 0.05 in study 2 ) . Survival analyses also revealed significant group differences in efficacy in both studies . Nicotine patches also suppressed a variety of withdrawal symptoms , including craving in the first weeks after patients quit smoking . CONCLUSION Transdermal nicotine effectively augments smoking cessation rates with two different types of counseling treatment . Overall , the nicotine patch approximately doubles the sustained rate of smoking cessation . Additionally , the nicotine patch provides relief from some tobacco withdrawal symptoms There are a lot of methods for smoking cessation but transdermal nicotine system ( TNS ) is one of the most popular . On a sample of more than 300 smokers we have formerly shown that TNS achieves higher abstinence rate than placebo ( 38%:21 % ) . In the present study we have tested the optimal administration of TNS . 160 smokers were subdivided in 4 groups of 40 , receiving either TNS or placebo , for 3 or 6 weeks . The abstinence rate was evaluated by appropriate question naires and measuring CO in the exhaled air . After 3 weeks of TNS 60 % of the examinees were abstaining compared to 50 % after 6 weeks ; the abstinence rates in the placebo groups were 17.5 % and 20 % , respectively ( p < 0.05 ) . Short TNS treatment ( 3 weeks ) is at least as effective as a longer one ( 6 weeks ) , which is relevant both medically and economically This r and omized , open-label , crossover study was conducted to compare the effects of a 24-hr nicotine patch and a 16-hr nicotine patch on morning smoking urges and sleep quality of dependent smokers during a short period of cigarette abstinence . A total of 20 smokers ( 9 women and 11 men ) smoking at least 20 cigarettes/day completed the two smoke-free study periods . For each period , cigarette abstinence started on the first evening and a nicotine patch was applied the next morning ( for 16 or 24 hr ) , after baseline measures ; a second patch was applied the next morning , 1 hr before the end of the experimental period . Smoking urges , mood and behavior self-reports , psychomotor performance , and polysomnographic recordings were compared between the two types of nicotine patch according to changes from baseline . Both patches decreased morning smoking urges , although results were significantly superior for the 24-hr patch . Furthermore , the 24-hr patch was more effective than the 16-hr patch in reducing the positive reinforcing dimension of smoking urges . Regarding polysomnographic recordings , the proportion of slow wave sleep was significantly increased from baseline with the 24-hr patch compared with the 16-hr patch . As for psychomotor performance measured through the critical flicker fusion test , significant improvement in morning alertness was observed in the 24-hr patch group . In conclusion , the 24-hr nicotine patch formulation is more effective than the 16-hr formulation in alleviating morning smoking urges and more specifically the positive reinforcing factor . The present findings do not support the idea that nicotine delivery during bedtime might disturb sleep , but rather it improves restorative sleep and postwaking arousal INTRODUCTION The development of evidence -based smoking cessation programs is in its infancy in developing countries , which continue to bear the main brunt of the tobacco epidemic . Adherence to treatment recommendations is an important determinant of the success of smoking cessation programs , but little is known about factors influencing adherence to either pharmacological or behavioral treatment in developing countries setting s. Our study represents the first attempt to examine the predictors of adherence to cessation treatment in a low-income developing country . METHODS Predictors of adherence to pharmacological and behavioral treatment were identified by analyzing data from a multi-site , two-group , parallel-arm , double-blind , r and omized , placebo-controlled smoking cessation trial in primary care clinics in Aleppo , Syria . Participants received 3 in-person behavioral counseling sessions plus 5 brief follow-up phone counseling sessions , and were r and omized to either 6 weeks of nicotine or placebo patch . RESULTS Of the 269 participants , 68 % adhered to pharmacological treatment , while 70 % adhered to behavioral counseling . In logistic regression modeling , lower adherence to pharmacological and behavioral treatment was associated with higher daily smoking at baseline , greater withdrawal symptoms , and perception of receiving placebo instead of active nicotine patch . Women showed lower adherence than men to behavioral treatment , while being assigned to placebo condition and baseline waterpipe use were associated with lower adherence to pharmacological treatment . CONCLUSION Adherence to cessation treatment for cigarette smokers in low-income countries such as Syria may benefit from integrated cessation components that provide intensive treatment for subjects with higher nicotine dependence , and address concurrent waterpipe use at all stages We examined the pharmacokinetics of a transdermal nicotine patch and evaluated the usefulness of such a patch in a pilot smoking‐cessation program . Use of the patch was associated with plasma nicotine concentrations that were comparable to smoking or to the use of other smoking‐cessation devices . However , these plasma concentrations were maintained for 24 hours , and the patch appeared to be suitable for use once a day . Its use in a 6‐week placebo‐controlled double‐blind study result ed in a significant degree of smoking cessation or in reduction of smoking activity . The findings suggest that it may be valuable to extend investigations to a larger population and that transdermal nicotine may have a useful role in smoking‐cessation therapy Abstract Adults with any DSM-IV diagnosed mental illness smoke nearly half of the cigarettes consumed in the U.S. ( Lasser et al. 2000 ) . This study compared two smoking cessation interventions for persons with schizophrenia or other serious mental illness because national data suggests that : ( 1 ) they smoke at two to three times the rate of the general population ; ( 2 ) cessation interventions for this population are understudied ; ( 3 ) most cessation studies exclude persons with serious mental illness ; and ( 4 ) cessation results in public health care savings and disposable income savings for clients . This study included a large number of persons with serious mental illness ( N = 181 ) who were r and omly assigned to one of three groups : contingent reinforcement ( CR ) , CR plus nicotine patch ( 21 mg , CR+NRT ) for 16 weeks , and a minimal intervention , self-quit control group . These participants were followed for 36 weeks . CR was accomplished with escalating financial compensation for achieving and maintaining abstinence as verified by expired carbon monoxide ( CO ) . Quit rates , as measured by expired CO , were higher and discordant with saliva cotinine quit rates . Cotinine showed lower quit rates and small differences between intervention and control partici pants at weeks 20 and 36 . There was , however , evidence of reduced smoking and importantly , no evidence of psychiatric exacerbation Few studies have investigated abstinence beyond three years among participants who stop smoking during trials of nicotine replacement therapy,1–3 and even fewer have followed up smokers who failed to quit during such trials . We carried out an eight year follow up of people who had participated in a r and omised controlled trial of the nicotine patch . Participants were the 1686 patients from general practice s in Oxfordshire who took part in a double blind r and omised controlled trial of the patch in 1991 - 2.4 5 At entry they smoked≥15 cigarettes a day and were aged 25–64 years . Participants wore the patches for 12 weeks . The main outcome was abstinence from smoking for one year , confirmed at 12 , 24 , and 52 weeks by a salivary cotinine concentration≤20 ng/ml ( 89 % of cases ) or expired carbon monoxide≤10 ppm ( 11 % ) . In 1999 - 2000 , we contacted 1532 of the 1625 living participants . We The efficacy of a nicotine transdermal therapeutic system ( TTS ) ( available size 10 , 20 and 30 cm2 ; nicotine delivery rate = 0.7 mg/cm2/24 h ) as an aid for smoking cessation , was evaluated in a r and omized , single-blind , placebo-controlled , monocenter study using 160 heavy-smokers ( > 20 cigarettes/day ) , male and female , who were divided into two matched parallel groups . The nicotine replacement treatment lasted for 3 months and was carried out according to the manufacturers recommendations . Abstinence was defined as smoking no cigarette during the last week of each month and COHb-levels < or = 1.2 % . Efficacy was assessed using abstinence rates , withdrawal symptoms and cigarette consumption . Although at the commencement of the study all subjects expressed a high motivation to stop smoking , about a third were lost to follow-up at 4 weeks . This was attributed mainly to the lack of counselling and group dynamics . The greatest effect on smoking cessation and cigarette consumption was attributable to a non-specific aspect of treatment , i.e. the motivation to stop smoking on application of the first patch . On an intention-to-treat basis ( all subjects ) , abstinence rates were 24 % and 18 % after 1 month , 24 % and 14 % after 2 months and 14 % and 6 % after 3 months for the nicotine-TTS and placebo-TTS , respectively . Nicotine-TTS was at least twice as effective as placebo in maintaining nicotine abstinence . The superiority of the nicotine-TTS was supported by the trend to a higher craving-for-cigarettes score and significantly higher blood COHb and cigarette consumption in the non-abstainers treated with placebo PURPOSE To determine whether ( 1 ) tailored nicotine patch therapy that is based on smoking rate can be carried out in a multisite oncology investigative group practice setting , ( 2 ) long-term use of bupropion reduces the rate of relapse to smoking in smokers who stop smoking with nicotine patch therapy , and ( 3 ) bupropion can initiate smoking abstinence among smokers who have failed to stop smoking after nicotine patch therapy . PARTICIPANTS AND METHODS Fourteen North Central Cancer Treatment Group sites recruited generally healthy adult smokers from the general population for nicotine patch therapy and based the patch dosage on smoking rates . At completion of nicotine patch therapy , nonsmoking participants were eligible to be assigned to bupropion or placebo for 6 months ( for relapse prevention ) . and smoking participants were eligible to be assigned to bupropion or placebo for 8 weeks of treatment . RESULTS Of 578 subjects , 31 % were abstinent from smoking at the end of nicotine patch therapy . Of those subjects not smoking at the end of nicotine patch therapy who entered the relapse prevention phase , 28 % and 25 % were not smoking at 6 months ( the end of the medication phase ) for bupropion and placebo , respectively ( P = .73 ) . For those still smoking at the end of nicotine patch therapy , 3.1 % and 0.0 % stopped smoking with bupropion or placebo , respectively ( P = .12 ) . CONCLUSION Tailored nicotine patch therapy for the general population of smokers can be provided in a multisite oncology investigative group setting . Bupropion did not reduce relapse to smoking in smokers who stopped smoking with nicotine patch therapy . Bupropion did not initiate abstinence among smokers who failed to stop smoking with nicotine patch therapy AIMS To assess the efficacy of nicotine replacement therapies ( NRT ) when the daily dose was adapted according to saliva cotinine concentrations . DESIGN R and omized , multi-centre , single-blind , controlled trial . SETTING Twenty-one smoking cessation clinics in France . PARTICIPANTS A total of 310 smokers with medical comorbidities , motivated to quit , smoking ≥ 10 cigarettes/day , for whom smoking cessation was m and atory . NRT was administered for 3 months . The st and ard care group received nicotine patches with monthly dose decreases ; buccal absorption NRT could be co-administered at the discretion of the investigator . In the dose adaptation group , the aim was a 100 ± 5 % nicotine substitution with respect to smoking state based on the determination of saliva cotinine concentrations . NRT daily doses were prescribed according to the previous week 's saliva cotinine concentrations in the dose adaptation group ; saliva cotinine concentrations were not provided in the st and ard care group . MEASUREMENTS Prolonged abstinence rate ( weeks 9 - 12 , main outcome measure ) , point-prevalence and continuous abstinence rate , saliva cotinine concentration , NRT daily dose , craving for cigarettes . FINDINGS The median daily prescribed NRT dose was 30 and 31 mg/day in the first study week and 17.25 and 35.5 mg/day during weeks 9 - 12 in the st and ard care group and dose adaptation group , respectively . Saliva cotinine remained stable in the dose adaptation group and decreased in the st and ard care group ( P < 0.01 ) by weeks 9 - 12 . The cotinine substitution rate was significantly lower in the st and ard care group than in the dose adaptation group . Despite differences in NRT doses and cotinine substitution rates , prolonged ( st and ard care group : 26.4 % , dose adaptation group : 30.3 % ) , continuous ( st and ard care group : 8 % , dose adaptation group : 12 % ) and point-prevalence abstinence rates were similar . CONCLUSIONS In smokers with medical comorbidities and highly motivated to quit , adaptation of the nicotine replacement therapy daily dose according to saliva cotinine does not appear to be substantially superior to st and ard nicotine replacement therapy use AIM Using nicotine gum can reduce the amount of weight gained when quitting . Here we examine the relationship between weight gain and use of adequate amounts of gum . To mitigate the confounders associated with correlational analyses , we contrast the effects of active gum and placebo , and analyze outcomes prospect ively . DESIGN AND SETTING R and omized double-blind placebo-controlled trial of nicotine gum . Participants were instructed to use nine to 15 pieces of gum/day for the first 2 months of treatment . PARTICIPANTS Participants ( n = 103 ) were r and omized to either active ( 2 mg or 4 mg ) or placebo gum . MEASUREMENTS We examined the effect on weight gain of the interaction between treatment ( active versus placebo ) and daily gum use [ ≥9 pieces/day ( compliant use ) versus < 9 pieces/day ] . FINDINGS After 30 days of abstinence , smokers treated with active gum had not gained significantly less weight than those on placebo ( 1.1 kg versus 1.6 kg , P = 0.175 ) . However , a significant compliance-treatment interaction was observed ( P = 0.005 ) : active gum users who used ≥9 pieces/day during the first 14 days of treatment had gained less weight at follow-up ( 0.6 kg versus 1.6 kg for those who used < 9 pieces/day , P = 0.017 ) , but participants r and omized to the placebo group saw no such benefit from compliant use . A similar compliance-treatment interaction ( P = 0.046 ) was also observed when the effect of compliance was examined within active treatment ( 2 mg versus 4 mg ) . CONCLUSIONS When smokers are quitting , those who use more pieces of nicotine gum experience less weight gain in the first 30 days . This relationship is not seen for smokers on placebo gum The overall effectiveness of nicotine replacement therapy could be greater if the therapy were targeted at those most likely to respond . Variants of the dopamine D2 receptor ( DRD2 32806 C/T ) have been implicated in the initiation and maintenance of smoking,1 2 and these variants may also be related to response to nicotine replacement therapy.3 Additionally , mechanisms of nicotine addiction may differ in men and women.4 With this evidence in mind , we examined whether the response to nicotine replacement therapy is modified by sex and genotype . A r and omised controlled trial of nicotine patches in 1991 - 2 recruited 1686 heavy smokers ( ≥15 cigarettes a day).5 The participants wore patches for 12 weeks . Abstinence from smoking was confirmed at one week by expired carbon monoxide concentration ≤ 10 ppm , and at 12 , 24 , and 52 weeks by salivary cotinine concentration ≤ 20 ng/ml ( 89 % of cases ) or by expired carbon monoxide concentration ≤10 ppm . In 1999 - 2000 , we contacted 1532 of the 1625 participants still alive ; the mean UNLABELLED The complete Multidimensional Measure of Stress ( MMOS ) measure may be made available to interested persons by contacting the corresponding author . CONTEXT Smoking rates are higher among inner-city and lower-income African Americans , perhaps due to psychosocial barriers to cessation efforts , including stress . OBJECTIVE To describe the development of the MMOS and examine the psychometric properties of the MMOS among African American light smokers . DESIGN Secondary analysis of data generated from a 2x2 r and omized clinical trial , design ed to examine the efficacy of nicotine replacement and cessation counseling among 755 African American light smokers . RESULTS Fourteen items were included in the final MMOS ( alpha = .83 ) . An exploratory factor analysis identified 3 factors : interpersonal ( alpha = .80 ) , safety ( alpha = .70 ) , and financial ( alpha = .75 ) . The MMOS was significantly correlated with the Perceived Stress scale ( r = 0.49 , p < .001 ) and was associated with several demographic , psychosocial , and tobacco-related variables . CONCLUSIONS The MMOS appears to be a valid measure of stress among African American light smokers enrolled in a cessation trial The effectiveness of nicotine gum in combination with a behavior modification program was studied . The nicotine dependence of participating smokers ( N = 322 ) was assessed . One hundred sixty-eight smokers were labeled as high nicotine dependent and 154 as moderate to low dependent . In a r and omized double-blind procedure , the high-dependent smokers were given gum containing 4 mg of nicotine ( 87 ) or 2 mg of nicotine ( 81 ) and the smokers with medium or low dependence were given gum containing 2 mg ( 76 ) or a placebo gum ( 78 ) . The smokers were also r and omized to familiarizing themselves with the medication a week before quit day ( 112 ) or to regular use , that is starting gum use on the quit day ( 122 ) . In the high-dependent group , sustained and chemically verified nonsmoking rates at 6 weeks , 1 year , and 2 years were , respectively , 60 % , 39 % , and 34 % in the subjects given the 4-mg dose compared with 41 % , 16 % , and 16 % for those using the 2-mg dose . In the group with medium or low dependence , the success rates at the same time periods were 70 % , 49 % , and 39 % for the subjects given the 2-mg dose and 38 % , 22 % , and 17 % for those given placebo gum . The differences in success rates were significant at least at the p < 0.02 % level for all comparisons . Familiarizing with the gum as compared with regular use gave fewer reports of side effects , 15 % vs 34 % , p < 0.001 . A trend toward better success rates at 6 weeks , although not statistically significant , was observed for the familiarization group , 61 % vs 52 % . The study shows that high nicotine-dependent smokers need higher doses of nicotine replacement , in this case the 4-mg dose rather than the 2-mg dose , whereas 2 mg is superior to placebo among less dependent smokers . These results compare favorably with those reported from the more recent nicotine patch therapy We used the Heaviness of Smoking Index , a subset of the Fagerstrom Test for Nicotine Dependence , to classify 608 cigarette smokers planning a cessation attempt as low or high in nicotine dependence . Subjects within each level of dependence were then r and omly assigned to placebo , 2-mg , or 4-mg nicotine gum treatment . Subjects were also provided brief ( 5 - 10 min per visit ) behavioral counseling during a 1-year period of follow-up . At 1 year post-cessation , quit rates were 11.2 , 19.5 , and 18.4 % for low-dependence smokers receiving placebo , 2-mg , and 4-mg gum , respectively ( plinear trend = 0.20 ) . For high-dependence smokers , quit rates at 1 year were 6.1 , 15.7 , and 20.7 % for the placebo , 2-mg , and 4-mg gum conditions , respectively ( plinear trend = 0.002 ) . The interaction of nicotine-gum dose and dependence group was not significant ( p = 0.42 ) , nor did the 2-mg and 4-mg doses differ significantly in effectiveness , though both 2-mg and 4-mg gum were significantly more effective than placebo gum . We also found a significant dose-related effect for nicotine gum to moderate post-cessation heart-rate decline . Other variables related to abstinence at 1 year post-cessation were a longer period of abstinence on a prior quit attempt , being married , higher education level , and having a non-smoking spouse or significant other . Results indicate that nicotine gum is a significant aid to smoking cessation , more than doubling the odds of successful cessation compared to the odds for placebo-gum users . The 4-mg dose provided a non-significant increase in cessation rates for high-dependence smokers . Smoking history and demographic variables also have a significant impact on the outcome of a quit-smoking attempt This study determined whether higher dose nicotine patches are more efficacious than lower dose patches among heavy smokers . A r and omized double-blind study compared 0 , 21 , 35 , and 42 mg/day of a 24-h patch in 1039 smokers ( > or = 30 cigarettes/day ) at 12 clinical sites in the USA and one in Australia . Daily patches were used for 6 weeks followed by tapering over the next 10 weeks . Weekly group therapy occurred . Biochemically vali date d self-reported quit rates at 6 , 12 , 26 , and 52 weeks post-cessation were measured . Quit rates were dose-related at all follow-ups ( p < 0.01 ) . Continuous , biochemically verified abstinence rates for the 0 , 21 , 35 , and 42 mg doses at the end of treatment ( 12 weeks ) were 16 , 24 , 30 , and 39 % . At 6 months , the rates were 13 , 20 , 20 , and 26 % . Among the 11 sites with 12 month follow-up ( n = 879 ) , the quit rates were 7 , 13 , 9 , and 19 % . In post-hoc tests , none of the active doses were significantly different from each other at any follow-up . The rates of dropouts due to adverse events for 0 , 21 , 35 , and 42 mg were 3 , 1 , 3 , and 6 % ( p = n.s . ) . Our results are similar to most prior smaller studies ; i.e. , in heavy smokers higher doses increase quit rates slightly . Longer duration s of treatment may be necessary to show greater advantages from higher doses The authors examined the effect of 24-hour nicotine patches in smoking cessation among over-the-counter customers in Denmark , based on a r and omized double-blind placebo-controlled trial . Participants were consecutive customers to whom nicotine patches were offered as the only treatment . Forty-two pharmacies in the areas of Aarhus and Copenhagen in Denmark participated in the trial , and 522 customers who smoked 10 or more cigarettes per day were r and omized to either nicotine patches or placebo from January to March 1994 . Customers with chronic diseases and pregnant or breastfeeding women were excluded from the trial . Twenty-four-hour patches were offered free of charge during a 3-month period . Those smoking 20 or more cigarettes per day started on a dose of 21-mg/day patches . Customers who smoked less started on patches of 14 mg/day ; and for all of the participants , the dose was gradually reduced to 7-mg/day patches during the study period . Smoking behavior and compliance were recorded by means of self-administered question naires and telephone interviews . Smoking status was recorded in intervals of 4 weeks , which was fixed to be a treatment period , and 26 weeks after inclusion . There was a significant increase in smoking cessation rates after 8 weeks of follow-up but only among smokers who started on 21-mg/day patches . There was a marked placebo effect at each time of contact during the trial , especially in those smoking fewer than 20 cigarettes per day . Although the noncompliance rate was high overall due to discontinuation in the use of patches by relapsed smokers , noncompliance among successful quitters was low . More side effects were seen in the nicotine group than in the placebo group , but none of the reported side effects were serious . It appears that regular healthy smokers who were customers of nonprescribed nicotine patches and who received 21-mg/day nicotine patches benefited from the active treatment ( 44.1 % stopped smoking after 4 weeks ) , but almost as many stopped smoking in the placebo group ( 37.3 % after 4 weeks ) . No significant differences in smoking cessation rates were seen among smokers who started with the low-dose nicotine or placebo patches Abstract Objective : To assess the efficacy and safety of a repeat course of treatment with transdermal nicotine for cessation of smoking in a brief intervention setting . Study design : R and omised , double blind , placebo controlled trial with follow up for 26 weeks . Subjects : 629 smokers who had unsuccessfully attempted to stop smoking by using active transdermal nicotine and brief behavioural counselling . Smokers were motivated to quit smoking for a second time and smoked > /=15 cigarettes a day . Interventions : Twelve weeks ' treatment with active transdermal nicotine patches or placebo and brief counselling at monthly visits . Main outcome measure > : Sustained smoking cessation for the 28 days before the visit at week 12 verified by expired carbon monoxide concentrations . Results : At 12 weeks 21/315 ( 6.7 % ) subjects allocated to active treatment had stopped smoking compared with 6/314 ( 1.9 % ) allocated to placebo ( absolute difference 4.7 % ; 95 % confidence interval 1.6 % to 7.9 % ; P=0.003 ) . At 26 weeks the rates were 20/315 ( 6.4 % ) and 8/314 ( 2.6 % ) ( 3.8 % ; 0.6 % to 7.0 % ; P=0.021 ) . Difficulty in sleeping was reported by 43/179 ( 24.0 % ) on active treatment and 19/143 ( 13.3 % ) on placebo ( P=0.015 ) . Severe reactions at the site of application were rare ( 6/322 ; 1.9 % ) . Conclusions : Repeated treatment with transdermal nicotine together with brief counselling can improve the low success rates of smoking cessation in recently relapsed , moderate to heavy smokers . Questions remain about whether more intensive interventions or higher doses of nicotine could be more effective . The likelihood of severe reactions at the site of application with repeated treatment is low A study with a 2 x 2 factorial design was performed to evaluate the effectiveness of acupuncture , of nicotine gum and the effect of the association on smoking cessation . After a one-year follow-up period , the success rates were in the same order of magnitude for nicotine gum ( active treatment : 10 % , placebo : 8 % ) group and for acupuncture ( active treatment : 8 % , placebo : 10 % ) group In a 2-week intervention to reduce cigarette smoking among out patients in treatment for cocaine addiction , 20 subjects were r and omly assigned to a contingent group , receiving monetary vouchers for breath sample s with carbon monoxide ( CO ) levels of 8 ppm or less , or to a noncontingent group , receiving vouchers regardless of CO level . Subjects wore either nicotine or placebo patches in a r and omized crossover design . Contingent subjects had significantly lower CO levels and met the 8 ppm target significantly more often than did noncontingent subjects ; however , number of cigarettes reported smoked did not differ between groups . Use of nicotine patches result ed in CO levels significantly lower than did use of placebo patches , but levels still exceeded 8 ppm regardless of type of patch . Because contingent reward helped cocaine-dependent smokers achieve nonsmoking CO targets , behavioral antismoking interventions merit continued study in similar population AIM People who quit smoking often gain 11 - 12 lb , on average , which can frequently lead to a relapse to smoking . This study evaluated whether extended vs. st and ard duration treatment with nicotine patch helps those able to quit smoking to reduce cessation-induced weight gain and explored nicotine patch adherence as a mediator of treatment effects . DESIGN AND SETTING We examined data from a completed r and omized placebo-controlled clinical trial of extended ( 24 weeks ) vs. st and ard ( 8 weeks plus 16 weeks of placebo ) transdermal nicotine patch therapy . Changes in measured weight over 24 weeks were compared across the two treatment arms , controlling for gender , baseline smoking rate , and previous weight . Adherence to patch use was assessed using self-report of daily use over 24 weeks . PARTICIPANTS 139 clinical trial participants who were confirmed to be abstinent at weeks 8 and 24 . FINDINGS Compared to participants who received 8 weeks of nicotine patch therapy , participants who received 24 weeks of treatment showed significantly less weight gain from pre-treatment to week 24 ( β=-4.76 , 95 % CI : -7.68 to -1.84 , p=.002 ) and significantly less weight gain from week 8 to week 24 ( β=-2.31 , 95 % CI : -4.39 to -0.23 , p=.03 ) . Extended treatment increased patch adherence which , in turn , reduced weight gain ; patch adherence accounted for 20 % of the effect of treatment arm on weight gain . CONCLUSION Compared to 8 weeks of transdermal nicotine therapy , 24 weeks of patch treatment may help to reduce the weight gain that is typical among smokers who are able to achieve abstinence from tobacco use . Extended treatment increased nicotine patch adherence which , in turn , reduced weight gain BACKGROUND Smoking during pregnancy causes many adverse pregnancy and birth outcomes . Nicotine replacement therapy ( NRT ) is effective for cessation outside pregnancy but efficacy and safety in pregnancy are unknown . We hypothesised that NRT would increase smoking cessation in pregnancy without adversely affecting infants . OBJECTIVES To compare ( 1 ) at delivery , the clinical effectiveness and cost-effectiveness for achieving biochemically vali date d smoking cessation of NRT patches with placebo patches in pregnancy and ( 2 ) in infants at 2 years of age , the effects of maternal NRT patch use with placebo patch use in pregnancy on behaviour , development and disability . DESIGN R and omised , placebo-controlled , parallel-group trial and economic evaluation with follow-up at 4 weeks after r and omisation , delivery and until infants were 2 years old . R and omisation was stratified by centre and a computer-generated sequence was used to allocate participants using a 1 : 1 ratio . Participants , site pharmacies and all study staff were blind to treatment allocation . SETTING Seven antenatal hospitals in the Midl and s and north-west Engl and . PARTICIPANTS Women between 12 and 24 weeks ' gestation who smoked ≥ 10 cigarettes a day before and ≥ 5 during pregnancy , with an exhaled carbon monoxide ( CO ) reading of ≥ 8 parts per million ( p.p.m . ) . INTERVENTIONS NRT patches ( 15 mg per 16 hours ) or matched placebo as an 8-week course issued in two equal batches . A second batch was dispensed at 4 weeks to those abstinent from smoking . MAIN OUTCOME MEASURES PARTICIPANTS self-reported , prolonged abstinence from smoking between a quit date and childbirth , vali date d at delivery by CO measurement and /or salivary cotinine ( COT ) ( primary outcome ) . Infants , at 2 years : absence of impairment , defined as no disability or problems with behaviour and development . Economic : cost per ' quitter ' . RESULTS One thous and and fifty women enrolled ( 521 NRT , 529 placebo ) . There were 1010 live singleton births and 12 participants had live twins , while there were 14 fetal deaths and no birth data for 14 participants . Numbers of adverse pregnancy and birth outcomes were similar in trial groups , except for a greater number of caesarean deliveries in the NRT group . Smoking : all participants were included in the intention-to-treat ( ITT ) analyses ; those lost to follow-up ( 7 % for primary outcome ) were assumed to be smoking . At 1 month after r and omisation , the vali date d cessation rate was higher in the NRT group { 21.3 % vs. 11.7 % , odds ratio [ OR ] , [ 95 % confidence interval ( CI ) ] for cessation with NRT , 2.05 [ 1.46 to 2.88]}. At delivery , there was no difference between groups ' smoking cessation rates : 9.4 % in the NRT and 7.6 % in the placebo group [ OR ( 95 % CI ) , 1.26 ( 0.82 to 1.96 ) ] . Infants : at 2 years , analyses were based on data from 888 out of 1010 ( 87.9 % ) singleton infants ( including four postnatal infant deaths ) [ 445/503 ( 88.5 % ) NRT , 443/507 ( 87.4 % ) placebo ] and used multiple imputation . In the NRT group , 72.6 % ( 323/445 ) had no impairment compared with 65.5 % ( 290/443 ) in placebo ( OR 1.40 , 95 % CI 1.05 to 1.86 ) . The incremental cost-effectiveness ratio for NRT use was £ 4156 per quitter ( £ 4926 including twins ) , but there was substantial uncertainty around these estimates . CONCLUSIONS Nicotine replacement therapy patches had no enduring , significant effect on smoking in pregnancy ; however , 2-year-olds born to women who used NRT were more likely to have survived without any developmental impairment . Further studies should investigate the clinical effectiveness and safety of higher doses of NRT . TRIAL REGISTRATION Current Controlled Trials IS RCT N07249128 . FUNDING This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol . 18 , No. 54 . See the NIHR Journals Library programme website for further project information A total of 424 smokers were r and omized in a 2 x 2 factorial experiment . A pharmacologic factor contained 2 levels : transdermal nicotine path ( TNP ; 21 mg ) and placebo . A self-help behavioral treatment factor contained 2 levels : video-enhanced self-help treatment manual and self-help treatment manual only . At 2 months , TNP produced a higher level of abstinence ( 36 % ) than placebo ( 20 % ) , p < .001 . No other comparison was significant . In secondary analyses , ( at 2 months ) and compliance with patch treatment regimen ( at 2 , 6 , and 12 months ) were associated with less relapse . Although nicotine replacement therapy has improved our ability to produce smoking cessation , the production of sustained , longer term abstinence remains an elusive goal In this follow-up of a r and omized placebo-controlled clinical trial of nicotine replacement transdermal patch for smoking cessation , 741 smokers of European ancestry who were r and omized to receive active patch or placebo patch were genotyped for the serotonin transporter gene-linked polymorphic region . The study setting was a primary care research network in Oxfordshire , United Kingdom . The primary outcome measures were biochemically verified sustained abstinence from cigarette smoking at end of treatment and 24-week follow-up . The main effect of genotype was not associated with sustained abstinence from smoking at either end of treatment ( SL : p=.33 ; SS : p=.81 ) or 24-week follow-up ( SL : p=.05 ; SS : p=.21 ) , and we found no evidence for a genotypextreatment interaction effect . In summary , despite the theoretically important contribution of serotonin neurotransmission to smoking cessation , the serotonin transporter gene was not associated with treatment response to nicotine patch for smoking cessation in this primary care-based trial BACKGROUND / AIMS Smoking cessation has been shown to be effective in r and omized controlled trials . It is unclear though , whether interventions also work in routine primary care . METHODS In 167 primary care setting s we conducted a r and omized four-armed smoking cessation trial to examine the efficacy of a minimal intervention ( MI ; n = 81 ) , cognitive-behavioral therapy ( CBT ; n = 175 ) , bupropion ( BUP ; n = 108 ) and nicotine replacements ( NRT ; n = 103 ) . Overall , 467 current smokers were enrolled . Abstinence rates at the end of treatment ( 12 weeks ) were 32.8 % for MI patients , 34.8 % for CBT , 35.3 % for NRT , and 46.5 % for BUP patients ( ITT , intention to treat ) ( no differential effects ) . Retention rates were highest in the BUP group ( 59.3 % ) and lowest in the NRT group ( 50.5 % ) . Completer findings were : MI , 56.4 % ; CBT , 64 % ; BUP , 79.3 % ; NRT , 69.2 % ( LOCF , lost to follow-up ) . No serious adverse events occurred during or after the medication phase . At 12-month follow-up continuous abstinence rates were : BUP , 29.0 % ; CBT , 20.9 % ; NRT , 29.6 % ; MI , 29.6 % . CONCLUSION Our findings suggest that established smoking cessation treatments are effective when applied by non-specialist primary care physicians . Our data supports a structured , multimodal treatment structure as core ingredient of successful smoking cessation in primary care Objective To examine the population effectiveness of nicotine replacement therapies ( NRTs ) , either with or without professional counselling , and provide evidence needed to better inform healthcare coverage decisions . Methods A prospect i ve cohort study was conducted in three waves on a probability sample of 787 Massachusetts adult smokers who had recently quit smoking . The baseline response rate was 46 % ; follow-up was completed with 56 % of the design ated cohort at wave 2 and 68 % at wave 3 . The relationship between relapse to smoking at follow-up interviews and assistance used , including NRT with or without professional help , was examined . Results About one-fourth of recent quitters at each wave reported to have relapsed by the subsequent interview . Odds of relapse were unaffected by use of NRT for > 6 weeks either with ( p=0.117 ) or without ( p=0.159 ) professional counselling and were highest among prior heavily dependent persons who reported NRT use for any length of time without professional counselling ( OR 2.68 ) . Conclusions This study finds that persons who have quit smoking relapsed at equivalent rates , whether or not they used NRT to help them in their quit attempts . Cessation medication policy should be made in the larger context of public health , and increasing individual treatment coverage should not be at the expense of population evidence -based programmes and policies Recent research on treatments to stop smoking has focused almost entirely on nicotine replacement , and several meta-analyses testify to the efficacy of four delivery systems.1 Although the ultimate goal of treatment is lifelong cessation , few trials have published results of abstinence beyond one year . Little consideration has therefore been given to whether the treatment is effective in reducing the major health risks of smoking . This effect would become evident only after many years of abstinence . Our r and omised trial showed that the use of nicotine nasal spray compared with a placebo spray was associated with more than double the number of abstainers at one year.2 We report the results from a longer term follow up to estimate the impact of relapse after one year on effectiveness . A total of 227 heavy smokers entered the trial ; 116 were given In a post hoc analysis of prior nicotine patch studies , we analysed findings in 357 subjects ( 43 recovering alcoholics , 314 non-alcoholics ) to determine if recovering alcoholic smokers were more nicotine dependent than non-alcoholics and whether the efficacy of nicotine patch therapy was comparable . The Self-Administered Alcoholism Screening Test was used to identify recovering alcoholics . Recovering alcoholics had significantly higher mean smoking rates ( cigarettes per day ) , Fagerström scores and baseline serum nicotine and cotinine than non-alcoholics . Among a subset of 240 subjects with a comparable treatment protocol , smoking cessation rates at the end of nicotine patch therapy were similar in recovering alcoholics ( 46 % ) and non-alcoholics ( 47 % ) receiving active 22 mg patches but higher than the respective placebo groups ( 17 % and 19 % ) . The 1-year rate was significantly ( p = 0.005 ) higher in the non-alcoholic group assigned to an active patch ( 31 % ) compared to placebo ( 14 % ) . For recovering alcoholics , the rates were lower and not significantly different ( active 0 % , placebo 11 % ) . Recovering alcoholic smokers are likely to be more nicotine dependent than non-alcoholic smokers but can achieve comparable short-term cessation rates with nicotine patch therapy . Use of an objective , vali date d measure of alcohol dependence is indicated in clinical trials when it is desirable to know whether the subjects are active or recovering alcoholics A double-blind trial on the effect of nicotine-containing chewing gum compared with a placebo gum in smoking cessation was organized in connection with smoking cessation course activity in North Karelia , Finl and . During the three-week course 70 % of the active group ( N = 84 ) and 54 % of the placebo group ( N = 76 ) stopped smoking ( P < 0.05 ) . A difference was found also after six months ( 35 % vs 28 % ) , although no more statistically significant . There were no major differences between the groups in the amount of withdrawal symptoms or side-effects BACKGROUND The purpose of this study was , to identify predictors of quitting following general practitioners ' ( GP ) anti-smoking counseling . METHODS We studied determinants ( characterized following the Precede framework ) of successful quitting ( 1 year sustained abstinence , biochemically confirmed at 6- and 12-month follow-up ) among 861 smokers r and omized to the intervention groups based on repeated counseling ( RC ) , RC + spirometric testing , and RC + nicotine gum , in a smoking cessation trial carried out in Turin , Italy . RESULTS GPs ' intervention worked best for male ( OR = 2.30 ; 95 % CI , 1.13 - 4.52 ) and married ( OR = 3.63 ; 95 % CI , 1.37 - 9.59 ) smokers , for smokers who had maintained abstinence for at least 1 month in the past ( OR = 6.78 ; 95 % CI , 1.56 - 29.52 ) or at their first quit attempt ( OR = 10.91 ; 95 % CI , 2.37 - 50.13 ) , and for those who spontaneously reduced their coffee consumption ( OR = 3.30 ; 95 % CI , 1.59 - 6.82 ) ; heavy smokers ( > = 20 cig/day OR = 0.48 ; 95 % CI , 0.24 - 0.93 ) and those living with other smokers ( > = 1 smokers in the household : OR = 0.44 ; 95 % CI , 0.22 - 0.90 ) were less likely to give up . Previous antismoking advice by the GP represented a strong barrier to success for healthy smokers ( OR = 0.19 ; 95 % CI , 0.07 - 0.52 ) , but not for those reporting symptoms of shortness of breath ( OR = 0.63 ; 95 % CI , 0.39 - 9.20 ) . There were no interactions between predictors and treatment conditions . CONCLUSIONS Assessment of factors influencing quitting would allow GPs to tailor their message to address existing barriers and to help patients utilize their re sources for change This article reports a series of r and omized controlled studies in four companies in the United Kingdom which were design ed to evaluate minimal smoking intervention programs based on the use of motivational videotapes or nicotine chewing gum . In the videotape studies , groups of smokers ( N = 603 ) were r and omly assigned to watch one of several different videotapes . They were followed-up , along with non participants ( N = 1,015 ) , at 3 months and again at 1 year , and a biochemical validation of abstinence was performed . There were significant differences between the videotape conditions with regard to attitudes assessed immediately after exposure ( intention and fear ) and the proportion of smokers who tried to stop , but there were no significant differences in cessation , even in the short term . Using a strict definition of abstinence , long-term abstinence rates were under 10 % in all four studies . In one company , we also investigated the effect of offering brief individual treatment based on nicotine chewing gum to a r and omly chosen 50 % sample of the videotape group ( N = 161 ) still smoking at the 3-month follow-up . The treatment course was administered by occupational health nurses and consisted of four short consultations over a 12-week period . The results were encouraging : 16 % of those who took the offer stopped during treatment and were still abstinent 1 year after the start of treatment compared with only 2 % of the r and omized no-intervention control group and 0 % of those who were invited but did not attend Previous research has linked depression to difficulties in smoking cessation . The authors followed 269 smokers who attempted to quit smoking for 3 months . Participants were given nicotine gum ( 2 or 4 mg ) or placebo gum and brief counseling . The study found that 34 % of the smokers met the criterion for current depression using the Center for Epidemiological Studies Depression Scale . Depressed smokers relapsed significantly earlier than the nondepressed . Nicotine gum was significantly more effective than placebo gum among all smokers . The benefits of nicotine gum were particularly apparent among the depressed . Only 12.5 % of depressed smokers quit successfully with placebo gum for 3 months , whereas 29.5 % quit with nicotine gum . Depressed smokers reported more stress , less coping re sources , more physical and psychological symptoms , and more frequent smoking in the presence of negative affect than did the nondepressed Nicotine replacement therapy ( NRT ) repeatedly has been shown to improve smoking treatment outcome . The major mechanism posited for this improvement in outcome is that NRT reduces nicotine craving and withdrawal . The authors tested this hypothesized mechanism of action using real-time data on craving and withdrawal , collected by ecological momentary assessment s administered on a palm-top computer . Smokers ( N = 324 ) were r and omized to receive either active high-dose ( 35 mg ) 24-hr patches or placebo . Increases in positive affect and decreases in craving , negative affect , and attention disturbance severity were related to lower risk of lapsing . Although NRT treatment did significantly decrease withdrawal and craving severity , these reductions only partially accounted for NRT 's impact on time to first lapse : The results from a mediation analysis showed that the hazard ratio for NRT , when controlling for withdrawal and craving severity , was only a third to a half lower than the uncontrolled hazard ratio for NRT alone . This suggests that other mechanisms for the effectiveness of NRT need to be examined BACKGROUND Nicotine replacement therapy ( NRT ) has been proven to be effective in heterogeneous groups of smokers . However , analyses have not specifically examined efficacy among light smokers ( < or = 15 cigarettes per day ) . The objective of this study is to assess the efficacy of a nicotine lozenge in light smokers . METHODS We conducted a secondary analysis of a r and omized , placebo-controlled clinical trial contrasting active 2 mg nicotine lozenge with placebo , and contrasting light smokers ( < or = 15 cigarettes per day ) with moderate-heavy smokers ( > 15 cigarettes per day ) . Participants were 917 smokers who smoked their first cigarette > 30 min after waking , and were r and omized to active ( n = 459 ) or placebo ( n = 458 ) lozenge . Biochemically verified continuous abstinence was measured at 6 weeks and 1 year . RESULTS Nicotine lozenge significantly increased quit rates relative to placebo at 6 weeks ( 45.7 % versus 31.1 % ; OR = 1.9 [ 1.3 - 2.8 ] ) and at 1 year ( 19.2 % versus 10.0 % ; OR = 2.3 [ 1.3 - 4.0 ] ) among light smokers . Efficacy among light smokers did not differ from that among heavier smokers ( ps>0.50 ) . CONCLUSION The nicotine lozenge is effective for light smokers The Freedom from Smoking clinic programs offered by the American Lung Association are in widespread use . These programs were developed in the 1970s prior to the availability of nicotine gum in the United States . It was hypothesized that the addition of nicotine gum to these clinics ( thereby including both behavioral and pharmacologic intervention ) would boost abstinence outcome significantly . Two-hundred and seventy-three persons were r and omly assigned to Freedom from Smoking clinics with or without prescription of nicotine gum . Abstinence outcomes at one week favored the nicotine gum conditions ( 86.3 % of nicotine gum subjects were abstinent as opposed to 70.9 % of comparison subjects , chi 2(1 ) = 9.79 , p = .002 ) . Effects for gum were no longer significant at later follow-ups , however , Overall duration and level of nicotine gum use were considerably less than optimal . In the absence of a placebo gum control group , expectancy can not be eliminated as a possible explanation of the short-term results AIMS Smokers who lapse during a cessation attempt are at particularly high risk of relapse , so interventions to help smokers recover from lapses are urgently needed . Two recent studies have suggested continuing to use nicotine patches following a lapse may be a beneficial relapse prevention strategy . However , to date no study that uses approved doses of nicotine patches under real-world conditions has tested this hypothesis . DESIGN AND SETTING Clinical trial conducted across eight US study sites . PARTICIPANTS AND MEASUREMENTS Using data from 509 subjects ( 240 active ; 269 placebo ) who lapsed during weeks 3 - 5 of treatment in a r and omized , double-blind placebo-controlled trial of 21-mg nicotine patches , we examined whether active nicotine patch use improved the chances of recovering abstinence ( 7-day point-prevalence ) at weeks 6 and 10 . FINDINGS Active patch use ( versus placebo ) increased the likelihood of recovery from a lapse both at 6 weeks [ 8.3 % versus 0.8 % ; relative risk ( RR ) = 11.0 , P < 0.001 ] and at 10 weeks ( 9.6 % versus 2.6 % ; RR = 3.7 , P < 0.001 ) . CONCLUSIONS Continuing treatment to aid smoking cessation with active patches promotes recovery from lapses . Smokers should be encouraged to persist with patch treatment if they lapse to smoking AIMS Effectiveness of nicotine replacement therapy ( NRT ) for smoking cessation has not been evaluated in low income countries , such as Syria , where it is expensive and not widely available . We evaluated whether nicotine patch boosts smoking cessation rates when used in conjunction with behavioral support in primary care clinics in Aleppo , Syria . DESIGN Two arm , parallel group , r and omized , placebo controlled , double-blinded multi-site trial . SETTING Four primary care clinics in Aleppo , Syria . PARTICIPANTS Two hundred and sixty-nine adult primary care patients received behavioral cessation counseling from a trained primary care physician and were r and omized to receive six weeks of treatment with nicotine versus placebo patch . MEASUREMENTS Primary end-points were prolonged abstinence ( no smoking after a 2-week grace period ) at end of treatment , and 6 and 12 months post-quit day , assessed by self-report and exhaled carbon monoxide levels of < 10 p.p.m . FINDINGS Treatment adherence was excellent and nicotine patch produced expected reductions in urges to smoke and withdrawal symptoms , but no treatment effect was observed . The proportion of patients in the nicotine and placebo groups with prolonged abstinence was 21.6 % and 20.0 % , respectively , at end of treatment , 13.4 % and 14.1 % at 6 months , and 12.7 % and 11.9 % at 12 months . CONCLUSIONS Nicotine patches may not be effective in helping smokers in low-income countries to stop when given as an adjunct to behavioural support BACKGROUND The use of nicotine chewing gum combined with psychological support improves the success rate in quitting smoking . We studied the safety and efficacy of a transdermal nicotine patch in smoking cessation . METHODS We conducted a double-blind r and omized study comparing the effects of a 16-hour nicotine patch ( 15 + /- 3.5 mg of nicotine in 16 hours ) with those of a placebo patch . Of the 289 smokers ( 207 women and 82 men ) enrolled in the study , 145 were treated with nicotine patches and 144 with placebo patches for 16 weeks . RESULTS Rates of sustained abstinence were significantly better with active treatment than with placebo : 53 , 41 , 24 , and 17 percent of those in the nicotine-patch group were abstinent after 6 , 12 , 26 , and 52 weeks , respectively , as compared with 17 , 10 , 5 , and 4 percent of those in the placebo-patch group ( P less than 0.0001 ) . Only two subjects with the nicotine patch and one with the placebo patch had to withdraw from the study because of side effects . CONCLUSIONS The nicotine skin patch proved to be safe and effective , as demonstrated by a higher rate of abstinence than with placebo . However , the absolute rate of abstinence after one year was only 17 percent , which is lower than the rate in studies that have combined the use of nicotine chewing gum with behavioral therapy Despite high smoking rates among those living in poverty , few cessation studies are conducted in these population s. This cluster-r and omized trial tested nicotine gum plus motivational interviewing ( MI ) for smoking cessation in 20 low-income housing developments ( HDs ) . Intervention participants ( 10 HDs , n = 66 ) received educational material s , 8 weeks of 4 mg nicotine gum , and 5 MI sessions on quitting smoking . Comparison participants ( 10 HDs , n = 107 ) received 5 MI sessions and educational material s addressing fruit and vegetable consumption . Participants had a mean age of 46.3 years and were predominantly female ( 70 % ) and African American ( 83 % ) . Biochemically-verified 7-day abstinence rates at 8 weeks were 6.1 % and 5.6 % in the intervention and comparison arms , respectively ( p = ns ) ; and at 26 weeks were 7.6 % and 9.3 % , respectively ( p = ns ) . Results suggest that nicotine gum plus MI were not effective for smoking cessation in low-income housing . Programs are needed to enhance the effectiveness of pharmacotherapy and counseling in underserved population BACKGROUND AND METHODS Use of nicotine-replacement therapies and the antidepressant bupropion helps people stop smoking . We conducted a double-blind , placebo-controlled comparison of sustained-release bupropion ( 244 subjects ) , a nicotine patch ( 244 subjects ) , bupropion and a nicotine patch ( 245 subjects ) , and placebo ( 160 subjects ) for smoking cessation . Smokers with clinical depression were excluded . Treatment consisted of nine weeks of bupropion ( 150 mg a day for the first three days , and then 150 mg twice daily ) or placebo , as well as eight weeks of nicotine-patch therapy ( 21 mg per day during weeks 2 through 7 , 14 mg per day during week 8 , and 7 mg per day during week 9 ) or placebo . The target day for quitting smoking was usually day 8 . RESULTS The abstinence rates at 12 months were 15.6 percent in the placebo group , as compared with 16.4 percent in the nicotine-patch group , 30.3 percent in the bupropion group ( P<0.001 ) , and 35.5 percent in the group given bupropion and the nicotine patch ( P<0.001 ) . By week 7 , subjects in the placebo group had gained an average of 2.1 kg , as compared with a gain of 1.6 kg in the nicotine-patch group , a gain of 1.7 kg in the bupropion group , and a gain of 1.1 kg in the combined-treatment group ( P<0.05 ) . Weight gain at seven weeks was significantly less in the combined-treatment group than in the bupropion group and the placebo group ( P<0.05 for both comparisons ) . A total of 311 subjects ( 34.8 percent ) discontinued one or both medications . Seventy-nine subjects stopped treatment because of adverse events : 6 in the placebo group ( 3.8 percent ) , 16 in the nicotine-patch group ( 6.6 percent ) , 29 in the bupropion group ( 11.9 percent ) , and 28 in the combined-treatment group ( 11.4 percent ) . The most common adverse events were insomnia and headache . CONCLUSIONS Treatment with sustained-release bupropion alone or in combination with a nicotine patch result ed in significantly higher long-term rates of smoking cessation than use of either the nicotine patch alone or placebo . Abstinence rates were higher with combination therapy than with bupropion alone , but the difference was not statistically significant BACKGROUND Transdermal nicotine therapy is widely used to aid smoking cessation , but there is uncertainty about its safety in patients with cardiac disease . METHODS In a r and omized , double-blind , placebo-controlled trial at 10 Veterans Affairs medical centers , we r and omly assigned 584 out patients ( of whom 576 were men ) with at least one diagnosis of cardiovascular disease to a 10-week course of transdermal nicotine or placebo as an aid to smoking cessation . The subjects were monitored for a total of 14 weeks for the primary end points of the study ( death , myocardial infa rct ion , cardiac arrest , and admission to the hospital due to increased severity of angina , arrhythmia , or congestive heart failure ) ; the secondary end points ( admission to the hospital for other reasons and outpatient visits necessitated by increased severity of heart disease ) ; any side effects of therapy ; and abstinence from smoking . RESULTS There were 48 primary and 78 secondary end points noted in a total of 95 subjects . At least one of the primary end points was reached by 5.4 percent of the subjects in the nicotine group and 7.9 percent of the subjects in the placebo group ( difference , 2.5 percent ; 95 percent confidence interval , -1.6 to 6.5 percent ; P=0.23 ) . In the nicotine group , 11.9 percent of the subjects had at least one of the secondary end points , as compared with 9.7 percent in the placebo group ( difference , 2.2 percent ; 95 percent confidence interval , -2.2 to 7.4 percent ; P= 0.37 ) . After 14 weeks the rate of abstinence from smoking was 21 percent in the nicotine group , as compared with 9 percent in the placebo group ( P=0.001 ) , but after 24 weeks the abstinence rates were not significantly different ( 14 percent vs. 11 percent , P= 0.67 ) . CONCLUSIONS Transdermal nicotine does not cause a significant increase in cardiovascular events in high-risk out patients with cardiac disease . However , the efficacy of transdermal nicotine as an aid to smoking cessation in such patients is limited and may not be sustained over time This study evaluated the relationship between precessation depressed mood and smoking abstinence and assessed the mediation of this effect by postcessation self-efficacy , urges to smoke , nicotine withdrawal , and coping behavior . The sample included 121 smokers previously treated in a r and omized controlled trial involving behavior therapy and the nicotine patch . The results showed that precessation depressed mood was inversely related to 6-month abstinence . This effect remained significant after controlling for treatment , possible depression history , baseline smoking rates , and several other demographic factors . Postcessation self-efficacy , at the 2- , 4- , and 8-week postquit assessment s , was the strongest mediator of the effects of precessation depressed mood on abstinence , accounting for 32 % , 38 % , and 48 % of the effect of mood on abstinence , respectively Laboratory trials have demonstrated the efficacy of nicotine replacement in smoking cessation but absolute success rates are low . For many , nicotine gum is hard to use and transdermal nicotine is slow-acting and passive . A new , faster-acting nicotine nasal spray ( NNS ) can provide easily self-administered relief from cigarette withdrawal . The NNS was tested for safety and efficacy in smoking cessation . Two hundred and fifty-five smokers were r and omized to NNS or a piperine placebo . Drug use was limited to 8 - 32 doses/day for 6 months . Subjects were tested while smoking and at post-cessation daily ( week 1 ) with follow-up at weeks 2 , 3 , 6 and at 3 months , 6 months and 1 year . Continuous abstinence analyses ( CO < or = 8 ppm ; no slips ) showed that NNS significantly enhanced success rates over placebo overall ( p < 0.001 ) and at all test intervals . Differences at key intervals between active and placebo were : 63 % vs. 40 % ( day 5 ) , 51 % vs. 30 % ( week 3 ) , 43 % vs. 20 % ( 6 weeks ) , 34 % vs. 13 % ( 3 months ) , 25 % vs. 10 % ( 6 months ) and 18 % vs. 8 % ( 1 year ) . Side effects were common but tolerable . Cotinine measures showed that replacement of nicotine approximated 30 % of smoking levels . Hazard functions revealed relapse risks peaked at day 1 , day 5 and 3 weeks for strict abstinence . It is concluded NNS is safe , efficacious and a viable alternative treatment for smoking cessation Background Partial adherence in Internet smoking cessation interventions presents treatment and evaluation challenges . Increasing adherence may improve outcomes . Purpose To present smoking outcomes from an Internet r and omized trial of two strategies to encourage adherence to tobacco dependence treatment components : ( i ) a social network ( SN ) strategy to integrate smokers into an online community and ( ii ) free nicotine replacement therapy ( NRT ) . In addition to intent-to-treat analyses , we used novel statistical methods to distinguish the impact of treatment assignment from treatment utilization . Methods A total of 5,290 current smokers on a cessation website ( WEB ) were r and omized to WEB , WEB + SN , WEB + NRT , or WEB + SN + NRT . The main outcome was 30-day point prevalence abstinence at 3 and 9 months post-r and omization . Adherence measures included self-reported medication use ( meds ) , and website metrics of skills training ( sk ) and community use ( comm ) . Inverse Probability of Retention Weighting and Inverse Probability of Treatment Weighting jointly addressed dropout and treatment selection . Propensity weights were used to calculate Average Treatment effects on the Treated . Results Treatment assignment analyses showed no effects on abstinence for either adherence strategy . Abstinence rates were 25.7%-32.2 % among participants that used all three treatment components ( sk+comm + meds).Treatment utilization analyses revealed that among such participants , sk+comm+meds yielded large percentage point increases in 3-month abstinence rates over sk alone across arms : WEB = 20.6 ( 95 % CI = 10.8 , 30.4 ) , WEB + SN = 19.2 ( 95 % CI = 11.1 , 27.3 ) , WEB + NRT = 13.1 ( 95 % CI = 4.1 , 22.0 ) , and WEB + SN + NRT = 20.0 ( 95 % CI = 12.2 , 27.7 ) . Conclusions Novel propensity weighting approaches can serve as a model for establishing efficacy of Internet interventions and yield important insights about mechanisms . Clinical Trials.gov NCT01544153 BACKGROUND The SNAP ( Smoking and Nicotine in Pregnancy ) trial compared nicotine replacement therapy ( NRT ) patches with placebo in pregnant smokers ; although NRT doubled cessation rates in the first 4 weeks , by delivery no differences in maternal smoking or birth outcomes were noted . As a result , NRT used in st and ard doses during pregnancy is considered ineffective for smoking cessation . Subsequent effects of NRT on the children of treated mothers are unknown because no trials have investigated the effect of gestational NRT use beyond birth . To assess whether NRT use in pregnancy might cause harm to infants , we aim ed to compare effects of NRT and placebo on infant development 2 years after delivery . METHODS 1050 pregnant smokers aged 16 - 45 years , at 12 - 24 weeks ' gestation , and smoking at least five cigarettes per day were recruited from seven hospitals in Engl and between May 1 , 2007 , and Feb 26 , 2010 , and followed up until their infants were 2 years old . Participants were r and omly assigned ( 1:1 ) to receive up to 8-weeks treatment with NRT ( 15 mg/16 h transdermal patches ) or identically packaged and visually matched placebo patches ( all patches manufactured by and purchased at market rate from United Pharmaceuticals , Amman , Jordan ) , issued as two 4-week supplies ( 521 for NRT group , 529 for placebo group ) [ Corrected ] . R and omisation was stratified by site with participants , health-care professionals , and research staff masked to treatment allocation . The primary results for participants and infants at delivery were published in 2012 ; we present results from the trial cohort 2 years after birth . After delivery , question naires were posted to participants and , if there was no response , to family physicians . The primary outcome at 2 years was infants ' survival without developmental impairment ( ie , no disability or problems with behaviour or development ) . Treatment groups were compared on an intention-to-treat basis . The trial is registered with Controlled-Trials.com , number IS RCT N07249128 . FINDINGS Question naires were returned at 2 years for 891 ( 88 % ) of 1010 live singleton births ( 445 of ( 88 % ) 503 given NRT and 446 ( 88 % ) of 507 given placebo ) . Because of missing data , developmental outcomes , including four infant deaths , were documented for 888 of ( 88 % ) 1010 singleton infants ; 445 ( 88 % ) of 503 infants in NRT group and 443 ( 87 % ) of 507 infants in placebo . In the NRT group , 323 ( 73 % ) of 445 infants had no impairment compared with 290 ( 65 % ) of 443 infants in the placebo group ( odds ratio [ OR ] 1.40 , 95 % CI 1.05 - 1.86 , p=0.023 ) . At 2 years , 15 ( 3 % ) of 521 mothers in the NRT group and nine ( 2 % ) of 529 mothers in the placebo groups self-reported prolonged smoking abstinence since a quit date set in pregnancy ( OR 1.71 , 95 % CI 0.74 - 3.94 , p=0.20 ) . Adverse events were not collected after delivery , but previously reported adverse pregnancy and birth outcomes were similar in the two groups . INTERPRETATION Infants born to women who used NRT for smoking cessation in pregnancy were more likely to have unimpaired development . NRT had no effect on prolonged abstinence from smoking but did cause a temporary doubling of smoking cessation shortly after r and omisation during pregnancy , which could explain findings . If findings are confirmed by subsequent research , this has potential implication s for the management of smoking in pregnancy . FUNDING National Institute for Health Research Health Technology Assessment Programme OBJECTIVE The authors conducted a r and omized , placebo-controlled study of nicotine replacement therapy for the reduction of agitation and aggression in smokers with schizophrenia . METHOD Participants were 40 smokers 18 - 65 years of age admitted to a psychiatric emergency service with a diagnosis of schizophrenia confirmed by the Mini International Neuropsychiatric Interview . Patients were screened for agitation with the excited component subscale of the Positive and Negative Syndrome Scale ( PANSS ) and for nicotine dependence with the Fagerström Test for Nicotine Dependence . A score of at least 14 on the PANSS excited component subscale and at least 6 on the Fagerström test were required for study eligibility . Participants in the nicotine replacement group received a 21-mg nicotine transdermal patch , and those in the placebo group were treated with a placebo patch . Participants received usual care with antipsychotics . The Agitated Behavior Scale and other agitation measures were administered at baseline and again at 4 and 24 hours . RESULTS At baseline , participants were at least moderately agitated , and 28 % reported aggressive behavior in the previous week . The mean Agitated Behavior Scale score for the nicotine replacement group was 33 % lower at 4 hours and 23 % lower at 24 hours than for the placebo group . Participants with lower levels of nicotine dependence responded better than those with higher levels of dependence . CONCLUSIONS The drug-placebo difference in this study was similar to that obtained in trials of parenteral antipsychotics in similar population s. This finding suggests that in patients with schizophrenia , smoking status should be included in the assessment of agitation and nicotine replacement included in the treatment of those who are smokers |
12,370 | 18,254,124 | Results showed no evidence that abstinence-plus programs can affect self-reported sexually transmitted infection ( STI ) incidence , and limited evidence that programs can reduce self-reported pregnancy incidence .
Consistently favorable program effects were found for HIV knowledge .
No adverse effects were observed .
Many abstinence-plus programs appear to reduce short-term and long-term HIV risk behavior among youth in high-income countries .
Evidence for program effects on biological measures is limited .
Evaluations consistently show no adverse program effects for any outcomes , including the incidence and frequency of sexual activity . | BACKGROUND Abstinence-plus interventions promote sexual abstinence as the best means of preventing acquisition of HIV , but also encourage safer-sex strategies ( eg condom use ) for sexually active participants .
OBJECTIVES To assess the effects of abstinence-plus programs for HIV prevention in high-income countries . | Acquired immunodeficiency syndrome ( AIDS ) continues to be a significant concern for adolescents , especially in minority population s. There is a scarcity of knowledge of the cultural context of sexual behavior in this age group and the influences that lead to early initiation of sex and unsafe sex . Few efforts targeting young adolescents have been community based , although there has been an increased awareness of the need for such research and intervention programs . Four key processes have been defined in gaining community participation in health education programs : ( a ) defining the community and reaching the community ; ( b ) recognizing tensions among service , research , and community participation ; ( c ) involving community residents ; and ( d ) considering cultural differences in a community . These processes are used to describe the " Focus on Kids " project , a human immunodeficiency virus ( HIV ) risk reduction intervention that result ed in significant increases in condom use demonstrated by a r and omized controlled trial To comprehend the results of a r and omised controlled trial ( RCT ) , readers must underst and its design , conduct , analysis , and interpretation . That goal can be achieved only through total transparency from authors . Despite several decades of educational efforts , the reporting of RCTs needs improvement . Investigators and editors developed the original CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to help authors improve reporting by use of a checklist and flow diagram . The revised CONSORT statement presented here incorporates new evidence and addresses some criticisms of the original statement . The checklist items pertain to the content of the Title , Abstract , Introduction , Methods , Results , and Discussion . The revised checklist includes 22 items selected because empirical evidence indicates that not reporting this information is associated with biased estimates of treatment effect , or because the information is essential to judge the reliability or relevance of the findings . We intended the flow diagram to depict the passage of participants through an RCT . The revised flow diagram depicts information from four stages of a trial ( enrolment , intervention allocation , follow- up , and analysis ) . The diagram explicitly shows the number of participants , for each intervention group , included in the primary data analysis . Inclusion of these numbers allows the reader to judge whether the authors have done an intention- to-treat analysis . In sum , the CONSORT statement is intended to improve the reporting of an RCT , enabling readers to underst and a trial 's conduct and to assess the validity of its results OBJECTIVE To test the efficacy of a prevention intervention to reduce sexual risk behavior among Latino adolescents . DESIGN R and omized controlled trial from April 2000 through March 2003 , with data collection before and after intervention and at 3 , 6 , and 12 months . SETTING Northeast Philadelphia schools . PARTICIPANTS Latinos aged 13 through 18 years ( 249 males and 304 females ) ; 81.6 % retained at 12-month follow-up . INTERVENTIONS The HIV and health-promotion control interventions consisted of six 50-minute modules delivered by adult facilitators to small , mixed-gender groups in English or Spanish . Main Outcome Measure Self-reported sexual behavior . RESULTS Analyses using generalized estimation equations over the follow-up period revealed that adolescents in the HIV intervention were less likely to report sexual intercourse ( odds ratio , 0.66 ; 95 % confidence interval [ CI ] , 0.46 - 0.96 ) , multiple partners ( odds ratio , 0.53 ; 95 % CI , 0.31 - 0.90 ) , and days of unprotected intercourse ( relative risk , 0.47 ; 95 % CI , 0.26 - 0.84 ) and more likely to report using condoms consistently ( odds ratio , 1.91 ; 95 % CI , 1.24 - 2.93 ) . Baseline sexual experience and language use moderated intervention efficacy . Adolescents assigned to the HIV intervention who were sexually inexperienced at baseline reported fewer days of unprotected sex ( relative risk , 0.22 ; 95 % CI , 0.08 - 0.63 ) ; Spanish speakers were more likely to have used a condom at last intercourse ( odds ratio , 4.73 ; 95 % CI , 1.72 - 12.97 ) and had a greater proportion of protected sex ( mean difference , 0.35 ; P<.01 ) compared with similar adolescents in the health-promotion intervention . CONCLUSION Results provide evidence for the efficacy of HIV intervention in decreasing sexual activity and increasing condom use among Latino adolescents The aim of this project was to conduct an initial evaluation among sexually transmitted disease ( STD ) patients of the psychometric properties of two instruments : the National Institute of Mental Health ( NIMH ) multisite condom use self-efficacy scale and the NIMH multisite condom use outcome expectancy scale . The condom use self-efficacy scale was design ed to measure one 's degree of confidence in various aspects of condom use , whereas the outcome expectancy scale was design ed to measure one 's belief about the consequences of using condoms . Using a sample of 641 patients from five geographically diverse STD clinics in the eastern United States , initial reliability coefficients were computed . The alpha coefficient for the self-efficacy scale was .91 and for the outcome expectancy scale .88 , indicating high internal consistency for both scales . Both scales were analyzed using common factor analytic procedures . Five factors emerged from the analysis of the self-efficacy scale and six factors from the analysis of the outcome expectancy scale . Reliability coefficients for the individual factors ranged from .76 to .86 . Construct validity of each scale was assessed by hypothesis testing . As predicted , participants with higher levels of self-efficacy and more positive outcome expectancies were more likely to use condoms A series of interactive videodisc programs design ed to reduce HIV/STD risk behaviors was developed and evaluated . Separate programs were developed for each of three race/ethnicities ( African American , Hispanic , and Caucasian ) at each of two age levels ( middle school and high school ) using extensive formative procedures . Each program uses scenarios with extensive branching story lines to teach decision-making skills and socially appropriate responses to potentially risky sexual situations . In a r and omized experiment with 827 students , significant changes were observed at posttest for the four constructs assessed : ( 1 ) belief that sex occurs as a result of decisions ( vs. " it just happens " ) , ( 2 ) belief that even a single incident of unprotected sex can result in an STD or pregnancy , ( 3 ) intentions and attitudes toward use of condoms , and ( 4 ) self-efficacy in remaining abstinent ( i.e. , avoiding sex ) . At 30-day follow-up , three of the four measures remained significant OBJECTIVE To determine whether the addition of a parental monitoring intervention ( Informed Parents and Children Together [ ImPACT ] ) alone or with " boosters " could enhance ( either broaden or sustain or both ) the effect of a small group , face-to-face adolescent risk reduction intervention Focus on Kids ( FOK ) . METHODS A longitudinal , r and omized , community-based cohort study was conducted of 35 low-income , community-based , in-town setting s. A total of 817 black youths aged 12 to 16 years at baseline were studied . After completion of baseline measures , youths were r and omized to receive a face-to-face intervention alone ( FOK only ) , a face-to-face intervention and a parental monitoring intervention ( FOK plus ImPACT ) , or both of the above plus boosters ( FOK plus ImPACT plus boosters ) . Risk and protective behaviors were assessed at 6 and 12 months after intervention . RESULTS At 6 months ' follow-up , youths in families that were assigned to FOK plus ImPACT reported significantly lower rates of sexual intercourse , sex without a condom , alcohol use , and cigarette use and marginally lower rates of " risky sexual behavior " compared with youths in families that were assigned to FOK only . At 12 months after intervention , rates of alcohol and marijuana use were significantly lower and cigarette use and overall risk intention were marginally lower among FOK plus ImPACT youths compared with FOK only youths . With regard to the boosters delivered at 7 and 10 months , 2 risk behaviors -- use of crack/cocaine and drug selling -- were significantly lower among the youths who were assigned to receive the additional boosters compared with youths without the boosters . The rates of the other risk behaviors and intentions did not differ significantly . CONCLUSIONS The results of this r and omized , controlled trial indicate that the inclusion of a parental monitoring intervention affords additional protection from involvement in adolescent risk behaviors 6 and 12 months later compared with the provision of an intervention that targets adolescents only . At the same time , the results of the present study do not provide sufficient evidence that booster sessions further improve targeted behaviors enough to include them in a combined parent and youth intervention Few studies have tested schoolwide interventions to reduce sexual risk behavior , and none have demonstrated significant schoolwide effects . This study evaluates the schoolwide effects of Safer Choices , a multicomponent , behavioral theory – based HIV , STD , and pregnancy prevention program , on risk behavior , school climate , and psychosocial variables . Twenty urban high schools were r and omized , and cross-sectional sample s of classes were surveyed at baseline , the end of intervention ( 19 months after baseline ) , and 31 months after baseline . At 19 months , the program had a positive effect on the frequency of sex without a condom . At 31 months , students in Safer Choices schools reported having sexual intercourse without a condom with fewer partners . The program positively affected psychosocial variables and school climate for HIV/STD and pregnancy prevention . The program did not influence the prevalence of recent sexual intercourse . Schoolwide changes in condom use demonstrated that a school-based program can reduce the sexual risk behavior of adolescents BACKGROUND Although numerous interventions have been demonstrated to reduce targeted adolescent risk behaviors for brief periods , sustained behavior changes covering multiple risk behaviors have been elusive . OBJECTIVE To determine whether a parental monitoring intervention ( Informed Parents and Children Together [ ImPACT ] ) with and without boosters can further reduce adolescent truancy , substance abuse , and sexual risk behaviors and can alter related perceptions 24 months after intervention among youth who have all received an adolescent risk-reduction intervention , Focus on Kids ( FOK ) . DESIGN R and omized , controlled , 3-celled longitudinal trial . SETTING Thirty-five low-income , urban community sites . PARTICIPANTS Eight hundred seventeen African American youth aged 13 to 16 at baseline . Intervention All youth participated in FOK , an 8-session , theory-based , small group , face-to-face risk-reduction intervention , 496 youth and parents received the 1-session ImPACT intervention ( a videotape and discussion ) , 238 of the ImPACT youth also received four 90-minute FOK boosters delivered in small groups . MAIN OUTCOME MEASURES Responses at baseline and 24 months after intervention to a question naire assessing risk and protective behaviors and perceptions . Analyses used General Linear Modeling , intraclass correlation coefficient , analysis of covariance , and multiple comparisons with least significant difference test adjustment . RESULTS After adjusting for the intraclass correlation coefficient , 6 of 16 risk behaviors were significantly reduced ( P < or = .05 ) among youth receiving ImPACT compared with youth who only received FOK ( respectively , mean number of days suspended , 0.65 vs 1.17 ; carry a bat as a weapon , 4.1 % vs 9.6 % ; smoked cigarettes , 12.5 % vs 22.7 % ; used marijuana , 18.3 % vs 26.8 % ; used other illicit drugs , 1.4 % vs 5.6 % ; and , asked sexual partner if condom always used , 77.9 % vs 64.9 % ) . Four of the 7 theory-based subscales reflected significant protective changes among youth who received ImPACT . ImPACT did not produce any significant adverse effects on behaviors or perceptions . CONCLUSION A parent monitoring intervention can significantly broaden and sustain protection beyond that conferred through an adolescent risk-reduction intervention PURPOSE To identify correlates of sexual risk variations among African-American adolescents , and to examine the influence of prior sexual experience on response to a HIV risk-reduction intervention . METHODS Eight hundred seventeen African-American youth aged 13 to 16 years living in and around urban public housing in Baltimore were recruited to participate in a HIV risk-reduction intervention targeting multiple risk behaviors . An instrument design ed to measure three levels of sexual risk ( " abstinent , " " protected sex " [ having sex with a condom ] , and " unprotected sex " [ having sex without a condom ] ) was administered at baseline , 6 months and 12 months postintervention . Multiple regression analyses were conducted to identify predictors of the degree of sexual risk using longitudinal data . Repeated measure analyses were conducted to assess behavioral changes over time among the three groups . RESULTS Data confirmed the co-variation of sexual risk behavior and other problem behaviors among adolescents , cross-sectionally and longitudinally . After exposure to an 8-session risk-reduction intervention , youth engaging in the highest degree of sexual risk demonstrated the greatest reduction in both sexual risk and other risks . These improvements were seen at both 6 months and 12 months postintervention . Youth who were abstinent at baseline maintained the lowest levels in risk involvement throughout the study period when compared with sexually active youth . However , abstinent youth risk involvement significantly increased at 6 months and 12 months after baseline . Youth engaging in protected sex at baseline demonstrated a significant increase in non-condom use and a significant decrease in multiple risk involvement over time . CONCLUSIONS Results support HIV risk-reduction intervention efforts that target multiple risk behaviors . Response of adolescents to the intervention is directly related to the sexual risk behavior at baseline . These data may suggest that the response to risk behavior intervention depends in part on the risk behavior profile of the population to which it is being applied The effectiveness of an intervention based upon the theories of Ajzen and Tri and is was evaluated among 698 junior and 306 senior high school students . The intervention to juniors was offered by senior students who were trained during a course integrated into the school curriculum . Respondents in the control and experimental groups completed a question naire at baseline and 9 months after the program . Compared to junior respondents in the control group , those in the experimental group positively modified their attitude , perceived behavioral control , personal normative beliefs , perceived role beliefs , anticipated regret and intention with respect to postponing sexual intercourse and with respect to condom use , as well as perceived self-efficacy to negotiate both behaviors . Compared to senior respondents in the control group , those in the experimental group showed a significant positive modification of all the above variables except perceived behavioral control ( indirect measure ) , anticipated regret and intention with respect to postponing sexual intercourse . At post-test , seniors in the experimental group were more likely to use condoms on a regular basis than those in the control group . Program effects occurred among both sexes , but a few differences in response were observed among males and females . Results suggest this type of theory-based program is effective in modifying psychosocial variables related to postponing sexual intercourse and related to condom use among adolescents . Personal involvement in design ing intervention appears to be effective in modifying the behavior of peer educators CONTEXT African American adolescents are at high risk of contracting sexually transmitted infection with human immunodeficiency virus ( HIV ) , but which behavioral interventions to reduce risk are most effective and who should conduct them is not known . OBJECTIVE To evaluate the effects of abstinence and safer-sex HIV risk-reduction interventions on young inner-city African American adolescents ' HIV sexual risk behaviors when implemented by adult facilitators as compared with peer cofacilitators . DESIGN R and omized controlled trial with 3- , 6- , and 12-month follow-up . SETTING Three middle schools serving low-income African American communities in Philadelphia , Pa. PARTICIPANTS A total of 659 African American adolescents recruited for a Saturday program . INTERVENTIONS Based on cognitive-behavioral theories and elicitation research , interventions involved 8 1-hour modules implemented by adult facilitators or peer cofacilitators . Abstinence intervention stressed delaying sexual intercourse or reducing its frequency ; safer-sex intervention stressed condom use ; control intervention concerned health issues unrelated to sexual behavior . MAIN OUTCOME MEASURES Self-reported sexual intercourse , condom use , and unprotected sexual intercourse . RESULTS Mean age of the enrollees was 11.8 years ; 53 % were female and 92.6 % were still enrolled at 12 months . Abstinence intervention participants were less likely to report having sexual intercourse in the 3 months after intervention than were control group participants ( 12.5 % vs 21.5 % , P=.02 ) , but not at 6- or 12-month follow-up ( 17.2 % vs 22.7 % , P=.14 ; 20.0 % vs 23.1 % , P=.42 , respectively ) . Safer-sex intervention participants reported significantly more consistent condom use than did control group participants at 3 months ( odds ratio [OR]=3.38 ; 95 % confidence interval [ CI ] , 1.25 - 9.16 ) and higher frequency of condom use at all follow-ups . Among adolescents who reported sexual experience at baseline , the safer-sex intervention group reported less sexual intercourse in the previous 3 months at 6- and 12-month follow-up than did control and abstinence intervention ( adjusted mean days over prior 3 months , 1.34 vs 3.77 and 3.03 , respectively ; P < or = .01 at 12- month follow-up ) and less unprotected intercourse at all follow-ups than did control group ( adjusted mean days , 0.04 vs 1.85 , respectively , P<.001 , at 12-month follow-up ) . There were no differences in intervention effects with adult facilitators as compared with peer cofacilitators . CONCLUSION Both abstinence and safer-sex interventions can reduce HIV sexual risk behaviors , but safer-sex interventions may be especially effective with sexually experienced adolescents and may have longer-lasting effects CONTEXT Despite the recent declines in rates of teenage pregnancy , relatively little is known about the few programs that have been successful in reducing adolescent pregnancy . METHODS Six agencies in New York City each r and omly assigned 100 disadvantaged 13 - 15-year-olds to their usual youth program or to the intervention being tested -- the Children 's Aid Society-Carrera program , a year-round afterschool program with a comprehensive youth development orientation . Both program and control youth were followed for three years . Multivariate regression analyses assessed the effects of program participation on the odds of current sexual activity , use of a condom along with a hormonal contraceptive , pregnancy and access to good health care . RESULTS Seventy-nine percent of participants remained in the program for three full years . Female program participants had significantly lower odds than controls of being sexually active ( odds ratio , 0.5 ) and of having experienced a pregnancy ( 0.3 ) . They had significantly elevated odds of having used a condom and a hormonal method at last coitus ( 2.4 ) . However , participation in the program created no significant impact on males ' sexual and reproductive behavior outcomes . Nonetheless , program participants of both genders had elevated odds of having received good primary health care ( 2.0 - 2.1 ) . CONCLUSIONS This program is one of only four whose evaluation has successfully documented declines in teenage pregnancy using a r and om-assignment design . Better outcomes among males may be achieved if programs reach them even earlier than their teenage years Substance-dependent adolescents ( N = 34 ) in a residential drug treatment facility received either a 6-session behavior skills training HIV-risk reduction intervention or st and ard HIV education . After the intervention , adolescents who received behavior skills training exhibited increased knowledge about HIV-AIDS , more favorable attitudes toward prevention and condom use , more internal locus of control , increased self-efficacy , increased recognition of HIV risk and decreases in high-risk sexual activity . Self-report data were corroborated by records for the treatment of sexually transmitted diseases . The results from this pilot demonstration effort suggest that skills training based on cognitive-behavioral principles may be effective in lowering high-risk adolescents ' vulnerability to HIV infection and warrant evaluation in a controlled comparison with a larger sample Objectives : Youth are increasingly at risk for contracting HIV infection , and community-level interventions are needed to reduce behavioral risk . Design : A r and omized , controlled , multi-site community-level intervention trial was undertaken with adolescents living in 15 low-income housing developments in five US cities . Methods : Baseline ( n = 1172 ) , short-term follow-up ( n = 865 ) , and long-term follow-up ( n = 763 ) risk assessment s were conducted among adolescents , ages 12–17 , in all 15 housing developments . The developments were r and omly assigned in equal numbers to each of three conditions : experimental community-level intervention ( five developments ) ; ‘ state-of-the-science ’ skills training workshops ( five developments ) ; and , education-only delayed control intervention ( five developments ) . Results : At long-term follow-up , adolescents living in the housing developments receiving the community-level intervention were more likely to delay onset of first intercourse ( 85 % ) than those in the control developments ( 76 % ) , while those in the workshop developments ( 78 % ) did not differ from control condition adolescents . Adolescents in both the community-level intervention ( 77 % ) and workshop ( 76 % ) developments were more likely to use a condom at last intercourse than those in control ( 62 % ) developments . Conclusions : Community-level interventions that include skills training and engage adolescents in neighborhood-based HIV prevention activities can produce and maintain reductions in sexual risk behavior , including delaying sexual debut and increasing condom use CONTEXT Initiation of sexual intercourse prior to high school is prevalent among inner-city black and Hispanic youths , and has multiple negative health and social consequences . A promising strategy for addressing early adolescent sexual activity is parent education that addresses normal pubertal changes and the challenges of becoming a teenager . METHODS A 2003 - 2005 r and omized trial to test the effectiveness of Saving Sex for Later , a parent education program presented on three audio CDs , enrolled 846 families with fifth- and sixth- grade students in seven New York City schools . Parent and youth surveys were conducted at baseline and three months postintervention . Multivariate logistic and linear regression analyses were performed to assess relationships between youth and parent outcomes and treatment condition . RESULTS At follow-up , parents in the intervention group were significantly more likely than controls to score high on indexes of communication with children about targeted risk behaviors , self-efficacy to discuss pubertal development and sexuality , and perceived influence over youths ' behaviors ( odds ratios , 1.9 - 2.5 ) . Youths in the intervention condition were more likely than controls to report high family support , and reported more family rules and fewer behavioral risks . Family support and rules partially mediate the relationship between treatment condition and behavioral risks . CONCLUSION Saving Sex for Later is a promising intervention for promoting youths ' sexual abstinence . The intervention may also be effective in enhancing positive parenting practice s among parents who are typically difficult to reach because of economic hardship , full schedules and complicated lives Two hundred forty-six African American adolescents were r and omly assigned to an educational program or an 8-week intervention that combined education with behavior skills training including correct condom use , sexual assertion , refusal , information provision , self-management , problem solving , and risk recognition . Skill-trained participants ( a ) reduced unprotected intercourse , ( b ) increased condom-protected intercourse , and ( c ) displayed increased behavioral skills to a greater extent than participants who received information alone . The patterns of change differed by gender . Risk reduction was maintained 1 year later for skill-trained youths . It was found that 31.1 % of youths in the education program who were abstinent at baseline had initiated sexual activity 1 year later , whereas only 11.5 % of skills training participants were sexually active . The results indicate that youths who were equipped with information and specific skills lowered their risk to a greater degree , maintained risk reduction changes better , and deferred the onset of sexual activity to a greater extent than youths who received information alone Background and Objectives : Condom use is one of the most important preventive measures sex workers can take to reduce the risk of becoming infected with a sexually transmitted disease . However , a client may refuse to use a condom when requested . Some sexually transmitted disease prevention programs are recommending that sex workers use spermicide as an alternative prophylaxis when a condom is refused , yet little is known about the effect of this recommendation on prophylactic condom use . Goal : To determine if using spermicide , either in conjunction with condoms or as a backup , influenced overall condom use among a group of sex workers at high risk of sexually transmitted diseases in Santa Fe de Bogota , Colombia . Study Design : Participants were assigned r and omly to one of three condom use groups : use of condoms only ( Condoms Only ) , use of condoms and spermicides concurrently ( Condom and Spermicide ) , or use of spermicide when condoms were refused ( Spermicide as a Backup ) . A total of 199 sex workers entered the study and were asked to return for follow‐up every 2 weeks for a period of 12 weeks . Results : Women assigned to the Spermicide as a Backup group used a condom for an average of 78.1 % of their reported acts of intercourse , compared with an average of 94.5 % in the Condom Only and 92.3 % in the Condom and Spermicide groups . However , women in the Spermicide as a Backup group used a condom or spermicide for an average of 96.9 % of their acts of intercourse . Condoms were used for every intercourse act by less than 5 % of the women in the Spermicide as a Backup group , compared with 50.7 % in the Condom Only group and 41.2 % in the Condom and Spermicide group ( P 0.001 ) . When condoms were not used , client refusal was the primary reason reported . The incidence of sexually transmitted diseases and other urogenital inflammations in all groups was lower than expected . Conclusions : Among Colombian sex workers , condom use declined substantially when women were instructed to use spermicides if they were unable to persuade their partner to use a condom . However , these same women usually used the study spermicide as an alternate prophylaxis OBJECTIVE To determine the longer-term effect ( mean + /- SD , 41.2 + /- 15.3 weeks ; range , 14.1 - 80.5 weeks ) of a middle school (MS)- and high school (HS)-based human immunodeficiency virus and sexuality intervention ( Rochester AIDS Prevention Project for Youth [ RAPP ] ) on knowledge , self-efficacy , behavior intention , and behaviors . DESIGN Quasi-experimental design with 3 intervention groups and 1 control group . SETTING Urban , predominantly ethnic , minority MS and HS health classes . PARTICIPANTS Middle school and HS students ( N = 4001 ) enrolled in health classes in 10 schools . Fifty percent were African American ; 16 % , Hispanic ; 20 % , white ; and 14 % , other . Less than 10 % of the students refused participation . INTERVENTIONS There were 4 study conditions : ( 1 ) control , usual health education curriculum taught by a classroom teacher ; ( 2 ) RAPP adult health educator , intervention curriculum implemented by highly trained health educators ; ( 3 ) RAPP peer educator , intervention implemented by extensively trained HS students ; and ( 4 ) a comparison of the RAPP intervention curriculum taught by regular health teachers , implemented with MS students only . MAIN OUTCOME MEASURE A confidential question naire was administered to all study subjects before and at long-term follow-up after the intervention , containing scales to measure knowledge , self-efficacy , behavior intention , and behaviors , including onset of sexual intercourse experience and engagement in risky sexual behaviors . RESULTS Rates of baseline sexual activity in the sample were comparable to those found in other urban school-based surveys . Long-term knowledge ( MS females , P<.001 ; and MS males , P<.01 ) and sexual self-efficacy ( MS females , P<.05 ; and HS females , P<.01 ) scores were higher among the intervention groups ( male and female are used in this study to describe those aged 9(1/2)-23 years ) . Intention to remain safe regarding sexual behavior was also greater among intervention groups in MS but not HS . However , subjects who were already sexually active at pretest were less likely to show a positive intervention effect . An intervention effect for the onset of intercourse and risky sexual behavior was found most significantly among MS females . CONCLUSIONS A positive long-term effect from the RAPP intervention was observed , particularly for youth who were involved in less risk ( eg , not yet sexually active ) at study enrollment . Thus , we propose that the most appropriate time for intervention implementation is earlier in adolescence , before the onset of risky behaviors Surveys of risk behaviors have been hobbled by their reliance on respondents to report accurately about engaging in behaviors that are highly sensitive and may be illegal . An audio computer-assisted self-interviewing ( audio-CASI ) technology for measuring those behaviors was tested with 1690 respondents in the 1995 National Survey of Adolescent Males . The respondents were r and omly assigned to answer questions using either audio-CASI or a more traditional self-administered question naire . Estimates of the prevalence of male-male sex , injection drug use , and sexual contact with intravenous drug users were higher by factors of 3 or more when audio-CASI was used . Increased reporting was also found for several other risk behaviors Objective . To determine if sexually transmitted diseases ( STDs ) , including human immunodeficiency virus ( HIV ) infection , risk assessment , and education tools provided as part of office-based primary care reduce adolescent risky sexual behaviors . Design . A r and omized intervention trial with 3- and 9-month follow-up . Setting . Five staff-model managed care sites in Washington , DC ( n = 19 pediatricians ) . Patients . Consecutive 12- to 15-year-olds receiving a general health examination ; 81 % minority . Participation rate = 215/432 ( 50 % ) . Nine-month follow-up rate = 197/215 ( 92 % ) . Intervention . Audiotaped STD risk assessment and education about staying safe ( safer = condoms , safest = abstinence ) . Main Outcome Measures . Adolescent-reported sexual intercourse and condom use . Results . More intervention adolescents reported pediatrician discussion on 11/13 sexual topics . Although more vaginal intercourse ( odds ratio [ OR ] = 2.46 , 95 % confidence interval [ CI ] = 1.04–5.84 ) was reported in the intervention group at 3 months , this was not true of overall sexual intercourse ( OR = 1.55 , 95 % CI = .73–3.32 ) . More sexually active adolescents reported condom use in the intervention group at 3 months ( OR = 18.05 , 95 % CI = 1.27–256.03 ) . At 9 months , there were no group differences in sexual behaviors ; however , more signs of STD were reported by the control ( 7/103 ) than the intervention group ( 0/94 ) . Conclusions . STD risk assessment and education tools administered in a single office visit facilitated STD/HIV prevention education . Any impact on sexual activity and condom use was short-lived . Further research is needed to develop brief , office-based sexual risk reduction for young adolescents CONTEXT The current public debate regarding whether oral sex constitutes having " had sex " or sexual relations has reflected a lack of empirical data on how Americans as a population define these terms . OBJECTIVE To determine which interactions individuals would consider as having " had sex . " METHODS A question was included in a survey conducted in 1991 that explored sexual behaviors and attitudes among a r and om stratified sample of 599 students representative of the undergraduate population of a state university in the Midwest . PARTICIPANTS The participants originated from 29 states , including all 4 US Census Bureau geographic regions . Approximately 79 % classified themselves as politically moderate to conservative . MAIN OUTCOME MEASURE Percentage of respondents who believed the interaction described constituted having " had sex . " RESULTS Individual attitudes varied regarding behaviors defined as having " had sex " : 59 % ( 95 % confidence interval , 54%-63 % ) of respondents indicated that oral-genital contact did not constitute having " had sex " with a partner . Nineteen percent responded similarly regarding penile-anal intercourse . CONCLUSIONS The findings support the view that Americans hold widely divergent opinions about what behaviors do and do not constitute having " had sex . OBJECTIVE To evaluate the cost-effectiveness and cost benefit of Safer Choices , a school-based human immunodeficiency virus , other sexually transmitted diseases , and unintended pregnancy prevention intervention for high school students . METHODS The baseline cost-effectiveness and cost benefit were derived in 4 steps : ( 1 ) estimation of intervention costs ; ( 2 ) adaptation of the Bernoulli model to translate increases in condom use into cases of human immunodeficiency virus and other sexually transmitted diseases averted , and development of a model to translate increases in contraceptive use into cases of pregnancy averted ; ( 3 ) translation of cases averted into medical costs and social costs averted ; and ( 4 ) calculation of the net benefit of the program . Multivariable sensitivity analysis was performed to determine the robustness of the base-case results . RESULTS Under base-case assumptions , at an intervention cost of $ 105,243 , Safer Choices achieved a 15 % increase in condom use and an 11 % increase in contraceptive use within 1 year among 345 sexually active students . An estimated 0.12 cases of human immunodeficiency virus , 24.37 cases of chlamydia , 2.77 cases of gonorrhea , 5.86 cases of pelvic inflammatory disease , and 18.5 pregnancies were prevented . For every dollar invested in the program , $ 2.65 in total medical and social costs were saved . Results of most of the scenarios remained cost saving under a wide range of model variable estimates . CONCLUSIONS The Safer Choices program is cost-effective and cost saving in most scenarios considered . School-based prevention programs of this type warrant careful consideration by policy makers and program planners . Program cost data should be routinely collected in evaluations of adolescent prevention programs PURPOSE To assess the effectiveness of a relatively unaltered version of a sexual risk reduction intervention previously shown to be effective among urban youth , " Original Focus on Kids " ( OFOK ) , compared with a version modified for West Virginia ( WVFOK ) and a control condition ( training in environmental conservation ) , in altering protective sexual behaviors and perceptions among rural , Appalachian youth . SUBJECTS Nine hundred ninety-nine youth aged 12 to 16 years from 12 rural counties in West Virginia . METHOD R and omized , controlled , longitudinal trial of a theory-based prevention intervention . Outcomes were self-reported sexual behaviors and perceptions assessed at baseline , 3 , 6 , and 9 months postintervention . RESULTS Both WVFOK and OFOK positively affected perceptions of abstinence but not behaviors . OFOK significantly enhanced some perceptions of condom use compared with both control youth and WVFOK youth , but again , not behaviors . CONCLUSIONS Overall , neither version was as effective as FOK had been in the original urban setting . The less altered version ( OFOK ) was more effective , especially with regard to condom-use perceptions , in this new population and cultural setting than the more culturally altered version ( WVFOK ) . In several of the implementation setting s , neither version was delivered as intended by the research ers because of logistic issues . Although many of these changes were seemingly minor , such deviations may have significant impact on intervention effect OBJECTIVES A theory-based curriculum design ed to delay the onset of intercourse and increase use of condoms was implemented in the classrooms of six Los Angeles middle schools . METHODS The curriculum activities were very interactive , emphasized skill building , and were implemented by well trained peer educators , including young HIV-positive males and teen mothers . To evaluate the impact of the curriculum , 102 classrooms of students were r and omly assigned to receive either the existing curriculum or the existing curriculum plus the intervention curriculum . Students completed confidential question naires before program implementation , five months later , and 17 months later . A total of 1,657 students completed both the baseline and 17-month follow-up question naires . RESULTS Analyses of these data revealed that the curriculum significantly increased knowledge , significantly improved only two out of 21 attitudes or beliefs , and did not significantly change sexual or contraceptive behaviors . CONCLUSIONS Well implemented programs that are based on upon theory , use interactive activities , and utilize well-trained peer educators do not always change important sexual attitudes and behaviors among middle school youth PURPOSE To describe a r and omized , controlled evaluation of a school-based intervention to delay sexual intercourse among urban junior high school students . METHODS Six Washington , D.C. , junior high schools were r and omly assigned to the intervention or nonintervention control condition for an educational program . During the first school year , seventh grade rs ( n = 582 ) from the six schools obtained written parental consent to participate . Three health professionals ( one per intervention school ) implemented the program , which consisted of reproductive health classes , the Postponing Sexual Involvement Curriculum , health risk screening , and " booster " educational activities during the following ( eighth grade ) school year . Cross-sectional surveys were administered at baseline , the end of the seventh grade , and the beginning and end of the eighth grade . Intervention and control group differences in virginity , attitudes toward delayed sex and childbearing , and sexual knowledge and behavior were assessed at all four time points . RESULTS At baseline , 44 % of the seventh grade males and 81 % of the seventh grade females reported being virgins . At the end of the seventh grade ( first follow-up ) , after controlling for baseline study group differences , intervention-group females were more likely to report virginity , self-efficacy to refuse sex with a boyfriend , and the intention to avoid sexual involvement during the following 6 months . At the end of the eighth grade , significantly more intervention- than control-group females reported virginity , birth control use at last intercourse ( for nonvirgins ) , and knowledge of adolescent reproductive health and confidentiality rights . No changes in virginity , self-efficacy to refuse sex , or sexual intent for the next 6 months were observed among male participants at any time during the study . However , on all three follow-up surveys , intervention-group males scored significantly higher than their control-group counterparts in knowledge of birth control method efficacy . No change in attitudes toward abstinence was observed for either gender at any follow-up point . CONCLUSIONS Gender differences in baseline sexual activity rates and in various study outcomes suggest a possible need for separate , gender-specific intervention activities that can adequately address the social and cognitive needs of both sexes CONTEXT Interventions to prevent adolescent pregnancy ( primarily curriculum-based programs ) have not produced convincing evidence as to their success . Moreover , many evaluation approaches have been inadequate to assess program effectiveness . Therefore , rigorous evaluation of different kinds of interventions may help identify potentially effective strategies to prevent adolescent pregnancy . METHODS An experimental design , in which clients were r and omized to treatment and control groups , was used to evaluate the effects of a " client-centered " approach to reducing pregnancy among high-risk young people in seven communities in Washington State . Four projects served 1,042 youth ( clients aged 9 - 13 ) , and three served 690 teenagers ( primarily clients aged 14 - 17 ) . Projects offered a wide variety of services tailored to individual clients ' needs , including counseling , mentoring and advocacy . RESULTS On average , clients in the treatment group at youth sites received 14 hours of service , and their teenage counterparts received 27 hours ; controls received only 2 - 5 hours of service . At one youth site , clients were less likely to intend to have intercourse after the intervention than before ; at another , they became less likely to intend to use substances . Clients at one teenage project reported reduced sexual behavior and improved contraceptive use after receiving services ; teenagers at another site reported reduced sexual intentions and drug use , and a greater intention to use contraceptives . The programs showed no other effects on factors that place young people at risk of becoming pregnant , including their sexual values and educational aspirations , communication with their parents ( measured at youth sites only ) , and sexual and contraceptive behavior ( assessed for teenagers only ) . CONCLUSIONS High-risk clients likely need considerably more intervention time and more intensive services than programs normally provide . Rigorous evaluation design s allow continued assessment that can guide program modifications to maximize effects PURPOSE This study was undertaken to determine whether the Adult Identity Mentoring ( AIM ) project successfully promotes abstinence , delays initiation of sex , and decreases intention to engage in sex . METHODS Twenty middle school classes of African-American seventh grade rs were r and omly assigned to receive either the AIM intervention or a st and ard health education control curriculum . The AIM is a 10-session curriculum based on the theory of possible selves . Class exercises encourage students to articulate a possible future self-identity and to develop self-promotion skills . Surveys about sexual activity were conducted before the intervention , 19 weeks after baseline , and again at 1 year after the intervention . RESULTS Hierarchical logistic regression analyses showed significant effects for the intervention on sexual intentions , abstinence , and a trend toward fewer virgins initiating intercourse for the first time , 19 weeks after baseline . Specifically , students who received the intervention showed decreased intention to engage in sex and increased abstinence compared with students not receiving the intervention . Effects for 1-year follow-up , with smaller sample size , showed only that AIM male participants maintained the significant abstinence effect . CONCLUSIONS A new intervention , AIM was evaluated among African-American seventh grade rs . This program , by focusing students on positive future selves , effectively modified sexual risk without directly providing instruction on sexually explicit topics PURPOSE ( a ) To test the longer-term ( 6 - 12 month ) effect of a school-based intervention design ed to delay the onset of sexual intercourse on continuation of abstinence , ( b ) to compare the effect of the intervention when delivered by different providers , and ( c ) to describe the factors that influence students ' transition from abstinence to sexual activity . METHODS This study was a nonr and omized control trial with one control and three intervention groups . The setting was health education classes in urban , predominantly ethnic minority schools . The participants were middle school students ( N = 1352 ; mean age , 13.1 years ) in five schools . Of participants , 50 % were African American , 20 % white , 16 % Hispanic , and 14 % other . Youth were assigned to one of four groups . The control group consisted of the regular school health curriculum and teacher . All three intervention groups received the Rochester AIDS Prevention Project curriculum , but implemented by different types of instructors , including ethnically diverse male-female pairs of adult professional educators ; male-female pairs of extensively trained high school peer educators ; and school district health teachers . A confidential question naire administered preintervention and at long-term follow-up ( mean , 44 weeks ) measured demographics , risk behaviors , and sexual intercourse history . RESULTS At preintervention , 27 % of girls and 62 % of boys reported sexual intercourse experience . At follow-up , 19 % and 32 % , respectively , of the previously abstinent girls and boys had " transitioned " to sexual activity . Increasing age ( p < .01 , females ; p < .001 , males ) , lower socioeconomic status ( p < .0001 ) , and higher general risk behaviors ( p < .0001 ) best predicted the transition . Logistic regression indicated that the intervention was effective for peer-taught males ( p = .02 ) and regular teacher-taught males ( p = .001 ) and females ( p = .05 ) . CONCLUSIONS Successful abstinence maintenance was only possible among those subjects who were not already sexually experienced at study enrollment . Baseline scores regarding intercourse and general life risks already evident by seventh grade suggest that urban , school-based primary prevention interventions must occur before adolescence . Early adolescence interventions need to include both abstinence and safer sex messages PURPOSE To evaluate the sustained effectiveness of a middle school service learning intervention on reducing sexual initiation and recent sex among urban African-American and Latino adolescents from 7th grade through the 10th grade . METHODS During the fall of seventh grade and again in eighth grade , students were r and omly assigned by classroom to participate either in community youth service ( CYS ) or not ( controls ) . Service learning is an educational strategy that couples meaningful service in the community with classroom instruction . Students in both intervention and control conditions received classroom health lessons . Surveys were conducted at seventh grade baseline and at the end of 10th grade , approximately 2 years after intervention . Self-reported sexual behaviors of youths who had participated in CYS were compared with those of controls receiving classroom curriculum alone ( n = 195 ) . RESULTS CYS participants were significantly less likely than controls to report sexual initiation ( 2 years CYS , odds ratio [ OR ] = 0.32 ; 1 year , OR = 0.49 ) as well as recent sex ( 2 years CYS , OR = 0.39 ; 1 year CYS , OR = 0.48 ) . Among those who were virgins at seventh grade , 80 % of males in the curriculum-only condition had initiated sex , compared with 61.5 % who received 1 year of CYS , and 50 % who received 2 years . Among females , the figures were 65.2 % , 48.3 % , and 39.6 % , respectively . CONCLUSION A service learning intervention that combines community involvement with health instruction can have a long-term benefit by reducing sexual risk taking among urban adolescents This study evaluated the effects of peer counseling in a culturally specific adolescent pregnancy prevention program for African American females . A r and om pretest and multiple posttest experimental and comparison group design was used to obtain data on a sample of 63 female African American adolescents , ages 12 to 16 , who lived in four public housing developments . Descriptive data and tests of significance revealed that none of the participants who received peer counseling became pregnant within three months of the intervention . Findings revealed a statistically significant increase in reproductive and other self-related knowledge topics among the experimental group when comparing pretest and eight-week posttest scores . Most participants had not had sexual intercourse ; the average age of sexual onset was 12 years in the experimental group and 11 years in the controls . Design ing and implementing culturally specific adolescent pregnancy prevention programs for adolescents younger than age 11 and /or before sexually active seems appropriate CONTEXT The quality of parent-child communications about sex and sexuality appears to be a strong determinant of adolescents ' sexual behavior . Evaluations of interventions aim ed at improving such communications can help identify strategies for preventing early onset of sexual behavior . METHODS A school-based abstinence-only curriculum was implemented among 351 middle school students , who were r and omly assigned to receive either the classroom instruction alone or the classroom instruction enhanced by five homework assignments design ed to be completed by the students and their parents . An experimental design involving pretest and posttest surveys was used to assess the relative efficacy of the curriculum delivered with and without the parent-child homework assignments . RESULTS In analyses of covariance controlling for baseline scores , immediately after the intervention , adolescents who received the enhanced curriculum reported greater self-efficacy for refusing high-risk behaviors than did those who received the classroom instruction only ( mean scores , 16.8 vs. 15.8 ) . They also reported less intention to have sex before finishing high school ( 0.4 vs. 0.5 ) , and more frequent parent-child communications about prevention ( 1.6 vs. 1.0 ) and sexual consequences ( 1.6 vs. 1.1 ) . In all significant comparisons , the direction of the findings favored adolescents who received the enhanced curriculum . Dose-response relationships supported the findings . CONCLUSIONS Parent-child homework assignments design ed to reinforce and support school-based prevention curricula can have an immediate impact on several key determinants of sexual behavior among middle school adolescents OBJECTIVES This study evaluated the effectiveness of a community youth service ( CYS ) program in reducing sexual risk behaviors among African American and Latino urban young adolescents . METHODS A total of 1061 students at 2 urban middle schools were surveyed at baseline and 6-month follow-up . Students at one school were r and omly assigned by classroom to receive either the Reach for Health CYS program or the Reach for Health classroom curriculum only . Students at the other school served as controls . RESULTS At follow-up . CYS participants reported significantly less recent sexual activity ( P < .05 ) and scored lower on a sexual activity index than those in the control condition ( P < .03 ) . The greatest effect was among eighth grade rs , who received the most intensive service program ( P < .03 ) . The benefit of the curriculum-only intervention appeared greatest among students in special education classes . CONCLUSIONS Well-organized CYS that couples community involvement with classroom health instruction can have a positive impact on the sexual behaviors of young adolescents at risk for HIV , sexually transmitted diseases , and unintended pregnancy . This study also suggests the importance of including students in special education classes in health education programs BACKGROUND Some interventions to reduce the risk of the acquired immunodeficiency syndrome ( AIDS ) that target youths have result ed in short-term increases in self-reported condom use . However , long-term intervention effects have not been assessed . STUDY QUESTION Can a theoretically and culturally based , AIDS-risk reduction intervention delivered to naturally formed peer groups increase self-reported condom use among African-American early adolescents at 6 and 12 months of follow-up ? METHOD A r and omized , controlled trial of a community-based intervention delivered in eight weekly sessions involved 76 naturally formed peer groups consisting of 383 ( 206 intervention and 177 control ) African-American youths 9 to 15 years of age . A theory-based , culturally and developmentally tailored instrument that assessed perceptions , intentions , and self-reported sexual behaviors was administered to all subjects at baseline ( preintervention ) and 6 and 12 months later . RESULTS At baseline , 36 % of youths were sexually experienced , and by 12 months of follow-up , 49 % were sexually experienced . Self-reported condom use rates were significantly higher among intervention than control youths ( 85 % vs 61 % ; P<.05 ) at the 6-month follow-up . However , by 12 months , rates were no longer significantly higher among intervention youths . The intervention impact at 6 months was especially strong among boys ( 85 % vs 57 % ; P<.05 ) and among early teens ( 13 to 15 years old ) ( 95 % vs 60 % ; P<.01 ) . Self-reported condom use intention was also increased among intervention youths at 6 months but not at 12 months . Some perceptions were positively affected at 6 months , but the change did not persist at 12 months . CONCLUSIONS High rates of sexual intercourse underscore the urgent need for effective AIDS-risk reduction interventions that target low-income urban , African-American preteens and early teens . A developmentally and culturally tailored intervention based on social-cognitive theory and delivered to naturally formed peer groups recruited from community setting s can increase self-reported condom use . The strong short-term improvements in behaviors and intentions followed by some relapse over longer periods argue for a strengthened program and research focus on sustainability OBJECTIVES We estimated HIV prevalence rates among young adults in the United States . METHODS We used survey data from the third wave of the National Longitudinal Study of Adolescent Health , a r and om sample of nearly 19000 young adults initiated in 1994 - 1995 . Consenting respondents were screened for the presence of antibodies to HIV-1 in oral mucosal transu date specimens . We calculated prevalence rates , accounting for survey design , response rates , and test performance . RESULTS Among the 13184 participants , the HIV prevalence rate was 1.0 per 1000 ( 95 % confidence interval [ CI ] = 0.4 , 1.7 ) . Gender-specific prevalence rates were similar , but rates differed markedly between non-Hispanic Blacks ( 4.9 per 1000 ; 95 % CI=1.8 , 8.7 ) and members of other racial/ethnic groups ( 0.22 per 1000 ; 95 % CI=0.00 , 0.64 ) . CONCLUSIONS Racial disparities in HIV in the United States are established early in the life span , and our data suggest that 15 % to 30 % of all cases of HIV occur among individuals younger than 25 years In battling HIV , many interventionists advocate the use of hierarchical messages that present multiple prevention options in order of decreasing effectiveness . The purpose of the present study was to determine if hierarchical messages provide women with additional prevention options without reducing the perceived efficacy of and willingness to use the primary method mentioned ( in this case , male condoms ) . African American and Mexican American women between 18 and 32 years of age ( n=112 ) at risk for HIV were r and omly assigned to receive either a male-condom-only message ( use male condoms ) or a hierarchical message ( use male condoms ; if not , use female condoms ; if not , use spermicide ) . Compared with women in the male-condom-only condition , a significantly smaller percentage of women who received the hierarchical message perceived male condoms as highly effective against HIV . Women currently not using male condoms who received the hierarchical , rather than the male-condom-only , message were less likely to consider using male condoms in the future . Among current male condom users , however , the hierarchical message did not influence intent to use male condoms . These data point to the need for examining both the intended and unintended effects of hierarchical health care messages Postponing Sexual Involvement ( PSI ) is a widely implemented middle school curriculum design ed to delay the onset of sexual intercourse . In an evaluation of its effectiveness among seventh and eighth grade rs in California , 10,600 youths from schools and community-based organizations statewide were recruited and participated in r and omly assigned intervention or control groups ; the curriculum was implemented by either adult or youth leaders . Survey data were collected before the program was implemented , and at three months and 17 months afterward . At three months , small but statistically significant changes were found in fewer than half of the measured attitudes , behaviors and intentions related to sexual activity ; at 17 months , none of these significant positive effects of the PSI program had been sustained . At neither follow-up were there significant positive changes in sexual behavior ; Youths in treatment and control groups were equally likely to have become sexually active , and youths in treatment groups were not less likely than youths in control groups to report a pregnancy or a sexually transmitted infection . The evaluation suggests that PSI may be too modest in length and scope to have an impact on youths ' sexual behavior PURPOSE To describe facilitators and barriers to participation and retention of Latino adolescents in a r and omized clinical trial . DESIGN AND METHODS Participants were part of a r and omized clinical trial design ed to reduce HIV sexual risk behavior among Latino youth . Responses from 106 r and omly selected respondents from the 3-month follow-up were content analyzed . RESULTS Four main facilitator patterns emerged : peer/family support , program incentives , commitment , and desire to help . Participation barriers included conflicts with other commitments , embarrassment , and lack of peer support . PRACTICE IMPLICATION S Recruitment and retention of Latino adolescents in research studies is critical to building a research base for nursing practice OBJECTIVES To develop and evaluate an intervention ( ImPACT ) seeking to increase monitoring ( supervision and communication ) by parents and guardians of African-American youth regarding high risk and protective behaviors ; and to develop an instrument to assess parental monitoring , the Parent-Adolescent Risk Behavior Concordance Scale . DESIGN /INTERVENTION This research was a r and omized , controlled longitudinal study . Baseline ( preintervention ) , and 2 and 6 months postintervention data were obtained via a talking MacIntosh computer regarding youth and parent perceptions of youth involvement in 10 risk behaviors , parental monitoring and youth-parent communication , and condom-use skills . Intervention parents and youth received the ImPACT program and a video emphasizing parental supervision and discussion , followed by a structured discussion and role-play emphasizing key points . Control parents and youth received an attention-control program on goal - setting , which also included an at-home video and discussion . PARTICIPANTS A total of 237 parents and one each of their youth ( ages 12 - 16 years ) recruited from eight public housing developments located in a city in the mid-Atlantic region . RESULTS Similarity of youth and parental reporting on the Parent-Adolescent Risk Behavior Concordance Scale was positively correlated with protective behaviors , perceived parental monitoring , and good parent-youth communication . At baseline , parents significantly underestimated their youth 's risk behaviors . However , 2 and 6 months postintervention , the ImPACT program increased similarity of reports by youth and their parents of youth involvement in risk and protective behaviors . In addition , at 6 months postintervention , intervention ( compared to control ) youths and parents also demonstrated higher levels of condom-use skills . CONCLUSION Parental monitoring interventions such as ImPACT should be given to parents in conjunction with more traditional youth-centered risk-reduction interventions Data from a r and omized , controlled longitudinal study of African-American parent-adolescent dyads were analyzed to assess the impact of a parental monitoring intervention on ( a ) the similarity of parent and adolescent reporting of adolescent involvement in risk and protective activities , and ( b ) the reported rates of risk involvement by youth . Self-reported and parental perception of youth risk and protective activities were collected at baseline and 12 months postintervention . There was no significant difference between self-report and parent perception of youth activities among intervention dyads at follow-up . By contrast , parents in the control dyads significantly underestimated youth protective and risk activities . There was no evidence of a direct intervention effect on self-reported risk behaviors . These data confirm earlier findings that a culturally-tailored parental monitoring intervention can increase agreement of youth risk involvement among youth and their parents and provide evidence that this effect endures over time . The data argue for the need to consider intervention strategies that address both parents and youth This project assessed the impact of a school-based AIDS prevention program on student participation in sexual risk and protective behaviors such as use of condoms and use of condoms with foam and intention to participate in such behaviors . The paper focuses on students who became sexually active for the first time between the seventh and eighth grade ( " changers , " n = 312 ) . The school-based intervention was developed using social cognitive theory and the social influences model of behavior change . Using an experimental , longitudinal design , 15 high-risk school districts were divided r and omly into two treatment ( 10 districts ) and one control ( five districts ) conditions . Students in both treatment conditions received a 10-lesson classroom program in the seventh grade with a five-lesson booster in the eighth grade , while control students received basic AIDS education ( current practice in their districts ) in compliance with state m and ates . Results indicated classroom programs had an impact on certain protective behaviors and on frequency of sexual activity the past month . Post-intervention measures also indicated the program affected students ' intentions to perform specific protective behaviors This r and omized controlled trial tested the effects of a theory-based culture-sensitive HIV risk-reduction intervention among 496 inner-city African American adolescents ( mean age = 13 years ) and examined the generality of its effects as a function of the facilitator 's race and gender and the gender composition of the intervention group . Adolescents who received the HIV risk-reduction intervention expressed more favorable behavioral beliefs about condoms , greater self-efficacy , and stronger condom-use intentions postintervention than did those who received a control intervention on other health issues . Six-month follow-up data collected on 93 % of the adolescents revealed that those who received the HIV risk-reduction intervention reported less HIV risk-associated sexual behavior , including unprotected coitus , than did their counterparts in the control condition . Self-reported sexual behavior and changes in self-reported behavior were unrelated to scores on a st and ard measure of social desirability response bias . There was strong evidence for the generality of intervention effects . Moderator analyses testing eight specific interaction hypotheses and correlational analyses indicated that the effects of the HIV risk-reduction intervention did not vary as a function of the facilitator 's race or gender , participant 's gender , or the gender composition of the intervention group A r and omized controlled trial assessed 3 interventions design ed to increase safer sex behaviors of substance-dependent adolescents . Participants ( N = 161 ) received 12 sessions of either a health information intervention ( I only ) , information plus skills-based safer sex training ( I + B ) , or the same experimental condition plus a risk-sensitization manipulation ( I + M + B ) . The I + B and I + M + B conditions , as compared with the I only condition , ( a ) produced more favorable attitudes toward condoms ; ( b ) reduced the frequency of unprotected vaginal sex ; and ( c ) increased behavioral skill performance , frequency of condom-protected sex , percentage of intercourse occasions that were condom protected , and number of adolescents who abstained from sex . The intervention that included the risk-sensitization procedure was more resistant to decay . An unexpected finding was that the I + B and I + M + B conditions produced substantial increases in sexual abstinence Conducted in diverse sociocultural communities in Los Angeles County , the project implemented and evaluated a family life education program design ed to prevent the negative outcomes of risky sexual behavior . A sample of 251 male and female early adolescents 9 through 14 years of age participated with their parents in this abstinence-based adolescent pregnancy prevention program . The project sought to improve parent-child communications and delay the onset of sex-related behaviors through direct involvement of parents in the education process . Naturally occurring community groups were r and omly assigned by site to treatment or delayed treatment conditions in a longitudinal quasi-experimental evaluation design . The evaluation demonstrated significant improvements in communication between parents and children immediately following the intervention ; however , these improvements were no longer present 12 months postintervention . The process and outcome evaluation methods employed in the study triangulated qualitative and quantitative data collection and analysis procedures . This combination provided other sources of data than the traditional outcome measures used in most evaluation studies , thus addressing some of the gaps in present program evaluations . Descriptions of the process evaluation , integrated with the outcome data , are intended to heighten nurses ’ awareness of the importance of this component of research and the rich qualitative data it may yield . The qualitative process components in the project captured the experience of the investigators when they encountered many of the complex challenges that confront research ers who implement and evaluate family life education programs among early adolescents . This experience provided the basis for suggested strategies that nurse clinicians and research ers can use in their work with early adolescents and their parents in clinical - , school- , and community-based setting PURPOSE To underst and how method ological factors influence prevalence estimates of health-risk behaviors obtained from surveys , we examined the effect of varying question wording and honesty appeals while holding other aspects of the surveys constant . METHODS A convenience sample of students ( n = 4140 ) in grade s 9 through 12 was r and omly assigned to complete one of six versions of a paper- and -pencil question naire in classrooms . Each question naire version represented a different combination of honesty appeal ( st and ard vs. strong ) and question naire type . The question naire types varied in wording and in the number of questions assessing particular types of behaviors . The question naires were based on those used in three national surveys -- the Youth Risk Behavior Survey , Monitoring the Future , and the National Household Survey on Drug Abuse . Logistic regression analyses examined how responses to each survey question assessing behavior were associated with question naire type , honesty appeal , and the interaction of those two variables . RESULTS Among 32 behaviors with different question wording across question naire types , 12 showed a significant effect of question naire type . Among 45 behaviors with identical question wording across question naire types , five showed a significant main effect of question naire type . Among all 77 behaviors , one showed a significant main effect for honesty appeal and two showed a significant interaction between honesty appeal and question naire type . CONCLUSIONS When population , setting , question naire context , mode of administration , and data -editing protocol s are held constant , differences in question wording can create statistically significant differences in some prevalence estimates . Varying honesty appeals does not have an effect on prevalence estimates PURPOSE To measure the relative impact of a school-based human immunodeficiency virus (HIV)- , sexually transmitted disease (STD)- , and pregnancy-prevention intervention on sexual risk-taking behaviors of different subgroups of students . METHODS Twenty schools were r and omly assigned to receive Safer Choices or a st and ard knowledge-based HIV-education program . Safer Choices was design ed to reduce unprotected sex by delaying initiation of sex , reducing its frequency , or increasing condom use . Its five components included : school organization , an intensive curriculum with staff development , peer re sources and school environment , parent education , and school-community linkages . A total of 3869 9th- grade students were tracked for 31 months . Results are presented for initiation of sex , frequency of unprotected sex , number of unprotected sexual partners , condom use , and contraceptive use . These results are presented separately by gender , race/ethnicity , prior sexual experience , and prior sexual risk-taking . Statistical analyses included multilevel , repeated measures logistic and Poisson regression models . RESULTS Safer Choices had one or more positive behavioral effects on all subgroups . On four outcomes that could be affected by condom use , it had a greater impact on males than on females . It had greater effects on Hispanics , including a delay in sexual activity , than on other racial/ethnic groups . Its greatest overall effect was an increase in condom use among students who had engaged in unprotected sex before the intervention . CONCLUSIONS Safer Choices reduced one or more measures of sexual risk taking over 31 months among all groups of youth , and was especially effective with males , Hispanics , and youth who engaged in unprotected sex and thus were at higher risk for HIV , other STD infections and pregnancy BACKGROUND The number of reported cases of acquired immune deficiency syndrome ( AIDS ) is increasing disproportionately among Blacks in the United States . The relatively high incidence of sexually transmitted diseases among Black adolescents suggest the need for AIDS prevention programs to reduce their risk of sexually transmitted human immunodeficiency virus ( HIV ) infection . METHODS Black male adolescents ( n = 157 ) were r and omly assigned to receive an AIDS risk reduction intervention aim ed at increasing AIDS-related knowledge and weakening problematic attitudes toward risky sexual behavior , or to receive a control intervention on career opportunities . RESULTS The adolescents who received the AIDS intervention subsequently had greater AIDS knowledge , less favorable attitudes toward risky sexual behavior , and lower intentions to engage in such behavior than did those in the control condition . Follow-up data collected 3 months later revealed that the adolescents who had received the AIDS intervention reported fewer occasions of coitus , fewer coital partners , greater use of condoms , and a lower incidence of heterosexual anal intercourse than did the other adolescents . CONCLUSIONS These results suggest that interventions that increase knowledge about AIDS and change attitudes toward risky sexual behavior may have salutary effects on Black adolescents ' risk of HIV infection Low-income African American inner city adolescent females continue to be at disproportionately high risk for contracting HIV . Though it has been speculated that mothers ' involvement in HIV risk reduction may be helpful in the fight against HIV , very few interventions involve mothers . The Mother/Daughter HIV Risk Reduction intervention ( MDRR ) , an innovative community-based intervention , trains mothers to be their daughters ' primary HIV educators . A split-plot repeated measures design was used to test the effectiveness of the MDRR in decreasing daughters ' sexual activity over a 2-month period . The mediating variables were daughters ' HIV transmission knowledge , self-efficacy and intention to refuse sex . The sample consisted of 262 daughters with a mean age of 12.4 years . The results revealed that mothers were effective in increasing the mediating variables and in reducing their daughters ' level of sexual activity . Active involvement of mothers is cost-effective and should be integrated into HIV intervention programs This study assessed the effects of 3 theoretically grounded , school-based HIV prevention interventions on inner-city minority high school students ' levels of HIV prevention information , motivation , behavioral skills , and behavior . It involved a quasi-experimental controlled trial comparing classroom-based , peer-based , and combined classroom- and peer-based HIV prevention interventions with a st and ard-of-care control condition in 4 urban high schools ( N = 1,532 , primarily 9th- grade students ) . At 12 months postintervention , the classroom-based intervention result ed in sustained changes in HIV prevention behavior . This article discusses why both of the interventions involving peers were less effective than the classroom-based intervention at the 12-month follow-up and , more generally , suggests a set of possible limiting conditions for the efficacy of peer-based interventions Background : The male condom is the most effective barrier method available for protection against sexually transmitted diseases ( STDs ) , including HIV infection . There is an urgent need to develop and evaluate other prevention methods , such as the female condom . This study estimated the additional protection against STDs offered to sex workers by giving them the option of using the female condom when clients refused to use a male condom . Methods : Sex establishments in four cities in Thail and were r and omized into two study groups : one in which sex workers were instructed to use male condoms consistently ( male condom group ) ; and one in which sex workers had the option of using the female condom if clients refused or were not able to use male condoms ( male/female condom group ) . R and omization was done by sex establishments , and not by individuals , to minimize sharing of female condoms across study groups . The proportion of unprotected sexual acts ( defined as sexual acts in which condoms were not used , tore , or slipped in or out ) and incidence rate of STDs ( gonorrhoea , chlamydial infection , trichomoniasis and genital ulcer disease ) were measured over a 24-week period and compared between the two study groups . Findings : Results are available from 34 sex establishments ( 249 women ) in the male/female condom group , and 37 sex establishments ( 255 women ) in the male condom group . Condom use was very high in both groups ( 97.9 and 97.3 % of all sexual acts , respectively , P > 0.05 ) . Male condom use was lower in the male/female condom group when compared with the male condom group ( 88.2 and 97.5 % , respectively , P < 0.001 ) . However , this reduction in male condom use was counterbalanced by the use of female condoms in 12.0 % of all sexual acts in the male/female condom group , contributing to a 17 % reduction in the proportion of unprotected sexual acts in this group when compared to the male condom group ( 5.9 versus 7.1 % , respectively , P = 0.16 ) . Female condom use was sustained over the entire study period . There was also a 24 % reduction in the weighted geometric mean incidence rate of STDs in the sex establishments of the male/female condom group compared to the male condom group ( 2.81 versus 3.69 per 100 person-weeks , P = 0.18 ) . Interpretation : The replacement of male condoms by female condoms in a proportion of sexual acts in the male/female condom group suggests that some sex workers and /or their clients preferred using the female condom . This switch in barrier method was accompanied by non-significant reductions in the proportion of unprotected sexual acts and in the incidence rate of STDs in the women of the male/female condom group . Special attention should be paid to a potential risk of slippage of the female condom in inexperienced users OBJECTIVES In this study , we test the effectiveness of involving parents in school-based AIDS education with respect to altering AIDS-related knowledge , attitudes , behavioral intentions , communications patterns , and behavior of students . METHODS Fifteen high risk school districts ( pre-test N = 2,392 ) were r and omly assigned to one of three conditions : parent-interactive ( classroom curricula + parent-interactive component ) ; parent non-interactive ( classroom curricula only ) ; control ( basic AIDS education ordinarily provided by the school ) . Students were tested over time in grade s 7 , 8 and 9 . RESULTS Results indicate that both treatment conditions ( parent-interactive and non-interactive ) had a strong positive impact in enhancing student 's knowledge , attitudes , communication patterns and behavioral intentions . Further , results indicate that there were no behavioral outcome differences between the treatment groups and the control condition . Results demonstrate few outcome differences between the two experimental conditions . CONCLUSIONS In the two treatment groups ( parent-interactive and parent non-interactive ) , the program effects appear to be the result of school-based curricula and of student self-determined intentions and behaviors , rather than the presence or absence of planned parental involvement . Whether or not structured or planned parental involvement becomes part of a school-based educational activity should perhaps be determined by ( a ) the existing level of parent-school interaction based on the nature of the community , ( b ) the amount of money readily available to follow through on a program of parent involvement without compromising on student programs , ( c ) the age of the child and the sensitivity of the issue , and ( d ) the ability of the parent/family to be involved effectively without extraordinary expense or sacrifice by either parent or school . Our findings speak to the positive role of the school regardless of parent participation Objectives . This study evaluated the long-term effectiveness of Safer Choices , a theory-based , multi-component educational program design ed to reduce sexual risk behaviors and increase protective behaviors in preventing HIV , other STDs , and pregnancy among high school students . Methods . The study used a r and omized controlled trial involving 20 high schools in California and Texas . A cohort of 3869 ninth- grade students was tracked for 31 months from fall semester 1993 ( baseline ) to spring semester 1996 ( 31-month follow-up ) . Data were collected using self-report surveys administered by trained data collectors . Response rate at 31-month follow-up was 79 % . Results . Safer Choices had its greatest effect on measures involving condom use . The program reduced the frequency of intercourse without a condom during the three months prior to the survey , reduced the number of sexual partners with whom students had intercourse without a condom , and increased use of condoms and other protection against pregnancy at last intercourse . Safer Choices also improved 7 of 13 psychosocial variables , many related to condom use , but did not have a significant effect upon rates of sexual initiation . Conclusions . The Safer Choices program was effective in reducing important risk behaviors for HIV , other STDs , and pregnancy and in enhancing most psychosocial determinants of such behavior OBJECTIVES We tested the efficacy of an intervention among 11- to 14-year-old adolescent boys to promote delay of sexual intercourse , condom use among those who were sexually active , and communication on sexuality between fathers ( or father figures ) and sons . METHODS Sites were r and omly assigned to the intervention and control groups . Assessment s were conducted prior to the intervention and at 3- , 6- , and 12-month follow-up interviews . RESULTS A total of 277 fathers and their sons completed baseline assessment s. Most participants were African American , and most fathers lived with their sons . Significantly higher rates of sexual abstinence and condom use and of intent to delay initiation of sexual intercourse were observed among adolescent boys whose fathers participated in the intervention . Fathers in the intervention group reported significantly more discussion s about sexuality and greater intentions to discuss sexuality than did control-group fathers . CONCLUSIONS The study demonstrates that fathers can serve as an important educator on HIV prevention and sexuality for their sons OBJECTIVE To determine the short-term effect of a middle and high school-based human immunodeficiency virus and sexuality intervention ( Rochester AIDS Prevention Project for Youth [ RAPP ] ) on knowledge , self-efficacy , and behavior intention . DESIGN Nonr and omized intervention study with 2 intervention groups and 1 control group . SETTING Middle and high school health classes in an urban , predominantly minority school district . PARTICIPANTS Middle and high school students ( N = 3635 ) enrolled in health classes in 9 schools ; 50 % African American , 16 % Hispanic , 20 % white , and 14 % other . Less than 10 % of students refused participation . INTERVENTION There were 3 study conditions : ( 1 ) Control , usual health education curriculum taught by classroom teacher ; ( 2 ) RAPP adult health educator , intervention curriculum implemented by ethnically diverse male-female pairs of highly trained health educators ; and ( 3 ) RAPP peer educator , intervention implemented by male-female pairs of extensively trained high school students . Health classes within schools were assigned to 1 of the 3 conditions each semester , and simultaneous implementation of the control program with health educators or peer educators in the same school and during the same semester was not permitted . MAIN OUTCOME MEASURE A confidential question naire administered to all study subjects before and immediately after the intervention , containing scales to measure knowledge , sexual self-efficacy , and safe behavior intention . RESULTS Preintervention data indicated that the study population was involved in sexual activity and other risk behaviors at rates comparable to those of other urban adolescent population s. Examination of 3 outcome constructs as dependent variables ( knowledge , sexual self-efficacy , and safe behavior intention ) revealed that the health educators and peer educators increased students ' knowledge significantly more than did the control condition for both middle ( females , P<.01 ; males , P<.01 ) and high ( females , P<.001 ; males , P<.001 ) school . Comparisons of self-efficacy changes across intervention groups did not reach statistical significance , and safe behavior intention changes differed significantly by intervention group for high school but not for middle school students . For all analyses , the preintervention scores for each outcome variable were the most powerful predictors of postintervention scores , and analysis of variance models predicted substantial overall variance . CONCLUSIONS At short-term follow-up , the RAPP intervention had a powerful effect on knowledge for all students and a moderate effect on sexual self-efficacy and safe behavior intention , particularly for high school students . The peer educators were found to be equally and , for some variables , more effective than the highly trained adult educators . The substantial effect of the baseline scores and the high prevalence of risk behavior already evident by seventh grade indicate the importance of early implementation of school-based sexuality programs This study evaluated the effectiveness of the first year of Safer Choices , a theoretically based , multicomponent HIV , STD , and pregnancy prevention program for high school youth . The study featured a r and omized trial involving 20 schools in California and Texas , with a cohort of 3,869 ninth- grade students . Students who completed both the baseline and the first follow-up survey approximately seven months later were included in the analysis ( n = 3,677 ) . Safer Choices enhanced 9 of 13 psychosocial variables including knowledge , self efficacy for condom use , normative beliefs and attitudes regarding condom use , perceived barriers to condom use , risk perceptions , and parent-child communication . Safer Choices also reduced selected risk behaviors . Specifically , Safer Choices reduced the frequency of intercourse without a condom in the three months prior to the survey , increased use of condoms at last intercourse , and increased use of selected contraceptives at last intercourse The purpose of this study was to evaluate the efficacy of a school-based knowledge- and cognitive-behavioral skills-building STD/HIV prevention intervention . Subjects were 513 ethnically and racially diverse students attending four urban public high schools . The sample was 59 % female and had a mean age of 14.4 years . A quasi-experimental design was utilized to evaluate the intervention which consisted of three class sessions . Results of hierarchical regression analyses , controlling for baseline scores and demographic factors , indicate that this intervention was effective at increasing STD knowledge ( p < .05 ) , and skills related to prevention of risky sexual ( p < .05 ) and drug use ( p < .001 ) behavior . Although significant changes in risk behaviors were not detected , it is too soon to conclude that school-based education and skills building STD/HIV prevention interventions are ineffective at changing risk behaviors in adolescents . Implication s for future study are addressed PURPOSE The purpose of this study was to assess the effectiveness of Focus on Kids ( FOK ) , a sexual risk reduction intervention , shown to be effective among urban , African-American adolescents living in communities with high rates of sexually transmitted diseases , in reducing sexual risk behaviors among rural , white adolescents living in communities with low rates of sexually transmitted diseases . The subjects were 1,131 youth ages 12 to 16 years from 12 rural counties in West Virginia . METHOD The study was a r and omized , controlled , longitudinal trial of a theory-based prevention intervention . Outcomes included self-reported sexual behaviors and perceptions assessed at baseline and at 3 , 6 , and 9 months after intervention . RESULTS At baseline , 21 % of youth were sexually experienced ; 80 % reported using a condom at last episode of intercourse . Rates of behaviors did not differ based on intervention assignment ( FOK vs control group ) after adjusting for baseline differences at any follow-up period among the full cohort or among the subset of youth who completed the intervention curriculum to which they were assigned . Perceptions of risk and protective behaviors were positively influenced by FOK at 3 , 6 , and 9 months in a fashion consistent with the guiding model of behavioral change and the FOK curriculum . CONCLUSIONS Consistent with previous studies of FOK in high-risk urban areas , some perceptions were positively altered by FOK in these rural areas , although many of these changes did not persist through 9 months of follow-up . In contrast to previous studies , self-reported sexual risk behaviors did not decrease among FOK youth . FOK was not associated with any increases in sexual risk behaviors BACKGROUND This article reports the results of the impact of a school-based HIV prevention intervention on students ' knowledge , attitudes , and behavior related to HIV infection . METHODS Seventeen schools within six Colorado school districts were assigned to either intervention or comparison conditions . Students in 10 schools received a 15-session , skills-based HIV prevention curriculum implemented by trained teachers . A total of 2,844 students completed at least one survey during the study period ; surveys were matched using demographic questions , yielding a cohort of 979 students who had baseline and 6-month follow-up data . RESULTS Intervention students exhibited greater knowledge about HIV and greater intent to engage in safer sexual practice s than the comparison students . Among sexually active students at the 6-month follow-up , intervention students reported fewer sexual partners within the past 2 months , greater frequency of using condoms , and greater intentions to engage in sex less frequently and to use a condom when having sex . Intervention students were also more likely to believe that teens their age who engage in HIV risk behaviors are vulnerable to infection . The intervention neither delayed the onset nor decreased the frequency of sexual intercourse and the frequency of alcohol and other drug use before sex by the 6-month follow-up assessment . CONCLUSIONS The results suggest that skills-based risk reduction programs can have an effect on student behavior . Among sexually active students , evidence suggests that school-based interventions can reduce behavior associated with risk of HIV infection This study evaluated All4You ! , a theoretically based curriculum design ed to reduce sexual risk behaviors associated with HIV , other STDs , and unintended pregnancy among students in alternative schools . The study featured a r and omized controlled trial involving 24 community day schools in northern California . A cohort of 988 students was assessed four times during an 18-month period using a self report question naire . At the 6-month follow-up , the intervention reduced the frequency of intercourse without a condom during the previous 3 months , the frequency of intercourse without a condom with steady partners , and the number of times students reported having intercourse in the previous 3 months . It also increased condom use at last intercourse . These behavioral effects were no longer statistically significant at the 12- and 18-month follow-ups . The All4You ! intervention was effective in reducing selected sexual risk behaviors among students in alternative school setting s ; however , the effects were modest and short term OBJECTIVES This study evaluated the long-term effectiveness of Draw the Line/Respect the Line , a theoretically based curriculum design ed to reduce sexual risk behaviors among middle school adolescents . METHODS The r and omized controlled trial involved 19 schools in northern California . A cohort of 2829 sixth grade rs was tracked for 36 months . RESULTS The intervention delayed sexual initiation among boys , but not girls . Boys in the intervention condition also exhibited significantly greater knowledge than control students , perceived fewer peer norms supporting sexual intercourse , had more positive attitudes toward not having sex , had stronger sexual limits , and were less likely to be in situations that could lead to sexual behaviors . Psychosocial effects for girls were limited . CONCLUSIONS The program was effective for boys , but not for girls Background : Many studies measure sex behavior to determine the efficacy of sexually transmitted disease (STD)/HIV prevention interventions . Goal : To determine how well measured behavior reflects STD incidence . Study Design : Data from a trial ( Project RESPECT ) were analyzed to compare behavior and incidence of STD ( gonorrhea , chlamydia , syphilis , HIV ) during two 6‐month intervals . Results : A total of 2879 persons had 5062 six‐monthly STD exams and interviews ; 8.9 % had a new STD in 6 months . Incidence was associated with demographic factors but only slightly associated with number of partners and number of unprotected sex acts with occasional partners . Many behaviors had paradoxical associations with STD incidence . After combining behavior variables to compare persons with highest and lowest risk behaviors , the STD incidence ratio was only 1.7 . Conclusion : Behavioral interventions have prevented STD . We found people tend to have safe sex with risky partners and risky sex with safe partners . Therefore , it is difficult to extrapolate the disease prevention efficacy of an intervention from a measured effect on behavior alone The authors evaluated the effectiveness of a school-based sex education program in decreasing rates of sexual intercourse , improving birth control use , and decreasing the incidence of pregnancies among teenagers 16 years of age and younger . Twenty-one schools received either the McMaster Teen Program or the conventional didactic sex education program . Preprogram , the mean age of the students was 12.6 years . There were no statistically significant differences between groups in time to first sexual activity for males , χ2(1 ) = 2.93 , p = 0.09 ; time to first sexual activity for females , χ2(1 ) = 0.50 , p = 0.48 ; and time to first pregnancy , χ2(1 ) = 1.90 , p = 0.17 . Significantly more experimental group males reported always using birth control at year 1 ( difference 8.9 % ; 95 % confidence interval [ CI ] = 0.4,17.4 ) . Limitations of the program that may have influenced the results were the exclusion of contraception information and its short duration Introduction Effective public health interventions to reduce the incidence of sexually transmitted disease ( STD ) , including HIV , among women are urgently needed . Methods A r and omized trial among STD clinic patients of two types of counseling regarding methods to reduce disease transmission : a ` hierarchical ' message ( HP ) , with counseling on male condoms , female condoms , diaphragms , cervical caps , and spermicides ( three formulations ) and a single method message ( SM ) covering male condoms only or female condoms only . For this analysis , 1591 subjects received one of three educational messages at the central public STD clinic in Philadelphia . Disease incidence data for up to 6 months following the index visit were extracted from the clinic 's electronic data base . The primary outcome was STD reinfection : laboratory-confirmed trichomonas infection and /or clinical diagnoses of at least one of four STD . Rates were based on the full sample of r and omized women ( full sample ) and on the subset who spontaneously returned between 22 days and 183 days following their initial visit ( returners ) . Results Rates of trichomonas infection ( SM 2.5 % full sample and 12.9 % returners versus HP 2.4 % full sample and 11.5 % returners ) and clinical diagnoses ( SM 6.3 % full sample and 39.7 % returners versus HP 6.9 % full sample and 41.2 % returners ) did not differ across the two arms of the r and omized trial , both as a straight percentage and in survival analysis ( P = .81 ) . Conclusion At least in this single-session intervention trial , increasing choices in protection for women did not produce a change in disease risk compared with single- method approaches 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 |
12,371 | 25,914,910 | There was evidence that adherence interventions led to modest improvements in rates of cessation .
There was no evidence that interventions to increase adherence to medication led to any adverse events .
There is some evidence that such interventions improve the chances of achieving abstinence but again the evidence for this is relatively weak | BACKGROUND Pharmacological treatments for tobacco dependence , such as nicotine replacement therapy ( NRT ) , have been shown to be safe and effective interventions for smoking cessation .
Higher levels of adherence to these medications increase the likelihood of sustained smoking cessation , but many smokers use them at a lower dose and for less time than is optimal .
It is therefore important to determine the effectiveness of interventions design ed specifically to increase medication adherence .
Such interventions may include further educating individuals about the value of taking medications and providing additional support to overcome problems with maintaining adherence .
Secondary objectives were to i ) assess which intervention approaches are most effective ; ii ) determine the impact of interventions on potential precursors of adherence , such as underst and ing of the treatment and efficacy perceptions ; and iii ) evaluate key outcomes influenced by prior adherence , principally smoking cessation . | This study examined the role of a Medication Event Monitoring System ( MEMS ) to assess pill-taking behavior and enhance compliance within a r and omized trial of bupropion-SR for smoking cessation . Female participants ( N = 97 ) received MEMS bottles containing bupropion-SR 150 mg or placebo , to be taken twice daily . A r and omly selected “ feedback ” group of participants was told about the recording device in the bottle cap and received weekly graphic feedback showing their pill-taking behavior with specific instructions for improving compliance . A “ no-feedback ” group was not informed about the MEMS bottles , and did not receive further instruction or feedback beyond the st and ard dosing instructions . Compliance outcomes were the total doses taken and number of doses taken within the prescribed time interval . Results indicated significantly higher compliance over time for the feedback group . Participation in the feedback group predicted higher compliance beyond demographic , smoking , and health belief variables , suggesting significant benefit in providing brief feedback and instruction throughout the medication regimen Medication noncompliance with smoking cessation pharmacotherapies is a significant problem in both research and clinical setting s. This r and omized , controlled , single-blind study compared three single-session psychological interventions to increase use of nicotine gum during a 15-day treatment period . A total of 97 adult smokers were r and omized to receive st and ard treatment ( ST , n = 31 ) , brief feedback ( BF , n = 32 ) plus ST , or contingency management ( CM ; i.e. , payment for chewing at least 12 pieces/day on 10 of 15 intervention days , n = 34 ) plus ST and BF . Only the CM condition led to significantly greater average daily gum use ( pieces/day : ST , 6.17 ; BF , 7.81 ; CM , 10.17 [ p values < .05 ] ) and higher rates of compliance ( ST , 13.6 % ; BF , 25.2 % ; CM , 65.6 % [ p values < .001 ] ) . No differences were observed in smoking abstinence , nicotine withdrawal , or urinary cotinine as a function of treatment . Implication s of the present findings are discussed , including application to clinical trials and extension to real-world use of nicotine gum INTRODUCTION Varenicline , a first-line non-nicotine medication , has not been evaluated in Black smokers , and limited attention has been paid to pharmacotherapy adherence in smoking cessation trials . This pilot study estimated quit rates for Black smokers treated with varenicline and tested a behavioral intervention to aid varenicline adherence . METHODS Seventy-two Black smokers ( > 10 cigarettes per day ; cpd ) were r and omly assigned to adherence support ( AS ; n = 36 ) or st and ard care ( n = 36 ) . All participants received 3 months of varenicline and a single counseling session focused on making a quit plan . AS participants received 5 additional counseling sessions to encourage medication use . Outcome measures included salivary cotinine , and carbon monoxide confirmed smoking abstinence , reductions in self-reported cpd , and pill counts of varenicline adherence at Months 1 , 2 , and 3 . RESULTS Sixty-one participants ( 84.7 % ) completed follow-up at Month 3 . Participants were female ( 62.5 % ) , 46.8 years of age , and smoked 16.3 cpd . No treatment group differences were found on the smoking or adherence outcome measures ( p > .05 ) . Collapsing across treatment , varenicline adherence was adequate ( 86.1 % ) , yet despite a reduction of 12.2 ( 6.5 ) cpd from baseline to Month 3 ( p < 0.001 ) , only 23.6 % were confirmed quit at Month 3 . Participants who were quit at Month 3 had higher varenicline adherence rates ( 95.8 % ) than those who continued to smoke ( 80.8 % , p ≤ .05 ) . CONCLUSIONS Studies are needed to examine the efficacy of varenicline among Black smokers . Interventions to facilitate adherence to pharmacotherapy warrant further attention as adherence is linked to improved tobacco abstinence Nicotine replacement therapy is an effective intervention for smoking cessation , but adherence tends to be low . This article presents results from a pilot evaluation of a brief smoking cessation treatment to improve adherence to the nicotine patch among Latino smokers living with HIV/AIDS . Forty smokers were r and omized to receive either a st and ard 5 As counseling session and 8-week treatment of nicotine patch , or a similar intervention that added a 10-min module to the 5 As counseling that focused on improving adherence to the nicotine patch . Smoking outcomes ( breath carbon monoxide monitoring verified 7-day point prevalence and continuous abstinence ) were evaluated through a 3-month follow-up . Patch usage during the follow-up period was also assessed . Intention to treat analyses indicated that abstinence rates were 2 to 3 times higher in the adherence condition compared with the st and ard condition ( 7-day point prevalence abstinence : 35.0 % vs. 15.0 % ; continuous abstinence : 30.0 % vs. 10.0 % ) . Nicotine patch compliance over an 8-week period was also higher in the adherence condition than in the st and ard condition ( 44 % vs. 25 % ) . Although this small pilot was conducted to estimate effect sizes and was not powered to detect group differences , results are promising and suggest that adding a 10-min module focused on nicotine patch adherence to a st and ard 5 As protocol can increase abstinence rates . Given that this smoking cessation treatment was not specifically tailored to either HIV-positive smokers or Latino smokers , future research should examine whether it may be a promising approach for improving nicotine patch adherence in the general population of smokers Smoking represents an important health risk for people living with HIV ( PLHIV ) . Low adherence to smoking cessation pharmacotherapy may limit treatment effectiveness . In this study , 158 participants recruited from three HIV care centers in New York City were r and omized to receive 12-weeks of varenicline ( Chantix ) either alone as st and ard care ( SC ) or in combination with text message ( TM ) support or TM plus cell phone-delivered adherence-focused motivational and behavioral therapy ( ABT ) . Generalized linear mixed-effect models found a significant decline in varenicline adherence from week 1–12 across treatment groups . At 12-weeks , the probability of smoking abstinence was significantly higher in SC+TM+ABT than in SC . The study demonstrates the feasibility of delivering adherence-focused interventions to PLHIV who smoke . Findings suggest intensive behavioral support is an important component of an effective smoking cessation intervention for this population , and a focus on improving adherence self-efficacy may lead to more consistent adherence and higher smoking abstinence AIMS To assess the long-term efficacy of a fully automated digital multi-media smoking cessation intervention . DESIGN Two-arm r and omized control trial ( RCT ) . Setting World Wide Web ( WWW ) study based in Norway . PARTICIPANTS Subjects ( n = 396 ) were recruited via internet advertisements and assigned r and omly to conditions . Inclusion criteria were willingness to quit smoking and being aged 18 years or older . INTERVENTION The treatment group received the internet- and cell-phone-based Happy Ending intervention . The intervention programme lasted 54 weeks and consisted of more than 400 contacts by e-mail , web-pages , interactive voice response ( IVR ) and short message service ( SMS ) technology . The control group received a self-help booklet . Additionally , both groups were offered free nicotine replacement therapy ( NRT ) . MEASUREMENTS Abstinence was defined as ' not even a puff of smoke , for the last 7 days ' , and assessed by means of internet surveys or telephone interviews . The main outcome was repeated point abstinence at 1 , 3 , 6 and 12 months following cessation . FINDINGS Participants in the treatment group reported clinical ly and statistically significantly higher repeated point abstinence rates than control participants [ 22.3 % versus 13.1 % ; odds ratio ( OR ) = 1.91 , 95 % confidence interval ( CI ) : 1.12 - 3.26 , P = 0.02 ; intent-to-treat ) . Improved adherence to NRT and a higher level of post-cessation self-efficacy were observed in the treatment group compared with the control group . CONCLUSIONS As the first RCT documenting the long-term treatment effects of such an intervention , this study adds to the promise of digital media in supporting behaviour change Background The behavioural impact of pharmacogenomics is untested ; informing smokers of genetic test results for responsiveness to smoking cessation medication may increase adherence to this medication . The objective of this trial is to estimate the impact upon adherence to nicotine replacement therapy ( NRT ) of informing smokers that their oral dose of NRT has been tailored to a DNA analysis . Hypotheses to be tested are as follows : IAdherence to NRT is greater among smokers informed that their oral dose of NRT is tailored to an analysis of DNA ( genotype ) , compared to one tailored to nicotine dependence question naire score (phenotype).II Amongst smokers who fail to quit at six months , motivation to make another quit attempt is lower when informed that their oral dose of NRT was tailored to genotype rather than phenotype . Methods / Design An open label , parallel groups r and omised trial in which 630 adult smokers ( smoking 10 or more cigarettes daily ) using National Health Service ( NHS ) stop smoking services in primary care are r and omly allocated to one of two groups : i . NRT oral dose tailored by DNA analysis ( OPRM1 gene ) ( genotype ) , orii . NRT oral dose tailored by nicotine dependence question naire score (phenotype)The primary outcome is proportion of prescribed NRT consumed in the first 28 days following an initial quit attempt , with the secondary outcome being motivation to make another quit attempt , amongst smokers not abstinent at six months . Other outcomes include adherence to NRT in the first seven days and biochemically vali date d smoking abstinence at six months . The primary outcome will be collected on 630 smokers allowing sufficient power to detect a 7.5 % difference in mean proportion of NRT consumed using a two-tailed test at the 5 % level of significance between groups . The proportion of all NRT consumed in the first four weeks of quitting will be compared between arms using an independent sample s t-test and by estimating the 95 % confidence interval for observed between-arm difference in mean NRT consumption ( Hypothesis I ) . Motivation to make another quit attempt will be compared between arms in those failing to quit by six months ( Hypothesis II ) . Discussion This is the first clinical trial evaluating the behavioural impact on adherence of prescribing medication using genetic rather than phenotypic information . Specific issues regarding the choice of design for trials of interventions of this kind are discussed . Trial detailsFunder : Medical Research Council (MRC)Grant number : G0500274IS RCT N : 14352545 Date trial stated : June 2007Expected end date : December 2009Expected reporting date : December INTRODUCTION Nicotine replacement therapy ( NRT ) medications have been shown to be effective in increasing smoking cessation rates . There is , however , a lack of good evidence describing how individuals in primary care use these medications and which factors are likely to affect this . The study objectives are to describe adherence and consumption , examine key factors that may determine use , and examine the relationship between consumption of NRT and abstinence from smoking . METHODS Secondary analysis of data from a r and omized controlled trial conducted in smoking cessation services in primary care . Adult smokers ( n = 633 ) starting a quit attempt within smoking cessation clinics were followed for 6 months , with NRT use closely monitored for an initial treatment period of 4 weeks . The main outcomes were 4-week adherence to prescribed NRT , mean daily consumption of NRT over the 4-week period , and abstinence from smoking at 4 weeks . RESULTS Levels of adherence to prescribed NRT were high : more than 94 % in participants who completed the treatment period . After controlling for possible confounders , prescribing higher doses of patch and oral NRT was associated with higher mean daily consumption of NRT . Using an inhalator to deliver oral NRT was associated with both higher adherence and higher consumption . The amount of NRT consumed predicted future abstinence when reverse causation was accounted for . CONCLUSIONS Most individuals within a clinical trial in primary care who persisted with a quit attempt adhered closely to their prescription . Prescribing higher doses of NRT led to higher consumption and higher consumption to higher abstinence INTRODUCTION There is increasing evidence that response to pharmacological treatment for nicotine dependence may be moderated by genetic polymorphisms . However , the feasibility , acceptability , and impact of genetically tailoring treatment in real-world clinical setting s are unknown . METHODS We conducted a multiphased , mixed- methods feasibility study with current smokers to develop and evaluate a patient-centered , theoretically grounded personalized medicine treatment protocol . The initial research phase included formative work to develop intervention material s. The second phase included a r and omized pilot trial to evaluate the intervention . Trial participants ( n = 36 ) were genotyped for ANKK1 rs1800497 and were r and omized to receive genetic feedback ( GF ) plus st and ard behavioral counseling ( BC ) for smoking cessation or BC without GF . All participants received genetically tailored pharmacotherapy ( nicotine patch or bupropion ) . RESULTS The intervention was feasible to implement and was acceptable to participants based on satisfaction ratings and objective measures of participation . There was no evidence that the GF result ed in adverse psychological outcomes ( e.g. , depression , fatalism , reduced perceived control over quitting , differential motivation for quitting ) based on quantitative or qualitative outcomes . CONCLUSIONS Study results suggest that it is feasible to offer treatment within a health care setting that includes genetically tailored pharmacotherapy and doing so had no apparent adverse psychological impacts . Further evaluation of pharmacogenetically tailored smoking cessation interventions appears warranted BACKGROUND Nicotine-replacement therapy is effective for smoking cessation outside pregnancy and its use is widely recommended during pregnancy . We investigated the efficacy and safety of nicotine patches during pregnancy . METHODS We recruited participants from seven hospitals in Engl and who were 16 to 50 years of age with pregnancies of 12 to 24 weeks ' gestation and who smoked five or more cigarettes per day . Participants received behavioral cessation support and were r and omly assigned to 8 weeks of treatment with active nicotine patches ( 15 mg per 16 hours ) or matched placebo patches . The primary outcome was abstinence from the date of smoking cessation until delivery , as vali date d by measurement of exhaled carbon monoxide or salivary cotinine . Safety was assessed by monitoring for adverse pregnancy and birth outcomes . RESULTS Of 1050 participants , 521 were r and omly assigned to nicotine-replacement therapy and 529 to placebo . There was no significant difference in the rate of abstinence from the quit date until delivery between the nicotine-replacement and placebo groups ( 9.4 % and 7.6 % , respectively ; unadjusted odds ratio with nicotine-replacement therapy , 1.26 ; 95 % confidence interval , 0.82 to 1.96 ) , although the rate was higher at 1 month in the nicotine-replacement group than in the placebo group ( 21.3 % vs. 11.7 % ) . Compliance was low ; only 7.2 % of women assigned to nicotine-replacement therapy and 2.8 % assigned to placebo used patches for more than 1 month . Rates of adverse pregnancy and birth outcomes were similar in the two groups . CONCLUSIONS Adding a nicotine patch ( 15 mg per 16 hours ) to behavioral cessation support for women who smoked during pregnancy did not significantly increase the rate of abstinence from smoking until delivery or the risk of adverse pregnancy or birth outcomes . However , low compliance rates substantially limited the assessment of safety . ( Funded by the National Institute for Health Research Health Technology Assessment Programme ; Current Controlled Trials number , IS RCT N07249128 . ) BACKGROUND Smoking is the leading preventable cause of death , and tobacco control professionals continue to make progress in cessation efforts . Pharmacists can assist smokers seeking to quit by offering counseling on smoking cessation pharmacotherapies . Pragmatic r and omized trials are useful for investigating practical questions about an intervention 's risks , benefits , and costs in routine clinical practice . OBJECTIVE To evaluate an enhanced pharmacy care ( EPC ) program involving personalized pharmacist-provided telephone counseling for supporting prescription smoking cessation medications compared with usual care ( UC ) . METHODS Cigarette smokers filling a newly prescribed smoking cessation pharmacotherapy and with pharmacy benefits managed by Express Scripts were recruited . Qualified subjects were r and omized 1:1 to EPC and UC . Subjects in EPC received 3 telephone-counseling sessions from specialist pharmacists during the early course of the study , while subjects in UC did not receive any counseling sessions . Study outcomes were collected through telephone contact and using the Express Scripts prescription data base . The primary outcome assessed the 1-week point prevalence ( PP ) of smoking abstinence at the end of the trial ( week 12 ) . Secondary outcomes included 4-week PP at week 12 and adherence , evaluated by proportion of days covered ( PDC ) , to prescribed smoking cessation pharmacotherapies . RESULTS There were 1,017 r and omized subjects . Among them , 1,002 subjects were included in the analysis , and 513 were r and omized into EPC and 489 into UC . Baseline demographics , smoking history , and prescribed smoking cessation pharmacotherapies were comparable . Varenicline and nicotine replacement therapy ( NRT ) were most frequently prescribed for smoking cessation . In EPC , 46.0 % received all 3 counseling sessions ; 29.4 % received 2 sessions ; and 14.6 % received 1 session . Overall , 353 subjects in EPC and 383 subjects in UC completed the week 12 assessment . In the analysis for 1-week PP of smoking abstinence at week 12 , the percentage of abstainers in EPC was numerically higher than in UC ( 42.3 % vs. 38.2 % ) with OR = 1.24 , 95 % CI = 0.96 - 1.61 . It was not statistically significant . Adherence to prescription smoking cessation medication was significantly higher in EPC versus UC ( 49.7 % vs. 45.6 % ; P = 0.033 ) . CONCLUSIONS This study evaluated whether a telephone-based pharmacy care program , provided by pharmacists and design ed to support attempted quitters , improved quitting and increased adherence over usual care . The findings suggest that an enhanced program may benefit smokers by increasing prescription smoking cessation medication adherence . Future research should explore this program 's effect on smokers who are compliant , based on insights on quitting provided by the post hoc analyses and limitations of the current study design . DISCLOSURES This study was sponsored by Pfizer . Gong , Baker , Zou , Bruno , Jumadilova , and Lawrence are employees and stockholders of Pfizer . Wilson and Ewel are employees of United Bio Source Corporation , which received funding from Pfizer for conducting this study and for the development of this manuscript . Study concept and design were contributed by Gong , Bruno , and Ewel , with assistance from Jumadilova , Lawrence , and Zou . Gong , Jumadilova , Lawrence , and Ewel collected the data . Data interpretation was performed by Baker , Zou , and Wilson , assisted by Gong , Lawrence , and Ewel . The manuscript was written by Baker , Ewel , and Gong , with assistance from the other authors , and revised by Baker , Wilson , Zou , and Gong , with assistance from Bruno and Jumadilova OBJECTIVE --To assess the effectiveness of 12 weeks ' treatment with a 24 hour transdermal nicotine patch in helping heavy smokers to stop smoking ; also to assess the value of a specially written support booklet about smoking cessation and patch use compared with a simple advice pamphlet . DESIGN --Double blind placebo controlled r and omised trial with a 2 x 2 factorial design . SETTING --19 general practice s in Oxfordshire . SUBJECTS--1686 heavy smokers aged 25 - 64 ( mean cigarette consumption 24/day ; mean duration of smoking 25 years ) . MAIN OUTCOME MEASURE -- Sustained cessation for the last four weeks of the 12 week treatment period , confirmed by saliva cotinine estimation ( 226/262 cases ; 86.3 % ) or expired carbon monoxide concentration ( 36/262 ; 13.7 % ) . Patients lost to follow up ( 155/1686 ; 9 % ) were assumed to have continued to smoke . RESULTS --Cessation was confirmed in 163 patients ( 19.4 % ) using the nicotine patch and 99 patients ( 11.7 % ) using the placebo patch ( difference 7.6 % ( 95 % confidence interval 4.2 % to 11.1 % ) ; p < 0.0001 ) . There was no significant advantage in using the more detailed written support material . The most important adverse effect of the patch was local skin irritation , which occurred in 15.8 % ( 133/842 ) and 5.1 % ( 43/844 ) of patients using the nicotine and placebo patches respectively , was grade d as severe in 4.8 % ( 40 ) and 1.1 % ( nine ) , and was stated as a reason for withdrawal from the trial in 9.5 % ( 80 ) and 2.8 % ( 24 ) . CONCLUSION --Nicotine patches are effective in a general practice setting with nursing support , but the extent to which this effect is sustained can not be assessed until the results of longer term follow up are known AIMS To examine the effectiveness of smoking reduction counselling plus free nicotine replacement therapy ( NRT ) for smokers not willing to quit . DESIGN , SETTING AND PARTICIPANTS A total of 1154 Chinese adult smokers not willing to quit but who were interested in reducing smoking were allocated r and omly to three arms . Intervention group A1 ( n=479 ) received face-to-face counselling on smoking reduction and adherence to NRT at baseline , 1 week and 4 weeks with 4 weeks of free NRT . Group A2 ( n=449 ) received the same intervention , but without the adherence intervention . Control group B ( n=226 ) received simple cessation advice at baseline . MEASUREMENTS Self-reported 7-day point prevalence of tobacco abstinence and reduction of cigarette consumption ( ≥50 % ) at 6 months and continuous use of NRT for 4 weeks at 3 months . FINDINGS Using intention-to-treat analysis , compared to control group B , the intervention groups ( A1+A2 ) had achieved higher 6-month tobacco abstinence ( 17.0 % versus 10.2 % , P=0.01 ) and reduction rates ( 50.9 % versus 25.7 % , P<0.001 ) . There was no significant difference in the 4-week NRT adherence rate at 3 months , but group A1 achieved a higher abstinence rate than group A2 at 6 months ( 20.9 % versus 12.9 % ; P=0.001 ) . CONCLUSIONS In smokers with no immediate plans to quit , smoking reduction programmes with behavioural support and nicotine replacement therapy are more effective than brief advice to quit . Current guidelines recommend advice to quit on medical grounds as the best clinical intervention in this group of smokers , but smoking reduction programmes offer an alternative and effective option This study was conducted to replicate and extend initial positive findings on the usefulness of a Medication Event Monitoring System ( MEMS ) to assess pill-taking behavior and enhance compliance with bupropion for smoking cessation . Participants ( N=55 ) received MEMS bottles containing bupropion-SR ( 150 mg ) to be taken twice daily for 7 weeks . For participants r and omly assigned to the Enhanced Therapy group ( n=27 ) , weekly individual smoking cessation therapy sessions included an additional 10 min of MEMS feedback and compliance enhancement counseling using CBT techniques . The Usual Care group ( n=28 ) received weekly individual smoking cessation sessions only . Compliance outcomes included total doses taken and number of doses taken within the prescribed time interval . Results indicated significantly higher compliance over time for the Enhanced Therapy group . Smoking abstinence rates did not differ between the two groups , although results from the pooled sample analysis showed a significant association between level of medication compliance and abstinence status at treatment weeks 3 and 6 . Incorporating MEMS-based compliance interventions into smoking pharmacotherapy trials is recommended AIMS To identify promising intervention components that help smokers attain and maintain abstinence during a quit attempt . DESIGN A 2 × 2 × 2 × 2 × 2 r and omized factorial experiment . SETTING Eleven primary care clinics in Wisconsin , USA . PARTICIPANTS A total of 544 smokers ( 59 % women , 86 % white ) recruited during primary care visits and motivated to quit . INTERVENTIONS Five intervention components design ed to help smokers attain and maintain abstinence : ( 1 ) extended medication ( 26 versus 8 weeks of nicotine patch + nicotine gum ) ; ( 2 ) maintenance ( phone ) counseling versus none ; ( 3 ) medication adherence counseling versus none ; ( 4 ) automated ( medication ) adherence calls versus none ; and ( 5 ) electronic medication monitoring with feedback and counseling versus electronic medication monitoring alone . MEASUREMENTS The primary outcome was 7-day self-reported point-prevalence abstinence 1 year after the target quit day . FINDINGS Only extended medication produced a main effect . Twenty-six versus 8 weeks of medication improved point-prevalence abstinence rates ( 43 versus 34 % at 6 months ; 34 versus 27 % at 1 year ; P = 0.01 for both ) . There were four interaction effects at 1 year , showing that an intervention component 's effectiveness depended upon the components with which it was combined . CONCLUSIONS Twenty-six weeks of nicotine patch + nicotine gum ( versus 8 weeks ) and maintenance counseling provided by phone are promising intervention components for the cessation and maintenance phases of smoking treatment BACKGROUND It has been reported that the efficacy of acute forms of nicotine replacement therapy , such as nicotine gum and lozenges , improves when sufficient quantities of medication are used . OBJECTIVE This analysis examined whether adherence with daily nicotine patch wear was associated with improved rates of smoking abstinence . METHODS This was a secondary analysis of data from a double-blind study in which subjects were r and omized to receive either an active nicotine patch or a placebo patch under simulated over-the-counter conditions . Subjects were asked to complete a daily diary on their patch use and smoking . Logistic regression , controlling for smoking in the first 3 weeks of treatment , was used to evaluate the likelihood of abstinence at 6 weeks as a function of treatment assignment ( active vs placebo ) and adherence ( ie , patch wear for > or=20 of the first 21 days of treatment ) . The relationship between reported adverse events and adherence was also examined . RESULTS This analysis involved data from 371 subjects , 204 using the active patch and 167 using the placebo patch . The study population was mainly white ( 87.3 % ) , had a mean age of 42.8 years , a mean weight of 77.3 kg , had been smoking for a mean of 24.4 years , and smoked a mean of 25.2 cigarettes per day . Two hundred fifty-three subjects were classified as adherent . Rates of adherence did not differ significantly between the active and placebo groups ( 139 [ 68.1 % ] and 114 [ 68.3 % ] , respectively ) . The likelihood of experiencing an adverse event did not differ significantly between adherent and nonadherent subjects in either group . Among active patch users , 61.5 % of nonadherent subjects experienced an adverse event , compared with 59.7 % of adherent subjects ; among placebo patch users , the corresponding proportions were 41.5 % and 43.9 % . Among active patch users , the odds of abstinence at 6 weeks were more than 3 times greater for adherent versus nonadherent subjects ( 53.2 % vs 21.5 % , respectively ; adjusted odds ratio [ OR ] = 3.25 ; 95 % CI , 1.30 - 8.09 ; P = 0.011 ) ; no benefit of adherence over nonadherence was seen among users of the placebo patch ( 16.7 % vs 15.1 % ; adjusted OR = 0.60 ; 95 % CI , 0.16 - 2.31 ) . The interaction between treatment group and adherence was statistically significant ( P = 0.022 ) . CONCLUSION Under conditions simulating over-the-counter use , adherence to daily nicotine patch wear within the first 3 weeks of treatment was associated with an improved likelihood of achieving smoking abstinence at 6 weeks BACKGROUND St and ard , generic self-help material s have been largely ineffective as behavioral treatments for smoking cessation . In contrast , self-help programs tailored to the needs of specific smokers have shown promise in facilitating quitting . OBJECTIVE To evaluate the incremental efficacy of the Committed Quitters Program ( CQP ) , a set of computer-tailored material s offered to purchasers of nicotine polacrilex gum , compared with a briefuntailored user 's guide and audiotape , both as supplements to nicotine replacement therapy . METHODS We conducted a r and omized , open-label trial with 3 parallel arms . Subjects were smokers who purchased 2- or 4-mg nicotine polacrilex gum and called the CQP toll-free enrollment line . Three thous and six hundred twenty-seven subjects consented to participate in 1 of 3 study arms : ( 1 ) those receiving the CQP material s ( CQP group , n= 1,217 ) , ( 2 ) those receiving CQP material s and an outbound telephone call ( CQP + C group , n= 1,207 ) ; and ( 3 ) those receiving no supplemental intervention beyond the user 's guide and audiotape that were prepackaged with the nicotine polacrilex gum ( UG group , n= 1,203 ) . Twenty-eight-day continuous abstinence rates were assessed by telephone interviews at 6 weeks and 10-week continuous rates at 12 weeks into treatment . RESULTS Abstinence rates among respondents at the 6- and 12-week assessment s were significantly higher for the CQP ( 36.2 % and 27.6 % ) and CQP + C ( 35.5 % and 27.3 % ) groups compared with the UG group ( 24.7 % and 17.7 % ) at both intervals . The quit rates for the CQP and CQP + C groups were almost identical . CONCLUSIONS The CQP proved to be an effective behavioral treatment , enhancing quit rates over and above nicotine replacement therapy and a brief untailored written guide and audiotape Background : There is insufficient and conflicting evidence about whether more intensive behavioural support is more effective than basic behavioural support for smoking cessation and whether primary care nurses can deliver effective behavioural support . Methods : A r and omised controlled trial was performed in 26 UK general practice s. 925 smokers of ⩾10 cigarettes per day were r and omly allocated to basic or weekly support . All participants were seen before quitting , telephoned around quit day , and seen 1 and 4 weeks after the initial appointment ( basic support ) . Participants receiving weekly support had an additional telephone call at 10 days and 3 weeks after the initial appointment and an additional visit at 2 weeks to motivate adherence to nicotine replacement and renew quit attempts . 15 mg/16 h nicotine patches were given to all participants . The outcome was assessed by intention to treat analyses of the percentage confirmed sustained abstinence at 4 , 12 , 26 and 52 weeks after quit day . Results : Of the 469 and 456 participants in the basic and weekly arms , the numbers ( % ) who quit and the percentage difference were 105 ( 22.4 % ) vs 102 ( 22.4 % ) , 0.1 % ( 95 % CI −5.3 % to 5.5 % ) at 4 weeks , 66 ( 14.1 % ) vs 52 ( 11.4 % ) , −2.6 % ( 95 % CI −6.9 % to 1.7 % ) at 12 weeks , 50 ( 10.7 % ) vs 40 ( 8.8 % ) , −1.9 % ( 95 % CI −5.7 % to 2.0 % ) at 26 weeks and 36 ( 7.7 % ) vs 30 ( 6.6 % ) , −1.1 % ( 95 % CI −4.4 % to 2.3 % ) at 52 weeks . Conclusions : The absolute quit rates achieved are those expected from nicotine replacement alone , implying that neither basic nor weekly support were effective . Primary care smoking cessation treatment should provide pharmacotherapy with sufficient support only to ensure it is used appropriately , and those in need of support should be referred to specialists AIM To assess the efficacy of World Wide Web-based tailored behavioral smoking cessation material s among nicotine patch users . DESIGN Two-group r and omized controlled trial . SETTING World Wide Web in Engl and and Republic of Irel and . PARTICIPANTS A total of 3971 subjects who purchased a particular br and of nicotine patch and logged-on to use a free web-based behavioral support program . INTERVENTION Web-based tailored behavioral smoking cessation material s or web-based non-tailored material s. MEASUREMENTS Twenty-eight-day continuous abstinence rates were assessed by internet-based survey at 6-week follow-up and 10-week continuous rates at 12-week follow-up . FINDINGS Using three approaches to the analyses of 6- and 12-week outcomes , participants in the tailored condition reported clinical ly and statistically significantly higher continuous abstinence rates than participants in the non-tailored condition . In our primary analyses using as a denominator all subjects who logged-on to the treatment site at least once , continuous abstinence rates at 6 weeks were 29.0 % in the tailored condition versus 23.9 % in the non-tailored condition ( OR = 1.30 ; P = 0.0006 ) ; at 12 weeks continuous abstinence rates were 22.8 % versus 18.1 % , respectively ( OR = 1.34 ; P = 0.0006 ) . Moreover , satisfaction with the program was significantly higher in the tailored than in the non-tailored condition . CONCLUSIONS The results of this study demonstrate a benefit of the web-based tailored behavioral support material s used in conjunction with nicotine replacement therapy . A web-based program that collects relevant information from users and tailors the intervention to their specific needs had significant advantages over a web-based non-tailored cessation program AIMS Most smokers attempt to stop smoking without using help . We evaluated the efficacy of a decision aid to motivate quitters to use efficacious treatment . SETTING AND PARTICIPANTS , A total of 1,014 were recruited from a convenience sample of 3,391 smokers who intended to quit smoking within 6 months . DESIGN AND Smokers were assigned r and omly to either receive the decision aid or no intervention . The decision aid was expected to motivate quitters to use efficacious cessation methods and contained neutral information on treatment methods , distinguishing between efficacious and non-efficacious treatments . MEASUREMENTS Baseline question naire and follow-ups were used 2 weeks and 6 months after the start of the intervention . FINDINGS The decision aid increased knowledge of cessation methods and induced a more positive attitude towards these methods . Furthermore , 45 % reported increased confidence about being able to quit and 43 % said it helped them to choose between treatments . However , no clear effect on usage of treatment aids was found , but the intervention group had more quit attempts ( OR=1.52 , 95 % CI 1.14 - 2.02 ) and higher point prevalence abstinence at 6-month follow-up ( 20.2 % versus 13.6 % ; OR=1.51 , 95 % CI=1.07 - 2.11 ) . CONCLUSIONS An aid to help smokers decide to use efficacious treatment when attempting to quit smoking had a positive effect on smoking cessation , while failing to increase the usage of efficacious treatment . This finding lends support to the notion that the mere promotion of efficacious treatments for tobacco addiction might increase the number of quit attempts , irrespective of the actual usage of treatment The objective of this study was to test the efficacy of specially design ed educational material s to correct misperceptions held by smokers about nicotine , nicotine medications , low tar cigarettes , filters and product ingredients . To accomplish this , 682 New York State Smokers ' Quitline callers were r and omized to one of two groups : control group received counseling , nicotine patches and quit smoking guide ; and experimental group received counseling , nicotine patches , quit guide , plus information about cigarette characteristics mailed in a br and -tailored box . Participants were contacted 1 month later to assess knowledge about cigarettes and actions taken to alter smoking behavior . The results found that respondents in the experimental condition were more likely to report using and sharing the test material s with others compared with the control condition . Overall mean knowledge scores for the experimental group were slightly higher compared with those who received the st and ard material s. Knowledge of cigarette ingredients was not related to quit attempts or quitting smoking . This study found that the experimental material s were better recalled and contributed to higher levels of knowledge about specific cigarette design features ; however , this did not translate into changes in smoking behavior BACKGROUND Smoking remains the primary preventable cause of death and illness in the U.S. Effective , convenient treatment programs are needed to reduce smoking prevalence . PURPOSE This study compared the effectiveness of three modalities of a behavioral smoking-cessation program in smokers using varenicline . METHODS Current treatment-seeking smokers ( n=1202 ) were recruited from a large healthcare organization between October 2006 and October 2007 . Eligible participants were r and omized to one of three smoking-cessation interventions : web-based counseling ( n=401 ) ; proactive telephone-based counseling ( PTC ; n=402 ) ; or combined PTC and web counseling ( n=399 ) . All participants received a st and ard 12-week FDA -approved course of varenicline . Self-report determined the primary outcomes ( 7-day point prevalent abstinence at 3- and 6-month follow-ups ) ; the number of days varenicline was taken ; and treatment-related symptoms . Behavioral measures determined utilization of both the web- and Phone-based counseling . RESULTS Intent-to-treat analyses revealed relatively high percentages of abstinence at 3 months ( 38.9 % , 48.5 % , 43.4 % ) and at 6 months ( 30.7 % , 34.3 % , 33.8 % ) for the web , PTC , and PTC-web groups , respectively . The PTC group had a significantly higher percentage of abstinence than the web group at 3 months ( OR=1.48 , 95 % CI=1.12 , 1.96 ) , but no between-group differences in abstinence outcomes were seen at 6 months . CONCLUSIONS Phone counseling had greater treatment advantage for early cessation and appeared to increase medication adherence , but the absence of differences at 6 months suggests that any of the interventions hold promise when used in conjunction with varenicline The effectiveness of nicotine chewing gum in a family practice setting was evaluated . Ninety-nine subjects who were given a prescription for nicotine chewing gum were evaluated after one year to determine smoking status . Forty-nine subjects received only the gum , and 50 received the gum along with extensive personal instruction regarding its use . The two groups were compared with a third control group of 40 smokers who expressed no desire to stop smoking . At the end of one year , 12.2 percent of those receiving only gum and 10 percent receiving gum and instruction had stopped smoking , compared with a 20 percent cessation rate for the control group . The observed difference was not statistically significant ( P greater than .05 ) . Results of this study suggest that the use of nicotine gum alone may not be a viable alternative for family physicians whose patients desire to quit smoking BACKGROUND There are several nicotine replacement products on the market , and physicians are likely to be asked with increasing frequency about which of these products their patients should use . OBJECTIVE To provide a basis for rational advice by comparing nicotine polacrilex ( gum ) , a transdermal patch , nasal spray , and an inhaler . DESIGN R and omized trial with assessment s at the quit date and 1 , 4 , and 12 weeks later . SETTING Hospital smokers ' clinic . PATIENTS Male and female community volunteers ( N = 504 ) smoking 10 or more cigarettes per day and seeking help to stop smoking . INTERVENTIONS Patients were given brief advice , and purchased their nicotine replacement treatment at approximately half the regular retail price . MAIN OUTCOME MEASURES Nicotine replacement treatment use , ratings of withdrawal symptoms , ratings of product characteristics and helpfulness , and biochemically vali date d continuous lapse-free abstinence . RESULTS The products did not differ in their effects on withdrawal discomfort , urges to smoke , or rates of abstinence . The continuous vali date d 12-week abstinence rates were 20 % , 21 % , 24 % , and 24 % in the gum , patch , spray , and inhaler groups , respectively . Compliance with recommended nicotine replacement treatment use was high for the patch , low for gum , and very low for the spray and the inhaler . The spray was underused because of adverse effects more often than the other products . In the subjects using the spray , the level of use among abstainers at week 1 predicted outcome at week 12 . The inhaler was rated as more embarrassing to use than the other products , but provided at least as much nicotine as the gum . CONCLUSION When asked about nicotine replacement treatment products available , physicians should note that , despite low compliance with the recommended dose of the spray and inhaler and differences in product ratings , overall , there are no notable differences between the products in their effects on withdrawal discomfort , perceived helpfulness , or general efficacy INTRODUCTION Telephone tobacco quitlines are effective and are widely used , with more than 500,000 U.S. callers in 2010 . This study investigated the clinical effectiveness and cost-effectiveness of 3 different quitline enhancements : combination nicotine replacement therapy ( NRT ) , longer duration of NRT , and counseling to increase NRT adherence . METHODS In this study , 987 quitline callers were r and omized to a combination of quitline treatments in a 2 × 2 × 2 factorial design : NRT duration ( 2 vs. 6 weeks ) , NRT type ( nicotine patch only vs. patch plus nicotine gum ) , and st and ard 4-call counseling ( SC ) versus SC plus medication adherence counseling ( MAC ) . The primary outcome was 7-day point-prevalence abstinence ( PPA ) at 6 months postquit in intention-to-treat ( ITT ) analyses . RESULTS Combination NRT for 6 weeks yielded the highest 6-month PPA rate ( 51.6 % ) compared with 2 weeks of nicotine patch ( 38.4 % ) , odds ratios [ OR ] = 1.71 ( 95 % confidence interval [CI]:1.20 - 2.45 ) . A similar result was found for 2 weeks of combination NRT ( 48.2 % ) , OR = 1.49 ( 95 % CI : 1.04 - 2.14 ) but not for 6 weeks of nicotine patch alone ( 46.2 % ) , OR = 1.38 ( 95 % CI : 0.96 - 1.97 ) . The MAC intervention effect was nonsignificant . Cost analyses showed that the 2-week combination NRT group had the lowest cost per quit ( $ 442 vs. $ 464 for 2-week patch only , $ 505 for 6-week patch only , and $ 675 for 6-week combination NRT ) . CONCLUSIONS Combination NRT for 2 or 6 weeks increased 6-month abstinence rates by 10 % and 13 % , respectively , over rates produced by 2 weeks of nicotine patch when offered with quitline counseling . A 10 % improvement would potentially yield an additional 50,000 quitters annually , assuming 500,000 callers to U.S. quitlines per year The present study assessed the incremental effectiveness of behavioral self-help material s specifically written to accompany nicotine gum . Subjects ( 187 women and 117 men ) were r and omly assigned either behavioral self-help booklets or a factual information pamphlet . All subjects received prescriptions for Nicorette from study physicians . Contrary to prediction , subjects provided self-help booklets fared no better than did subjects provided comparison pamphlets . Overall abstinence levels were encouraging , however . Nicotine gum users were far more likely than nonusers to maintain abstinence through 6-month follow-up . Perhaps self-help material s could be improved by condensing and simplifying content and by adopting a more attractive multicolored pictorial format The few extant reports examining the relationship between diurnal patterns of pre-cessation smoking and cessation nicotine replacement use suggest that this relationship may be important in preventing smoking relapse . The current study evaluated three interventions to increase nicotine gum use : st and ard treatment ( ST , N = 31 ) , ST plus brief feedback about nicotine attitudes and knowledge ( BF , N = 32 ) , or BF plus contingent monetary reinforcement for nicotine gum use ( CM , N = 34 ) . Subsets of the 97 r and omized subjects were selected based on availability of adequate data for analyses : baseline phase ( i.e. , 6 - 7 days of ad libitum smoking , N = 63 ) or the treatment phase ( i.e. , 13 - 15 days of treatment , N = 47 ) . For both cigarettes and nicotine gum , participants showed a characteristic pattern of increasing use during the morning hours , followed by stable use in the afternoon and evening , with a steep decrease prior to sleep onset . Patterns of diurnal gum use did not differ by compliance intervention . Greater morning use of cigarettes or gum was associated with smoking relapse while greater evening and night use of cigarettes or gum was associated with abstinence . Underst and ing of diurnal patterns of smoking and NRT use may ultimately inform tailored scheduling of NRT The purpose of this study was to test two combination motivational plus pharmacological interventions for smoking cessation among HIV positive smokers . Participants were 40 adults receiving HIV care who smoked daily reporting interest in smoking reduction . Measures were administered at baseline , 1-month , and 3-month follow-ups . Participants were r and omly assigned to self-guided reading plus nicotine patch ( n = 18 ) or motivational interviewing plus nicotine patch ( n = 22 ) . Groups did not differ at 3 months on biochemically-verified abstinence . The sample reduced cigarettes per day by half a pack and the percent of smoking days by 41 % , and 22 % were abstinent at 3-month follow-up . Compliance with the nicotine patch was poor and declined over time , but patch use was unrelated to carbon monoxide level at 3-month follow-up . Smoking cessation interventions for people with HIV can be helpful and should include components that encourage some smoke-free days , increase self-efficacy , and attend to adherence to nicotine replacement treatment Objective To test the hypothesis that communicating risk of developing Crohn ’s disease based on genotype and that stopping smoking can reduce this risk , motivates behaviour change among smokers at familial risk . Design Parallel group , cluster r and omised controlled trial . Setting Families with Crohn ’s disease in the United Kingdom . Participants 497 smokers ( mean age 42.6 ( SD 14.4 ) years ) who were first degree relatives of prob and s with Crohn ’s disease , with outcomes assessed on 209/251 ( based on DNA analysis ) and 217/246 ( st and ard risk assessment ) . Intervention Communication of risk assessment for Crohn ’s disease by postal booklet based on family history of the disease and smoking status alone , or with additional DNA analysis for the NOD2 genotype . Participants were then telephoned by a National Health Service Stop Smoking counsellor to review the booklet and deliver brief st and ard smoking cessation intervention . Calls were tape recorded and a r and om sub sample selected to assess fidelity to the clinical protocol . Main outcome measure The primary outcome was smoking cessation for 24 hours or longer , assessed at six months . Results The proportion of participants stopping smoking for 24 hours or longer did not differ between arms : 35 % ( 73/209 ) in the DNA arm versus 36 % ( 78/217 ) in the non-DNA arm ( difference −1 % , 95 % confidence interval −10 % to 8 % , P=0.83 ) . The proportion making a quit attempt within the DNA arm did not differ between those who were told they had mutations putting them at increased risk ( 36 % ) , those told they had none ( 35 % ) , and those in the non-DNA arm ( 36 % ) . Conclusion Among relatives of patients with Crohn ’s disease , feedback of DNA based risk assessment s does not motivate behaviour change to reduce risk any more or less than st and ard risk assessment . These findings accord with those across a range of population s and behaviours . They do not support the promulgation of commercial DNA based tests nor the search for gene variants that confer increased risk of common complex diseases on the basis that they effectively motivate health related behaviour change . Trial registration Current Controlled Trials IS RCT N21633644 INTRODUCTION Despite decades of tobacco use decline among the general population in the United States , tobacco use among low-income population s continues to be a major public health concern . Smoking rates are higher among individuals with less than a high school education , those with no health insurance , and among individuals living below the federal poverty level . Despite these disparities , smoking cessation treatments for low-income population s have not been extensively tested . In the current study , the efficacy of 2 adjunctive smoking cessation interventions was evaluated among low-income smokers who were seen in a primary care setting . METHODS A total of 846 participants were r and omly assigned either to motivational enhancement treatment plus brief physician advice and 8 weeks of nicotine replacement therapy ( NRT ) or to st and ard care , which consisted of brief physician advice and 8 weeks of NRT . Tobacco smoking abstinence was at 1 , 2 , 6 , and 12 months following baseline . RESULTS The use of the nicotine patch , telephone counseling , and positive decisional balance were predictive of increased abstinence rates , and elevated stress levels and temptation to smoke in both social/habit and negative affect situations decreased abstinence rates across time . Analyses showed intervention effects on smoking temptations , length of patch use , and number of telephone contacts . Direct intervention effects on abstinence rates were not significant , after adjusting for model predictors and selection bias due to perir and omization attrition . CONCLUSIONS Integrating therapeutic approaches that promote use of and adherence to medications for quitting smoking and that target stress management and reducing negative affect may enhance smoking cessation among low-income smokers INTRODUCTION This secondary analysis examined the association between adherence to nicotine replacement therapy ( NRT ) and smoking cessation among pregnant smokers enrolled in Baby Steps , an open-label r and omized controlled trial testing cognitive-behavioral therapy ( CBT ) versus CBT plus NRT . METHOD The analysis included only women who received NRT for whom we had complete data ( N = 104 ) . Data came from daily calendars created from recordings of counseling sessions and from telephone surveys at baseline and 38 weeks gestation . RESULTS Overall , 29 % of the 104 women used NRT for the recommended 6 weeks and 41 % used NRT as directed in the first 48 hr after a quit attempt . Ordinal logistic regression modeling indicated that using NRT as directed in the first 48 hr and having made a previous quit attempt were the strongest predictors of longer NRT use . Univariate analyses suggested that primigravid women and women who used NRT longer were more likely to report quitting at 38 weeks gestation . DISCUSSION Findings indicated that adherence to NRT is low among pregnant smokers , but adherence was a predictor of cessation . Future trials should emphasize adherence , particularly more days on NRT , to promote cessation during pregnancy INTRODUCTION Detailed analysis of adherence to tobacco cessation medications and predictors of adherence is sparse in published literature . In this analysis , we assessed adherence to tobacco dependence treatment , association of adherence with abstinence , and predictors of adherence . METHODS We analyzed pooled results from 2 r and omized controlled trials . Adult smokers ( N = 2,045 ) who were r and omly assigned to 12 weeks of treatment and took at least 1 dose of the assigned medication ( varenicline [ 692 ] , bupropion sustained release [ 669 ] , or placebo [ 684 ] ) were included . Treatment adherence was defined as any subject who took > or=1 dose of study drug for > or=80 % days during the 12-week treatment period ( " completers " ) . Smoking abstinence was assessed using carbon monoxide-confirmed 4-week continuous abstinence rate at end of treatment ( Weeks 9 - 12 ) . RESULTS Adherence rates for completers who received varenicline , bupropion , and placebo groups , respectively , were 99.3 % , 98.8 % , and 99.2 % . There was a positive correlation between adherence to treatment and tobacco abstinence in all treatment groups . Treatment effect sizes ( odds ratios ) for active therapy compared with placebo were similar whether considering all subjects or only the completer subset . Age , cigarettes per day , and Week-2 abstinence were significant predictors of adherence for all treatment groups ( all p < .05 ) , with Week-2 abstinence the strongest predictor . DISCUSSION Adherence to pharmacotherapy for smoking cessation is highly correlated with improved tobacco abstinence . Early abstinence experience is a strong driver of adherence The authors compared 9- , 16- , 26- , and 52-week outcomes for two r and omly assigned groups of nicotine-dependent subjects : 1 ) nicotine patch plus four smoking cessation sessions with a nurse-practitioner giving advice and instruction ( n = 36 ; moderate-intensity condition , MI ) ; or 2 ) the foregoing treatments plus 16 weekly individual cognitive/ behavioral relapse-prevention therapy sessions ( n = 33 ; high-intensity condition , HI ) . Patch completion rates were 69.7 % in the HI group and 55.6 % in the MI group ( NS ) . Self-reported abstinence rates at the four follow-up points were comparable for the two treatment groups ; HI : 39 % , 36 % , 36 % , and 36 % ; MI : 44 % , 28 % , 25 % , and 28 % , respectively . There was some indication that MI patients with high nicotine dependence had lower abstinence rates than highly dependent HI patients factor and terminal transverse defect . It would be necessary to test this finding in a study with the measurement of cigarette related markers , such as maternal serum or urine cotinine concentrations . The low relative risk ( about 1 5 ) for such a common exposure as smoking has important public health implication s for congenital limb deficiency in the population ( the attributable risk is about 14 % ) . This risk is obviously more important than the association of congenital limb deficiency with chorionic villus sampling.2"28 The confirmed teratogenic effect of maternal smoking may be a further strong indication for public health interventions aim ed at preventing smoking during pregnancy Background Mobile health ( mHealth ) interventions hold great promise for helping smokers quit since these programs can have wide reach and facilitate access to comprehensive , interactive , and adaptive treatment content . However , the feasibility , acceptability , and effectiveness of these programs remain largely untested . Objective To assess feasibility and acceptability of the My Mobile Advice Program ( MyMAP ) smoking cessation program and estimate its effects on smoking cessation and medication adherence to inform future research planning . Methods Sixty-six smokers ready to quit were recruited from a large regional health care system and r and omized to one of two mHealth programs : ( 1 ) st and ard self-help including psychoeducational material s and guidance how to quit smoking or ( 2 ) an adaptive and interactive program consisting of the same st and ard mHealth self-help content as controls received plus a ) real-time , adaptively tailored advice for managing nicotine withdrawal symptoms and medication side-effects and b ) asynchronous secure messaging with a cessation counselor . Participants in both arms were also prescribed a 12-week course of varenicline . Follow-up assessment s were conducted at 2 weeks post-target quit date ( TQD ) , 3 months post-TQD , and 5 months post-TQD . Indices of program feasibility and acceptability included acceptability ratings , utilization metrics including use of each MyMAP program component ( self-help content , secure messaging , and adaptively tailored advice ) , and open-ended feedback from participants . Smoking abstinence and medication adherence were also assessed to estimate effects on these treatment outcomes . Results Utilization data indicated the MyMAP program was actively used , with higher mean program log-ins by experimental than control participants ( 10.6 vs 2.7 , P<.001 ) . The majority of experimental respondents thought the MyMAP program could help other people quit smoking ( 22/24 , 92 % ) and consistently take their stop-smoking medication ( 17/22 , 97 % ) and would recommend the program to others ( 20/23 , 87 % ) . They also rated the program as convenient , responsive to their needs , and easy to use . Abstinence rates at 5-month follow-up were 36 % in the experimental arm versus 24 % among controls ( odds ratio 1.79 [ 0.61 - 5.19 ] , P=.42 ) . Experimental participants used their varenicline an average of 46 days versus 39 among controls ( P=.49 ) . More than two-thirds ( 22/33 , 67 % ) of experimental participants and three-quarters ( 25/33 , 76 % ) of controls prematurely discontinued their varenicline use ( P=.29 ) . Conclusions The MyMAP intervention was found to be feasible and acceptable . Since the study was not powered for statistical significance , no conclusions can be drawn about the program ’s effects on smoking abstinence or medication adherence , but the overall study results suggest further evaluation in a larger r and omized trial is warranted . Clinical Trial Clinical Trials.gov NCT02136498 ; https:// clinical trials.gov/ct2/show/NCT02136498 ( Archived by WebCite at http://www.webcitation.org/6jT3UMFLj PURPOSE To conduct an exploratory study of two interventions to help smokers abstain over a period of 3 months . The specific aims were to describe the outcomes , test feasibility of the study design , and evaluate effect size . DESIGN AND METHODS A r and omized experimental design was used in a sample of 42 patients who received multicomponent treatment intervention ( MTI ) or st and ard care ( SC ) in a midwestern city in the United States . Variables were behavioral ( quit rate , self-efficacy , motivation ) , psychosocial ( depression , partner interaction ) , and symptom management ( use of nicotine replacement therapy [ NRT ] ) . Data analysis included descriptive statistics and repeated measures ANOVA . RESULTS The typical participant was Caucasian , middle aged , nicotine dependent , married or partnered , and employed , and had a high school education . Participants in the MTI group were more likely to use NRT and to have higher self-reported quit rates at follow-up . Statistically significant differences were found between groups over time for self-efficacy and positive to negative behavior ratio . Barriers to quitting were relapse , stress , weight gain , lack of support , and depression that were more frequent in the SC group . For effect size ( 0.25 ) , probability level ( .05 ) , and power ( .80 ) , a sample size of 140 patients was calculated . CONCLUSIONS The MTI group had higher quit rates , more NRT , higher self-efficacy , and more positive behavioral interactions . Limitations of the study included self-report of tobacco use , small sample , and attrition . The investigators suggest a future study with a larger sample to test whether multicomponent interventions with telephone calls after discharge are more effective than is st and ard care in helping patients to quit and continue to abstain from smoking AIMS Despite the existence of effective cessation methods , the vast majority of smokers attempt to quit on their own . To date , there is little evidence to explain the low adoption rates for effective forms of cessation assistance , including pharmaceutical aids . This study sought to assess smokers ' awareness and perceived effectiveness of cessation methods and to examine the relationship of this knowledge to cessation behaviour . DESIGN A r and om-digit-dial telephone survey ( response rate = 76 % ) with 3-month follow-up was conducted with 616 adult daily smokers in South-Western Ontario , Canada . MEASUREMENTS A baseline survey assessed smoking behaviour , as well as smokers ' awareness and perceived effectiveness of cessation assistance . A follow-up survey measured changes in smoking behaviour and adoption of cessation assistance at 3 months . FINDINGS Participants demonstrated a poor recall of cessation methods : 45 % of participants did not recall nicotine gum , 33 % did not recall the nicotine patch and 57 % did not recall bupropion . Also , many participants did not believe that the following cessation methods would increase their likelihood of quitting : nicotine replacement therapies ( 36 % ) , bupropion ( 35 % ) , counselling from a health professional ( 66 % ) and group counselling/quit programmes ( 50 % ) . In addition , 78 % of smokers indicated that they were just as likely to quit on their own as they were with assistance . Most important , participants who perceived cessation methods to be effective at baseline , were more likely to intend to quit ( OR = 1.80 , 95 % CI : 1.12 - 2.90 ) , make a quit attempt at follow-up ( OR = 1.80 , 95 % CI : 1.03 - 3.16 ) and to adopt cessation assistance when doing so ( OR = 3.62 , 95 % CI : 1.04 - 12.58 ) . CONCLUSIONS This research suggests that many smokers may be unaware of effective cessation methods and most underestimate their benefit . Further , this lack of knowledge may represent a significant barrier to treatment adoption This study , which tested two motivational interviewing treatment approaches , assessed the feasibility of conducting a community-based smoking cessation intervention among homeless smokers . Participants ( N = 46 ) were recruited from multiple facilities in the Kansas City area and were r and omized to two counseling conditions in which they received five individual motivational interviewing sessions , six group meetings , and their choice of 8 weeks of 21-mg nicotine patch or 4-mg nicotine lozenge . The two counseling conditions consisted of motivational interviewing targeted either to smoking behaviors exclusively ( smoking only ) or to smoking and other addictions or life events that could affect ability to quit ( smoking plus ) . Group meetings were design ed to provide educational information and social support . Measures of feasibility assessed included the proportion of participants who returned for r and omization among those eligible , adherence to prescribed nicotine replacement therapies , retention rates at the week 26 final study visit , and biochemically verified 7-day abstinence at week 26 . Most participants ( 69.6 % ) chose nicotine patches , and 32 % of those participants reported using at least four patches per week . Carbon monoxide verified 7-day abstinence rates in the smoking-only and smoking-plus groups were 13.04 % and 17.39 % ( ns ) , respectively , at week 8 and 8.70 % and 17.39 % ( ns ) , respectively , at week 26 . Participants who used at least four patches per week were more likely to have quit at 8 weeks than were those who used fewer patches ( 33.3 % vs. 10.5 % , p = .30 ) . Results support the feasibility of conducting a smoking cessation intervention among homeless smokers . Findings also show promising effects for nicotine replacement therapy and counseling in this population . Developing programs to improve smoking cessation outcomes in underserved population s is an essential step toward achieving national health objectives and for ultimately reducing tobacco-related health disparities AIMS To assess the efficacy of nicotine replacement therapies ( NRT ) when the daily dose was adapted according to saliva cotinine concentrations . DESIGN R and omized , multi-centre , single-blind , controlled trial . SETTING Twenty-one smoking cessation clinics in France . PARTICIPANTS A total of 310 smokers with medical comorbidities , motivated to quit , smoking ≥ 10 cigarettes/day , for whom smoking cessation was m and atory . NRT was administered for 3 months . The st and ard care group received nicotine patches with monthly dose decreases ; buccal absorption NRT could be co-administered at the discretion of the investigator . In the dose adaptation group , the aim was a 100 ± 5 % nicotine substitution with respect to smoking state based on the determination of saliva cotinine concentrations . NRT daily doses were prescribed according to the previous week 's saliva cotinine concentrations in the dose adaptation group ; saliva cotinine concentrations were not provided in the st and ard care group . MEASUREMENTS Prolonged abstinence rate ( weeks 9 - 12 , main outcome measure ) , point-prevalence and continuous abstinence rate , saliva cotinine concentration , NRT daily dose , craving for cigarettes . FINDINGS The median daily prescribed NRT dose was 30 and 31 mg/day in the first study week and 17.25 and 35.5 mg/day during weeks 9 - 12 in the st and ard care group and dose adaptation group , respectively . Saliva cotinine remained stable in the dose adaptation group and decreased in the st and ard care group ( P < 0.01 ) by weeks 9 - 12 . The cotinine substitution rate was significantly lower in the st and ard care group than in the dose adaptation group . Despite differences in NRT doses and cotinine substitution rates , prolonged ( st and ard care group : 26.4 % , dose adaptation group : 30.3 % ) , continuous ( st and ard care group : 8 % , dose adaptation group : 12 % ) and point-prevalence abstinence rates were similar . CONCLUSIONS In smokers with medical comorbidities and highly motivated to quit , adaptation of the nicotine replacement therapy daily dose according to saliva cotinine does not appear to be substantially superior to st and ard nicotine replacement therapy use BACKGROUND Individuals in the criminal justice system demonstrate high rates of cigarette use ( 70 - 80 % ) and low adherence to smoking cessation medication . Educational approaches have not been shown to promote adherence or cessation , though medication sampling has boosted both use and cessation . The objective of the present study was to determine whether In vivo nicotine replacement therapy ( NRT ) sampling approach increases NRT adherence among criminal justice smokers during a subsequent quit attempt . METHODS We conducted a pilot study with 43 community corrections smokers r and omized to a 4-session ( one 30-min session per week ) precessation intervention of either In vivo NRT sampling ( Session 1 : patch ; Session 2 : gum ; Session 3 : combination NRT ( cNRT ) ; Session 4 : review ) vs. 4 time-matched sessions of st and ard smoking cessation with cNRT started after Session 1 . Both groups received an additional 8weeks of cNRT following the four intervention sessions . RESULTS During the in vivo administration of NRT , total withdrawal and craving severity significantly decreased from pre- to post-session compared to Control participants . In vivo participants evinced greater patch use at Session 4 and greater gum use through Week 8 relative to Controls . DISCUSSION In vivo NRT sampling may increase NRT adherence relative to st and ard counseling sessions among criminal justice smokers . A larger trial of this novel intervention appears to be warranted AIMS To assess the effects of adding motivational interviewing ( MI ) counseling to nicotine patch for smoking cessation among homeless smokers . DESIGN Two-group r and omized controlled trial with 26-week follow-up . PARTICIPANTS AND SETTING A total of 430 homeless smokers from emergency shelters and transitional housing units in Minneapolis/St Paul , Minnesota , USA . INTERVENTION AND MEASUREMENTS All participants received 8-week treatment of 21-mg nicotine patch . In addition , participants in the intervention group received six individual sessions of MI counseling which aim ed to increase adherence to nicotine patches and to motivate cessation . Participants in the st and ard care control group received one session of brief advice to quit smoking . Primary outcome was 7-day abstinence from cigarette smoking at 26 weeks , as vali date d by exhaled carbon monoxide and salivary cotinine . FINDINGS Using intention-to-treat analysis , verified 7-day abstinence rate at week 26 for the intervention group was non-significantly higher than for the control group ( 9.3 % versus 5.6 % , P = 0.15 ) . Among participants who did not quit smoking , reduction in number of cigarettes from baseline to week 26 was equally high in both study groups ( -13.7 ± 11.9 for MI versus -13.5 ± 16.2 for st and ard care ) . CONCLUSIONS Adding motivational interviewing counseling to nicotine patch did not increase smoking rate significantly at 26-week follow-up for homeless smokers This historical cohort study conducted in a University Hospital between and 2006 included 322 smokers willing to quit and assessed whether adding a teaching session on nicotine addiction to a smoking cessation program could increase the proportion of participants using pharmacotherapy . The control cohort received the st and ard course while two short talks were added to the course for a consecutive intervention cohort . These talks used the metaphor of a pizza delivery service to explain neural mechanisms underlying nicotine addiction . Medication use was significantly more common in the intervention than control cohort ( 82.1%% vs. 51.2%% ; adjusted odds ratio 4.0 ; 2.34–6.83 ) |
12,372 | 21,942,506 | No difference in bleeding complications was observed between IC and IV regimens .
An accumulating body of evidence suggests the superiority of IC over IV abciximab administration in STEMI patients . | OBJECTIVES To perform a systematic review to provide rationale for intracoronary ( IC ) abciximab administration in patients with ST-segment elevation myocardial infa rct ion ( STEMI ) , to summarize recent studies comparing IC vs. intravenous ( IV ) abciximab administration in this setting and to define questions that need to be answered in future trials determining the optimal abciximab regimen .
RESULTS IC administration allows one to obtain a much higher concentration of abciximab than IV injection at the culprit lesion .
Therefore it is hypothesized that IC abciximab administration provides more efficient GP IIb/IIIa receptor inhibition and more pronounced additional dose-dependent antiplatelet , antithrombotic , and anti-inflammatory effects when compared to the IV route . | INTRODUCTION AND OBJECTIVES It has been clearly demonstrated that abciximab is useful in percutaneous coronary interventions . However , it is not known if intracoronary administration of the initial abciximab bolus improves outcome . Moreover , there may be safety concerns . METHODS The study was a single-center prospect i ve r and omized trial that included all patients undergoing coronary angioplasty involving the use of abciximab . Patients were r and omized to either intracoronary or intravenous administration of the abciximab bolus . The primary endpoint was the incidence of major adverse cardiac events ( i.e. , death , myocardial infa rct ion , or the need for revascularization ) ; secondary endpoints were hemorrhagic complications and the troponin-I level . RESULTS The study included 137 patients ; 72 received an intracoronary abciximab bolus and 65 , an intravenous bolus . Clinical characteristics and baseline angiographic findings were similar in the two groups . All patients underwent coronary stent implantation . No difference was observed between the intracoronary bolus group and the intravenous bolus group in type of stent used ( drug eluting stent 47.2 % vs 50.8 % , respectively ) , total stent length , or final TIMI flow grade ( 3 vs 2.97 , respectively ) . The intervention success rates were also similar ( 98.5 % vs. 99 % , respectively ) . No complication associated with the administration route was reported . However , the level of the myocardial injury marker troponin I increased significantly in the intravenous bolus group . Clinical follow-up at 1 year did not reveal any difference in the incidence of major adverse cardiac events : 8.5 % in the intracoronary bolus group versus 6.2 % in the intravenous bolus group . CONCLUSIONS Intracoronary administration of an abciximab bolus did not appear to be less safe or effective than intravenous administration . Less post-procedural myocardial damage was observed in the intracoronary bolus group Background — Abciximab reduces major adverse cardiac events in patients with ST-elevation myocardial infa rct ion undergoing primary percutaneous coronary intervention ( PCI ) . Intracoronary abciximab bolus application results in high local drug concentrations and may be more effective than a st and ard intravenous bolus . Methods and Results — Patients undergoing primary PCI were r and omized to either intracoronary ( n=77 ) or intravenous ( n=77 ) bolus abciximab administration with subsequent 12-hour intravenous infusion . The primary end point was infa rct size and extent of microvascular obstruction as assessed by delayed enhancement magnetic resonance . Secondary end points were ST-segment resolution at 90 minutes , Thrombolysis in Myocardial Infa rct ion flow and perfusion grade s after PCI , and the occurrence of major adverse cardiac events within 30 days . The median infa rct size was 15.1 % ( interquartile range , 6.1 % to 25.2 % ) in the intracoronary versus 23.4 % ( interquartile range , 13.6 % to 33.2 % ) in the intravenous group ( P=0.01 ) . Similarly , the extent of microvascular obstruction was significantly smaller in intracoronary compared with intravenous abciximab patients ( P=0.01 ) . Myocardial perfusion measured as early ST-segment resolution was significantly improved in intracoronary patients with an absolute ST-segment resolution of 77.8 % ( interquartile range , 66.7 % to 100.0 % ) versus 70.0 % ( interquartile range , 45.2 % to 83.5 % ; P=0.006 ) . The Thrombolysis in Myocardial Infa rct ion flow after PCI was not different between treatment groups ( P=0.51 ) , but there was a trend toward an improved perfusion grade ( P=0.09 ) . There also was a trend toward a lower major adverse cardiac event rate after intracoronary versus intravenous abciximab application ( 5.2 % versus 15.6 % ; P=0.06 ; relative risk , 0.33 ; 95 % CI , 0.09 to 1.05 ) . Conclusions — Intracoronary bolus administration of abciximab in primary PCI is superior to st and ard intravenous treatment with respect to infa rct size , extent of microvascular obstruction , and perfusion Background —In patients with acute myocardial infa rct ion or unstable angina undergoing coronary angioplasty , abciximab reduces major adverse cardiac events ( MACE ) . Clinical trials have studied intravenous administration only . Intracoronary bolus application of abciximab causes very high local drug concentrations and may be more effective . We studied whether intracoronary bolus administration of abciximab is associated with a reduced MACE rate compared with the st and ard intravenous bolus application . Methods and Results —We stratified 403 consecutive patients with acute myocardial infa rct ion or unstable angina undergoing coronary angioplasty according to the type of application of abciximab . A 20-mg bolus of abciximab was given intravenously in 109 patients and intracoronarily in 294 patients . There were no differences between the groups with regard to diabetes mellitus , cardiogenic shock , successful intervention , or preprocedural and postprocedural TIMI flow . At 30 days , the incidence of MACE ( death , myocardial infa rct ion , urgent revascularization ) was significantly lower in the patients with intracoronary compared with intravenous administration of abciximab ( 10.2 % versus 20.2%;P < 0.008 ) , which was independent from stenting in multivariate analysis . The effect was most pronounced in patients with preprocedural TIMI 0/1 flow ( MACE : intracoronary 11.8 % versus intravenous 27.5 % , P < 0.002 ; n=273 ) . Conclusions —In patients with acute myocardial infa rct ion or unstable angina undergoing emergency coronary angioplasty , intracoronary bolus application of abciximab is associated with a reduction of MACE compared with the st and ard intravenous bolus application of abciximab . Prospect i ve , r and omized trials are warranted to further assess intracoronary application of abciximab BACKGROUND Thrombosis has been implicated as central to the clinical complications of coronary angioplasty ( PTCA ) . Chimeric monoclonal 7E3 Fab ( c7E3 Fab ) is the first of a new class of antiplatelet drugs directed at the platelet glycoprotein IIb/IIIa integrin . This study was performed to determine the pharmacodynamics of c7E3 Fab administration during PTCA and to gain an initial clinical experience with this novel agent . METHODS AND RESULTS The study was a multicenter , open-label , dose-escalation study conducted in two stages . Enrollment included 56 patients scheduled for elective PTCA who were estimated to be at moderate to high risk of sustaining ischemic complications . All patients were given aspirin and heparin . The study drug was given at least 10 minutes before PTCA . In stage 1 , increasing bolus doses of c7E3 Fab were given to 15 patients ; a bolus dose of 0.25 mg/kg was found to result in blockade of > 80 % of the receptors and reduce platelet aggregation to < 20 % compared with baseline , establishing this dose as that necessary to sufficiently suppress platelet activity . In stage 2 , additional c7E3 Fab was administered by continuous infusion to 32 patients for progressively longer periods of time ( up to 24 hours ) to confirm that platelet inhibition could be maintained with prolonged drug infusion . Also , 9 patients otherwise meeting entry criteria were given placebo . There were no thrombotic events among patients receiving c7E3 Fab . Overall procedural and clinical success and complication rates as well as rates of bleeding were statistically similar among groups . However , minor bleeding was more frequent with administration of the active drug . CONCLUSIONS The novel antiplatelet agent c7E3 Fab can be administered during PTCA in combination with aspirin and heparin . Suppression of platelet activity is dose dependent and can be maintained for up to 24 hours . Further evaluation will be required to determine the extent of improvement in ischemic complication and restenosis rates and to provide additional insight into the safety profile of this potent monoclonal platelet antibody Background —Trials of platelet glycoprotein IIb/IIIa inhibitors as adjuncts to primary percutaneous coronary intervention for acute myocardial infa rct ion ( MI ) have shown improved early clinical and angiographic outcomes with treatment . However , variations in trial design s , modest sample sizes , and limited long-term follow-up have precluded these studies from being definitive . Methods and Results —As a prespecified secondary analysis of the CADILLAC trial , we compared early and late outcomes by abciximab assignment among 2082 patients r and omized in an open-label , 2 × 2 factorial- design trial of primary stenting versus angioplasty and abciximab treatment ( n=1052 ) versus no abciximab treatment ( n=1030 ) . Baseline characteristics were balanced between groups . Abciximab treatment was associated with a significant reduction in the composite end point of death , MI , ischemia-driven target-vessel revascularization ( TVR ) , or disabling stroke at 30 days ( 4.6 % versus 7.0 % ; relative risk , 0.65 ; 95 % CI , 0.46 to 0.93 ; P = 0.01 ) . Subacute thrombosis also was significantly reduced with abciximab treatment . At 12 months , however , rates of the composite end point did not differ significantly ( 18.4 % for controls versus 16.9 % for abciximab-treated patients ; relative risk , 0.92 ; 95 % CI , 0.76 to 1.10 ; P = 0.29 ) , reflecting a decrease in the relative difference in TVR rates ( ie , no effect of abciximab on reducing restenosis ) . In an angiographic sub study ( n=656 ) , myocardial salvage , restenosis , and infa rct -artery reocclusion at 7 months were unaffected by abciximab treatment . There was no significant interaction between stenting and abciximab treatment . Conclusions —Adjunctive abciximab treatment during primary percutaneous coronary intervention significantly enhanced 30-day event-free survival , predominantly by reducing ischemia-driven TVR . Abciximab treatment did not affect the composite end point at 1 year , reflecting a lack of effect on restenosis Background —Diabetic patients are at increased risk of adverse outcomes after percutaneous coronary interventions . Although subset analyses suggest particular benefit from the administration of abciximab in diabetic patients , no dedicated large r and omized trials have been performed in diabetic patients undergoing percutaneous coronary intervention , and certainly not after pretreatment with a high loading dose of clopidogrel . Methods and Results —This study ( Intracoronary Stenting and Antithrombotic Regimen : Is Abciximab a Superior Way to Eliminate Elevated Thrombotic Risk in Diabetics [ ISAR-SWEET ] Study ) enrolled 701 diabetic patients with coronary artery disease who underwent an elective percutaneous coronary intervention after pretreatment with a 600-mg dose of clopidogrel > 2 hours before the procedure : 351 patients were r and omly assigned to abciximab and 350 patients to placebo . The primary end point of the trial was the composite incidence of death and myocardial infa rct ion at 1 year . The frequency of angiographic restenosis ( diameter stenosis ≥50 % ) was the secondary end point . The incidence of death or myocardial infa rct ion was 8.3 % in the abciximab group and 8.6 % in the placebo group ( P=0.91 ) , with a relative risk of 0.97 ( 95 % CI , 0.58 to 1.62 ) . The incidence of angiographic restenosis was 28.9 % in the abciximab group and 37.8 % in the placebo group ( P=0.01 ) , with a relative risk of 0.76 ( 95 % CI , 0.62 to 0.94 ) . The incidence of target lesion revascularization was 23.2 % in the abciximab group and 30.4 % in the placebo group ( P=0.03 ) . Conclusions —The findings of this study do not support a significant impact of abciximab on the risk of death and myocardial infa rct ion in diabetic patients undergoing percutaneous coronary interventions after pretreatment with a 600-mg loading dose of clopidogrel at least 2 hours before the procedure . The present findings suggest , however , that abciximab reduces the risk of restenosis in diabetic patients receiving coronary bare metal stents BACKGROUND In the EASY trial , we have shown the clinical equivalence between abciximab bolus-only and abciximab bolus followed by 12-h infusion in a wide spectrum of patients after percutaneous coronary intervention ( PCI ) . Some reports have suggested better outcomes following intracoronary ( IC ) abciximab administration compared to intravenous ( IV ) delivery . We sought to compare cardiac biomarkers release and early and late clinical outcomes after IC or IV abciximab bolus delivery . METHODS From 1005 patients r and omized in the EASY trial and undergoing transradial coronary stent implantation , 208 received IC abciximab bolus and 797 received IV abciximab bolus . Route of administration was left to operators ' discretion . Creatine Kinase-MB , and Troponin-T ( Tn-T ) were obtained immediately prior to angiography , 4 - 6 h after PCI and the next day . MACE ( death , MI , TVR ) rate was evaluated at 30 days , 6 months and 12 months . RESULTS There were more patients with acute coronary syndrome ( 75 % vs 64 % , P=0.004 ) and previous MI ( 53 % vs 42 % , P=0.005 ) in the IC group and more patients with > or=3 dilated sites in the IV group ( 2 % IC vs 7 % IV , P=0.03 ) . After PCI , the extent of Tn-T and CK-MB release remained comparable in both groups . The MACE rate was 2 % in both groups at 30 days , 9 % in IC bolus vs 5 % in IV bolus ( P=0.04 ) at 6 months and 10 % in IC bolus vs 9 % in IV bolus ( P=0.50 ) at 12 months . By multivariate analysis , IC abciximab bolus was not associated with better outcomes at 12 months compared to IV bolus ( HR 1.07 , 95 % CI 0.82 - 1.35 , P=0.62 ) . CONCLUSION Compared to IV abciximab administration , IC abciximab was not associated with less cardiac biomarkers release or better clinical outcomes after uncomplicated transradial PCI . Further studies are required in clinical scenarios including patients with higher thrombotic burden and /or occluded vessels as in primary and rescue PCI BACKGROUND Intravenous abciximab reduces major adverse cardiac events in patients with ST-elevation myocardial infa rct ion ( STEMI ) undergoing primary percutaneous coronary intervention ( PCI ) . Intracoronary abciximab bolus application during PCI results in high local drug concentration , improved perfusion , reduction of infa rct size , and less microvascular obstruction . The hypothesis of this trial is that abciximab bolus intracoronary in comparison to st and ard intravenous application will improve the outcome of patients undergoing primary PCI in STEMI . STUDY DESIGN The Abciximab Intracoronary versus intravenously Drug Application in STEMI ( AIDA STEMI ) study is a 1,912-patient , prospect i ve , multicenter , r and omized , open-label , controlled trial . The study is design ed to compare the efficacy and safety of intracoronary versus intravenous bolus abciximab administration during primary PCI with subsequent intravenous infusion for 12 hours . Patients will be r and omized in a 1:1 fashion to 1 of the 2 treatments . The primary efficacy end point of AIDA STEMI is the composite of all-cause mortality , recurrent MI , or new congestive heart failure within 90 days of r and omization . The primary safety outcome assessment will be major bleeding . CONCLUSIONS The AIDA STEMI study addresses important questions regarding the efficacy and safety of intracoronary abciximab bolus administration during primary PCI in patients with STEMI , potentially optimizing the route of administration of glycoprotein IIb/IIIa inhibitors in the catheterization laboratory BACKGROUND Coronary microvascular dysfunction is frequently seen in patients with ST-elevation myocardial infa rct ion after primary percutaneous coronary intervention . Previous studies have suggested that the administration of intravenous adenosine result ed in an improvement of myocardial perfusion and a reduction in infa rct size . Intracoronary adenosine ( bolus of 30 to 60 microg ) is a guideline -recommended therapy to improve myocardial reperfusion . The effect of intracoronary adenosine during primary percutaneous coronary intervention has not been investigated in a large r and omized trial . METHODS AND RESULTS Patients presenting with acute ST-elevation myocardial infa rct ion were r and omized to 2 bolus injections of intracoronary adenosine ( 2 x 120 microg in 20 mL NaCl ) or placebo ( 2 x 20 mL NaCl ) . The first bolus injection was given after thrombus aspiration and the second after stenting of the infa rct -related artery . The primary end point was the incidence of residual ST-segment deviation < 0.2 mV , 30 to 60 minutes after percutaneous coronary intervention . Secondary end points were ST-segment elevation resolution , myocardial blush grade , Thrombolysis in Myocardial Infa rct ion flow on the angiogram after percutaneous coronary intervention , enzymatic infa rct size , and clinical outcome at 30 days . A total of 448 patients were r and omized to intracoronary adenosine ( N=226 ) or placebo ( N=222 ) . The incidence of residual ST-segment deviation < 0.2 mV did not differ between patients r and omized to adenosine or placebo ( 46.2 % versus 52.2 % , P = NS ) . In addition , there were no significant differences in secondary outcome measures . CONCLUSIONS In this r and omized placebo controlled trial enrolling 448 patients with ST-elevation myocardial infa rct ion , administration of intracoronary adenosine after thrombus aspiration and after stenting of the infa rct -related artery did not result in improved myocardial perfusion BACKGROUND The glycoprotein ( GP ) IIb/IIIa receptor antagonist abciximab is approved for use in high-risk percutaneous coronary interventions . The purpose of the present study was to establish the pharmacodynamic profile and platelet-bound life span of abciximab . METHODS AND RESULTS The pharmacodynamics of abciximab ( inhibition of ex vivo platelet aggregation and GP IIb/IIIa receptor blockade ) were measured in 41 individuals who were r and omized to receive a 0.25-mg/kg bolus and a 12-hour infusion of either 10 microg/min ( EPIC regimen ) or 0.125 microg x kg(-1 ) x min(-1 ) ( EPILOG regimen ) of the antiplatelet agent . At extended times , the amount and distribution of platelet-bound abciximab were monitored by flow cytometry . The EPIC and EPILOG infusion regimens exhibited equivalent blockade of both GP IIb/IIIa receptors and platelet aggregation throughout the duration of abciximab treatment . Flow cytometry revealed a single , highly fluorescent platelet population during treatment , consistent with complete saturation and homogeneous distribution of abciximab on circulating platelets . For 15 days after treatment , the fluorescence histograms remained unimodal with gradually diminishing fluorescence intensity , indicating decreasing levels of platelet-bound abciximab . At 8 and 15 days , which exceeds the normal circulating life span of platelets , median relative fluorescence intensity corresponded to 29100 ( 29 % GP IIb/IIIa receptor blockade ) and 13300 ( 13 % GP IIb/IIIa receptor blockade ) abciximab molecules bound per platelet , respectively . CONCLUSIONS These results are consistent with continuous reequilibration of abciximab among circulating platelets and may explain the gradual recovery of platelet function and long-term prevention of ischemic complications by abciximab after coronary intervention There have been animal and human studies looking at intracoronary ( IC ) use of abciximab with good short‐term clinical outcomes . There exists no data comparing intracoronary with intravenous ( IV ) administration of abciximab beyond 30 days . We compared the clinical outcomes between the IC ( n = 101 ) and IV ( n = 72 ) group of patients . Patients who had coronary stenting and received abciximab were included in the study . All the patients received the st and ard systemic bolus dose of abciximab 0.25 mg/kg either via the IC or IV route , followed by a 12‐hr IV infusion at 0.125 μg/kg/min . The 6‐month composite endpoint of death or myocardial infa rct ion was slightly higher in the IV ( 13.9 % ) than in the IC group ( 5.9 % ; P = 0.04 ) . The frequency of bleeding complications was similar in both groups . The IC bolus route of abciximab may be superior to the intravenous route . Prospect i ve r and omized trials are warranted to vali date these findings . Catheter Cardiovasc Interv 2004;61:31–34 . © 2004 Wiley‐Liss , OBJECTIVES We investigated whether local abciximab delivery to the site of intracoronary thrombus is more effective than intracoronary bolus infusion in patients with acute coronary syndromes ( ACS ) undergoing percutaneous coronary intervention and downstream clopidogrel administration . BACKGROUND The intracoronary route of administration does not allow an optimal contact between the plaque components and abciximab , which is rapidly washed out by the coronary flow . METHODS A total of 50 patients with ACS and a significant lesion in the culprit artery indicative of local thrombosis were r and omly assigned to receive local intracoronary delivery of abciximab through a dedicated perfusion catheter or intracoronary infusion through the guiding catheter . The primary end point was the change in thrombus score after angioplasty by optical coherence tomography . RESULTS After the intervention , the mean percentage change of the thrombus score was significantly higher among patients of the local delivery group compared with those of the intracoronary infusion group ( 33.8 % vs. 3.9 % , p = 0.002 ) . Post-procedural corrected Thrombolysis in Myocardial Infa rct ion frame count was shorter in the local delivery group compared with the intracoronary infusion group ( 15.3 ± 10.2 vs. 21.1 ± 9.9 , p = 0.049 ) . Procedure-related myocardial infa rct ion was observed in 10 % and 43 % of patients in the local delivery and intracoronary infusion groups , respectively ( p = 0.018 ) . At 1 year , MACE were observed in 5.9 % and 27.2 % of patients in the local delivery and intracoronary infusion groups , respectively ( p = 0.046 ) . CONCLUSIONS Local intracoronary delivery of abciximab by means of a dedicated perfusion catheter reduces thrombus burden with the potential to improve coronary microcirculation BACKGROUND Recent data suggest that the intracoronary ( i.c . ) administration of a systemic bolus dose of abciximab during PCI may increase the efficacy of this antiplatelet drug . However , the effect of i.c . abciximab on coronary angiographic flow has been not clarified . METHODS We studied 37 consecutive patients with acute coronary syndromes ( ACS ) who underwent successful urgent PCI on the target vessel and were treated by an i.c . abciximab bolus ( 0.25 mg/kg ) prior to the first balloon inflation ( Group IC ) , and 37 matched controls who were treated by intravenous ( i.v . ) abciximab bolus at the same dose ( Group IV ) . Corrected TIMI frame count ( CTFC ) in the culprit and in a non-culprit coronary artery branch was assessed before treatment , immediately after intracoronary administration of abciximab bolus and at the end of the procedure . RESULTS After administration of abciximab , CTFC significantly decreased from 48 + 37 to 33 + 30 ( P=0.001 ) in the culprit vessel while in the non-culprit vessel it remained unchanged ( 16 + 7 pre-treatment and 16 + 7 post-treatment , P=0.68 ) . Final CTFC was 12 + 4 in Group IC and 14 + 5 in Group IV ( P=0.069 ) . Post-treatment mean peak of the cardiac enzymes showed a trend toward reduction in Group IC compared with Group IV . CONCLUSIONS The i.c . administration of abciximab bolus acutely decreases CTFC through culprit vessels of patients with ACS undergoing urgent PCI . Further studies evaluating the potential clinical benefits associated with i.c . abciximab administration are warranted INTRODUCTION CD40 lig and has been suggested to play a pathogenic role in atherogenesis and coronary artery disease progression . Clinical studies suggest that intravenous ( IV ) abciximab administration attenuates the acute inflammatory response associated with percutaneous coronary intervention ( PCI ) . The anti-inflammatory effects of intracoronary ( IC ) versus IV administration of abciximab have not been systematic ally investigated . We assessed changes in soluble CD40 lig and ( sCD40L ) concentrations in response to IC versus IV abciximab in patients with ST-elevation myocardial infa rct ion ( STEMI ) undergoing thrombus-aspirating device during primary PCI . METHODS Patients were r and omized to receive IC ( n=25 ) or IV ( n=25 ) bolus abciximab followed in every case by a 12-h IV abciximab infusion . sCD40L was measured immediately before the administration of abciximab ( baseline ) and 60min post bolus administration . RESULTS Clinical baseline and angiographic characteristics were similar in both patient groups . Similarly , there were no significant differences in baseline serum sCD40L levels in the IC group compared to IV group ( 116.6+/-42.13pg/mL vs 124.9+/-43.04pg/mL , P=0.49 ) . At 60min post PCI , however , sCD40L levels decreased by 23 % ( P<0.001 ) in the IC group and by 11 % ( P<0.001 ) in the IV group . sCD40L levels 60min post PCI were significantly reduced , particularly in the IC group compared to the IV group ( 73.04+/-12.21pg/mL vs 99.92+/-25.89pg/mL , P<0.001 ) . CONCLUSION In STEMI patients undergoing primary PCI , IC bolus administration of abciximab was associated with a larger reduction in sCD40L levels compared to st and ard IV bolus . Whether this more powerful anti-inflammatory effect of IC abciximab translates into improved clinical outcomes deserves investigation In this prospect i ve r and omized trial on patients with acute myocardial infa rct ion ( AMI ) treated with primary percutaneous coronary intervention ( PCI ) , we hypothesized that abciximab administered intracoronarily , downstream of the coronary occlusion , leads to a greater degree of myocardial salvage and better left ventricular function recovery compared with the usual abciximab administration . Forty‐five consecutive patients with first AMI and infa rct ‐related artery TIMI flow 0–1 undergoing primary PCI were enrolled . Twenty‐two patients were r and omly assigned to the intracoronary treatment and 23 to the usual treatment . The initial perfusion defect , final infa rct size , myocardial salvage , salvage index , and left ventricular function recovery were assessed by serial scintigraphic scans performed at admission and 7 days and 1 month after PCI . Angiographic myocardial blush grade , corrected TIMI frame count , and electrocardiographic ST segment elevation reduction were also assessed as markers of myocardial reperfusion . Final infa rct size was significantly smaller ( P = 0.043 ) and salvage index significantly higher ( P = 0.003 ) in the intracoronary treatment group as a result of a greater degree of myocardial salvage ( P = 0.0001 ) . The increase of left ventricular ejection fraction at 1 month was significantly higher in the intracoronary treatment patients ( P = 0.013 ) . The markers of myocardial reperfusion were also significantly better in the intracoronary treatment group . In patients with AMI and occluded infa rct ‐related artery treated with primary PCI , intracoronary abciximab given just before PCI downstream of the occlusion is associated to a greater degree of myocardial salvage than the usual abciximab protocol . This benefit is mainly related to a substantial reduction in final infa rct size , which leads to an improvement in left ventricular ejection fraction . Catheter Cardiovasc Interv 2004;62:186–192 . © 2004 Wiley‐Liss , Background Percutaneous coronary intervention ( PCI ) is a highly effective therapy for acute ST-elevation myocardial infa rct ion . Adjunctive therapy with platelet glycoprotein ( GP ) IIb/IIIa inhibitor can result in increased vessel patency and improved outcomes in ST-elevation myocardial infa rct ion patients undergoing PCI . The investigation of novel dosing and delivery strategies of this therapy may help to further improve outcomes . Methods IC-Clearly is a r and omized , open-label , multicenter trial , with the purpose of evaluating the effectiveness of an intracoronary bolus dose of abciximab delivered using the ClearWay RX catheter vs. an intravenous bolus of abciximab for ST-elevation myocardial infa rct ion with angiographically visible thrombus ( thrombus grade ≥2 ) . A total of 150 patients will be r and omized 1 : 1 to treatment of the culprit artery with intracoronary abciximab ( 75 patients ) or intravenous abciximab ( 75 patients ) in addition to a maintenance infusion regimen of abciximab administered intravenously for 12 h after PCI . The number of patients included in this study is based on the estimation of sample size needed to identify a statistically significant difference in the primary endpoints between the two groups . The primary endpoint chosen to evaluate this hypothesis is infa rct size assessed by cardiac magnetic resonance . Clinical outcomes will be assessed for each patient through hospital discharge and at 30-day follow-up . Conclusion The purpose of this study is to evaluate whether an intracoronary bolus of abciximab delivered with the ClearWay RX catheter prior to the 12 h post-PCI intravenous infusion regimen of abciximab will result in significant additional clot resolution in vivo and improved myocardial perfusion when compared with an intravenous bolus of abciximab on top of the 12 h post-PCI intravenous infusion regimen of abciximab as per st and ard practice . The primary endpoint chosen to evaluate this hypothesis is infa rct size as assessed by cardiac magnetic resonance BACKGROUND Whether thrombus aspiration and local glycoprotein IIb/IIIa administration reduce infa rct size in patients with ST-elevation myocardial infa rct ion ( STEMI ) undergoing primary percutaneous coronary intervention ( PCI ) has not been established in multicenter studies . DESIGN INFUSE-AMI is a multicenter , open-label , controlled , single-blind r and omized study enrolling 452 subjects with anterior STEMI and an occluded proximal or mid-left anterior descending artery with thrombosis in myocardial infa rct ion 0 , 1 , or 2 grade flow undergoing primary PCI with bivalirudin anticoagulation . Subjects are r and omized in a 2 × 2 factorial to one of the following 4 arms : ( 1 ) local infusion of abciximab using the ClearWay RX Local Therapeutic Infusion Catheter ( ClearWay , Atrium Medical Corp , Hudson , NH ) after aspiration with a 6F Export Aspiration Catheter ( Medtronic , Inc , Minneapolis , MN ) , ( 2 ) local infusion of abciximab using the ClearWay RX Infusion Catheter and no aspiration , ( 3 ) no local infusion of abciximab and aspiration with a 6F Export Aspiration Catheter , or ( 4 ) no local infusion of abciximab and no aspiration . The primary end point is infa rct size ( percentage of total left ventricular mass ) at 30 days measured by cardiac magnetic resonance imaging . Other secondary end points include microvascular obstruction by cardiac magnetic resonance imaging at 5 days , ST-segment resolution , angiographic myocardial perfusion , thrombus burden , angiographic complications , and clinical events through 1-year follow-up . Safety end points include major and minor bleeding . SUMMARY INFUSE-AMI is testing the hypothesis that the intracoronary administration of an abciximab bolus with or without thrombus aspiration before stent implantation compared to no infusion with or without thrombus aspiration reduces infa rct size among patients undergoing primary PCI for anterior STEMI who are treated with bivalirudin BACKGROUND Abciximab is beneficial in patients with ST-segment elevation myocardial infa rct ion ( STEMI ) undergoing primary percutaneous coronary intervention ( pPCI ) . However , the optimal administration route of the initial bolus of abciximab , that is , intravenous ( IV ) versus intracoronary ( IC ) , has been question ed . Preliminary studies suggest that IC-bolus is superior , probably due to high local concentration . In this study , we assess the short-term efficacy and safety of IC compared to IV bolus of abciximab in patients with STEMI during pPCI . METHODS In 2006 - 2008 , we r and omized 355 STEMI patients who underwent pPCI and had indication for abciximab to either IV or IC bolus followed by a 12-hour IV infusion . Primary end-points at 30 days were target vessel revascularization ( TVR ) , recurrent myocardial infa rct ion ( MI ) or death , and the composite of the three . Secondary end-points were bleeding complications . RESULTS The two groups ( IV n = 170;IC n = 185 ) were similar with respect to baseline characteristics . Mortality at 30 days was 5.3 % in the IV group compared to only 1.1 % in the IC group ( P = 0.02 ) . TVR was performed in 9.4 % in the IV group compared to 3.8 % in the IC group ( P = 0.03 ) . No significant difference in MI rates was seen ( IV 4.7 % vs. IC 2.7 % ; P = 0.32 ) . We found a significant reduction in the composite end-point ( IV 19.4 % vs. IC 7.6 % ; P = 0.001 ) in favor of IC use . Major bleeding complications were similar ( IV 2.4 % vs. IC 1.6 % ; P = 0.62 ) . Neither difference was observed in minor bleedings ( IV 14.1 % vs. IC 9.7 % ; P = 0.20 ) . CONCLUSION IC administration of bolus abciximab in STEMI patients undergoing pPCI reduces 30-day mortality and TVR and tends to reduce MI , compared to IV-bolus OBJECTIVES This prospect i ve r and omized study investigated platelet-induced upregulation of Mac-1 on monocytes and its inhibition by glycoprotein ( GP ) IIb/IIIa blockage in patients with acute myocardial infa rct ion ( AMI ) . BACKGROUND In experimental AMI , Mac-1 on leukocytes is the pivotal adhesion molecule for detrimental inflammatory responses . In vitro , platelet adhesion to monocytes upregulates Mac-1 . METHODS Patients undergoing stenting in AMI within 48 h after onset of symptoms were r and omly assigned to receive either st and ard-dose heparin ( n = 50 ) or abciximab plus low-dose heparin ( n = 50 ) . In serial blood sample s , we assessed platelet-monocyte interaction and Mac-1 surface expression by triple color immunofluorescence flow cytometry . RESULTS Compared with platelet-negative monocytes , Mac-1 surface expression on monocytes with attached platelets was upregulated ( median fluorescence intensity [ interquartile range ] : 259 [ 179 to 367 ] vs. 135 [ 78 to 195 ] arbitrary units , p < 0.001 ) . As an indicator of platelet-monocyte interaction , mean fluorescence of the platelet marker GP Ib alpha in the monocytes population decreased after abciximab , although it remained unaffected by heparin alone . Abciximab achieved this effect by a reduction in platelet mass attached to monocytes ( GP Ib alpha fluorescence intensity of heterotypic aggregates at 24 h [ arbitrary units ] : 187 [ 143 to 236 ] after abciximab vs. 228 [ 156 to 332 ] after heparin , p = 0.02 ) , whereas it did not affect the percentage of monocytes with adherent platelets . Reduction of platelet-monocyte interaction result ed in decreased Mac-1 surface expression ( fluorescence intensity at 24 h [ arbitrary units ] : 116 [ 68 to 153 ] after abciximab vs. 162 [ 117 to 239 ] after heparin , p = 0.001 ) . CONCLUSIONS In patients with AMI , platelet-leukocyte interactions modulate Mac-1 expression on monocytes . Glycoprotein IIb/IIIa blockade is a therapeutic option to interfere with this mechanism BACKGROUND Large , r and omized , and blinded clinical trials ( EPIC , EPILOG , and CAPTURE ) have demonstrated that abciximab ( ReoPro , chimeric 7E3 Fab ) markedly reduces thrombotic events associated with percutaneous transluminal coronary interventions . The marked early benefits at 30 days were sustained at 6 months and 3 years . Initially developed because of its efficacy in blocking GP IIb/IIIa ( alphaIIb/beta3 ) receptors on platelets , abciximab also binds with equivalent affinity to alpha(v)beta3 . METHODS AND RESULTS This study presents a detailed characterization of the alphavss3 interaction , including the ability of abciximab to ( 1 ) bind with comparable affinity to alpha(v)beta3 and GP IIb/IIIa , ( 2 ) inhibit alpha(v)beta3 and GP IIb/IIIa-mediated cell adhesion in vitro with IC50 values approximating binding KD values , and ( 3 ) redistribute between GP IIb/IIIa and alpha(v)beta3 integrins in vitro . CONCLUSIONS As an antagonist of not only GP IIb/IIIa but also alpha(v)beta3 , abciximab may provide additional clinical benefit in preventing alpha(v)beta3-mediated effects such as thrombin generation , clot retraction , or smooth muscle cell migration and proliferation . Abciximab binds with equivalent affinity to both GP IIb/IIIa and alphavss3 and redistributes between the 2 integrin receptors in vitro . Abciximab has been previously shown to circulate on platelets for up to 2 weeks . Taken together , these findings suggest that abciximab may have the ability to inhibit both GP IIb/IIIa and alpha(v)beta3 for extended periods OBJECTIVE To investigate the effects of abciximab , eptifibatide and no GPIIb-IIIa antagonist ( control ) on soluble CD40 lig and ( sCD40L ) and the formation of leukocyte-platelet aggregates ( LPA ) in 98 ACS patients undergoing percutaneous coronary intervention ( PCI ) . BACKGROUND sCD40L and LPA are increased in patients with ACS . METHODS sCD40L was measured by enzyme-linked immunosorbent assay ( ELISA ) and LPA by whole blood flow cytometry . RESULTS There were no baseline differences between the three groups in sCD40L and LPA . At the end of PCI , sCD40L was unchanged in the controls , decreased by 30 % ( P < 0.001 ) in the abciximab group and by 11 % ( P < 0.02 ) in the eptifibatide group . Eighteen to 24 h after PCI , sCD40L was unchanged in the controls , reduced 30 % ( P < 0.001 ) in the abciximab-treated group and 9 % ( P < 0.01 ) in the eptifibatide-treated group . At the end of PCI , circulating monocyte-platelet aggregates ( MPA ) were reduced by 12 % ( P = NS ) in the abciximab-treated group , 13 % in the eptifibatide-treated group ( P = NS ) , but slightly increased in the controls ( P = NS ) . Eighteen to 24 h after PCI , MPA were reduced by 41 % ( P < 0.001 ) compared to baseline in the abciximab-treated group , by 23 % ( P = NS ) in the eptifibatide-treated group , and 15 % ( P = NS ) in the controls . In contrast to control patients presenting while on clopidogrel , control patients presenting not on clopidogrel demonstrated a reduction in sCD40L and LPA 18 - 24 h post-PCI ( P = NS ) . At low receptor occupancy , GPIIb-IIIa antagonists did not augment the release of sCD40L or the number of circulating LPA . CONCLUSIONS GPIIb-IIIa antagonists reduce circulating sCD40L and LPA formation in patients with ACS undergoing PCI . At low receptor occupancy , GPIIb-IIIa antagonists do not activate platelets Platelet aggregation inhibition ( PAI ) of > or = 95 % has been associated with improved outcomes after percutaneous coronary intervention ( PCI ) and glycoprotein IIb/IIIa inhibitor treatment . A greater thrombotic burden in acute ST-segment elevation myocardial infa rct ion ( STEMI ) might require higher doses and /or intracoronary delivery of glycoprotein IIb/IIIa inhibitors to achieve optimal PAI . Using a 2 x 2 factorial placebo-controlled design , 105 patients with STEMI who had been referred for primary PCI within 6 hours of symptom onset were r and omized to intracoronary ( IC ) or intravenous ( IV ) delivery of an abciximab bolus at a st and ard dose ( 0.25 mg/kg ) or high dose ( > or = 0.30 mg/kg ) of abciximab . The primary end point was PAI measured at 10 minutes after the bolus of abciximab . Secondary end points included the acute and 6-month outcomes using angiographic parameters , cardiac biomarkers , cardiovascular magnetic resonance imaging , and clinical end points . At 10 minutes after the bolus , the proportion of patients with > or = 95 % PAI was not different between the IC and IV groups ( 53 % vs 54 % , p = 1.00 ) nor between the high-dose and st and ard-dose bolus groups ( 56 % vs 51 % , p = 0.70 ) . Acutely , the angiographic myocardial blush grade s , peak release of cardiac biomarkers , necrosis size , myocardial perfusion , and no reflow as assessed by magnetic resonance imaging , and clinical end points were similar between the groups and did not suggest a benefit for IC compared to IV or high-dose versus st and ard-dose bolus of abciximab . No increase occurred in bleeding complications with the high-dose bolus or IC delivery . The clinical , angiographic and cardiac magnetic resonance imaging outcomes at 6 and 12 months were similar between the 4 groups . In conclusion , in patients with STEMI presenting with symptom onset < 6 hours and undergoing transradial primary PCI , PAI remained suboptimal , despite a higher dose bolus of abciximab . A higher dose bolus or IC delivery of abciximab bolus was not associated with improved acute or late results compared to the st and ard IV dosing and administration Background — Administration of the glycoprotein IIb/IIIa inhibitor abciximab is an effective adjunctive treatment strategy during primary percutaneous coronary intervention for ST-segment elevation myocardial infa rct ion . Although small-scale studies have suggested beneficial effects of intracoronary over intravenous administration of abciximab , this has not been investigated in a medium-scale r and omized clinical trial . Methods and Results — A total of 534 ST-segment elevation myocardial infa rct ion patients undergoing primary percutaneous coronary intervention with thrombus aspiration within 12 hours of symptom onset were r and omized to either an intracoronary or an intravenous bolus of abciximab ( 0.25 mg/kg ) . Patients were pretreated with aspirin , heparin , and clopidogrel . The primary end point was the incidence of restored myocardial reperfusion , defined as complete ST-segment resolution . Secondary end points included myocardial reperfusion as assessed by myocardial blush grade , enzymatic infa rct size , and major adverse cardiac events at 30 days . The incidence of complete ST-segment resolution was similar in the intracoronary and intravenous groups ( 64 % versus 62 % ; P=0.562 ) . However , the incidence of myocardial blush grade 2/3 was higher in the intracoronary group than in the intravenous group ( 76 % versus 67 % ; P=0.022 ) . Furthermore , enzymatic infa rct size was smaller in the intracoronary than in the intravenous group ( P=0.008 ) . The incidence of major adverse cardiac events was similar in both groups ( 5.5 % versus 6.1 % ; P=0.786 ) . Conclusions — In ST-segment elevation myocardial infa rct ion patients undergoing primary percutaneous coronary intervention with thrombus aspiration , intracoronary administration of abciximab compared with intravenous administration does not improve myocardial reperfusion as assessed by ST-segment resolution . However , intracoronary administration is associated with improved myocardial reperfusion as assessed by myocardial blush grade and a smaller enzymatic infa rct size . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00927615 |
12,373 | 29,470,723 | Similarly , overall response rate and clinical benefit rate were higher for patients who received the combination therapy than for patients allocated to AI alone .
Conclusion The addition of CDK 4/6 inhibitors ( either abemaciclib , palbociclib , or ribociclib ) to an AI ( anastrozole or letrozole ) significantly improved PFS , overall response rate , and clinical benefit rate in comparison with a nonsteroidal AI alone | Background To compare the efficacy and toxicity of the combination of cyclin-dependent kinase 4/6 ( CDK 4/6 ) inhibitors and nonsteroidal aromatase inhibitors ( AI ) versus AI alone as first-line therapy for patients with advanced hormone receptor-positive breast cancer . | Purpose Abemaciclib , a cyclin-dependent kinase 4 and 6 inhibitor , demonstrated efficacy as monotherapy and in combination with fulvestrant in women with hormone receptor (HR)-positive , human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer previously treated with endocrine therapy . Methods MONARCH 3 is a double-blind , r and omized phase III study of abemaciclib or placebo plus a nonsteroidal aromatase inhibitor in 493 postmenopausal women with HR-positive , HER2-negative advanced breast cancer who had no prior systemic therapy in the advanced setting . Patients received abemaciclib or placebo ( 150 mg twice daily continuous schedule ) plus either 1 mg anastrozole or 2.5 mg letrozole , daily . The primary objective was investigator-assessed progression-free survival . Secondary objectives included response evaluation and safety . A planned interim analysis occurred after 189 events . Results Median progression-free survival was significantly prolonged in the abemaciclib arm ( hazard ratio , 0.54 ; 95 % CI , 0.41 to 0.72 ; P = .000021 ; median : not reached in the abemaciclib arm , 14.7 months in the placebo arm ) . In patients with measurable disease , the objective response rate was 59 % in the abemaciclib arm and 44 % in the placebo arm ( P = .004 ) . In the abemaciclib arm , diarrhea was the most frequent adverse effect ( 81.3 % ) but was mainly grade 1 ( 44.6 % ) . Comparing abemaciclib and placebo , the most frequent grade 3 or 4 adverse events were neutropenia ( 21.1 % v 1.2 % ) , diarrhea ( 9.5 % v 1.2 % ) , and leukopenia ( 7.6 % v 0.6 % ) . Conclusion Abemaciclib plus a nonsteroidal aromatase inhibitor was effective as initial therapy , significantly improving progression-free survival and objective response rate and demonstrating a tolerable safety profile in women with HR-positive , HER2-negative advanced breast cancer PURPOSE To compare the efficacy and tolerability of tamoxifen with that of letrozole , an oral aromatase inhibitor , with tamoxifen as first-line therapy in postmenopausal women with advanced breast cancer . PATIENTS AND METHODS Nine hundred seven patients were r and omly assigned letrozole 2.5 mg once daily ( 453 patients ) or tamoxifen 20 mg once daily ( 454 patients ) . Patients had estrogen receptor- and /or progesterone receptor-positive tumors , or both receptors were unknown . Recurrence during adjuvant antiestrogen therapy or within the following 12 months or prior endocrine therapy for advanced disease precluded enrollment . One prior chemotherapy regimen for metastatic disease was allowed . The primary end point was time to progression ( TTP ) . Secondary end points included overall objective response rate ( ORR ) , its duration , rate and duration of clinical benefit , time to treatment failure ( TTF ) , overall survival , and tolerability . RESULTS TTP was significantly longer for letrozole than for tamoxifen ( median , 41 v 26 weeks ) . Treatment with letrozole reduced the risk of progression by 30 % ( hazards ratio , 0.70 ; 95 % confidence interval , 0.60 to 0.82 , P = .0001 ) . TTP was significantly longer for letrozole irrespective of dominant site of disease , receptor status , or prior adjuvant antiestrogen therapy . Similarly , TTF was significantly longer for letrozole ( median , 40 v 25 weeks ) . ORR was higher for letrozole ( 30 % v 20 % ; P = .0006 ) , as was the rate of clinical benefit ( 49 % v 38 % ; P = .001 ) . Survival data are currently immature and not reported here . Both treatments were well tolerated . CONCLUSION Letrozole was significantly superior to tamoxifen in TTP , TTF , ORR , and clinical benefit rate . Our results support its use as first-line endocrine therapy in postmenopausal women with advanced breast cancer PURPOSE The efficacy and tolerability of anastrozole ( Arimidex ; AstraZeneca , Wilmington , DE , and Macclesfield , United Kingdom ) and tamoxifen were compared as first-line therapy for advanced breast cancer in 353 postmenopausal women . PATIENTS AND METHODS The r and omized , double-blind , multicenter study was design ed to evaluate anastrozole 1 mg once daily relative to tamoxifen 20 mg once daily in patients with hormone receptor-positive tumors or tumors of unknown receptor status who were eligible for endocrine therapy . Primary end points were objective response ( OR ) , defined as complete ( CR ) or partial ( PR ) response , time to progression ( TTP ) , and tolerability . RESULTS Anastrozole was as effective as tamoxifen in terms of OR ( 21 % v 17 % of patients , respectively ) , with clinical benefit ( CR + PR + stabilization > or = 24 weeks ) observed in 59 % of patients on anastrozole and 46 % on tamoxifen ( two-sided P = .0098 , retrospective analysis ) . Anastrozole had a significant advantage over tamoxifen in terms of TTP ( median TTP of 11.1 and 5.6 months for anastrozole and tamoxifen , respectively ; two-sided P = .005 ) . The tamoxifen : anastrozole hazards ratio was 1.44 ( lower one-sided 95 % confidence limit , 1.16 ) . Both treatments were well tolerated . However , thromboembolic events and vaginal bleeding were reported in fewer patients who received anastrozole compared with those who received tamoxifen ( 4.1 % v 8.2 % [ thromboembolic events ] and 1.2 % v 3.8 % [ vaginal bleeding ] , respectively ) . CONCLUSION Anastrozole satisfied the predefined criteria for equivalence to tamoxifen . Furthermore , we observed both a significant increase in TTP and a lower incidence of thromboembolic events and vaginal bleeding with anastrozole . These findings indicate that anastrozole should be considered as first-line therapy for postmenopausal women with advanced breast cancer This paper is an overview of the new response evaluation criteria in solid tumours : revised RECIST guideline ( version 1 . 1 ) , with a focus on up date d contents BACKGROUND A phase 2 study showed that progression-free survival was longer with palbociclib plus letrozole than with letrozole alone in the initial treatment of postmenopausal women with estrogen-receptor (ER)-positive , human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer . We performed a phase 3 study that was design ed to confirm and exp and the efficacy and safety data for palbociclib plus letrozole for this indication . METHODS In this double-blind study , we r and omly assigned , in a 2:1 ratio , 666 postmenopausal women with ER-positive , HER2-negative breast cancer , who had not had prior treatment for advanced disease , to receive palbociclib plus letrozole or placebo plus letrozole . The primary end point was progression-free survival , as assessed by the investigators ; secondary end points were overall survival , objective response , clinical benefit response , patient-reported outcomes , pharmacokinetic effects , and safety . RESULTS The median progression-free survival was 24.8 months ( 95 % confidence interval [ CI ] , 22.1 to not estimable ) in the palbociclib-letrozole group , as compared with 14.5 months ( 95 % CI , 12.9 to 17.1 ) in the placebo-letrozole group ( hazard ratio for disease progression or death , 0.58 ; 95 % CI , 0.46 to 0.72 ; P<0.001 ) . The most common grade 3 or 4 adverse events were neutropenia ( occurring in 66.4 % of the patients in the palbociclib-letrozole group vs. 1.4 % in the placebo-letrozole group ) , leukopenia ( 24.8 % vs. 0 % ) , anemia ( 5.4 % vs. 1.8 % ) , and fatigue ( 1.8 % vs. 0.5 % ) . Febrile neutropenia was reported in 1.8 % of patients in the palbociclib-letrozole group and in none of the patients in the placebo-letrozole group . Permanent discontinuation of any study treatment as a result of adverse events occurred in 43 patients ( 9.7 % ) in the palbociclib-letrozole group and in 13 patients ( 5.9 % ) in the placebo-letrozole group . CONCLUSIONS Among patients with previously untreated ER-positive , HER2-negative advanced breast cancer , palbociclib combined with letrozole result ed in significantly longer progression-free survival than that with letrozole alone , although the rates of myelotoxic effects were higher with palbociclib-letrozole . ( Funded by Pfizer ; PALOMA-2 Clinical Trials.gov number , NCT01740427 . ) PURPOSE To compare the clinical activity of the pure antiestrogen fulvestrant at 500 mg/mo ( double the approved dose ) with the aromatase inhibitor anastrozole as first-line endocrine therapy for advanced hormone receptor-positive breast cancer in postmenopausal women . PATIENTS AND METHODS FIRST ( Fulvestrant First-Line Study Comparing Endocrine Treatments ) is a phase II , r and omized , open-label , multicenter study of a fulvestrant high-dose ( HD ) regimen ( 500 mg/mo plus 500 mg on day 14 of month 1 ) versus anastrozole ( 1 mg/d ) . The primary efficacy end point was clinical benefit rate ( CBR ) , defined as the proportion of patients experiencing an objective response ( OR ) or stable disease for > or = 24 weeks . The primary analysis was performed 6 months after the last patient was r and omly assigned . RESULTS CBR was similar for fulvestrant HD ( n = 102 ) and anastrozole ( n = 103 ) , 72.5 % v 67.0 % , respectively ( odds ratio , 1.30 ; 95 % CI , 0.72 to 2.38 ; P = .386 ) . Objective response rate ( ORR ) was also similar between treatments : fulvestrant HD , 36.0 % ; anastrozole , 35.5 % . Time to progression ( TTP ) was significantly longer for fulvestrant versus anastrozole ( median TTP not reached for fulvestrant HD v 12.5 months for anastrozole ; hazard ratio , 0.63 ; 95 % CI , 0.39 to 1.00 ; P = .0496 ) . Duration of OR and CB also numerically favored fulvestrant HD . Both treatments were well tolerated , with no significant differences in the incidence of prespecified adverse events . CONCLUSION First-line fulvestrant HD was at least as effective as anastrozole for CBR and ORR and was associated with significantly longer TTP . Fulvestrant HD was generally well tolerated , with a safety profile similar to that of anastrozole |
12,374 | 31,935,866 | The included studies that examined the improvement of nausea and vomiting in pregnancy , inflammation , metabolic syndromes , digestive function , and colorectal cancer ’s markers were consistently supported , whereas other expected functions were relatively controversial .
In addition to the quality assessment result , small population s and unst and ardized evaluation systems were the observed shortcomings in ginger clinical trials .
Further studies with adequate design s are warranted to vali date the reported clinical functions of ginger | Clinical applications of ginger with an expectation of clinical benefits are receiving significant attention .
This systematic review aims to provide a comprehensive discussion in terms of the clinical effects of ginger in all reported areas . | Abstract The effects of the powdered rhizome of Zingiber officinale on the symptoms of motion sickness were compared with those of dimenhydrinate and placebo in 36 undergraduate men and women who reported very high susceptibility to motion sickness . Motion sickness was induced by placing the blindfolded subject in a tilted rotating chair . Measurements of perceived degree of gastrointestinal distress were reported every 15 s for up to 6 minutes by means of psychophysical methods . Z. officinale was superior to dimenhydrinate in reducing motion sickness Objective Ginger has been reported to improve upper gastrointestinal symptoms . Little information about the effects of ginger on gastric motor function , exists , however . Our aim was to investigate the effects of ginger on gastric emptying , antral motility , proximal gastric dimensions , and postpr and ial symptoms . Methods Twenty-four healthy volunteers were studied twice in a r and omized double-blind manner . After an 8 h fast , the volunteers ingested three ginger capsules ( total 1200 mg ) or placebo , followed after 1 h by 500 ml low-nutrient soup . Antral area , fundus area and diameter , and the frequency of antral contractions were measured using ultrasound at frequent intervals over 90 min , and the gastric half-emptying time was calculated from the change in antral area . Gastrointestinal sensations and appetite were scored using visual analog question naires . Data are expressed in terms of mean±st and ard error . Results Antral area decreased more rapidly ( P<0.001 ) and the gastric half-emptying time was less after ginger than placebo ingestion ( 13.1±1.1 vs. 26.7±3.1 min , P<0.01 ) , whereas the frequency of antral contractions was greater ( P<0.005 ) . Fundus dimensions did not differ , and there was no significant difference in any gastrointestinal symptoms . Conclusion Ginger accelerates gastric emptying and stimulates antral contractions in healthy volunteers . These effects could potentially be beneficial in symptomatic patient groups Background : Nausea and vomiting are common and unpleasant complications in pregnancy . Although many alternative therapists support the use of ginger for nausea and vomiting of pregnancy , there is currently insufficient clinical evidence to support its use in this condition Objectives : The present study was performed to assess the effectiveness of ginger in the treatment of nausea and vomiting in pregnancy . Patients and Methods : This seven-day clinical trial was performed on 120 eligible pregnant women with symptoms of mild to moderate nausea and vomiting before 16 weeks gestation . They were divided into ; ginger , placebo and control groups , by block r and omization . Women were asked to record their nausea and vomiting for three days , and then participants received either ginger capsules , or a placebo for four days . No intervention was done with the control group . Data measure was self-recorded symptoms according to the Rhodes Index . Data were analyzed by ANOVA , ANCOVA , Kruskal-Wallis , Chi-square , and Fisher ’s exact test , for the quantitative and qualitative variables . Results : There were no statistical differences in the baseline demographics between the three groups apart from age of marriage and wanted or unwanted pregnancy . An ANCOVA test ( covariance test ) showed significant differences in mean scores after the intervention in the three groups ( P < 0.001 ) . Conclusions : Ginger was effective for the relief of mild to moderate nausea and vomiting in pregnant women at less than 16 weeks gestation In a placebo-controlled study the effect of ginger and fenugreek was examined on blood lipids , blood sugar , platelet aggregation , fibrinogen and fibrinolytic activity . The subjects included in this study were healthy individuals , patients with coronary artery disease ( CAD ) , and patients with non-insulin-dependent diabetes mellitus ( NIDDM ) who either had CAD or were without CAD . In patients with CAD powdered ginger administered in a dose of 4 g daily for 3 months did not affect ADP- and epinephrine-induced platelet aggregation . Also , no change in the fibrinolytic activity and fibrinogen level was observed . However , a single dose of 10 g powdered ginger administered to CAD patients produced a significant reduction in platelet aggregation induced by the two agonists . Ginger did not affect the blood lipids and blood sugar . Fenugreek given in a dose of 2.5 g twice daily for 3 months to healthy individuals did not affect the blood lipids and blood sugar ( fasting and post pr and ial ) . However , administered in the same daily dose for the same duration to CAD patients also with NIDDM , fenugreek decreased significantly the blood lipids ( total cholesterol and triglycerides ) without affecting the HDL-c . When administered in the same daily dose to NIDDM ( non-CAD ) patients ( mild cases ) , fenugreek reduced significantly the blood sugar ( fasting and post pr and ial ) . In severe NIDDM cases , blood sugar ( both fasting and post pr and ial ) was only slightly reduced . The changes were not significant . Fenugreek administration did not affect platelet aggregation , fibrinolytic activity and fibrinogen ♦ Background : In peritoneal dialysis ( PD ) patients , one of the major risk factors for cardiovascular disease is lipid abnormalities . This study was design ed to investigate the effects of ginger supplementation on serum lipids and lipoproteins in PD patients . ♦ Methods : In this r and omized , double-blind , placebo-controlled trial , 36 PD patients were r and omly assigned to either the ginger or the placebo group . The patients in the ginger group received 1,000 mg ginger daily for 10 weeks , while the placebo group received corresponding placebos . At baseline and at the end of week 10 , 7 mL of blood were obtained from each patient after a 12- to 14-hour fast , and serum concentrations of triglyceride , total cholesterol , low density lipoprotein-cholesterol ( LDL-C ) , high density lipoprotein-cholesterol ( HDL-C ) , and lipoprotein ( a ) [ Lp ( a ) ] were measured . ♦ Results : Serum triglyceride concentration decreased significantly up to 15 % in the ginger group at the end of week 10 compared with baseline ( p < 0.01 ) , and the reduction was significant in comparison with the placebo group ( p < 0.05 ) . There were no significant differences between the 2 groups in mean changes of serum total cholesterol , LDL-C , HDL-C , and Lp ( a ) . ♦ Conclusion : This study indicates that daily administration of 1,000 mg ginger reduces serum triglyceride concentration , which is a risk factor for cardiovascular disease , in PD patients Background The activity of ginger in the management of chemotherapy-induced nausea and vomiting ( CINV ) has been suggested , but design inadequacies , heterogeneity of the population , small numbers and poor quality of tested products limit the possibility to offer generalizable results . Patients and methods We conducted a r and omized , double-blind , placebo-controlled , multicenter study in patients planned to receive ≥2 chemotherapy cycles with high dose ( > 50 mg/m2 ) cisplatin . Patients received ginger 160 mg/day ( with st and ardized dose of bioactive compounds ) or placebo in addition to the st and ard antiemetic prophylaxis for CINV , starting from the day after cisplatin administration . CINV was assessed through daily visual-analogue scale and Functional Living Index Emesis question naires . The main objective was protection from delayed nausea ; secondary end points included intercycle nausea and nausea anticipatory symptoms . Results In total , 121 patients received ginger and 123 placebo . Lung ( 49 % ) and head and neck cancer ( HNC ; 35 % ) were the most represented tumors . No differences were reported in terms of safety profile or compliance . The incidence of delayed , intercycle and anticipatory nausea did not differ between the two arms in the first cycle and second cycle . A benefit of ginger over placebo in Functional Living Index Emesis nausea score differences ( day 6-day 1 ) was identified for females ( P = 0.048 ) and HNC patients ( P = 0.038 ) . Conclusions In patients treated with high-dose cisplatin , the daily addition of ginger , even if safe , did not result in a protective effect on CINV . The favorable effect observed on nausea in subgroups at particular risk of nausea ( females ; HNC ) deserves specific investigation Chilli peppers have been shown to enhance diet-induced thermogenesis ( DIT ) and reduce energy intake ( EI ) in some studies , but there are few data on other pungent spices . The primary aim of the present study was to test the acute effects of black pepper ( pepper ) , ginger , horseradish and mustard in a meal on 4 h postpr and ial DIT . The secondary aim was to examine the effects on subjective appetite measures , ad libitum EI and energy balance . In a five-way placebo-controlled , single-blind , cross-over trial , twenty-two young ( age 24·9 ( SD 4·6 ) years ) , normal-weight ( BMI 21·8 ( SD 2·1 ) kg/m² ) males were r and omly assigned to receive a brunch meal with either pepper ( 1·3 g ) , ginger ( 20 g ) , horseradish ( 8·3 g ) , mustard ( 21 g ) or no spices ( placebo ) . The amounts of spices were chosen from pre-testing to make the meal spicy but palatable . No significant treatment effects were observed on DIT , but mustard produced DIT , which tended to be larger than that of placebo ( 14 % , 59 ( SE 3 ) v. 52 ( SE 2 ) kJ/h , respectively , P=0·08 ) . No other spice induced thermogenic effects approaching statistical significance . Subjective measures of appetite ( P>0·85 ) , ad libitum EI ( P=0·63 ) and energy balance ( P=0·67 ) also did not differ between the treatments . Finally , horseradish decreased heart rate ( P=0·048 ) and increased diastolic blood pressure ( P= 0·049 ) compared with placebo . In conclusion , no reliable treatment effects on appetite , EI or energy balance were observed , although mustard tended to be thermogenic at this dose . Further studies should explore the possible strength and mechanisms of the potential thermogenic effect of mustard actives , and potential enhancement by , for example , combinations with other food components Abstract 6-Gingerol is a natural compound extracted from ginger . Pre clinical studies demonstrated that 6-gingerol has an anti-emetic activity by inhibiting neurokinin-1 , serotonin , and dopamine receptors . Several clinical trials examined crude ginger powder for preventing chemotherapy-induced nausea and vomiting ( CINV ) , but none of them was conducted with a st and ardized bioactive compound . Patients who received moderately to highly emetogenic adjuvant chemotherapy were r and omized to receive 6-gingerol 10 mg or placebo orally twice daily for 12 weeks . Ondansetron , metoclopramide , and dexamethasone were given to all patients . The primary endpoint was complete response ( CR ) rate defined as no emesis or rescue treatment at any time . Eighty-eight patients were r and omized to receive 6-gingerol ( N = 42 ) or placebo ( N = 46 ) . Most patients received highly emetogenic chemotherapy ( 93 % ) . Overall CR rate was significantly higher in 6-gingerol group as compared with that of the placebo ( 77 vs. 32 % ; P < 0.001 ) . The difference in means of appetite score was significant ( P = 0.001 ) and more noticeable over time . Mean FACT-G score indicating quality of life was significantly higher ( 86.21 ) in 6-gingerol group at 64 days as compared with that of placebo group ( 72.36 ) ( P < 0.001 ) . No toxicity related to 6-gingerol was observed . Patients treated with 6-gingerol reported significantly less grade 3 fatigue ( 2 vs. 20 % ; P = 0.020 ) . 6-Gingerol significantly improved overall CR rate in CINV , appetite and quality of life in cancer patients receiving adjuvant chemotherapy . A phase III r and omized study of 6-gingerol is warranted to confirm these results Purpose The aim of the study was to compare the effect of mefenamic acid and ginger on pain management in primary dysmenorrhea . Methods One hundred and twenty-two female students with moderate to severe primary dysmenorrhea were r and omly allocated to the ginger and mefenamic groups in a r and omized clinical trial . The mefenamic group received 250 mg capsules every 8 h , and the ginger group received 250 mg capsules ( zintoma ) every 6 h from the onset of menstruation until pain relief lasted 2 cycles . The intensity of pain was assessed by the visual analog scale . Data were analyzed by descriptive statistics , t test , Chi-square , Fisher exact test and repeated measurement . Results The pain intensity in the mefenamic and ginger group was 39.01 ± 17.77 and 43.49 ± 19.99 , respectively , in the first month , and 33.75 ± 17.71 and 38.19 ± 20.47 , respectively , in the second month ( p > 0.05 ) . The severity of dysmenorrhea , pain duration , cycle duration and bleeding volume was not significantly different between groups during the study . The menstrual days were more in the ginger group in the first ( p = 0.01 ) and second cycle ( p = 0.04 ) . Repeated measurement showed a significant difference in pain intensity within the groups by time , but not between groups . Conclusion Ginger is as effective as mefenamic acid on pain relief in primary dysmenorrhea . Ginger does not have adverse effects and is an alternative treatment for primary dysmenorrhea OBJECTIVE To identify the effect of some herbal products on insulin resistance . Regarding the scientific evidence s existing about ginger , this research was therefore carried out to identify the effect of ginger supplementation on insulin resistance and glycemic indices in diabetes mellitus . METHODS This is a r and omized , double-blind , placebo-controlled trial in which 88 participants affected by diabetes were r and omly assigned into ginger ( GG ) and placebo ( PG ) groups . The GG received 3 one-gram capsules containing ginger powder whereas the PG received 3 one-gram microcrystalline-containing capsules daily for 8 weeks . HbA1c , fructosamine , fasting blood sugar ( FBS ) , fasting insulin , homeostasis model assessment insulin resistance index ( HOMA-IR ) , β-cell function ( β% ) , insulin sensitivity ( S% ) and the quantitative insulin sensitivity check index ( QUICKI ) were assessed before and after the intervention . RESULTS FBS mean showed a decrease of 10.5 % ( p=0.003 ) in the GG whereas the mean had an increase of 21 % in the PG ( p=0.01 ) . Variation in HbA1c mean was in line with that of FBS . Statistical difference was found in the two groups before and after the intervention in terms of median of fasting insulin level , S% and HOMA-IR ( P<0.005 ) . Moreover QUICKI mean increased significantly in the two groups , the mean difference , however , was significantly higher in the GG . CONCLUSIONS The study demonstrated that daily consumption of 3 one-gram capsules of ginger powder for 8 weeks is useful for patients with type 2 diabetes due to FBS and HbA1c reduction and improvement of insulin resistance indices such as QUICKI index OBJECTIVE The aim of this study was to determine the effects of ginger in nausea and vomiting of pregnancy . DESIGN This was a single blind clinical trial study . SETTING The study was conducted in a selected prenatal care clinic of Isfahan City hospitals . SUBJECTS The subjects included 67 pregnant women who complained of nausea and vomiting from Isfahan city hospitals participated in the study . INTERVENTION The participants were r and omly assigned to two groups , an experimental group and a control group . The groups were matched according to the age , gestational age , parity , occupational status , and educational level of the participants . The experimental group received ginger 250 mg capsules for 4 days , and the control group received placebo with the same prescription form . OUTCOME MEASURES Effects of treatment of nausea were evaluated twice daily for 4 days by a before- and -after treatment question naire . RESULTS The mean ages of the experimental and control groups were 24.1 + /- 4.8 and 23.3 + /- 5 years , respectively . The mean gestational age was 13 + /- 3 weeks , and the mean parity was 1.6 + /- 0.8 . The ginger users demonstrated a higher rate of improvement than the placebo users did ( 85 % versus 56 % ; p < 0.01 ) . The decrease in vomiting times among ginger users was also significantly greater than among the women who received the placebo ( 50 % versus 9 % ; p < 0.05 ) . DISCUSSION A daily total of 1000 mg of ginger in a capsule preparation can be suggested by care providers as a means of decreasing pregnancy nausea and vomiting in women who tend to herbal medicines . CONCLUSION Ginger is an effective herbal remedy for decreasing nausea and vomiting during pregnancy OBJECTIVE Alternative medicine is used extensively by patients with chronic pain due to e.g. , osteoarthritis . Only few of these drugs have be tested in a controlled setting and the present study was undertaken to examine the effect of ginger extract , one of the most popular herbal medications . DESIGN Ginger extract was compared to placebo and Ibuprofen in patients with osteoarthritis of the hip or knee in a controlled , double blind , double dummy , cross-over study with a wash-out period of one week followed by three treatment periods in a r and omized sequence , each of three weeks duration . Acetaminophen was used as rescue medication throughout the study . The study was conducted in accordance with Good Clinical Practice ( European Guideline for GCP ) . RESULTS A ranking of efficacy of the three treatment periods : Ibuprofen > ginger extract > placebo was found for visual analogue scale of pain ( Friedman test : 24.65 , P < 0.00001 ) and the Lequesne-index ( Friedman test : 20.76 , P < 0.00005 ) . In the cross-over study , no significant difference between placebo and ginger extract could be demonstrated ( Siegel-Castellan test ) , while explorative tests of differences in the first treatment period showed a better effect of both Ibuprofen and ginger extract than placebo ( Chi-square , P < 0.05 ) . There were no serious adverse events reported during the periods with active medications . CONCLUSION In the present study a statistically significant effect of ginger extract could only be demonstrated by explorative statistical methods in the first period of treatment before cross-over , while a significant difference was not observed in the study as a whole OBJECTIVE To study the efficacy of ginger and dimenhydrinate in the treatment of nausea and vomiting in pregnancy . STUDY DESIGN Double blind r and omized controlled trial . SETTING Department of Obstetrics and Gynecology , Thammasat Hospital , Faculty of Medicine , Thammasat University . MATERIAL AND METHOD Between January 2005 and December 2005 , 170 pregnant women who attended at antenatal clinic Thammasat University Hospital with the symptoms of nausea and vomiting in pregnancy were r and omly allocated into group A ( n = 85 ) and group B ( n = 85 ) . The patients in group A received one capsule of ginger twice daily ( one capsule contained 0.5 gm of ginger powder ) while the patients in group B received the identical capsule of 50 mg dimenhydrinate twice daily . The visual analogue nausea scores ( VANS ) and vomiting times were evaluated at day 0 - 7 of the treatment . RESULTS There was no significant difference in the visual analogue nausea scores ( VANS ) between group A and group B in day 1 - 7 of the treatment . The vomiting episodes of group A were greater than group B during the first and second day of the treatment with statistically significant difference . No difference in vomiting episodes during the day 3 - 7 of treatment was found in both groups . There was a statistically significant difference in the side effect of drowsiness after treatment in group B greater ( 77.64 % ) than group A ( 5.88 % ) ( p < 0.01 ) . CONCLUSION From the presented data , ginger is as effective as dimenhydrinate in the treatment of nausea and vomiting during pregnancy and has fewer side effects OBJECTIVE The aim of this study was to investigate the effects of ginger supplementation on serum glucose , advanced glycation end products , oxidative stress , and systemic and vascular inflammatory markers in patients on peritoneal dialysis ( PD ) . METHODS In this r and omized , double-blind , placebo-controlled trial , 36 patients on PD were r and omly assigned to either the ginger or the placebo group . The patients in the ginger group received 1000 mg/d ginger for 10 wk , whereas the placebo group received corresponding placebos . At baseline and the end of week 10 , serum concentrations of glucose , carboxymethyl lysine , pentosidine , malondialdehyde ( MDA ) , high-sensitivity C-reactive protein ( hs-CRP ) , soluble intercellular adhesion molecule type 1 ( sICAM-1 ) , soluble vascular cell adhesion molecule type 1 ( sVCAM-1 ) , and sE-selectin were measured after a 12- to 14-h fast . RESULTS Serum fasting glucose decreased significantly up to 20 % in the ginger group at the end of week 10 compared with baseline ( P < 0.05 ) , and the reduction was significant in comparison with the placebo group ( P < 0.05 ) . There were no significant differences between the two groups in mean changes of serum carboxymethyl lysine , pentosidine , MDA , hs-CRP , sICAM-1 , sVCAM-1 , and sE-selectin . CONCLUSION This study indicated that daily administration of 1000 mg ginger reduces serum fasting glucose , which is a risk factor for hyperinsulinemia , dyslipidemia , peritoneal membrane fibrosis , and cardiovascular disease , in patients on PD Ginger has long been used as an alternative medication to prevent motion sickness . The mechanism of its action , however , is unknown . We hypothesize that ginger ameliorates the nausea associated with motion sickness by preventing the development of gastric dysrhythmias and the elevation of plasma vasopressin . Thirteen volunteers with a history of motion sickness underwent circular vection , during which nausea ( scored 0 - 3 , i.e. , none to severe ) , electrogastrographic recordings , and plasma vasopressin levels were assessed with or without ginger pretreatment in a crossover- design , double-blind , r and omized placebo-controlled study . Circular vection induced a maximal nausea score of 2.5 + /- 0.2 and increased tachygastric activity and plasma vasopressin . Pretreatment with ginger ( 1,000 and 2,000 mg ) reduced the nausea , tachygastria , and plasma vasopressin . Ginger also prolonged the latency before nausea onset and shortened the recovery time after vection cessation . Intravenous vasopressin infusion at 0.1 and 0.2 U/min induced nausea and increased bradygastric activity ; ginger pretreatment ( 2,000 mg ) affected neither . Ginger effectively reduces nausea , tachygastric activity , and vasopressin release induced by circular vection . In this manner , ginger may act as a novel agent in the prevention and treatment of motion sickness Obesity and its metabolic consequences are major risk factors for cardiovascular morbidity and mortality . However , lifestyle interventions , including exercise training and dietary components may decrease cardiovascular risk . Hence , this study was conducted to assess the effects of ginger supplementation and progressive resistance training on some cardiovascular risk factors in obese men . In a r and omized double-blind design , 32 obese Iranian men ( BMI ≥ 30 ) were assigned in to one of four groups : Placebo ( PL , n = 8) ; ginger group ( GI , n = 8) that consumed 1 gr ginger/d for 10 wk ; resistance training plus placebo ( RTPL , n = 8) ; and 1gr ginger plus resistance exercise ( RTGI , n = 8) . Progressive resistance training was performed three days per week for 10 weeks and included eight exercises . At baseline and after 10 weeks , body composition and anthropometric indices were measured . To identify other risk factors , venous blood sample s were obtained before and 48 - 72 hours after the last training session for measurement of blood lipids ( LDL-C , HDL-C , TG ) , systemic inflammation ( CRP ) , and insulin resistance ( HOMA-IR ) . After 10 weeks both RTGI and RTPL groups showed significant decreases in waist circumference ( WC ) , waist-to-hip ratio ( WHR ) , body fat percent , body fat mass , total cholesterol , and insulin resistance ( p < 0.05 ) and a significant increase in fat free mass ( FFM ) ( p < 0.05 ) , while it remained unchanged in PL and GI . Further , significant decreases in the mean values of CRP were observed in all groups except PL ( p < 0.05 ) . Our results reveal that resistance training is an effective therapeutic strategy to reduce cardiovascular risk in obese Iranian men . Further , ginger supplementation alone or in combination with resistance training , also reduces chronic inflammation . However more research on the efficacy of this supplement to reduce cardiovascular risk in humans is required . Key pointsLong- term resistance training reduced cardiovascular risk factors in obese men . Ginger supplementation can also decrease chronic low grade inflammation in obese men . More research es are warranted to elicit the effects of these interventions on cardiovascular risk factors in humans Background Nausea and vomiting are one of the most common complications of cesarean sections under spinal anesthesia . Recently , the use of drugs to treat nausea and vomiting has decreased , and nonpharmaceutical and alternative traditional medicine are often preferred . Objectives This study aim ed to determine the effect of ginger extract on the incidence and severity of nausea and vomiting after cesarean section under spinal anesthesia . Methods In this double-blind r and omized clinical trial , 92 pregnant women , each of whom underwent a cesarean section under spinal anesthesia , were divided in two groups : a control group and an intervention group . The intervention group received 25 drops of ginger extract in 30 cc of water , and the control group received 30 cc of water one hour before surgery . The incidence and severity of nausea and vomiting were assessed during the surgery and two and four hours after the surgery using a self-report scale . Data analysis was performed using SPSS software and statistical tests . Results There was no statistically significant difference between the two groups in terms of maternal age , duration of fasting , duration of surgery , and confounding factors ( P > 0.05 ) . According to an independent t-test , there was a significant relationship between the two groups in terms of the incidence and mean severity score of nausea and vomiting during the cesarean section ( P < 0.05 ) . However , no statistically significant relationship was found between the two groups in terms of the incidence and mean severity score of nausea and vomiting two and four hours after surgery ( P > 0.05 ) . Conclusions The findings of this study showed that ginger extract can be used for the prevention of nausea and vomiting during cesarean section under spinal anesthesia Acute hyperglycemia evokes gastric slow wave dysrhythmias via endogenous prostagl and in generation . Ginger exhibits slow wave antiarrhythmic effects in other models , but its actions on hyperglycemia-evoked gastric dysrhythmias are unexplored . We hypothesized that ginger prevents disruption of slow wave rhythm by acute hyperglycemia via inhibition of prostagl and in production but not its actions . Twenty-two healthy humans underwent fasting electrogastrography during hyperglycemic clamping to 250 to 290 mg/dl after double-blind placebo or ginger root ( 1 g ) . Responses were compared with the prostagl and in E1 analog misoprostol ( 400 μg ) . Dominant frequencies ( DF ) and the percentage of recording times in the bradygastric [ 0.5–2 cycles/min ( cpm ) ] , normal ( 2–4 cpm ) , and tachygastric ( 4–9 cpm ) frequency ranges were analyzed . After placebo , hyperglycemia reduced normal 2 to 4 cpm activity from 94.4 ± 2.6 to 66.0 ± 10.4 % , increased the DF from 2.96 ± 0.04 to 4.09 ± 0.45 cpm , and increased tachygastria from 2.0 ± 1.4 to 29.3 ± 10.7 % ( P < 0.05 ) . Hyperglycemia effects on normal activity ( 77.3 ± 8.3 % ) , DF ( 3.46 ± 0.37 cpm ) , and tachygastria ( 15.6 ± 8.6 % ) were significantly reduced by ginger ( P < 0.05 ) . Misoprostol evoked decreases in normal activity from 95.4 ± 2.0 to 81.7 ± 3.0 % and increases in tachygastria from 3.1 ± 1.6 to 11.2 ± 2.4 % ( P < 0.05 ) . However , ginger did not correct these abnormalities versus placebo ( P = N.S. ) . In conclusion , acute hyperglycemia evokes gastric slow wave dysrhythmias that are prevented by ginger root . Conversely , the compound has no effect on dysrhythmias elicited by a prostagl and in E1 analog , indicating that ginger likely acts to blunt production of prostagl and ins rather than inhibiting their action . These findings suggest novel mechanisms for the traditional Chinese herbal remedy ginger BACKGROUND Breast cancer is one of the most frequent diseases in women today . Little information exists on modifiable lifestyle factors including effects of ginger supplements ( as an anti-oxidant and anti-inflammatory herbal ) and water-based exercise on biomarkers related to oxidative stress such as malondialdehyde ( MDA ) , nitric oxide ( NO ) and glutathione peroxidase ( GPx ) and adiponectin in obese women with breast cancer . The aim of this study was to determine the single and concomitant effect of 6-wks water-based exercise and oral ginger supplement on the aforesaid markers in obese women with breast cancer . MATERIAL S AND METHODS Forty women diagnosed with breast cancer ( 48 ± 5.4 years , 76 ± 9 kg , fat mass 41.8 ± 4 % ) , volunteered to participate in the study . Subjects were r and omly assigned into four groups ; placebo , water-based exercise , ginger supplement and water-based exercise+ginger supplement groups . Subjects in the ginger supplement group and the water-based exercise+ginger supplement group orally received 4 capsules ( each capsule contained 750 mg ) , 7 days a week for 6 weeks . The water-based exercise program featured progressive increase in intensity and time , ranging from 50 % to 75 % of heart rate reserve , in a pool with 15 meters width , 4 times a week for 6 weeks . Fasting blood sample s were collected at pre-test and post-test time points . RESULTS The ginger supplementation and or the water-base exercise result ed in an increase of adiponectin , NO and GPx and reduction MDA , as compared to pre-test values . However , the combined intervention ( water-base exercise and ginger supplement ) group showed significantly a far better effect on the biomarkers related to oxidative stress and adiponectin levels , as compared to the water- base exercise or ginger supplement alone groups and the age-matched placebo group . CONCLUSIONS Our results revealed that water-base exercise is a non-drug therapeutic strategy to reduce systemic stress in obese women suffering from breast cancer . Further , ginger supplementation alone or in combination with training , also play an important role in the pathogenesis of oxidative stress in obese women diagnosed with breast cancer Abstract Background : The aim of this study was to compare the prophylactic effects of dexamethasone plus ginger and dexamethasone alone on postoperative nausea and vomiting ( PONV ) in patients undergoing thyroidectomy . Methods : One hundred and twenty patients undergoing general anaesthesia for thyroidectomy were enrolled in this r and omised , double-blind study . Patients received oral diazepam 10 mg with either oral placebo ( group I ) or 0.5 g of ginger ( group II ) as premedication 1 hour prior to surgery . St and ard general anaesthetic techniques and postoperative analgesia were employed . Both group I and group II received intravenous dexamethasone 150 μg/kg immediately before the induction of anaesthesia . Data were recorded over a 24-hour observation period after surgery . Results : In the dexamethasone-treated group , 14 patients experienced nausea , two patients retched , three patients vomited once , two patients vomited repeatedly , and 14 patients required a rescue antiemetic . In the dexamethasone-plus-gingertreated group , 12 patients experienced nausea , one patient retched , four patients vomited once , no patients vomited repeatedly , and 13 patients required a rescue antiemetic . Dexamethasone plus ginger did not significantly reduce nausea and vomiting compared with dexamethasone alone during the observation period . Conclusion : In conclusion , the prophylactic combination of antiemetic treatment with dexamethasone and ginger was not clinical ly or statistically superior to dexamethasone alone in preventing PONV in patients undergoing thyroidectomy PURPOSE The purpose of this study is to evaluate the effects of an enteral diet enriched with ginger extract on inflammatory factors , respiratory profile , and outcome of patients with acute respiratory distress syndrome ( ARDS ) . MATERIAL S AND METHODS Thirty-two patients with ARDS were r and omized to receive a high-protein enteral diet enriched with ginger or placebo . Serum levels of interleukin ( IL ) 1 , IL-6 , tumor necrosis factor α , and leukotriene B4 ; red blood cell glutathione ; oxygenation ; and static compliance were measured on days 0 , 5 , and 10 . RESULTS Patients fed enteral diet enriched with ginger had significantly lower serum levels of IL-1 , IL-6 , and tumor necrosis factor α and higher level of RBC glutathione on days 5 and 10 compared with control group ( P < .05 ) . Significant improvement in oxygenation was observed on day 5 ( P = .02 ) and 10 ( P = .003 ) in ginger group compared with control group . Static compliance was increased on day 5 ( P = .01 ) in ginger group compared with control group . A significant difference was found in duration of mechanical ventilation ( P = .02 ) and length of intensive care unit stay ( P = .04 ) in favor of ginger group . We did not find any difference in barotraumas , organ failure , and mortality between the study groups . CONCLUSIONS An enteral diet supplemented with ginger in patients with ARDS may be beneficial for gas exchange and could decrease duration of mechanical ventilation and length of stay in intensive care unit The effectiveness of ginger ( Zingiber officinale ) as an antiemetic agent was compared with placebo and metoclopramide in 60 women who had major gynaecological surgery in a double‐blind , r and omised study . There were statistically significantly fewer recorded incidences of nausea in the group that received ginger root compared with placebo ( p < 0.05 ) . The number of incidences of nausea in the groups that received either ginger root or metoclopramide were similar . The administration of antiemetic after operation was significantly greater in the placebo group compared to the other two groups ( p < 0.05 ) BACKGROUND Chemotherapy-induced nausea and vomiting ( CINV ) is among the most common and distressing symptoms experienced by patients receiving cancer treatment . Nurses play a substantial role in the prevention and management of CINV . Ginger ( Zingiber officinale Roscoe ) is often advocated as beneficial for nausea and vomiting . Whether the herb is truly efficacious for this condition is , however , still a matter of debate . OBJECTIVES This experimental r and omized , controlled trial was done to assess the effect of ginger on chemotherapy-related nausea and vomiting . METHODS All patients in the study ( N = 60 ) received st and ard antiemetic drugs . The patients in the study group ( n = 30 ) also received oral ginger for the first three days of the chemotherapy cycle . No intervention was performed in the control group ( n = 30 ) except for the routine antiemetic treatment . Nausea severity and the number of vomiting and retching episodes were measured four times each day for the first five days of the chemotherapy cycle in the patient diary . Nausea severity was evaluated using a numeric scale ranging from 0 ( no nausea ) to 10 ( very severe nausea ) . FINDINGS The research ers analyzed the five-day mean score of nausea severity and the number of vomiting and retching episodes . Based on this comparison , nausea severity and the number of vomiting episodes were significantly lower in the intervention group than in the control group ( p > 0.05 ) . However , the change in the number of retching episodes between the intervention and control groups was not statistically significant ( p > 0.05 ) PURPOSE Chemotherapy-induced nausea and vomiting ( CINV ) are major adverse effects of chemotherapy . Ginger has been used in postoperative and pregnancy-induced nausea and vomiting . Data on its utility in reducing CINV in children and young adults are lacking . PATIENTS AND METHODS Sixty chemotherapy cycles of cisplatin/doxorubicin in bone sarcoma patients were r and omized to ginger root powder capsules or placebo capsules as an additional antiemetic to ondensetron and dexamethasone in a double-blind design . Acute CINV was defined as nausea and vomiting occurring within 24 hr of start of chemotherapy ( days 1 - 4 ) and delayed CINV as that occurring after 24 hr of completion of chemotherapy ( days 5 - 10 ) . CINV was evaluated as per Edmonton 's Symptom Assessment Scale and National Cancer Institute criteria respectively . RESULTS Acute moderate to severe nausea was observed in 28/30 ( 93.3 % ) cycles in control group as compared to 15/27 ( 55.6 % ) cycles in experimental group ( P = 0.003 ) . Acute moderate to severe vomiting was significantly more in the control group compared to the experimental group [ 23/30 ( 76.7 % ) vs. 9/27 ( 33.33 % ) respectively ( P= 0.002 ) ] . Delayed moderate to severe nausea was observed in 22/30 ( 73.3 % ) cycles in the control group as compared to 7/27 ( 25.9 % ) in the experimental group ( P < 0.001 ) . Delayed moderate to severe vomiting was significantly more in the control group compared to the experimental group [ 14/30 ( 46.67 % ) vs. 4/27 ( 14.81 % ) ( P = 0.022 ) ] . CONCLUSION Ginger root powder was effective in reducing severity of acute and delayed CINV as additional therapy to ondensetron and dexamethasone in patients receiving high emetogenic chemotherapy ( Clinical Trials.gov identifier : NCT00940368 ) Ginger has known hypoalgesic and anti-inflammatory properties . The effects of an oral dose of ginger on quadriceps muscle pain , rating of perceived exertion ( RPE ) , and recovery of oxygen consumption were examined during and after moderate-intensity cycling exercise . Twenty-five college-age participants ingested a 2-g dose of ginger or placebo in a double-blind , crossover design and 30 min later completed 30 min of cycling at 60 % of VO2peak . Quadriceps muscle pain , RPE , work rate , heart rate ( HR ) , and oxygen uptake ( VO2 ) were recorded every 5 min during exercise , and HR and VO2 were recorded for 20 min after exercise . Compared with placebo , ginger had no clinical ly meaningful or statistically significant effect on perceptions of muscle pain , RPE , work rate , HR , or VO2 during exercise . Recovery of VO2 and HR after the 30-min exercise bout followed a similar time course in the ginger and placebo conditions . The results were consistent with related findings showing that ingesting a large dose of aspirin does not acutely alter quadriceps muscle pain during cycling , and this suggests that prostagl and ins do not play a large role in this type of exercise-induced skeletal-muscle pain . Ginger consumption has also been shown to improve VO2 recovery in an equine exercise model , but these results show that this is not the case in humans To determine the anti‐emetic effect of ginger as compared to droperidol , 120 patients scheduled to have gynaecological diagnostic laparoscopy as day cases were r and omly allocated into placebo , droperidol , ginger and ginger plus droperidol groups to receive either 2 g of ginger or 1.25 mg of droperidol or both . There were no significant differences in the incidences of postoperative nausea which were 32 % , 20 % , 22 % and 33 % , and vomiting which were 35 % , 15 % , 25 % and 25 % in the four groups , respectively . We conclude that ginger powder , in the dose of 2 g , droperidol 1.25 mg or both are ineffective in reducing the incidence of postoperative nausea and vomiting after day case gynaecological laparoscopy OBJECTIVES Ginger ( Zingiber Officinale Roscoe ) has been cl aim ed to exert an anti-thrombotic effect in humans as ginger extracts inhibit cyclo-oxygenase activity of platelets in vitro . Effects of ginger consumption on ex vivo platelet function , however , are contradictory . We therefore investigated whether daily consumption of raw or cooked ginger decreases platelet cyclo-oxygenase activity as assessed by ex vivo maximally stimulated platelet thromboxane B2 production . DESIGN We carried out a r and omized placebo-controlled cross-over study of 3 x 2 weeks . SUBJECTS Eighteen healthy volunteers aged 22 + /- 3 y ( mean + /- s.d . ) participated in the study ; there were no dropouts . INTERVENTIONS Subjects consumed 15 g of raw ginger root , 40 g of cooked stem ginger , or placebo daily for two weeks . We took fasted venous blood sample s and measured thromboxane B2 production in maximally stimulated platelet-rich plasma at days 12 and 14 of each treatment period . RESULTS Mean decrease in thromboxane production relative to placebo was 1 + /- 9 % for ginger root , and -1 + /- 8 % for stem ginger , with no effect of treatment order ( P = 0.984 ) . CONCLUSIONS We can not confirm the putative anti-thrombotic activity of ginger in humans This study was design ed to evaluate the antimotion sickness activity of ginger root ( Zingiber officinale ) and to characterize the effects of ginger on gastric function . Twenty-eight human volunteers participated in the project . Subjects made timed head movements in a rotating chair until they reached an endpoint of motion sickness short of vomiting ( malaise III or M-III ) . Each subject was tested with either ginger or scopolamine and a placebo . A substance was judged to possess antimotion sickness activity if it allowed a greater number of head movements compared to placebo control . Gastric emptying of a liquid was measured by nuclear medicine techniques in normal and motion sick subjects . Gastric electrical activity was monitored by cutaneous ( surface ) electrodes positioned over the abdominal area . Powder ginger ( whole root , 500 or 1,000 mg ) or fresh ginger root ( 1,000 mg ) provided no protection against motion sickness . In contrast , subjects performed an average of 147.5 more head movements ( p less than 0.01 ) after scopolamine ( 0.6 mg p.o . ) than after placebo . The rate of gastric emptying was significantly ( p less than 0.05 ) slowed when tested immediately after M-III but was inhibited less when tested 15 min after M-III . Powdered ginger ( 500 mg ) had no effect on gastric emptying in normal or motion-sick subjects . Gastric motility was also changed during motion sickness . The frequency of the electrogastrogram ( EGG ) was increased after M-III ( tachygastria ) and the normal increase in EGG amplitude after liquid ingestion was reduced in motion sick subjects . Although powdered ginger ( 500 mg ) partially inhibited tachygastria in motion sickness , it did not enhance the EGG amplitude in motion sick subjects . We conclude that ginger does not possess antimotion sickness activity , nor does it significantly alter gastric function during motion sickness To determine whether ginger had antiemetic effect in cisplatin-induced emesis , we conducted a r and omized , double-blinded crossover study in 48 gynecologic cancer patients recieving cisplatin-based chemotherapy . Subjects were r and omly allocated to regimen A or regimen B in their first cycle of the study . All patients received st and ard antiemetics in the first day of cisplatin administration . In regimen A , capsules of ginger root powder were given orally 1 g /day for 5 days , starting on the first day of chemotherapy . In regimen B , placebo was given on the first day and metoclopramide was given orally thereafter for 4 days . The patients were then crossed over to receive the other antiemetic regimen in their next cycle of chemotherapy . Among 43 evaluable patients who received both cycles of treatment , success in controls of nausea and emesis were not significantly different between the two regimens in both acute and delayed phases . Restlessness , as a side effect , occurred more often in metoclopramide arm compared to ginger arm ( P = 0.109 ) . In conclusion , addition of ginger to st and ard antiemetic regimen has no advantage in reducing nausea or vomiting in acute phase of cisplatin-induced emesis . In delayed phase , ginger and metoclopramide have no statistically significant difference in efficacy Osteoarthritis ( OA ) is a chronic degenerative disorder of synovial joints and a common cause of locomotor disability . NSAIDs are routinely used for symptomatic treatment and are associated with side effects which have led to the increased interest towards alternative treatment options . This study was conducted to evaluate the safety and efficacy of ginger in management of OA . Sixty patients of OA of knee were enrolled in r and omized open label study and divided into three groups of 20 each . Group I received tab . Diclofenac 50 mg and cap . placebo , group II received cap . ginger 750 mg and cap . placebo and group III received cap . ginger 750 mg and tab . diclofenac 50 mg . The assessment of efficacy was done at every 2 weeks till 12 weeks , by using Western Ontario and McMaster Universities osteoarthritis ( WOMAC ) index , Visual Analogue Scale ( VAS ) and the safety assessment was done by noting adverse events during the study . The analysis of WOMAC score and VAS score in all the three groups showed statistically significant improvement with time in all groups . On comparison among three groups , group III patients who received both ginger and diclofenac showed numerically superior improvement than the individual treatments . There was no statistically significant difference among three groups in case of adverse events . Ginger powder has add-on effect on reducing the symptoms of OA of knee with acceptable safety profile OBJECTIVE To assess the effectiveness of ginger in providing relief to patients of primary dysmenorrhoea . METHODS The clinical trial was conducted at Toyserkan Azad University in western Iran from July 10 to September 5 , 2010 . It comprised of 70 female students of the university with primary dysmenorrhoea . The subjects were r and omly divided in to two equal groups and were given either placebo or ginger in capsule form for 3 days in first menstruation cycles . They grade d the severity of their pain using a visual analogue scale . A 5-point Likert scale was used to assess response to treatment . Wilcoxor 's rank-sum test was used to compare the severity of pain in the two groups . RESULTS Compared with the baseline , the decrease in the visual analogue scores of post-therapy pain in the ginger group was significantly greater than that for placebo group . In the ginger group , 29 ( 82.85 % ) subjects reported an improvement in nausea symptoms , compared with 16 ( 47.05 % ) in the placebo group . CONCLUSION Ginger is effective in minimising the pain severity in primary dysmenorrhoea Abstract Background : Tuberculosis ( TB ) has reemerged to become the world ’s leading cause of death from a single infectious agent . Inflammatory cytokines play an important role during the course of the disease and may be responsible for tissue damage by lipid peroxidation . The study was aim ed to explore the anti-inflammatory and antioxidant effect of ginger in pulmonary TB patients . Methods : A total of 69 pulmonary TB patients participated in a r and omized and placebo-controlled study . The intervention group received 3 g of ginger extract daily for 1 month and placebo group was supplemented with starch capsule . Participants of both groups were taking st and ard antitubercular treatment during the study . The concentrations of tumor necrosis factor ( TNF ) alpha , ferritin and malondialdehyde ( MDA ) in blood sample s were analyzed before and after the intervention by using enzyme-linked immunosorbent assay for TNF alpha and ferritin and spectrophotometry for MDA . Results : Ginger supplementation significantly reduced the levels of TNF alpha , ferritin and MDA in ginger supplemented group in comparison to baseline . Ginger supplementation with antitubercular treatment significantly lowered TNF alpha , ferritin and MDA concentrations in comparison to control group . Conclusions : Ginger was found to be effective as an anti-inflammatory and antioxidant supplement along with anti-TB therapy as it possesses strong free radical scavenging property OBJECTIVE To study the effectiveness of ginger for prevention of nausea and vomiting after gynecological laparoscopy . MATERIAL AND METHOD From July 2005 to October 2005 , 60 in patients who underwent laparoscopic operations for non-cancer gynecologic conditions at Bangkok Metropolitan Administration Medical College or Vajira Hospital were r and omized into Group A ( n = 30 ) or Group B ( n = 30 ) . Group A received 3 capsules of ginger ( 1 capsule contained 0.5 g of ginger powder ) while Group B received 3 capsules of placebo . Both groups received their medicine 1 hour prior the operation . Nausea and vomiting were assessed with the Visual Analogue Scores ( VAS ) and presence of vomiting at 2 and 6 hours after the operation . RESULTS Median VAS at 2 hours post operation of Group A was not significantly different from that of Group B with the median of 0 ( range , 0 - 5.4 ) and 0.15 ( range , 0 - 10 ) respectively ( 95 % CI from -2.59 to 0.90 and p = 0.142 ) . At 6 hours post operation , the median VAS of Group A was significantly lower than group B , 0.55 ( range , 0 - 7.4 ) versus 2.80 ( range , 0 - 10 ) ( 95 % CI from -3.61 to -0.73 and p = 0.015 ) . Presence of vomiting at 2 hours was not different between the two groups , 10 % in Group A and 20 % in Group B ( 95 % CI from -28 % to 8 % and p = 0.278 ) . At 6 hours , 23.3 % of group A had an episode of vomiting compared to 46.7 % of group B ( 95 % CI from -47 % to 1 % and p = 0.058 ) . CONCLUSION Ginger has shown efficacy for prevention of nausea and borderline significance to prevention vomiting after gynecological laparoscopy at 6 hour post operation CONTEXT Ginger ( Zingiber officinale ) has been used to ameliorate symptoms of nausea . A beverage containing ginger in a syrup may be easier to consume than a capsule or solid food . OBJECTIVE To determine if ginger syrup mixed in water is an effective remedy for the relief of nausea and vomiting in the first trimester of pregnancy . DESIGN Double-blind , placebo-controlled , r and omized clinical trial . SETTING Subjects were enrolled from the University of South Florida department of obstetrics and gynecology private practice office . PATIENTS 26 subjects in the first trimester of pregnancy . INTERVENTION Subjects ingested 1 tablespoon of commercially prepared study syrup ( or placebo ) in 4 to 8 ounces of hot or cold water 4 times daily . MAIN OUTCOME MEASURES Duration and severity of nausea and vomiting over a 2-week period measured on a 10-point scale . RESULTS After 9 days , 10 of the 13 ( 77 % ) subjects receiving ginger had at least a 4-point improvement on the nausea scale . Only 2 of the 10 ( 20 % ) remaining subjects in the placebo group had the same improvement . Conversely , no woman in the ginger group , but 7 ( 70 % ) of the women in the placebo group , had a 2-point or less improvement on the nausea scale . Eight of the 12 ( 67 % ) women in the ginger group who were vomiting daily at the beginning of the treatment stopped vomiting by day 6 . Only 2 of the 10 ( 20 % ) women in the placebo group who were vomiting stopped by day 6 . CONCLUSION The ingestion of 1 g of ginger in syrup in a divided dose daily may be useful in some patients experiencing nausea and vomiting in the first trimester of pregnancy Frequency and torment caused by migraines direct patients toward a variety of remedies . Few studies to date have proposed ginger derivates for migraine relief . This study aims to evaluate the efficacy of ginger in the ablation of common migraine attack in comparison to sumatriptan therapy . In this double-blinded r and omized clinical trial , 100 patients who had acute migraine without aura were r and omly allocated to receive either ginger powder or sumatriptan . Time of headache onset , its severity , time interval from headache beginning to taking drug and patient self-estimation about response for five subsequent migraine attacks were recorded by patients . Patients ( , ) satisfaction from treatment efficacy and their willingness to continue it was also evaluated after 1 month following intervention . Two hours after using either drug , mean headaches severity decreased significantly . Efficacy of ginger powder and sumatriptan was similar . Clinical adverse effects of ginger powder were less than sumatriptan . Patients ' satisfaction and willingness to continue did not differ . The effectiveness of ginger powder in the treatment of common migraine attacks is statistically comparable to sumatriptan . Ginger also poses a better side effect profile than sumatriptan In a double-blind r and omized placebo trial , the effect of the powdered rhizome of ginger ( Zingiber officinale ) was tested on seasickness . Eighty naval cadets , unaccustomed to sailing in heavy seas reported during voyages on the high seas , symptoms of seasickness every hour for 4 consecutive hours after ingestion of 1 g of the drug or placebo . Ginger root reduced the tendency to vomiting and cold sweating significantly better than placebo did ( p less than 0.05 ) . With regard to vomiting , a modified Protection Index ( PI ) = 72 % was calculated . Remarkably fewer symptoms of nausea and vertigo were reported after ginger root ingestion , but the difference was not statistically significant . For all symptom categories , PI = 38 % was calculated PURPOSE The purpose of this study was to evaluate the effect of ginger extract on delayed gastric emptying , developing ventilator-associated pneumonia , and clinical outcomes in adult respiratory distress syndrome ( ARDS ) . MATERIAL S AND METHODS Thirty-two ARDS patients who were dependent on mechanical ventilation and fed via nasogastric tube were studied . After enrollment , patients were r and omized to 2 groups . The control group received 1 g of coconut oil as placebo , and the study group received 120 mg of ginger extract . The amount of feeding tolerated at the first 48 hours of feeding , amount of feeding tolerated during the entire study period , nosocomial pneumonia , number of intensive care unit (ICU)-free days , number of ventilator-free days , and mortality were evaluated during 21 days of intervention . RESULTS There was a significant difference between the ginger group and the control group in the amount of feeding tolerated at the first 48 hours of enteral feeding ( 51 % vs 57 % , P < .005 ) . There was a trend toward a decrease in pneumonia in the ginger group ( P = .07 ) . The overall in-ICU mortality was 15.6 % , with no significant difference in the 2 groups . The number of ventilator-free days and that of ICU-free days were lower in the control group compared with the ginger group ( P = .04 and P = .02 ) . CONCLUSION This study showed that gastric feed supplementation with ginger extract might reduce delayed gastric emptying and help reduce the incidence of ventilator-associated pneumonia in ARDS OBJECTIVE To study the effect of fine powder of ginger on lipid level in volunteer patients . METHODS This is a double blind controlled clinical trial study in 2 cardiac clinics Cardiac Disease Clinic , Babol , north of Iran , between April to May 2004 . We r and omly divided the patients with hyperlipidemia into 2 groups , treatment group ( receiving ginger capsules 3 g/day in 3 divided doses ) and placebo group ( lactose capsule 3 g/day in 3 divided doses ) for 45 days . All subjects with diabetes mellitus , hypothyroidism , nephrotic syndrome , and alcohol drinking , pregnancy and peptic ulcer were excluded . Lipid concentrations profile before and after treatment was measured by enzymatic assay . RESULTS Forty-five patients in the treatment group and 40 patients in placebo group participated in this study . There was a significant reduce in triglyceride , cholesterol , low density lipoprotein ( LDL ) , very low density lipoprotein ( VLDL ) , levels of before and after study separately in each group ( p<0.05 ) . Mean changes in triglyceride and cholesterol levels of ginger group were significantly higher than placebo group ( p<0.05 ) . Mean reduction in LDL level and increase in high density lipoprotein level of ginger group were higher than the placebo group , but in VLDL level of placebo was higher than ginger ( p>0.05 ) . CONCLUSION The results show that ginger has a significant lipid lowering effect compared to placebo A controlled , double-blind study was carried out to determine whether nystagmus response to optokinetic or vestibular stimuli might be altered by some agent contained in powdered ginger root ( Zingiber officinale ) . For comparative purpose s , the test subjects were examined after medication with ginger root , placebo and with dimenhydrinate . Eye movements were recorded using st and ard ENG equipment and evaluation was performed by automatic nystagmus analysis . It could be demonstrated that the effect of ginger root did not differ from that found at baseline , or with placebo , i.e. it had no influence on the experimentally induced nystagmus . Dimenhydrinate , on the other h and , was found to cause a reduction in the nystagmus response to caloric , rotatory and optokinetic stimuli . From the present study it can be concluded that neither the vestibular nor the oculomotor system , both of which are of decisive importance in the occurrence of motion sickness , are influenced by ginger . A CNS mechanism , which is characteristic of the conventional anti-motion sickness drugs , can thus be excluded as regards ginger root . It is more likely that any reduction of motion-sickness symptoms derives from the influence of the ginger root agents on the gastric system The effect of powdered ginger root was compared with metoclopramide and placebo . In a prospect i ve , r and omised , double‐blind trial the incidence of postoperative nausea and vomiting was measured in 120 women presenting for elective laparoscopic gynaecological surgery on a day stay basis . The incidence of nausea and vomiting was similar in patients given metoclopramide and ginger ( 27 % and 21 % ) and less than in those who received placebo ( 41 % ) . The requirement for postoperative antiemetics was lower in those patients receiving ginger . The requirements for postoperative analgesia , recovery time and time until discharge were the same in all groups . There was no difference in the incidence of possible side effects such as sedation , abnormal movement , itch and visual disturbance between the three groups . Zingiber officinale is an effective and promising prophylactic antiemetic , which may be especially useful for day case The present study investigated the impact of a single oral ingestion of ginger on thermoregulatory function and fat oxidation in humans . Morning and afternoon oral intake of 1.0 g dried ginger root powder did not alter rectal temperature , skin blood flow , O2 consumption , CO2 production , and thermal sensation and comfort , or induce sweating at an ambient temperature of 28 ° C . Ginger ingestion had no effect on threshold temperatures for skin blood flow or thermal sweating . Serum levels of free fatty acids were significantly elevated at 120 min after ginger ingestion in both the morning and afternoon . Morning ginger intake significantly reduced respiratory exchange ratios and elevated fat oxidation by 13.5 % at 120 min after ingestion . This was not the case in the afternoon . These results suggest that the effect of a single oral ginger administration on the peripheral and central thermoregulatory function is miniscule , but does facilitate fat utilization although the timing of the administration may be relevant BACKGROUND Nonsteroid anti-inflammatory drugs represent an important osteoarthritis ( OA ) therapy component , but also a leading cause of gastropathy : one of the most frequent and serious OA therapy complications . The aim of the present study was to study the influence of GI health in an OA population receiving either ginger or diclofenac . METHODS Forty-three ( 43 ) patients with confirmed OA ( knee and hip ) were included in a r and omized controlled study . A ginger group of 21 patients ( 17 women , 4 men ) was given a specific ginger combination daily ( 340 mg EV.EXT 35 Zingiber officinalis extract ) for 4 weeks . A diclofenac group ( positive control ) of 22 patients ( 18 women , 4 men ) received 100 mg diclofenac daily for the same period . Both groups also received 1000 mg glucosamine daily . Gastrointestinal pain and dyspepsia were evaluated according to the severity of dyspepsia assessment ( SODA ) form . Patients also underwent esophagogastroduodenoscopy ( EGDS ) including biopsy before and after the treatment . Serum gastrin-17 levels , and stomach mucosa prostagl and ins ( PG ) E1 , E2 , F2α , and 6-keto PGF1α ( PGI2 ) levels were measured . Arthritic pain was evaluated using the visual analogue scale ( VAS ) on st and ing and moving . RESULTS The ginger group showed a slight but significantly lowered SODA pain and no change of SODA dyspepsia . EGDS showed significantly increased levels of PGE1 , PGE2 , and PGF2α in the stomach mucosa . This rise in gastric mucosa PG levels correlated with an increase in serum gastrin-17 . On the other h and , the diclofenac group showed increased SODA pain and dyspepsia values with a corresponding significant decrease of stomach mucosa prostagl and ins and general negative stomach mucosa degeneration . Both groups showed a relevant and significantly lowered VAS pain both on st and ing and moving . CONCLUSIONS The ginger combination is as effective as diclofenac but safer in treating OA , being without effect on the stomach mucosa . The increased mucosal PGs synthesis in the ginger group supports an increased mucosa-protective potential . VAS ; visual analogue scale , 0 - 100 mm Abstract Background : Ginger ( Zingiber officinale ) is one of the functional foods which contains biological compounds including gingerol , shogaol , paradol and zingerone . Ginger has been proposed to have anti-cancer , anti-thrombotic , anti-inflammatory , anti-arthritic , hypolipidemic and analgesic properties . Here , we report the effect of ginger supplementation on glycemic indices in Iranian patients with type 2 diabetes . Methods : A double-blind , placebo-controlled , r and omized clinical trial was conducted on 20–60 -year-old patients with type 2 diabetes who did not receive insulin . Participants in the intervention and control groups were received 3 g of powdered ginger or placebo ( lactose ) ( in capsules ) daily for 3 months . Glycemic indices , total antioxidant capacity ( TAC ) , malondialdehyde ( MDA ) , C-reactive protein ( CRP ) , serum paraoxonase , dietary intake and physical activity were measured at the beginning and end of the study , and after 12 h fasting . Results : Comparison of the indices after 3 months showed that the differences between the ginger and placebo groups were statistically significant as follows : serum glucose ( –19.41±18.83 vs. 1.63±4.28 mg/dL , p<0.001 ) , HbA1c percentage ( –0.77±0.88 vs. 0.02±0.16 % , p<0.001 ) , insulin ( –1.46±1.7 vs. 0.09±0.34 μIU/mL , p<0.001 ) , insulin resistance ( –16.38±19.2 vs. 0.68±2.7 , p<0.001 ) , high-sensitive CRP ( –2.78±4.07 vs. 0.2±0.77 mg/L , p<0.001 ) , paraoxonase-1 ( PON-1 ) ( 22.04±24.53 vs. 1.71±2.72 U/L , p<0.006 ) , TAC ( 0.78±0.71 vs. –0.04±0.29 µIU/mL , p<0.01 ) and MDA ( –0.85±1.08 vs. 0.06±0.08 µmol/L , p<0.001 ) were significantly different . Conclusions : This report shows that the 3 months supplementation of ginger improved glycemic indices , TAC and PON-1 activity in patients with type 2 diabetes Objective : In this r and omized clinical trial ginger efficacy for prevention of antiretroviral-induced nausea and vomiting ( N/V ) was investigated . Methods : From July 2011 until the end of June 2013 , 102 HIV positive patients attending the HIV clinic of Imam Khomeini Hospital participated in the study . In a double blinded manner , participants r and omly received either 500 mg ginger or placebo two times per day , 30 min before each dose of antiretroviral regimen for 14 days . The severity of nausea was assessed based on the visual analogue scale . The number of vomiting episodes were also recorded during the study period . Results : A total of 46 ( 90.2 % ) and 29 ( 56.4 % ) of the patients in placebo and ginger groups experienced some degree of nausea during the first 2 weeks of antiretroviral therapy ( ART ) , respectively ( p = 0.001 ) . Frequency of mild , moderate and severe nausea were significantly lower in the ginger than placebo group ( p = 0 . 001 ) . Also , 24 ( 47.1 % ) and 5 ( 9.8 % ) of the patients in the placebo and ginger groups reported at least one episode of vomiting during their time on ART , respectively ( p = 0.01 ) . Conclusion : Ginger was effective in ameliorating of antiretroviral-induced Abstract Herbal medicines with high amounts of phytochemicals have been shown to have beneficial effects on blood pressure ( BP ) , endothelial function and anthropometric measures . This study aim ed to determine the effect of herbal treatment on BP , endothelial function and anthropometric measures in patients with type 2 diabetes mellitus ( T2DM ) . This clinical trial included 204 T2DM patients r and omly assigned to four intervention groups receiving 3 g cinnamon , 3 g cardamom , 1 g saffron or 3 g ginger with three glasses of black tea , and one control group consuming only three glasses of tea without any herbals , for 8 weeks . Intercellular adhesion molecule-1 ( ICAM-1 ) , systolic and diastolic BP and anthropometric measures were collected at baseline and after 8 weeks . No significant difference was found between various medicinal plants in terms of influencing BP , serum soluble (s)ICAM-1 concentrations and anthropometric measures . However , in within-group comparison saffron and ginger intakes significantly reduced sICAM-1 concentrations ( 340.9 ± 14.4 vs 339.69 ± 14.4 ng/ml , p = 0.01 , and 391.78 ± 16.0 vs 390.97 ± 15.8 ng/ml , p = 0.009 , respectively ) and ginger intake affected systolic BP ( 143.06 ± 0.2 vs 142.07 ± 0.2 mmHg , p = 0.02 ) . Although administration of these herbal medicines as supplementary remedies could affect BP and sICAM-1 concentrations , there was no significant difference between the plants in terms of influencing anthropometric measures , BP and endothelial function AIM The aim of this study was to investigate the effect of two common herbal medicines , ginkgo and ginger , on the pharmacokinetics and pharmacodynamics of warfarin and the independent effect of these herbs on clotting status . METHODS This was an open label , three-way crossover r and omized study in 12 healthy male subjects , who received a single 25 mg dose of warfarin alone or after 7 days pretreatment with recommended doses of ginkgo or ginger from herbal medicine products of known quality . Dosing with ginkgo or ginger was continued for 7 days after administration of the warfarin dose . Platelet aggregation , international normalized ratio ( INR ) of prothrombin time , warfarin enantiomer protein binding , warfarin enantiomer concentrations in plasma and S-7-hydroxywarfarin concentration in urine were measured . Statistical comparisons were made using anova and the 90 % confidence intervals ( CIs ) of the ratio of log transformed parameters are reported . RESULTS INR and platelet aggregation were not affected by administration of ginkgo or ginger alone . The mean ( 95 % CI ) apparent clearances of S-warfarin after warfarin alone , with ginkgo or ginger were 189 ( 167 - 210 ) ml h(-1 ) , 200 ( 173 - 227 ) ml h(-1 ) and 201 ( 171 - 231 ) ml h(-1 ) , respectively . The respective apparent clearances of R-warfarin were 127 ( 106 - 149 ) ml h(-1 ) , 126 ( 111 - 141 ) ml h(-1 ) and 131 ( 106 - 156 ) ml h(-1 ) . The mean ratio ( 90 % CI ) of apparent clearance for S-warfarin was 1.05 ( 0.98 - 1.21 ) and for R-warfarin was 1.00 ( 0.93 - 1.08 ) when coadministered with ginkgo . The mean ratio ( 90 % CI ) of AUC(0 - 168 ) of INR was 0.93 ( 0.81 - 1.05 ) when coadministered with ginkgo . The mean ratio ( 90 % CI ) of apparent clearance for S-warfarin was 1.05 ( 0.97 - 1.13 ) and for R-warfarin was 1.02 ( 0.95 - 1.10 ) when coadministered with ginger . The mean ratio ( 90 % CI ) of AUC(0 - 168 ) of INR was 1.01 ( 0.93 - 1.15 ) when coadministered with ginger . The mean ratio ( 90 % CI ) for S-7-hydroxywarfarin urinary excretion rate was 1.07 ( 0.85 - 1.32 ) for ginkgo treatment , and 1.00 ( 0.81 - 1.23 ) for ginger coadministration suggesting these herbs did not affect CYP2C9 activity . Ginkgo and ginger did not affect the apparent volumes of distribution or protein binding of either S-warfarin or R-warfarin . CONCLUSIONS Ginkgo and ginger at recommended doses do not significantly affect clotting status , the pharmacokinetics or pharmacodynamics of warfarin in healthy subjects OBJECTIVE To evaluate the efficacy of dry powdered ginger , given orally , on nausea and vomiting during and after an elective cesarean section performed under combined spinal epidural anesthesia . STUDY DESIGN 239 women , ginger ( n=116 ) and placebo ( n=123 ) , who underwent elective cesarean section at term under combined spinal-epidural anesthesia were provided with st and ard preoperative antiemetic treatment in addition to a r and omized study drug . They were given two capsules ( 1 g each ) of either dry powdered ginger or placebo , one capsule a half-hour before induction of anesthesia and the second 2h after surgery . The study was double-blinded and the incidences of nausea and vomiting were assessed both intraoperatively and postoperatively . Levels of pain and pruritus were also assessed postoperatively . RESULTS The intraoperative incidence of nausea was 52 % and 61 % , ginger versus placebo ( p=0.149 ) . The number of episodes of intraoperative nausea was less in the ginger group compared to placebo ( mean difference was -0.396 , 95 % CI -0.738 , -0.054 ) and the result was statistically significant ( p=0.023 ) . The incidence of intraoperative vomiting was 27.35 % in the ginger group and 36.59 % in the placebo group , and the difference was not statistically significant ( p=0.126 ) . The number of episodes of vomiting during surgery was less in the ginger group compared to placebo : ( mean difference -0.158 , 95 % CI -0.626 , 0.311 ) although statistically insignificant ( p=0.505 ) . Furthermore , postoperatively , there was no statistical difference in the incidence of nausea and vomiting assessed at 0 , 2 , 2 ½ and 24h after surgery . There were also no differences in postoperative pain or pruritus . CONCLUSION Ginger given in dry powdered form reduced the number of episodes of intraoperative nausea compared to a placebo , but it had no effect on incidence of nausea , vomiting , or pain during and after an elective cesarean section performed under combined spinal epidural anesthesia AIM To evaluate the effects of ginger on gastric motility and emptying , abdominal symptoms , and hormones that influence motility in dyspepsia . METHODS Eleven patients with functional dyspepsia were studied twice in a r and omized double-blind manner . After an 8-h fast , the patients ingested three capsules that contained ginger ( total 1.2 g ) or placebo , followed after 1 h by 500 mL low-nutrient soup . Antral area , fundus area and diameter , and the frequency of antral contractions were measured using ultrasound at frequent intervals , and the gastric half-emptying time was calculated from the change in antral area . Gastrointestinal sensations and appetite were scored using visual analog question naires , and blood was taken for measurement of plasma glucagon-like peptide-1 ( GLP-1 ) , motilin and ghrelin concentrations , at intervals throughout the study . RESULTS Gastric emptying was more rapid after ginger than placebo [ median ( range ) half-emptying time 12.3 ( 8.5 - 17.0 ) min after ginger , 16.1 ( 8.3 - 22.6 ) min after placebo , P≤0.05 ] . There was a trend for more antral contractions ( P=0.06 ) , but fundus dimensions and gastrointestinal symptoms did not differ , nor did serum concentrations of GLP-1 , motilin and ghrelin . CONCLUSION Ginger stimulated gastric emptying and antral contractions in patients with functional dyspepsia , but had no impact on gastrointestinal symptoms or gut peptides OBJECTIVE To study the efficacy of ginger in prevention of nausea and vomiting after major gynecologic surgery . STUDY DESIGN Double blind r and omized controlled trial . SETTING Department of Obstetrics and Gynecology , Thammasat University Hospital , Faculty of Medicine , Thammasat University , Pathumthani , 12120 , Thail and . MATERIAL AND METHOD From March 2005 to April 2006 , 120 patients who underwent major gynecologic surgery were r and omized into group A ( n = 60 ) and group B ( n = 60 ) . The patients in group A received two capsules of ginger taken one hour before the procedure ( one capsule contains 0.5 gram of ginger powder ) . The patients in group B received the placebo . The visual analog nausea score ( VANS ) and frequency of vomiting were evaluated at 0 , 2 , 6 , 12 , and 24 hours after the operation . RESULTS The results demonstrated the statistically significant differences in nausea between group A ( 48.3 % ) and group B ( 66.7 % ) . The VANS was lower in group A compared to group B at 2 , 6 , 12 , and 24 hours . The most statistically significant differences occurred at 2 and 6 hour . The incidence and frequency of vomiting in group A were lower than group B. Side effects caused by ginger were not detected . CONCLUSION Ginger has efficacy in prevention of nausea and vomiting after major gynecologic surgery OBJECTIVE Menstrual pain is a periodic pain which happens during the days of menses . The menstrual disturbances as a health problem among young girls affect not only reproductive , but also psychical health and quality of life . This study was done with the goal of comparing the effect of Ginger and Novafen on the menstrual pain . MATERIAL S AND METHODS This crossover clinical trial study was done in Iran on 168 single girl students 18 - 26 years old in Babol University of Medical Sciences with primary menstrual pain . The participants were r and omly allocated to two groups receiving the drugs Novafen and Ginger . At the beginning of pain , in the two groups 200 mg capsule was given every 6 h for two serial cycles . Pain severity was measured by the visual scale before treatment , 1 h after consuming the drug ( for 24 h ) and 48 h after the onset of drug . RESULTS The mean age of participants was 21.83 ± 2.07 years . It has been reported that the intensity of pain from dysmenorrhea decreased in the Novafen and Ginger groups . Before treatment , the average pain intensity in Novafen and Ginger users were 7.12 ± 2.32 and 7.60 ± 1.84 , respectively and after treatment pain intensity decreased to 3.10 ± 2.69 and 2.97 ± 2.69 , respectively . Differences between two groups each time showed no statistical significance ( p > 0.05 ) . CONCLUSION Both drugs reduced menstrual pain . Ginger as well as Novafen is effective in relieving pain in girls with primary dysmenorrhea . Therefore , treatment with natural herbal medicine , non-synthetic drug , to reduce primary dysmenorrhea is recommended BACKGROUND Dysmenorrhea is a common gynecologic problem . In some cases , non-medical treatments are considered to be more effective , with fewer side effects . Ginger and exercise are alternative treatments for dysmenorrhea , but in the present study they were not combined . OBJECTIVE In this study , the effects of ginger and exercise on primary dysmenorrhea were compared . DESIGN , SETTING , PARTICIPANTS AND INTERVENTIONS This r and omized controlled trial was performed in Maz and aran University of Medical Sciences , Iran . Two groups of female students were recruited by simple r and om allocation . In each group , 61 students with moderate to severe primary dysmenorrhea with regular menstrual cycles and without a history of regular exercise were assessed . The ginger group received 250 mg ginger capsules from the onset of menstruation . In the exercise group , belly and pelvic stretching exercises were performed for 10 min , 3 times per week . MAIN OUTCOME MEASURES Intensity of pain was assessed according to a visual analogue scale after the first and the second month . RESULTS Exercise was significantly more effective than ginger for pain relief ( 31.57 ± 16.03 vs 38.19 ± 20.47 , P = 0.02 ) , severity of dysmenorrhea ( 63.9 % vs 44.3 % mild dysmenorrhea , P = 0.02 ) and decrease in menstrual duration ( 6.08 ± 1.22 vs 6.67 ± 1.24 , P = 0.006 ) , in the second cycle . CONCLUSION Stretching exercises , as a safe and low-cost treatment , are more effective than ginger for pain relief in primary dysmenorrhea . TRIAL REGISTRATION The trial was registered in www . I RCT .ir with No. 201203118822N2 Background . Nausea and vomiting are among the most prevalent and disturbing side effects of chemotherapy . Therefore , there is a need for additional antiemetic agents that could effectively reduce chemotherapy-induced nausea and vomiting ( CINV ) , whether alone or in combination with current st and ard therapies . Since clinical data on the effectiveness of ginger in patients with advanced breast cancer is lacking , the present study aim ed to evaluate the effects of ginger against both acute and delayed forms of CINV in a population with advanced breast cancer as the main malignancy . Methods . In this pilot , r and omized , open-label clinical trial , 100 women ( mean age = 51.83 ± 9.18 years ) with advanced breast cancer who were initially assigned to st and ard chemotherapy protocol with docetaxel , epirubicin , and cyclophosphamide ( the TEC regimen ) were r and omized to receive ginger ( 1.5 g/d in 3 divided doses every 8 hours ) plus st and ard antiemetic regimen ( granisetron plus dexamethasone ; the ginger group ) or st and ard antiemetic regimen alone ( control group ) . The duration of treatment with ginger was specified to 4 days from the initiation of chemotherapy . Prevalence , score , and severity of nausea , vomiting , and retching were assessed using a simplified form of Rhodes index in the first 6 hours , between 6 to 24 hours , and days 2 , 3 , and 4 postchemotherapy . Results . A significantly lower prevalence of nausea was observed in the ginger group during 6 to 24 hours postchemotherapy . Despite this effect , no other significant additional benefit from ginger ( 1.5 g/d ) was observed against prevalence or severity of nausea , vomiting , and retching in any of the assessed periods . Conclusion . Addition of ginger ( 1.5 g/d ) to st and ard antiemetic therapy ( granisetron plus dexamethasone ) in patients with advanced breast cancer effectively reduces the prevalence of nausea 6 to 24 hours postchemotherapy . However , there is no other additional advantage for ginger in reducing prevalence or severity of acute or delayed CINV |
12,375 | 26,072,142 | For second-line treatment , the use of platinum – paclitaxel combination or platinum monotherapy was cost-effective compared with platinum monotherapy or best supportive care , respectively , in women with recurrent platinum-sensitive disease .
Conclusions Despite varying method ological approaches and multiple sources for cost and effectiveness inputs , this systematic review demonstrated that st and ard platinum – taxane combination chemotherapy for first-line treatment was most cost-effective .
There was unanimous agreement that bevacizumab was not a cost-effective front-line therapy compared with platinum – taxane combination for the overall ovarian cancer population , though its use in the high-use population may yield better value .
For second-line treatment , platinum-based chemotherapy remained cost-effective among patients with recurrent platinum-sensitive disease , while there was limited evidence to conclude the most valuable treatment alternative among patients with recurrent platinum-resistant disease . | Background Adjuvant chemotherapy is a key component of advanced ovarian cancer treatment , when surgery alone is not sufficient .
Recurrence is common in ovarian cancer patients and most women require prolonged second-line and higher-line chemotherapy .
With newer targeted therapies , modest improvements in survival and quality of life may be attained at substantial cost , but the relative economic efficiency of these newer agents remains unknown .
Objective We undertook this systematic review to comprehensively evaluate the cost-effectiveness of various chemotherapeutic and targeted therapy alternatives for ovarian cancer . | Purpose .To provide a practical quantitative tool for appraising the quality of cost-effectiveness ( CE ) studies . Methods .A committee comprised of health economists selected a set of criteria for the instrument from an item pool . Data collected with a conjoint analysis survey on 120 international health economists were used to estimate weights for each criterion with a r and om effects regression model . To vali date the grading system , a survey was sent to 60 individuals with health economics expertise . Participants first rated the quality of three CE studies on a visual analogue scale , and then evaluated each study using the grading system . Spearman rho and Wilcoxon tests were used to detect convergent validity and analysis of covariance ( ANCOVA ) for discriminant validity . Agreement between the global rating by experts and the grading system was also examined . Results .Sixteen criteria were selected . Their coefficient estimates ranged from 1.2 to 8.9 , with a sum of 93.5 on a 100-point scale . The only insignificant criterion was “ use of subgroup analyses . ” Both convergent validity and discriminant validity of the grading system were shown by the results of the Spearman rho ( correlation coefficient = 0.78 , P < 0.0001 ) , Wilcoxon test ( P = 0.53 ) , and ANCOVA ( F3,146 = 5.97 , P = 0.001 ) . The grading system had good agreement with global rating by experts . Conclusions . The instrument appears to be simple , internally consistent , and valid for measuring the perceived quality of CE studies . Applicability for use in clinical and re source allocation decision-making deserves further study Abstract Objective : To assess the economic impact of two polychemotherapy regimens for patients with advanced ovarian cancer from the perspective of the Belgian health insurance and financing system . Design : An economic evaluation was integrated in an intergroup r and omised controlled trial ( EORTC 55931 ) in which patients were r and omised to receive the new treatment of paclitaxel and cisplatin or the st and ard therapy of cyclophosphamide and cisplatin . Data on the use of medical re sources were collected prospect ively for the 231 European Organization for Research and Treatment of Cancer ( EORTC ) patients in the trial and costs were valued by using unit prices . The outcome for the economic evaluation was mean survival time as determined by the so-called restricted means method , with the time point of restriction fixed by statistical criteria . A correction of censoring of the cost data collected in the trial was also performed . Main outcome measures and results : The paclitaxel and cisplatin group experienced a statistically significant improvement in mean survival time of 4 months , which was associated with an increase in the average total cost per patient of 6795 euros ( EUR ; 1998 values ) , when costs were assessed over the same period as the gain in mean survival time . This corresponds to a point estimate of the incremental cost-effectiveness ratio of EUR20 385 per life-year gained . The impact of uncertainty was assessed by using a bias-corrected and accelerated bootstrap method with 5000 re sample s , and the final results of the analysis are expressed in terms of a cost-effectiveness acceptability curve . Conclusions : The present economic evaluation has shown that the substitution of paclitaxel for cyclophosphamide in the chemotherapy regimen for women with advanced ovarian cancer leads to a significant improvement in patient survival , which is associated with an increase in costs for the Belgian health insurance system PURPOSE To determine the side effects and feasibility of cisplatin and carboplatin each in combination with paclitaxel as front-line therapy in advanced epithelial ovarian cancer . PATIENTS AND METHODS Patients were r and omly allocated to receive paclitaxel 175 mg/m(2 ) intravenously as a 3-hour infusion followed by either cisplatin 75 mg/m(2 ) or carboplatin ( area under the plasma concentration-time curve of 5 ) , both on day 1 . The schedule was repeated every 3 weeks for at least six cycles . Women allocated to paclitaxel-cisplatin were admitted to the hospital , whereas the carboplatin regimen was administered to out patients . RESULTS A total of 208 eligible patients were r and omized . Both regimens could be delivered in an optimal dose and without significant delay . Paclitaxel-carboplatin produced significantly less nausea and vomiting ( P : < .01 ) and less peripheral neurotoxicity ( P : = .04 ) but more granulocytopenia and thrombocytopenia ( P : < .01 ) . The overall response rate in 132 patients with measurable disease was 64 % ( 84 of 132 patients ) , and in patients with elevated CA 125 levels at start , it was 74 % ( 132 of 178 patients ) . With a median follow-up time of 37 months , the median progression-free survival time of all patients was 16 months and the median overall survival time was 31 months . The small number of patients entered onto the study caused wide confidence intervals ( CIs ) around the hazards ratio for progression-free survival of paclitaxel-carboplatin compared with paclitaxel-cisplatin ( hazards ratio , 1.07 ; 95 % CI , 0.78 to 1.48 ) and did not allow conclusions about efficacy . CONCLUSION Paclitaxel-carboplatin is a feasible regimen for out patients with ovarian cancer and has a better toxicity profile than paclitaxel-cisplatin BACKGROUND Despite considerable improvement in the treatment of advanced ovarian cancer , the optimization of efficacy and tolerability remains an important issue . Therefore , we performed a r and omized , phase III non-inferiority trial comparing paclitaxel plus cisplatin ( PT ) with paclitaxel plus carboplatin ( TC ) in patients with advanced ovarian cancer . METHODS A total of 798 patients with International Federation of Gynecology and Obstetrics stage IIB-IV were r and omly assigned to receive six courses of either PT or TC at 3-week intervals . The primary endpoint was the proportion of patients without progression at 2 years . Secondary endpoints included toxicity , response to treatment , quality of life , and overall and progression-free survival time . Quality of life was evaluated using the European Organization for Research and Treatment of Cancer quality -of-life question naire (QLQ)-C30 , version 2.0 . Survival curves were calculated using the Kaplan-Meier method , and hazard ratios were estimated using the Cox proportional hazards model . RESULTS The proportion of patients without progression at 2 years was not statistically significantly different between the two treatment arms ( 40.0 % for PT versus 37.5 % for TC , difference = 2.5 % , one-sided 95 % confidence interval [ CI ] = - infinity to 8.2 % ) . Median progression-free survival time in the TC arm ( 17.2 months , 95 % CI = 15.2 to 19.3 months ) and the PT arm ( 19.1 months , 95 % CI = 16.7 to 21.5 months ) were also not statistically significantly different ; the same was true of median overall survival time ( 43.3 months , 95 % CI = 37.2 to 47.8 months versus 44.1 months , 95 % CI = 40.2 to 49.4 months , for the TC and PT arms , respectively ) . The TC regimen was associated with a higher frequency of hematologic toxicity , but a lower frequency of gastrointestinal and neurologic toxicity , than the PT regimen . Mean global quality -of-life scores at the end of treatment were statistically significantly better in the TC arm than in the PT arm ( 65.25 versus 51.97 , respectively ; difference = -13.28 , 95 % CI = -18.88 to -7.68 ) . CONCLUSION The TC regimen achieved comparable efficacy to the PT regimen but was associated with better tolerability and quality of life , and should , therefore , be considered as an important alternative for st and ard first-line chemotherapy in patients with advanced ovarian cancer OBJECTIVE Compared with every-3-week paclitaxel ( q3 T ) plus carboplatin , dose-dense weekly paclitaxel ( ddT ) plus carboplatin improved the survival of ovarian cancer patients . We performed a cost analysis comparing these two regimens . METHODS Using a Markov decision model , an acceptable incremental cost-effectiveness ratio ( ICER ) per progression-free life-year saved ( PFLYS ) was estimated . Cost of drugs , growth colony-stimulating factors , and transfusions were derived from Medicare reimbursement data . Survival and rates of complications were estimated based on the clinical trial . RESULTS Using a body weight and surface area of an average woman age 63 , the estimated cost per cycle of ddT was $ 107 vs. $ 80 for q3 T . The costs per cycle of combination chemotherapy including treatment administration were $ 873 for ddT and $ 535 for q3 T . With a median progression-free survival ( PFS ) of 28 months with ddT vs. 17.2 months with q3 T , the ICER was $ 5809 per PFLYS for ddT compared with q3 T arm . Using a maximum ICER of $ 100,000 per LYS as cost-effective threshold , the ddT regimen was cost-effective . The ICER was most sensitive to the hazard rate for difference in PFS between the two regimens . A 4-month difference in PFS result ed in a $ 1200 change of ICER per PFLYS . The ICER was also sensitive to overall survival difference , rate of hematological toxicity , and rate of discontinuation . CONCLUSIONS In this economic model , dose-dense weekly paclitaxel is a cost-effective treatment option for advanced ovarian cancer PURPOSE In r and omized trials the combination of cisplatin and paclitaxel was superior to cisplatin and cyclophosphamide in advanced-stage epithelial ovarian cancer . Although in nonr and omized trials , carboplatin and paclitaxel was a less toxic and highly active combination regimen , there remained concern regarding its efficacy in patients with small-volume , resected , stage III disease . Thus , we conducted a noninferiority trial of cisplatin and paclitaxel versus carboplatin and paclitaxel in this population . PATIENTS AND METHODS Patients with advanced ovarian cancer and no residual mass greater than 1.0 cm after surgery were r and omly assigned to receive cisplatin 75 mg/m2 plus a 24-hour infusion of paclitaxel 135 mg/m2 ( arm I ) , or carboplatin area under the curve 7.5 intravenously plus paclitaxel 175 mg/m2 over 3 hours ( arm II ) . RESULTS Seven hundred ninety-two eligible patients were enrolled onto the study . Prognostic factors were similar in the two treatment groups . Gastrointestinal , renal , and metabolic toxicity , as well as grade 4 leukopenia , were significantly more frequent in arm I. Grade 2 or greater thrombocytopenia was more common in arm II . Neurologic toxicity was similar in both regimens . Median progression-free survival and overall survival were 19.4 and 48.7 months , respectively , for arm I compared with 20.7 and 57.4 months , respectively , for arm II . The relative risk ( RR ) of progression for the carboplatin plus paclitaxel group was 0.88 ( 95 % confidence interval [ CI ] , 0.75 to 1.03 ) and the RR of death was 0.84 ( 95 % CI , 0.70 to 1.02 ) . CONCLUSION In patients with advanced ovarian cancer , a chemotherapy regimen consisting of carboplatin plus paclitaxel results in less toxicity , is easier to administer , and is not inferior , when compared with cisplatin plus paclitaxel INTRODUCTION Paclitaxel plus cisplatin is considered to be the st and ard first-line therapy for advanced ovarian cancer . Previous to this study , economic data on this combination result ed from r and omised clinical trials ( RCTs ) . Therefore , the objective of this study was to compare the clinical and economic outcomes associated with paclitaxel-cisplatin ( PC ) and cyclophosphamide-cisplatin ( CC ) regimens using a pragmatic perspective based on daily clinical practice in a French university hospital . METHOD A retrospective cost-effectiveness analysis , from the hospital-payer perspective , was carried out as a before-after case study in fifty-nine consecutive women with verified International Federation of Gynaecology and Obstetrics ( FIGO ) stage II , III or IV ovarian cancer treated between 1995 and 2000 . Median overall survival ( OS ) was used as the primary endpoint . The quality -adjusted time was assessed by the quality -adjusted time without symptoms or toxicity ( Q-TWiST ) method . Direct medical costs were collected for each patient . Monetary values for French prices in the year 2000 were used and converted to US dollars using an exchange rate of USD 1 = 7 French francs . Several univariate sensitivity analyses were carried out varying unit costs , medical practice s and administration of paclitaxel . RESULTS The incremental cost of the PC regimen was USD 10,716 per patient . OS and quality -adjusted time were improved by 10.8 and 9.3 months with the PC regimen . The cost per life-year gained and per added QALY were USD 11,907 and USD 13,827 , respectively . The robustness of the results was confirmed in sensitivity analyses . CONCLUSION Our study suggests that PC may be a cost-effective regimen for advanced ovarian cancer in a French university hospital setting . We reported higher incremental costs and lower clinical benefits than RCT -based findings , suggesting that RCT -based findings were clearly balanced by our pragmatic approach based on clinical practice s. Observational studies can provide complementary and balanced data for decision making In a r and omized controlled trial ( RCT ) of patients with recurrent , platinum‐sensitive ovarian cancer , the combination weekly docetaxel and carboplatin was associated a with progression‐free survival ( PFS ) of 13.7 months compared with 8.4 months for sequential , single‐agent docetaxel followed by carboplatin . The objective of the current study was to construct a cost‐utility model to compare these 2 regimens with the incorporation of prospect ively collected quality ‐of‐life ( QoL ) data PURPOSE Epithelial ovarian cancer is the fourth leading cause of cancer-related death in women . Five-year survival is about 25 % , and new approaches to the treatment of this disease are dearly warranted . This study was design ed to determine the feasibility of using an in vitro assay for drug resistance to guide treatment after cytoreductive surgery . We present preliminary results of this study after a median follow-up of 24 months . MATERIAL S AND METHODS We treated 66 patients with advanced ovarian cancer by use of a combination of cytoreductive surgery and chemotherapy . Patient inclusion criteria included histologic confirmation of epithelial ovarian cancer , International Federation of Gynecology and Obstectrics ( FIGO ) stage III , no prior chemotherapy or radiation therapy , no coexisting neoplasm , and optimal residual disease ( < 2 cm ) . Malignant tissue from the involved ovary of each patient was tested in vitro for drug resistance , and chemotherapy was directed individually by assay results . On the basis of the assay we treated 19 patients with platinum/paclitaxel ( TP ) and 47 with platinum/cyclophosphamide ( CP ) . RESULTS Three-year survival ( Kaplan-Meier estimate ) was 69 % ; the 95 % confidence interval was 58 % to 80 % . There was no difference in 3-year survival between the 19 patients treated with TP ( 66 % ) and the 47 patients treated with CP ( 74 % ) . The cost-effectiveness of each treatment option was determined . It cost $ 4615 to achieve 3-year survival for patients receiving CP and $ 17,988 to obtain a similar survival with TP . The cost-effectiveness of assay-directed therapy was $ 9768 . DISCUSSION Because of the high recurrence rate and the poor long-term survival of women with advanced ovarian cancer , improved therapies for this disease are needed . After surgical debulking , we used results of an in vitro assay for drug resistance to individually select chemotherapy for the patients in this study . Although the 3-year survival of 69 % obtained in the present study appears good compared with previously published studies of optimally debulked patients , the results must be viewed with caution . Patients were not r and omized , and differences in prognostic factors , such as tumor grade , patient age , and performance status , could account in part for the higher survival found in the current study compared with previously published studies . Treatment with either CP or TP result ed in equivalent 3-year survival . The cost to achieve 3-year survival with this protocol , including the cost of the drug resistance assay , was $ 9768 . We believe that consideration of costs avoided by the elimination of ineffective treatments , needless toxicity , and loss of quality of life would likely increase the cost-effectiveness of assay-directed therapy compared with conventional therapy . This study demonstrates that it is feasible to use an in vitro assay in routine clinical practice to eliminate ineffective chemotherapeutic agents INTRODUCTION R and omized trials have demonstrated significant improvements in progression-free survival ( PFS ) with consolidation paclitaxel ( P ) and bevacizumab ( B ) following cytoreduction and adjuvant carboplatin/paclitaxel ( CP ) for advanced epithelial ovarian cancer ( EOC ) . We sought to evaluate the cost-effectiveness ( C/E ) of these consolidation strategies . METHODS A decision model was developed based on Gynecologic Oncology Group ( GOG ) protocol s # 178 and # 218 . Arm 1 is 6 cycles of CP . Arm 2 is 6 cycles of CP followed by 12 cycles of P ( CP+P ) . Arm 3 is 1 cycle of CP , 5 cycles of CPB , and 16 cycles of B ( CPB+B ) . Parameters include PFS , overall survival ( OS ) , cost , complications ( neuropathy for P and bowel perforation for B ) , and quality -of-life utility values . Sensitivity analyses were performed . RESULTS The incremental cost-effectiveness ratio ( ICER ) for CT+T is $ 13,402/ quality adjusted life year ( QALY ) gained compared to CP . For CPB+B compared to CP , the ICER is $ 326,530/QALY . When compared simultaneously , CPB+B is dominated , i.e. is more costly and less effective than CP+P. Results were robust to parameter variation . At a willingness to pay threshold of $ 100,000/QALY , CP+P was the preferred option throughout most of the decision space . Sensitivity analyses suggest that CPB+B would become the preferred option if it were to improve OS by 6.1 years over CP+P. CONCLUSIONS In this model , B consolidation for advanced EOC was associated with a modest improvement in effectiveness that is less than that with P consolidation and more costly . A statistically significant improvement in survival may improve the value of B consolidation The st and ard treatment for patients with advanced ovarian cancer ( AOC ) has been cyclophosphamide and cisplatin ( CP ) . Recently , the results of a large r and omized comparative trial demonstrated that the combination of paclitaxel and cisplatin ( TP ) provided a progression-free survival benefit of 5 months . In this study , a cost-utility analysis was performed from a Canadian health care system perspective to estimate the incremental cost-effectiveness of the TP combination . Twelve AOC patients who received treatment with TP were matched for age and disease stage on a 1-to-2 basis with a CP control . Total hospital re source consumption was then collected for all patients . Treatment preferences were estimated from a cohort of 20 patients and 40 healthy female volunteers using the time trade-off technique . The outcomes were then generated through a decision-analytic model . First-line treatment costs with TP were approximately fourfold greater on a per-cycle basis than the CP alternative ( Can$1911 vs Can$459 ) . When progression-free survival benefit and patient treatment preferences were incorporated into the analysis , the results of the decision model revealed an incremental cost between Can$12,000 and Can$24,000 per quality -adjusted progression-free year with the TP protocol . Even though the TP combination has a considerably higher drug acquisition cost , the results of the current analysis suggest that this new chemotherapy regimen does provide patients with substantial quality -adjusted progression-free survival benefit at a reasonable cost to the Canadian health care system OBJECTIVE We wished to compare the cost-effectiveness of three chemotherapy regimens for treatment of recurrent platinum-sensitive ovarian cancer . METHODS A Markov decision tree was constructed comparing three chemotherapy regimens : ( 1 ) carboplatin alone ( C ) ; ( 2 ) paclitaxel/carboplatin ( PC ) ; ( 3 ) gemcitabine/carboplatin ( GC ) . Progression-free survival ( PFS ) and adverse event rates were estimated from published r and omized controlled trials ( RCTs ) . Costs of treatment and adverse events were obtained using Medicare reimbursement data . RESULTS Estimated mean and median progression-free survival were 8.0 and 6.0 months for C , 10.1 and 7.8 months for PC , 10.5 and 8.4 months for GC , respectively . C was the least expensive strategy , costing $ 501 per progression-free month ( PFM ) . PC had an incremental cost-effectiveness ratio ( ICER ) of $ 1297 per additional PFM ( $ 15,564 per additional progression-free year ( PFY ) ) compared to C. GC had an ICER of $ 23,199 per additional PFM ( $ 278,388 per additional PFY ) compared to PC . Results were insensitive to variation in the rates and costs of toxicities over clinical ly reasonable ranges . The model was sensitive to changes in PFS estimates . When the PFS of GC was assumed to be equivalent to that of PC , GC was strongly dominated ( more expensive and no more effective ) by PC due to the additional costs . Adjustment for neurotoxicity-associated quality of life ( QoL ) did not change rankings of strategies . CONCLUSIONS PC appears to be relatively cost-effective compared to C for the treatment of recurrent platinum-sensitive ovarian cancer . GC appears to be less cost-effective compared to PC , with an ICER ten times higher Ovarian cancer accounts for a significant burden of healthcare costs worldwide . Therapy of this disease consists of a combined surgical and chemotherapeutic approach . Remarkable advances in chemotherapy have been made with the introduction of new agents such as paclitaxel . Based on positive clinical data from r and omized trials , numerous cost studies have been undertaken to analyze the cost – effectiveness of paclitaxel . Review ing all the available cost studies , the authors conclude that paclitaxel plus cisplatin treatment is cost effective . Paclitaxel demonstrated survival and utility gains in combination with cisplatin as first-line treatment in patients with Stage II – IV ovarian cancer compared with cyclophosphamide and cisplatin . Incremental costs of US$ 6600–22,000 per life year gained are within an accepted range for new treatments Analysis of published survival curves has recently been proposed as a method for conducting incremental cost‐effectiveness analysis in which two treatments are compared with each other in terms of cost per year of life gained . In patients with advanced ovarian carcinoma , the combination of paclitaxel and cisplatin has been reported to improve survival more significantly than st and ard therapy with cyclophosphamide and cisplatin . However , the high cost of paclitaxel indicates a need for an evaluation of the pharmacoeconomic profile of these treatments BACKGROUND A r and omized trial conducted by the Gynecologic Oncology Group ( GOG , study # 111 ) in the United States showed a better outcome for patients with advanced ovarian cancer on the paclitaxel-cisplatin regimen than for those on a st and ard cyclophosphamide-cisplatin regimen . Before considering the paclitaxel-cisplatin regimen as the new " st and ard , " a group of European and Canadian investigators planned a confirmatory phase III trial . METHODS This intergroup trial recruited 680 patients with broader selection criteria than the GOG # 111 study and administered paclitaxel as a 3-hour instead of a 24-hour infusion ; progression-free survival was the primary end point . Patient survival was analyzed by use of the Kaplan-Meier technique . Treatment effects on patient survival were estimated by Cox proportional hazards regression models . All statistical tests were two-sided . RESULTS The overall clinical response rate was 59 % in the paclitaxel group and 45 % in the cyclophosphamide group ; the complete clinical remission rates were 41 % and 27 % , respectively ; both differences were statistically significant ( P = .01 for both ) . At a median follow-up of 38.5 months and despite a high rate of crossover ( 48 % ) from the cyclophosphamide arm to the paclitaxel arm at first detection of progression of disease , a longer progression-free survival ( log-rank P = .0005 ; median of 15.5 months versus 11.5 months ) and a longer overall survival ( log-rank P = . 0016 ; median of 35.6 months versus 25.8 months ) were seen in the paclitaxel regimen compared with the cyclophosphamide regimen . CONCLUSIONS There is strong and confirmatory evidence from two large r and omized phase III trials to support paclitaxel-cisplatin as the new st and ard regimen for treatment of patients with advanced ovarian cancer OBJECTIVES Most economic evaluations of chemotherapies for ovarian cancer patients have used hypothetical cohorts or r and omized control trials , but evidence integrating real-world survival , cost , and utility data is limited . METHODS A propensity score-matched cohort of 6856 elderly ( ≥65 years ) ovarian cancer patients diagnosed from 1991 to 2005 from the Surveillance , Epidemiology , and End Results -Medicare data cohort were included . Treatment regimens ( i.e. , no chemotherapy , platinum-based only , platinum plus taxane , and other nonplatinum ) were identified in the 6 months postdiagnosis . Patients were followed until death or end of study ( December 2006 ) . Effectiveness was measured in quality -adjusted life-years ( QALYs ) , and total health care costs were measured by using a payer 's perspective ( 2009 US dollars ) . Method ological and statistical uncertainties were accounted by including alternative scenarios ( for utility values ) and net monetary benefit approach . Incremental cost-effectiveness ratios ( ICERs ) were calculated , and stratified analyses were performed by tumor stages and age groups . RESULTS On comparing the platinum-based group versus no chemotherapy , we found that the ICER was $ 30,073/QALY and $ 58,151/QALY for early- and late-stage disease , respectively , while other nonplatinum and platinum plus taxane groups were dominated ( less effective and more costly ) . Similar results were found across alternative scenarios and age groups . For patients 85 years or older , platinum plus taxane , however , was not dominated by the platinum-based group , with an ICER of $ 133,892/QALY . CONCLUSIONS Following elderly ovarian cancer patients over a lifetime using real-world longitudinal data and adjusting for quality of life , we found that treatment with platinum-based regimen was the most cost-effective treatment alternative |
12,376 | 22,726,453 | Results The results show consistent support for a positive relation between more autonomous forms of motivation and exercise , with a trend towards identified regulation predicting initial/short-term adoption more strongly than intrinsic motivation , and intrinsic motivation being more predictive of long-term exercise adherence .
The literature is also consistent in that competence satisfaction and more intrinsic motives positively predict exercise participation across a range of sample s and setting s. Mixed evidence was found concerning the role of other types of motives ( e.g. , health/fitness and body-related ) , and also the specific nature and consequences of introjected regulation .
The majority of studies have employed descriptive ( i.e. , non-experimental ) design s but similar results are found across cross-sectional , prospect i ve , and experimental design s. Conclusion Overall , the literature provides good evidence for the value of SDT in underst and ing exercise behavior , demonstrating the importance of autonomous ( identified and intrinsic ) regulations in fostering physical activity .
Nevertheless , there remain some inconsistencies and mixed evidence with regard to the relations between specific SDT constructs and exercise . | Background Motivation is a critical factor in supporting sustained exercise , which in turn is associated with important health outcomes .
Accordingly , research on exercise motivation from the perspective of self-determination theory ( SDT ) has grown considerably in recent years .
Previous review s have been mostly narrative and theoretical .
Aim ing at a more comprehensive review of empirical data , this article examines the empirical literature on the relations between key SDT-based constructs and exercise and physical activity behavioral outcomes . | Purpose . To examine the effect of a mail-mediated intervention , based on self-determination theory , on adults ' exercise behavior . Methods . The study was a r and omized control trial conducted over a 2-month period . Of the initial 185 volunteer participants , 126 ( 68.1 % ) completed question naires at baseline , 1 month , and 2 months . Participants in intervention-only and intervention-plus-booster groups received a mail-delivered packet containing strategies design ed to promote perceptions of autonomy , competence , and relatedness regarding exercise . Those in a control group received an American Heart Association physical-activity facts packet . After 1 month , those in the intervention-plus-booster group received a booster postcard , reiterating the main points of the initial intervention packet . Exercise behavior was the primary outcome variable . Perceptions of autonomy , competence , and relatedness were evaluated as mediating variables . Results . Separate 3 ( group ) × 3 ( time ) repeated measures analyses of variance conducted for men and women revealed that for women , all three groups significantly increased exercise levels over the 2-month period . No significant interactions were found regarding the influence of the intervention on the mediating variables . A process evaluation indicated a lack of compliance regarding completing intervention-packet worksheets . Discussion . Findings suggested that more intensive interventions and greater fidelity of treatment may be needed to evidence change in exercise behavior Background Research on the motivational model proposed by Self-Determination Theory ( SDT ) provides theoretically sound insights into reasons why people adopt and maintain exercise and other health behaviors , and allows for a meaningful analysis of the motivational processes involved in behavioral self-regulation . Although obesity is notoriously difficult to reverse and its recidivism is high , adopting and maintaining a physically active lifestyle is arguably the most effective strategy to counteract it in the long-term . The purpose s of this study are twofold : i ) to describe a 3-year r and omized controlled trial ( RCT ) aim ed at testing a novel obesity treatment program based on SDT , and ii ) to present the rationale behind SDT 's utility in facilitating and explaining health behavior change , especially physical activity/exercise , during obesity treatment . Methods Study design , recruitment , inclusion criteria , measurements , and a detailed description of the intervention ( general format , goals for the participants , intervention curriculum , and main SDT strategies ) are presented . The intervention consists of a 1-year group behavioral program for overweight and moderately obese women , aged 25 to 50 ( and pre-menopausal ) , recruited from the community at large through media advertisement . Participants in the intervention group meet weekly or bi-weekly with a multidisciplinary intervention team ( 30 2 h sessions in total ) , and go through a program covering most topics considered critical for successful weight control . These topics and especially their delivery were adapted to comply with SDT and Motivational Interviewing guidelines . Comparison group receive a general health education curriculum . After the program , all subjects are follow-up for a period of 2 years . Discussion Results from this RCT will contribute to a better underst and ing of how motivational characteristics , particularly those related to physical activity/exercise behavioral self-regulation , influence treatment success , while exploring the utility of Self-Determination Theory for promoting health behavior change in the context of obesity . Trial Registration Clinical Trials Gov. Identifier This study was set out to test if autonomous motivation mediated the relationship between self-efficacy and 12-month physical activity ( PA ) in adults with type 2 diabetes involved in a r and omized exercise trial . Participants ( n = 234 ) completed question naires measuring barrier self-efficacy at 3 months , autonomous motivation at 6 months , and PA at 12 months . A mediational analysis of longitudinal data revealed that autonomous motivation mediated the relationship between barrier-self-efficacy and PA . High barrier self-efficacy can therefore help predict 12-month PA in adults with type 2 diabetes , although this effect is attenuated by autonomous motivation . Hence , participating in PA for autonomous reasons such as by choice and /or for fun further explains PA at 12 months in this population . Results of this study extend our underst and ing of the motivational constructs involved in PA in the maintenance phase . This study has important theoretical implication s in that it helps to organize and consoli date well-known correlates of PA by proposing a temporal relationship between them that could be tailored in interventions PURPOSE This study evaluated exercise-related predictors of successful long-term weight control in women by analyzing the extent to which sustained exercise participation and self-determination theory (SDT)-based exercise motivation variables mediated the impact of a behavioral weight control intervention on 3-yr weight change . METHODS Longitudinal r and omized controlled trial consisting of a 1-yr SDT-based intervention and a 2-yr follow-up with 221 female participants ( means ± SD : age = 37.6 ± 7 yr , body mass index = 31.6 ± 4.1 kg·m(-2 ) ) . The tested model incorporated experimentally manipulated perceived need support , motivational regulations , and 2-yr exercise adherence as mediators of the intervention 's impact on 3-yr weight change . Paths were tested using partial least squares analysis . Where there were significant intervening paths , tests of mediation were conducted . RESULTS Treatment had significant effects on 1- and 2-yr autonomous regulations , 2-yr physical activity , and 3-yr weight change , fully mediated by the tested paths ( effect ratio = 0.10 - 0.61 ) . Moderate and vigorous exercise at 2 yr had a significant effect ( P < 0.001 ) on weight loss success at 3 yr and partially mediated the effect of treatment on weight change . The 2-yr autonomous regulation effects on follow-up weight change were only partially mediated by physical activity ( effect ratio = 0.42 ) . CONCLUSIONS This application of SDT to physical activity and weight management showed that not all types of motivation predict long-term behavioral outcomes and that sustained moderate and vigorous exercise mediated long-term weight change . It provides strong evidence for a link between experimentally increased autonomous motivation and exercise and long-term weight loss maintenance . Results highlight the importance of interventions targeting the internalization of exercise behavioral regulation and making exercise and physical activity positive and meaningful experiences rather than simply focusing on immediate behavior change in overweight/obese women Background The National Institute of Clinical Excellence in the UK has recommended that the effectiveness of ongoing exercise referral schemes to promote physical activity should be examined in research trials . Recent empirical evidence in health care and physical activity promotion context s provides a foundation for testing the utility of a Self Determination Theory (SDT)-based exercise referral consultation . Methods / Design Design : An exploratory cluster r and omised controlled trial comparing st and ard provision exercise on prescription with a Self Determination Theory-based ( SDT ) exercise on prescription intervention . Participants : 347 people referred to the Birmingham Exercise on Prescription scheme between November 2007 and July 2008 . The 13 exercise on prescription sites in Birmingham were r and omised to current practice ( n = 7 ) or to the SDT-based intervention ( n = 6 ) . Outcomes measured at 3 and 6-months : Minutes of moderate or vigorous physical activity per week assessed using the 7-day Physical Activity Recall ; physical health : blood pressure and weight ; health status measured using the Dartmouth CO-OP charts ; anxiety and depression measured by the Hospital Anxiety and Depression Scale and vitality measured by the subjective vitality score ; motivation and processes of change : perceptions of autonomy support from the advisor , satisfaction of the needs for competence , autonomy , and relatedness via physical activity , and motivational regulations for exercise . Discussion This trial will determine whether an exercise referral programme based on Self Determination Theory increases physical activity and other health outcomes compared to a st and ard programme and will test the underlying SDT-based process model ( perceived autonomy support , need satisfaction , motivation regulations , outcomes ) via structural equation modelling . Trial registration The trial is registered as Current Controlled trials IS RCT N07682833 BACKGROUND Regular physical activity can help to prevent cardiovascular disease in women . Underst and ing midlife women 's exercise goals could offer insight into their motivational facilitators and barriers , and assist in the development of better primary prevention strategies for this population . OBJECTIVES We sought to investigate the relationship between midlife women 's physical activity goals and their physical activity participation over time . METHODS A r and om sample of healthy , midlife women ( 40 - 60 years of age ) was selected to participate in a longitudinal study ( n = 156 ) . This study fit a linear mixed model to the data to investigate the fixed effects of physical activity goals on physical activity participation , controlling for Body Mass Index ( BMI ) and Social Support . Mediational analyses were conducted to investigate whether commitment and planning mediated these results . RESULTS There were significant differences between participants with distinct types of goals on physical activity participation over time ( i.e. , baseline , 1 month , and 1 year postbaseline ) , controlling for the effects of BMI and Social Support . Participants with Weight Loss and Health Benefits goals participated in significantly less physical activity than those with Sense of Well-being and Stress Reduction goals . Commitment and Planning each mediated the relationship between participant goals and their physical activity participation . CONCLUSIONS These data suggest having physical activity goals that aim to decrease weight or benefit health may not bode well for healthy midlife women who desire to sustain physically active lives . Instead , health care providers and health promotion specialists might better facilitate long-term participation among healthy women if they emphasize physical activity as a means to enhance their quality of life Assessment of habitual physical activity in epidemiologic and health education studies has been difficult . A seven-day physical activity recall interview was developed and administered in a community health survey , a r and omized clinical trial , and two worksite health promotion programs during 1979 - 1982 . These studies were conducted in several population s in California , Texas , Pennsylvania , and New Jersey . Energy expenditure estimates from the physical activity recall conformed to expected age- and sex-specific values in the cross-sectional community survey . Estimates of energy expenditure were also congruent with other questions on physical activity and job classification . In a r and omized , one-year exercise trial , the physical activity recall detected increases in energy expenditure in the treated group and was positively associated with miles run during training ( p less than 0.05 ) . Changes in energy expenditure were associated with changes in maximal oxygen uptake ( VO2max ( r = 0.33 , p less than 0.05 ) and body fatness ( r = -0.50 , p less than 0.01 ) at six months , and in high density lipoprotein-cholesterol ( r = 0.31 , p less than 0.05 ) and triglyceride ( r = -0.41 , p less than 0.01 ) at one year . The physical activity recall detected significant ( p less than 0.01 ) increases in energy expenditure in treatment groups in two worksite health promotion projects . These data suggest that the physical activity recall provides useful estimates of habitual physical activity for research in epidemiologic and health education studies The purpose of this study was to propose and test a motivational model of high school dropout . The model posits that teachers , parents , and the school administration 's behaviors towards students influence students ' perceptions of competence and autonomy . The less autonomy supportive the social agents ' behaviors are , the less positive the students ' perceptions of competence and autonomy . In turn , the less positive students ' perceptions are , the lower their level of self-determined school motivation are . Finally , low levels of self-determined motivation lead students to develop intentions to drop out of high school , which are later implemented , leading to actual dropout behavior . This model was tested with high school students ( N = 4,537 ) by means of a prospect i ve design . Results from analyses of variance and a structural equation modeling analysis ( with LISREL ) were found to support the model for all participants and for each gender separately The assertion that both the content of goals and the motives behind goals affect psychological well-being has been controversial . Three studies examined this issue directly , showing that both what goals people pursue ( i.e. , whether they strive for extrinsic vs. intrinsic goal contents ) and why people pursue them ( i.e. , whether they strive for autonomous vs. controlled motives ) make significant independent contributions to psychological well-being . The pattern emerged in between-person and within-person studies of cross-sectional well-being and also emerged in a year-long study of prospect i ve change in well-being . Implication s for prescriptive theories of happiness are discussed OBJECTIVE Using self-determination theory ( SDT ) , we examined relationships between cardiac rehabilitation ( CR ) participants ' perceived autonomy support , motivation for exercise , and exercise behavior . RESEARCH METHOD / DESIGN Male CR out patients ( N = 53 ; M age = 62.83 + /- 10.78 years ) . The design was correlational ( cross-sectional and prospect i ve ) , examining relationships between perceived autonomy support and motivation for exercise at Week 4 of CR participation as well as motivation and CR attendance and other indicators of exercise behavior ( frequency , duration , total exercise time ) at a 1-week follow-up , 10 weeks later . RESULTS Perceived autonomy support was correlated with self-determined motivation , r(53 ) = .32 , p < .05 . Self-determined motivation predicted total exercise volume at follow-up , r(53 ) = .34 , p < .05 , as well as length of exercise session duration ( R(2 ) = .27 ; beta = .52 , p < .001 ) . CONCLUSION Results support SDT and the potential for autonomy support from interventionists to affect self-determined motivation and exercise behavior of participants involved in CR Aims : We examined whether autonomy supportive and self-efficacy enhancing individual lifestyle counselling was associated with improved maintenance of exercise and physical capacity compared with group based counselling . We also tested whether self-efficacy beliefs and autonomous motivation was associated with improved maintenance of exercise over time . Methods : R and omised controlled trial and longitudinal study of predictor variables . One hundred and seventy six ( 38 female ) patients mainly with coronary heart disease were r and omized to either have st and ard group based rehabilitation or to additionally receive the intervention . Patients were recruited from a 4-week cardiac rehabilitation programme with two years follow-up at Krokeide Centre in Bergen , Norway . Results : We found no statistically significant between-group differences . The groups showed an overall improvement of their self-evaluated physical capacity during the two years of the study , corresponding 7 % change of score ( p<0.001 ) . The composite exercise score improved 6 % during follow-up ( p<0.001 ) . Intensity of exercise activities improved 17 % from inclusion to 24 months ' follow-up ( p<0.001 ) . Self-efficacy for increased exercise , general expectancy and autonomous motivation were significant predictors of increased exercise and physical capacity . Controlled motivation hampered physical capacity improvement . Conclusions : Among this self-selected and motivated group of rehabilitation patients we found no additional effect of adding individual counselling to group-based interventions . Based on longitudinal documentation this cardiac rehabilitation programme improves long-term maintenance of exercise and physical capacity and this maintenance is related to autonomous motivation , general expectancy and self-efficacy OBJECTIVE To investigate self-determined motivation as a predictor of exercise behavior 3 and 6 weeks following completion of cardiac rehabilitation ( CR ) as well as the relationship between psychological need satisfaction and self-determined motivation to exercise . PARTICIPANTS AND DESIGN CR out patients ( n = 68 ; M(age ) = 64.90 + /- 8.86 years ) . The design was correlational ( cross-sectional and prospect i ve ) , with psychological need satisfaction predicting self-determined motivation at the completion of CR and self-determined motivation predicting exercise behavior at 3- and 6-week follow-ups . RESULTS Psychological need satisfaction for competence predicted self-determined motivation to exercise ( beta = .32 , p < .05 , pr(2 ) = .08 ) . Self-determined motivation at the end of CR was correlated with exercise behavior at 3-week follow-up ( r(68 ) = .22 , p < .05 ) and predicted exercise at 6 weeks ( R(2 ) ( adjusted ) = .11 ; beta = .35 , p < .01 ) . CONCLUSION CR participants who report higher levels of psychological need satisfaction regarding exercise report greater self-determined motivation . Greater self-determined motivation to exercise , in turn , relates to higher levels of subsequent independent exercise behavior . Nurturing psychological needs and self-determined motivation during CR may assist participants in maintaining exercise following CR |
12,377 | 26,882,040 | CONCLUSION cf-PWV is increased in both ulcerative colitis and Crohn 's disease patients | BACKGROUND Arterial stiffness is increased with chronic inflammatory disorders .
The reduction of inflammation by immunomodulatory therapy is associated with a restoration of arterial function .
The aims of the study were to perform a meta- analysis to determine whether arterial stiffness is increased in patients with inflammatory bowel disease ( IBD ) and a meta-regression analysis to correlate arterial stiffness with anti-TNFα therapy . | Background — Aortic stiffness is a marker of cardiovascular disease and an independent predictor of cardiovascular risk . Although an association between inflammatory markers and increased arterial stiffness has been suggested , the causative relationship between inflammation and arterial stiffness has not been investigated . Methods and Results — One hundred healthy individuals were studied according to a r and omized , double-blind , sham procedure-controlled design . Each sub study consisted of 2 treatment arms , 1 with Salmonella typhi vaccination and 1 with sham vaccination . Vaccination produced a significant ( P<0.01 ) increase in pulse wave velocity ( at 8 hours by 0.43 m/s ) , denoting an increase in aortic stiffness . Wave reflections were reduced significantly ( P<0.01 ) by vaccination ( decrease in augmentation index of 5.0 % at 8 hours and 2.5 % at 32 hours ) as a result of peripheral vasodilatation . These effects were associated with significant increases in inflammatory markers such as high-sensitivity C-reactive protein ( P<0.001 ) , high-sensitivity interleukin-6 ( P<0.001 ) , and matrix metalloproteinase-9 ( P<0.01 ) . With aspirin pretreatment ( 1200 mg PO ) , neither pulse wave velocity nor augmentation index changed significantly after vaccination ( increase of 0.11 m/s and 0.4 % , respectively ; P = NS for both ) . Conclusions — This is the first study to show through a cause- and -effect relationship that acute systemic inflammation leads to deterioration of large-artery stiffness and to a decrease in wave reflections . These findings have important implication s , given the importance of aortic stiffness for cardiovascular function and risk and the potential of therapeutic interventions with antiinflammatory properties Background New 2007 European Society of Hypertension guidelines recommend measuring arterial stiffness in patients with arterial hypertension , suggesting a carotid – femoral pulse wave velocity over 12 m/s as an estimate of sub clinical organ damage . Considering this cutoff point , it is worth exploring whether or not there are significant differences in results obtained using various techniques for measuring aortic pulse wave velocity . The aim of the study was to compare aortic pulse wave velocity measurements using Complior , SphygmoCor , and Arteriograph devices , and to assess the effect of pulse wave transit time and traveled distance on pulse wave velocity values . Methods Aortic pulse wave velocity was measured on a single visit , using these devices , in r and omized order , in a group of 64 patients with grade 1 or 2 arterial hypertension . Results Aortic pulse wave velocity measured using Complior ( 10.1 ± 1.7 m/s ) was significantly higher than that obtained using SphygmoCor ( 8.1 ± 1.1 m/s ) or Arteriograph ( 8.6 ± 1.3 m/s ) . No differences were noted between pulse wave velocity measurements using SphygmoCor and Arteriograph . Between- method comparison revealed that differences in traveled distance were significant : Complior versus Arteriograph [ 0.09 m , Confidence interval ( CI ) : 0.08–0.12 m , P < 0.05 ] , Complior versus SphygmoCor ( 0.15 m , CI : 0.13–0.16 m , P < 0.05 ) , Arteriograph versus SphygmoCor ( 0.05 m , CI : 0.03–0.07 m , P < 0.05 ) . No between- method differences were found for transit times . Conclusion Differences in pulse wave velocity obtained by compared devices result ed primarily from using various methods for measuring traveled distance . It appears reasonable to establish uniform principles for the measurement of traveled distance . Because a large number of prognosis/survival studies used direct distance between carotid and femoral sites of pulse wave recording , this distance should be mostly recommended 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 Arterial stiffness , estimated by pulse wave velocity ( PWV ) , is an independent predictor of cardiovascular mortality and morbidity . However , the clinical applicability of these measurements and the elaboration of reference PWV values are difficult due to differences between the various devices used . In a population of 50 subjects aged 20–84 years , we compared PWV measurements with three frequently used devices : the Complior and the PulsePen , both of which determine aortic PWV as the delay between carotid and femoral pressure wave and the PulseTrace , which estimates the Stiffness Index ( SI ) by analyzing photoplethysmographic waves acquired on the fingertip . PWV was measured twice by each device . Coefficient of variation of PWV was 12.3 , 12.4 and 14.5 % for PulsePen , Complior and PulseTrace , respectively . These measurements were compared with the reference method , that is , a simultaneous acquisition of pressure waves using two tonometers . High correlation coefficients with the reference method were observed for PulsePen ( r=0.99 ) and Complior ( r=0.83 ) , whereas for PulseTrace correlation with the reference method was much lower ( r=0.55 ) . Upon Bl and –Altman analysis , mean differences of values±2s.d . versus the reference method were −0.15±0.62 m/s , 2.09±2.68 m/s and −1.12±4.92 m/s , for PulsePen , Complior and PulseTrace , respectively . This study confirms the reliability of Complior and PulsePen devices in estimating PWV , while the SI determined by the PulseTrace device was found to be inappropriate as a surrogate of PWV . The present results indicate the urgent need for evaluation and comparison of the different devices to st and ardize PWV measurements and establish reference values BACKGROUND Premature arterial stiffening and atherosclerosis are increased in patients with inflammatory arthropathies such as rheumatoid arthritis ( RA ) , ankylosing spondylitis ( AS ) and psoriatic arthritis ( PsA ) . The proinflammatory protein calprotectin is associated with inflammatory arthropathies , vascular pathology , and acute coronary events . We examined the long-term effects of treatment with tumor necrosis factor (TNF)-α antagonists on aortic stiffness and carotid intima media thickness ( CIMT ) in patients with inflammatory arthropathies , and the relationships to the levels of calprotectin . METHODS Fifty-five patients with RA , AS , or PsA and a clinical indication for anti-TNF-α therapy were included and followed with regular examinations for 1 year . Thirty-six patients starting with anti-TNF-α therapy were compared with a nontreatment group of 19 patients . Examinations included assessment s of aortic stiffness ( aortic pulse wave velocity , aPWV ) , CIMT , and plasma calprotectin . RESULTS After 1 year , aPWV ( mean ( s.d . ) ) was improved in the treatment group , but not in the control group ( -0.54 [ 0.79 ] m/s vs. 0.06 [ 0.61 ] m/s , respectively ; P = 0.004 ) , and CIMT progression ( median ( quartile cut-points , 25th and 75th percentiles ) ) was reduced in the treatment group compared to the control group ( -0.002 [ -0.038 , 0.030 ] mm vs. 0.030 [ 0.011 , 0.043 ] mm , respectively ; P = 0.01 ) . In multivariable analyses , anti-TNF-α therapy over time was associated with improved aPWV ( P = 0.02 ) and reduced CIMT progression ( P = 0.04 ) , and calprotectin was longitudinally associated with aPWV ( P = 0.02 ) . CONCLUSIONS Long-term anti-TNF-α therapy improved aortic stiffness and CIMT progression in patients with inflammatory arthropathies . Calprotectin may be a soluble biomarker reflecting aortic stiffening in these patients |
12,378 | 26,307,238 | Data Synthesis : Foods of lower nutritional value and lower- quality diets generally cost less per calorie and tended to be selected by groups of lower socioeconomic status .
A number of nutrient-dense foods were available at low cost but were not always palatable or culturally acceptable to the low-income consumer .
Acceptable healthier diets were uniformly associated with higher costs .
Food budgets in poverty were insufficient to ensure optimum diets .
Conclusions : Socioeconomic disparities in diet quality may be explained by the higher cost of healthy diets . | Context : It is well established in the literature that healthier diets cost more than unhealthy diets .
Objective : The aim of this review was to examine the contribution of food prices and diet cost to socioeconomic inequalities in diet quality . | Background Lowering the price of fruit and vegetables is a promising strategy in stimulating the purchase of those foods . However , the true effects of this strategy are not well studied and it is unclear how the money saved is spent . The aim of this study is to examine the effects of a 25 % discount on fruits and vegetables on food purchases in a supermarket environment . Methods A r and omized controlled trial with two research conditions was conducted : a control condition with regular prices ( n = 52 ) and an experimental condition with a 25 % discount on fruits and vegetables ( n = 63 ) . The experiment was carried out using a three-dimensional web-based supermarket , which is a software application in the image of a real supermarket . Data were collected in 2010 in the Netherl and s. Participants received a fixed budget and were asked to buy weekly household groceries at the web-based supermarket . Differences in fruit and vegetable purchases , differences in expenditures in other food categories and differences in total calories were analyzed using independent sample s t-tests and multiple linear regression models accounting for potential effect modifiers and confounders . Results The purchased amount of fruit plus vegetables was significantly higher in the experimental condition compared to the control condition ( Δ984 g per household per week , p = .03 ) after appropriate adjustments . This corresponds to a 25 % difference compared to the control group . Both groups had similar expenditures in unhealthier food categories , including desserts , soda , crisps , c and y and chocolate . Furthermore , both groups purchased an equal number of food items and an equal amount of calories , indicating that participants in the discount condition did not spend the money they saved from the discounts on other foods than fruits and vegetables . Conclusion A 25 % discount on fruits and vegetables was effective in stimulating purchases of those products and did neither lead to higher expenditures in unhealthier food categories nor to higher total calories purchased . Future studies in real supermarkets need to confirm these findings The role of dietary fat in the regulation of energy intake was assessed by manipulating a conventional diet and measuring spontaneous food consumption . Twenty-four women each consumed a sequence of three 2-wk dietary treatments in which 15 - 20 % , 30 - 35 % , or 45 - 50 % of the energy was derived from fat . These diets consisted of foods that were similar in appearance and palatability but differed in the amount of high-fat ingredients used . Relative to their energy consumption on the medium-fat diet , the subjects spontaneously consumed an 11.3 % deficit on the low-fat diet and a 15.4 % surfeit on the high-fat diet ( p less than 0.0001 ) , result ing in significant changes in body weight ( p less than 0.001 ) . A small amount of caloric compensation did occur ( p less than 0.02 ) , which was greatest in the leanest subjects ( p less than 0.03 ) . These results suggest that habitual , unrestricted consumption of low-fat diets may be an effective approach to weight control The purpose of this study was to evaluate the impact of adopting a Mediterranean diet on dietary cost and energy density in free-living conditions . The 12-wk nutritional intervention consisted of 2 group courses and 7 individual sessions with a dietician in a sample of 73 healthy women . To evaluate the dietary response to the nutritional intervention , a registered dietician administered a FFQ at 0 , 6 , 12 , and 24 wk . Total daily dietary cost was calculated using a price list including all items from the FFQ . Our findings indicated that daily energy cost evaluated at wk 12 vs. wk 0 [ 1046 + /- 217 vs. 967 + /- 192 kJ/Canadian dollars ( CAN$ ) , respectively , P = 0.18 ] and total daily dietary cost ( 8.61 + /- 2.13 vs. 8.75 + /- 2.50 CAN$/d per participant , respectively , P = 0.58 ) did not change . Total daily energy density at wk 12 decreased compared with wk 0 ( 2.56 + /- 0.76 vs. 2.20 + /- 0.67 kJ/g ; P < 0.0001 ) . Adherence to the Mediterranean diet led to increased cost related to vegetables , fruits , legumes , nuts and seeds , canola/olive oil , whole grains , poultry , and fish ( P < or = 0.01 ) and to reduced dietary cost for red meat , refined grains , desserts and sweets , and fast food ( P < or = 0.008 ) . In conclusion , these data suggest that adherence to a nutritional intervention program promoting the Mediterranean food pattern is not associated with increased daily dietary cost or energy cost but led to a reduction in energy density . Consequently , increased cost should not be considered a barrier to the promotion and adoption of a Mediterranean diet PURPOSE Degrees of nutrient intake and food groups have been linked to differential chronic disease risk . However , intakes of specific nutrients may also be associated with differential diet costs and unobserved differences in socioeconomic status ( SES ) . The present study examined degrees of nutrient intake , for every key nutrient in the diet , in relation to diet cost and SES . METHODS Socio-demographic data for a stratified r and om sample of adult respondents in the Seattle Obesity Study were obtained through telephone survey . Dietary intakes were assessed using food frequency question naire ( FFQ ) ( n = 1,266 ) . Following st and ard procedures , nutrient intakes were energy-adjusted using the residual method and converted into quintiles . Diet cost for each respondent was estimated using Seattle supermarket retail prices for 384 FFQ component foods . RESULTS Higher intakes of dietary fiber , vitamins A , C , D , E , and B12 , beta carotene , folate , iron , calcium , potassium , and magnesium were associated with higher diet costs . The cost gradient was most pronounced for vitamin C , beta carotene , potassium , and magnesium . Higher intakes of saturated fats , trans fats and added sugars were associated with lower diet costs . Lower cost lower quality diets were more likely to be consumed by lower SES . CONCLUSION Nutrients commonly associated with a lower risk of chronic disease were associated with higher diet costs . By contrast , nutrients associated with higher disease risk were associated with lower diet costs . The cost variable may help somewhat explain why lower income groups fail to comply with dietary guidelines and have highest rates of diet related chronic disease BACKGROUND The inverse relation between energy density ( kcal/g ) and energy cost ( price/kcal ) has been interpreted to suggest that produce ( fruit , vegetables ) is more expensive than snacks ( cookies , chips ) . OBJECTIVE The objective of this study was to show the method ologic weakness of comparing energy density with energy cost . DESIGN The relation between energy density and energy cost was replicated in a r and om-number data set . Additionally , observational data were collected for produce and snacks from an online supermarket . Variables included total energy ( kcal ) , total weight ( g ) , total number of servings , serving size ( g/serving ) , and energy density ( kcal/g ) . Price measures included energy cost ( $ /kcal ) , total price ( $ ) , unit price ( $ /g ) , and serving price ( $ /serving ) . Two-tailed t tests were used to compare price measures by food category . Relations between energy density and price measures within food categories were examined with the use of Spearman rank correlation analysis . RESULTS The relation between energy density and energy cost was shown to be driven by the algebraic properties of these variables . Food category was strongly correlated with both energy density and food price measures . Energy cost was higher for produce than for snacks . However , total price and unit price were lower for produce . Serving price and serving size were greater for produce than for snacks . Within food categories , energy density was uncorrelated with most measures of food price , except for a weak positive correlation with serving price within the produce category . CONCLUSION The findings suggest the relation between energy density and food price is confounded by food category and depends on which measure of price is used OBJECTIVE To examine the effectiveness of two methods of increasing fruit and fruit juice intake in pregnancy : midwives ' advice and vouchers exchangeable for juice . DESIGN Pregnant women were r and omly allocated to three groups : a control group , who received usual care ; an advice group , given advice and leaflets promoting fruit and fruit juice consumption ; and a voucher group , given vouchers exchangeable for fruit juice from a milk delivery firm . Dietary question naires were administered at ~16 , 20 and 32 weeks of pregnancy . Serum beta-carotene was measured at 16 and 32 weeks . SETTING An antenatal clinic in a deprived area . SUBJECTS Pregnant women aged 17 years and over . RESULTS The study comprised 190 women . Frequency of fruit consumption declined during pregnancy in all groups , but that of fruit juice increased substantially in the voucher group . Serum beta-carotene concentration increased in the voucher group , from 106.2 to 141.8 micromol l(-1 ) in women with measurements on both occasions ( P = 0.003 ) , decreased from 120.0 to 99.8 micromol l(-1 ) in the control group ( P = 0.005 ) , and was unchanged in the advice group . CONCLUSIONS Pregnant women drink more fruit juice if they receive vouchers exchangeable for juice supplied by the milk delivery service . Midwives ' advice to eat more fruit has no great effect . Providing vouchers for fruit juice is a simple method of increasing its intake in a deprived population and may be useful for other sections of the community Here , we describe the measurement characteristics of a 13-item dietary screener used in the Prostate Cancer Prevention Trial . We used data from 10,913 men who completed the 13-item dietary screener , a food frequency question naire ( FFQ ) , and question naires on demographic and health-related characteristics and from 146 men who also completed multiple 24-h dietary recalls in a sub study . The analyses in this report focused on percentage energy from fat and saturated fat and used the mean estimates from the dietary recalls as the criterion measures . Absolute nutrient estimates from the screener were about one-third of the estimates from the recalls and the FFQ . Validity was defined as the Pearson correlation of the criterion measures of fat with the corresponding measures from the FFQ and the screener . The FFQ was a statistically significantly more precise measure of percentage energy from fat ( r = 0.71 ) and saturated fat ( r = 0.72 ) than was the screener ( r = 0.50 and 0.53 , respectively ) . There were also statistically significant differences in how well these instruments could detect variation in dietary fat across various participant characteristics , suggesting that the screener may not perform as well as the FFQ across demographic strata such as education ( P < 0.001 ) . The results from this study suggest that the use of short dietary screeners as the sole assessment instrument may result in a serious loss of information regarding important exposures ( e.g. , fat intake ) and lost opportunities to enhance our knowledge regarding dietary factors and cancer risk The Dietary Approaches to Stop Hypertension ( DASH ) diet is perhaps the best example of how a nutrient dense dietary pattern can prevent chronic disease . In r and omized trials , DASH dietary patterns lowered blood pressure in hypertensive individuals.1 Subsequent trials and observational studies have consistently found that DASH-type diets reduced cardiovascular and metabolic BACKGROUND Reducing fruit and vegetable ( F&V ) prices is a frequently considered policy to improve dietary habits in the context of health promotion . However , evidence on the effectiveness of this intervention is limited . OBJECTIVE The objective was to examine the effects of a 50 % price discount on F&Vs or nutrition education or a combination of both on supermarket purchases . DESIGN A 6-mo r and omized controlled trial within Dutch supermarkets was conducted . Regular supermarket shoppers were r and omly assigned to 1 of 4 conditions : 50 % price discounts on F&Vs , nutrition education , 50 % price discounts plus nutrition education , or no intervention . A total of 199 participants provided baseline data ; 151 ( 76 % ) were included in the final analysis . F&V purchases were measured by using supermarket register receipts at baseline , at 1 mo after the start of the intervention , at 3 mo , at 6 mo ( end of the intervention period ) , and 3 mo after the intervention ended ( 9 mo ) . RESULTS Adjusted multilevel models showed significantly higher F&V purchases ( per household/2 wk ) as a result of the price discount ( + 3.9 kg ; 95 % CI : 1.5 , 6.3 kg ) and the discount plus education intervention ( + 5.6 kg ; 95 % CI : 3.2 , 7.9 kg ) at 6 mo compared with control . Moreover , the percentage of participants who consumed recommended amounts of F&Vs ( ≥400 g/d ) increased from 42.5 % at baseline to 61.3 % at 6 mo in both discount groups ( P = 0.03 ) . Education alone had no significant effect . CONCLUSIONS Discounting F&Vs is a promising intervention strategy because it result ed in substantially higher F&V purchases , and no adverse effects were observed . Therefore , pricing strategies form an important focus for future interventions or policy . However , the long-term effects and the ultimate health outcomes require further investigation . This trial was registered at the IS RCT N Trial Register as number IS RCT N56596945 and at the Dutch Trial Register ( http://www.trialregister.nl/trialreg/index.asp ) as number NL22568.029.08 OBJECTIVES To compare a widely used Australian food-frequency question naire ( FFQ ) with diet records and consider the results in relation to its use in nutrition surveillance . DESIGN Inter- method reliability study . SETTING A r and omised trial in subjects with past asbestos exposure . SUBJECTS Seventy-two adults living in Western Australia . METHODS A semi-quantitative FFQ developed by the Commonwealth Scientific Industrial Research Organisation in South Australia was administered after the completion of four 7-day diet records ( DRs ) . RESULTS Mean agreement between methods was not significantly different from 100 % for many nutrients , but the limits of agreement indicated that , at the individual level , the FFQ over- or underestimated the DR by at least 50 % . Mean agreement between methods decreased significantly with increasing intakes for the majority of nutrients . Pearson 's correlation coefficients were less informative indicators of agreement compared with the limits of agreement . CONCLUSIONS These results indicate poor agreement between the FFQ and DR when estimating absolute intakes . Therefore , comparing intakes collected using this FFQ with specific cut-off points such as Recommended Dietary Intakes for nutrition surveillance may lead to seriously flawed conclusions about population intakes OBJECTIVE This study evaluated the Michigan Farmers ' Market Nutrition Program in one Michigan county to determine its effect on fruit and vegetable consumption behavior . SUBJECTS/ SETTING Subjects were selected from WIC and Community Action Agency population s : 564 low income women completed the pretest ; 455 completed the posttest . Attrition rate was 19.3 % . INTERVENTION Subjects were assigned to one of 4 interventions : education about the use , storage and nutritional value of fruits and vegetables , distribution of farmers ' market coupons , both education and coupons , or no intervention . DESIGN Education-only and coupon and education groups were r and omly assigned ; clinic appointment timing determined assignment to no-intervention and coupon-only groups . MAIN OUTCOME MEASURES A self-administered question naire before and after intervention measured attitudes about fruit and vegetable consumption and intake of fruits and vegetables . WIC records documented redemption of coupons . STATISTICAL ANALYSES Data analysis included 2-way multivariate analysis of covariance , univariate analysis of covariance , logistic regression , and covariance structure modeling . RESULTS Both the education interventions and the coupon interventions had positive effects . Coupons had a direct effect on increasing fruit and vegetable consumption behavior but no effect on attitudes . Education had a direct effect on attitudes and seemed to exert an effect on consumption behavior through attitudes . The maximum impact of the intervention was achieved through a combination of education and coupons . APPLICATIONS This study demonstrated that a low-income population may be more likely to increase its fruit and vegetable consumption behavior when incentives such as coupons improve affordability OBJECTIVE Data on the economic value of nutrition education programs , such as the Exp and ed Food and Nutrition Education Program ( EFNEP ) , can help decision makers choose among alternative programs based on costs and benefits . A cost-benefit analysis of EFNEP was conducted to determine if participants ' savings in food expenditures exceeded program implementation costs . DESIGN /SUBJECTS Costs were collected over 6 months using expenditure reports and other records . Benefits were determined using prospect i ve data from 371 women enrolled in EFNEP who completed a 24-hour food recall and behavior survey , and recorded the amount of money spent monthly on food at program entry and exit . Two treatment groups received nutrition education and one group did not receive education . One treatment group estimated food expenditures from recall and the other collected register receipts or recorded expenditures . Control group subjects reported expenditures from recall . Net present value ( NPV ) was calculated using mean EFNEP cost per participant subtracted from the mean change in family food expenditures per participant over a 5-year period at three discount rates . STATISTICAL ANALYSES Analysis was design ed to compare food expenditures among the two experimental groups and control group and food and nutrient intakes and survey scores between the combined experimental group and control group . RESULTS The average EFNEP program cost perparticipant was $ 388 , and graduating participants reported that family food expenditures decreased on average by $ 10 to $ 20 per month or $ 124 to $ 234 over a year . When benefits were projected to last 5 years , the NPV was $ 147 to $ 696 depending on the method of food expenditure estimation and the discount rate . At the same time individuals reduced food expenditures , they increased intakes of iron , vitamin C , vitamin B-6 , and fiber . They added less salt when cooking and read nutrition labels more often . They also reported not running out of food at the end of the month as often . APPLICATIONS/ CONCLUSIONS Findings from this research showed that EFNEP is cost-beneficial . The magnitude of the savings in food expenditures is sensitive to the method of food expenditure reporting and assumptions about how long participants will retain the behaviors they learn The relative effects of energy density and palatability on energy intake , and whether there are familial influences on these effects , are not known . We investigated this issue in 7 pairs of healthy , male monozygotic twins ( mean+/-SD age 26.3+/-8.6 years , BMI 23.7+/-3.2 kg/m(2 ) ) in a clinical study involving covert ad libitum feeding of high-fat ( HF , approximately 40 % ) and low-fat ( LF , approximately 20 % ) diets in two 9-day phases . Diets were matched for average energy density , protein , fiber , and initial reported taste pleasantness , but these factors varied among the individual foods . Relationships between energy density , palatability , and energy intake were explored using regression and path analyses . Food energy density was positively associated with average taste pleasantness ( r=0.46 , P=0.03 ) independent of fat content , while energy intake from individual foods was positively associated with both energy density ( r=0.56 , P=0.007 ) and taste pleasantness ( r=0.73 , P<0.0001 ) . In path analysis , both energy density and taste pleasantness directly influenced energy intake , and energy density also indirectly influenced energy intake by influencing taste pleasantness . In addition , there were significant within-twin pair similarities for the energy density-taste pleasantness and energy density-energy intake relationships ( P<0.03 ) with the result that some twin pairs but not others identified foods high in energy density as more pleasant tasting and consumed relatively more energy from them compared to foods low in energy density . These results suggest that there are familial influences on the extent to which high energy density foods are preferred and contribute to total energy intake BACKGROUND Numerous studies support the protective effect of high fruit and vegetable consumption on chronic disease risk , mainly against cancer and cardiovascular diseases . The increase of fruit and vegetable intake has become a public health priority in many countries . OBJECTIVE The aim of the study was to investigate the relationships of socioeconomic , demographic , and behavioral factors with both quantity and variety of fruit and vegetable consumption . DESIGN /SUBJECTS Fruit and vegetable intake was assessed using repeated 24-hour dietary records collected during a 2-year period from 4,282 French subjects ( 2,373 men and 1,909 women ) , aged 45 to 62 years , who participated in a large prospect i ve study . STATISTICAL ANALYSIS Both education level and occupation categories were used as socioeconomic indicators . Logistic regression models were applied to assess factors related to meeting the 5 A Day fruit and vegetable recommendation . Covariance analyses were performed to compare the fruit and vegetable variety scores and the contributions of fruit and vegetables to the total daily diet cost across socioeconomic indicators within each sex . RESULTS Meeting the 5 A Day recommendation was more likely in subjects aged 50 years and older , higher education levels , nonsmokers , moderate alcohol drinkers and in women engaging in regular physical activity . The odds ratio ( 95 % confidence interval ) for the lower vs higher education level was 0.70 ( 0.54 to 0.92 ) in men and 0.65 ( 0.48 to 0.85 ) in women . No significant difference was observed between occupation categories . A positive relationship between vegetable variety and education level was found in both sexes . Fruit variety was positively associated with both education and occupation categories , but only in men . The contribution of fruits to the total daily diet cost increased with occupation ( P<0.02 ) and education ( P<0.0001 ) in men , but decreased with occupation in women ( P<0.05 ) . CONCLUSIONS Although cost constraints may explain the lower fruit and vegetable intake in lower socioeconomic groups , the relative influence of budgetary re sources , nutrition knowledge , and social and environmental barriers in socioeconomic disparities need further investigation OBJECTIVE To assess perceived and actual barriers to dietary fat reduction . DESIGN A 20-week intervention study was carried out to investigate the problems encountered by persons attempting to reduce their fat intake . SUBJECTS Seventy subjects initially consuming moderately high-fat diets were recruited from the local area by newspaper advertisement . Sixty-one completed the study . INTERVENTION Subjects were r and omized into either a control or an experimental group . Subjects in the experimental group ( n = 45 ) received instruction on reducing their intake of fat using current dietary recommendations . All subjects initially completed a question naire to assess their beliefs and attitudes regarding selected dietary changes , and the experimental group also completed a similar question naire at intervals during the study . Weighed diet records were completed by all subjects throughout the study . STATISTICAL ANALYSIS Repeated measures analysis of variance was used to examine changes in nutrient intake . Univariate analysis of variance was used to examine differences in barriers encountered by most and least successful fat reducers . RESULTS Perceived barriers reflected actual problems encountered . One of the most consistently reported problems was that of reduction in taste quality of the diet . Other problems included an increase in cost , decrease in convenience , lack of family support for certain changes , and an inability to judge the fat content of diets . APPLICATIONS/ CONCLUSIONS Strategies aim ed at improving the taste of low-fat diets , increasing awareness of fat intake , and increasing family support may be most effective in promoting greater adherence to dietary guidelines intended to achieve reductions in fat consumption BACKGROUND Research has shown that lower socioeconomic groups purchase foods that are less consistent with dietary recommendations . The price and availability of foods are thought to be important mediating factors between socioeconomic position and food purchasing . OBJECTIVES We examined the relative contribution of the perceived and objective ly measured price and availability of recommended foods to household income differences in food purchasing . METHODS Using a face-to-face interview , a r and om sample of Brisbane residents ( n=812 ) were asked about their food purchasing choices in 2000 . They were also asked about their perceptions of the price and availability of ' recommended ' foods ( i.e. choices lower in fat , saturated fat , sugar , salt or higher in fibre ) in the supermarkets where they usually shopped . Audits measuring the actual availability and price of identical foods were conducted in the same supermarkets . RESULTS Lower socioeconomic groups were less likely to make food purchasing choices consistent with dietary guideline recommendations . Objective availability and price differences were not associated with purchasing choices , nor did they contribute to socioeconomic inequalities in food purchasing choices . Perceived availability and price differences were associated with the purchase of recommended foods . Perceived availability made a small contribution to inequalities in food purchasing , however perceived price differences did not . CONCLUSION Socioeconomic inequalities in food purchasing are not mediated by differential availability of recommended foods and differences in price between recommended and regular foods in supermarkets , or by perceptions of their relative price . However , differential perceptions of the availability of recommended foods may play a small role in food purchasing inequalities OBJECTIVE To assess the affordability of a nutritious diet for households earning minimum wage in Nova Scotia . METHODS Food costing data were collected in 43 r and omly selected grocery stores throughout NS in 2002 using the National Nutritious Food Basket ( NNFB ) . To estimate the affordability of a nutritious diet for households earning minimum wage , average monthly costs for essential expenses were subtracted from overall income to see if enough money remained for the cost of the NNFB . This was calculated for three types of household : 1 ) two parents and two children ; 2 ) lone parent and two children ; and 3 ) single male . Calculations were also made for the proposed 2006 minimum wage increase with expenses adjusted using the Consumer Price Index ( CPI ) . RESULTS The monthly cost of the NNFB priced in 2002 for the three types of household was 572.90 dollars , 351.68 dollars , and 198.73 dollars , respectively . Put into the context of basic living , these data showed that Nova Scotians relying on minimum wage could not afford to purchase a nutritious diet and meet their basic needs , placing their health at risk . These basic expenses do not include other routine costs , such as personal hygiene products , household and laundry cleaners , and prescriptions and costs associated with physical activity , education or savings for unexpected expenses . CONCLUSION People working at minimum wage in Nova Scotia have not had adequate income to meet basic needs , including a nutritious diet . The 2006 increase in minimum wage to 7.15 dollars/hr is inadequate to ensure that Nova Scotians working at minimum wage are able to meet these basic needs . Wage increases and supplements , along with supports for expenses such as childcare and transportation , are indicated to address this public health problem Background : There is a scarcity of studies evaluating the relationship between food costs and adherence to different food patterns and obesity . Methods : This was a dynamic cohort of Spanish university graduates ( n = 17 197 for the cross-sectional baseline assessment and n = 11 195 for the prospect i ve follow-up analyses ) . Mean age was 38.6 ( SD 12.2 ) years , and 60 % of participants were women . A 136-item food frequency question naire previously vali date d in Spain was used . Principal component analysis ( PCA ) was used to derive dietary patterns . Average cost of food was calculated from official Spanish government data . Self-reported weight was previously vali date d in the cohort . Body weight was assessed both at baseline and during follow-up . Results : PCA identified two dietary patterns , design ated as western and Mediterranean . Participants with the highest scores on the western dietary pattern ( fifth quintile vs first quintile ) spent less money ( –€0.64 ( −$0.80 ) per 1000 kcal ( 95 % CI −€0.68 to −€0.61 , p for trend < 0.001 ) ) on their daily food costs , whereas the opposite was true for the Mediterranean dietary pattern ( + € 0.71 ( + $ 0.90 ) ( 95 % CI + € 0.67 to + € 0.74 , p for trend < 0.001 ) . After adjusting for dietary pattern scores and other potential confounders , higher daily food costs were significantly associated with greater weight gain . Conclusions : These data suggest that a Mediterranean dietary pattern is more expensive to follow than a western dietary pattern . This economic barrier should be considered when counselling patients about following a healthy diet because cost may be a prohibitive factor |
12,379 | 24,817,897 | Based on available evidence , we could find that psychoeducational interventions , music interventions , acupuncture plus drug therapy , Chinese herbal medicine plus cancer therapy , compound kushen injection , reflexology , lycopene , TENS , qigong , cupping , cannabis , Reiki , homeopathy ( Traumeel ) , and creative arts therapies might have beneficial effects on adult cancer pain .
No benefits were found for acupuncture ( versus drug therapy or shame acupuncture ) , and the results were inconsistent for massage therapy , transcutaneous electric nerve stimulation ( TENS ) , and Viscum album L plus cancer treatment .
Conclusion . | Background and Objective .
Now with more and more published systematic review s of Complementary and Alternative Medicine ( CAM ) on adult cancer pain , it is necessary to use the methods of overview of systematic review to summarize available evidence , appraise the evidence level , and give suggestions to future research and practice . | The objective of this study was to assess the evidence for or against the effectiveness of cupping as a treatment option for pain . Fourteen data bases were search ed . R and omized clinical trials ( RCTs ) testing cupping in patients with pain of any origin were considered . Trials using cupping with or without drawing blood were included , while trials comparing cupping with other treatments of unproven efficacy were excluded . Trials with cupping as concomitant treatment together with other treatments of unproven efficacy were excluded . Trials were also excluded if pain was not a central symptom of the condition . The selection of studies , data extraction and validation were performed independently by three review ers . Seven RCTs met all the inclusion criteria . Two RCTs suggested significant pain reduction for cupping in low back pain compared with usual care ( P < .01 ) and analgesia ( P < .001 ) . Another two RCTs also showed positive effects of cupping in cancer pain ( P < .05 ) and trigeminal neuralgia ( P < .01 ) compared with anticancer drugs and analgesics , respectively . Two RCTs reported favorable effects of cupping on pain in brachialgia compared with usual care ( P = .03 ) or heat pad ( P < .001 ) . The other RCT failed to show superior effects of cupping on pain in herpes zoster compared with anti-viral medication ( P = .065 ) . Currently there are few RCTs testing the effectiveness of cupping in the management of pain . Most of the existing trials are of poor quality . Therefore , more rigorous studies are required before the effectiveness of cupping for the treatment of pain can be determined Women diagnosed with breast cancer received massage therapy or practice d progressive muscle relaxation ( PMR ) for 30-min sessions 3 times a week for 5 weeks or received st and ard treatment . The massage therapy and relaxation groups reported less depressed mood , anxiety , and pain immediately after their first and last sessions . By the end of the study , however , only the massage therapy group reported being less depressed and less angry and having more vigor . Dopamine levels , Natural Killer cells , and lymphocytes also increased from the first to the last day of the study for the massage therapy group . These findings highlight the benefit of these complementary therapies , most particularly massage therapy , for women with breast cancer OBJECTIVE Our purpose was to measure the agreement , reliability , construct validity , and feasibility of a measurement tool to assess systematic review s ( AMSTAR ) . STUDY DESIGN AND SETTING We r and omly selected 30 systematic review s from a data base . Each was assessed by two review ers using : ( 1 ) the enhanced quality assessment question naire ( Overview of Quality Assessment Question naire [ OQAQ ] ) ; ( 2 ) Sacks ' instrument ; and ( 3 ) our newly developed measurement tool ( AMSTAR ) . We report on reliability ( interobserver kappas of the 11 AMSTAR items ) , intraclass correlation coefficients ( ICCs ) of the sum scores , construct validity ( ICCs of the sum scores of AMSTAR compared with those of other instruments ) , and completion times . RESULTS The interrater agreement of the individual items of AMSTAR was substantial with a mean kappa of 0.70 ( 95 % confidence interval [ CI ] : 0.57 , 0.83 ) ( range : 0.38 - 1.0 ) . Kappas recorded for the other instruments were 0.63 ( 95 % CI : 0.38 , 0.78 ) for enhanced OQAQ and 0.40 ( 95 % CI : 0.29 , 0.50 ) for the Sacks ' instrument . The ICC of the total score for AMSTAR was 0.84 ( 95 % CI : 0.65 , 0.92 ) compared with 0.91 ( 95 % CI : 0.82 , 0.96 ) for OQAQ and 0.86 ( 95 % CI : 0.71 , 0.94 ) for the Sacks ' instrument . AMSTAR proved easy to apply , each review taking about 15 minutes to complete . CONCLUSIONS AMSTAR has good agreement , reliability , construct validity , and feasibility . These findings need confirmation by a broader range of assessors and a more diverse range of review Evaluating the effectiveness of nursing interventions in decreasing pain is a top priority for clinical research . Unfortunately , most of the research on cancer pain relief has been limited to treatment studies involving the administration of analgesics . Research is needed to determine which nonanalgesic methods of pain control are effective and under what conditions . Consequently , an experimental study was design ed to test the effectiveness of massage as an intervention for cancer pain . Twenty-eight patients were r and omly assigned to a massage or control group . The patients in the massage group were given a 10 minute massage to the back ; the patients in the control group were visited for 10 minutes . For males , there was a significant decrease in pain level immediately after the massage . For females , there was not a significant decrease in pain level immediately after the massage . There were no significant differences between pain 1 hour and 2 hours after the massage in comparison with the initial pain for males or females . Massage was shown to be an effective short-term nursing intervention for pain in males in this sample Complementary therapies are increasingly used to reduce side effects of cancer treatment , without evidence for their effectiveness . In a r and omized , prospect i ve , 2-period , crossover intervention study , the authors tested the effects of therapeutic massage ( MT ) and healing touch ( HT ) , in comparison to presence alone or st and ard care , in inducing relaxation and reducing symptoms in 230 subjects . MT and HT lowered blood pressure , respiratory rate ( RR ) , and heart rate ( HR ) . MT lowered anxiety and HT lowered fatigue , and both lowered totalmooddisturbance . Pain ratings were lower after MT and HT , with 4-week nonsteroidal antiinflammatory drug use less during MT . There were no effects on nausea . Presence reduced RR and HR but did not differ from st and ard care on any measure of pain , nausea , mood states , anxiety , or fatigue . MT and HT are more effective than presence alone or st and ard care in reducing pain , mood disturbance , and fatigue in patients receiving cancer chemotherapy BACKGROUND To investigate the method ological quality of r and omized controlled trials in three areas of complementary medicine . METHODS The method ological quality of 207 r and omized trials collected for five previously published systematic review s on homeopathy , herbal medicine ( Hypericum for depression , Echinacea for common cold ) , and acupuncture ( for asthma and chronic headache ) was assessed using a vali date d scale ( the Jadad scale ) and single quality items . RESULTS While the method ological quality of the trials was highly variable , the majority had important shortcomings in reporting and /or methodology . Major problems in most trials were the description of allocation concealment and the reporting of drop-outs and withdrawals . There were relevant differences in single quality components between the different complementary therapies : For example , acupuncture trials reported adequate allocation concealment less often ( 6 % versus 32 % of homeopathy and 26 % of herb trials ) , and trials on herbal extracts had better summary scores ( mean score 3.12 versus 2.33 for homeopathy and 2.19 for acupuncture trials ) . Larger trials published more recently in journals listed in Medline and in English language scored significantly higher than trials not meeting these criteria . CONCLUSION Trials of complementary therapies often have relevant method ological weaknesses . The type of weaknesses varies considerably across interventions Goal of workBreast cancer survivors have limited options for the treatment of hot flashes and related symptoms . Further , therapies widely used to prevent recurrence in survivors , such as tamoxifen , tend to induce or exacerbate menopausal symptoms . The aim of this preliminary , r and omized controlled trial was to evaluate the effects of a yoga intervention on menopausal symptoms in a sample of survivors of early-stage breast cancer ( stages IA – IIB ) . Material s and methods Thirty-seven disease-free women experiencing hot flashes were r and omized to the 8-week Yoga of Awareness program ( gentle yoga poses , meditation , and breathing exercises ) or to wait-list control . The primary outcome was daily reports of hot flashes collected at baseline , posttreatment , and 3 months after treatment via an interactive telephone system . Data were analyzed by intention to treat . Main results At posttreatment , women who received the yoga program showed significantly greater improvements relative to the control condition in hot-flash frequency , severity , and total scores and in levels of joint pain , fatigue , sleep disturbance , symptom-related bother , and vigor . At 3 months follow-up , patients maintained their treatment gains in hot flashes , joint pain , fatigue , symptom-related bother , and vigor and showed additional significant gains in negative mood , relaxation , and acceptance . Conclusions This pilot study provides promising support for the beneficial effects of a comprehensive yoga program for hot flashes and other menopausal symptoms in early-stage breast cancer survivors Context Some patients nearing death seek pain relief with massage , but little is known about the effectiveness of massage in managing pain in palliative care setting s. Contribution In this r and omized trial in 380 patients with advanced cancer , improvement in pain and mood immediately after treatment was greater with massage than with simple touch . Unfortunately , there were no sustained differences in pain , quality of life , or analgesic use during 3 weeks . Adverse effects were infrequent and similar in both groups . Implication Massage may offer some immediate relief for patients with advanced cancer , but the absence of sustained effects demonstrates the need for more effective strategies to manage pain at the end of life . The Editors Symptom relief is central to end-of-life care ; however , many terminally ill individuals experience serious pain and other physical and emotional symptoms ( 14 ) . Studies examining the efficacy of therapies that may mediate these symptoms deserve the highest priority . The Institute of Medicine and the National Institutes of Health recommend research directed at improving end-of-life care ( 5 , 6 ) . Pain associated with advanced cancer can cause physical and emotional distress , leading to decreased functional ability and quality of life . Massage may interrupt the cycle of distress through the therapist 's intention ( presence , communication , and desire to produce a therapeutic response ) , induction of a relaxation response , increased blood and lymphatic circulation , potentiation of analgesic effects , decreased inflammation and edema , manual release of muscle spasms , increased endogenous endorphin release , and competing sensory stimuli that override pain signals ( 711 ) . Despite theoretical bases supporting the use and growing acceptance of massage therapy , few r and omized clinical trials have assessed its efficacy . Large trials have been difficult to design and carry out ; challenges include frailty of patients with late-stage cancer and reluctance of health care providers to refer patients because of the possibility of r and omization to nonmassage therapy control ( 12 ) . Therapeutic massage can reduce pain and improve symptom distress and quality of life for patients with cancer at the end of life . The purpose of the REST ( Reducing End-of-Life Symptoms with Touch ) study was to evaluate the efficacy of massage compared with an exposure controlling for time , attention , and touch . We hypothesized that massage would decrease pain and explored effects on quality of life , physical and emotional symptom distress , and analgesic medicine use . Methods Design Overview We conducted this prospect i ve , 2-group , r and omized , single-blind trial between November 2003 and October 2006 . After we evaluated patients for inclusion and exclusion criteria , patients provided written informed consent . Then we r and omly assigned patients to a treatment group ( massage ) or control exposure ( simple touch ) . Figure 1 depicts the timing of the study procedures for a hypothetical participant . We collected individual characteristics , disease , pain characteristics , symptom distress , quality of life , functional status ( Karnofsky Performance Scale score ) ( 13 ) , expected helpfulness of massage for pain , and concurrent interventions ( pharmacologic and nonpharmacologic ) at baseline ( within 72 hours of study enrollment ) and at 3 subsequent weekly visits over the 3 to 4 weeks of participation ( sustained outcomes ) . Final data collection occurred approximately 1 week after the final treatment . Data collectors were blinded to treatment assignment . Participants received up to six 30-minute treatments over 2 weeks , with at least 24 hours between treatment sessions . The initial treatment session occurred within 48 hours of baseline data collection . The treatment provider and patient determined the scheduling of treatment sessions . Treatment providers who were not blinded to treatment assignment obtained the immediate outcomes just before and after every treatment session . All participants received routine care in addition to the specified interventions . The Colorado Multiple Institutional Review Board and , where applicable , site-specific institutional review boards approved the study . Figure 1 . Study overview : timing of study procedures . Setting and Participants Study sites included 15 U.S. hospices that are members of the Population -based Palliative Care Research Network ( PoPCRN ) ( 14 ) and the University of Colorado Cancer Center , Aurora , Colorado . Eligible participants were English-speaking adults with advanced cancer ( stage III or IV , all cancer types , any care setting ) who had at least moderate pain ( score 4 on a 0- to 10-point scale ) in the week before enrollment , an anticipated life expectancy of at least 3 weeks , and the ability to consent . Exclusion criteria included receipt of professional massage within 1 month of enrollment , anticoagulant therapy , known platelet count less than 10109 cells/L , or known unstable spine . R and omization and Interventions Verification of eligibility was forwarded by a study coordinator from each study site to the University of Colorado research ers . Two design ated investigators r and omly assigned patients ; assignments were transmitted back to the requesting site . All study personnel other than the on-site study coordinators and these 2 design ated investigators were blinded to the r and omization sequence . An SAS software program ( SAS Institute , Cary , North Carolina ) generated the r and omization sequence by producing a r and omized block design stratified by study site . Block size r and omly varied among 2 , 4 , and 6 so that it was not possible to predict the next assignment . To minimize the likelihood that potential participants would decline enrollment because of reluctance to be r and omly assigned , we offered massage after study completion to those assigned to the control group . Experimental Treatment : Massage Therapy The massage intervention included gentle effleurage , petrissage , and myofascial trigger point release . Effleurage is a smooth , gliding stroke ; petrissage is squeezing , rolling , and kneading the muscles ; and trigger point release provides concentrated finger pressure to painful localized areas in muscles to break cycles of spasm and pain ( 15 ) . Individual therapist judgment dictated the frequency of rhythm , rate , or stroke ; sequence or mix of strokes ; time spent in each stroke ; stroke length ; and body area massaged ( 16 ) . Massage therapists spent 65 % of the time in effleurage and 35 % in petrissage . The most frequently massaged areas of the body were the neck and upper back ( about 80 % of the time ) and arms , h and s , lower legs , and feet ( about 75 % of the time ) . Other areas , such as the chest , abdomen , buttocks , back of the thighs , and forehead were massaged less than 50 % of the time . Therapists appropriately modified massage in persons with skin fragility , postural limitations , edema , osteoporosis , or bone metastasis . Therapists avoided sites of inflammation or infection , hyperesthesias , injury , surgery , ports , catheters , deep venous thrombosis , and tumors . Therapists identified and treated up to 3 myofascial trigger points per session ( located 15 % to 25 % of the time in the neck , upper trapezius , and lower trapezius regions ) . One half of the sessions were provided with the patient supine , 25 % seated , and the remainder split between side-lying and prone positions . Temperature and level of privacy varied with setting . Fewer than 25 % of participants were unclothed during treatments . Massage was performed by licensed massage therapists who had at least 6 months of experience treating patients with advanced cancer or hospice patients and completed a minimum 500-hour program of study in massage from an institution recognized by their state as a vocational school . Control Exposure We design ed the control exposure , simple touch , to control for the time , attention , touch , and healing intent components of the intervention ( 17 ) . The control consisted of placement of both h and s on the participant for 3 minutes at each of the following locations bilaterally : base of neck , shoulder blades , lower back , calves , heels , clavicles , lower arms , h and s , patellae , and feet . Pressure was light and consistent , with no side-to-side h and movement . Control therapy providers interrupted conscious healing intention by silently counting backward from 100 by 7 , reciting nursery rhymes , or planning their day 's activities ( 18 , 19 ) . The control treatments were provided by individuals with no past body or energy work experience . All treatment providers participated in st and ardized h and s-on training , received a study manual and training video , and were evaluated for competency in study procedures . We monitored adherence to study protocol s during twice-yearly site visits . Treatment providers in both groups used Biotone hypoallergenic unscented massage cream ( Biotone , San Diego , California ) . For the purpose s of st and ardization and to mediate the presence of intervening variables , we did not permit music , essential oils , or energy work and instructed treatment providers to limit their communication to providing instructions or responding to therapy-related questions . To minimize variation by treatment provider , 1 primary massage therapist or simple-touch provider per participant at each study site administered study treatments . Outcomes and Follow-up We used face-to-face , interviewer-administered question naires to collect all study data . We measured neuropathic pain at baseline only by the Neuropathy Pain Scale ( 0- to 10-point scale ) , which is sensitive to pain qualities most common to neuropathic pain syndromes ( 20 , 21 ) . Presence of neuropathic pain was defined as a Neuropathy Pain Scale summary score greater than 3 . Primary Outcomes : Immediate and Sustained Change in Pain The immediate effect was measured by the pain intensity scale of the Memorial Pain Assessment Card ( MPAC ) ( 0 to 10 points ; 10 = worst pain ) ( 22 ) . The sustained effect was measured This article reports findings from a r and omized controlled trial of massage and guided meditation with patients at the end of life . Using data from 167 r and omized patients , the authors considered patient outcomes through 10 weeks post-enrolment , as well as next-of-kin ratings of the quality of the final week of life for 106 patients who died during study participation . Multiple regression models demonstrated no significant treatment effects of either massage or guided meditation , delivered up to twice a week , when compared with outcomes of an active control group that received visits from hospice-trained volunteers on a schedule similar to that of the active treatment arms . The authors discuss the implication s of their findings for integration of these complementary and alternative medicine therapies into st and ard hospice care OBJECTIVE To investigate major methods of design and statistical analysis in controlled clinical acupuncture trials published in the West during the past six years ( 2003 - 2009 ) and , based on this analysis , to provide recommendations that address method ological issues and challenges in clinical acupuncture research . METHOD PubMed was search ed for acupuncture RCTs published in Western journals in English between 2003 and 2009 . The keyword used was acupuncture . RESULTS One hundred and eight qualified reports of acupuncture trials that included more than 30 symptoms/conditions were identified , analyzed , and grouped into efficacy ( explanatory ) , effectiveness ( pragmatically beneficial ) , and other ( unspecified ) studies . All were r and omized controlled clinical trials ( RCTs ) . In spite of significant improvement in the quality of acupuncture RCTs in the last 30 years , these reports show that some method ological issues and shortcomings in design and analysis remain . Moreover , the quality of the efficacy studies was not superior to that of the other types of studies . Research design and reporting problems include unclear patient criteria and inadequate practitioner eligibility , inadequate r and omization , and blinding , deficiencies in the selection of controls , and improper outcome measurements . The problems in statistical analysis included insufficient sample sizes and power calculations , inadequate h and ling of missing data and multiple comparisons , and inefficient methods for dealing with repeated measure and cluster data , baseline value adjustment , and confounding issues . CONCLUSION Despite recent advancements in acupuncture research , acupuncture RCTs can be improved , and more rigorous research methods should be carefully considered This article describes the findings of an empirical study on the use of foot massage as a nursing intervention in patients hospitalized with cancer . The study was developed from the earlier work of Ferrell-Torry and Glick ( 1992 ) . In a sample of 87 subjects , a 10-minute foot massage ( 5 minutes per foot ) was found to have a significant immediate effect on the perceptions of pain , nausea , and relaxation when measured with a visual analog scale . The use of foot massage as a complementary method is recommended as a relatively simple nursing intervention for patients experiencing nausea or pain related to the cancer experience . Further research into its effectiveness in the management of these symptoms by the family at home is warranted ABSTRACT Aims : In a r and omized controlled clinical trial ( RCCT ) , we examined the effects of four massages on pain intensity , prescribed IM morphine equivalent doses ( IMMSEQ ) , hospital admissions , and quality of life ( QoL ) . Methods : Of 173 referred patients , 29 ( 14 control , 15 massage ) completed this pilot study . Subjects were 69 % male and aged 63 years on average . Licensed therapists administered four , twice-weekly massages . Baseline and outcome measurements were obtained by other team members before the first and after the fourth massages . Results : Pain intensity , pulse rate , and respiratory rate were significantly reduced immediately after the massages . At study entry , the massage group reported higher pain intensity ( 2.4 ± 2.8 vs. 1.6 ± 2.1 ) which decreased by 42 % ( 1.4 ± 1.5 ) compared to a 25 % reduction in the control group ( 1.2 ± 1.3 ) ( p > .05 ) . IMMSEQ doses were stable or decreased for eight patients in each group and increased for seven massage and six control group patients . One massage group and two control group patients were hospitalized . All initial QoL scores were higher in the massage group than in the control group , but only current QoL was statistically significant . Both groups reported improved global QoL. The control group reported slight improvement in current QoL and satisfaction with QoL whereas these two aspects of QoL declined in the massage group even though their average QoL scores were higher than the control group at the end of the study . Conclusions : We demonstrated feasibility of conducting an RCCT in which we systematic ally implemented massage as a nonpharmacologic comfort therapy along with our usual hospice care . The massage intervention produced immediate relaxation and pain relief effects . A power analysis based on trends in the longer-term effects indicate that a study with 80 subjects per group is likely to detect statistically significant effects of usual hospice care with twice-weekly massage therapy sessions on pain intensity , analgesic dosages , and quality of life . Lessons we learned from conducting this pilot study are being used to improve documentation of our hospice program outcomes and to plan a definitive study . [ Article copies available for a fee from The Haworth Document Delivery Service : 1 - 800 - 342 - 9678 . E-mail address : [email protected] PURPOSE / OBJECTIVES To evaluate the safety and efficacy of reflexology , a complementary therapy that applies pressure to specific areas of the feet . DESIGN Longitudinal , r and omized clinical trial . SETTING Thirteen community-based medical oncology clinics across the midwestern United States . SAMPLE A convenience sample of 385 predominantly Caucasian women with advanced-stage breast cancer receiving chemotherapy and /or hormonal therapy . METHODS Following the baseline interview , women were r and omized into three primary groups : reflexology ( n = 95 ) , lay foot manipulation ( LFM ) ( n = 95 ) , or conventional care ( n = 96 ) . Two preliminary reflexology ( n = 51 ) and LFM ( n = 48 ) test groups were used to establish the protocol s. Participants were interviewed again postintervention at study weeks 5 and 11 . MAIN RESEARCH VARIABLES Breast cancer-specific health-related quality of life ( HRQOL ) , physical functioning , and symptoms . FINDINGS No adverse events were reported . A longitudinal comparison revealed significant improvements in physical functioning for the reflexology group compared to the control group ( p = 0.04 ) . Severity of dyspnea was reduced in the reflexology group compared to the control group ( p < 0.01 ) and the LFM group ( p = 0.02 ) . No differences were found on breast cancer-specific HRQOL , depressive symptomatology , state anxiety , pain , and nausea . CONCLUSIONS Reflexology may be added to existing evidence -based supportive care to improve HRQOL for patients with advanced-stage breast cancer during chemotherapy and /or hormonal therapy . IMPLICATION S FOR NURSING Reflexology can be recommended for safety and usefulness in relieving dyspnea and enhancing functional status among women with advanced-stage breast cancer BACKGROUND . A r and omized controlled trial was conducted to investigate the efficacy of classical massage treatment in reducing breast cancer-related symptoms and in improving mood disturbances . METHODS . Women diagnosed with primary breast cancer were r and omized into an intervention group and a control group . For a period of 5 weeks , the intervention group received bi-weekly 30-min classical massages in the back and head-neck areas . The control group received no additional treatment to their routine healthcare . To evaluate treatment efficacy , the following vali date d question naires were administrated at baseline ( T1 ) , at the end of the intervention ( T2 ) , and at a followup at 11 weeks ( T3 ) : the Short Form-8 Health Survey , the European Organization of Research and Treatment of Cancer quality of life question naire breast module ( EORTC QLQ-BR23 ) , the Giessen Complaints Inventory ( GBB ) , and the Berlin Mood Question naire ( BSF ) . RESULTS . Eighty-six eligible women ( mean age : 59 years ) were enrolled in the study . A significantly higher reduction of physical discomfort was found in the intervention group compared with the control group at T2 ( p=0.001 ) and at T3 ( p=0.038 ) . A decrease in fatigue was also observed . Women in the intervention group reported significantly lower mood disturbances at T2 ( p<0.01 ) but not at T3 . The effect of treatment on mood disturbances was significantly higher if a patient was treated continuously by the same masseur . CONCLUSION . Classical massage seems to be an effective adjuvant treatment for reducing physical discomfort and fatigue , and improving mood disturbances in women with early stage breast cancer Background Many patients suffer from severe shoulder complaints after breast cancer surgery and axillary lymph node dissection . Physiotherapy has been clinical ly observed to improve treatment of these patients . However , it is not a st and ard treatment regime . The purpose of this study is to investigate the efficacy of physiotherapy treatment of shoulder function , pain and quality of life in patients who have undergone breast cancer surgery and axillary lymph node dissection . Methods Thirty patients following breast cancer surgery and axillary lymph node dissection were included in a r and omised controlled study . Assessment s were made at baseline and after three and six months . The treatment group received st and ardised physiotherapy treatment of advice and exercises for the arm and shoulder for three months ; the control group received a leaflet containing advice and exercises . If necessary soft tissue massage to the surgical scar was applied . Primary outcome variables were amount of pain in the shoulder/arm recorded on the Visual Analogue Scale , and shoulder mobility ( flexion , abduction ) measured using a digital inclinometer under st and ardized conditions . Secondary outcome measures were shoulder disabilities during daily activities , edema , grip strength of both h and s and quality of life . The research er was blinded to treatment allocation . Results All thirty patients completed the trial . After three and six months the treatment group showed a significant improvement in shoulder mobility and had significantly less pain than the control group . Quality of life improved significantly , however , h and grip strength and arm volume did not alter significantly . Conclusion Physiotherapy reduces pain and improves shoulder function and quality of life following axillary dissection after breast cancer . Trial registration IS RCT |
12,380 | 21,984,590 | A few studies found that HIT may offer cost advantages despite their increased acquisition costs .
Sophisticated concurrent prospect i ve economic evaluations need to be conducted to address whether HIT interventions in the medication management process are cost-effective | OBJECTIVE To conduct a systematic review and synthesis of the evidence surrounding the cost-effectiveness of health information technology ( HIT ) in the medication process . | Background Interventions design ed to narrow the gap between research findings and clinical practice may be effective , but also costly . Economic evaluations are necessary to judge whether such interventions are worth the effort . We have evaluated the economic effects of a tailored intervention to support the implementation of guidelines for the use of antihypertensive and cholesterol-lowering drugs . The tailored intervention was evaluated in a r and omized trial , and was shown to significantly increase the use of thiazides for patients started on antihypertensive medication , but had little or no impact on other outcomes . The increased use of thiazides was not expected to have an impact on health outcomes . Methods and Findings We performed cost-minimization and cost-effectiveness analyses on data from a r and omized trial involving 146 general practice s from two geographical areas in Norway . Each practice was r and omized to either the tailored intervention ( 70 practice s ; 257 physicians ) or control group ( 69 practice s ; 244 physicians ) . Only patients that were being started on antihypertensive medication were included in the analyses . A multifaceted intervention was tailored to address identified barriers to change . Key components were an educational outreach visit with audit and feedback , and computerized reminders . Pharmacists conducted the visits . A cost-minimization framework was adopted , where the costs of intervention were set against the reduced treatment costs ( principally due to increased use of thiazides rather than more expensive medication ) . The cost-effectiveness of the intervention was estimated as the cost per additional patient being started on thiazides . The net annual cost ( cost minimization ) in our study population was US$ 53,395 , corresponding to US$ 763 per practice . The cost per additional patient started on thiazides ( cost-effectiveness ) was US$ 454 . The net annual savings in a national program was modeled to be US$ 761,998 , or US$ 540 per practice after 2 y. In this scenario the savings exceeded the costs in all but two of the sensitivity analyses we conducted , and the cost-effectiveness was estimated to be US$ 183 . Conclusions We found a significant shift in prescribing of antihypertensive drugs towards the use of thiazides in our trial . A major reason to promote the use of thiazides is their lower price compared to other drugs . The cost of the intervention was more than twice the savings within the time frame of our study . However , we predict modest savings over a 2-y period OBJECTIVE Computerized medical decision support tools have been shown to improve the quality of care and have been cited by the Institute of Medicine as one method to reduce pharmaceutical errors . We evaluated the impact of an antiinfective decision support tool in a pediatric intensive care unit ( PICU ) . METHODS We enhanced an existing adult antiinfective management tool by adding and changing medical logic to make it appropriate for pediatric patients . Process and outcomes measures were monitored prospect ively during a 6-month control and a 6-month intervention period . M and atory use of the decision support tool was initiated for all antiinfective orders in a 26-bed PICU during the intervention period . Clinician opinions of the decision support tool were surveyed via question naire . RESULTS The rate of pharmacy interventions for erroneous drug doses declined by 59 % . The rate of anti-infective subtherapeutic patient days decreased by 36 % , and the rate of excessive-dose days declined by 28 % . The number of orders placed per antiinfective course decreased 11.5 % , and the robust estimate of the antiinfective costs per patient decreased 9 % . The type of anti-infectives ordered and the number of antiinfective doses per patient remained similar , as did the rates of adverse drug events and antibiotic-bacterial susceptibility mismatches . The surveyed clinicians reported that use of the program improved their antiinfective agent choices as well as their awareness of impairments in renal function and reduced the likelihood of adverse drug events . CONCLUSIONS Use of the pediatric antiinfective decision support tool in a PICU was considered beneficial to patient care by the clinicians and reduced the rates of erroneous drug orders , improved therapeutic dosage targets , and was associated with a decreased robust estimate of antiinfective costs per patient . antiinfective agents , decision support systems , drug therapy , medication errors , child , infant OBJECTIVE Many hospitals utilize antimicrobial management teams ( AMTs ) to improve patient care . However , most function with minimal computer support . We evaluated the effectiveness and cost-effectiveness of a computerized clinical decision support system for the management of antimicrobial utilization . DESIGN A r and omized controlled trial in adult in patients between May 10 and August 3 , 2004 . Antimicrobial utilization was managed by an existing AMT using the system in the intervention arm and without the system in the control arm . The system was developed to alert the AMT of potentially inadequate antimicrobial therapy . MEASUREMENTS Outcomes assessed were hospital antimicrobial expenditures , mortality , length of hospitalization , and time spent managing antimicrobial utilization . RESULTS The AMT intervened on 359 ( 16 % ) of 2,237 patients in the intervention arm and 180 ( 8 % ) of 2,270 in the control arm , while spending approximately one hour less each day on the intervention arm . Hospital antimicrobial expenditures were $ 285,812 in the intervention arm and $ 370,006 in the control arm , for a savings of $ 84,194 ( 23 % ) , or $ 37.64 per patient . No significant difference was observed in mortality ( 3.26 % vs. 2.95 % , p = 0.55 ) or length of hospitalization ( 3.84 vs. 3.99 days , p = 0.38 ) . CONCLUSION Use of the system facilitated the management of antimicrobial utilization by allowing the AMT to intervene on more patients receiving inadequate antimicrobial therapy and to achieve substantial time and cost savings for the hospital . This is the first study that demonstrates in a patient-r and omized controlled trial that computerized clinical decision support systems can improve existing antimicrobial management programs BACKGROUND The Institute of Medicine has urged the adoption of electronic prescribing systems in all health-care organizations by 2010 . Accordingly , computerized physician order entry ( CPOE ) warrants detailed evaluation . Mixed results have been reported about the benefit of this system . No review of its application in surgical patients has been reported to date . We present the implementation of CPOE in the management of surgical patients within an academic multispecialty practice . STUDY DESIGN Retrospective and prospect i ve analyses of patient-safety measures were done pre- and post-CPOE institution , respectively . Other metrics evaluated included medication errors , order-implementation times , efficiencies , personnel requirements , and physician time . Sampling of time span for the order placement process was assessed with direct hidden observation of the provider . RESULTS A total of 15 ( 0.22 % ) medication errors were discovered in 6,815 surgical procedures performed during the 6 months before CPOE use . After implementation , 10 medication errors were found ( 5,963 surgical procedures [ 0.16 % ] ) in the initial 6 months and 13 ( 0.21 % ) in the second 6 months ( 6,106 surgical procedures ) ( p = NS ) . Mean total time from placement of order to nurse receipt before implementation was 41.2 minutes per order ( 2.05 minutes finding chart , 0.72 minutes writing order , 38.4 minutes for unit secretary transcription ) compared with 27 seconds per order using CPOE ( p < 0.01 ) . Four additional informational technology specialists were temporarily required for assistance in implementing CPOE . After CPOE adoption , 11 of 56 ( 19.6 % ) ancillary personnel positions were eliminated related to order-entry efficiencies . CONCLUSIONS Present CPOE technology can allow major efficiency gains , but refinements will be required for improvements in patient safety OBJECTIVE To assess the effects on health care re source utilization of a network of microcomputer workstations for writing all inpatient orders . DESIGN R and omized controlled clinical trial . SETTING Inpatient internal medicine service of an urban public hospital . SUBJECTS A total of 5219 internal medicine patients and the 68 teams of house officers , medical students , and faculty internists who cared for them . INTERVENTION Microcomputer workstations , linked to a comprehensive electronic medical record system , for writing all inpatient orders . MAIN OUTCOME MEASURES Total inpatient charges for each admission and charges for specific categories of orders . A time-motion study of selected interns assessed the ordering system 's time consumption . RESULTS Intervention teams generated charges that were $ 887 ( 12.7 % ) lower per admission than did control teams ( P = .02 ) . Significant reductions ( P < .05 ) were demonstrated separately for bed charges , diagnostic test charges , and drug charges . Reductions of similar proportion and statistical significance were found for hospital costs . The mean length of stay was 0.89 day shorter for intervention resident teams ( P = .11 ) . Interns in the intervention group spent an average of 33 minutes longer ( 5.5 minutes per patient ) during a 10-hour observation period writing orders than did interns in the control group ( P < .0001 ) . CONCLUSIONS A network of microcomputer workstations for writing all inpatient orders significantly lowered patient charges and hospital costs . This would amount to savings of more than $ 3 million in charges annually for this hospital 's medicine service and potentially tens of billions of dollars nationwide . However , the system required more physician time than did the paper charts . Research at other sites and system advances to reduce time requirements are warranted BACKGROUND Physicians frequently need to start antibiotic therapy before the results of bacterial cultures and antibiotic susceptibility tests are available . We developed and evaluated a computerized antibiotic consultant to assist physicians in the selection of appropriate empiric antibiotics . METHODS We used a two-stage r and om- selection study to compare antibiotics suggested by the antibiotic consultant with 482 associated antibiotic susceptibility results and the concurrent antibiotics ordered by physicians . The antibiotics ordered by r and omized physicians were then compared between crossover periods of antibiotic consultant use . RESULTS The antibiotic consultant suggested an antibiotic regimen to which all isolated pathogens were shown to be susceptible for 453 ( 94 % ) of 482 culture results , while physicians ordered an antibiotic regimen to which all isolated pathogens were susceptible for 369 culture results ( 77 % ) ( P < .001 ) . The physicians who prescribed antibiotics to which all pathogens were susceptible did so a mean of 21 hours after the culture specimens were collected . Physicians ordered appropriate antibiotics within 12 hours of the culture collection significantly more often when they had use of the antibiotic consultant than during the period before use ( P < .035 ) . Moreover , 88 % of the physicians stated they would recommend the program to other physicians , 85 % said the program improved their antibiotic selection , and 81 % said they felt use of the program improved patient care . CONCLUSIONS Information from computer-based medical records can be used to help improve physicians ' selection of empiric antibiotics for infections ABSTRACT Studies have shown benefits to patients from improved interventions involving antimicrobial therapy . The purpose of the present study was to evaluate prospect ively the impact of improved interventions by ( i ) the use of TheraTrac 2 , a computer software program which electronically links susceptibility testing results immediately to the pharmacy and alerts pharmacists of potential interventions , and ( ii ) the education of pharmacists involving microbiologic topics . The study group had the new intervention program . The control group had interventions performed the way that they had previously been done by manually review ing hard copies of susceptibility testing data . In a 5-month period , all in patients whose last names began with A to K were the study group ; in patients whose last names began with L to Z were controls . Three analyses were done ; one analysis ( analysis A ) involved only patients with interventions , one analysis ( analysis B ) involved all patients for whom antimicrobial testing was done and who were matched for diagnosis-related groups ( DRGs ) , regardless of whether an intervention occurred , and one analysis ( analysis C ) involved these DRG-matched patients by using severity-adjusted data . In analysis A , the study group had a 4.8 % decreased rate of mortality , an average of a 16.5-day decreased length of stay per patient , and $ 20,886 decreased variable direct costs per patient . None of these differences was statistically significant . In analysis B , the study patients had a 1.2 % higher mortality rate ( P = 0.741 ) , an average of a 2.7-day decreased length of stay per patient ( P = 0.035 ) , and $ 2,626 decreased variable direct costs per patient ( P = 0.008 ) . In analysis C , the study patients had a 1.4 % lower mortality rate , a 1.2-day decreased length of stay per patient , and $ 1,466 decreased variable direct costs per patient . In conclusion , the institution of this program caused substantial cost savings OBJECTIVE Although computerized physician order entry ( CPOE ) may decrease errors and improve quality , hospital adoption has been slow . The high costs and limited data on financial benefits of CPOE systems are a major barrier to adoption . The authors assessed the costs and financial benefits of the CPOE system at Brigham and Women 's Hospital over ten years . DESIGN Cost and benefit estimates of a hospital CPOE system at Brigham and Women 's Hospital ( BWH ) , a 720-adult bed , tertiary care , academic hospital in Boston . MEASUREMENTS Institutional experts provided data about the costs of the CPOE system . Benefits were determined from published studies of the BWH CPOE system , interviews with hospital experts , and relevant internal documents . Net overall savings to the institution and operating budget savings were determined . All data are presented as value figures represented in 2002 dollars . RESULTS Between 1993 and 2002 , the BWH spent $ 11.8 million to develop , implement , and operate CPOE . Over ten years , the system saved BWH $ 28.5 million for cumulative net savings of $ 16.7 million and net operating budget savings of $ 9.5 million given the institutional 80 % prospect i ve reimbursement rate . The CPOE system elements that result ed in the greatest cumulative savings were renal dosing guidance , nursing time utilization , specific drug guidance , and adverse drug event prevention . The CPOE system at BWH has result ed in substantial savings , including operating budget savings , to the institution over ten years . CONCLUSION Other hospitals may be able to save money and improve patient safety by investing in CPOE systems BACKGROUND Appropriate antibiotic treatment decreases mortality , while superfluous treatment is associated with antibiotic resistance . We built a computerized decision support system for antibiotic treatment ( TREAT ) targeting these outcomes . METHODS Prospect i ve cohort study comparing TREAT 's advice to physician 's treatment followed by a cluster r and omized trial comparing wards using TREAT ( intervention ) versus antibiotic monitoring without TREAT ( control ) . We included patients suspected of harbouring bacterial infections in three hospitals ( Israel , Germany and Italy ) . The primary outcome , appropriate antibiotic treatment , was assessed among patients with microbiologically documented infections ( MDI ) . Length of hospital stay , adverse events , mortality ( interventional trial ) and antibiotic costs ( both studies ) , including costs related to future antibiotic resistance , were compared among all included patients . RESULTS Among 1203 patients included in the cohort study ( 350 with MDI ) , TREAT prescribed appropriate empirical antibiotic treatment significantly more frequently than physicians ( 70 % versus 57 % , P < 0.001 ) using less broad-spectrum antibiotics at half physicians ' antibiotic costs . The r and omized trial included 2326 patients , 570 with MDI . The rate of appropriate empirical antibiotic treatment was higher in intervention versus control wards [ 73 % versus 64 % , odds ratio ( OR ) : 1.48 , 95 % confidence interval ( CI ) : 0.95 - 2.29 , intention to treat , adjusted for location and clustering ] . For patients treated according to TREAT 's advice in intervention wards , the difference with controls was highly significant ( OR : 3.40 , 95 % CI : 2.25 - 5.14 ) . Length of hospital stay , costs related to future resistance and total antibiotic costs were lower in intervention versus control wards . CONCLUSIONS TREAT improved the rate of appropriate empirical antibiotic treatment while reducing antibiotic costs and the use of broad-spectrum antibiotic treatment We analyze the effect of a decision support tool design ed to help physicians detect and correct medical " missteps " . The data comes from a r and omized trial of the technology on a population of commercial HMO patients . The key findings are that the new information technology lowers average charges by 6 % relative to the control group . This reduction in re source utilization was the result of reduced in-patient charges ( and associated professional charges ) for the most costly patients . The rate at which identified issues were resolved was generally higher in the study group than in the control group , suggesting the possibility of improvements in care quality along measured dimensions and enhanced diffusion of new protocol s based on new clinical evidence OBJECTIVE Evaluation of the safety and potential cost savings of a computerized , laboratory-based program to manage inpatient warfarin thromboprophylaxis after major joint arthroplasty . DESIGN A consecutive-case study of adults . SETTING A tertiary care orthopedic institution . PATIENTS Patients requiring joint arthroplasty who had no recent episodes of thromboembolic disease , no mechanical heart valve , atrial fibrillation , severe liver disease or baseline international normalized ratio [ INR ] greater than 1.3 admitted over a 54-month period ( July 1994-December 1998 ) . All patients received a st and ard regimen of warfarin beginning on the evening after the operation . Four hundred and thirty r and omly selected patients managed by the program were followed up by telephone survey 3 months after discharge . Patients exhibiting erratic responses to warfarin were withdrawn from the program and managed individually thereafter . INTERVENTION Major joint arthroplasty with warfarin therapy administered through the computerized program . MAIN OUTCOME MEASURES Test results maintained within the desired therapeutic range ( INR 2.0 - 3.0 ) , clinical ly severe bleeding episodes , readmission rates , clinical ly symptomatic and venographically proven episodes of venous thrombosis or pulmonary embolism . RESULTS Over the study period 5629 patients underwent joint arthroplasty ; 5,372 patients were considered for the program ; 332 patients were ineligible and were managed individually ; 311 entered patients did not complete the program . This left 4,729 patients who completed the program . In 2932 ( 62 % ) patients test results were maintained in the desired therapeutic range . The major bleeding rate was less than 0.5 % , the readmission rate was 3.8 % , the deep venous thrombosis rate was 3.7 % and the pulmonary embolism rate was 0.2 % with no thromboembolic related deaths in the small sample cohort . CONCLUSIONS The majority of patients requiring warfarin thromboprophylaxis can be safely and effectively managed by this laboratory-based computerized program while in hospital . Significant potential cost savings in nursing time could be achieved OBJECTIVE To assess the effect of three computerized reminder systems on compliance with tetanus vaccination . DESIGN Prospect i ve r and omized controlled trial . SETTING Ottawa Civic Hospital Family Medicine Centre . PARTICIPANTS Of 8069 patients 20 years of age or more who were not in a hospital or institution 5589 were r and omly assigned , by family , to a control group , a physician reminder group , a telephone reminder group or a letter reminder group . The remaining 2480 patients were not included in the r and omized portion of the study but were monitored . Results are presented for the 5242 r and omized patients and the 2369 nonr and omized patients for whom there was no up-to- date record of tetanus vaccination at the start of the trial . INTERVENTIONS For the patients in the physician reminder group the physician was reminded at an office visit to assess the patient 's tetanus vaccination status and to recommend vaccination ; those in the other two reminder groups received a telephone call or letter enquiring about their tetanus vaccination status and recommending a booster dose . MAIN OUTCOME MEASURE Proportion of patients who received tetanus toxoid during the study year or who had a cl aim of vaccination in the previous 10 years . MAIN RESULTS The rate of recorded tetanus vaccination in the r and omized control group was 3.2 % . The difference between that rate and those for the three reminder groups was 19.6 % in the physician reminder group ( 95 % confidence interval [ CI ] 17.1 % to 22.2 % , p less than 0.00001 ) , 20.8 % in the telephone reminder group ( 95 % CI 18.3 % to 23.5 % , p less than 0.00001 ) and 27.4 % in the letter reminder group ( 95 % CI 24.8 % to 30.2 % , p less than 0.00001 ) ) . The letter reminders were more effective than either the telephone reminders ( p = 0.00013 ) or the physician reminders ( p less than 0.00001 ) in improving compliance . The cost to the practice per additional vaccination recorded was 43 for the physician reminders , $ 5.43 for the telephone reminders and $ 6.05 for the letter reminders . CONCLUSIONS Although all three reminder systems increased the rate of recorded tetanus vaccination they fell far short of achieving complete population coverage . More intensive interventions would be required to approach that goal . However , such interventions do not appear to be justified given the rarity of tetanus OBJECTIVE To demonstrate the potential effect of deploying a sentinel system that scans administrative cl aims information and clinical data to detect and mitigate errors in care and deviations from best medical practice s. METHODS Members ( n = 39 462 ; age range , 12 - 64 years ) of a midwestern managed care plan were r and omly assigned to an intervention or a control group . The sentinel system was programmed with more than 1000 decision rules that were capable of generating clinical recommendations . Clinical recommendations triggered for subjects in the intervention group were relayed to treating physicians , and those for the control group were deferred to study end . RESULTS Nine hundred eight clinical recommendations were issued to the intervention group . Among those in both groups who triggered recommendations , there were 19 % fewer hospital admissions in the intervention group compared with the control group ( P < .001 ) . Charges among those whose recommendations were communicated were dollar 77.91 per member per month ( pmpm ) lower and paid cl aims were dollar 68.08 pmpm lower than among controls compared with the baseline values ( P = .003 for both ) . Paid cl aims for the entire intervention group ( with or without recommendations ) were dollar 8.07 pmpm lower than those for the entire control group . In contrast , the intervention cost dollar 1.00 pmpm , suggesting an 8-fold return on investment . CONCLUSION Ongoing use of a sentinel system to prompt clinical ly actionable , patient-specific alerts generated from administratively derived clinical data was associated with a reduction in hospitalization , medical costs , and morbidity BACKGROUND AND OBJECTIVE To assess the cost-effectiveness of an intervention based on the Global INitiative for Asthma ( GINA ) recommendations as compared to usual care . SUBJECTS AND METHOD Pragmatic , cluster-r and omised trial . Ten pneumologists and 10 general practitioners were r and omised to an intervention or control group , recruiting 98 and 100 asthma patients , respectively . The intervention consisted of an education program and a clinical decision support system ( CDSS ) providing recommendations based on the GINA . The control group was characterized by usual care . Effectiveness was assessed by the health related quality of life as measured by the St. George 's Respiratory Question naire ( SGRQ ) . Costs were computed from the re source consumption recorded during a 12 months follow-up period , and the cost-effectiveness of the intervention was investigated in an incremental analysis . RESULTS The intervention effect on the SGRQ total score was estimated as a 6.8 point reduction ( 95 % confidence interval , 2.5 - 11.1 ; p = 0.0021 ) , and a significant improvement in the SGRQ subscores and in the symptoms-free periods were also observed . From the social perspective , the mean total costs showed savings of -1,022 Euros ( 95 % confidence interval , -2,165 to 122 ; p = 0.0795 ) in intervention group as compared to usual care . The incremental analysis confirmed that the intervention was cost-effective . CONCLUSIONS The implementation of an asthma management program based in GINA recommendations improved the patient 's health related quality of life and was cost-effective as compared to usual care BACKGROUND : Electronic information systems have been proposed as one means to reduce medical errors of commission ( doing the wrong thing ) and omission ( not providing indicated care ) . OBJECTIVE : To assess the effects of computer-based cardiac care suggestions . DESIGN : A r and omized , controlled trial targeting primary care physicians and pharmacists . SUBJECTS : A total of 706 out patients with heart failure and /or ischemic heart disease . INTERVENTIONS : Evidence -based cardiac care suggestions , approved by a panel of local cardiologists and general internists , were displayed to physicians and pharmacists as they cared for enrolled patients . MEASUREMENTS : Adherence with the care suggestions , generic and condition-specific quality of life , acute exacerbations of their cardiac disease , medication compliance , health care costs , satisfaction with care , and physicians ’ attitudes toward guidelines . RESULTS : Subjects were followed for 1 year during which they made 3,419 primary care visits and were eligible for 2,609 separate cardiac care suggestions . The intervention had no effect on physicians ’ adherence to the care suggestions ( 23 % for intervention patients vs 22 % for controls ) . There were no intervention-control differences in quality of life , medication compliance , health care utilization , costs , or satisfaction with care . Physicians viewed guidelines as providing helpful information but constraining their practice and not helpful in making decisions for individual patients . CONCLUSIONS : Care suggestions generated by a sophisticated electronic medical record system failed to improve adherence to accepted practice guidelines or outcomes for patients with heart disease . Future studies must weigh the benefits and costs of different ( and perhaps more Draconian ) methods of affecting clinician behavior OBJECTIVE Translation of evidence -based guidelines into clinical practice has been inconsistent . We performed a r and omized , controlled trial of guideline -based care suggestions delivered to physicians when writing orders on computer workstations . STUDY SETTING Inner-city academic general internal medicine practice . STUDY DESIGN R and omized , controlled trial of 246 physicians ( 25 percent faculty general internists , 75 percent internal medicine residents ) and 20 outpatient pharmacists . We enrolled 706 of their primary care patients with asthma or chronic obstructive pulmonary disease . Care suggestions concerning drugs and monitoring were delivered to a r and om half of the physicians and pharmacists when writing orders or filling prescriptions using computer workstations . A 2 x 2 factorial r and omization of practice sessions and pharmacists result ed in four groups of patients : physician intervention , pharmacist intervention , both interventions , and controls . DATA EXTRACTION / COLLECTION METHODS : Adherence to the guidelines and clinical activity was assessed using patients ' electronic medical records . Health-related quality of life , medication adherence , and satisfaction with care were assessed using telephone question naires . PRINCIPAL FINDINGS During their year in the study , patients made an average of five scheduled primary care visits . There were no differences between groups in adherence to the care suggestions , generic or condition-specific quality of life , satisfaction with physicians or pharmacists , medication compliance , emergency department visits , or hospitalizations . Physicians receiving the intervention had significantly higher total health care costs . Physician attitudes toward guidelines were mixed . CONCLUSIONS Care suggestions shown to physicians and pharmacists on computer workstations had no effect on the delivery or outcomes of care for patients with reactive airways disease We developed a decision support tool to assist physicians anticipating the need for antibiotic therapy . The initial screen alerts physicians of pertinent patient information , provides direct access to other essential medical information , and stimulates clinical judgment by suggesting an antibiotic regimen . The decision support tool also suggests the dose and interval for any ordered antibiotics selected by the physicians . During a 7-month pilot study , all antibiotics for patients admitted to the Shock/Trauma/Respiratory Intensive Care Unit ( STRICU ) were ordered using the decision support tool . Clinical data from the study period and a 12-month control period ( the previous year ) were collected and compared . The decision support tool was used to order antibiotics 588 times during the study period and the suggested antibiotics were used 218 ( 37 % ) times . The computer suggested dosages were used over 90 % of the time . The mean cost of antibiotics was $ 87.00 ( p < 0.04 ) less per patient during the study period as compared to the control period . Prospect i ve assessment revealed only 3 antibiotic adverse drug events ( ADEs ) ( 0.9 % ) among 336 study patients as compared to 15 ADEs ( 2.4 % ) among 626 control patients ( p = 0.164 ) BACKGROUND AND METHODS Optimal decisions about the use of antibiotics and other antiinfective agents in critically ill patients require access to a large amount of complex information . We have developed a computerized decision-support program linked to computer-based patient records that can assist physicians in the use of antiinfective agents and improve the quality of care . This program presents epidemiologic information , along with detailed recommendations and warnings . The program recommends antiinfective regimens and courses of therapy for particular patients and provides immediate feedback . We prospect ively studied the use of the computerized antiinfectives-management program for one year in a 12-bed intensive care unit . RESULTS During the intervention period , all 545 patients admitted were cared for with the aid of the antiinfectives-management program . Measures of processes and outcomes were compared with those for the 1136 patients admitted to the same unit during the two years before the intervention period . The use of the program led to significant reductions in orders for drugs to which the patients had reported allergies ( 35 , vs. 146 during the preintervention period ; P<0.01 ) , excess drug dosages ( 87 vs. 405 , P<0.01 ) , and antibiotic-susceptibility mismatches ( 12 vs. 206 , P<0.01 ) . There were also marked reductions in the mean number of days of excessive drug dosage ( 2.7 vs. 5.9 , P<0.002 ) and in adverse events caused by antiinfective agents ( 4 vs. 28 , P<0.02 ) . In analyses of patients who received antiinfective agents , those treated during the intervention period who always received the regimens recommended by the computer program ( n=203 ) had significant reductions , as compared with those who did not always receive the recommended regimens ( n= 195 ) and those in the preintervention cohort ( n = 766 ) , in the cost of antiinfective agents ( adjusted mean , $ 102 vs. $ 427 and $ 340 , respectively ; P<0.001 ) , in total hospital costs ( adjusted mean , $ 26,315 vs. $ 44,865 and $ 35,283 ; P<0.001 ) , and in the length of the hospital stay days ( adjusted mean , 10.0 vs. 16.7 and 12.9 ; P<0.001 ) . CONCLUSIONS ; A computerized antiinfectives-management program can improve the quality of patient care and reduce costs |
12,381 | 27,039,304 | The evidence on the effectiveness of using QoL tools was inconsistent for patient management , but somewhat more consistent in favour of improving patient – physician communication .
Interviews identified unharnessed potential and growing interest in QoL tool use and associated challenges to address . | Purpose Patient-reported data are playing an increasing role in health care .
In oncology , data from quality of life ( QoL ) assessment tools may be particularly important for those with limited survival prospect s , where treatments aim to prolong survival while maintaining or improving QoL. This paper examines the use and impact of using QoL measures on health care of cancer patients within a clinical setting , particularly those with brain cancer .
It also examines facilitators and challenges , and provides implication s for policy and practice . | Background : Despite thous and s of papers , the value of quality of life ( QoL ) in curing disease remains uncertain . Until now , we lacked tools for the diagnosis and specific treatment of diseased QoL. We approached this problem stepwise by theory building , modelling , an exploratory trial and now a definitive r and omised controlled trial ( RCT ) in breast cancer , whose results we report here . Methods : In all , 200 representative Bavarian primary breast cancer patients were recruited by five hospitals and treated by 146 care professionals . Patients were r and omised to either ( 1 ) a novel care pathway including diagnosis of ‘ diseased ’ QoL ( any QoL measure below 50 points ) using a QoL profile and expert report sent to the patient 's coordinating practitioner , who arranged QoL therapy consisting of up to five st and ardised treatments for specific QoL defects or ( 2 ) st and ard postoperative care adhering to the German national guideline for breast cancer . The primary end point was the proportion of patients in each group with diseased QoL 6 months after surgery . Patients were blinded to their allocated group . Results : At 0 and 3 months after surgery , diseased QoL was diagnosed in 70 % of patients . The QoL pathway reduced rates of diseased QoL to 56 % at 6 months , especially in emotion and coping , compared with 71 % in controls ( P=0.048 ) . Relative risk reduction was 21 % ( 95 % confidence interval ( CI ) : 0–37 ) , absolute risk reduction 15 % ( 95 % CI : 0.3–29 ) , number needed to treat (NNT)=7 ( 95 % CI : 3–37 ) . When QoL therapy finished after successful treatment , diseased QoL often returned again , indicating good responsiveness of the QoL pathway . Conclusion : A three-component outcome system including clinician-derived objective , patient-reported subjective end points and qualitative analysis of clinical relevance was developed in the last 10 years for cancer as a complex intervention . A separate QoL pathway was implemented for the diagnosis and treatment of diseased QoL and its effectiveness tested in a community-based , pragmatic , definitive RCT . While the pathway was active , it was effective with an NNT of 7 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 PURPOSE Radiation Therapy Oncology Group trial 0525 tested whether dose-intensifying temozolomide versus st and ard chemoradiotherapy improves overall survival ( OS ) or progression-free survival ( PFS ) in newly diagnosed glioblastoma . Tests of neurocognitive function ( NCF ) and symptoms ( using the MD And erson Symptom Inventory-Brain Tumor module ; MDASI-BT ) and of quality of life ( European Organisation for the Research and Treatment of Cancer Quality of Life Question naire [ EORTC QLQ ] -C30/BN20 ) examined the net clinical benefit ( NCB ) of therapy . PATIENTS AND METHODS NCF tests ( Hopkins Verbal Learning Test-Revised , Trail Making Test , and Controlled Oral Word Association ) , MDASI-BT , and EORTC QLQ-C30/BN20 were completed in a subset of patients . Multivariate Cox proportional hazard regression modeling determined the prognostic value of baseline and early change from baseline to cycle 1 for OS and PFS . Two- sample proportional test statistic was used to evaluate differences between treatments ( dose-dense v st and ard-dose ) on NCB measures from baseline to cycle 4 in stable patients . RESULTS Overall , 182 patients participated in the study . Baseline NCF tests and the physical functioning quality of life scale were associated with OS and PFS . Baseline to cycle 1 in all NCB components were associated with OS and PFS . There was greater deterioration in the dose-dense arm from baseline to cycle 4 in the Global Health and Motor Function subscales ( EORTC QLQ-C30/BN20 ) as well as in overall symptom burden , overall symptom interference , and activity-related symptom interference subscales ( MDASI-BT ) . There were no between-arm differences in NCF . CONCLUSION Longitudinal collection of NCB measures is feasible in cooperative group studies and provides an added dimension to st and ard outcome measures . Greater adverse symptom burden and functional interference , as well as decreased global health and motor function were observed in patients r and omly assigned to the dose-dense arm . Baseline and early change in NCB measures were associated with decreased rates of survival PURPOSE Although patient-reported cancer symptoms and quality -of-life issues ( SQLIs ) have been promoted as essential to a comprehensive assessment , efficient and efficacious methods have not been widely tested in clinical setting s. The purpose of this trial was to determine the effect of the Electronic Self-Report Assessment -Cancer ( ESRA-C ) on the likelihood of SQLIs discussed between clinicians and patients with cancer in ambulatory clinic visits . Secondary objectives included comparison of visit duration between groups and usefulness of the ESRA-C as reported by clinicians . PATIENTS AND METHODS This r and omized controlled trial was conducted in 660 patients with various cancer diagnoses and stages at two institutions of a comprehensive cancer center . Patient-reported SQLIs were automatically displayed on a graphical summary and provided to the clinical team before an on-treatment visit ( n = 327 ) ; in the control group , no summary was provided ( n = 333 ) . SQLIs were scored for level of severity or distress . One on-treatment clinic visit was audio recorded for each participant and then scored for discussion of each SQLI . We hypothesized that problematic SQLIs would be discussed more often when the intervention was delivered to the clinicians . RESULTS The likelihood of SQLIs being discussed differed by r and omized group and depended on whether an SQLI was first reported as problematic ( P = .032 ) . Clinic visits were similar with regard to duration between groups , and clinicians reported the summary as useful . CONCLUSION The ESRA-C is the first electronic self-report application to increase discussion of SQLIs in a US r and omized clinical trial This is one of the few studies that have explored the value of baseline symptoms and health-related quality of life ( HRQOL ) in predicting survival in brain cancer patients . Baseline HRQOL scores ( from the EORTC QLQ-C30 and the Brain Cancer Module ( BN 20 ) ) were examined in 490 newly diagnosed glioblastoma cancer patients for the relationship with overall survival by using Cox proportional hazards regression models . Refined techniques as the bootstrap re-sampling procedure and the computation of C-indexes and R2-coefficients were used to try and vali date the model . Classical analysis controlled for major clinical prognostic factors selected cognitive functioning ( P=0.0001 ) , global health status ( P=0.0055 ) and social functioning ( P<0.0001 ) as statistically significant prognostic factors of survival . However , several issues question the validity of these findings . C-indexes and R2-coefficients , which are measures of the predictive ability of the models , did not exhibit major improvements when adding selected or all HRQOL scores to clinical factors . While classical techniques lead to positive results , more refined analyses suggest that baseline HRQOL scores add relatively little to clinical factors to predict survival . These results may have implication s for future use of HRQOL as a prognostic factor in cancer patients PURPOSE This study aim ed to determine whether feeding back patient-reported outcomes ( PROs ) to providers and families of children with advanced cancer improves symptom distress and health-related quality of life ( HRQoL ) . PATIENTS AND METHODS This study was a parallel , multicentered pilot r and omized controlled trial . At most once per week , children age ≥ 2 years old with advanced cancer or their parent completed the computer-based Pediatric Quality of Life and Evaluation of Symptoms Technology ( PediQUEST ) survey consisting of age- and respondent-adapted versions of the Memorial Symptom Assessment Scale ( MSAS ) , Pediatric Quality of Life Inventory 4.0 Generic Core Scales ( PedsQL4.0 ) , and an overall Sickness question . In the intervention group ( n = 51 ) , oncologists and families received printed reports summarizing PROs ; e-mails were sent to oncologists and subspecialists when predetermined scores were exceeded . No feedback was provided in the control group ( n = 53 ) . Primary outcomes included linear trends of MSAS , PedsQL4.0 total and subscale scores , and Sickness scores during 20 weeks of follow-up , along with child , parent , and provider satisfaction with PediQUEST feedback . RESULTS Feedback did not significantly affect average MSAS , PedsQL4.0 , or Sickness score trends . Post hoc subgroup analyses among children age ≥ 8 years who survived 20 weeks showed that feedback improved PedsQL4.0 emotional ( + 8.1 ; 95 % CI , 1.8 to 14.4 ) and Sickness ( -8.2 ; 95 % CI , -14.2 to -2.2 ) scores . PediQUEST reports were valued by children , parents , and providers and contributed at least sometimes to physician initiation of a psychosocial consult ( 56 % ) . CONCLUSION Although routine feedback of PROs did not significantly affect the child 's symptoms or HRQoL , changes were in expected directions and improvements observed in emotional HRQoL through exploratory analyses were encouraging . Importantly , children , parents , and providers value PRO feedback The potential benefits of health-related quality of life ( HRQL ) assessment in oncology clinical practice include better detection of problems , enhanced disease and treatment monitoring and improved care . However , few empirical studies have investigated the effects of incorporating such assessment s into routine clinical care . Recent r and omized studies have reported improved detection of and communication about patients ' concerns , but few have found effects on patient HRQL or satisfaction . This study examined whether offering interpretive assistance of HRQL results would improve these patient outcomes . Two hundred and thirteen participants with metastatic breast , lung or colorectal cancer were r and omly assigned to one of three conditions : usual care ; HRQL assessment or HRQL assessment followed by a structured interview and discussion . Interviews about patients ' assessment responses were conducted by a research nurse , who then presented HRQL information to the treating nurse . HRQL and treatment satisfaction outcomes were assessed at 3 and 6 months . No significant differences were found between study conditions in HRQL or satisfaction . Results suggest that routine HRQL assessment , even with description of results , is insufficient to improve patient HRQL and satisfaction . It is suggested that positive effects may require supplementing assessment results with specific suggestions for clinical management changes It is well recognized that oncologists should consider patients ' quality of life and functioning when planning and delivering anticancer treatment , but a comprehensive assessment of how a patient feels requires a thorough inquiry . A st and ardized measurement of patients ' quality of life may support clinicians in identifying important problems for discussion during the limited time of the medical consultations . The aim of this study was to assess the feasibility of computer-administered individual quality of life measurements in oncology clinics with immediate feedback of results to clinicians and to examine the impact of the information on consultations . The study employed a prospect i ve non-r and omized design with pre-test post-test within subjects comparisons and involved three medical oncologists and 28 cancer patients receiving chemotherapy . The intervention consisted of completion of quality of life question naires before the consultations and informing clinicians of the results . The main outcome measures were patients ' perceptions of the content of baseline and intervention consultations and satisfaction with communication . A qualitative analysis of clinicians ' interviews was performed . When clinicians had the quality of life results they enquired more often about daily activities ( Z=−2.71 , P=0.007 ) , emotional problems ( Z=−2.11 , P=0.035 ) and work related issues ( Z=−1.89 , P=0.058 ) . There was an increase in the number of issues discussed during the intervention consultation ( Z=−1.89 , P=0.059 ) . Patients were highly satisfied with both consultations . The computer measurement was well accepted by patients who felt that the question naires were a useful tool to tell the doctors about their problems . The clinicians perceived that the quality of life data broadened the range of the clinical inquiry and helped them identify issues for discussion . Having symptoms and functional problems expressed quantitatively on a scale was useful for detection of change over time Purpose The aims of this study were to investigate the impact of individual health-related quality of life ( HRQL ) evaluation on the attention towards symptom control and psychosocial function in advanced cancer patients . Methods Patients with advanced lung cancer or mesothelioma who attended a pulmonary oncology outpatient clinic were r and omized to either of two strategies for HRQL assessment . The experimental group ( EG ) answered the EORTC QLQ-C30 + LC13 question naire using a digital table interface , with outprint of aggregated scale scores presented to the consulting physician as a support for evaluation . The control group ( CG ) answered a paper version of the same question naire , which was stored for later analysis . Consultations were audio-recorded . Outcome measures were a quantitative content analysis of audio-recorded consultations and medical and psychosocial interventions abstract ed from clinical records . Results One hundred seventy-one patients were r and omized and participated in the study . Issues regarding emotional function were more frequently discussed during consultations in the EG ( p < 0.05 ) . Similarly , interventions directed to emotional and social concerns were more frequent in the EG ( p = 0.013 and p = 0.0036 , respectively ) . HRQL measures over time were similar across the groups . Conclusion Individual HRQL assessment increased the attention to psychosocial functioning in patients with chest malignancies PURPOSE Regularly collecting patient-reported outcomes ( PROs ) of health-related quality of life with feedback to oncologists may assist in eliciting and monitoring patients ' problems during cancer treatment . This study examined how PRO feedback had an impact on patient-physician communication over time to gain a better underst and ing of how it may influence patient care . PATIENTS AND METHODS Exploratory analyses were performed on a data set from a previous study . Patients were r and omly assigned to intervention ( regular completion of European Organisation for Research and Treatment of Cancer Quality of Life Question naire-Core 30 and Hospital Anxiety and Depression Scale with feedback to oncologists ) , attention-control ( completion of same question naires without feedback ) , and control ( st and ard care ) arms . The content of consultation audio recordings between 28 oncologists and 198 patients over four consecutive visits ( 792 consultations ) was analyzed . Mixed-effects models and multivariate regressions were used to examine the longitudinal impact of the intervention on patient-physician communication , dynamics of patient-physician interaction , and the association between PROs and the content of clinic discussion . RESULTS Patients in the intervention arm discussed more symptoms over time compared with patients in the attention-control ( P = .008 ) and control ( P = .04 ) arms . No study arm effect was observed for function discussion s. Discussion topics were predominantly raised by patients /relatives , regardless of arm allocation . Clinic discussion s were associated with severity of patient-reported symptoms but not with patient-reported functional concerns . CONCLUSION A positive longitudinal impact of the intervention on symptom discussion was observed , but not for function discussion , suggesting that potentially serious problems may remain unaddressed . Training oncologists in responding to patient-reported functional concerns may increase the impact of this intervention Background : The health-related quality of life ( HRQOL ) measures serve as valuable indicators of survival in patients with newly diagnosed primary brain tumors ( PBTs ) . HRQOL outcomes may benefit clinical decision-making by individualizing patient treatment and improving communications between the doctor , patient , and families . Exploring the individual items of the European Organization and Research and Treatment of Cancer Quality of Life Question naire ( EORTC QOL ) measures may be predictive of prognosis . Methods : We prospect ively collected the vali date d HRQOL and st and ard clinical and radiological measures from 48 patients with newly diagnosed PBT . The patients were followed every 3 months over 2 years . No proxies were allowed . Question naire responses were compared between two groups : Patients with recurrence and /or death ( n = 26 ) and patients without a recurrence ( n = 22 ) . A total of 17 patients succumbed to a tumor-related death . Statistical analysis utilizing nonparametric t-tests and Wilcoxon sign tests assessed QOL responses . Results : Significant group differences were noted in the QOL measures with more negative responses in the recurrence group . EORTC QLQ-C30 questions revealed a poor global HRQOL scale ( P < 0.005 ) and pain interfering with daily activities ( P < 0.05 ) . EORTC QLQ-BN20 questions revealed weakness of the legs ( P < 0.05 ) , coordination difficulties ( P < 0.005 ) , and unsteady gait ( P < 0.05 ) . Hospital Anxiety and Depression Scale ( HADS ) questions reflected a patient who is slowed down ( P < 0.01 ) and “ frightened ” ( P < 0.05 ) . Conclusion : Our analysis of longitudinal HRQOL measures may shed light on the prognostic significance of HRQOL measures in patients with newly diagnosed PBT . Further research is warranted to determine which selected individual measures of the EORTC QOL measures may be predictive of a patient 's progression-free and overall survival and to test their validity and reliability in clinical trials Purpose We conducted a secondary qualitative analysis of consultations between oncologists and their patients to explore how patient-reported outcome measures ( PROMs ) data were referred to in the process of ( 1 ) eliciting and exploring patients ’ concerns ; ( 2 ) making decisions about supportive treatment and ( 3 ) making decisions about chemotherapy and other systemic treatments . Methods We purposively sample d audio recordings of 18 consultations from the intervention arm and 4 from the attention control arm of a previous UK r and omised controlled trial of the feedback of PROMs data to doctors ( Velikova et al. in J Clin Oncol 22(4):714–724 [ 1 ] ) . We used a combination of content and conversation analysis to examine how opportunities for discussion of health-related quality of life issues are opened up or closed down within the consultation and explore why this may or may not lead to changes in patient management . Findings Explicit reference to the PROMs data provided an opportunity for the patient to clarify and further elaborate on the side effects of chemotherapy . High scores on the PROMs data were not explored further if the patient indicated they were not a problem or were not related to the cancer or chemotherapy . Symptomatic treatment was more often offered for problems like nausea , constipation , pain and depression but much less so for fatigue . Doctors discussed fatigue by providing a cause for the fatigue ( e.g. the chemotherapy ) , presenting this as ‘ something to be expected ’ , minimising its impact or moving on to another topic . Chemotherapy regimens were not changed on the basis of the PROMs data alone , but PROMs data were sometimes used to legitimise changes . Conclusions Explicit mention of PROMs data in the consultation may strengthen opportunities for patients to elaborate on their problems , but doctors may not always know how to do this . Our findings have informed the development of a training package to enable doctors to optimise their use of PROMs data within the consultation BACKGROUND A r and omised controlled trial of radiotherapy alone versus radiotherapy with concomitant and adjuvant temozolomide for patients with glioblastoma showed that survival was higher for patients assigned combination treatment compared with those assigned st and ard radiotherapy alone . This paper reports the health-related quality of life ( HRQOL ) of the patients in this trial . METHODS 573 patients with newly diagnosed glioblastoma were r and omly allocated either radiotherapy alone or radiotherapy and temozolomide . The primary endpoint was survival , and HRQOL was a secondary endpoint . We assessed HRQOL at baseline and at every 3 months during treatment until progression using the European Organisation for Research and Treatment of Cancer ( EORTC ) quality of life question naire core-30 ( QLQ-C30 ) and the EORTC brain cancer module ( EORTC BN-20 ) . We calculated changes from baseline score for seven predefined HRQOL measures ( fatigue , overall health , social function , emotional function , future uncertainty , insomnia , and communication deficit ) and differences between groups for these measures at every time point . The significance of , and proportions of patients with , improved HRQOL scores -- defined as a change of 10 points or more -- were recorded . This trial is registered on the US National Cancer Institute website http://www.cancer.gov/ search /New Clinical Trials , NCT00006353 . FINDINGS Baseline question naires were available for 490 ( 86 % ) patients . Baseline HRQOL scores did not differ between groups . At first follow-up , groups differed only in social functioning , favouring the radiotherapy-only group ( mean score 79.0 [ SD 3.2 ] for patients assigned radiotherapy vs 67.4 [ 2.7 ] for those assigned radiotherapy and temozolomide ; difference between groups 11.6 points [ 95 % CI 3.5 - 19.7 ] , p=0.0052 ) . Over subsequent assessment s , HRQOL was much the same between treatment groups . INTERPRETATION Addition of temozolomide during and after radiotherapy for patients with newly diagnosed glioblastoma significantly improved survival without a negative effect on HRQOL 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 PURPOSE Little is known about the health-related quality of life ( HRQOL ) of patients treated for anaplastic oligodendrogliomas . The impact of combined procarbazine , CCNU ( lomustine ) , and vincristine ( PCV ) chemotherapy after radiotherapy ( RT ) compared with RT alone on HRQOL in the r and omized European Organisation for Research and Treatment of Cancer ( EORTC ) 26951 trial was studied . PATIENTS AND METHODS Adult patients with anaplastic oligodendrogliomas received RT alone or RT plus PCV chemotherapy . HRQOL was assessed with the EORTC Quality of Life Question naire C30 and Brain Cancer Module . Seven prespecified HRQOL end points were selected . We hypothesized that chemotherapy would impair HRQOL during treatment but that there would be a similar HRQOL between treatment arms once off treatment . Assessment s were performed at r and omization , at the end of RT , and then every 3 to 6 months until progression . RESULTS A total of 368 patients were r and omly assigned to one of the two arms ; overall , 58 % were male , and the median age was 49 years . Compliance with HRQOL was 78 % at baseline and dropped to 55 % to 72 % up to 2.5 years post-RT . Baseline scores demonstrated considerable impairments in HRQOL for both treatment groups . The longitudinal analysis showed a significant increase in nausea/vomiting in the RT plus PCV chemotherapy arm during and shortly after chemotherapy . Because of a difference in baseline scores for fatigue and physical functioning , the differences between treatment arms during PCV did not reach significance . The nonselected scales of appetite loss and drowsiness demonstrated significant differences between treatment arms during chemotherapy in favor of the RT arm . The long-term results showed no difference between arms . CONCLUSION The major impact of PCV on HRQOL is on nausea/vomiting , loss of appetite , and drowsiness during and shortly after treatment . There are no long-term effects of PCV chemotherapy INTRODUCTION AND AIM In a r and omised trial investigating the effects of regular use of health-related quality of life ( HRQOL ) in oncology practice , we previously reported an improvement in communication ( objective analysis of recorded encounters ) and patient well-being . The secondary aims of the trial were to measure any impact on patient satisfaction and patients ' perspectives on continuity and coordination of their care . METHODS In a prospect i ve trial involving 28 oncologists , 286 cancer patients were r and omised to : ( 1 ) intervention arm : regular touch-screen completion of HRQOL with feedback to physicians ; ( 2 ) attention-control arm : completion of HRQOL without feedback ; and ( 3 ) control arm : no HRQOL assessment . Secondary outcomes were patients ' experience of continuity of care ( Medical Care Question naire , MCQ ) including ' Communication ' , ' Coordination ' and ' Preferences to see usual doctor ' subscales , patients ' satisfaction , and patients ' and physicians ' evaluation of the intervention . Analysis employed mixed-effects modelling , multiple regression and descriptive statistics . RESULTS Patients in the intervention arm rated their continuity of care as better than the control group for ' Communication ' subscale ( p=0.03 ) . No significant effects were found for ' Coordination ' or ' Preferences to see usual doctor ' . Patients ' evaluation of the intervention was positive . More patients in the intervention group rated the HRQOL assessment as useful compared to the attention-control group ( 86 % versus 29 % ) , and reported their doctors considered daily activities , emotions and quality of life . CONCLUSION Regular use of HRQOL measures in oncology practice brought changes to doctor-patient communication of sufficient magnitude and importance to be reported by patients . HRQOL data may improve care through facilitating rapport and building inter-personal relationships 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 PatientViewpoint website collects patient-reported outcomes and links them with the electronic health record to aid patient management . This pilot test evaluated PatientViewpoint 's use , usefulness , and acceptability to patients and clinicians . METHODS This was a single-arm prospect i ve study that enrolled breast and prostate cancer patients undergoing treatment and the clinicians who managed them . Patients completed patient-reported outcomes every 2 weeks , and clinicians could access the results for patient visits . Scores that were poor relative to norms or substantially worse than the previous assessment were highlighted . After three on- study visits , we assessed patient and clinician perspectives on PatientViewpoint using close-ended and open-ended questions . RESULTS Eleven out of 12 eligible clinicians ( 92 % ) and 52/76 eligible patients ( 68 % ) enrolled . Patients completed a median of 71 % of assigned question naires ; clinicians reported using the information for 79 % of patients , most commonly as a source of additional information ( 51 % ) . At the median , score reports identified three potential issues , of which 1 was discussed during the visit . Patients reported the system was easy to use ( 92 % ) , useful ( 70 % ) , aided recall of symptoms/side effects ( 72 % ) , helped them feel more in control of their care ( 60 % ) , improved discussion s with their provider ( 49 % ) , and improved care quality ( 39 % ) . Patients and clinicians desired more information on score interpretation and minor adjustments to site navigation . CONCLUSIONS These results support the feasibility and value of PatientViewpoint . An ongoing study is using a continuous quality improvement approach to further refine PatientViewpoint . Future studies will evaluate its impact on patient care and outcomes PURPOSE To examine the effects on process of care and patient well-being , of the regular collection and use of health-related quality -of-life ( HRQL ) data in oncology practice . PATIENTS AND METHODS In a prospect i ve study with repeated measures involving 28 oncologists , 286 cancer patients were r and omly assigned to either the intervention group ( regular completion of European Organization for Research and Treatment of Cancer-Core Quality of Life Question naire version 3.0 , and Hospital Anxiety and Depression Scale on touch-screen computers in clinic and feedback of results to physicians ) ; attention-control group ( completion of question naires , but no feedback ) ; or control group ( no HRQL measurement in clinic before encounters ) . Primary outcomes were patient HRQL over time , measured by the Functional Assessment of Cancer Therapy-General question naire , physician-patient communication , and clinical management , measured by content analysis of tape-recorded encounters . Analysis employed mixed-effects modeling and multiple regression . RESULTS Patients in the intervention and attention-control groups had better HRQL than the control group ( P = .006 and P = .01 , respectively ) , but the intervention and attention-control groups were not significantly different ( P = .80 ) . A positive effect on emotional well-being was associated with feedback of data ( P = .008 ) , but not with instrument completion ( P = .12 ) . A larger proportion of intervention patients showed clinical ly meaningful improvement in HRQL . More frequent discussion of chronic nonspecific symptoms ( P = .03 ) was found in the intervention group , without prolonging encounters . There was no detectable effect on patient management ( P = .60 ) . In the intervention patients , HRQL improvement was associated with explicit use of HRQL data ( P = .016 ) , discussion of pain , and role function ( P = .046 ) . CONCLUSION Routine assessment of cancer patients ' HRQL had an impact on physician-patient communication and result ed in benefits for some patients , who had better HRQL and emotional functioning The current study evaluated the efficacy of incorporating st and ardized health‐related quality of life ( HRQL ) assessment s as a routine part of the outpatient chemotherapy treatment of cancer patients in a community hospital in terms of : 1 ) facilitating nurse‐patient communication , 2 ) increasing nurses ' awareness of patients ' HRQL , 3 ) patient management , 4 ) patients ' satisfaction , and 5 ) patients ' HRQL CONTEXT There has been increasing interest in the use of health-related quality -of-life ( HRQL ) assessment s in daily clinical practice , yet few empirical studies have been conducted to evaluate the usefulness of such assessment s. OBJECTIVE To evaluate the efficacy of st and ardized HRQL assessment s in facilitating patient-physician communication and increasing physicians ' awareness of their patients ' HRQL-related problems . DESIGN Prospect i ve , r and omized crossover trial . SETTING Outpatient clinic of a cancer hospital in the Netherl and s. PARTICIPANTS Ten physicians and 214 patients ( 76 % women ; mean age , 57 years ) undergoing palliative chemotherapy who were invited to participate between June 1996 and June 1998 . INTERVENTION At 3 successive outpatient visits , patients completed an HRQL question naire ( European Organization for Research and Treatment of Cancer Quality of Life Question naire-Core 30 ) . The responses were computer scored and transformed into a graphic summary . Physicians and patients received a copy of the summary before the consultation . MAIN OUTCOME MEASURES Audiotapes of the consultations were content analyzed to evaluate patient-physician communication . Physicians ' awareness of their patients ' health problems was assessed by comparing physicians ' and patients ' ratings on the Dartmouth Primary Care Cooperative Information Functional Health Assessment ( COOP ) and the World Organisation Project of National Colleges and Academics ( WONCA ) charts . RESULTS The HRQL-related issues were discussed significantly more frequently in the intervention than in the control group ( mean [ SD ] communication composite scores : 4.5 [ 2.3 ] vs 3.7 [ 1.9 ] , respectively ( P = .01 ) . Physicians in the intervention group identified a greater percentage of patients with moderate-to-severe health problems in several HRQL domains than did those in the control group . All physicians and 87 % of the patients believed that the intervention facilitated communication and expressed interest in its continued use . CONCLUSION Incorporating st and ardized HRQL assessment s in daily clinical oncology practice facilitates the discussion of HRQL issues and can heighten physicians ' awareness of their patients ' HRQL The purpose of this paper was to determine if providing patient specific Quality of Life ( QL ) information to clinic staff before a clinic appointment improved patient care in a lung cancer outpatient clinic . Patients were sequentially assigned to either a usual care control group or the experimental group , which completed a computerized version of the European Organization for Research and Treatment of Cancer ( EORTC ) QLQ-C30 question naire in order to provide the clinic staff with QL information prior to the clinic appointment . The control group completed the EORTC QLQ-C30 paper version after the clinic appointment . Outcome measures were patient satisfaction , the degree to which issues identified on the QL question naire were addressed in the appointment , and a chart audit , which measured charting of QL issues and actions taken by the clincian relating to QL . In the experimental group , more QL issues identified by the patient on the EORTC QLQ-C30 were addressed during the clinic appointment than in the control group . As well , marginally more categories were charted and a trend towards more actions being taken was seen in the experimental group . Patients reported being equally and highly satisfied with the treatment in both groups . The clinical implication is that the computerized administration of the EORTC QLQ-C30 question naire and providing staff with a report highlighting patient-specific QL deficits is a simple , time-effective and acceptable means of improving patient-provider communication in a busy outpatient clinic . Large trials study ing its effectiveness in different patient population s and regions would further eluci date the nature of this effect and potentially improve the overall quality of care that patients receive |
12,382 | 23,608,713 | In conclusion , this meta- analysis suggests that K-RAS mutations are associated with a worse overall survival in patients with NSCLC , especially in patients with adenocarcinoma and early stage | K-RAS gene mutations have been found in 20 - 30 % of non-small cell lung cancer and occur most commonly in adenocarcinoma , however , there was no definitive conclusion about the prognostic role of K-RAS mutations in NSCLC .
Herein we performed a systematic review of the literature s with meta- analysis to assess K-RAS mutations ' prognostic value in NSCLC . | BACKGROUND Somatic mutations in EGFR and K-RAS may predict for sensitivity and resistance to EGFR tyrosine kinase inhibitors ( TKIs ) . Whether EGFR and K-RAS mutations could also predict clinical outcome of non-small cell lung cancer ( NSCLC ) patients following front-line chemotherapy has not yet been established . PATIENTS AND METHODS One hundred and sixty-two chemotherapy-naïve patients with locally advanced/metastatic NSCLC who received front-line chemotherapy were included in this retrospective study and their clinical outcome data was analyzed according to EGFR and K-RAS mutation status of their tumors . RESULTS Classical activating EGFR and K-RAS mutations were found in 8.2 and 22.6 % of patients respectively and were not associated with patients ' clinicopathological characteristics . Patients with classical EGFR mutations had a higher probability of response to front-line chemotherapy as compared to those with wild type EGFR ( p=0.023 ) . Multivariate analysis showed that the presence of activating EGFR mutations was an independent factor associated with response to front-line chemotherapy ( HR=4.85 ; 95 % CI : 1.13 - 20.83 , p=0.034 ) . K-RAS mutation status was not associated with response to front-line chemotherapy . The presence of activating EGFR but not of K-RAS mutations was associated with a significantly higher overall survival compared to patients without mutations treated with platinum-based front-line chemotherapy ( p=0.043 ) . CONCLUSIONS The data indicate that EGFR mutation status could be predictive for response to cytotoxic front-line chemotherapy in patients with NSCLC . Additional prospect i ve studies are needed in order to vali date this observation and to define whether these patients should be preferentially treated with front-line TKIs or chemotherapy PURPOSE The phase III , r and omized , placebo-controlled Sequential Tarceva in Unresectable NSCLC ( SATURN ; BO18192 ) study found that erlotinib maintenance therapy extended progression-free survival ( PFS ) and overall survival in patients with advanced non-small-cell lung cancer ( NSCLC ) who had nonprogressive disease following first-line platinum-doublet chemotherapy . This study included prospect i ve analysis of the prognostic and predictive value of several biomarkers . PATIENTS AND METHODS M and atory diagnostic tumor specimens were collected before initiating first-line chemotherapy and were tested for epidermal growth factor receptor ( EGFR ) protein expression by using immunohistochemistry ( IHC ) , EGFR gene copy number by using fluorescent in situ hybridization ( FISH ) , and EGFR and KRAS mutations by using DNA sequencing . An EGFR CA simple sequence repeat in intron 1 ( CA-SSR1 ) polymorphism was evaluated in blood . RESULTS All 889 r and omly assigned patients provided tumor sample s. EGFR IHC , EGFR FISH , KRAS mutation , and EGFR CA-SSR1 repeat length status were not predictive for erlotinib efficacy . A profound predictive effect on PFS of erlotinib relative to placebo was observed in the EGFR mutation-positive subgroup ( hazard ratio [ HR ] , 0.10 ; P < .001 ) . Significant PFS benefits were also observed with erlotinib in the wild-type EGFR subgroup ( HR , 0.78 ; P = .0185 ) . KRAS mutation status was a significant negative prognostic factor for PFS . CONCLUSION This large prospect i ve biomarker study found that patients with activating EGFR mutations derive the greatest PFS benefit from erlotinib maintenance therapy . No other biomarkers were predictive for outcomes with erlotinib , although the study was not powered for clinical outcomes in biomarker subgroups other than EGFR IHC-positive [ corrected ] . KRAS mutations were prognostic for reduced PFS . The study demonstrated the feasibility of prospect i ve tissue collection for biomarker analyses in NSCLC BACKGROUND Because there is no clear consensus as to the predictive value of K-ras gene mutation for survival in patients with lung cancer , we examined the occurrence of K-ras mutations in a large , prospect i ve case series of non-small-cell lung cancer ( NSCLC ) . Our goals were to define the patient characteristics associated with K-ras mutation and to determine whether mutation of this gene might be a biomarker of patient prognosis . METHODS Consecutive , newly diagnosed patients with lung cancer treated with potentially curative resection over a 4-year period were recruited for study . The mutation status of K-ras codon 12 in each patient 's tumor DNA was determined by means of polymerase chain reaction-restriction fragment length polymorphism analysis of archived pathology specimens . Analyses were restricted to adenocarcinoma . RESULTS There was a statistically significant association between female sex and K-ras mutation after adjustment for carcinogen exposures ( odds ratio = 3.3 ; 95 % confidence interval [ CI ] = 1.3 - 7.9 ) ; mutations were found only in smokers . Comparison of Kaplan-Meier curves indicated a strong association between K-ras mutation and decreased patient survival ( two-sided P = .009 ) ; analysis stratified by pathologic staging groups revealed that this association was statistically significant only for stage I tumors ( two-sided P = .002 ) . Cox proportional hazards modeling indicated that K-ras codon 12 mutation was a statistically significant predictor of patient survival , after adjustment for the effects of age , sex , and stage ( risk ratio = 1.8 ; 95 % CI = 1.1 - 3.1 ) . CONCLUSIONS After adjustment for environmental exposures , non-small-cell lung tumors in women appear to be more likely than those in men to harbor K-ras mutations , suggesting a possible role of estrogen exposure in either the initiation or the selection of K-ras mutant clones in adenocarcinoma . In addition , our data suggest that K-ras codon 12 mutation is a marker of aggressive NSCLC , as evidence d by its association with decreased patient survival , particularly for early-stage disease Background . The main attention regarding prognostic and predictive markers in NSCLC directs towards the EGFR-targeted pathway , where the most studied genetic alterations include EGFR mutations , EGFR copy number , and KRAS mutations . We wanted to explore the prognostic impact of mutated KRAS in the stage III setting treated with high-dose radiochemotherapy . Methods . Sample s were obtained from patients participating in two prospect i ve studies of locally advanced NSCLC receiving combined radiochemotherapy : the RAKET study , a r and omized phase II study where patients were treated with induction chemotherapy ( carboplatin/paclitaxel ) followed by concurrent radiochemotherapy , and the Satellite trial , a phase II study with induction chemotherapy ( cisplatin/docetaxel ) followed by radiotherapy concurrent cetuximab . The sample s were analysed regarding KRAS mutations , EGFR mutations , and EGFR FISH positivity . Results . Patients with mutated KRAS had a significantly inferior survival , which maintained its significance in a multivariate analysis when other possible prognostic factors were taken into account . The prevalence of KRAS mutations , EGFR mutations , and EGFR FISH positivity were 28.8 % , 7.5 % , and 19.7 % , respectively . Conclusion . Mutated KRAS is an independent negative prognostic factor for survival in NSCLC stage III disease treated with combined radiochemotherapy . The prevalence of KRAS mutations and EGFR mutations are as expected in this Sc and inavian population Introduction : Relationships between clinical outcomes and epidermal growth factor receptor (EGFR)-related tumor markers were investigated in patients with advanced non-small cell lung cancer . Methods : Patients with stage IIIB/IV non-small cell lung cancer ( 0–2 prior regimens ) received erlotinib ( 150 mg PO per day ) . Response and survival were evaluated , and tumor sample s were assessed by immunohistochemistry ( EGFR , phosphorylated mitogen-activated protein kinase , and phosphorylated AKT protein expression ) , fluorescence in situ hybridization ( FISH ; EGFR gene copy number ) , and DNA sequencing ( EGFR , KRAS gene mutations ) . Results : Among 311 patients , 8 % had a complete/partial response ; the disease control rate was 66 % . Median Overall survival ( OS ) was 6.1 months ; 1-year survival rate was 27.2 % . Two of 4 patients with EGFR mutations had tumor responses , versus 2/68 with wild-type EGFR ( p = 0.014 ) . Progression-free survival ( PFS ) ( HR = 0.31 ) and OS ( HR = 0.33 ) were significantly prolonged in patients with EGFR mutations . Response rate was significantly higher in patients with EGFR FISH-positive ( 17 % ) than FISH-negative tumors ( 6 % ) , and both PFS ( HR = 0.58 ) and OS ( HR = 0.63 ) significantly favored patients with EGFR FISH-positive tumors ; median OS was 8.6 months in the EGFR FISH-positive group . None of 17 patients with a KRAS mutation had a tumor response , but the impact of KRAS mutation status on survival outcomes was of borderline statistical significance . Neither phosphorylated mitogen-activated protein kinase nor phosphorylated AKT immunohistochemistry status had a significant effect on PFS and OS with erlotinib . Conclusions : The presence of EGFR mutations and EGFR FISH-positive tumors may predispose patients to achieving better outcomes on erlotinib , but may have a beneficial impact on prognosis ( irrespective of treatment ) . Prospect i ve , placebo-controlled studies are needed to determine the predictive value of the putative biomarkers A prospect i ve study was performed in patients with non-small cell lung cancer ( NSCLC ) to evaluate the prognostic importance of multiple molecular marker ( p53 , c-Ki-ras , c-erbB-2 ) testing . 103 patients with potentially curative resections ( RO resection ) for NSCLC in histopathological stages I – IIIA were included . SSCP analysis and DNA sequencing for p53 and c-Ki-ras genes were performed on paired tumour and normal lung tissue sample s and immunohistochemistry ( c-erbB-2 ) was done on frozen tissue sections with a specific anti-c-erbB-2 monoclonal antibody . 46/103 ( 44.6 % ) NSCLC showed p53 mutations and 17/103 ( 16.5 % ) c-Ki-ras mutations including 12/37 ( 32.4 % ) adenocarcinomas . Overexpression of c-erbB-2 ( p185 ) was detected in 56/103 ( 54.4 % ) tumours . 24/103 ( 23.3 % ) NSCLC were negative for alterations in all 3 parameters ( c-Ki-ras , p53 and p185 ) whereas 79/103 ( 76.7 % ) were positive for at least one of the 3 parameters . In a regression model including a multiple molecular marker parameter ( negative for all 3 markers versus positive for at least one marker ) , histopathological stage ( P < 0.00001 ) , respectively the pT ( P < 0.01 ) and pN ( P < 0.00001 ) categories and the multiple molecular marker parameter ( P < 0.01 ) were of significant prognostic importance . This study demonstrates that testing 3 molecular markers ( c-Ki-ras , p53 and c-erbB-2 ) improves estimation of prognosis compared to single marker testing and appears to define low ( 82.6 % ± 7.9 % 5-year survival ) and high risk ( 40.2 % ± 5.5 % 5-year survival ) groups for treatment failure in potentially curative ( RO ) resected NSCLC . © 2000 Cancer Research Introduction : Although mutation of the epidermal growth factor receptor ( EGFR ) gene is predictive for the response to EGFR-tyrosine kinase inhibitor , its prognostic impact for patients without EGFR-tyrosine kinase inhibitor treatment remains controversial . We examined for EGFR , KRAS or TP53 mutations in a consecutive large cohort of patients with lung adenocarcinoma , and evaluated their prognostic impact . Methods : We analyzed 397 patients with lung adenocarcinoma who underwent potentially curative pulmonary resection . Total ribonucleic acid was extracted and direct sequencing of each gene was performed after reverse transcription-polymerase chain reaction . Results : We found that 196 patients ( 49 % ) had EGFR mutations . Of these , 83 were exon 19 deletions ( 42 % ) and 92 were L858R ( 47 % ) . Univariate analysis showed that patients with EGFR mutations survived for a longer period than those without mutations ( p = 0.0046 ) . However , there was no difference in overall survival between the patients with exon 19 deletion and those with L858R ( p = 0.4144 ) . Patients with KRAS mutations or TP53 mutations tended to survive for a shorter period ( p = 0.2183 and 0.0230 , respectively ) . Multivariate analysis using the Cox proportional hazards model revealed that smoking status ( p = 0.0310 ) and disease stage ( p < 0.0001 ) were independent prognostic factors . However , none of the gene mutations was independent prognostic factors ( EGFR , p = 0.3225 ; KRAS , p = 0.8500 ; TP53 , p = 0.3191 ) . Conclusions : EGFR , KRAS , and TP53 gene mutations were not independently associated with the prognosis for Japanese patients with surgically treated lung adenocarcinoma Introduction : Serum proteomics and mutations in the epidermal growth factor receptor ( EGFR ) and KRAS have been associated with benefit after therapy with EGFR-targeted therapies in non-small cell lung cancer , but all three have not been evaluated in any one study . Hypothesis : Pretreatment serum proteomics predicts survival in Western advanced non-small cell lung cancer patients with wild-type EGFR and independent of KRAS mutation status . Methods : We analyzed available biospecimens from Eastern Cooperative Oncology Group 3503 , a single-arm phase II study of erlotinib in first-line advanced lung cancer , for proteomics signatures in the previously described serum matrix-assisted laser desorption ionization proteomic classifier ( VeriStrat ) as well as for KRAS and EGFR mutations . Results : Out of 137 enrolled patients , analyzable biologic sample s were available on 102 . Nine of 41 ( 22 % ) demonstrated KRAS mutations and 3 of 41 ( 7 % ) harbored EGFR mutations . VeriStrat classification identified 64 of 88 ( 73 % ) as predicted to have “ good ” and 24 of 88 ( 27 % ) predicted to have “ poor ” outcomes . A statistically significant correlation of VeriStrat status ( p < 0.001 ) was found with survival . EGFR mutations , but not KRAS mutations , also correlated with survival . Conclusions : The previously defined matrix-assisted laser desorption ionization predictor remains a potent and highly clinical ly significant predictor of survival after first-line treatment with erlotinib in patients with wild-type EGFR and independent of mutations in KRAS PURPOSE To determine the prognostic and predictive significance of p53 and K-ras mutations in patients with completely resected non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS Patients were r and omized preoperatively to receive adjuvant postoperative radiotherapy ( Arm A ) or radiotherapy plus concurrent chemotherapy ( Arm B ) . p53 protein expression was studied by immunohistochemistry ( IHC ) and p53 mutations in exons 5 to 8 were evaluated by single-str and conformational analysis . K-ras mutations in codons 12 , 13 , and 61 were determined using engineered restriction fragment length polymorphisms . RESULTS Four hundred eighty-eight patients were entered onto E3590 ; 197 tumors were assessable for analysis . Neither presence nor absence of p53 mutations , p53 protein expression , or K-ras mutations correlated with survival or progression-free survival . There was a trend toward improved survival for patients with wildtype K-ras ( median , 42 months ) compared with survival of patients with mutant K-ras who were r and omized to chemotherapy plus radiotherapy ( median , 25 months ; P = .09 ) . Multivariate analysis revealed only age and tumor stage to be significant prognostic factors , although there was a trend bordering on statistical significance for K-ras ( P = .066 ) . Analysis of survival difference by p53 by single-str and ed conformational polymorphism and IHC , interaction of p53 and K-ras , interaction of p53 and treatment arm , nodal station , extent of surgery , weight loss , and histology did not reach statistical significance . CONCLUSION p53 mutations and protein overexpression are not significant prognostic or predictive factors in resected stage II or IIIA NSCLC . K-ras mutations may be a weak prognostic marker . p53 or K-ras should not be routinely used in the clinical management of these patients Background : EGFR and KRAS mutations are mutually exclusive and predict outcomes with epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitor ( TKI ) treatment in patients with stage IV lung cancers . The clinical significance of these mutations in patients with resected stage I – III lung cancers is unclear . Methods : At our institution , resection specimens from patients with stage I – III lung adenocarcinomas are tested for the presence of EGFR or KRAS mutations during routine pathology analysis such that the results are available before consideration of adjuvant therapy . In a cohort of 1118 patients tested over 8 years , overall survival was analyzed using multivariate analysis to control for potential confounders , including age , sex , stage , and smoking history . The impact of adjuvant erlotinib or gefitinib was examined in an independent data set of patients exclusively with EGFR mutation , in which date of recurrence was recorded . Results : In the overall population , we identified 227 KRAS ( 25 % ) and 222 EGFR ( 20 % ) mutations . Patients with EGFR-mutant lung cancers had a lower risk of death compared with those without EGFR mutations , overall survival ( OS ) HR 0.51 ( 95 % confidence interval [ CI ] : 0.34–0.76 , p < 0.001 ) . Patients with KRAS-mutant lung cancers had similar outcomes compared with individuals with KRAS wild-type tumors , OS HR 1.17 ( 95 % CI : 0.87–1.57 , p = 0.30 ) . A separate data set includes only patients with EGFR-mutant lung cancers identified over 10 years ( n = 286 ) . In patients with resected lung cancers and EGFR mutation , treatment with adjuvant erlotinib or gefitinib was associated with a lower risk of recurrence or death , disease-free survival HR 0.43 ( 95 % CI : 0.26–0.72 , p = 0.001 ) , and a trend toward improved OS . Conclusions : Patients with resected stage I – III lung cancers and EGFR mutation have a lower risk of death compared with patients without EGFR mutation . This may be because of treatment with EGFR TKIs . Patients with , and without KRAS mutation have similar OS . These data support reflex testing of resected lung adenocarcinomas for EGFR mutation to provide prognostic information and identify patients for enrollment on prospect i ve clinical trials of adjuvant EGFR TKIs The observation that the proteins encoded by ras genes play a central role in the signalling pathways used by cells to respond to growth factors and the fact that mutated ras proteins are constantly promoting cell division have led to a PCR-based hunt for additional clinical information . In the present study , K-ras analysis draws the following conclusions : ( 1 ) K-ras point mutation frequency was higher in the surgery group ( 10 of 24 patients ) than in the chemotherapy-surgery group ( 3 of 20 patients ) . ( 2 ) Mutated K-ras was predominantly observed at codon 12 but five mutations appeared at codon 61 . ( 3 ) Mutations were identified in the squamous cell carcinoma histological NSCLC subtype except in four cases corresponding to adenocarcinoma . ( 4 ) A multifarious pattern of substitutions , especially at codon 12 , were noted with aspartic K 12 substitutions more prone to develop bone metastases . ( 5 ) Although a genotypic K-ras classification of NSCLC may not yet be formulated , our accumulated data ( unpublished ) suggest a trend toward it . ( 6 ) Patients with mutated K-ras tumors in the surgery group had no different survival than those with normal K-ras . However our pooled data as well as other authors ' results assert that mutated K-ras constitute an additional prognostic datum that deserves to be included together with TNM classification . In the design of new preoperative ( neoadjuvant ) chemotherapy trials , stratification of tumors by K-ras status deserves to be further investigated in order to correlate with response , relapse and survival . Mutated K-ras genotype merits further research . Finally , the paradigm of uneven histological distribution and mutated K-ras spectra among research ers should serve as a stimulus to search for further contributions in this field Background : Epidermal growth factor and v-Ki-ras2 Kirsten ras sarcoma ( KRAS ) mutation status , although associated with EGFR- tyrosine kinase inhibitor ( TKI ) efficacy , has not been used in clinical practice until recently . The prospect i ve Evaluation of the EGFR Mutation status for the administration of EGFR-TKIs in non small cell lung Carcinoma ( ERMETIC ) study aim ed to implement these biomarkers in France . Methods : Between March 2007 and April 2008 , EGFR and KRAS were studied by sequencing DNA tumor specimens from 522 consecutive advanced non – small-cell lung cancer patients treated with EGFR-TKI , mostly in second- or third-line setting s. Cox models were used to investigate the impact of patient characteristics and mutations on progression-free survival ( PFS ) and overall survival ( OS ) . Added value from mutation status was evaluated using likelihood ratio ( LR ) tests . Classification and regression tree analysis aim ed to identify homogeneous groups in terms of survival . Results : Among the 522 patients , 87 % were white , 32 % were women , and 18 % were never-smokers , with 65 % presenting with adenocarcinoma . Biological data were available for 307 patients , showing 44 EGFR mutations ( 14 % ) and 42 KRAS ( 14 % ) mutations . Median PFS was 2.4 months ( interquartile range , 1.4–4.6 ) and median OS 5.6 months ( interquartile range , 2.2–14.0 ) . Factors independently associated with PFS were performance status 1 or 2 to 3 ( hazards ratio [ HR ] = 1.5 , 95 % confidence interval [ CI ] 1.1–1.9 ; and HR = 2.3 , CI 1.7–3.1 , respectively ; p < 0.001 ) ; former or current smoker status ( HR = 1.8 , CI 1.4–2.4 and 2.0,CI 1.4–2.8 , respectively ; p < 0.001 ) ; nonadenocarcinoma histology ( squamous cell : HR = 0.9 CI 0.7–1.2 ] ; others : HR = 1.6 , 1.3–2.1 ; p < 0.001 ) ; at least two metastatic sites ( HR = 1.3 , CI 1.1–1.6 and 1.6 , CI 1.3–2.1 , respectively ; p < 0.001 ) ; prior taxane-based chemotherapy ( HR = 1.3 , CI 1.0–1.3 , p = 0.01 ) ; non-white ( HR = 0.7 , CI 0.5–0.9 , p = 0.009 ) . Similar results were found for OS . In addition , EGFR and KRAS mutations were significantly associated with PFS ( HR = 0.5 , CI 0.3–0.7 and HR = 1.2 , CI 0.8–1.8 , respectively , versus no mutation ; LR p = 0.001 ) . In the OS model , adjusted HR was 0.7 ( 0.4–1.0 ) for EGFR mutation and 1.7 ( 1.1–2.4 ) for KRAS ( LR p = 0.004 ) . Classification and regression tree analysis revealed EGFR mutation to be the primary factor for identifying homogeneous patient subgroups in terms of PFS . Conclusions : EGFR and KRAS status independently impacts outcomes in advanced non – small-cell lung cancer patients treated with EGFR-TKI . However , EGFR status impacts both PFS and OS whereas KRAS only impacts OS . These findings support the nationwide use of EGFR status for patient selection before EGFR-TKI therapy . The role of KRAS mutations remains to be eluci date Long-term beta blockade for perhaps a year or so following discharge after an MI is now of proven value , and for many such patients mortality reductions of about 25 % can be achieved . No important differences are clearly apparent among the benefits of different beta blockers , although some are more convenient than others ( or have slightly fewer side effects ) , and it appears that those with appreciable intrinsic sympathomimetic activity may confer less benefit . If monitored , the side effects of long-term therapy are not a major problem , as when they occur they are easily reversible by changing the beta blocker or by discontinuation of treatment . By contrast , although very early IV short-term beta blockade can definitely limit infa rct size , more reliable information about the effects of such treatment on mortality will not be available until a large trial ( ISIS ) reports later this year , with data on some thous and s of patients entered within less than 4 hours of the onset of pain . Our aim has been not only to review the 65-odd r and omized beta blocker trials but also to demonstrate that when many r and omized trials have all applied one general approach to treatment , it is often not appropriate to base inference on individual trial results . Although there will usually be important differences from one trial to another ( in eligibility , treatment , end-point assessment , and so on ) , physicians who wish to decide whether to adopt a particular treatment policy should try to make their decision in the light of an overview of all these related r and omized trials and not just a few particular trial results . Although most trials are too small to be individually reliable , this defect of size may be rectified by an overview of many trials , as long as appropriate statistical methods are used . Fortunately , robust statistical methods exist -- based on direct , unweighted summation of one O-E value from each trial -- that are simple for physicians to use and underst and yet provide full statistical sensitivity . These methods allow combination of information from different trials while avoiding the unjustified direct comparison of patients in one trial with patients in another . ( Moreover , they can be extended of such data that there is no real need for the introduction of any more complex statistical methods that might be more difficult for physicians to trust . ) Their robustness , sensitivity , and avoidance of unnecessary complexity make these particular methods an important tool in trial overviews PURPOSE The anti-epidermal growth factor receptor ( EGFR ) antibody cetuximab is efficacious in multiple tumor types . Patient selection with markers predictive of benefit may enhance its therapeutic index . This retrospective , correlative analysis of the phase III trial BMS099 of cetuximab in advanced non-small-cell lung cancer ( NSCLC ) was conducted to identify molecular markers for the selection of patients most likely to benefit from cetuximab . METHODS In BMS099 , 676 chemotherapy-naïve patients with stage IIIB ( pleural effusion ) or stage IV NSCLC of any histology or EGFR expression status were r and omly assigned to taxane/carboplatin ( T/C ) with or without cetuximab . Biomarkers analyzed included K-Ras and EGFR mutations by direct sequencing , EGFR protein expression by immunohistochemistry ( IHC ) , and EGFR gene copy number by fluorescent in situ hybridization ( FISH ) . Relationships between biomarker status and progression-free survival ( PFS ) , overall survival ( OS ) , and overall response rate ( ORR ) were assessed by log-rank tests per treatment arm for treatment-specific effects and across the total evaluable population . Results Tumor sample s were available from 225 r and omly assigned patients . K-Ras mutations were found in 17 % of evaluable patients ( 35 of 202 patients ) , EGFR mutations were found in 10 % ( 17 of 166 patients ) , EGFR positivity by IHC was found in 89 % ( 131 of 148 patients ) , and FISH positivity was found in 52 % ( 54 of 104 patients ) . No significant associations were found between biomarker status and PFS , OS , and ORR in the treatment-specific analyses . CONCLUSION In contrast with colorectal cancer , and within the limitations of the data set , efficacy parameters did not appear to correlate with K-Ras mutation status or with any of the EGFR-related biomarkers evaluated . Additional exploratory analyses are essential to identify predictive markers and to optimize patient selection for cetuximab therapy in NSCLC |
12,383 | 18,171,491 | RESULTS The review revealed evidence to support the effectiveness of weight training exercises to increase BMD in postmenopausal women .
Weighted exercises can help in maintaining BMD in postmenopausal women and increasing BMD of the spine and hip in women with osteopenia and osteoporosis . | PURPOSE Osteoporosis is both preventable and treatable with exercise playing an important role in osteogenesis .
The purpose of this systematic review was to determine which specific exercise programs utilizing weights were effective in maintaining or increasing bone mineral density ( BMD ) in postmenopausal women . | PURPOSE The purpose of this study was to determine the effects of 6 months of whole-body resistive training ( RT ) on total and regional bone mineral density ( BMD ) and bone mineral content ( BMC ) by age and gender in young and older men and women . METHODS Younger men ( n=10 ) and women ( n=7 ) aged 20 - 29 years ( 25+/-1 years ) and older men ( n=10 ) and women ( n=10 ) aged 65 - 74 years ( 69+/-1 years ) participated in 6 months of progressive whole-body RT . Upper- and lower-body strength was assessed by the one repetition maximum ( 1RM ) test , and total body fat , lean tissue mass , femoral neck BMD , Ward 's triangle BMD , greater trochanter BMD , total-body BMD , and L2-L4 spine BMD were determined by dual-energy X-ray absorptiometry before and after 6 months of RT . RESULTS Percent body fat decreased only in the young men ( P<0.05 ) . Lean tissue mass increased after training in young men and women and older men ( P<0.05 ) but did not change significantly in older women . Upper- and lower-body 1RM strength increased in all groups ( P<0.01 ) . Overall , there was a significant increase in BMD at the femoral neck , ward 's triangle and greater trochanter BMD , as well as total body BMC and leg BMC ( P<0.05 ) . Total-body BMD and L2-L4 spine BMD did not change with RT . There were no gender differences in the training response between men and women for any of the BMD regions and no age differences in the training response , except for a trend between young and older subjects for femoral neck ( P<0.08 ) . CONCLUSION A 6-month RT program increases muscle mass and improves BMD of the femoral region in young and healthy older men and women as a group , with a trend for this to be greater in young subjects STUDY OBJECTIVE To assess the effect of weight-bearing exercise training and subsequent detraining on lumbar bone mineral content in postmenopausal women . DESIGN Non-r and omized , controlled , short-term ( 9 months ) trial and long-term ( 22 months ) exercise training and detraining ( 13 months ) . SETTING Section of applied physiology at a university school of medicine . PATIENTS Thirty-five healthy , sedentary postmenopausal women , 55 to 70 years old . All women completed the study . There was 90 % compliance with exercise training . INTERVENTIONS All women were given calcium , 1500 mg daily . The exercise group did weight-bearing exercise ( walking , jogging , stair climbing ) at 70 % to 90 % of maximal oxygen uptake capacity for 50 to 60 min , 3 times weekly . MEASUREMENTS AND MAIN RESULTS Bone mineral content increased 5.2 % ( 95 % confidence interval [ CI ] , 2.0 % to 8.4 % ; P = 0.0037 ) above baseline after short-term training whereas there was no change ( -1.4 % ) in the control group . After 22 months of exercise , bone mineral content was 6.1 % ( 95 % CI , 3.9 % to 8.3 % above baseline ; P = 0.0001 ) in the long-term training group . After 13 months of decreased activity , bone mass was 1.1 % above baseline in the detraining group . CONCLUSIONS Weight-bearing exercise led to significant increases above baseline in bone mineral content which were maintained with continued training in older , postmenopausal women . With reduced weight-bearing exercise , bone mass reverted to baseline levels . Further studies are needed to determine the threshold exercise prescription that will produce significant increases in bone mass Abstract . There is evidence that high intensity resistance training promotes bone maintenance in older women , however , the effect of high intensity free weight training has not been investigated in older men or women . Furthermore , little is known about the chronic effect of weight training on serum insulin growth factor-I ( IGF-I ) in this population . We compared the effects of a moderate intensity seated resistance-training program with a high intensity st and ing free weight exercise program on bone mass and serum levels of IGF-I and IGFBP3 in healthy older men and women . Twenty-eight men ( 54.6 ± 3.2 years ) and 26 nonestrogen-replaced women ( 52.8 ± 3.3 years ) served as their own controls for 12 weeks , then were r and omly assigned to a moderate or high intensity training group and trained three times/week for 24 weeks . Prior to and after the control period and at the end of training , bone mass and body composition were assessed by dual energy X-ray absorptiometry ( DXA ) , muscle strength by isokinetic dynamometry , muscular power by Wingate Anaerobic Power Test , and IGF-I by radioimmunoassay ( RIA ) . A repeated measures analysis of covariance ( ANCOVA ) revealed that high intensity training result ed in a gain in spine BMD in men ( 1.9 % ) , P < 0.05 , but not in women , whereas moderate intensity training produced no changes in either gender at this site . Increases were observed at the greater trochanter , P < 0.03 , in men regardless of training intensity , but not in women at any hip site . However , when compared with zero , both men and women in the high intensity group demonstrated significant increases in trochanteric BMD ( 1.3 % and 2.0 % , respectively ) and a decrease in femoral BMD ( −1.8 % ) . Neither circulating serum IGF-I nor IGFBP3 were altered by either training regimen , but both training programs result ed in improvements in total body strength ( 37.62 % ) and lean mass ( males 4.1 % , females 3.1 % ) . We conclude that although resistance training of moderate to high intensity produced similar muscle changes in older adults , a higher magnitude is necessary to stimulate osteogenesis at the spine . However , at the spine , intensity was not sufficient to offset low levels of estrogen in early postmenopausal women . Furthermore , bone changes were not accompanied by changes in circulating serum levels of IGF-I or IGFBP3 The effects of weighted vest walking and strength-training exercises on bone mineral density ( BMD ) , balance , strength , and self-efficacy were tested in older women . Eighteen women , age 69.2 ± 3.5 years , were r and omly assigned to an exercise group ( EG ) ( n = 9 ) , or a sedentary control group ( CG ) ( n = 9 ) . The EG participated in 32 weeks ( three 1-h sessions/week ) of supervised strength training and walking , stair climbing , and balance exercises while wearing weighted vests . The CG did not exercise . All women took Ca²+ and vitamin D during the study period . Measures included 1 ) BMD of the hip and lumbar spine measured by dual-energy X-ray absorptiometry , 2 ) strength , 3 ) balance , and 4 ) scores on a self-efficacy instrument . The EG had significant improvements in bone density of the femoral neck and balance and a significant weight loss ( P < 0.05 ) . There were no changes in self-efficacy in either group The purpose of this study was to determine the effects of 12 months of weight bearing and resistance exercise on bone mineral density ( BMD ) and bone remodeling ( bone formation and bone resorption ) in 2 groups of postmenopausal women either with or without hormone replacement therapy ( HRT ) . Secondary aims were to characterize the changes in insulin-like growth factors-1 and -2 ( IGF-1 and -2 ) and IGF binding protein 3 ( IGFBP3 ) in response to exercise training . Women who were 3–10 years postmenopausal ( aged 40–65 years ) were included in the study . Women in the HRT and no HRT groups were r and omized into the exercise intervention , result ing in four groups : ( 1 ) women not taking HRT , not exercising ; ( 2 ) those taking HRT , not exercising ; ( 3 ) those exercising , not taking HRT ; and ( 4 ) women exercising , taking HRT . The number of subjects per group after 1 year was 27 , 21 , 25 , and 17 , respectively . HRT increased BMD at most sites whereas the combination of exercise and HRT produced increases in BMD greater than either treatment alone . Exercise training alone result ed in modest site-specific increases in BMD . Bone remodeling was suppressed in the groups taking HRT regardless of exercise status . The bone remodeling response to exercise training in women not taking HRT was not significantly different from those not exercising . However , the direction of change suggests an elevation in bone remodeling in response to exercise training , a phenomenon usually associated with bone loss . No training-induced differences in IGF-1 , IGF-2 , IGF-l : IGF-2 ( IGF-1 : IGF-2 ) , and IGFBP3 were detected This study compared the effects of two exercise training programs , 11 months in duration , on bone mineral density ( BMD ) in older , sedentary women . Thirty-nine women , aged 60 - 74 years , were assigned to the following groups : ( a ) a group that performed exercises that introduced stress to the skeleton through ground-reaction forces ( GRF ) ( i.e. , walking , jogging , stairs ) ; ( b ) a group that performed exercises that introduced stress to the skeleton through joint-reaction forces ( JRF ) ( i.e. , weight lifting , rowing ) ; or ( c ) a no-exercise control group . BMD of the whole body , lumbar spine , proximal femur , and distal forearm was assessed five times at approximately 3-month intervals . The GRF and JRF exercise programs result ed in significant and similar increases in BMD of the whole body ( 2.0 + /- 0.8 % and 1.6 + /- 0.4 % , respectively ) , lumbar spine ( 1.8 + /- 0.7 % and 1.5 + /- 0.5 % , respectively ) , and Ward 's triangle region of the proximal femur ( 6.1 + /- 1.5 % and 5.1 + /- 2.1 % , respectively ) . There was a significant in BMD of the femoral neck only in response to the GRF exercise program ( GRF , 3.5 + /- 0.8 % ; JRF , -0.2 + /- 0.7 % ) . There were no significant changes in BMD in control subjects . Among all exercisers , there was a significant inverse ( r = -0.52 , p < 0.01 ) relationship between increases in whole body BMD and reductions in fat mass , suggesting a dose response effect of exercise on bone mass . Although femoral neck BMD was responsive only to the GRF exercise program , some adaptations ( i.e. , increase in lean body mass and strength ) that were specific to the JRF exercise program may be important in preventing osteoporotic fractures by reducing the risk for falls . It remains to be determined whether all of these benefits can be gained through a training program that combines the different types of exercises employed in this study PURPOSE The purpose of this study was to compare the effects of a high-load ( 80 % , 1-repetition maximum ( RM ) , 8 reps ) and a high-repetition ( 40 % , 1-RM , 16 reps ) resistance training protocol on muscular strength and bone mineral density ( BMD ) in early postmenopausal , estrogen-deficient women . The 6-month programs were matched initially for training volume ( 3 sets , 3 d x wk(-1 ) ) for 12 exercises selected to specifically load the spine and hip . METHODS Subjects included 25 women ( 41 - 60 yr ) who were matched by spine BMD then r and omly assigned to either the high-load ( HL , N = 10 ) , high-repetition ( HR , N = 7 ) , or control ( C , N = 8) groups . Dietary calcium intakes were supplemented to approximately 1500 mg x d(-1 ) . Total body , spine , and hip BMD ( DXA , Lunar Model DPX-IQ ) , upper and lower body muscular strength , and biochemical markers of bone turnover were measured at baseline and after 6 months of training . RESULTS There were no group differences in the baseline measures . Both training groups showed similar increases in biceps ( 20 % ) and rectus femoris ( 28 - 33 % ) cross-sectional areas , in lower body strength ( approximately 30 % ) and in hip strength ( 37 - 40 % ) . HL showed greater improvements in upper body strength ( HL 25 % , HR 16 % ) . Neither training group experienced significant increases in spine or hip BMD , although the HL total body BMD tended to decrease ( -1.1%+/-0.4 , P = 0.054 ) after training . Osteocalcin tended to increase ( P = 0.08 ) in all groups after training , and the % change in osteocalcin was positively related to % changes in the total hip ( r = 0.41 , P = 0.048 ) and the trochanter ( r = 0.42 , P = 0.04 ) BMD . CONCLUSION The high-load and high-repetition resistance training protocol s were both effective in improving muscular strength and size in postmenopausal women , indicating low-intensity resistance training can be beneficial for the muscular fitness in women for whom high-intensity exercise is contraindicated Osteoporosis is a bone disease associated with reduced bone mineral density result ing in debilitating bone fractures . According to the National Institutes of Health Women 's Health Initiative , effective interventions for bone loss need to be developed . The osteogenic stimulus provided by weight-bearing exercise indicates it is an important lifestyle factor that can be used for prevention of bone loss . Prospect i ve research studies have documented that both aerobic exercise and weight training can be effective in the maintenance and building of bone mineral density in postmenopausal women . Additional benefits of weight training include increased muscular strength , coordination , and balance which could decrease risk for falling and subsequent fractures Abstract . Osteoporosis is one of the most common skeletal disorders affecting postmenopausal women . The purpose of this study was to investigate whether a 24-week program of aerobic high-impact loading exercise was beneficial for enhancing physical fitness and bone mineral density ( BMD ) in osteopenic postmenopausal women . Forty-three postmenopausal women aged 48–65 years participated in this study . The BMD of the spine ( L2–L4 ) and right femoral neck of each woman was below 1 SD of the mean of premenopausal women , as examined by dual X-ray absorptiometry . The assignment of subjects into exercise or control group was not r and omized but based on each subject 's anticipated compliance to the 6-month long exercise program . Twenty-two subjects joined the exercise group and attended the training programs and 21 served as the control group . Exercise programs included treadmill walking at an intensity above 70 % of maximal oxygen consumption ( VO2max ) for 30 minutes , followed by 10 minutes of stepping exercise using a 20-cm-high bench . The program was conducted three times per week for 24 weeks . Physical fitness measurements included testing of flexibility , muscular strength and endurance , body composition , and cardiopulmonary fitness . The results showed that the quadriceps strength , muscular endurance , and VO2max in the exercise group had significant improvements , whereas no improvement was found in any of the physical fitness parameters in the control group . The BMD of the L2–L4 and the femoral neck in the exercise group increased 2.0 % ( P > 0.05 ) and 6.8 % ( P < 0.05 ) and those in the control group decreased 2.3 % ( P < 0.05 ) and 1.5 % ( P > 0.05 ) , respectively . In conclusion , aerobics combined with high-impact exercise at a moderate intensity was effective in off setting the decline in BMD in osteopenic postmenopausal women The effects of brief daily exercise on bone mineral density ( BMD ) were assessed in a r and omized controlled trial in 44 healthy postmenopausal women using weight-bearing exercise in a regimen adapted from osteogenic protocol s reported in animal studies . BMD was assessed masked using dual energy X-ray absorptiometry at 0 , 6 , and 12 months . The sites assessed were the proximal femur ( neck , Ward 's triangle , and trochanter ) and the lateral spine ( L2 - 3 ) to assess the effects of the exercise , and the radius ( ultradistal and 33 % distal ) as a marker for systemic effects . The test group was required to perform 50 " heel drops " daily at home ( raising the body weight onto the toes and then letting it drop to the floor keeping the knees and hips extended ) and to attend a weekly class of mixed exercises , which included some high-impact activity . The control group also attended a weekly exercise class run by the same teacher , which included only low-impact activity , and did flexibility exercises at home daily . The ground reaction forces ( as a ratio of body weight ) during heel drops were 2.5 to 3.0 N/N , with a rate of rise of 50 - 100 kN/sec . A patient with an instrumented femoral implant allowed comparison of compressive axial forces in the shaft of the proximal femur with the ground reaction forces , and these appeared to be transmitted undamped to the shaft of the femur . Initial analysis of BMD in the women showed no significant increases after 12 months of exercise at any site in either group , and the groups did not differ significantly from each other in this respect . Proximity to menopause was not associated with rapid bone loss , and in those who were more than 6 years postmenopausal , there was evidence for a maintenance effect of the exercise in the test group . Compliance ( 83 % ) and increases in leg extensor power ( 15 % ) were similar in both groups , and when they were combined , BMD was maintained at the trochanter but fell significantly at the radius ( p < 0.001 ) Physical exercise is often recommended as a therapeutic tool to combat pre- and postmenopausal loss of bone density . However , the relationship between training dosage ( intensity , duration , frequency ) and the effect on bone density still is undergoing discussion . Furthermore , the exercise quantification programs are often described so inadequately that they are neither quantitatively nor qualitatively reproducible . The aim of this investigation was to determine whether a clearly defined training of muscle strength , under defined safety aspects , performed only twice weekly , can counteract bone density loss in women with postmenopausal osteopenia . Data from 16 women in the training group ( age , 63.6 + /- 6.2 yr ) and 15 women in the control group ( age , 67.4 + /-9.7 yr ) , of comparable height and weight , were evaluated . Strength training was performed for 6 mo as continually adapted strength training , providing an intensity of about 70 % of each test person 's one repetition maximum . Bone mineral density of lumbar vertebrae 2 to 4 and the femoral neck was measured by dual-energy x-ray absorptiometry . Maximum performance in watts and parameters of hemodynamics were controlled with a bicycle ergometer test to maximal effort . In addition , metabolic data were assessed . In the lumbar spine and femoral neck , the training group showed no significant changes , whereas the control group demonstrated a significant loss of bone mineral density , especially in the femoral neck ( P<0.05 ) . The strength increase was highly significant in all exercised muscle groups , rising to about 70 % above the pretraining status ( P<0.001 ) . Heart rate and blood pressure data indicated a slight economization , metabolism was not significantly influenced . Based on these findings , we conclude that continually adapted strength training is an effective , safe , reproducible , and adaptable method of therapeutic strength training , following only two exercise sessions per week The effects of a vertical jumping exercise regime on bone mineral density ( BMD ) have been assessed using r and omized controlled trials in both pre- and postmenopausal women , the latter stratified for hormone replacement therapy ( HRT ) . Women were screened for contraindications or medication likely to influence bone . The premenopausal women were at least 12 months postpartum and not lactating ; the postmenopausal women had been stable on , or off , HRT for the previous 12 months and throughout the study . BMD was measured blind using dual-energy X-ray absorptiometry at the spine ( L2-L4 ) and the proximal femur . The exercise consisted of 50 vertical jumps on 6 days/week of mean height 8.5 cm , which produced mean ground reactions of 3.0 times body weight in the young women and 4.0 times in the older women . In the premenopausal women , the exercise result ed in a significant increase of 2.8 % in femoral BMD after 5 months ( p < 0.001 , n = 31 ) . This change was significantly greater ( p < 0.05 ) than that found in the control group ( n = 26 ) . In the postmenopausal women , there was no significant difference between the exercise and control groups after 12 months ( total n = 123 ) nor after 18 months ( total n = 38 ) . HRT status did not affect this outcome , at least up to 12 months . It appears that premenopausal women respond positively to this brief high-impact exercise but postmenopausal women do not PURPOSE The aim of this study was to examine the relationship between weight lifted in 1 yr of progressive strength training and change in bone mineral density ( BMD ) in a group of calcium-replete , postmenopausal women . METHODS As part of a large clinical trial , 140 calcium-supplemented women , 44 - 66 yr old , were r and omized to a 1-yr progressive strength-training program . Half of the women were using hormone replacement therapy . Three times weekly , subjects completed two sets of six to eight repetitions in eight core exercises at 70 - 80 % of one repetition maximum . BMD was measured at baseline and 1 yr . RESULTS In multiple linear regression , the increase in femur trochanter ( FT ) BMD was positively related to total weight lifted ( 0.001 g.cm ( -2 ) ) for a SD of weight lifted , P < 0.01 ) after adjusting for age , baseline factors , HRT status , weight change , cohort , and fitness center . The weighted squats showed the strongest ( 0.002 g.cm(-2 ) ) for a SD of weight lifted , P < 0.001 ) , whereas the back extension exhibited the weakest ( 0.0005 g.cm(-2 ) ) for a SD of weight lifted , P < 0.26 ) association with change in FT BMD . The amount of weight lifted in the weighted march exercise was significantly related to total body BMD ( 0.0006 g.cm(-2 ) ) for a SD of weight lifted , P < 0.01 ) . The associations between weight lifted and BMD for the femur neck or lumbar spine were not significant . CONCLUSION Evidence of a linear relationship between BMD change and total and exercise-specific weight lifted in a 1-yr strength-training program reinforces the positive association between this type of exercise and BMD in postmenopausal women Underst and ing the stress/strain relationship between exercise and bone is critical to underst and ing the potential benefit of exercise in preventing postmenopausal bone loss . This study examined the effect of a 2-year exercise intervention and calcium supplementation ( 600 mg ) on bone mineral density ( BMD ) in 126 postmenopausal women ( mean age , 60 + /- 5 years ) . Assignment was by block r and omization to one of three groups : strength ( S ) , fitness ( F ) , or nonexercise control ( C ) . The two exercise groups completed three sets of the same nine exercises , three times a week . The S group increased the loading , while the F group had additional stationary bicycle riding with minimal increase in loading . Retention at 2 years was 71 % ( 59 % in the S group , 69 % in the F group , and 83 % in the C group ) , while the exercise compliance did not differ between the exercise groups ( S group , 74 + /- 13 % ; F group , 77 + /- 14 % ) . BMD was measured at the hip , lumbar spine , and forearm sites every 6 months using a Hologic 4500 . Whole body BMD also was measured every 6 months on a Hologic 2000 . There was no difference between the groups at the forearm , lumbar spine , or whole body sites . There was a significant effect of the strength program at the total ( 0.9 + /- 2.6 % ; p < 0.05 ) and intertrochanter hip site ( 1.1 + /- 3.0 % ; p < 0.01 ) . There was a significant time and group interaction ( p < 0.05 ) at the intertrochanter site by repeated measures . This study shows the effectiveness of a progressive strength program in increasing bone density at the clinical ly important hip site . We concluded that a strength program could be recommended as an adjunct lifestyle approach to osteoporosis treatment or used in combination with other therapies Objectives —There is a paucity of long term studies on exercise training in elderly women . The purpose of this study was to investigate the effects of one year of progressive resistance exercise ( PRE ) on dynamic muscular strength and the relations to bone mineral density ( BMD ) in elderly women . Methods —Forty four healthy sedentary women ( mean age 68.8 years ) volunteered for this study and were r and omly assigned to either an exercise group or a control group . The exercise group were involved in three one hour sessions a week for 52 weeks of supervised PRE to strengthen the large muscle groups of the body , while the control group were instructed to continue their normal lifestyle . The exercise circuit included three sets of eight repetitions at 75 % of one repetition maximum focused on the large muscle groups . BMD was measured by dual energy x ray absoptiometry ( Lunar DPX ) at the lumbar spine and at three sites in the proximal femur . Other selected parameters of physical fitness were also measured . Results —Statistical analyses ( analysis of covariance ) showed significant strength gains ( p<0.01 ) in bilateral bench press ( > 29 % ) , bilateral leg press ( > 19 % ) , and unilateral biceps curl ( > 20 % ) . No significant difference between groups was evident in body weight , grip strength , flexibility , waist to hip ratio , or the sum of eight skinfolds . Significant relations ( p<0.05 ) were recorded between dynamic leg strength and the BMD of the femoral neck , Ward 's triangle , and the lumbar spine . Conclusions —Significant strength changes , after one year of PRE , were evident in elderly women , and the muscle increases may parallel changes in BMD ; however , correlation coefficients were moderate It is considered that skeletal mass in humans may respond to loading or the number of loading cycles . The aim of this study was to examine the effect of a 1 year progressive resistance training program on the bone mass of 56 postmenopausal women . Assignment was by block r and omization to one of two resistance training groups : a strength trained group ( 3 x 8 repetition maximum ) or an endurance group ( 3 x 20 repetition maximum ) . The resistance exercises were selected to stress the ipsilateral forearm and hip region . The exercising side was r and omly assigned with one side exercised while the alternate side acted as the nonexercise control . Bone mineral density ( BMD ) was measured every 3 months at the radial forearm and four hip sites using the Hologic QDR 2000 bone densitometer . A linear regression function was fitted for each individual 's bone density results , and the slope was compared for the exercise and control side using paired t-tests . The bone mass increase with the strength regimen was significantly greater at the trochanteric hip site ( control -0.6 + /- 2.2 % , exercise 1.7 + /- 4.1 % , p < 0.01 ) , at the intertrochanteric hip site ( control -0.1 + /- 2.1 % , exercise 1.5 + /- 3.0 % , p < 0.05 ) , Ward 's triangle ( control 0.8 + /- 5.2 % , exercise 2.3 + /- 4.0 % , p < 0.05 ) , and at the ultradistal radial site ( control -1.4 + /- 2.3 % , exercise 2.4 + /- 4.3 % , p < 0.01 ) . There was no significant increase in BMD with the endurance regimen except at the radius midsite ( control -1.0 + /- 2.3 % , exercise 0.1 + /- 1.4 % , p < 0.01 ) . In both the endurance and the strength group , muscle strength , tested by a one-repetition maximum ( 1RM ) test , increased significantly for all 10 exercises ( p < 0.01 ) and to a similar degree in the two groups . In the strength group but not the endurance group there were significant correlations between the slope of the change in BMD and the percentage increase in strength as follows : trochanter with leg press ; intertrochanter with leg press ( p < 0.05 ) ; and Ward 's triangle with hip extension and hip adduction ( p < 0.05 ) . Thus these results support the notion of a site-specific response of bone to maximal loading from resistance exercise in that although the trochanter and intertrochanter bone density was elevated by the resistance exercises undertaken , there was no effect on the femoral neck value . Postmenopausal bone mass can be significantly increased by a strength regimen that uses high-load low repetitions but not by an endurance regimen that uses low-load high repetitions . We conclude that the peak load is more important than the number of loading cycles in increasing bone mass in early postmenopausal women The long-term protective effect of stronger back muscles on the spine was determined in 50 healthy white postmenopausal women , aged 58 - 75 years , 8 years after they had completed a 2 year r and omized , controlled trial . Twenty-seven subjects had performed progressive , resistive back-strengthening exercises for 2 years and 23 had served as controls . Bone mineral density , spine radiographs , back extensor strength , biochemical marker values , and level of physical activity were obtained for all subjects at baseline , 2 years , and 10 years . Mean back extensor strength ( BES ) in the back-exercise ( BE ) group was 39.4 kg at baseline , 66.8 kg at 2 years ( after 2 years of prescribed exercises ) , and 32.9 kg at 10 years ( 8 years after cessation of the prescribed exercises ) . Mean BES in the control ( C ) group was 36.9 kg at baseline , 49.0 kg at 2 years , and 26.9 kg at 10 years . The difference between the two groups was still statistically significant at 10 year follow-up ( p = 0.001 ) . The difference in bone mineral density , which was not significant between the two groups at baseline and 2 year follow-up , was significant at 10 year follow-up ( p = 0.0004 ) . The incidence of vertebral compression fracture was 14 fractures in 322 vertebral bodies examined ( 4.3 % ) in the C group and 6 fractures in 378 vertebral bodies examined ( 1.6 % ) in the BE group ( chi-square test , p = 0.0290 ) . The relative risk for compression fracture was 2.7 times greater in the C group than in the BE group . To our knowledge , this is the first study reported in the literature demonstrating the long-term effect of strong back muscles on the reduction of vertebral fractures in estrogen-deficient women The purpose of this study was to determine the effect of a 1-year trunk resistive exercise program on bone mineral density at the lumbar spine and hip in postmenopausal women . Forty-nine subjects were divided into exercise and control groups . Dual photon absorptiometry was used to measure bone mineral density and the Muscle Examination and Exercise Dosimeter 3000 system was used to assess trunk muscle strength . Resistive exercise target levels for the exercise group were based on the results of the trunk muscle strength tests . The exercise group performed 3 sets of 10 repetitions for each of the sit-up , prone trunk extension , and double leg flexion exercises . The subjects were seen once per month and performed the exercises a minimum of three times per week . The bone mineral density and strength tests were done at baseline , at 6 months and at 12 months . The results of the study showed that 1 ) the dual photon absorptiometry method and the Muscle Examination and Exercise Dosimeter 3000 system were highly reliable in measuring bone mineral density and trunk muscle strength , respectively ; and 2 ) no significant differences were found between the exercise and control groups at lumbar vertebrae L2 , L3 , L4 , L2-L4 , and the femoral neck , Ward 's triangle , and trochanteric region of the proximal femur at baseline , 6-month , and 12-month evaluation sessions Knowledge of the effects of exercise on bone mass in postmenopausal women is limited and controversial . Animal studies have shown that the response of bone to bending strain is an alteration of bone geometry . We studied 250 postmenopausal women , aged 52 - 72 years , willing to participate in a 6-month exercise program . The first 125 started the program immediately and the remaining 125 served as controls . The training program included exercises design ed to maximize the stress on the wrist . One hundred and eighteen of the active group and 116 of the control group completed the study and were reassessed 6 months later . Bone mineral density ( BMD ) of the femoral neck , lumbar spine , ultradistal and proximal radius was measured by dual-energy X-ray absorptiometry ( DXA ) both before and at the end of the exercise program . The forearm was also evaluated by peripheral quantitative computed tomography , which measures the area , bone mineral content ( BMC ) , and volumetric density for both the cortical and the trabecular component . The results showed that the DXA measurements at the femoral neck , lumbar spine , ultradistal and proximal radius were similar between the two groups . No significant difference was detected after the exercise program at the proximal radius . At the ultradistal radius , the cross-sectional area of cortical bone rose by 2.8 + /- 15.0 % ( SD , p < 0.05 ) , apparently for both periosteal apposition and corticalization of the trabecular tissue . The volumetric density of cortical bone rose by 2 . 2 + /- 15.8 % ( p < 0.1 ) , and that of trabecular bone decreased by 2.6 + /- 10.7 % ( p < 0.01 ) . The combined changes in both bone volume and density in the exercise group were associated with marked increase in cortical BMC ( 3.1 + /- 10.7 % , p < 0.01 ) and decrease in trabecular BMC ( -3.4 + /- 14.2 % , p < 0.05 ) , which were statistically different from those observed in the control group ( p < 0.05 ) . In conclusion , these results confirm that site-specific moderate physical exercises have very little effect on bone mass . However , it appears that some exercises may reshape the bone segment under stress by increasing both the cross-sectional area and the density of the cortical component . These structural changes are theoretically associated with increases in the bending strength |
12,384 | 29,239,021 | We evaluated 11 studies published from January 2006 to March 2016 : two studies vali date d a parent satisfaction question naire , and nine developed or modified previous question naires to use as outcome measures in their local setting s. Most instruments were not tested on reliability and validity . | This systematic review synthesis ed and described instruments measuring parent satisfaction with the increasing st and ard practice of family-centred care ( FCC ) in neonatal intensive care units . | INTRODUCTION Healthcare quality is usually evaluated through analysing medical outcomes including neonatal readmission and patient and family satisfaction . Parental involvement in neonatal care is considered as one of the most important factors , which directly affects these outcomes . The aim of the present study was to determine the effect of family-centered care including maternal participation , presence , and information about neonatal care , on maternal satisfaction and neonatal readmission ; the care services were provided by the primiparous mothers of preterm infants . MATERIAL S AND METHODS One hundred and ten primiparous mothers with preterm infants participated in this clinical trial . All sample s were r and omly divided into family-centered care ( FCC ) and control groups , through simple r and om sampling . The FCC program , which consisted of information about neonatal care , maternal presence , and participation in the care process , was implemented in the FCC group , while the control group was provided with routine care . Data were obtained using demographic and satisfaction question naires and readmission checklist . RESULTS In the FCC group , the mean score of satisfaction increased after the implementation of the program ( 22.36 and 59.28 before and after the program , respectively ) ( p<0.001 ) ; however , this increase in the control group was not significant . The obtained results regarding the different aspects of satisfaction indicated that mothers in the FCC group were more satisfied with maternal presence in the neonatal intensive care unit ( NICU ) , compared with aspects of information and participation . In addition , the number of neonatal readmission was less in the FCC group compared with the control group , and the mean duration of hospitalization was 6.96 and 12.96 days in the FCC and control groups , respectively ( p<0.001 ) . CONCLUSION FCC program seems to be effective in increasing maternal satisfaction and decreasing neonatal readmission . Therefore , it seems necessary that healthcare authorities of the departments of obstetrics and gynecology in Iran provide the opportunity for the implementation of such programs in clinical environments , which follow the policy of parental absence and participation in the intensive care units Objective : With neonatal intensive care units ( NICUs ) evolving from multipatient wards toward family-friendly , single-family room units , the study objective was to compare satisfaction levels of families and health-care staff across these differing NICU facility design s. Study Design : This prospect i ve study documented , by means of institutional review board-approved question naire survey protocol s , the perceptions of parents and staff from two contrasting NICU environments . Result : Findings showed that demographic subgroups of parents and staff perceived the advantages and disadvantages of the two facility design s differently . Staff perceptions varied with previous experience , acclimation time and employment position , whereas parental perceptions revealed a naiveté bias through surveys of transitional parents with experience in both NICU facilities . Conclusion : Use of transitional parent surveys showed a subject naiveté bias inherent in perceptions of inexperienced parents . Grouping all survey participants demographically provided more informative interpretations of data , and revealed staff perceptions to vary with position , previous training and hospital experience Objective : To compare , in a large representative sample of European neonatal intensive care units , the policies and practice s regarding parental involvement and holding babies in the kangaroo care position as well as differences in the tasks mothers and fathers are allowed to carry out . Design : Prospect i ve multicenter survey . Setting : Neonatal intensive care units in eight European countries ( Belgium , Denmark , France , Italy , The Netherl and s , Spain , Sweden , and the United Kingdom ) . Patients : Patients were not involved in this study . Interventions : None . Measurements and Main Results : A structured question naire was mailed to 362 units ( response rate 78 % ) ; only units with ≥50 very-low-birth-weight annual admissions were considered for this study . Facilities for parents such as reclining chairs near the babies ’ cots , beds , and a dedicated room were common , but less so in Italy and Spain . All units in Sweden , Denmark , the United Kingdom , and Belgium reported encouraging parental participation in the care of the babies , whereas policies were more restrictive in Italy ( 80 % of units ) , France ( 73 % ) , and Spain ( 41 % ) . Holding babies in the kangaroo care position was widespread . However , in the United Kingdom , France , Italy , and Spain , many units applied restrictions regarding its frequency ( sometimes or on parents request only , rather than routinely ) , method ( conventional rather than skin-to-skin ) , and clinical conditions ( especially mechanical ventilation and presence of umbilical lines ) that would prevent its practice . In these countries , fathers were routinely offered kangaroo care less frequently than mothers ( p < .001 ) and less often it was skin-to-skin ( p < .0001 ) . Conclusions : This study showed that , although the majority of units in all countries reported a policy of encouraging both parents to take part in the care of their babies , the intensity and ways of involvement as well as the role played by mothers and fathers varied within and between countries OBJECTIVE To evaluate the impact of individualized , developmentally supportive family-centered care on infant physiological variables , growth , behavioral stress cues , return to sleep state , medical and developmental progress , complications , re source utilization , parental perception of the neonatal intensive-care unit experience , and overall parental satisfaction . DESIGN Quasi-experimental , repeated measures design . SETTING Developmental and a control nursery in a 78-bed , level II/III neonatal intensive-care unit . PARTICIPANTS A convenience sample of 114 premature infants and their parents . INTERVENTIONS Control group infants received the routine neonatal intensive-care unit st and ard of care . Experimental infants received routine care plus the addition of individualized , developmentally supportive family-centered interventions . MAIN OUTCOME MEASURES Between groups , there were no statistically significant differences in demographic factors , days to medical or developmental milestones , length of stay , or direct cost/case . Repeated measures analysis of variance determined that at every point of data collection , the average number of baseline , activity , and postactivity stress cues were lower in the developmentally supportive group . Infants in the developmental group had 8 % less sedatives/narcotics and 15 % less vasopressors costs than the control group . There were no differences in complication rates , parental perceptions of the neonatal intensive-care unit experience , or parental satisfaction between groups . CONCLUSIONS Preterm infants who received developmentally supportive family-centered care demonstrated fewer behavioral stress cues and comparable short-term outcomes and re source utilization than infants who received routine care Objective : Family-centered care is becoming a st and ard of care in neonatal intensive care units ( NICUs ) . The purpose of this study was to evaluate the impact of a national program design ed to promote family-centered care in NICUs and to provide information and comfort to families during the NICU hospitalization of their newborn . Study Design : A quasi-experimental , post-only design was utilized , examining eight March of Dimes NICU Family Support ® ( NFS ) sites . Data were gathered via telephone interviews with NICU administrators and surveys of both NICU staff and NICU families . Result : NICU administrators interviewed identified benefits of NFS , including culture change and additional support to families . Surveys of NICU staff showed that NFS enhances the overall quality of NICU care result ing in less stressed , more informed and confident parents . Surveys of NICU families showed that NFS both reduced their stress and made them feel more confident as their baby 's parent . Conclusion : March of Dimes NFS has had a positive impact on the stress level , comfort level and parenting confidence of NICU families . In addition , it has enhanced the receptivity of staff to the presence and benefits of family-centered care BACKGROUND Family-centred care ( FCC ) is a state-of-the-art practice in neonatal intensive care units ( NICU ) based on its shown benefits on the well-being of both infants and parents . However , there is no systematic knowledge about how FCC is implemented in different European context s. OBJECTIVES To describe parents ' presence and the quality of FCC from the perspectives of mothers , fathers and nurses in 11 European NICUs . METHODS A prospect i ve survey was conducted in Finl and , Sweden , Norway , Estonia , Spain and Italy . The perceived quality of FCC was measured using 8 text-message questions sent to the parents ' mobile phones , one question each day , during the infant 's hospital stay . Nurses answered corresponding questions through a Web question naire during a 3-month period . The responses were rated on a 7-point Likert scale . Parents who were not present in the unit during the day used a " 0 " response . RESULTS A total of 262 families of preterm infants born before 35 gestational weeks participated in the study . Mothers gave 5045 responses , fathers gave 3971 responses and nurses gave 11,132 answers . The mothers were present during 92.7 % and the fathers during 77.9 % of the study days . The mothers rated the quality of FCC slightly higher than the fathers did ( 5.8 [ 95 % CI 5.7 - 5.9 ] vs. 5.7 [ 95 % CI 5.6 - 5.8 ] , mean difference of 0.12 [ 95 % CI 0.05 - 0.2 ] , p<0.001 ) . There was wide variation in the parents ' presence and the quality of FCC between the units . The weakest aspects of FCC were emotional support , parents ' participation in decision-making and fathers ' participation in infant care . The perceived quality of FCC between the nurses and parents were comparable . CONCLUSIONS This study showed a high perceived quality of FCC in 11 European units , as indicated by both parents and nurses . The innovative data - collection method and instrument successfully quantified each unit 's FCC profile for further quality improvement and should be trialled in other NICUs and countries |
12,385 | 31,313,676 | Conclusions : The use of long-term VKAs , for any indication , is associated with lower cancer incidence . | Objectives : Vitamin K antagonists ( VKAs ) remain one of the most commonly used anticoagulation therapies .
The potential anticancer effect of long-term use of VKAs has been a matter of debate with conflicting results .
Our goal was to perform a systematic review and meta- analysis examining the association between long-term VKAs use and cancer risk . | Purpose A few recent epidemiological observations suggest that anticoagulant medications may protect against prostate cancer development . Most studies have been small or subjected to method ological issues , including potential confounding . We provide here new evidence on this association in the context of a population -based case – control study of prostate cancer conducted in Montreal , Canada . Methods Cases were 1,588 men with incident prostate cancer , aged ≤75 years , diagnosed across French hospitals in the Montreal area between 2005 and 2009 . Concurrently , 1,618 population controls from the same residential area and age distribution ( ±5 years ) were r and omly selected from the electoral list of French-speaking men . In-person interviews elicited information on socio-demographic , lifestyle and environmental factors , along with a detailed medical history . Unconditional logistic regression was used to assess the association between lifetime use of anticoagulants and prostate cancer risk . Results 102 subjects ( 2.6 % of cases and 3.7 % of controls ) reported a history of oral anticoagulant therapy . After controlling for age , ancestry , education , family history of prostate cancer , prostate cancer screening frequency , diabetes , body mass index and statin use , ever use of oral anticoagulants showed a weak inverse , non-statistically significant association with prostate cancer ( odds ratio 0.76 , 95 % confidence interval 0.50–1.16 ) . Similar results were observed in analyses considering duration of use or indication for use , restricted to subjects recently screened or stratified by cancer aggressiveness . Conclusions Our findings provide weak support for a protective effect of oral anticoagulant therapy against prostate cancer . Further confirmation is required , especially in light of potential bleeding complications associated with anticoagulants BACKGROUND The influence of the duration of anticoagulant therapy after venous thromboembolism ( VTE ) on the long-term morbidity and mortality is unclear . AIM To investigate the long-term sequelae of VTE in patients r and omized to different duration of secondary prophylaxis . METHODS In a multicenter trial comparing secondary prophylaxis with vitamin K antagonists for 6 weeks or 6 months , we extended the originally planned 2 years follow-up to 10 years . The patients had annual visits and at the last visit clinical assessment of the post-thrombotic syndrome ( PTS ) was performed . Recurrent thromboembolism was adjudicated by a radiologist , blinded to treatment allocation . Causes of death were obtained from the Swedish Death Registry . RESULTS Of the 897 patients r and omized , 545 could be evaluated at the 10 years follow-up . The probability of developing severe PTS was 6 % and any sign of PTS was seen in 56.3 % of the evaluated patients . In multivariate analysis , old age and signs of impaired circulation at discharge from the hospital were independent risk factors at baseline for development of PTS after 10 years . Recurrent thromboembolism occurred in 29.1 % of the patients with a higher rate among males , older patients , those with permanent triggering risk factor - especially with venous insufficiency at baseline - signs of impaired venous circulation at discharge , proximal deep vein thrombosis , or pulmonary embolism . Death occurred in 28.5 % , which was a higher mortality than expected with a st and ardized incidence ratio ( SIR ) of 1.43 ( 95 % CI 1.28 - 1.58 ) , mainly because of a higher mortality than expected from cancer ( SIR 1.83 ; 95 % CI 1.44 - 2.23 ) or from myocardial infa rct ion or stroke ( SIR 1.28 ; 95 % CI 1.00 - 1.56 ) . The duration of anticoagulation did not have a statistically significant effect on any of the long-term outcomes . CONCLUSION The morbidity and mortality during 10 years after the first episode of VTE is high and not reduced by extension of secondary prophylaxis from 6 weeks to 6 months . A strategy to reduce recurrence of VTE as well as mortality from arterial disease is needed Purpose Recent evidence suggests that warfarin use may be associated with a reduced risk of prostate cancer . We aim ed to determine whether exposure to warfarin is also associated with a reduced risk of prostate cancer death . Methods A nested case – control study was conducted within a population -based cohort of 10,012 men aged ≥50 years with newly diagnosed prostate cancer between 1985 and 2002 and with no history of cancer since 1970 using the linked records of Saskatchewan Health and Saskatchewan Cancer Agency registry . We identified 2,309 cases who died of prostate cancer during follow-up . For each case , one control alive at the time of the case ’s death and matched for length of follow-up ( ±6 months ) was r and omly selected . Prescription counts were used to define warfarin exposure . Multivariate conditional logistic regression analysis was used to calculate the adjusted incidence rates of prostate cancer death in relation to warfarin use while adjusting for confounding by age , year of prostate cancer diagnosis , clinical stage and grade of cancer at diagnosis , Chronic Disease Score , and use of warfarin before diagnosis . Results Ever use of warfarin following a diagnosis of prostate cancer was associated with an adjusted rate ratio of 1.44 ( 95 % confidence interval ( CI ) 1.33–1.84 ) for prostate cancer death . The adjusted rate ratio with one-year use of warfarin was 1.77 ( 95 % CI 1.25–2.50 ) compared to never use . The unadjusted rate ratio with five-year use of warfarin was 0.64 ( 95 % CI 0.40–1.00 ) and remained unchanged in the adjusted analysis ( 0.65 , 95 % CI 0.37–1.13 ) , although no longer statistically significant . Conclusion Our study does not provide conclusive evidence for a protective effect of long-term warfarin on prostate cancer-specific mortality . Moreover , short-term warfarin use may be associated with an increased risk of prostate cancer death BACKGROUND The length of time after an episode of venous thromboembolism during which the risk of newly diagnosed cancer is increased is not known , and whether vitamin K antagonists have an antineoplastic effect is controversial . METHODS In a prospect i ve , r and omized study of the duration of oral anticoagulation ( six weeks or six months ) after a first episode of venous thromboembolism , patients were question ed annually about any newly diagnosed cancer . After a mean follow-up of 8.1 years , we used the Swedish Cancer Registry to identify all diagnoses of cancer and causes of death in the study population . The observed numbers of cases of cancer were compared with expected numbers based on national incidence rates , and the st and ardized incidence ratios were calculated . RESULTS A first cancer was diagnosed in 111 of 854 patients ( 13.0 percent ) during follow-up . The st and ardized incidence ratio for newly diagnosed cancer was 3.4 ( 95 percent confidence interval , 2.2 to 4.6 ) during the first year after the thromboembolic event and remained between 1.3 and 2.2 for the following five years . Cancer was diagnosed in 66 of 419 patients ( 15.8 percent ) who were treated for six weeks with oral anticoagulants , as compared with 45 of 435 patients ( 10.3 percent ) who were treated for six months ( odds ratio , 1.6 ; 95 percent confidence interval , 1.1 to 2.4 ) . The difference was mainly due to the occurrence of new urogenital cancers , of which there were 28 cases in the six-week group ( 6.7 percent ) and 12 cases in the six-month group ( 2.8 percent ) ( odds ratio , 2.5 ; 95 percent confidence interval , 1.3 to 5.0 ) . The difference in the incidence of cancer between the treatment groups became evident only after two years of follow-up , and it remained significant after adjustment for sex , age , and whether the thromboembolism was idiopathic or nonidiopathic . Older age at the time of the venous thrombosis and an idiopathic thromboembolism were also independent risk factors for a diagnosis of cancer . No difference in the incidence of cancer-related deaths was detected . CONCLUSIONS The risk of newly diagnosed cancer after a first episode of venous thromboembolism is elevated during at least the following two years . Subsequently , the risk seems to be lower among patients treated with oral anticoagulants for six months than among those treated for six weeks BACKGROUND Indirect evidence suggests that prolonged treatment with warfarin might be associated with a decreased incidence of urogenital cancer . We aim ed to assess this association in a large population -based study . METHODS Beneficiaries of Saskatchewan Health who were eligible for prescription drug benefits and aged 50 years or over with no history of cancer since 1967 were enrolled into a nested , matched case-control study . 19 412 new cases of urogenital cancer diagnosed between Jan 1 , 1981 , and Dec 31 , 2002 , were identified by use of information from the Saskatchewan Cancer Agency registry . For each case , six controls , totalling 116 470 , who were matched for age , sex , and time of diagnosis were selected r and omly . Conditional logistic regression analysis was used to calculate adjusted incidence rates of urogenital cancer in relation to warfarin use . FINDINGS Compared with men who never used warfarin , men with 4 years of warfarin use had an adjusted incidence rate of 0.80 ( 95 % CI [ 0.65 - 0.99 ] ) . For warfarin use 76 - 100 % of the time , the adjusted rate ratios were 0.80 ( 0.66 - 0.96 ) during year 2 preceding diagnosis of prostate cancer , 0.76 ( 0.62 - 0.94 ) during year 3 , and 0.67 ( 0.53 - 0.86 ) during year 4 . No significant association was found between warfarin and risk of other urogenital cancers . INTERPRETATION Our results suggest that warfarin has an antitumour effect that is specific to prostate cancer . Further investigation , with more complete assessment of confounders and that addresses the effect of warfarin on mortality of prostate cancer , is warranted IMPORTANCE A substantial proportion of patients with atrial fibrillation ( AF ) die of noncardiovascular causes , and recent studies suggest a link between AF and cancer . OBJECTIVE To evaluate the associations between AF and cancer in a large , long-term prospect i ve cohort study . DESIGN , SETTING , AND PARTICIPANTS In this cohort study , a total of 34 691 women 45 years or older and free of AF , cardiovascular disease , and cancer at baseline were prospect ively followed up between 1993 and 2013 , for incident AF and malignant cancer within the Women 's Health Study , a r and omized clinical trial of aspirin and vitamin E for the prevention of cardiovascular disease and cancer . Cox proportional hazards models using time-up date d covariates were constructed to assess the association of new-onset AF with subsequent cancer and to adjust for potential confounders . Data analysis was performed from December 2014 to May 2015 . EXPOSURE New-onset AF . MAIN OUTCOMES AND MEASURES Incident malignant cancer confirmed by an end point committee . RESULTS During a median follow-up of 19.1 years of 34 691 study participants ( interquartile range [ IQR ] , 17.6 - 19.7 years ) , new-onset AF and malignant cancer were confirmed among 1467 ( 4.2 % ) and 5130 ( 14.8 % ) participants , respectively . Median age at baseline among participants with new-onset AF and new-onset cancer during follow-up was 58 years ( IQR , 52 - 64 years ) and 55 years ( IQR , 50 - 61 years ) , respectively . Atrial fibrillation was a significant risk factor for incident cancer in age-adjusted ( hazard ratio [ HR ] , 1.58 ; 95 % CI , 1.34 - 1.87 ; P < .001 ) and multivariable-adjusted ( HR , 1.48 ; 95 % CI , 1.25 - 1.75 ; P < .001 ) models . The relative risk of cancer was highest in the first 3 months after new-onset AF ( HR , 3.54 ; 95 % CI , 2.05 - 6.10 ; P < .001 ) but remained significant beyond 1 year after new-onset AF ( adjusted HR , 1.42 ; 95 % CI , 1.18 - 1.71 ; P < .001 ) , and a trend toward an increased cancer mortality was observed ( adjusted HR , 1.32 ; 95 % CI , 0.98 - 1.79 ; P = .07 ) . In contrast , among women with new-onset cancer , the relative risk of AF was increased only within the first 3 months ( HR , 4.67 ; 95 % CI , 2.85 - 7.64 ; P < .001 ) but not thereafter ( HR , 1.15 ; 95 % CI , 0.95 - 1.39 ; P = .15 ) . CONCLUSIONS AND RELEVANCE In this large , initially healthy cohort , women with new-onset AF had an elevated cancer risk beyond 1 year of AF diagnosis . Shared risk factors and /or common systemic disease processes might underlie this association BACKGROUND A prolonged treatment with oral anticoagulants has been cl aim ed to reduce the incidence of newly diagnosed cancer in the long-term follow-up of patients with venous thromboembolism . OBJECTIVES In a multicenter prospect i ve study we assessed the incidence of newly diagnosed clinical ly overt cancer in patients with a first episode of idiopathic venous thromboembolism ( VTE ) treated with oral anticoagulants for 3 months or 1 year . PATIENTS AND METHODS Consecutive patients with an idiopathic venous thromboembolism who had completed 3 months of oral anticoagulant therapy without having a recurrence , bleeding or newly diagnosed cancer were r and omized to discontinue oral anticoagulant therapy or to continue it for nine additional months . Idiopathic venous thromboembolism was defined as thrombosis occurring in the absence of known cancer , known thrombophilia , or temporary risk factors for venous thromboembolism . All patients were followed up for at least 1 year after r and omization . RESULTS A total of 429 patients , 265 patients with DVT and 164 with PE , were followed up for an average of 43.7 months after r and omization . A newly diagnosed cancer occurred in 32 patients ( 7.5 % ) , 13 ( 6.2 % ) of the 210 patients treated for 3 months and 19 ( 8.7 % ) of the 219 patients treated for 1 year ( RR = 0.71 , 95 % confidence interval 0.36 - 1.41 ) . CONCLUSIONS The incidence of newly diagnosed clinical ly overt cancer is not reduced in patients with idiopathic venous thromboembolism treated with 1-year anticoagulant treatment compared with patients treated for 3 months There has been growing interest in study ing the biological effects of certain drugs and their potential to reduce the risk of various cancers . One study reported a decrease in the incidence of urogenital cancers in a trial with patients who received warfarin for treatment of venous thromboembolism , but a limitation to this study of urogenital cancers was the very small number of bladder cancer cases that developed following warfarin therapy . The objective of the present study is to measure the association between warfarin use and bladder cancer . A total of 330 cases with bladder cancer were identified at the James A. Haley Veterans ' Administration ( VA ) Hospital in Tampa , Florida , using a combination of computerized pathology records and inpatient and outpatient diagnoses . Controls were r and omly selected from the VA computerized administrative data base and 1293 controls were included for analysis . Unconditional logistic regression analysis was performed to assess the risk of bladder cancer after adjusting for age , gender , and cigarette smoking . Among warfarin users , although there was a 27 % elevation in risk , it did not differ significantly from nonusers ( OR = 1.27 , 95 % CI = 0.85 , 1.89 ) . No duration -response relationship was observed between anticoagulant use and risk of bladder cancer . The results suggest that warfarin does not protect against bladder cancer , at least in male smokers , the highest risk population for bladder cancer |
12,386 | 23,543,514 | Dietary advice appears to be effective in bringing about modest beneficial changes in diet and cardiovascular risk factors over approximately 12 months , but longer-term effects are not known | BACKGROUND Changes in population diet are likely to reduce cardiovascular disease and cancer , but the effect of dietary advice is uncertain .
This review is an up date of a previous review published in 2007 .
OBJECTIVES To assess the effects of providing dietary advice to achieve sustained dietary changes or improved cardiovascular risk profile among healthy adults . | OBJECTIVE --To evaluate the long term efficacy of diets in lowering serum cholesterol concentration . DESIGN --Descriptive overview of 16 published controlled trials of six months ' duration or longer . SETTING --Trials had been conducted in hospital clinics ( 6 ) , industry ( 3 ) , mental hospitals or institutions ( 3 ) , and in general population s ( 4 ) . PATIENTS --Trials had been conducted in high risk subjects ( 5 ) , in unselected healthy subjects ( 6 ) , or for secondary prevention in patients with coronary heart disease ( 5 ) . Women were included in only four trials . INTERVENTIONS --Diets equivalent to the step 1 diet were employed in eight trials , with individual intervention by dietitians ( 3 ) or occupational physicians ( 2 ) or with population advice ( 3 ) . Intensive diets which were more rigorous than the step 2 diet were employed in eight trials . MAIN OUTCOME MEASURES --Net change in serum total cholesterol concentration in subjects receiving treatment with diet compared with values in control subjects after six months to 10 years . RESULTS --In five trials with the step 1 diet as individual intervention the net reduction in serum cholesterol concentration ranged from 0 % to 4.0 % over six months to six years . In trials with population education reductions in cholesterol concentrations were 0.6 - 2.0 % over five to 10 years . When population and individual dietary advice were combined changes in cholesterol concentration ranged from a fall of 2.1 % to a rise of 1.0 % over four to 10 years . Diets more intensive than the step 2 diet reduced serum cholesterol concentration by 13 % over five years in selected high risk men in the population ; by 6.5 - 15.1 % over two to five years in hospital out patients ; and by 12.8 - 15.5 % over one to four and a half years in patients in institutions . CONCLUSIONS --The response to a step 1 diet is too small to have any value in the clinical management of adults with serum cholesterol concentrations above 6.5 mmol/l . Current guidelines recommend screening of serum cholesterol concentration in healthy subjects , followed by treatment with a step 1 diet . The guidelines should be review ed to provide a more realistic estimate of the effect of a step 1 diet and of the likely need for lipid lowering drugs Diet is an important factor in the causation of cancer . Previous systematic review s of one-to-one interventions to encourage dietary change have found that such interventions can achieve modest improvements in diet . However , such interventions are re source intensive and unlikely to be good value for money at a population level . Interventions that address groups , communities or whole population s may be less re source intensive and effect change in a wider population . We report a systematic review of such interventions . We set wide inclusion criteria , including before- and -after studies and studies with a non-r and omized comparison group as well as r and omized trials . We found eighteen studies based in the community , seventeen based on worksites , five based in churches and one based in a supermarket . Interventions which targeted fruit and vegetable intake were most likely to be successful , particularly in worksites and churches . There was also evidence of small positive effects on reducing fat intake in worksites and churches . Overall the community-based interventions showed little effect . The studies included in the present review were generally poorly reported . Dietary changes are reported in the relatively short-term studies review ed here but may not be sustained in the long term . The effects that we have identified are small but the reach is potentially very wide , in some cases as wide as a whole country . The cost effectiveness of such strategies remains to be evaluated A controlled intervention trial , with the purpose of testing the hypothesis that the incidence of coronary heart disease ( CHD ) could be decreased by the use of serum-cholesterol-lowering ( SCL ) diet , was carried out in 2 mental hospitals near Helsinki in 1959 - -71 . The subjects were hospitalized middle-aged men . One of the hospitals received the SCL diet , i.e. a diet low in saturated fats and cholesterol and relatively high in polyunsaturated fats , while the other served as the control with a normal hospital diet . Six years later the diets were reversed , and the trial was continued another 6 years . The use of the SCL diet was associated with markedly lowered serum-cholesterol values . The incidence of CHD , as measured by the appearance of certain electrocardiographic patterns and by the occurrence of coronary deaths , was in both hospitals during the SCL-diet periods about half that during the normal-diet periods . An examination of a number of potential confounding variables indicated that the changes in them were small and failed to account for the considerable reduction in the incidence of CHD . It is concluded that the use of the serum-cholesterol-lowering diet exerted a substantial preventive effect on CHD |
12,387 | 23,740,538 | Overall the available evidence does not allow conclusions about the effect of media campaigns on illicit drug use among young people . | BACKGROUND Substance-specific mass media campaigns which address young people are widely used to prevent illicit drug use .
They aim to reduce use and raise awareness of the problem .
OBJECTIVES To assess the effectiveness of mass media campaigns in preventing or reducing the use of or intention to use illicit drugs amongst young people . | 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 This article review s major risk factors for cigarette smoking , alcohol , and other drug abuse and promising community-based approaches to primary prevention . In a longitudinal experimental study , 8 representative Kansas City communities were assigned r and omly to program ( school , parent , mass media , and community organization ) and control ( mass media and community organization only ) conditions . Programs were delivered at either 6th or 7th grade , and panels were followed through Grade 9 or 10 . The primary findings were ( a ) significant reductions at 3 years in tobacco and marijuana use and ( b ) equivalent reductions for youth at different levels of risk . This study provides evidence that a comprehensive community program-based approach can prevent the onset of substance abuse and that the benefits are experienced equally by youth at high and low risk The authors evaluated the efficacy of a brief image-based prevention intervention and assessed current drug use as a moderator of intervention effects . In a clinical trial , 416 high school-age adolescents were r and omized to either the brief intervention or usual care control , with data collected at baseline and 3-month follow-up . The brief intervention consisted of a tailored in-person communication and a series of parent/guardian print material s based on the behavior-image model . Health behavior goal setting increased for participants receiving the brief intervention , with an effect size in the small range ( d = 0.33 ) . Overall effect sizes for cigarette smoking frequency and quantity and alcohol use frequency and quantity were small ( ds = 0.16 - 0.21 ) and in favor of the brief intervention . However , adolescents reporting current substance use who received the brief intervention reduced their frequency and heavy use of alcohol , frequency and quantity of cigarette smoking , and reported fewer alcohol/drug problems , with larger effects ranging from small to approaching medium in size ( ds = 0.32 - 0.43 , ps < .01 ) . This study suggests that brief image-based messages may increase health behavior goal setting and reduce substance use , particularly among drug-using older adolescents Effects of anti-tobacco and anti-marijuana TV advertisements on explicit ( i.e. , semantic differential ratings ) and implicit ( i.e. Implicit Association Test , IAT ) attitudes toward tobacco and marijuana were compared . Two hundred twenty nine , 18- to 19-year-old U.S. college students were r and omly assigned to anti-tobacco or anti-marijuana PSA viewing conditions . Participants completed a short survey on attitudes to tobacco and marijuana . Afterwards they watched 15 PSAs embedded in a 15-min science program . At the end , all participants completed IAT for marijuana , IAT for tobacco and the assessment of explicit attitudes . Results of ANCOVA revealed a significant interaction between type of TV PSAs watched and implicit attitudes , F(1,223)=7.12 , p<0.01 when controlling for preexisting attitudes to both substances ; the implicit attitudes were more negative toward the substance that corresponded to the content of advertisements watched ( i.e. , anti-tobacco or anti-marijuana ) . However , analogical analysis on explicit measures showed that attitudes to marijuana became less negative among students that watched anti-marijuana ads than the group with anti-tobacco ads , F(1,222)=5.79 , p<0.02 . The discussion focused on the practical and theoretical implication s of the observed dissociation between implicit and explicit attitudes to marijuana after the exposure to anti-marijuana PSAs OBJECTIVES This study examined the relative perceived effectiveness of 30 antidrug public service announcements ( PSAs ) and assessed the extent to which judgments of effectiveness are related to judgments of realism , amount learned , and positive and negative emotional responses . METHODS Data were obtained from 3608 students in grade s 5 through 12 in 10 schools . The ethnically diverse sample was 50.8 % male . Students in 5 experimental conditions viewed sets of 6 antidrug PSAs and filled out a brief evaluation question naire following each PSA . Those in the control condition viewed a non-drug-related television program . RESULTS The relative perceived effectiveness of the 30 PSAs varied considerably . Sixteen were rated as significantly more effective , and 6 as significantly less effective , than the control program . Relative rated effectiveness was highly related to realism ( r = .87 ) , amount learned ( r = .88 ) , negative emotion ( r = .87 ) , and positive emotion ( r = -.35 ) . CONCLUSIONS Evaluative research is necessary to prevent broadcast of PSAs that could have a negative impact . PSAs should point out the negative consequences of drug use behavior rather than telling adolescents to " just say no. BACKGROUND Despite the availability of an increasing array of empirically vali date d adolescent drug abuse prevention programs , program material s and evaluation findings are poorly disseminated . CD-ROM and the Internet hold promise for disseminating this information to schools and agencies that directly serve youth , and to policy-making bodies that exercise control over funds to support adolescent drug abuse prevention programming . However , data on the relative efficacy of these newer technologies over conventional print means of dissemination are lacking . METHODS Recruited through schools , community agencies , and policy-making bodies , 188 professionals were r and omized to receive prevention program material s via pamphlets ( 55 participants ) , CD-ROM ( 64 participants ) , and the Internet ( 69 participants ) . Participants completed pretest , posttest , and 6-month follow-up measures that assessed their access to prevention program material s ; self-efficacy for identifying , obtaining , and recommending these programs ; and their likelihood of requesting , implementing , and recommending prevention programs to their constituents . RESULTS Participants exposed to dissemination via CD-ROM and the Internet evidence d the greatest short- and long-term gains on accessibility , self-efficacy , and behavioral intention variables . CONCLUSIONS CD-ROM and the Internet are viable means for disseminating adolescent drug abuse prevention programs to schools , community agencies , and policy-making bodies , and should be increasingly used for dissemination purpose Despite clear need , brief web-based interventions for marijuana-using college students have not been evaluated in the literature . The current study was design ed to evaluate a brief , web-based personalized feedback intervention for at-risk marijuana users transitioning to college . All entering first-year students were invited to complete a brief question naire . Participants meeting criteria completed a baseline assessment ( N = 341 ) and were r and omly assigned to web-based personalized feedback or assessment -only control conditions . Participants completed 3-month ( 95.0 % ) and 6-month ( 94.4 % ) follow-up assessment s. Results indicated that although there was no overall intervention effect , moderator analyses found promising effects for those with a family history of drug problems and , to a smaller extent , students who were higher in contemplation of changing marijuana use at baseline . Implication s of these findings for selective intervention of college marijuana use and web-based interventions in general are discussed Two media-based interventions design ed to reduce adolescent marijuana use ran concurrently from 2005 to 2009 . Both interventions used similar message strategies , emphasizing marijuana ’s inconsistency with personal aspirations and autonomy . “ Be Under Your Own Influence ” was a r and omized community and school trial replicating and extending a successful earlier intervention of the same name ( Slater et al. Health Education Research 21:157–167 , 2006 ) . “ Above the Influence ” is a continuing national television , radio , and print campaign sponsored by the Office of National Drug Control Policy ( ONDCP ) . This study assessed the simultaneous impact of the interventions in the 20 U.S. communities . Results indicate that earlier effects of the “ Be Under Your Own Influence ” intervention replicated only in part and that the most plausible explanation of the weaker effects is high exposure to the similar but more extensive ONDCP “ Above the Influence ” national campaign . Self-reported exposure to the ONDCP campaign predicted reduced marijuana use , and analyses partially support indirect effects of the two campaigns via aspirations and autonomy Successful anti-marijuana messages can be hypothesized to have two types of effects , namely persuasion effects , that is , a change in people 's beliefs about using marijuana , and priming effects , that is , a strengthened correlation between beliefs and associated variables such as attitude and intention . This study examined different sets of anti-drug advertisements for persuasion and priming effects . The ads targeted the belief that marijuana is a gateway to stronger drugs , a belief that is often endorsed by campaign planning officials and health educators . A sample of 418 middle and high school students was r and omly assigned to a control video or one of three series of ads , two of which included the gateway message in either an explicit or implicit way . Results did not support the use of the gateway belief in anti-marijuana interventions . Whereas no clear persuasion or priming effects were found for any of the ad sequences , there is some possibility that an explicit gateway argument may actually boomerang . In comparison to the control condition , adolescents in the explicit gateway condition tended to agree less with the gateway message and displayed weaker correlations between anti-marijuana beliefs and their attitude toward marijuana use . The results suggest that the gateway message should not be used in anti-drug interventions OBJECTIVES The authors describe computer services design ed to make patients better informed and more motivated to participate in treatment . Patients use these services through their touch-tone telephone ; access to a home computer or a modem is not needed . METHODS The authors tested the impact of these computer services on the management of 179 pregnant women who had used cocaine during pregnancy or 1 month before pregnancy ( as reported by the woman ) . Patients were r and omly assigned to control and experimental groups ; only the experimental group had access to the computer services . Patients were enrolled during the prenatal period and followed for 6 months after the birth of a live child . Self-reported data on the subjects ' participation in drug treatment programs , health status ( using the SF-36 ) , and addiction severity ( using the addiction severity index ) were collected . The computer collected data on the frequency of the use of the service . The dependent variables were participation in formal treatment during the course of the project , and drug and alcohol use at exit interview . Multiple and logistic regressions were used to identify the effects of the intervention after controlling for demographic and baseline variables . RESULTS Data showed that poor , pregnant , undereducated clients who use drugs and lived in multiple residences could use the services ; about one-third of clients used the services more than three times a week . Access to the service did not lead to significant change in patients ' health status , drug use , or utilization of services . Use of the services did lead to significant changes in participation in drug treatment : subjects who used the service more than three times a week were 1.5 times more likely to participate in formal drug treatment than subjects who used the service less often . Participation in formal drug treatment , however , was not effective in reducing the drug or the alcohol use . CONCLUSIONS Almost all patients used the computer services to some extent , but there seems to be a threshold after which the use of the services had a more positive impact This study investigates an approach for reducing inhalant initiation among younger adolescents : altering Socio-Personal Expectations ( SPEs ) , a term referring to perceived linkages between behavior and personally relevant social outcomes . The study focuses specifically on SPEs regarding outcomes associated with increased social status and popularity . An anti-inhalant message was embedded within a short anti-bullying education video . Young adolescents ( N = 893 ) were assigned r and omly to receive a message focused on the physical or the social harms of inhalant use . The objectives of this study were to test : ( 1 ) the malleability of SPEs , ( 2 ) SPEs ’ predictive validity for future inhalant use , and ( 3 ) whether being exposed to a socio-personal threat , rather than a physical threat , led to different variables affecting drug-relevant decision-making processes . Analysis of variance suggested the malleability of SPEs ( p < .001 ) . Multiple regression analysis revealed that SPEs were predictive of future inhalant use . SPEs accounted for a significant portion of variance in future intentions over and above demographic variables , prior use , psychosocial variables , and perceived physical harm ( R2 = .26 , p < .01 ) . Moreover , being exposed to a social , rather than a physical threat , message result ed in different variables being predictive of future intentions to use inhalants AIMS Continued progress in etiological research and prevention science requires more precise information concerning the specific stages at which socio-demographic variables are implicated most strongly in transition from initial substance use to dependence . The present study examines prospect i ve associations between socio-demographic variables and the subsequent onset of alcohol and drug dependence using data from the National Comorbidity Survey ( NCS ) and the NCS Follow-up survey ( NCS-2 ) . DESIGN The NCS was a nationally representative survey of the prevalence and correlates of DSM-III-R mental and substance disorders in the United States carried out in 1990 - 2002 . The NCS-2 re-interviewed a probability sub sample of NCS respondents a decade after the baseline survey . Baseline NCS socio-demographic characteristics and substance use history were examined as predictors of the first onset of DSM-IV alcohol and drug dependence in the NCS-2 . PARTICIPANTS A total of 5001 NCS respondents were re-interviewed in the NCS-2 ( 87.6 % of baseline sample ) . FINDINGS Aggregate analyses demonstrated significant associations between some baseline socio-demographic variables ( young age , low education , non-white ethnicity , occupational status ) but not others ( sex , number of children , residential area ) and the subsequent onset of DSM-IV alcohol or drug dependence . However , conditional models showed that these risk factors were limited to specific stages of baseline use . Moreover , many socio-demographic variables that were not significant in the aggregate analyses were significant predictors of dependence when examined by stage of use . CONCLUSIONS The findings underscore the potential for socio-demographic risk factors to have highly specific associations with different stages of the substance use trajectory This study tests the impact of an in-school mediated communication campaign based on social marketing principles , in combination with a participatory , community-based media effort , on marijuana , alcohol and tobacco uptake among middle-school students . Eight media treatment and eight control communities throughout the US were r and omly assigned to condition . Within both media treatment and media control communities , one school received a research -based prevention curriculum and one school did not , result ing in a crossed , split-plot design . Four waves of longitudinal data were collected over 2 years in each school and were analyzed using generalized linear mixed models to account for clustering effects . Youth in intervention communities ( N = 4,216 ) showed fewer users at final post-test for marijuana [ odds ratio ( OR ) = 0.50 , P = 0.019 ] , alcohol ( OR = 0.40 , P = 0.009 ) and cigarettes ( OR = 0.49 , P = 0.039 ) , one-tailed . Growth trajectory results were significant for marijuana ( P = 0.040 ) , marginal for alcohol ( P = 0.051 ) and non-significant for cigarettes ( P = 0.114 ) . Results suggest that an appropriately design ed in-school and community-based media effort can reduce youth substance uptake . Effectiveness does not depend on the presence of an in-school prevention curriculum College students who have high stress levels tend to experience an increased risk of academic difficulties , substance abuse , and emotional problems . To enhance student stress management and health promoting behaviors , an online stress management intervention called MyStudentBody – Stress ( MyStudentBody – Stress ) was developed and tested . College students at six U.S. colleges were r and omized to one of three conditions : MyStudentBody – Stress , a control health information website , or no intervention . The differences between groups on stress control and health behavior measures were compared at baseline , and at 1 , 3 , and 6 months after baseline . Although there were no between-group differences on primary outcome variables , secondary analyses indicated that MyStudentBody – Stress participants were more likely to increase weekly physical activity , use specific stress management methods , and exhibit decreased anxiety and family problems . These findings indicate some potentially beneficial effects of online stress management programming for college students . Implication s for college health practitioners are discussed OBJECTIVE To determine whether an online intervention reduces references to sex and substance abuse on social networking Web sites among at-risk adolescents . DESIGN R and omized controlled intervention trial . SETTING www.MySpace.com . PARTICIPANTS Self-described 18- to 20-year-olds with public MySpace profiles who met our criteria for being at risk ( N = 190 ) . Intervention Single physician e-mail . MAIN OUTCOME MEASURES Web profiles were evaluated for references to sex and substance use and for security setting s before and 3 months after the intervention . RESULTS Of 190 subjects , 58.4 % were male . At baseline , 54.2 % of subjects referenced sex and 85.3 % referenced substance use on their social networking site profiles . The proportion of profiles in which references decreased to 0 was 13.7 % in the intervention group vs 5.3 % in the control group for sex ( P = .05 ) and 26.0 % vs 22 % for substance use ( P = .61 ) . The proportion of profiles set to " private " at follow-up was 10.5 % in the intervention group and 7.4 % in the control group ( P = .45 ) . The proportion of profiles in which any of these 3 protective changes were made was 42.1 % in the intervention group and 29.5 % in the control group ( P = .07 ) . CONCLUSIONS A brief e-mail intervention using social networking sites shows promise in reducing sexual references in the online profiles of at-risk adolescents . Further study should assess how adolescents view different risk behavior disclosures to promote safe use of the Internet The purpose of the present study was to examine the efficacy of a substance abuse – preventive intervention using CD-ROM technology among adolescents in the sixth and seventh grade s ( 12- to 13-years-old ) . The CD-ROM program used interactive audio and video content to teach social resistance skills , general personal and social competence skills , and normative education . Rates of substance-use behavior , attitudes , knowledge , normative expectations , and related variables were examined . From approximately 23 schools , students ( n = 123 ) were r and omly assigned to either receive the CD-ROM preventive intervention ( n = 61 ) or to serve as a control group ( n = 62 ) . Study participants were 50 % male , predominantly white ( 75 % ) , and 94 % came from two-parent families . Self-report data were collected using a self-administered web-based survey . Findings indicated that there were significant intervention effects on pro-drug attitudes , normative expectations for peer and adult substance use , anxiety reduction skills , and relaxation skills knowledge , with intervention students reporting improved scores on these outcomes at the posttest relative to control students . Findings indicate that a substance abuse – preventive intervention derived from an effective , school-based prevention approach is efficacious when delivered using CD-ROM technology . Research is needed to determine potential differences in the efficacy of CD-ROM prevention tools delivered in schools compared to home setting OBJECTIVES We evaluated the effects of the Marijuana Initiative portion of the Office of National Drug Control Policy 's National Youth Anti-Drug Media Campaign on high-sensation-seeking and low-sensation-seeking adolescents . METHODS Personal interviews were conducted via laptop computers with independent monthly r and om sample s of 100 youths from the same age cohort in each of 2 moderate-sized communities over 48 months ( April 1999-March 2003 ) of the campaign , including the critical first 6 months of the 9-month initiative . The start of the initiative was treated as an " interruption " in time-series analyses of the combined community sample . RESULTS The Marijuana Initiative reversed upward developmental trends in 30-day marijuana use among high-sensation-seeking adolescents ( P<.001 ) and significantly reduced positive marijuana attitudes and beliefs in this at-risk population . Use of control substances was not affected . As expected , low-sensation-seeking adolescents had low marijuana-use levels , and the campaign had no detectable effects on them . Other analyses indicated that the initiative 's dramatic depiction of negative consequences of marijuana use was principally responsible for its effects on high-sensation-seeking youths . CONCLUSIONS Substance use prevention campaigns can be effective within an approach using dramatic negative-consequence messages targeted to high-sensation seekers Developed because of the need to promote public underst and ing of the link between addictions and child maltreatment , a multimedia campaign helped to increase by 62 % the average monthly number of people who called a telephone service for information about how to aid abused and neglected children . The campaign was supported by market research and professional experience that indicated the campaign should focus on easy action a citizen could take , avoid inducing fear or blame , and target third party helpers and younger families-at-risk . Campaign exposure was promoted through the support of corporate partners . A r and om household survey found that 61 % of the general population had seen or heard the campaign slogan . The average monthly calls to the child maltreatment information service regarding alcohol and other drug abuse tripled and the requests regarding at-risk children almost doubled . An auxiliary project provided interprofessional education to increase the probability that people seeking help would get it when referrals were made . The project yielded several lessons for future public awareness campaigns : focus on helping action rather than the problem ; use of client-based market research ; a strategic plan to assure necessary exposure ; reliance on public-private-nonprofit sector partnerships ; preparation of the service system ; promotion of personal ways of helping This study developed and tested an Internet-based gender-specific drug abuse prevention program for adolescent girls . A sample of seventh , eighth , and ninth grade girls ( N = 236 ) from 42 states and 4 Canadian provinces were r and omly assigned to an intervention or control group . All girls completed an online pretest battery . Following pretest , intervention girls interacted with a 12-session , Internet-based gender-specific drug prevention program . Girls in both groups completed the measurement battery at posttest and 6-month follow-up . Analysis of posttest scores revealed no differences between groups for 30-day reports of alcohol , marijuana , poly drug use , or total substance use ( alcohol and drugs ) . At 6-month follow-up , between-group effects were found on measures of 30-day alcohol use , marijuana use , poly drug use , and total substance use . Relative to girls in the control group , girls exposed to the Internet-based intervention reported lower rates of use for these substances . Moreover , girls receiving the intervention achieved gains over girls in the control group on normative beliefs and self-efficacy at posttest and 6-month follow-up , respectively This analysis examined the possible synergistic effect of exposure to the National Youth Anti-Drug Media Campaign and a classroom-based drug prevention curriculum among 9th grade students participating in a r and omized trial of ALERT Plus . A total of 45 South Dakota high schools and their middle-school feeder(s ) were r and omly assigned to an ALERT condition ( basic prevention curriculum delivered in 7th and 8th grade s ) , an ALERT Plus condition ( basic curriculum with booster lessons added for 9th and 10th grade s ) , or a control condition . Marijuana use in the past month was significantly less likely among ALERT Plus students reporting at least weekly exposure to anti-drug media messages . The National Youth Anti-Drug Media Campaign may have led to reductions in marijuana use among youth who simultaneously received school-based drug prevention OBJECTIVES This study evaluated the effectiveness of targeted televised public service announcement campaigns in reducing marijuana use among high-sensation-seeking adolescents . METHODS The study used a controlled interrupted time-series design in 2 matched communities . Two televised antimarijuana campaigns were conducted in 1 county and 1 campaign in the comparison community . Personal interviews were conducted with 100 r and omly selected teenagers monthly in each county for 32 months . RESULTS All 3 campaigns reversed upward developmental trends in 30-day marijuana use among high-sensation seekers ( P < .002 ) . As expected , low-sensation seekers had low use levels , and no campaign effects were evident . CONCLUSIONS Televised campaigns with high reach and frequency that use public service announcements design ed for and targeted at high-sensation-seeking adolescents can significantly reduce substance use in this high-risk population The Campuswide Alcohol and Drug Abuse Prevention Program ( CADAPP ) was implemented and evaluated over a 1.5-year span at the University of New Mexico ( UNM ) . Drawing on self-regulation theory as a basis for underst and ing motivation for change , the program was design ed to increase risk perceptions and thereby reduce the use of alcohol and other drugs among university students . The program was evaluated from 1988 to 1989 through repeated anonymous r and om sample surveys of all enrolled students on the UNM campus and on a similar control campus not implementing newprevention efforts during the same period . As predicted , relative to the control campus , students on the CADAPP campus after the program showed significantly higher perceived risks from substance use and significantly reduced levels of alcohol and marijuana use . These findings provide encouraging evidence for this theory-based approach to primary and secondary prevention The integrative model of behavior prediction and priming theory were used to evaluate the effects of antimarijuana advertisements in an experimental context . In 1 original study and 2 replications , 435 adolescents were r and omly assigned to condition , and those in the experimental condition viewed 3 ads that challenged undesirable normative beliefs about marijuana use . The results showed that ad exposure had small but positive ( antidrug ) effects on adolescents ' considerations of the outcomes of using marijuana and their perceptions of the social normative climate surrounding marijuana use . Priming effects also were observed but generally ran counter to predictions . Implication s of the findings for antidrug campaigns are discussed . Potential explanations for the unexpected priming effects also are offered AIMS To establish the long-term efficacy of a universal internet-based alcohol and cannabis prevention programme in schools . METHODS A cluster-r and omized controlled trial was conducted to assess the effectiveness of the Climate Schools : Alcohol and Cannabis Course . The evidence -based course , aim ed at reducing alcohol and cannabis use , is facilitated by the internet and consists of 12 novel and curriculum consistent lessons delivered over 6 months . PARTICIPANTS A total of 764 year 8 students ( 13 years ) from 10 Australian secondary schools were allocated r and omly to the internet-based prevention programme ( n = 397 , five schools ) , or to their usual health classes ( n = 367 , five schools ) . MEASURES Participants were assessed at baseline , immediately post , and 6 and 12 months following completion of the intervention , on measures of alcohol and cannabis knowledge , attitudes , use and related harms . RESULTS This paper reports the final results of the intervention trial , 12 months following the completion of the Climate Schools : Alcohol and Cannabis Course . The effectiveness of the course 6 months following the intervention has been reported previously . At the 12-month follow-up , compared to the control group , students in the intervention group showed significant improvements in alcohol and cannabis knowledge , a reduction in average weekly alcohol consumption and a reduction in frequency of drinking to excess . No differences between groups were found on alcohol expectancies , cannabis attitudes or alcohol- and cannabis-related harms . The course was found to be acceptable by teachers and students as a means of delivering drug education in schools . CONCLUSIONS Internet-based prevention programs for school-age children can improve student 's knowledge about alcohol and cannabis , and may also reduce alcohol use twelve months after completion PURPOSE This study examined the efficacy and generalizability of a family-oriented , web-based substance use prevention program to young Asian-American adolescent girls . METHODS Between September and December 2007 , a total of 108 Asian-American girls aged 10 - 14 years and their mothers were recruited through online advertisements and from community service agencies . Mother-daughter dyads were r and omly assigned to an intervention arm or to a test-only control arm . After pretest measurement , intervention-arm dyads completed a 9-session web-based substance use prevention program . Guided by family interaction theory , the program aim ed to improve girls ' psychological states , strengthen substance use prevention skills , increase mother-daughter interactions , enhance maternal monitoring , and prevent girls ' substance use . Study outcomes were assessed using generalized estimating equations . RESULTS At posttest , relative to control-arm girls , intervention-arm girls showed less depressed mood ; reported improved self-efficacy and refusal skills ; had higher levels of mother-daughter closeness , mother-daughter communication , and maternal monitoring ; and reported more family rules against substance use . Intervention-arm girls also reported fewer instances of alcohol , marijuana , and illicit prescription drug use , and expressed lower intentions to use substances in the future . CONCLUSIONS A family-oriented , web-based substance use prevention program was efficacious in preventing substance use behavior among early Asian-American adolescent girls OBJECTIVE To establish the efficacy of an internet based prevention program to reduce alcohol and cannabis use in adolescents . METHOD A cluster r and omised controlled trial was conducted with 764 13-year olds from ten Australian secondary schools in 2007 - 2008 . Half the schools were r and omly allocated to the computerised prevention program ( n=397 ) , and half to their usual health classes ( n=367 ) . The Climate Schools : Alcohol and Cannabis prevention course is facilitated by the internet and consists of novel , evidence -based , curriculum consistent lessons aim ed at reducing alcohol and cannabis use . Participants were assessed at baseline , immediately post , and at six months following the intervention . RESULTS Compared to the control group , students in the intervention group showed significant improvements in alcohol and cannabis knowledge at the end of the course and the six month follow-up . In addition , the intervention group showed a reduction in average weekly alcohol consumption and frequency of cannabis use at the six month follow-up . No differences between groups were found on alcohol expectancies , cannabis attitudes , or alcohol and cannabis related harms . CONCLUSIONS The course is acceptable , scalable and fidelity is assured . It increased knowledge regarding alcohol and cannabis , and decreased use of these drugs |
12,388 | 27,389,906 | Secondary outcomes of kidney injury , new-onset atrial fibrillation , and major bleeding favoured TAVI , while major vascular complications , incidence of permanent pacemaker implantation , and paravalvular regurgitation favoured SAVR .
CONCLUSION Compared with SAVR , TAVI is associated with a significant survival benefit throughout 2 years of follow-up .
Importantly , this superiority is observed irrespective of the TAVI device across the spectrum of intermediate and high-risk patients , and is particularly pronounced among patients undergoing transfemoral TAVI and in females | AIMS In view of the currently available evidence from r and omized trials , we aim ed to compare the collective safety and efficacy of transcatheter aortic valve implantation ( TAVI ) vs. surgical aortic valve replacement ( SAVR ) across the spectrum of risk and in important subgroups . | BACKGROUND Transcatheter aortic valve replacement ( TAVR ) is an option in certain high-risk surgical patients with severe aortic valve stenosis . It is unknown whether TAVR can be safely introduced to lower-risk patients . OBJECTIVES The NOTION ( Nordic Aortic Valve Intervention Trial ) r and omized clinical trial compared TAVR with surgical aortic valve replacement ( SAVR ) in an all-comers patient cohort . METHODS Patients ≥ 70 years old with severe aortic valve stenosis and no significant coronary artery disease were r and omized 1:1 to TAVR using a self-exp and ing bioprosthesis versus SAVR . The primary outcome was the composite rate of death from any cause , stroke , or myocardial infa rct ion ( MI ) at 1 year . RESULTS A total of 280 patients were r and omized at 3 Nordic centers . Mean age was 79.1 years , and 81.8 % were considered low-risk patients . In the intention-to-treat population , no significant difference in the primary endpoint was found ( 13.1 % vs. 16.3 % ; p = 0.43 for superiority ) . The result did not change in the as-treated population . No difference in the rate of cardiovascular death or prosthesis reintervention was found . Compared with SAVR-treated patients , TAVR-treated patients had more conduction abnormalities requiring pacemaker implantation , larger improvement in effective orifice area , more total aortic valve regurgitation , and higher New York Heart Association functional class at 1 year . SAVR-treated patients had more major or life-threatening bleeding , cardiogenic shock , acute kidney injury ( stage II or III ) , and new-onset or worsening atrial fibrillation at 30 days than did TAVR-treated patients . CONCLUSIONS In the NOTION trial , no significant difference between TAVR and SAVR was found for the composite rate of death from any cause , stroke , or MI after 1 year . ( Nordic Aortic Valve Intervention Trial [ NOTION ] ; NCT01057173 ) Context Whether female sex is associated with an increased risk for adverse events among patients having transcatheter aortic valve replacement ( TAVR ) is unclear . Contribution In this secondary analysis of data from the Placement of Aortic Transcatheter Valves trial , women who had TAVR had more postprocedural major bleeding and vascular complications and improved 1-year survival than men . Caution Other factors , such as paravalvular leak or patientprosthesis mismatch , may have confounded the results . Implication The sex-specific risk associated with TAVR is the reverse of that for surgical aortic valve replacement , for which female sex is associated with an increased risk for adverse events . During the past 50 years , the st and ard of care for patients with severe , symptomatic aortic stenosis ( AS ) has been surgical aortic valve replacement ( SAVR ) , which has been shown to prolong survival and alleviate symptoms compared with medical therapy alone ( 1 , 2 ) . However , at least one third of patients with AS are deemed to be high-risk or inoperable for SAVR due to comorbidities or unfavorable anatomy ( 3 ) . For these patients , transcatheter aortic valve replacement ( TAVR ) has emerged as an alternative ( 1 , 2 , 411 ) . The PARTNER ( Placement of Aortic Transcatheter Valves ) trial was the first to show the safety and efficacy of TAVR compared with accepted st and ard therapies in high-risk and inoperable patients with AS ( 49 ) . The results of this trial ultimately led to the approval of the SAPIEN transcatheter valve ( Edwards Lifesciences ) by the U.S. Food and Drug Administration . Since the PARTNER trial , many other trials and international registries have shown the benefits of TAVR in higher-risk patients ( 1012 ) . Female sex has been shown to be associated with increased risk for adverse events after SAVR ( 1317 ) but has been shown to be a potentially favorable characteristic for patients having TAVR ( 1823 ) . However , prior trials examining sex-based differences in patients having TAVR have been limited in size or have involved only single- or dual-center experiences . Furthermore , not all studies agree that TAVR may be more beneficial in women , with some finding no difference in outcomes or increased adverse events in women ( 2428 ) . Given the conflicting data in the literature , we sought to perform a comprehensive analysis of sex-based differences in patients having TAVR by using the clinical trial structure of the PARTNER experience ( encompassing all TAVR patients treated in not only the r and omized PARTNER trials but also the r and omized and nonr and omized continued access registries ) . We report the baseline demographic characteristics and core laboratoryassessed echocardiographic parameters of women and men treated with TAVR , as well as adjudicated 30-day and 1-year outcomes stratified by sex . Methods Study Design and Patients The PARTNER trial incorporated 2 parallel prospect i ve , multicenter , r and omized , active treatmentcontrolled clinical trials . Patients were divided into 2 cohorts . Cohort A comprised patients who were considered to be high-risk c and i date s for surgery , as defined by a Society of Thoracic Surgeons Predicted Risk of Mortality ( STS-PROM ) score of at least 8 % ( on a scale of 0 % to 100 % , with higher scores indicating greater risk for death within 30 days after surgery ) ( 13 ) and /or by the presence of coexisting conditions associated with a 15 % or greater risk for death at 30 days . Cohort B comprised those who were not considered to be suitable c and i date s for surgery because they had coexisting conditions associated with a 50 % or greater probability of death or serious irreversible morbidity after surgery based on a multidisciplinary heart team assessment . In cohort A , patients were r and omly assigned to TAVR or SAVR ; in cohort B , patients were r and omly assigned to TAVR or medical therapy . Patients in cohort A were enrolled from 11 May 2007 to 28 August 2009 , and those in cohort B were enrolled from 11 May 2007 to 16 March 2009 . After enrollment in the r and omized PARTNER trial , sites were able to continue to consecutively enroll patients in a continued access registry using the same inclusion and exclusion criteria . The purpose of the continued access registry was to accumulate greater real-world experience with regard to the safety and efficacy of TAVR while approval by the U.S. Food and Drug Administration was pending . At the time of initiation of the registry , TAVR could not be performed in the United States unless the patient was formally enrolled in the registry or a comparable clinical trial . Because enrollment in the inoperable trial ( cohort B ) was completed 6 months before enrollment in the high-risk trial ( cohort A ) was completed , investigators decided to extend r and omization of cohort B into the continued access registry to prevent enrollment bias in the ongoing high-risk trial . Once enrollment in the high-risk trial was completed , both cohorts were enrolled in a nonr and omized continued access registry . Enrollment in this registry concluded on 9 January 2012 . The same data collection procedures and follow-up used for the r and omized PARTNER trial were used for the continued access registry . The same clinical events committee , adjudication process , and core laboratory interpretation of echocardiographic data were also used for both the r and omized and continued access portions of the PARTNER trial . The institutional review board at each site approved the study , and all patients provided written informed consent . End Points The 30-day and 1-year frequencies of all-cause mortality , cardiovascular mortality , rehospitalization , stroke , major vascular complications , major bleeding , myocardial infa rct ion , acute kidney injury , and need for a permanent pacemaker were recorded per the PARTNER trial protocol ( 4 , 5 ) . Major vascular complications were defined as any thoracic aortic dissection ; access site or access-related vascular injury leading to death , need for significant blood transfusions , or unplanned percutaneous or surgical intervention ; or distal embolization from a vascular source . Major bleeding was defined as a bleeding event that caused death or permanent disability , caused or prolonged a hospitalization , or required an open or endovascular procedure or a transfusion . All adverse events were fully adjudicated by an independent clinical events committee . Echocardiograms were obtained at baseline ; at discharge or 7 days , whichever came first ; and at 30 days , 6 months , and 1 year after the procedure . All echocardiograms were analyzed at an independent core laboratory that followed the American Society of Echocardiography st and ards for echocardiography core laboratories ( 29 ) . Statistical Analysis The current analysis was an as-treated analysis , which included all TAVR patients from cohort A , cohort B , and the continued access registry . Patients were stratified on the basis of sex . Continuous variables are presented as means and SDs and were compared using the t test ; categorical variables were compared by using the chi-square test or the Fisher exact test , as appropriate . KaplanMeier techniques were used for outcomes that contained all-cause death . All nonmortality outcomes were modeled by using a proportional subdistribution hazards regression to account for the competing risk for death ; the corresponding hazard ratios ( HRs ) and P values are reported from this model . For each sex , the cumulative incidence for 30-day and 1-year outcomes is summarized in the presence of all-cause death . A 2-sided level of 0.05 was used to indicate statistical significance . To assess the association between sex and all-cause mortality at 1 year , Cox multivariable regression analyses were performed . The multivariable model was created by forcing sex into a stepwise model selection procedure with clinical ly relevant c and i date variables using an entry/stay criterion of a P value less than 0.10 . Variables of clinical interest were included if the variable was significant ( P < 0.10 ) in the univariate Cox model . A supplemental model included moderate or severe paravalvular regurgitation at discharge and any major vascular complication as a time-dependent covariate along with variables selected in the final model . Using the same variables as those selected for the multivariable model for mortality , we tested for an association between sex and rehospitalization while accounting for the competing risk for death . We also tested for an interaction between sex and treatment approach ( transfemoral vs. transapical TAVR ) on 1-year all-cause mortality . Analyses were done using the FREQ , TTEST , UNIVARIATE , PHREG , and LIFETEST procedures in SAS , version 9.2 ( SAS Institute ) . Clinical Trial Registration The PARTNER trial was registered at Clinical Trials.gov on 14 September 2007 , slightly more than 4 months after the first patient was enrolled on 11 May 2007 . Only 41 ( 1.3 % ) of the 3216 total patients were enrolled before registration of the trial , and no interval analysis was conducted between enrollment of the first patient and registration of the trial . Role of the Funding Source The PARTNER trial was funded by Edwards Lifesciences , and the protocol was developed collaboratively by the sponsor and the steering committee . The funding source had no involvement in the design , analysis , or interpretation of this sub study or the decision to publish the manuscript . Results Baseline Characteristics All 2559 patients who had TAVR in the PARTNER trial were analyzed on the basis of their sex ( Table 1 ) . Of these , 2000 were in the nonr and omized continued access registry , 40 were in the r and omized continued access registry , and 519 were in the r and omized trial . Five patients in cohort A , 1 in cohort B , and none in the continued access registries were lost to follow-up . A total of 47.7 % of all patients were women , and 52.3 % were men . Table 1 . Study Population The baseline presenting characteristics varied between sexes in terms of demographic variables and AIMS In a prospect i ve r and omised trial we aim ed to compare transapical transcatheter aortic valve implantation ( a-TAVI ) with surgical aortic valve replacement ( SAVR ) in operable elderly patients . METHODS AND RESULTS The study was design ed as a r and omised controlled trial of a-TAVI ( Edwards SAPIEN heart valve system ; Edwards Lifesciences , Irvine , CA , USA ) vs. SAVR . Operable patients with isolated aortic valve stenosis and an age ≥75 years were included . The primary endpoint was the composite of all-cause mortality , cerebral stroke and /or renal failure requiring haemodialysis at 30 days . After advice from the Data Safety Monitoring Board , the study was prematurely terminated after the inclusion of 70 patients because of an excess of events in the a-TAVI group . The primary endpoint was met in five a-TAVI patients ( two deaths , two strokes , and one case of renal failure requiring dialysis ) vs. one stroke in the SAVR group ( p=0.07 ) . In the a-TAVI group , one patient was converted to SAVR because of an abnormally positioned heart , and four patients were re-operated with open heart surgery because of annulus rupture ( n=1 ) , severe paravalvular leakage ( n=2 ) , and blockage of the left coronary artery ( n=1 ) . In the SAVR group , one patient was converted to TAVI because of a large intra-thoracic goitre . CONCLUSIONS Given the limitations of a small prematurely terminated study , our results suggest that a-TAVI in its present form may be associated with complications and device success rates in low-risk patients similar or even inferior to those found in high-risk patients with aortic valve stenosis . This will probably change in the near future with improved catheter based devices and better pre-procedural assessment Background —Atrial fibrillation ( AF ) is an important risk factor for stroke and is common among elderly patients undergoing transcatheter aortic valve implantation . The aim of this study was to assess the impact of AF on clinical outcomes among patients undergoing transcatheter aortic valve implantation . Methods and Results —Between August 2007 and October 2011 , a total of 389 high-risk patients undergoing transcatheter aortic valve implantation were included into a prospect i ve registry . AF was recorded in 131 patients ( 33.7 % ) with a mean CHA2DS2–VASC score of 4.5±1.2 and was paroxysmal in 26 ( 25.0 % ) , persistent in 8 ( 7.7 % ) , and permanent in 70 patients ( 67.3 % ) . Patients with and without AF had similar baseline characteristics except for fewer revascularization procedures ( coronary artery bypass grafting : 12 % versus 22 % ; P=0.03 ) among AF patients . At 1 year , all-cause mortality was higher among patients with AF ( 30.9 % ) compared with those without AF ( 13.9 % ; hazard ratio [ HR ] , 2.36 ; 95 % confidence interval [ CI ] , 1.43–3.90 ; P=0.0008 ) . This was observed irrespective of the type of AF ( permanent , HR , 2.47 ; 95 % CI , 1.40–4.38 ; persistent , HR , 3.60 ; 95 % CI , 1.10–11.78 ; paroxysmal , HR , 2.88 ; 95 % CI , 1.37–6.05 ) . Mortality gradually increased with higher CHA2DS2–VASC scores ( score 1–3 : HR , 2.20 ; 95 % CI , 0.92–5.27 ; score 6–8 : HR , 4.12 ; 95 % CI , 2.07–8.20 ) . The risks of stroke ( 3.9 % versus 5.1 % ; HR , 0.76 ; 95 % CI , 0.23–1.96 ; P=0.47 ) and life-threatening bleeding ( 19.8 % versus 14.7 % ; HR , 1.37 ; 95 % CI , 0.86–2.19 ; P=0.19 ) were similar among patients with and without AF . Conclusions —AF is common among high-risk patients with severe aortic stenosis undergoing transcatheter aortic valve implantation and is associated with a > 2-fold increased risk of all-cause and cardiovascular mortality , irrespective of the type of AF . The gradient of risk directly correlates with the CHA2DS2–VASC score Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more OBJECTIVES This study sought to present the U.K. experience to date with the second-generation LOTUS bioprosthesis ( Boston Scientific , Natick , Massachusetts ) . BACKGROUND First-generation transcatheter aortic valves have limitations . Second-generation repositionable valves may improve on some of those limitations . METHODS Prospect ively collected data relating to procedural and in-hospital outcome was analyzed from 10 implantation centers in the United Kingdom . RESULTS Implants in 228 patients age 81.4 ± 7.6 years were studied ; 53.5 % were male . Mean logistic EuroScore was 17.5 ± 12.4 . One hundred eighty-seven ( 82.0 % ) were undertaken for aortic stenosis , 7 ( 3.1 % ) for aortic regurgitation , and 34 ( 14.9 % ) for mixed aortic valve disease . A total of 67.1 % of cases were done under local anesthetic and /or sedation with transfemoral access in 94.7 % and transaortic in 5.3 % . Three device sizes were used : 23 mm ( n = 66 , 28.9 % ) , 25 mm ( n = 39 , 17.1 % ) , and 27 mm ( n = 123 , 53.9 % ) . The valve was successfully deployed in 99.1 % of procedures . After implantation , the mean aortic gradient was 11.4 ± 5.4 mm Hg and aortic valve area 1.6 ± 0.5 cm(2 ) . In-hospital mortality was 1.8 % ( n = 4 ) . Complications included cardiac tamponade ( 1.8 % ) , conversion to sternotomy ( 1.3 % ) , stroke ( 3.9 % ) , vascular access-related ( 7.0 % ) , and acute kidney injury ( 7.9 % ) . The incidence of moderate/severe aortic regurgitation was 0.8 % ( n = 2 ) . A total of 31.8 % of patients required new permanent pacemaker implantation . CONCLUSIONS This analysis represents the largest published series on use of the LOTUS valve . Outcomes using this valve are excellent . In-hospital mortality is very low . Complication rates are low , and the LOTUS valve improves on first-generation valves , particularly with regard to residual aortic regurgitation BACKGROUND We compared transcatheter aortic-valve replacement ( TAVR ) , using a self-exp and ing transcatheter aortic-valve bioprosthesis , with surgical aortic-valve replacement in patients with severe aortic stenosis and an increased risk of death during surgery . METHODS We recruited patients with severe aortic stenosis who were at increased surgical risk as determined by the heart team at each study center . Risk assessment included the Society of Thoracic Surgeons Predictor Risk of Mortality estimate and consideration of other key risk factors . Eligible patients were r and omly assigned in a 1:1 ratio to TAVR with the self-exp and ing transcatheter valve ( TAVR group ) or to surgical aortic-valve replacement ( surgical group ) . The primary end point was the rate of death from any cause at 1 year , evaluated with the use of both noninferiority and superiority testing . RESULTS A total of 795 patients underwent r and omization at 45 centers in the United States . In the as-treated analysis , the rate of death from any cause at 1 year was significantly lower in the TAVR group than in the surgical group ( 14.2 % vs. 19.1 % ) , with an absolute reduction in risk of 4.9 percentage points ( upper boundary of the 95 % confidence interval , -0.4 ; P<0.001 for noninferiority ; P = 0.04 for superiority ) . The results were similar in the intention-to-treat analysis . In a hierarchical testing procedure , TAVR was noninferior with respect to echocardiographic indexes of valve stenosis , functional status , and quality of life . Exploratory analyses suggested a reduction in the rate of major adverse cardiovascular and cerebrovascular events and no increase in the risk of stroke . CONCLUSIONS In patients with severe aortic stenosis who are at increased surgical risk , TAVR with a self-exp and ing transcatheter aortic-valve bioprosthesis was associated with a significantly higher rate of survival at 1 year than surgical aortic-valve replacement . ( Funded by Medtronic ; U.S. CoreValve High Risk Study Clinical Trials.gov number , NCT01240902 . ) Background —New generation transcatheter heart valves ( THV ) may improve clinical outcomes of transcatheter aortic valve implantation . Methods and Results —In a nationwide , prospect i ve , multicenter cohort study ( Swiss Transcatheter Aortic Valve Implantation Registry , NCT01368250 ) , outcomes of consecutive transfemoral transcatheter aortic valve implantation patients treated with the Sapien 3 THV ( S3 ) versus the Sapien XT THV ( XT ) were investigated . An overall of 153 consecutive S3 patients were compared with 445 consecutive XT patients . Postprocedural mean transprosthetic gradient ( 6.5±3.0 versus 7.8±6.3 mm Hg , P=0.17 ) did not differ between S3 and XT patients , respectively . The rate of more than mild paravalvular regurgitation ( 1.3 % versus 5.3 % , P=0.04 ) and of vascular ( 5.3 % versus 16.9 % , P<0.01 ) complications were significantly lower in S3 patients . A higher rate of new permanent pacemaker implantations was observed in patients receiving the S3 valve ( 17.0 % versus 11.0 % , P=0.01 ) . There were no significant differences for disabling stroke ( S3 1.3 % versus XT 3.1 % , P=0.29 ) and all-cause mortality ( S3 3.3 % versus XT 4.5 % , P=0.27 ) . Conclusions —The use of the new generation S3 balloon-exp and able THV reduced the risk of more than mild paravalvular regurgitation and vascular complications but was associated with an increased permanent pacemaker rate compared with the XT . Transcatheter aortic valve implantation using the newest generation balloon-exp and able THV is associated with a low risk of stroke and favorable clinical outcomes . Clinical Trial Registration —URL : http://www . clinical trials.gov . Unique identifier : NCT01368250 OBJECTIVES The U.K. Transcatheter Aortic Valve Implantation Registry reported 30-day and 1-year mortality rates of 7.1 % and 21.4 % , respectively , for patients who underwent transcatheter aortic valve replacement ( TAVR ) in the United Kingdom between 2007 and 2009 . The study aim was to report long-term outcomes in this same cohort of patients . BACKGROUND There are few data on outcomes beyond 3 years after TAVR in any notable number of patients . METHODS Data from all TAVR procedures performed in the United Kingdom between January 2007 and December 2009 were prospect ively collected . All-cause mortality status was reported in March 2014 . Mortality tracking was achieved in 97.7 % patients . RESULTS The minimal time from replacement to census was 4.1 years , and the maximal time was 7.0 years . The 3- and 5-year survival rates were 61.2 % and 45.5 % , respectively . Independent predictors of 3-year mortality were renal dysfunction ( hazard ratio [ HR ] : 1.65 ) , atrial fibrillation ( HR : 1.36 ) , logistic European System for Cardiac Operative Risk Evaluation ( EuroSCORE ) ≥18.5 ( HR : 1.33 ) , respiratory dysfunction ( HR : 1.28 ) , and ventricular dysfunction ( left ventricular ejection fraction < 30 % ) ( HR : 1.53 ) . Coronary artery disease ( HR : 1.28 ) and age ( HR : 1.03 ) were additional independent predictors of mortality at 5 years . Stroke within 30 days of TAVR was the only independent procedural predictor of mortality at 3 and 5 years ( HR : 2.17 at 3 years ) . Device type , access route , and paravalvular leak did not independently predict long-term outcome . CONCLUSIONS In the large U.K. Transcatheter Aortic Valve Implantation Registry , long-term outcomes after TAVR are favorable with 3- and 5-year survival rates of 61.2 % and 45.5 % , respectively . Long-term survival after TAVR is largely determined by intrinsic patient factors . Other than stroke , procedural variables , including paravalvular aortic leak , did not appear to be independent predictors of long-term survival BACKGROUND Little is known about the incidence of prosthesis-patient mismatch ( PPM ) and its impact on outcomes after transcatheter aortic valve replacement ( TAVR ) . OBJECTIVES The objectives of this study were : 1 ) to compare the incidence of PPM in the TAVR and surgical aortic valve replacement ( SAVR ) r and omized control trial ( RCT ) arms of the PARTNER ( Placement of AoRTic TraNscathetER Valves ) I Trial cohort A ; and 2 ) to assess the impact of PPM on regression of left ventricular ( LV ) hypertrophy and mortality in these 2 arms and in the TAVR nonr and omized continued access ( NRCA ) registry cohort . METHODS The PARTNER Trial cohort A r and omized patients 1:1 to TAVR or bioprosthetic SAVR . Postoperative PPM was defined as absent if the indexed effective orifice area ( EOA ) was > 0.85 cm(2)/m(2 ) , moderate if the indexed EOA was ≥0.65 but ≤0.85 cm(2)/m(2 ) , or severe if the indexed EOA was < 0.65 cm(2)/m(2 ) . LV mass regression and mortality were analyzed using the SAVR- RCT ( n = 270 ) , TAVR- RCT ( n = 304 ) , and TAVR-NRCA ( n = 1,637 ) cohorts . RESULTS The incidence of PPM was 60.0 % ( severe : 28.1 % ) in the SAVR- RCT cohort versus 46.4 % ( severe : 19.7 % ) in the TAVR- RCT cohort ( p < 0.001 ) and 43.8 % ( severe : 13.6 % ) in the TAVR-NRCA cohort . In patients with an aortic annulus diameter < 20 mm , severe PPM developed in 33.7 % undergoing SAVR compared with 19.0 % undergoing TAVR ( p = 0.002 ) . PPM was an independent predictor of less LV mass regression at 1 year in the SAVR- RCT ( p = 0.017 ) and TAVR-NRCA ( p = 0.012 ) cohorts but not in the TAVR- RCT cohort ( p = 0.35 ) . Severe PPM was an independent predictor of 2-year mortality in the SAVR- RCT cohort ( hazard ratio [ HR ] : 1.78 ; p = 0.041 ) but not in the TAVR- RCT cohort ( HR : 0.58 ; p = 0.11 ) . In the TAVR-NRCA cohort , severe PPM was not a predictor of 1-year mortality in all patients ( HR : 1.05 ; p = 0.60 ) but did independently predict mortality in the subset of patients with no post-procedural aortic regurgitation ( HR : 1.88 ; p = 0.02 ) . CONCLUSIONS In patients with severe aortic stenosis and high surgical risk , PPM is more frequent and more often severe after SAVR than TAVR . Patients with PPM after SAVR have worse survival and less LV mass regression than those without PPM . Severe PPM also has a significant impact on survival after TAVR in the subset of patients with no post-procedural aortic regurgitation . TAVR may be preferable to SAVR in patients with a small aortic annulus who are susceptible to PPM to avoid its adverse impact on LV mass regression and survival . ( The PARTNER Trial : Placement of AoRTic TraNscathetER Valve Trial ; NCT00530894 ) BACKGROUND Transcatheter aortic valve replacement ( TAVR ) has evolved into a routine procedure with good outcomes in high-risk patients . OBJECTIVES TAVR complication rates were evaluated based on prospect i ve data from the German Aortic Valve Registry ( GARY ) . METHODS From 2011 to 2013 , a total of 15,964 TAVR procedures were registered . We evaluated the total cohort for severe vital complications ( SVCs ) , including the following : death on the day of intervention , conversion to sternotomy , low cardiac output that required mechanical support , aortic dissection , and annular rupture ; technical complications of the procedures ( TCOs ) , such as repositioning or retrieval of the valve prosthesis and embolization of the prosthesis ; and other complications . RESULTS Mean patient age was 81 ± 6 years , 54 % of the patients were women , the median logistic Euroscore I was 18.3 , the German aortic valve score was 5.6 , and the Society of Thoracic Surgeons score was 5.0 . Overall in-hospital mortality was 5.2 % , whereas SVCs occurred in 5.0 % of the population . Independent predictors for SVCs were female sex , pre-operative New York Heart Association functional class IV , ejection fraction < 30 % , pre-operative intravenous inotropes , arterial vascular disease , and higher degree of calcifications . TCOs occurred in 4.7 % of patients and decreased significantly from 2011 to 2013 . An emergency sternotomy was performed in 1.3 % of the patients ; however , multivariate analysis did not identify any predictors for conversion to sternotomy . CONCLUSIONS The all-comers GARY registry revealed good outcomes after TAVR and a regression in complications . Survival of approximately 60 % of patients who experienced SVCs or who required sternotomy underlines the need for heart team-led indication , intervention , and follow-up care of TAVR patients BACKGROUND In patients with severe aortic stenosis at increased risk for surgery , self-exp and ing transcatheter aortic valve replacement ( TAVR ) is associated with improved 2-year survival compared with surgery . OBJECTIVES This study sought to determine whether this clinical benefit was sustained over time . METHODS Patients with severe aortic stenosis deemed at increased risk for surgery by a multidisciplinary heart team were r and omized 1:1 to TAVR or open surgical valve replacement ( SAVR ) . Three-year clinical and echocardiographic outcomes were obtained in those patients with an attempted procedure . RESULTS A total of 797 patients underwent r and omization at 45 U.S. centers ; 750 patients underwent an attempted procedure . Three-year all-cause mortality or stroke was significantly lower in TAVR patients ( 37.3 % vs. 46.7 % in SAVR ; p = 0.006 ) . Adverse clinical outcome components were also reduced in TAVR patients compared with SAVR patients , including all-cause mortality ( 32.9 % vs. 39.1 % , respectively ; p = 0.068 ) , all stroke ( 12.6 % vs. 19.0 % , respectively ; p = 0.034 ) , and major adverse cardiovascular or cerebrovascular events ( 40.2 % vs. 47.9 % , respectively ; p = 0.025 ) . At 3 years aortic valve hemodynamics were better with TAVR patients ( mean aortic valve gradient 7.62 ± 3.57 mm Hg vs. 11.40 ± 6.81 mm Hg in SAVR ; p < 0.001 ) , although moderate or severe residual aortic regurgitation was higher in TAVR patients ( 6.8 % vs. 0.0 % in SAVR ; p < 0.001 ) . There was no clinical evidence of valve thrombosis in either group . CONCLUSIONS Patients with severe aortic stenosis at increased risk for surgery had improved 3-year clinical outcomes after TAVR compared with surgery . Aortic valve hemodynamics were more favorable in TAVR patients without differences in structural valve deterioration . ( Safety and Efficacy Study of the Medtronic CoreValve ( ® ) System in the Treatment of Symptomatic Severe Aortic Stenosis in High Risk and Very High Risk Subjects Who Need Aortic Valve Replacement ; NCT01240902 ) OBJECTIVES The purpose of this study was to determine the safety and effectiveness of the SAPIEN XT versus SAPIEN systems ( Edwards Lifesciences , Irvine , California ) in patients with symptomatic , severe aortic stenosis ( AS ) who were not c and i date s for surgery . BACKGROUND Transcatheter aortic valve replacement ( TAVR ) has become the st and ard of care for inoperable patients with severe , symptomatic AS . In the PARTNER ( Placement of Aortic Transcatheter Valves ) IB trial , a reduction in all-cause mortality was observed in patients undergoing TAVR with the balloon-exp and able SAPIEN transcatheter heart valve compared with st and ard therapy , but the SAPIEN valve was associated with adverse periprocedural complications , including vascular complications , major bleeding , and paravalvular regurgitation . The newer , low-profile SAPIEN XT system was developed to reduce these adverse events . METHODS A total of 560 patients were enrolled at 28 sites in the United States from April 2011 to February 2012 . Patients were r and omized to receive the SAPIEN or SAPIEN XT systems . The primary endpoint was a nonhierarchical composite of all-cause mortality , major stroke , and rehospitalization at 1 year in the intention-to-treat population , assessed by noninferiority testing . Pre-specified secondary endpoints included cardiovascular death , New York Heart Association functional class , myocardial infa rct ion , stroke , acute kidney injury , vascular complications , bleeding , 6-min walk distance , and valve performance ( by echocardiography ) . RESULTS Both overall and major vascular complications were higher at 30 days in patients undergoing TAVR with SAPIEN compared with SAPIEN XT ( overall : 22.1 % vs. 15.5 % ; p = 0.04 ; major : 15.2 % vs. 9.5 % ; p = 0.04 ) . Bleeding requiring blood transfusions was also more frequent with SAPIEN compared with SAPIEN XT ( 10.6 % vs. 5.3 % ; p = 0.02 ) . At 1-year follow-up , the nonhierarchical composite of all-cause mortality , major stroke , or rehospitalization was similar ( 37.7 % SAPIEN vs. 37.2 % SAPIEN XT ; noninferiority p value < 0.002 ) ; no differences in the other major pre-specified endpoints were found . CONCLUSIONS In inoperable patients with severe , symptomatic AS , the lower-profile SAPIEN XT is noninferior to SAPIEN with fewer vascular complications and a lesser need for blood transfusion . ( The PARTNER II Trial : Placement of AoRTic TraNscathetER Valves ; NCT01314313 ) OBJECTIVES The purpose of this study was to prospect ively evaluate the safety and clinical performance of the CoreValve Evolut R transcatheter aortic valve replacement ( TAVR ) system ( Medtronic , Inc. , Minneapolis , Minnesota ) in a single-arm , multicenter pivotal study in high- or extreme-risk patients with symptomatic aortic valve stenosis . BACKGROUND Although outcomes following TAVR are improving , challenges still exist . The repositionable 14-F equivalent CoreValve Evolut R TAVR system was developed to mitigate some of these challenges . METHODS Suitable patients ( n = 60 ) underwent TAVR with a 26- or 29-mm Evolut R valve . Primary safety endpoints were mortality and stroke at 30 days . Primary clinical performance endpoints were device success per the VARC-2 ( Valve Academic Research Consortium-2 ) and the percent of patients with mild or less aortic regurgitation 24 h to 7 days post-procedure . RESULTS Patients ( 66.7 % female ; mean age 82.8 ± 6.1 years ; Society of Thoracic Surgeons Score 7.0 ± 3.7 % ) underwent TAVR via the transfemoral route in 98.3 % , using a 29-mm valve in 68.3 % of patients . All attempts at repositioning were successful . No death or stroke was observed up to 30 days . The VARC-2 overall device success rate was 78.6 % . Paravalvular regurgitation post TAVR was mild or less in 96.6 % , moderate in 3.4 % , and severe in 0 % at 30 days . Major vascular complications occurred in 8.3 % , and permanent pacemaker implantation was required in 11.7 % of patients . CONCLUSIONS The repositionable 14-F equivalent Evolut R TAVR system is safe and effective at treating high-risk symptomatic aortic stenosis patients . Repositioning was successful when required in all patients , with low rates of moderate or severe paravalvular aortic regurgitation and low permanent pacemaker implantation . ( The Medtronic CoreValve ™ Evolut R ™ CE Mark Clinical Study ; NCT01876420 ) BACKGROUND The Placement of Aortic Transcatheter Valves ( PARTNER ) trial showed that mortality at 1 year , 2 years , and 3 years is much the same with transcatheter aortic valve replacement ( TAVR ) or surgical aortic valve replacement ( SAVR ) for high-risk patients with aortic stenosis . We report here the 5-year outcomes . METHODS We did this r and omised controlled trial at 25 hospitals , in Canada ( two ) , Germany ( one ) , and the USA ( 23 ) . We used a computer-generated r and omisation sequence to r and omly assign high-risk patients with severe aortic stenosis to either SAVR or TAVR with a balloon-exp and able bovine pericardial tissue valve by either a transfemoral or transapical approach . Patients and their treating physicians were not masked to treatment allocation . The primary outcome of the trial was all-cause mortality in the intention-to-treat population at 1 year , we present here predefined outcomes at 5 years . The study is registered with Clinical Trials.gov , number NCT00530894 . FINDINGS We screened 3105 patients , of whom 699 were enrolled ( 348 assigned to TAVR , 351 assigned to SAVR ) . Overall mean Society of Thoracic Surgeons Predicted Risk of Mortality score was 11·7 % . At 5 years , risk of death was 67·8 % in the TAVR group compared with 62·4 % in the SAVR group ( hazard ratio 1·04 , 95 % CI 0·86 - 1·24 ; p=0·76 ) . We recorded no structural valve deterioration requiring surgical valve replacement in either group . Moderate or severe aortic regurgitation occurred in 40 ( 14 % ) of 280 patients in the TAVR group and two ( 1 % ) of 228 in the SAVR group ( p<0·0001 ) , and was associated with increased 5-year risk of mortality in the TAVR group ( 72·4 % for moderate or severe aortic regurgitation vs 56·6 % for those with mild aortic regurgitation or less ; p=0·003 ) . INTERPRETATION Our findings show that TAVR as an alternative to surgery for patients with high surgical risk results in similar clinical outcomes . FUNDING Edwards Lifesciences IMPORTANCE Introducing new medical devices into routine practice raises concerns because patients and outcomes may differ from those in r and omized trials . OBJECTIVE To up date the previous report of 30-day outcomes and present 1-year outcomes following transcatheter aortic valve replacement ( TAVR ) in the United States . DESIGN , SETTING , AND PARTICIPANTS Data from the Society of Thoracic Surgeons/American College of Cardiology ( STS/ACC ) Transcatheter Valve Therapies Registry were linked with patient-specific Centers for Medicare & Medicaid Services ( CMS ) administrative cl aims data . At 299 US hospitals , 12 182 patients linked with CMS data underwent TAVR procedures performed from November 2011 through June 30 , 2013 , and the end of the follow-up period was June 30 , 2014 . EXPOSURE Transcatheter aortic valve replacement . MAIN OUTCOMES AND MEASURES One-year outcomes including mortality , stroke , and rehospitalization were evaluated using multivariate modeling . RESULTS The median age of patients was 84 years and 52 % were women , with a median STS Predicted Risk of Operative Mortality ( STS PROM ) score of 7.1 % . Following the TAVR procedure , 59.8 % were discharged to home and the 30-day mortality was 7.0 % ( 95 % CI , 6.5%-7.4 % ) ( n = 847 deaths ) . In the first year after TAVR , patients were alive and out of the hospital for a median of 353 days ( interquartile range , 312 - 359 days ) ; 24.4 % ( n = 2074 ) of survivors were rehospitalized once and 12.5 % ( n = 1525 ) were rehospitalized twice . By 1 year , the overall mortality rate was 23.7 % ( 95 % CI , 22.8%-24.5 % ) ( n = 2450 deaths ) , the stroke rate was 4.1 % ( 95 % CI , 3.7%-4.5 % ) ( n = 455 stroke events ) , and the rate of the composite outcome of mortality and stroke was 26.0 % ( 25.1%-26.8 % ) ( n = 2719 events ) . Characteristics significantly associated with 1-year mortality included advanced age ( hazard ratio [ HR ] for ≥95 vs < 75 years , 1.61 [ 95 % CI , 1.24 - 2.09 ] ; HR for 85 - 94 years vs < 75 years , 1.35 [ 95 % CI , 1.18 - 1.55 ] ; and HR for 75 - 84 years vs < 75 years , 1.23 [ 95 % CI , 1.08 - 1.41 ] ) , male sex ( HR , 1.21 ; 95 % CI , 1.12 - 1.31 ) , end-stage renal disease ( HR , 1.66 ; 95 % CI , 1.41 - 1.95 ) , severe chronic obstructive pulmonary disease ( HR , 1.39 ; 95 % CI , 1.25 - 1.55 ) , nontransfemoral access ( HR , 1.37 ; 95 % CI , 1.27 - 1.48 ) , STS PROM score greater than 15 % vs less than 8 % ( HR , 1.82 ; 95 % CI , 1.60 - 2.06 ) , and preoperative atrial fibrillation/flutter ( HR , 1.37 ; 95 % CI , 1.27 - 1.48 ) . Compared with men , women had a higher risk of stroke ( HR , 1.40 ; 95 % CI , 1.15 - 1.71 ) . CONCLUSIONS AND RELEVANCE Among patients undergoing TAVR in US clinical practice , at 1-year follow-up , overall mortality was 23.7 % , the stroke rate was 4.1 % , and the rate of the composite outcome of death and stroke was 26.0 % . These findings should be helpful in discussion s with patients undergoing TAVR BACKGROUND Previous trials have shown that among high-risk patients with aortic stenosis , survival rates are similar with transcatheter aortic-valve replacement ( TAVR ) and surgical aortic-valve replacement . We evaluated the two procedures in a r and omized trial involving intermediate-risk patients . METHODS We r and omly assigned 2032 intermediate-risk patients with severe aortic stenosis , at 57 centers , to undergo either TAVR or surgical replacement . The primary end point was death from any cause or disabling stroke at 2 years . The primary hypothesis was that TAVR would not be inferior to surgical replacement . Before r and omization , patients were entered into one of two cohorts on the basis of clinical and imaging findings ; 76.3 % of the patients were included in the transfemoral-access cohort and 23.7 % in the transthoracic-access cohort . RESULTS The rate of death from any cause or disabling stroke was similar in the TAVR group and the surgery group ( P=0.001 for noninferiority ) . At 2 years , the Kaplan-Meier event rates were 19.3 % in the TAVR group and 21.1 % in the surgery group ( hazard ratio in the TAVR group , 0.89 ; 95 % confidence interval [ CI ] , 0.73 to 1.09 ; P=0.25 ) . In the transfemoral-access cohort , TAVR result ed in a lower rate of death or disabling stroke than surgery ( hazard ratio , 0.79 ; 95 % CI , 0.62 to 1.00 ; P=0.05 ) , whereas in the transthoracic-access cohort , outcomes were similar in the two groups . TAVR result ed in larger aortic-valve areas than did surgery and also result ed in lower rates of acute kidney injury , severe bleeding , and new-onset atrial fibrillation ; surgery result ed in fewer major vascular complications and less paravalvular aortic regurgitation . CONCLUSIONS In intermediate-risk patients , TAVR was similar to surgical aortic-valve replacement with respect to the primary end point of death or disabling stroke . ( Funded by Edwards Lifesciences ; PARTNER 2 Clinical Trials.gov number , NCT01314313 . ) OBJECTIVES This study sought to determine the incidence of new-onset atrial fibrillation ( AF ) associated with different methods of isolated aortic valve replacement (AVR)-transfemoral ( TF ) , transapical ( TA ) , and transaortic ( TAo ) catheter-based valve replacement and conventional surgical approaches . BACKGROUND The relative incidences of AF associated with the various access routes for AVR have not been well characterized . METHODS In this single-center , retrospective cohort study , we evaluated a total of 231 consecutive patients who underwent AVR for degenerative aortic stenosis ( AS ) between March 2010 and September 2012 . Patients with a history of paroxysmal , persistent , or chronic AF , with bicuspid aortic valves , and patients who died within 48 h after AVR were excluded . A total of 123 patients ( 53 % of total group ) qualified for inclusion . Data on documented episodes of new-onset AF , along with all clinical , echocardiographic , procedural , and 30-day follow-up data , were collated . RESULTS AF occurred in 52 patients ( 42.3 % ) . AF incidence varied according to the procedural method . AF occurred in 60 % of patients who underwent surgical AVR ( SAVR ) , in 53 % after TA-TAVR , in 33 % after TAo-TAVR cases , and 14 % after TF-TAVR . The episodes occurred at a median time interval of 53 ( 25th to 75th percentile , 41 to 87 ) h after completion of the procedure . Procedures without pericardiotomy had an 82 % risk reduction of AF compared with those with pericardiotomy ( adjusted odds ratio : 0.18 ; 95 % confidence interval : 0.05 to 0.59 ) . CONCLUSIONS AF was a common complication of AVR with a cumulative incidence of > 40 % in elderly patients with degenerative AS who underwent either SAVR or TAVR . AF was most common with SAVR and least common with TF-TAVR . Procedures without pericardiotomy were associated with a lower incidence of AF BACKGROUND The U.S. pivotal trial for the self-exp and ing valve found that among patients with severe aortic stenosis at increased risk for surgery , the 1-year survival rate was 4.9 percentage points higher in patients treated with a self-exp and ing transcatheter aortic valve bioprosthesis than in those treated with a surgical bioprosthesis . OBJECTIVES Longer-term clinical outcomes were examined to confirm if this mortality benefit is sustained . METHODS Patients with severe aortic stenosis who were at increased surgical risk were recruited . Eligible patients were r and omly assigned in a 1:1 ratio to transcatheter aortic valve replacement with the self-exp and ing transcatheter valve ( transcatheter aortic valve replacement [ TAVR ] group ) or to aortic valve replacement with a surgical bioprosthesis ( surgical group ) . The 2-year clinical and echocardiographic outcomes were evaluated in these patients . RESULTS A total of 797 patients underwent r and omization at 45 centers in the United States . The rate of 2-year all-cause mortality was significantly lower in the TAVR group ( 22.2 % ) than in the surgical group ( 28.6 % ; log-rank test p < 0.05 ) in the as-treated cohort , with an absolute reduction in risk of 6.5 percentage points . Similar results were found in the intention-to-treat cohort ( log-rank test p < 0.05 ) . The rate of 2-year death or major stroke was significantly lower in the TAVR group ( 24.2 % ) than in the surgical group ( 32.5 % ; log-rank test p = 0.01 ) . CONCLUSIONS In patients with severe aortic stenosis who are at increased surgical risk , the higher rate of survival with a self-exp and ing TAVR compared with surgery was sustained at 2 years . ( Safety and Efficacy Study of the Medtronic CoreValve System in the Treatment of Symptomatic Severe Aortic Stenosis in High Risk and Very High Risk Subjects Who Need Aortic Valve Replacement ; NCT01240902 ) |
12,389 | 23,152,265 | Some unwanted effects have also been reported with components of IE nutrition in critical care patients and it is unknown whether there would be detrimental effects by administering IE nutrition to patients who could require critical care support after their surgery . | BACKGROUND Post-operative management in gastrointestinal ( GI ) surgery is becoming well established with ' Enhanced Recovery After Surgery ' protocol s starting 24 hours prior to surgery with carbohydrate loading and early oral or enteral feeding given to patients the first day following surgery .
However , whether or not nutritional intervention should be initiated earlier in the preoperative period remains unclear .
Poor pre-operative nutritional status has been linked consistently to an increase in post-operative complications and poorer surgical outcome .
OBJECTIVES To review the literature on preoperative nutritional support in patients undergoing gastrointestinal surgery ( GI ) . | BACKGROUND : This study was undertaken to test the hypothesis that early enteral nutrition might reduce the incidence of serious complications after major abdominal surgery . METHODS : In a r and omised double blind prospect i ve trial 30 patients received Nutri-drink and 30 patients received placebo through a nasoduodenal feeding tube . On the day of operation the patients were given median 600 ml of either nutrition or placebo , 60 ml per hour . On the first postoperative day the patients received either 1000 ml ( median ) of nutrition or placebo , on day 2 1200 ml ( median ) nutrition , 1400 ml placebo , on day 3 1000 ml ( median ) nutrition , 1150 ml placebo , and on day 4 1000 ml ( median ) nutrition , 800 ml placebo . All patients were followed up for 30 days by the same investigator . RESULTS : The two groups were similar with regard to nutritional status and type of operation . The rate of postoperative infectious complications was significantly lower in the nutrition group , two of 30 compared with 14 of 30 in the placebo group ( p = 0.0009 ) . CONCLUSION : Early enteral nutrition given to patients after major abdominal surgery results in an important reduction in infectious complications BACKGROUND & AIM The immunomodulating nutrition was supposed to reduce the incidence of complications in surgical patients , but many authors have question ed its value recently . The aim of the study was to assess the impact of enteral immunonutrition in postoperative period . METHODS Between January 2003 and December 2009 , 305 malnourished patients ( 123 F , 182 M , m. age 60.8 ) undergoing resection for pancreatic or gastric cancer , after preoperative 14 days of parenteral feeding , were r and omized in double-blind manner to receive either postoperative immunomodulating enteral diet ( IMEN ) or st and ard oligopeptide diet ( SEN ) . Outcome measures of the intend-to-treat analysis were : number and type of complications , length of hospitalization , mortality , and vital organ function . RESULTS Median postoperative hospital stay was 17.1 days in SEN and 13.1 days in IMEN group ( p = 0.006 ) . Infectious complications were observed in 60 patients ( 39.2 % ) in SEN and 43 ( 28.3 % ) in IMEN group ( p = 0.04 ) . Differences were also observed in overall morbidity ( 47.1 vs 33.5 % , p = 0.01 ) and mortality ( 5.9 vs 1.3 % , p = 0.03 ) , but the ratio of surgical complications , organ function , and treatment tolerance did not differ . CONCLUSIONS The study proved that postoperative immunomodulating enteral nutrition should be the treatment of choice in malnourished surgical cancer patients . The Clinical Trials Data base registry number : NCT00576940 Postoperative oral nutritional supplementation has been shown to be of clinical benefit . This study examined the clinical effects and cost of administration of oral supplements both before and after surgery Background / Aim Perioperative administration of immunoenriched diets attenuates the perioperative inflammatory response and reduces postoperative infection complications . However , many questions still remain unresolved in this area , such as the length of diet administration , diet composition , and the mechanisms involved . We performed an open , r and omized , triple-arm study comparing the effect of two perioperative feeding regimens with a postoperative one . Methods 46 c and i date s for major elective surgery for malignancy in the upper gastrointestinal tract were r and omized to drink preoperatively either 1 L of an immunoenriched formula ( Impact ) for 5 days ( IEF group ) or 1 L of Impact plus ( Impact enriched with glycine ) for 2 days ( IEF plus group ) . The same product as the patient received preoperatively was given to both groups for 7 days postoperatively . In the control group ( CON group ) , patients only received Impact for 7 days postoperatively ; there was no preoperative treatment . The main outcome measures were postoperative C-reactive protein ( CRP ) serum levels . Results In the two preoperatively supplemented groups ( treatment groups ) , perioperative endotoxin levels , CRP ( postoperative day 7 ) , and TNF-α ( postoperative days 1 and 3 ) levels were significantly lower compared to the CON group ( p < .01 ) . Furthermore , the length of postoperative IMU/ICU stay ( Impact 1.9 ± 1.3 days ; Impact plus 2.2 ± 1.1 days ; control group 5.9 ± 0.8 days ) and length of hospital stay ( Impact 19.7 ± 2.3 days ; Impact plus 20.1 ± 1.3 days ; control group 29.1 ± 3.6 days ) were both reduced in the treatment groups compared to the control group . Infectious complications ( Impact 2/14 ( 14 % ) ; Impact plus 5/17 ( 29 % ) ; control group 10/15 ( 67 % ) ) also showed a trend toward reduction in the treatment groups . Conclusions Perioperative administration of an immunoenriched diet significantly reduces systemic perioperative inflammation and postoperative complications in patients undergoing major abdominal cancer surgery , when compared with postoperative diet administration alone . A shortened preoperative feeding regimen of 2 days with Impact enriched with glycine ( Impact plus ) was as effective as Impact administered for 5 days preoperatively Castrostomy feeding has been a well established form of nutritional support for patients presenting with total dysphgia for carcinoma of the oesophagus . More recently , total parenteral nutrition has proved to be efficient and safe , offering an alternative to gastrostomy feeding . Twenty‐four patients were r and omly selected into two groups to compare the efficacy of total parenteral nutrition and gastrostomy feeding with respect to nitrogen balance and weight gain BACKGROUND Although current opinion favours the use of enteral over parenteral nutrition , the clinical benefits of early postoperative nutrition in patients undergoing elective surgery have never been clearly shown . We aim ed to test the hypothesis that postoperative enteral nutrition is better ( fewer postoperative complications ) than parenteral nutrition containing similar energy and nitrogen amounts ( 112 kJ kg(-1 ) day(-1 ) and 1.4 g aminoacid kg(-1 ) day(-1 ) ) . METHODS We did a r and omised multicentre clinical trial in patients with gastrointestinal cancer who were malnourished and c and i date s for major elective surgery . 159 patients were assigned to enteral nutrition and 158 to parenteral nutrition . The primary endpoint was the occurrence of postoperative complications , and secondary endpoints were length of postoperative hospital stay , adverse effects , and treatment crossover . Analysis was by intention to treat . FINDINGS Postoperative complications occurred in 54 ( 34 % ) patients fed enterally versus 78 ( 49 % ) fed parenterally ( relative risk 0.69 , 95 % CI 0.53 - 0.90 , p=0.005 ) . Length of postoperative stay was 13.4 days and 15.0 days in the enteral nutrition and parenteral nutrition groups , respectively ( p=0.009 ) . Adverse effects occurred in 56 ( 35 % ) patients fed enterally versus 22 ( 14 % ) patients fed parenterally ( 2.50 , 1.61 - 3.86 , p<0.0001 ) . 14 ( 9 % ) patients on enteral nutrition had to switch to parenteral nutrition , whereas none of those fed parenterally crossed over to enteral feeding . INTERPRETATION We conclude that early enteral nutrition significantly reduces the complication rate and duration of postoperative stay compared with parenteral nutrition , although parenteral nutrition is better tolerated than enteral nutrition In a comparative clinical trial to examine the influence of 10 days of preoperative parenteral nutrition ( PPN ) on the postoperative complication rate for gastrointestinal carcinoma 59 patients ( controls ) received the regular hospital diet and 66 received PPN . The two groups were similar in nutritional status and in distribution of site and stage of tumour and type of operation . The rates of postoperative wound infection , pneumonia , major complications , and mortality were generally lower in the PPN group , but the differences were significant only for major complications and mortality . The clinical results can be explained by the improvement in various indices of humoral and cellular immunocompetence and the protein status in the PPN group and their deterioration in the control group during the preoperative course HYPOTHESIS Perioperatively administered enteral immunonutrition will improve early postoperative morbidity and cost-effectiveness after gastrointestinal tract surgery . DESIGN A prospect i ve , r and omized , double-blind , multicenter clinical trial . SETTING Surgical departments in German university and teaching hospitals . PATIENTS One hundred fifty-four patients with upper gastrointestinal tract malignant neoplasms who were eligible for analysis . INTERVENTION Preoperatively , patients received 5 days of oral immunonutrition ( an arginine- , RNA- , and omega3 fatty acid-supplemented diet ) or an isoenergetic control diet ( 1 L/d ) . Early postoperative enteral feeding with immunonutrition or an isoenergetic , isonitrogenous control diet using a catheter jejunostomy was performed for 10 days . MAIN OUTCOME MEASURES Postoperative infectious complications , their treatment costs , and cost-effectiveness of immunonutrition were analyzed . Plasma levels of the fatty acids eicosapentaenoic acid and docosahexaenoic acid were measured . RESULTS In the immunonutrition group , significantly fewer infectious complication events occurred ( 14 vs 27 ; P = .05 ) . The number of patients with complications was significantly lower in the supplemented diet group after postoperative day 3 ( 7 vs 16 ; P = .04 ) . The treatment costs of complications in the supplemented diet group were suggestively lower than in the control diet group ( DM 75172 vs DM 204273 ) . Cost-effectiveness was DM 1503 in the experimental group vs DM 3587 in the control group , where DM denotes deutsche mark ( German currency ) . CONCLUSION The perioperative administration of an enteral immunonutrition significantly ( P = .05 ) decreased the early occurrence of postoperative infections and reduced substantially the treatment costs of the complications after major upper gastrointestinal tract surgery BACKGROUND & AIMS Malnutrition is a recognized risk factor for perioperative morbidity , but there is currently no st and ardized definition of malnutrition . The Nutrition Risk Screening 2002 score was recently proposed to identify patients at nutritional risk who may benefit from nutritional support therapy , and has been officially adopted by the European Society of Parenteral and Enteral Nutrition . The aim of this study was to assess the value of the Nutrition Risk Screening 2002 score in predicting the incidence and severity of postoperative complications in gastrointestinal surgery . METHODS We prospect ively evaluated 608 patients admitted for elective gastrointestinal surgery . Nutritional risk was defined by the Nutrition Risk Screening 2002 score and correlated to the incidence and severity of postoperative complications . Complications were classified using an established surgical complication classification . RESULTS The overall incidence of nutritional risk was 14 % . We observed a significantly higher complication rate of 40 % ( 35 out of 87 ) in patients at nutritional risk , compared to 15 % ( 81 out of 521 ) in patients with a normal score ( p<0.001 ) . The incidence of severe complications was significantly higher in patients at nutritional risk ( 54 % versus 15 % ; p<0.001 ) . The odds ratio to develop a complication was 2.8 in patients at risk ( p=0.001 ) , and 3.0 in patients with malignant disease ( p<0.001 ) . The median length of stay in nutritional risk patients was significantly longer ( 10 versus 4 days , p<0.001 ) . CONCLUSION The prevalence of nutritional risk patients in gastrointestinal surgery is high . We showed that nutritional risk screening using the NRS 2002 strongly predicts the incidence and severity of complications Objectives The purpose of this study was to evaluate the effect of preoperative immunonutrition pharmaceutics ( IMPACT ) diet versus st and ard enteral nutrition ( EN ) on the nutritional status and immunity of patients with colorectal or gastrointestinal ( GI ) cancer and to evaluate whether it influences the incidence of postoperative complication . Methods Sixty patients with GI cancer were r and omly divided into 2 groups , immunonutrition ( IM ) and control diet ( CT ) , each of which was fed with IMPACT and conventional diet , respectively , for 7 days before surgical procedures . Variables of nutritional status and immunity , postoperative complications , infections , and the days of postoperative hospitalization were measured . Results There were no significant differences in the immunological and nutritional variables between the 2 groups preoperatively . The incidence of postoperative complications was significantly lower and the days of postoperative hospitalization were significantly decreased in the IM group . Serum concentrations of both prealbumin ( PALB ) and transferrin ( TRF ) were lower in the IM than in the CT group on postoperative day 3 ( P < 0.01 ) . TRF continued to be significantly lower in the CT group than in the IM group between day 4 and day 7 . However , PALB was significantly lower than before operation in the IM group on postoperative day 3 and TRF was significantly higher in the IM than the CT group on postoperative day 3 ( P < 0.05 ) . Both PALB and TRF were significantly higher in the IM than the CT group on postoperative day 7 ( P < 0.05 ) . Postoperative immunoglobulin G ( IgG ) level in the IM group was higher than that in the CT group ( 13.35 ± 2.06 g/l vs. 9.59 ± 2.23 g/l , P < 0.05 ) . CD4/CD8 ratio was significantly higher in the IM group ( 2.10 ± 0.51 vs. 1.62 ± 0.52 , P < 0.05 ) . Conclusions Preoperative enteral IM in patients with GI cancer improves nutritional status and immunity and decreases the incidence of postoperative complications and infections BACKGROUND Malnutrition in gastrointestinal ( GI ) surgery is associated with increased morbidity . Therefore , careful screening remains crucial to identify patients at risk for malnutrition and consequently postoperative complications . The aim of this study was to evaluate the ability of 3 established score systems to identify patients at risk of developing postoperative complications in GI surgery and to assess the correlation among the score systems . METHODS We evaluated prospect ively 200 patients admitted for elective GI surgery using ( 1 ) nutrition risk index , ( 2 ) nutrition risk score , and ( 3 ) bioelectrical impedance analysis . Complications were assessed using a st and ardized complication classification . The findings of the score systems were correlated with the incidence and severity of complications . Parametric and nonparametric correlation analysis was performed among the different score systems . RESULTS All 3 score systems correlated significantly with the incidence and severity of postoperative complications and the duration of hospital stay . Using multiple regression analysis , only nutrition risk score and malignancy remained prognostic factors for the development of complications with odds ratios of 4.2 ( P = .024 ) and 5.6 ( P < .001 ) , respectively . The correlation between nutrition risk score and nutrition risk index was only moderate ( Pearson coefficient = 0.54 ) . Bioelectrical impedance analysis displayed only weak to trivial correlation to the nutrition risk index ( 0.32 ) and nutrition risk score ( 0.19 ) , respectively . CONCLUSION The nutrition risk score , nutrition risk index , and bioimpedance analysis correlate with the incidence and severity of perioperative complications in GI surgery . The nutrition risk score was the best score in predicting patients who will develop complications in this study population . The correlation between the individual scores was only moderate , and therefore , they do not necessarily identify the same patients BACKGROUND Anesthetic st and ard of care is to restrict oral intake for 8 hours before elective surgery . There is no research addressing appropriate preoperative discontinuation of jejunostomy tube ( J-tube ) feedings . We hypothesized that patients could be fed safely , via a J-tube , until the time of surgery . METHODS Patients admitted to a Level I Trauma Center , having J-tubes and undergoing a nonabdominal operation , were prospect ively evaluated . Group I patients received J-tube feedings until transport to the operating room . Group II patients had tube feedings discontinued for at least 8 hours before surgery . Data were compared using the Student 's t test and contingency table analysis . RESULTS There were 46 patients in group I and 36 in group II . There was no incidence of aspiration . Patient groups did not differ in age , mortality , length of stay , injury severity score , or ventilator days . Group I patients had tube feedings discontinued for fewer hours before and after surgery than group II patients ( before surgery : 1.40 + /- 1.20 vs 11.61 + /- 5.01 , respectively ; p < .001 ; after surgery : 2.99 + /- 7.49 vs 7.11 + /- 9.03 , respectively ; p = .043 ) ; received more kilocalories/ grams of protein on the day of surgery ( group I vs group II , 1676.15/89.57 + /- 1133.21/38.04 vs 791.14/57.58 + /-498.66/79.87 , respectively ; p = .001/p = .032 ) and more kilocalories/grams of protein on the first postoperative day ( group I vs group II , 1580.74/92.57 + /- 600.53/37.96 vs 1152.47/63.53 + /- 733.96/39.40 , respectively ; p = .006/p = .001 ) . CONCLUSIONS Patients receiving J-tubes who are undergoing nonabdominal operations may safely continue enteral nutrition at maximum protein and caloric intake until surgery Introduction : Current studies suggest immunonutrition decreases the inflammatory process , infection rates and reduces length of hospital stay in surgical patients , however studies are often conducted on heterogeneous groups of patients with varying composition of the immunonutrition . We aim to investigate the effect of immunonutrition on patients undergoing major upper gastrointestinal surgery by assessment of ( i ) the inflammatory and immune response and ( ii ) changes in clinical outcome when compared to a r and omised control receiving conventional feeding . Method : A prospect i ve double-blind r and omised controlled study was undertaken to compare a feed supplemented with glutamine , arginine , ω-3 fatty acids and tributyrin , vitamin C , E and B-carotene and micronutrients ( zinc , selenium and chromium ) to an isonitrogenous , isocaloric control feed in patients undergoing major upper GI surgery . The primary end-points were defined as C-reactive protein ( CRP ) , prealbumin and retinol binding protein ( RBP ) levels . Secondary end-points included performance scoring systems , length of hospital stay , adverse events and protein and nutrient assays . Variables were measured pre-operatively and routinely up to the 4th post-operative day . Results : There was no statistically significant change in primary end-points between the immunonutrition group and the control group . There was no difference in length of hospital stay between the groups . The vitamin C level in the study group was significantly higher at the end of the study period . Both groups tolerated the feeds well with adequate target feeding rate . There were no other significant changes in clinical outcomes between the two groups . Conclusion : This study has not shown a benefit of immunonutrition through changes in inflammatory or nutritional markers , a decrease in length of hospital stay , or other morbidity . This may be because of inadequate numbers recruited to the study . Further , multi-centre , r and omised trials on homogeneous patient groups are necessary to investigate the role of immunonutrition in major upper GI surgery Patients undergoing major gastrointestinal surgery who had a prognostic nutritional index ( PNI ) score of greater than 30 % were r and omized to receive a preoperative course of 10 days of intravenous nutrition or to undergo surgery at the next convenient operation list . Two groups of 17 patients were well matched for age , sex , and nutritional status . Although they underwent diverse operations , the extent of these was similar : 12 + /- 3 days of parenteral nutrition result ed in weight gain , 3.2 + /- 2.3 kg p less than 0.01 ; increased triceps skinfold , 0.6 + /- 1.2 mm p less than 0.05 ; improved immunological state , p less than 0.02 ; and improved PNI , 5.5 + /- 10.1 % p less than 0.05 . The changes in serum albumin and transferrin were not significant . There were only three major complications with one death in the treatment group but this was not significantly different from the control group which had six major complications and three deaths . This study suggests that patients with demonstrable nutritional depletion who require major gastrointestinal surgery will benefit from a preoperative course of parenteral nutrition , but to conclusively prove this a large and probably multicentre study will be required Background Perioperative nutrition for patients undergoing colon surgery seems to be effective in reducing catabolism and improving immunologic parameters . A relatively low-fiber and highly absorbable diet may facilitate the intestinal cleansing and loop relaxation fundamental for laparoscopic surgery with a lower dose of iso-osmotic laxative . Methods From 1 February 2004 to 30 July 2005 , 28 patients referred to our unit with colon disease ( neoplasms and diverticular disease ) amenable to laparoscopic surgery were prospect ively r and omized into two groups of 14 patients each . For 6 days preoperatively , the patients in group 1 were given 750 ml/day of a diet enriched with arginine , omega-3 fatty acids , and ribonucleic acid ( RNA ) associated with low-fiber foods . They had 1 day of intestinal preparation with 3 l of iso-osmotic laxative . On postoperative day 2 , they were fed orally with the same diet . The patients in group 2 preoperatively received a low-fiber diet . They had 2 days of preparation with iso-osmotic laxative ( 3 l/day ) . On postoperative day 3 , oral nutrition was restored . Intraoperatively , we evaluated loop relaxation and intestinal cleanliness . Clinical trends were monitored in both groups , as well as adverse reactions to early nutrition . The nutritional ( albumin , prealbumin ) and immunologic ( lymphocyte sub population s , immunoglobulins ) biohumoral parameters were evaluated at the first visit , on the day before surgery , on postoperative day 7 , and 1 month after surgery . Results The two groups did not differ in terms of age , gender , distribution of disease , or baseline anthropometric , biohumoral , or immunologic parameters . There was a significant increase in CD4 lymphocytes on the day before surgery as compared with baseline parameters ( p < 0.05 ) in group 1 , but not in group 2 . There was no statistically significant difference between the two groups in intestinal loop relaxation or cleanliness or in postoperative infectious complications . Conclusions Perioperative immunonutrition proved to be safe and useful in increasing the perioperative immunologic cell response . It may contribute toward improving the preparation and relaxation of the intestinal loops despite the shorter intestinal preparation Purpose A prospect i ve study was conducted to ascertain the effects of preoperative enteral immunonutrition on a surgical site infection ( SSI ) in patients with colorectal cancer without malnutrition . Methods Patients with colorectal cancer undergoing elective surgery without malnutrition , bowel obstruction , severe cardiopulmonary complications , diabetes , collagen disease , or renal failure were sequentially divided into an immunonutrition group ( n = 33 ) and a control group ( n = 34 ) . In the immunonutrition group , an enteral diet supplemented with arginine , dietary nucleotides , and ω-3 fatty acids was administered for 5 days ( 750 ml/day ) prior to surgery . Results The mean age was slightly higher in the immunonutrition group ( 69 ± 9 years ) than in the control group ( 63 ± 11 years ; P < 0.05 ) , but no significant differences between the groups were noted for the body mass index , total protein , albumin , hemoglobin , surgical methods , operation time , or volume of intraoperative bleeding . The frequencies of superficial incisional SSI , deep incisional SSI and organ/space SSI in the immunonutrition and control groups were 0 % and 11.8 % ( 4/34 ; P < 0.05 ) , 0 % and 0 % , and 0 % and 2.9 % ( 1/34 ) , respectively . Conclusion Preoperative enteral immunonutrition appears to be effective for preventing SSI in patients with colorectal cancer without malnutrition BACKGROUND The uptake of ω-3 polyunsaturated fatty acids ( PUFAs ) into the liver , gut mucosa , and tumor tissue and plasma levels after preoperative administration of supplemented enteral nutrition was investigated in patients with malignancies of the upper gastrointestinal tract . The objective of the study was to evaluate the incorporation of preoperatively administrated PUFAs , eicosapentaenoic acid ( EPA ) , and docosahexaenoic acid ( DHA ) into cell phospholipids . METHODS Patients undergoing major gastrointestinal surgery ( n = 40 ) were prospect ively r and omized to receive a PUFA-supplemented liquid oral diet 5 days preoperatively or an isocaloric control diet . The planned diet intake was 1000 mL/d providing 3.7 g of PUFA . The diet was given in addition to the usual hospital diet . The phospholipid fractions in plasma were analyzed on the day of surgery . Tissue sample s of liver , gut mucosa ( small intestine ) , and tumor were taken during surgery and homogenized . EPA and DHA content was analyzed using liquid gas chromatography . RESULTS Both patient groups ( PUFA group : n = 20 ; control group : n = 20 ) were similar in age , weight , and surgical procedures . As compared with the control group , the PUFA group had significantly increased levels of EPA in liver tissue ( 0.4 vs 1.3 weight % ) , gut mucosa ( 0.3 vs 1.0 weight % ) , and tumor tissue ( 0.3 vs 0.8 weight % ) . Also , the DHA levels in the PUFA group were significantly higher than the control group : liver tissue ( 4.1 vs 7.5 weight % ) , gut mucosa ( 2.1 vs 3.7 weight % ) and tumor tissue ( 1.9 vs 4.2 weight % ) . CONCLUSIONS This study suggests that administration of PUFA-enriched diets leads to increased incorporation of EPA and DHA not only in liver and gut mucosa tissue , but also in tumor tissue in patients with solid gastrointestinal tumors . Thus , preoperative administration of oral PUFA-enriched diets could have an impact on the postoperative inflammatory response after major abdominal surgery HYPOTHESIS Perioperative administration of a supplemented enteral formula may reduce the rate of postoperative infections . DESIGN Prospect i ve , r and omized , double-blind clinical trial . SETTING Department of surgery at a university hospital . PATIENTS Two hundred six patients with neoplasm of colorectum , stomach , or pancreas . INTERVENTION Patients were r and omized to drink 1 L/d of either a control enteral formula ( n = 104 ) or the same formula enriched with arginine , RNA , and omega3 fatty acids ( n = 102 ) for 7 consecutive days before surgery . The 2 diets were isoenergetic and isonitrogenous . Jejunal infusion with the same formulas was started 6 hours after operation and continued until postoperative day 7 . MAIN OUTCOME MEASURES Rate of postoperative infectious complications and length of hospital stay . RESULTS Both groups were comparable for age , sex , weight loss , Karnofsky scale score , nutritional status , hemoglobin level , duration of surgery , blood loss , and rate of homologous transfusion . Intent-to-treat analysis showed a 14 % ( 14/102 ) infectious complication rate in the supplemented group vs 30 % ( 31/104 ) in the control group ( P = .009 ) . In the eligible population , the postoperative infection rate was 11 % ( 9/85 ) in the supplemented group vs. 24 % ( 21/86 ) in the control group ( P = .02 ) . The mean + /- SD length of postoperative stay was 11.1+/-4.4 days in the supplemented group and 12.9+/-4.6 in the control group ( P = .01 ) . CONCLUSION Perioperative administration of a supplemented enteral formula significantly reduced postoperative infections and length of stay in patients undergoing surgery for cancer Objective : Currently most nutritional assessment techniques are based on their ability to predict clinical outcomes . However , the validity of any of these techniques to truly measure “ nutritional risk ” has not been proved . We have therefore prospect ively assessed the prognostic value of two nutritional assessment techniques and nonnutritional factors in determining outcome after major abdominal surgery . Methods : At admission and discharge , 100 patients undergoing major abdominal surgery were assessed on the following items : Subjective Global Assessment , Nutritional Risk Index , anthropometric measurements , serum total protein , serum albumin , lymphocyte count , total serum cholesterol . Patients were monitored for postoperative complications until death or discharge . Results : At admission , 44 % of the patients were malnourished according to the Subjective Global Assessment , while 61 % of the patients were malnourished according to the Nutritional Risk Index . At discharge , these numbers were 67 % and 82 % , respectively . Higher death rates were found in the malnourished groups . The risk of complication was increased in malnourished patients with both assessment techniques . The odds ratios for the association between malnutrition and complications varied between 1.926 and 9.854 with both assessment s. The presence of cancer in the patient was predictive for complication . Conclusions : Malnutrition is a marker of bad outcomes . Both Subjective Global Assessment and Nutritional Risk Index nutrition tests are predictive for malnutrition and postoperative complications in patients undergoing major abdominal surgery AIM To evaluate the effects of preoperative immunonutrition and other nutrition models on the cellular immunity parameters of patients with gastrointestinal tumors before surgical intervention . In addition , effects on postoperative complications were examined . METHODS Patients with gastrointestinal tumors were r and omized into 3 groups . The immunonutrition group received a combination of arginine , fatty acids and nucleotides . The second and third group received normal nutrition and st and ard enteral nutrition , respectively . Nutrition protocol s were administered for 7 d prior to the operation . Nutritional parameters , in particular prealbumin levels and lymphocyte sub population s ( CD4 + , CD8 + , CD16+/56 + , and CD69 cells ) were evaluated before and after the nutrition protocol s. Groups were compared in terms of postoperative complications and duration of hospital stay . RESULTS Of the 42 patients who completed the study , 16 received immunonutrition , 13 received normal nutrition and 13 received st and ard enteral nutrition . prealbumin values were low in every group , but this parameter was improved after the nutritional protocol only in the immunonutrition group ( 13.64+/-8.83 vs 15.98+/-8.66 , P=0.037 ) . Groups were similar in terms of CD4 + , CD16+/56 , and CD69 + prior to the nutritional protocol ; whereas CD8 + was higher in the st and ard nutrition group compared to the immunonutrition group . After nutritional protocol s , none of the groups had an increase in their lymphocyte sub population s. Also , groups did not differ in terms of postoperative complications and postoperative duration s of hospital stay . CONCLUSION Preoperative immunonutrition provided a significant increase in prealbumin levels , while it did not significantly alter T lymphocyte sub population counts , the rate of postoperative complications and the duration of hospital stay Background Past trials have shown perioperative immunonutrition to improve the outcome for patients with gastric cancer . The present study was design ed to evaluate the effect of preoperative oral immunonutrition on cellular immunity , the duration of the systemic inflammatory response syndrome ( SIRS ) , and detailed postoperative complications in patients with gastric cancer . Methods Sixty patients with gastric cancer were r and omly assigned to two groups : one group received immune-enhanced formulas supplemented with arginine and ω-3 fatty acids ( immune-enhancing diet ( ID ) group , n = 30 ) ; the other received st and ard formulas ( conventional diet ( CD ) group , n = 30 ) for 7 days before the operation . These groups were well matched in terms of age , sex , operations , cancer stages , and intraoperative variables . The postoperative outcome was evaluated based on clinical variables , including postoperative infectious complications , noninfectious complications , and SIRS duration . In addition , the perioperative state of cellular immunity was evaluated and compared between the two groups . Results The incidence of postoperative infectious complications in the ID group ( 6 % ) was significantly ( p < 0.05 ) lower than that of the CD group ( 28 % ) . The duration of SIRS in the ID group ( 0.77 ± 0.9 days ) was significantly ( p < 0.05 ) shorter than that in the CD group ( 1.34 ± 1.45 days ) . The postoperative lymphocyte and CD4+T-cell counts significantly decreased ( p < 0.05 ) in both groups . However , the number of CD4+T-cells on preoperative day 1 and postoperative day 7 was significantly ( p < 0.05 ) higher in the ID group than in the CD group . Conclusions Preoperative oral immune-enhanced formulas supplemented with arginine and ω-3 fatty acids enhanced the immune status of the patients , reduced the duration of SIRS , and decreased the incidence of postoperative infectious complications . CD4+T-cell immunity likely played an important role in the modulation of the postoperative immune and inflammatory response after gastrectomy BACKGROUND & AIMS The aim of the study was to implement nutritional risk screening ( NRS-2002 ) and to assess the association between nutritional risk and clinical outcome . METHODS NRS-2002 was implemented in 26 hospital departments ( surgery , internal medicine , oncology , intensive care , gastroenterology and geriatrics ) in Austria , the Czech Republic , Egypt , Germany , Hungary , Lebanon , Libya , Pol and , Romania , Slovakia , Spain and Switzerl and . Being a prospect i ve cohort study , r and omly selected adult patients were included at admission and followed during their hospitalisation . Data were collected on the nutritional risk screening , complications , mortality , length of stay and discharge . The correlation between risk status and clinical outcome was assessed and adjusted for confounders ( age , speciality , diagnoses , comorbidity , surgery , cancer and region ) by multivariate regression analysis . RESULTS Of the 5051 study patients , 32.6 % were defined as ' at-risk ' by NRS-2002 . ' At-risk ' patients had more complications , higher mortality and longer lengths of stay than ' not at-risk ' patients and these variables were significantly related to components of NRS-2002 , also when adjusted for confounders . CONCLUSIONS Components of NRS-2002 are independent predictors of poor clinical outcome BACKGROUND & AIMS Perioperative nutrition with specialized enteral diets improves outcome when compared with st and ard formulas . A post-hoc analysis suggested preoperative administration as the most important period . Thus , we design ed a study to underst and prospect ively whether preoperative supplementation could be as efficacious as the perioperative approach and superior to a conventional treatment ( no artificial nutrition ) in reducing postoperative infections and length of hospital stay . METHODS A total of 305 patients with preoperative weight loss < 10 % and cancer of the gastrointestinal tract were r and omized to receive the following : ( 1 ) oral supplementation for 5 days before surgery with 1 L/day of a formula enriched with arginine , omega-3 fatty acids , and RNA , with no nutritional support given after surgery ( preoperative group , n = 102 ) ; ( 2 ) the same preoperative treatment plus postoperative jejunal infusion with the same enriched formula ( perioperative group , n = 101 ) ; and ( 3 ) no artificial nutrition before and after surgery ( conventional group ; n = 102 ) . RESULTS The 3 groups were comparable for all baseline and surgical characteristics . Intention-to-treat analysis showed a 13.7 % incidence of postoperative infections in the preoperative group , 15.8 % in the perioperative group , and 30.4 % in the conventional group ( P = 0.006 vs. preoperative ; P = 0.02 vs. perioperative ) . Length of hospital stay was 11.6 + /- 4.7 days in the preoperative group , 12.2 + /- 4.1 days in the perioperative group , and 14.0 + /- 7.7 days in the conventional group ( P = 0.008 vs. preoperative and P = 0.03 vs. perioperative ) . CONCLUSIONS Preoperative supplementation is as effective as perioperative administration in improving outcome . Both strategies seem superior to the conventional approach BACKGROUND Perioperative oral supplementation has been shown to reduce post-operative complications . However , the use of preoperative st and ard oral supplements in a cohort of colorectal cancer patients has not been evaluated . The present study examined whether preoperative supplements are beneficial in this group . METHODS In a r and omised controlled trial , patients were assigned to receive 400 mL of oral supplement and dietary advice or dietary advice alone . Primary outcome was the number of post-operative complications . One hundred and twenty-five patients were recruited ( 59 r and omised to the intervention group and 66 to the control group ) and nine were excluded . RESULTS In the intervention group , 24 ( 44 % ) patients had a complication compared to 26 ( 42 % ) in the control group ( P = 0.780 ) . In the intervention and control groups , there were eight ( 15 % ) and 16 ( 25 % ) surgical site infections , respectively ( P = 0.140 ) and seven ( 13 % ) and 11 ( 17 % ) chest infections , respectively ( P = 0.470 ) . Subgroup analysis for hypothesis generation included 83 ( 71 % ) weight-losing patients , where there was a significant reduction in surgical site infections using the Buzby definition ( P = 0.034 ) , although this was not the case for the Centre for Disease Control definition ( P = 0.052 ) . CONCLUSIONS There was no evidence that preoperative supplements were beneficial in reducing the number of complications , although there may be some benefit for surgical site infections in selected weight-losing preoperative patients BACKGROUND Early postoperative enteral nutrition with immune-enhancing supplements has helped to restore immune function and reduce infectious complications in patients with cancer undergoing major gastrointestinal operations . The aim of this study was to evaluate the effectiveness of similar supplements ( containing arginine and arginine plus omega-3 fatty acids ) given preoperatively for 1 week before cancer surgery . METHODS In this r and omized , double-blinded study , patients scheduled to undergo elective resection of upper gastrointestinal tumors were given one of three different oral liquid supplemental diets ( control , arginine , arginine plus omega-3 fatty acids ) to be taken each day for 7 days before surgery . Blood sample s were obtained upon enrollment , on the morning of surgery , and on postoperative day 1 for analysis of immunologic function . RESULTS Mean serum ornithine ( a metabolite of arginine ) levels were significantly higher compared with controls , but no significant increase in mean serum arginine levels was noted on the morning of surgery for those patients who received arginine as part of the supplement . In conjunction with these findings , there were no differences among groups in mean lymphocyte mitogenesis , mean peripheral blood mononuclear cell production of cytokines , or clinical outcomes . CONCLUSIONS Use of oral liquid supplements in this fashion did not improve lymphocyte proliferation or monocyte functions in patients with cancer undergoing major surgery Seventy-four patients with a pre-operative diagnosis of stomach or oesophageal cancer were entered into a r and omized , controlled clinical trial to assess the value of a short course of pre-operative intravenous nutrition . The effectiveness of this treatment was assessed by the clinical course and monitored by means of immune and biochemical profiles . Pre-operative parenteral nutrition given over a 7 - 10-day period result ed in a significant reduction in the incidence of postoperative wound infections . Clinical benefit was confined to those patients who had a low serum albumin on admission to hospital . It is doubtful whether this limited benefit justifies the routine use of intravenous feeding , with its attendant hazards , in the pre-operative preparation of patients with upper gastrointestinal cancer OBJECTIVE Although the perioperative use of immune-enhancing enteral formula ( IEEF ) effectively reduces the rate of infectious complications , whether chronic use of IEEF is beneficial is unknown . A prospect i ve r and omized clinical trial was performed to examine the safety and effectiveness of long-term IEEF on nutritional and immunologic status in non-surgical patients receiving total enteral nutrition through the gastrostomy access route . METHODS A total of 30 patients were r and omly assigned to two groups in which they received total enteral nutrition , an IEEF ( n = 15 ) or a regular polymeric enteral formula ( control group ; n = 15 ) for 12 wk . Nutritional and immunologic variables were periodically examined . RESULTS Serum concentrations of insulin-like growth factor-I increased significantly for the IEEF group throughout the study . Although serum concentrations of dihomo-gamma-linoleic acid decreased significantly in the IEEF group , serum concentrations of eicosapentaenoic acid and docosahexaenoic acid increased significantly , as did concentrations of serum arginine and ornithine . The CD4/CD8 ratio and natural killer cell activity also increased for the IEEF group , but the differences were not significant . The B-cell fraction increased and the T-cell fraction of peripheral lymphocytes decreased for the IEEF group . Neither infectious nor non-infectious complications occurred during the study period in either group , except for a significant increase in serum urea nitrogen and uric acid concentrations for the IEEF group . CONCLUSION Long-term use of IEEF is safe in non-surgical patients and results in a significant increase in serum insulin-like growth factor-I concentrations in association with increased humoral immunity Background The use of radiofrequency ( RF ) energy has been described to perform open liver resection safely and with minimal blood loss . Yet no data are available on the potential contribution of RF energy to the limitation of intraoperative blood loss during laparoscopic liver resection ( LLR ) . The aim of this prospect i ve , nonr and omized study was to investigate the potential contribution of RF energy to the limitation of intraoperative blood loss in patients undergoing LLR . Methods Forty-five patients [ male/female ratio 22/23 , age 57 years ( 26–80 ) ] underwent LLR . Eleven benign and 47 malignant lesions ( mostly colorectal metastases ) were resected . Median number [ 1 ( 1–3 ) ] and maximum diameter [ 40 mm ( 8–170 ) ] of tumors as well as median tumor free margins [ 10 mm ( 1–30 ) ] were comparable in patients undergoing LLR with ( 20 patients ) or without ( 25 patients ) RF-assistance . Thirty-eight minor ( ≤2 segments ) and 9 major ( > 3 segments ) resections were performed . Eighteen patients simultaneously underwent additional surgery . Results No mortality occurred . Median intraoperative blood loss was 200 ( 5–4000 ) ml and was similar in patients undergoing LLR with or without RF-assistance . The type of surgical procedure was a determinant for the amount of intraoperative blood loss ( p = 0.0002 ) . Significant bleeding occurred from large hepatic vessels at major resections . Median operation time was 115 ( 45–360 ) minutes . RF-assistance did n’t seem to reduce perioperative morbidity . Conclusions LLR can be performed with minimal intraoperative blood loss , which is determined by the type of hepatectomy . Significant intraoperative bleeding occurs from large hepatic vessels during major resections . RF-assisted parenchymal transection in LLR does n’t seem to reduce blood loss , operation time , or perioperative morbidity Ever since methods of artificial nutritional support became available , attempts have been made using this form of treatment to reduce mortality and morbidity in surgical patients . Many trials have addressed this question , but very few have given a meaningful answer because of conceptual and method ological flaws . We therefore undertook a prospect i ve r and omised trial investigating the effects of at least 10 days pre-operative total parenteral nutrition ( TPN ) ( n = 51 ) or total enteral nutrition ( TEN ) ( n = 50 ) providing 150 % basal energy expenditure ( BEE ) non-protein energy , to reduce major postoperative complications and mortality in a homogeneous patient group with signs of depletion . 50 patients served as a depleted control group ( D ) and 49 patients served as a non-depleted reference group ( ND ) and were operated upon without delay . Depleted control patients suffered significantly more septic complications than did patients in the non-depleted reference group ( p < 0.05 ) . There was no significant difference , however , in septic complications between either of the nutritional support groups and the non-depleted control group . In high risk patients , with weight loss > 10 % of body weight and over 500 ml blood loss during operation , a significant decrease in major complications was observed ( p < 0.05 ) as a result of nutritional support . We conclude that pre-operative nutritional support , in patients with severe depletion , results in a reduction in major complications to a degree that justifies its routine use in this selected group of patients Background : Esophagectomy represents an exemplar of controlled major trauma , with marked metabolic , immunologic , and physiologic changes as well as an associated high incidence of complications . Eicosapentaenoic acid ( EPA ) enriched enteral nutrition ( EN ) modulates immune function and limits catabolism in patients with advanced cancer , but its impact in the peri-operative period is unclear . Objectives : To examine the effects of perioperative EPA enriched EN on the metabolic , nutritional , and immuno-inflammatory response to esophagectomy , and on postoperative complications . Methods : In a double-blind design , patients were r and omized to a st and ard EN formula or a formula enriched with 2.2 g EPA/d for 5 days preoperatively ( orally ) and 21 days postoperatively ( jejunostomy ) . Segmental bioelectrical impedance analysis was performed preoperatively and on POD 21 . Postoperative complications were monitored , as well as the acute phase response , coagulation markers , and serum cytokines . Results : Fifty-three patients ( 28 EPA , 25 st and ard ) completed the study , and both groups were well matched . Serum and peripheral blood mononuclear cell ( P BMC ) membrane EPA levels were significantly increased in the EPA group . There was no difference in the incidence of major complications . The EPA group maintained all aspects of body composition postoperatively , whereas patients in the st and ard EN group lost significant amounts of fat-free mass ( 1.9 kg , P = 0.030 ) compared with the EPA group [ leg ( 0.3 kg , P = 0.05 ) , arm ( 0.17 kg , P = 0.01 ) , and trunk ( 1.44 kg , P = 0.03 ) ] . The EPA group had a significantly ( P < 0.05 ) attenuated stress response for TNFα , IL-10 , and IL-8 compared with the st and ard group . Conclusions : EPA supplemented early EN is associated with preservation of lean body mass post esophagectomy compared with a st and ard EN . These properties may merit longer-term study to address its impact on recovery of function and quality of life in models of complex surgery or multimodal cancer treatment regimens BACKGROUND The use of immune-enhancing enteral diets in the postoperative period has given contrasting results . The purpose of this prospect i ve , r and omized , double-blinded clinical study was to evaluate the effect of immunonutrition given perioperatively on cytokine release and nutritional parameters . METHODS Patients with cancer of the stomach or colo-rectum were eligible . Subjects consumed 1 L/d of either a control enteral formula ( n = 25 ; control group ) or a formula supplemented with arginine , omega-3 fatty acids , and RNA ( n = 25 ; verum group ) for 1 week before surgery . Both formulas were given by mouth . Six hours after the operation , jejunal infusion with the same diets was started and maintained for 7 days . Blood was drawn at different time points to assess albumin , prealbumin ( PA ) , transferrin , cholinesterase activity , retinol binding protein ( RBP ) , interleukin-2 receptors alpha ( IL-2Ralpha ) , IL-6 , and IL-1 soluble receptors ( IL-1RII ) . The composite score of delayed hypersensitivity response ( DHR ) to skin test also was determined ( the higher the score , the lower the immune response ) . RESULTS During the 7 days of presurgical feeding , none of the above parameters changed in either group . Eight days after operation , in the control group , the concentration of PA and RBP was lower than in the verum group ( 0.18 vs 0.26 g/L for PA and 30.5 vs 38.7 mg/L for RBP ; p < .05 ) . IL-2Ralpha concentration was 507 pg/mL in the verum group vs 238 pg/mL in the control group ( p < .001 ) , whereas IL-6 and IL-1RII were higher in the control group than in the verum group ( 104 vs 49 and 328 vs 183 pg/mL , respectively ; p < .01 ) . The DHR score was 0.68 in the control group vs 0.42 in the verum group ( p < .05 ) . CONCLUSIONS Perioperative feeding with a supplemented enteral diet modulates cytokine production and enhances cell-mediated immunity and the synthesis of short half-life proteins Previous human studies have investigated the influences of nutritional routes on the serum kinetics of cytokines following intravenous administration of lipopolysaccharide . However , it is unclear whether preoperative nutritional routes influence responses of systemic cytokines in patients after surgery . This study was design ed to investigate whether preoperative total parental nutrition ( TPN ) influences systemic interleukin-6 ( IL-6 ) and interleukin-8 ( IL-8 ) responses in patients following surgery for colorectal cancer . Patients with colorectal cancer received TPN ( TPN group , n = 6 ) or an oral diet ( oral group n = 6 ) for more than 7 d before the operation . Patients in the TPN group received st and ard TPN . Patients in the oral group received an ordinary hospital diet . Blood sample s were collected before the operation , on postoperative day 1 ( POD1 ) , POD3 , and POD7 . Levels of IL-6 , IL-8 , and C-reactive protein ( CRP ) in plasma were determined . The characteristics of patients in the TPN and oral groups were comparable . Mean carbohydrate intake was greater ( 28 versus 19 kCal/kg ) , and lipid intake was smaller ( 0 versus 7 kCal/kg ) in the TPN group than in the oral group . Plasma CRP levels did not differ between the two groups . Plasma IL-6 and IL-8 levels were marginally higher before the operation and were significantly higher on POD1 in the TPN group than in the oral group . The IL-6 levels showed a positive regression relation with the amounts of blood loss only in the TPN group ( P < 0.05 , r = 0.881 ) . The slope of the regression line was steeper in the TPN group than in the total enteral nutrition ( TEN ) group ( P < 0.01 ) . In conclusion , routes of nutritional supply have an impact on the production of systemic cytokines after insult . The postoperative systemic IL-6 and IL-8 responses in patients who received st and ard TPN preoperatively were greater than in patients who received an oral diet . Preoperative nutrition via the enteral route may provide better regulation of cytokine responses after surgery than parenteral nutrition BACKGROUND : Previous work has shown that the administration of oral dietary supplements to patients who have undergone gastrointestinal surgery results in clinical ly significant short term benefits . AIMS : This study aim ed firstly to re-evaluate these short term effects , and secondly to establish whether there are any long term benefits . SUBJECTS : One hundred patients admitted for elective moderate or major gastrointestinal surgery . METHODS : In the inpatient phase , patients were r and omised to receive a normal ward diet postoperatively , or the same diet supplemented with an oral dietary supplement . In the outpatient phase , patients were further r and omised to receive their home diet , or their home diet supplemented with the oral dietary supplement for four months . RESULTS : During the inpatient phase , patients treated with oral supplements had a significantly improved nutritional intake and lost less weight ( 2.2 , 95 % confidence interval ( 95 % CI ) 0.9 kg ) compared with control patients ( 4.2 ( 0.78 ) kg , p < 0.001 ) . Supplemented patients maintained their h and grip strength whereas control patients showed a significant reduction in grip strength ( p < 0.01 ) . Subjective levels of fatigue increased significantly above preoperative levels in control patients ( p < 0.01 ) but not in the supplemented group . Twelve patients in the control group developed complications compared with four in the supplemented group ( p < 0.05 ) . In the outpatient phase , supplemented patients had improved nutrient intakes but there were no significant differences in indices of nutritional status or wellbeing between the groups . CONCLUSIONS : The prescription of oral dietary supplements to patients who have undergone gastrointestinal surgery results in clinical ly significant benefits . These benefits , however , are restricted to the inpatient phase POSSUM , a Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity , is described . This system has been devised from both a retrospective and prospect i ve analysis and the present paper attempts to vali date it prospect ively . Logistic regression analysis yielded statistically significant equations for both mortality and morbidity ( P < 0.001 ) . When displayed graphically zones of increasing morbidity and mortality rates could be defined which could be of value in surgical audit . The scoring system produced assessment s for morbidity and mortality rates which did not significantly differ from observed rates |
12,390 | 27,518,544 | A third drug , bevacizumab ( Avastin ) , is only licensed for colorectal cancer , and therefore , use in the eye is ‘ off label’.1 Yet , all three are effective . | Anti-vascular endothelial growth factor ( anti-VEGF ) injections have revolutionised vision for patients with macular degeneration or diabetic macular oedema .
However , the choice of anti-VEGF is controversial .
Two drugs licensed for macular oedema are ranibizumab ( Lucentis ) and aflibercept ( Eylea ) . | Objective To assess the incremental cost and cost-effectiveness of continuous and discontinuous regimens of bevacizumab ( Avastin ) and ranibizumab ( Lucentis ) for neovascular age-related macular degeneration ( nAMD ) from a UK National Health Service ( NHS ) perspective . Design A within-trial cost-utility analysis with a 2-year time horizon , based on a multicentre factorial , non-inferiority r and omised controlled trial . Setting 23 hospital ophthalmology clinics . Participants 610 patients aged ≥50 years with untreated nAMD in the study eye . Interventions 0.5 mg ranibizumab or 1.25 mg bevacizumab given continuously ( monthly ) or discontinuously ( as-needed ) for 2 years . Main outcome measures Quality -adjusted life-years ( QALYs ) . Results Total 2-year costs ranged from £ 3002/patient ( $ 4700 ; 95 % CI £ 2601 to £ 3403 ) for discontinuous bevacizumab to £ 18 590/patient ( $ 29 106 ; 95 % CI £ 18 258 to £ 18 922 ) for continuous ranibizumab . Ranibizumab was significantly more costly than bevacizumab for both continuous ( + £ 14 989/patient ( $ 23 468 ) ; 95 % CI £ 14 522 to £ 15 456 ; p<0.001 ) and discontinuous treatment ( + £ 8498 ( $ 13 305 ) ; 95 % CI £ 7700 to £ 9295 ; p<0.001 ) , with negligible difference in QALYs . Continuous ranibizumab would only be cost-effective compared with continuous bevacizumab if the NHS were willing to pay £ 3.5 million ( $ 5.5 million ) per additional QALY gained . Patients receiving continuous bevacizumab accrued higher total costs ( + £ 599 ( $ 938 ) ; 95 % CI £ 91 to £ 1107 ; p=0.021 ) than those receiving discontinuous bevacizumab , but also accrued non-significantly more QALYs ( + 0.020 ; 95 % CI −0.032 to 0.071 ; p=0.452 ) . Continuous bevacizumab therefore cost £ 30 220 ( $ 47 316 ) per QALY gained versus discontinuous bevacizumab . However , bootstrapping demonstrated that if the NHS is willing to pay £ 20 000/QALY gained , there is a 37 % chance that continuous bevacizumab is cost-effective versus discontinuous bevacizumab . Conclusions Ranibizumab is not cost-effective compared with bevacizumab , being substantially more costly and producing little or no QALY gain . Discontinuous bevacizumab is likely to be the most cost-effective of the four treatment strategies evaluated in this UK trial , although there is a 37 % chance that continuous bevacizumab is cost-effective . Trial registration number IS RCT N92166560 BACKGROUND Bevacizumab has been suggested to have similar effectiveness to ranibizumab for treatment of neovascular age-related macular degeneration . The Inhibition of VEGF in Age-related choroidal Neovascularisation ( IVAN ) trial was design ed to compare these drugs and different regimens . Here , we report the findings at the prespecified 2-year timepoint . METHODS In a multicentre , 2 × 2 factorial , non-inferiority r and omised trial , we enrolled adults aged at least 50 years with active , previously untreated neovascular age-related macular degeneration and a best corrected distance visual acuity ( BCVA ) of at least 25 letters from 23 hospitals in the UK . Participants were r and omly assigned ( 1:1:1:1 ) to intravitreal injections of ranibizumab ( 0·5 mg ) or bevacizumab ( 1·25 mg ) in continuous ( every month ) or discontinuous ( as needed ) regimens , with monthly review . Study participants and clinical assessors were masked to drug allocation . Allocation to continuous or discontinuous treatment was masked up to 3 months , at which point investigators and participants were unmasked . The primary outcome was BCVA at 2 years , with a prespecified non-inferiority limit of 3·5 letters . The primary safety outcome was arterial thrombotic event or hospital admission for heart failure . Analyses were by modified intention to treat . This trial is registered , number IS RCT N92166560 . FINDINGS Between March 27 , 2008 , and Oct 15 , 2010 , 628 patients underwent r and omisation . 18 were withdrawn ; 610 received study drugs ( 314 ranibizumab ; 296 bevacizumab ) and were included in analyses . 525 participants reached the visit at 2 years : 134 ranibizumab in continuous regimen , 137 ranibizumab in discontinuous regimen , 127 bevacizumab in continuous regimen , and 127 bevacizumab in discontinuous regimen . For BCVA , bevacizumab was neither non-inferior nor inferior to ranibizumab ( mean difference -1·37 letters , 95 % CI -3·75 to 1·01 ; p=0·26 ) . Discontinuous treatment was neither non-inferior nor inferior to continuous treatment ( -1·63 letters , -4·01 to 0·75 ; p=0·18 ) . Frequency of arterial thrombotic events or hospital admission for heart failure did not differ between groups given ranibizumab ( 20 [ 6 % ] of 314 participants ) and bevacizumab ( 12 [ 4 % ] of 296 ; odds ratio [ OR ] 1·69 , 95 % CI 0·80 - 3·57 ; p=0·16 ) , or those given continuous ( 12 [ 4 % ] of 308 ) and discontinuous treatment ( 20 [ 7 % ] of 302 ; 0·56 , 0·27 - 1·19 ; p=0·13 ) . Mortality was lower with continuous than discontinuous treatment ( OR 0·47 , 95 % CI 0·22 - 1·03 ; p=0·05 ) , but did not differ by drug group ( 0·96 , 0·46 - 2·02 ; p=0·91 ) . INTERPRETATION Ranibizumab and bevacizumab have similar efficacy . Reduction in the frequency of retreatment result ed in a small loss of efficacy irrespective of drug . Safety was worse when treatment was administered discontinuously . These findings highlight that the choice of anti-VEGF treatment strategy is less straightforward than previously thought . FUNDING UK National Institute for Health Research Health Technology Assessment programme Background The effectiveness of ranibizumab in the treatment of diabetic macular edema has been proven with large clinical trials . For bevacizumab only two clinical trials have been published and a head-to-head comparison is lacking to date . However , if proved non-inferior to ranibizumab , use of the off-label bevacizumab could reduce costs enormously without a loss in visual acuity . A cost-effectiveness study has been design ed to substantiate this hypothesis . Aim To compare the effectiveness and costs of 1.25 mg of bevacizumab to 0.5 mg ranibizumab given as monthly intravitreal injections during 6 months in patients with diabetic macular edema . It is hypothesized that bevacizumab is non-inferior to ranibizumab regarding its effectiveness . Design This is a r and omized , controlled , double masked , clinical trial in 246 patients in seven academic trial centres in The Netherl and s. Outcomes The primary outcome measure is the change in best-corrected visual acuity ( BCVA ) in the study eye from baseline to month 6 . Secondary outcomes are the proportions of patients with a gain or loss of 15 letters or more or a BCVA of 20/40 or more at 6 months , the change in leakage on fluorescein angiography and the change in foveal thickness by optical coherence tomography at 6 months , the number of adverse events in 6 months , and the costs per quality adjusted life-year of the two treatments BACKGROUND Clinical trials have established the efficacy of ranibizumab for the treatment of neovascular age-related macular degeneration ( AMD ) . In addition , bevacizumab is used off-label to treat AMD , despite the absence of similar supporting data . METHODS In a multicenter , single-blind , noninferiority trial , we r and omly assigned 1208 patients with neovascular AMD to receive intravitreal injections of ranibizumab or bevacizumab on either a monthly schedule or as needed with monthly evaluation . The primary outcome was the mean change in visual acuity at 1 year , with a noninferiority limit of 5 letters on the eye chart . RESULTS Bevacizumab administered monthly was equivalent to ranibizumab administered monthly , with 8.0 and 8.5 letters gained , respectively . Bevacizumab administered as needed was equivalent to ranibizumab as needed , with 5.9 and 6.8 letters gained , respectively . Ranibizumab as needed was equivalent to monthly ranibizumab , although the comparison between bevacizumab as needed and monthly bevacizumab was inconclusive . The mean decrease in central retinal thickness was greater in the ranibizumab-monthly group ( 196 μm ) than in the other groups ( 152 to 168 μm , P=0.03 by analysis of variance ) . Rates of death , myocardial infa rct ion , and stroke were similar for patients receiving either bevacizumab or ranibizumab ( P>0.20 ) . The proportion of patients with serious systemic adverse events ( primarily hospitalizations ) was higher with bevacizumab than with ranibizumab ( 24.1 % vs. 19.0 % ; risk ratio , 1.29 ; 95 % confidence interval , 1.01 to 1.66 ) , with excess events broadly distributed in disease categories not identified in previous studies as areas of concern . CONCLUSIONS At 1 year , bevacizumab and ranibizumab had equivalent effects on visual acuity when administered according to the same schedule . Ranibizumab given as needed with monthly evaluation had effects on vision that were equivalent to those of ranibizumab administered monthly . Differences in rates of serious adverse events require further study . ( Funded by the National Eye Institute ; Clinical Trials.gov number , NCT00593450 . ) PURPOSE To assess long-term outcomes 7 to 8 years after initiation of intensive ranibizumab therapy in exudative age-related macular degeneration ( AMD ) patients . DESIGN Multicenter , noninterventional cohort study . PARTICIPANTS Sixty-five AMD patients originally treated with ranibizumab in the phase 3 Anti-VEGF Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization in AMD ( ANCHOR ) trial , Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular AMD ( MARINA ) trial , and Open-Label Extension Trial of Ranibizumab for Choroidal Neovascularization Secondary to Age-Related Macular Degeneration ( HORIZON ) . METHODS Fourteen clinical trial sites recruited their original subjects for a return evaluation . Individual subject comparisons were obtained from the ANCHOR , MARINA , and HORIZON data bases . MAIN OUTCOME MEASURES The primary end point was percentage with best-corrected visual acuity ( BCVA ) of 20/70 or better ; secondary outcomes included mean change in letter score compared with previous time points and anatomic results on fluorescein angiography , spectral-domain ocular coherence tomography ( OCT ) , and fundus autofluorescence ( FAF ) . RESULTS At a mean of 7.3 years ( range , 6.3 - 8.5 years ) after entry into ANCHOR or MARINA , 37 % of study eyes met the primary end point of 20/70 or better BCVA , with 23 % achieving a BCVA of 20/40 or better . Thirty-seven percent of study eyes had BCVA of 20/200 or worse . Forty-three percent of study eyes had a stable or improved letter score ( ≥0-letter gain ) compared with ANCHOR or MARINA baseline measurements , whereas 34 % declined by 15 letters or more , with overall a mean decline of 8.6 letters ( P<0.005 ) . Since exit from the HORIZON study , study eyes had received a mean of 6.8 anti-vascular endothelial growth factor ( VEGF ) injections during the mean 3.4-year interval ; a subgroup of patients who received 11 or more anti-VEGF injections had a significantly better mean gain in letter score since HORIZON exit ( P<0.05 ) . Active exudative disease was detected by spectral-domain OCT in 68 % of study eyes , and 46 % were receiving ongoing ocular anti-VEGF treatments . Macular atrophy was detected by FAF in 98 % of eyes , with a mean area of 9.4 mm(2 ) ; the area of atrophy correlated significantly with poor visual outcome ( P<0.0001 ) . CONCLUSIONS Approximately 7 years after ranibizumab therapy in the ANCHOR or MARINA trials , one third of patients demonstrated good visual outcomes , whereas another third had poor outcomes . Compared with baseline , almost half of eyes were stable , whereas one third declined by 15 letters or more . Even at this late stage in the therapeutic course , exudative AMD patients remain at risk for substantial visual decline |
12,391 | 27,499,161 | Studies on teledermatology and teleradiology indicated a favorable level of economic efficiency .
Overall , telemedicine programs in Japan were indicated to have a favorable level of economic efficiency . | OBJECTIVES There is no systematic review on economic evaluations of telemedicine in Japan , despite over 1000 trials implemented .
Our systematic review aims to examine whether Japan 's telemedicine is cost-saving or cost-effective , examine the method ological rigorousness of the economic evaluations , and discuss future studies needed to improve telemedicine 's financial sustainability . | Background . Comprehensive economic evaluations have not been conducted on telemedicine consultations to children in rural emergency departments ( EDs ) . Objective . We conducted an economic evaluation to estimate the cost , effectiveness , and return on investment ( ROI ) of telemedicine consultations provided to health care providers of acutely ill and injured children in rural EDs compared with telephone consultations from a health care payer prospect i ve . Methods . We built a decision model with parameters from primary programmatic data , national data , and the literature . We performed a base-case cost-effectiveness analysis ( CEA ) , a probabilistic CEA with Monte Carlo simulation , and ROI estimation when CEA suggested cost-saving . The CEA was based on program effectiveness , derived from transfer decisions following telemedicine and telephone consultations . Results . The average cost for a telemedicine consultation was $ 3641 per child/ED/year in 2013 US dollars . Telemedicine consultations result ed in 31 % fewer patient transfers compared with telephone consultations and a cost reduction of $ 4662 per child/ED/year . Our probabilistic CEA demonstrated telemedicine consultations were less costly than telephone consultations in 57 % of simulation iterations . The ROI was calculated to be 1.28 ( $ 4662/$3641 ) from the base-case analysis and estimated to be 1.96 from the probabilistic analysis , suggesting a $ 1.96 return for each dollar invested in telemedicine . Treating 10 acutely ill and injured children at each rural ED with telemedicine result ed in an annual cost-savings of $ 46,620 per ED . Limitations . Telephone and telemedicine consultations were not r and omly assigned , potentially result ing in biased results . Conclusions . From a health care payer perspective , telemedicine consultations to health care providers of acutely ill and injured children presenting to rural EDs are cost-saving ( base-case and more than half of Monte Carlo simulation iterations ) or cost-effective compared with telephone consultations Background Increasing use of teledermatology should be based on demonstration of favourable accuracy and cost – benefit analysis for the different methods of use of this technique Telehospice ( TH ) utilizes telemedicine technology to provide care at the end of life . A bistate project was launched in 1998 to study the use of home-based telemedicine for routine hospice care . Videophones were deployed for telenursing visits and evaluations by social workers . In order to determine what proportion of home hospice visits could be performed using currently available telemedicine technology , we review ed clinical records retrospectively for hospice nurse home visits . Clinical notes documenting home nursing visits were obtained from two large hospices , one based in Kansas , and the other in Michigan . Records were r and omly selected for patients who received hospice nurse visits during the month of January 2000 . The charts were review ed for patient demographic information , patient assessment s , teaching activities , and interventions . Five hundred ninety-seven nursing notes were analyzed using an 85-item coding instrument . After careful review of the records , the coders also made a subjective observation regarding the suitability of each visit for telemedicine . As part of this analysis , we found that 64.5 % of home hospice nursing visits could be performed by telemedicine . Using TH , it is possible to reduce the number of in-person visits , thereby significantly decreasing the cost of providing hospice care PURPOSE The purpose of this study was to assess the accuracy of a virtual consultation ( VC ) process in determining treatment strategy for patients with malignant epidural spinal cord compression ( MESCC ) . METHODS AND MATERIAL S A prospect i ve clinical data base was maintained for patients with MESCC . A virtual consultation process ( involving exchange of key predetermined clinical information and diagnostic imaging ) facilitated rapid decision-making between oncologists and spinal surgeons . Diagnostic imaging was review ed retrospectively ( by R.R. ) for surgical opinions in all patients . The primary outcome was the accuracy of virtual consultation opinion in predicting the final treatment recommendation . RESULTS After excluding 20 patients who were referred directly to the spinal surgeon , 125 patients were eligible for virtual consultation . Of the 46 patients who had a VC , surgery was recommended in 28 patients and actually given to 23 . A retrospective review revealed that 5/79 patients who did not have a VC would have been considered surgical c and i date s. The overall accuracy of the virtual consultation process was estimated at 92 % . CONCLUSION The VC process for MESCC patients provides a reliable means of arriving at a multidisciplinary opinion while minimizing patient transfer . This can potentially shorten treatment decision time and enhance clinical outcomes A r and omized controlled trial was carried out to measure the cost-effectiveness of realtime teledermatology compared with conventional outpatient dermatology care for patients from urban and rural areas . One urban and one rural health centre were linked to a regional hospital in Northern Irel and by ISDN at 128 kbit/s . Over two years , 274 patients required a hospital outpatient dermatology referral - 126 patients ( 46 % ) were r and omized to a telemedicine consultation and 148 ( 54 % ) to a conventional hospital outpatient consultation . Of those seen by telemedicine , 61 % were registered with an urban practice , compared with 71 % of those seen conventionally . The clinical outcomes of the two types of consultation were similar - almost half the patients were managed after a single consultation with the dermatologist . The observed marginal cost per patient of the initial realtime teledermatology consultation was 52.85 for those in urban areas and 59.93 per patient for those from rural areas . The observed marginal cost of the initial conventional consultation was 47.13 for urban patients and 48.77 for rural patients . The total observed costs of teledermatology were higher than the costs of conventional care in both urban and rural areas , mainly because of the fixed equipment costs . Sensitivity analysis using a real-world scenario showed that in urban areas the average costs of the telemedicine and conventional consultations were about equal , while in rural areas the average cost of the telemedicine consultation was less than that of the conventional consultation 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 Videotelephony ( real-time audio-visual communication ) has been used successfully in adult palliative home care . This paper describes two attempts to complete an RCT ( both of which were ab and oned following difficulties with family recruitment ) , design ed to investigate the use of videotelephony with families receiving palliative care from a tertiary paediatric oncology service in Brisbane , Australia . To investigate whether providing videotelephone-based support was acceptable to these families , a 12-month non-r and omised acceptability trial was completed . Seventeen palliative care families were offered access to a videotelephone support service in addition to the 24 hours ‘ on-call ’ service already offered . A 92 % participation rate in this study provided some reassurance that the use of videotelephones themselves was not a factor in poor RCT participation rates . The next phase of research is to investigate the integration of videotelephone-based support from the time of diagnosis , through outpatient care and support , and for palliative care rather than for palliative care in isolation . Trial registration ACTRN The clinical effectiveness of realtime teledermatology , store- and -forward teledermatology and conventional outpatient dermatological care were evaluated in a r and omized control trial . A total of 204 patients took part – 102 patients were r and omized to the realtime teledermatology consultation , 96 of whose cases were also referred using a store- and -forward technique , and 102 to the conventional outpatient consultation . There were no differences in the reported clinical outcomes of realtime teledermatology and conventional dermatology . Of those r and omized to the realtime teledermatology consultation , 46 % required at least one subsequent hospital appointment compared with 45 % of those r and omized to the conventional outpatient consultation . In contrast , the dermatologist requested a subsequent hospital appointment for 69 % of those seen by store- and -forward teledermatology . An analysis of costs showed that realtime teledermatology was clinical ly feasible but more expensive than conventional care , while the store- and -forward teledermatology consultation was less expensive but its clinical usefulness was limited . Sensitivity analysis indicated that realtime teledermatology was as economical as conventional care when less artificial assumptions were made about equipment utilization , costs and travel distances to hospital |
12,392 | 23,579,502 | However , results were highly discordant with some studies suggesting less pronounced OS after laparoscopic surgery , other studies suggesting potentiation of OS after laparoscopic surgery and some studies demonstrating no difference in OS between open and laparoscopic surgery | This systematic review aim ed to investigate : ( a ) the impact of laparoscopic surgery on oxidative stress ( OS ) and ( b ) the effect of laparoscopic surgery on OS in comparison with open surgery . | STUDY OBJECTIVE To investigate the effects of peritoneal exposure to carbon dioxide ( CO2 ) on peritoneal microcirculation and free radical scavenger ( FRS ) metabolism , and its role in potential adhesion formation after operative laparoscopy . DESIGN R and omized , controlled study ( Canadian Task Force classification I ) . SETTING University-affiliated hospital . PATIENTS Twenty-eight women undergoing operative laparoscopy for adnexal masses . INTERVENTION For each patient , a 1 x 1-cm sidewall peritoneal flap was excised at the end of laparoscopy and numbered r and omly . Similar flaps obtained from 24 women immediately after entering the abdomen during laparotomy served as controls . MEASUREMENTS AND MAIN RESULTS Changes in glutathione peroxidase ( GSH-Px ) , superoxide dismutase ( SOD ) , catalase ( CAT ) , and glutathione ( GSH ) levels were studied in homogenized peritoneal tissues . The duration of CO2 exposure and amount of CO2 used were correlated with levels of free radical scavengers and compared with controls . Mean CO2 exposure , amount of CO2 used , and CO2 pressure ( 15 mm Hg ) was similar between low irrigation and irrigated laparoscopy ( 118.3 + /- 25 and 39.2 + /- 8.81 min and 125 + /- 20 and 44.5 + /- 6.81 min , respectively ) . The change in FRS levels was significantly correlated with duration and amount of CO2 exposure ( r = -0.92 ) . Levels of GSH-Px , SOD , CAT , and GSH were significantly lower in the CO2 exposure group than in controls ( 0.57 micro mol , 1.8 ng , 48.5 micro mol , 1.5 nmol vs 0.8 micro mol , 2.6 + /- 0.4 ng , 79 micro mol , 3.6 nmol , respectively ) . CONCLUSION Exposure to CO2 has adverse effects on peritoneal microcirculation and cell-protective systems , which are proposed mechanisms in adhesion formation . Avoiding long CO2 exposure and copiously irrigating the abdominal cavity throughout surgery may lessen these effects . The potential role of the peritoneal FRS system on postoperative adhesion formation and its relation to estrogen status m and ates further studies Three groups of 11 New Zeal and women each received , for 32 wk , yeast tablets with no added selenium ( placebo ) or 200 micrograms Se/d in tablets either as selenate or as selenium-enriched yeast ( SeMet ) in a double-blind selenium trial . Plasma and erythrocyte ( RBC ) sample s were collected bimonthly . Gel filtration of plasma from women taking SeMet revealed two major selenium-containing peaks with most of the selenium in the second peak . In contrast , the first peak contained most of the selenium in plasma from women taking selenate . Chromatography of RBC lysates indicated that the majority of the selenium was with hemoglobin ( Hb ) in women taking SeMet but was about equally distributed between glutathione peroxidase ( GSH-Px ) and Hb in women taking selenate . The percentage of selenium associated with GSH-Px was found to be greater in RBCs and plasma of women taking selenate than of those taking SeMet In this prospect i ve study the free radical mediated reactions , the changes of endogenous antioxidant defense mechanism and activation of leukocytes were measured from the blood of patients undergoing elective cholecystectomy because of symptomatic cholecystolithiasis . The patients were r and omised into two groups . Group one contained 21 patients treated by open cholecystectomy(OC ) . Group two consisted of 21 patients treated by laparoscopic cholecystectomy ( LC ) . Both groups had similar patient characteristics . Patients with acute cholecystitis , pancreatitis , choledocholithiasis or other disease were excluded . Values from patients in both groups were compared . The measured biochemical parameters are the following : malondialdehyde ( MDA ) as a marker of the free radical induced lipid peroxidations , reduced and oxidised glutathione ( GSH-GSSG ) , as endogenous scavengers as well as markers of oxidative stress and myeloperoxidase activity ( MPO ) of leukocytes . The results showed significantly lower values of postoperatively measured MDA , GSH-GSSG , and MPO activity of leukocytes in patients with laparoscopic cholecystectomy , indicating a lesser stress response and tissue trauma in this group of patients . The results correspond to the favourable results of most other trials evaluating clinical aspect of LC The patient ’s position during laparoscopic surgery can have a clinical ly relevant effect on lower limb and splanchnic circulation ; this factor has not yet been investigated with respect to oxidative stress markers . In order to assess this effect , a prospect i ve clinical trial was design ed wherein 2 groups of patients were studied . In group A , 15 patients underwent upper abdominal nonhepatobiliary operations ( 13 modified Nissen fundoplications and 2 Taylor vagotomies ) in the head-up position . In group B , 15 patients underwent lower abdominal operations ( 10 laparoscopic colectomies and 5 inguinal hernia repairs ) in the head-down position . The pneumoperitoneum was maintained at 14 mm Hg in all cases . Plasma concentrations of thiobarbituric-acid reactive substances ( TBARS ) , a marker of lipid peroxidation , plasma total antioxidant status ( TAS ) , and serum uric acid concentrations were measured preoperatively , 5 minutes after deflation of the pneumoperitoneum , and 24 hours postoperatively . Aspartate aminotransferase ( AST ) and alanine aminotransferase ( ALT ) serum activities were measured preoperatively and 24 hours postoperatively . In group A , there was a significant increase in TBARS levels ( p<0.005 ) immediately after deflation of the pneumoperitoneum and a significant decrease in TAS and uric acid levels ( p<0.005 ) in the first postoperative day . There was also a significant postoperative elevation in both ALT and AST activities ( p<0.001 ) . In group B , no significant increase was found in postoperative TBARS or transaminase levels . TAS and uric acid levels decreased significantly in the first postoperative day ( p<0.05 ) and ( p<0.005 , respectively ) . In conclusion , these results show that a combination of pneumoperitoneum and the head-up position causes significant increase in lipid peroxidation , decrease in plasma TAS , and increase in transaminases . The mechanism responsible for these events could be the low-flow ischemia-reperfusion syndrome induced by the pneumoperitoneum and aggravated by the head-up position Background and objective : To compare the effects of sevoflurane and desflurane anaesthesia on lipid peroxidation . Methods : We studied 40 healthy patients undergoing elective laparoscopic cholecystectomy . Patients were r and omly allocated to be anaesthetized either with sevoflurane ( n = 20 ) or desflurane ( n = 20 ) . Anaesthesia was maintained with inspiratory concentrations of sevoflurane 1 - 1.5 MAC ( n = 20 ) or desflurane ( n = 20 ) . Sample s were taken for plasma malondialdehyde and superoxide dismutase assays before induction of anaesthesia , before skin incision and at the end of surgery . Alveolar cell sample s were obtained from the lungs using the technique of protective blind bronchoalveolar lavage , after induction of anaesthesia and at the end of surgery for malondialdehyde and superoxide dismutase concentrations . Results : Plasma malondialdehyde increased more after the administration of desflurane than after sevoflurane : after induction 5.9 ± 0.6 nmol mL−1 for desflurane vs. 3.8 ± 0.5 nmol L−1 for sevoflurane ( P < 0.001 ) ; at the end of the surgery : 6.7 ± 0.4 nmol mL−1 for desflurane vs. 4.2 ± 0.3 nmol mL−1 for sevoflurane ( P < 0.001 ) . There was a small but significant increase in plasma superoxide dismutase concentration after desflurane - from 24.2 ± 1.2 to 24.9 ± 0.9 U mL−1 after induction and 25 ± 1 U mL−1 at the end of the surgery ( P < 0.01 ) - but no increase with sevoflurane . Malondialdehyde concentrations increased significantly in the cells obtained by protective blind bronchoalveolar lavage at the end of surgery in the desflurane group ( from 0.3 ± 0.1 to 1.7 ± 0.2 nmol mL−1 ( P < 0.001 ) ) , but not in the sevoflurane group . There were no significant differences between the two anaesthetics in the amounts of superoxide dismutase in the sample s obtained by protective blind bronchoalveolar lavage . Conclusions : Desflurane may cause more systemic and regional lipid peroxidation than sevoflurane during laparoscopic cholecystectomy in healthy human beings BACKGROUND The aim of this work was to determine and compare plasma levels of proinflammatory cytokines ( IL-1beta , IL-6 and TNF-alpha ) , C-reactive protein ( CRP ) and lipoperoxides in patients su bmi tted to laparoscopic cholecystectomy under general anesthesia or regional anesthesia . METHODS Two groups of 15 patients of both sexes were su bmi tted to laparoscopic cholecystectomy either with general or regional anesthesia . In all cases we obtained three sample s of plasma . The first sample was collected immediately before surgery , whereas the other sample s were collected 60 min and 24 h after the cholecystectomy . Using commercial kits , plasma levels of IL-1beta , IL-6 and TNF-alpha were quantified by ELISA , whereas lipoperoxides were determined by a colorimetric method . The ultrasensitive CRP was determined in the hospital by the Prestige 24I automated method . RESULTS In all determinations , proinflammatory cytokines increased 24 h after surgery except plasma levels of IL-1beta in the regional anesthesia group . Comparison of the two different groups showed that the general anesthesia group had a similar or higher quantity of proinflammatory cytokines and oxidative stress when compared to the regional anesthesia group ( p < 0.05 ) . In contrast , plasma levels of CRP were lower in the general anesthesia group ( p < 0.005 ) . CONCLUSIONS The type of anesthesia influences in a different manner the secretion of soluble mediators of inflammation . These observations may have important clinical repercussions BACKGROUND Surgical injury is associated with oxidative stress , often due to ischemia/reperfusion injury . During laparoscopy , increased intra-abdominal pressure caused by pneumoperitoneum may cause splanchnic ischemia followed by reperfusion due to deflation . We measured several markers of oxidative stress in patients undergoing laparoscopic cholecystectomy ( LC ) versus open cholecystectomy ( OC ) to find if these surgical procedures result in different patterns of oxidative stress . METHODS This prospect i ve study enrolled 43 patients with symptomatic cholelithiasis , of whom 21 underwent open , and 22 laparoscopic , cholecystectomy . Twenty healthy adults comprised the control group . Total antioxidant status ( TAS ) , superoxide dismutase ( SOD ) , endogenous peroxide level ( POX ) , oxidized low density lipoprotein ( oLDL ) autoantibodies ( oLAb ) , and neopterin were measured preoperatively and on postoperative days 1 , 3 , and 7 . RESULTS POX values decreased significantly on postoperative day 1 in the OC ( P<0.01 ) , but not in the LC , group . On postoperative day 7 , POX values were higher than preoperatively in both groups ( P<0.01 ) with no difference between the LC and OC groups . Significant postoperative elevations of oLAb and neopterin levels were observed only on postoperative day 7 in the OC group . There were no changes of oLAb and neopterin levels in the LC group . TAS and SOD levels did not change after either LC or OC . CONCLUSION Cholecystectomy , either open or laparoscopic , caused only moderate oxidative stress . Open cholecystectomy caused changes of oLAb and neopterin , suggesting more severe oxidative stress , and a possible role of reactive oxygen species in the healing of the laparotomic wound Background : Although it has been been shown that the elevation of abdominal pressure causes splanchnic ischemia , the pathophysiological changes that occur during laparoscopic cholecystectomy are still under investigation . Our aim was to evaluate the changes in nitric oxide ( NO ) , malondialdehyde ( MDA ) , and gastric intramucosal pH ( pHi ) during laparoscopic surgery to verify whether splanchnic ischemia had occurred . Methods : Forty patients ( 11 men and 29 women ) scheduled for cholecystectomy were r and omly divided to undergo either open ( OC ) or laparoscopic cholecystectomy ( LC ) . Repeated blood sample s were collected for the measurement of NO and MDA concentrations . End-tidal carbon dioxide ( ETCO2 ) levels were measured using a capnograph , and pHi was assessed using a tonometric nasogastric catheter . Results : Although no significant change in pH was observed in the LC group during the procedure , it decreased significantly in the OC group and then returned to normal immediately after the procedure . ETCO2 did not change in the LC group but it increased in the OC group . Although it was not statistically significant , NO concentrations were slightly increased inthe LC group . The same magnitude of increase was seen in MDA levels but it was not significant . Neither NO nor MDA levels changed in the OC group . Conclusion : LC has no adverse effects on gut perfusion . Even if the abdominal organs are hypoperfused during the procedure , compensates for this hypoperfusion so that it pulsatile NO secretion does not cause any harm . Since LC is a short procedure , the significance of these events for extended procedures still needs to be clarified To determine differences in systemic stress responses in patients undergoing three different types of surgery for benign prostatic hyperplasia ( BPH ) , evaluated by measuring levels of stress variables , i.e. cortisol ; acute‐phase reactants , i.e. C‐reactive protein ( CRP ) and fibrinogen ; and antioxidants , i.e. total antioxidant status ( TAS ) and superoxide dismutase ( SOD ) We studied the effects of Propofol , Desflurane , and Sevoflurane on the systemic redox balance in patients undergoing laparohysterectomy . We measured blood concentration of glutathione ( GSH ) , plasma antioxidant capacity ( Trolox Equivalent Antioxidant Capacity-TEAC ) , and lipid peroxidation products ( malondialdehyde ( aMDA ) and 4-hydroxynonenal ( aHNE ) protein adducts ) . Sixty patients were r and omly placed into three groups of twenty people each . In Group P anesthesia was induced with Propofol 2 mg/kg and maintained with 12–10–8 mg/kg/min ; in Groups S and D anesthesia was induced with 3 mg/kg Sodium Thiopental and maintained with 2 % Sevoflurane and 6 % Desflurane , respectively . Blood sample s were collected prior to induction ( T0 bas ) , 60min and 24h postoperatively ( T1 60 ' and T2 24 h ) . In Group P , GSH increased on T1 60 ' ( p<0.02 ) and returned to baseline on T24h , while TEAC remained unmodified ; in Groups S , GSH and TEAC decreased on T1 60 ' ( p<0.01 vs. T0 bas , p<0.03 vs. T0 bas , respectively ) ; in Group D , on T160 ' there was a slight decrease of GSH and TEAC . The levels of aMDA slightly decreased throughout the study periods in Group P , increased in Group D , and remained stable in Group S. Propofol showed antioxidant properties , while Sevoflurane and Desflurane seemed to shift the redox balance towards oxidation , yet without inducing overt oxidative damage Elective laparoscopic cholecystectomy is established as the treatment of choice for symptomatic cholecystolithiasis and is now proposed for the treatment of acute cholecystitis . The aim of this study is to evaluate biochemical aspects of open ( OC ) and laparoscopic cholecystectomy ( LC ) . We measured the levels of malondialdehyde ( MDA ) and the levels of nitrite+nitrate as stable end products of nitric oxide ( NO ) . MDA and nitrite+nitrate levels were increased at both surgical procedures compared to preoperative period , but the rise was more significant in OC than LC . These results showed that both OC and LC caused an increase in oxidative stress . However LC caused significantly less oxidative stress and the changes during surgery returned to preoperative values after LC in a shorter period . The beneficial effects of laparoscopic surgery may be related , partially , to less oxidative stress in the immediate postoperative period OBJECTIVE This prospect i ve r and omized study was conducted in order to define the contribution of the generated oxygen and nitrogen reactive species on postlobectomy morbidity and mortality . PATIENTS AND METHODS Between 2001 and 2003 , 132 patients with non-small cell lung cancer ( NSCLC ) were prospect ively studied . The patients were grouped according to one-lung ventilation ( OLV ) use or not and to the duration of lung 's atelectasis . Group A included 50 patients with confirmed non-small cell lung cancer who were subjected to lobectomy without one-lung ventilation . Group B included 30 patients subjected to 60 min OLV . Group C included 30 patients subjected to 90 min OLV . Group D included 22 patients subjected to 120 min OLV . Preoperative , intraoperative and postoperative strict blood sampling protocol was followed . Malondialdehyde ( MDA ) plasma levels were measured . The groups were statistically compared for the occurrence of postoperative complications . OLV ( groups B-D ) along with other clinical parameters were entered in multivariate analysis as risk factors for complication development . MEASUREMENTS AND RESULTS Comparison of group A with groups B-D ( OLV ) documented significant increase ( p<0.001 ) of MDA levels during lung reexpansion . The magnitude of oxidative stress was related to OLV duration ( group D > group C > group B , all p<0.001 ) . Univariate analysis disclosed a higher incidence of acute respiratory failure , cardiac arrhythmias and pulmonary hypertension in group D. Multivariate analysis revealed OLV as an independent risk factor for postoperative development of cardiac arrhythmias and pulmonary hypertension . CONCLUSION Protracted ( > 1h ) OLV should be considered a potential cause for cardiovascular complications through the generation of severe oxidative stress due to lung reexpansion A variety of methods are available for analysing repeated measurements data where the outcome is continuous . However , there is little information on how established methods , such as summary statistics and repeated measures analysis of variance ( RMAOV ) , compare in practice with methods that have become available to applied statisticians more recently , such as marginal models ( based on generalized estimating equation methodology ) and multilevel models ( that is , hierarchical r and om effects models ) . The aim of this paper is to exemplify the use of these methods , and directly compare their results by application to a clinical trial data set . The focus is on practical aspects rather than technical issues . The data considered were taken from a clinical trial of treatments for asthma in 240 children , in which a baseline and four post-r and omization measurements of outcomes were taken . The simplicity of the method of summary statistics using the post-r and omization mean of observations provided a useful initial analysis . However , fixed time effects or treatment-time interactions can not be included in such an analysis , and choice of appropriate weighting when there is substantial missing data is problematic . RMAOV , marginal models and multilevel models generally provided similar estimates and st and ard errors for the treatment effects , although in one example with a relatively complex variance structure the marginal model produced less efficient estimates . Two advantages of multilevel models are that they provide direct estimates of variance components which are often of interest in their own right , and that they can be naturally extended to h and le multivariate outcomes Background : The induction of the pneumoperitoneum increases intraabdominal pressure ( IAP ) , causing splanchnic ischemia , whereas its deflation normalizes IAP and splanchnic blood flow . This procedure appears to represent an ischemia-reperfusion model in humans . Methods : Thirty laparoscopic cholecystectomies ( LC ) were performed in 30 patients with a mean age of 54.6 ± 15.6 years . A group of 20 patients mean age , 57.3 ± 9.65 who underwent open cholecystectomy ( OC ) was also studied . Vein plasma levels of thiobarbituric acid-reactive substances ( TBARS ) , a marker of free radical production ; plasma total antioxidant status ( TAS ) ; and uric acid ( UA ) levels were measured preoperatively , 5 min after deflation of the pneumoperitoneum or at the end of operation , and 24 h postoperatively . Aspartate aminotransferase ( AST ) , alanine aminotransferase ( ALT ) , and total bilirubin ( TBL ) levels were measured preoperatively and 24 h after the operation . Results : In the LC group , significant elevations in the concentration of TBARS were observed in the early postoperative measurements in comparison with the preoperative measurements . TAS and UA levels were decreased significantly 24 h postoperatively compared to preoperative levels . The postoperative levels of AST , ALT , and TBL increased significantly in comparison with the preoperative levels . In the OC group , no alterations in the concentration of TBARS were observed in the postoperative period . The other parameters had changes similar to those recorded for the LC group . Conclusions : Free radical-induced lipid peroxidation associated with a decrease in plasma antioxidant capacity and UA levels as well as altered hepatic function is observed after deflation of the pneumoperitoneum . These results suggest that free radicals are generated at the end of a laparoscopic procedure , possibly as a result of an ischemia-reperfusion phenomenon induced by the inflation and deflation of the pneumoperitoneum The objective demonstration of improved postoperative recovery suggests that surgical injury induced by the laparoscopic approach is less intense than that after open surgery . Forty-two patients diagnosed as having noncomplicated gallstones were studied prospect ively . They were operated on by laparoscopy ( LC , n = 21 ) or open surgery ( OC , n = 21 ) . Both surgical procedures induced significant changes of investigated parameters ( acute-phase response , free radical mediated reactions , neutrophil functions ) . Comparison of the results of the two cholecystectomy techniques showed that laparoscopic cholecystectomy induced a significantly less intense acute-phase response , a more attenuated oxidative stress characterising by free radical mediated reactions and that is less disruptive to neutrophil function . The results and the data from the literature suggest that surgical injury causing by the laparoscopic cholecystectomy is less intense than that after open cholecystectomy , which can explain partially the better clinical outcome following laparoscopic versus open procedure OBJECTIVE To measure the amount of lipid peroxidation and erythrocyte antioxidation in patients undergoing laparoscopic and open cholecystectomy and healthy controls . DESIGN Non-r and omised study . SETTING University hospital , Istanbul . SUBJECTS 31 patients , of whom 14 underwent open and 17 laparoscopic cholecystectomy , and 15 healthy controls . INTERVENTIONS Heparinised blood sample s were taken from the patients immediately after operation and from the healthy controls . MAIN OUTCOME MEASURES Lipid peroxidation index as expressed by thiobarbituric-acid-reactive substances ( TBARS ) and components of the erythrocyte antioxidant defence system , namely reduced glutathione , reduced glutathione peroxidase ( glutathione-Px ) and CuZn superoxide dismutase ( CuZn SOD ) in patients undergoing open or laparoscopic cholecystectomy and healthy controls . RESULTS All 4 variables were significantly higher in the cholecystectomy groups than in controls ( p < 0.001 ) , and laparoscopic cholecystectomy caused significantly less oxidative stress than the open operation ( p < 0.001 ) . CONCLUSION Both types of cholecystectomy cause oxidative stress and lead to an adaptive antioxidant response in the body . However ; both oxidative stress and the antioxidant response are more pronounced after traditional open cholecystectomy Abstract . Purpose : We conducted a prospect i ve study to evaluate the effect of CO2 pneumoperitoneum and increased intra-abdominal pressure on arterial blood gases , end-tidal CO2 ( ETCO2 ) , nitric oxide ( NO ) , blood and tissue malondialdehyde ( MDA ) , and total antioxidant ( TAOx ) levels during laparoscopic cholecystectomy . Methods : Fifty selected patients with cholelithiasis were r and omized to undergo either laparoscopic or open surgery . Blood sample s were taken pre- , mid- , and postinsufflation , and 24 h postoperatively . To determine the tissue MDA level , tissue sample s were taken from the gallbladder just after removal . Results : The increased levels of ETCO2 and PCO2 , caused by CO2 pneumoperitoneum result ed in a minimal decrease in blood pH during the laparoscopic surgery . Although low levels of blood MDA were seen 30 min after the start of laparoscopy , due to less oxidative stress response and tissue trauma , increased levels of tissue MDA levels indicated that the gallbladder was more traumatized during laparoscopic dissection and h and ling . NO levels were slightly lower in the laparoscopic cholecystectomy ( LC ) group , but there were no significant differences compared with the open cholecystectomy group ( OC ) . TAOx levels were similar in both groups 30 min after the start the procedure , but were much lower in the LC group 24 h postoperatively . Conclusions : These findings suggest that the antioxidant defense system is stimulated less with less oxidative stress , providing further evidence to support the opinion that LC is a safe technique BACKGROUND AND PURPOSE As laparoscopic surgery has evolved , it has become part of the urologic surgical armamentarium and is now used to perform more complex procedures . Carbon dioxide , used to create pneumoperitoneum , produces physiologic changes in various organs , including the kidneys . Such changes are associated with altered redox status because of the release of free radicals and changes in oxidative stress signals . It is unknown whether prolonged pneumoperitoneum is associated with an increase in oxidative stress compared with open surgery . The objective of this study was to compare oxidative stress in patients undergoing urologic laparoscopic and open operations . PATIENTS AND METHODS Urine sample s were obtained immediately preoperatively , immediately postoperatively , and at 6 and 18 hours after surgery from 10 patients who underwent urologic laparoscopic surgery and 10 patients who underwent open surgery . Concentrations of the oxidative stress marker isoprostane ( 8- iso-prostagl and in F2a ) were measured , and the results were analyzed with respect to clinical factors associated with the type of surgery . RESULTS Urinary isoprostane concentrations ( mean + /- SEM ) in the laparoscopic and open groups showed an increase immediately after surgery to 189.0 + /- 64.2 % and 141.1 + /- 45.8 % of the preoperative values , respectively . A decrease in isoprostane was subsequently observed in both groups at 6 hours postoperatively , with preoperative values restored at 18 hours postoperatively ( 126.3 + /- 19.7 % and 89.5 + /- 55.9 % at 6 and 18 hours , respectively , in the laparoscopic group and 130.7 + /- 41.6 % and 88.7 + /- 20.4 % at 6 and 18 hours , respectively , in the open-surgery group ) . Although in both groups the peak PGF 2a concentration was observed immediately ( 0 hours ) postoperatively , no significant differences were observed between the groups at 0 , 6 , and 18 hours . In the laparoscopic-surgery group , the mean increase tended to be higher and the decrease to be less prolonged than in the open-surgery group . CONCLUSION Oxidative stress , as measured by urinary 8-iso-prostagl and in F2a , is produced by both laparoscopic and open urologic surgery . The findings of our nonr and omized study suggest a pattern of increased oxidative stress postoperatively with either type of surgery , with subsequent return almost to preoperative levels . Prolonged laparoscopic operative time did not affect oxidative stress levels OBJECTIVE To evaluate the effect of laparoscopic surgery on and lipid hyperoxidation in patients with hysteromyoma . METHODS Forty patients with hysteromyoma were r and omly divided into 2 equal groups : laparoscopy group and laparotomy group . The plasma advanced oxidation protein products ( AOPP ) , malondialdehyde ( MDA ) , antioxidant activity ( AOA ) , and glutathione peroxidase ( GPx ) activity were measured before operation , just after operation ( 5 minutes after deflation ) and 24 hours after operation . RESULTS ( 1 ) In the laparoscopy group , the levels of AOPP and MDA were ( 50.20 + /- 9.23 ) micromol/L and ( 1.85 + /- 0.19 ) micromol/L before operation , increased significantly just after operation [ ( 68.75 + /- 12.69 ) micromol/L and ( 2.52 + /- 0.55 ) micromol/L respectively , both P < 0.01 ] , and recovered to the normal level 24 hour postoperatively [ ( 49.70 + /- 9.92 ) micromol/L and ( 2.05 + /- 0.68 ) micromol/L respectively , both P > 0.05 ] . The levels of GPx and AOA decreased significantly just after operation [ ( 0.29 + /- 0.09 ) U/ml vs. ( 0.62 + /- 0.27 ) U/mL and ( 0.90 + /- 0.24 ) mmol/L vs. ( 1.41 + /- 0.39 ) mmol/L respectively , both P < 0.01 ] , and the GPx level recovered 24 hours after operation [ ( 0.52 + /- 0.06 ) U/mL , P > 0.05 ] , however , the AOA level was still lower [ ( 1.00 + /- 0.31 ) mmol/L , P < 0.01 ] . In the laparotomy group , the levels of plasma AOPP and MDA level slightly increased just after operation in comparison with those before operation [ ( 53.39 + /- 9.86 ) micromol/L vs. ( 52.30 + /- 7.10 ) micromol/L and ( 2.09 + /- 0.51 ) micromol/L vs. ( 1.83 + /- 0.64 ) micromol/L respectively , both P > 0.05 ] and continued to increase 24 hours after operation [ ( 63.40 + /- 15.5 ) micromol/L , P < 0.05 , and ( 2.42 + /- 0.44 ) micromol/L , P < 0.01 ] ; the GPx and AOA levels decreased a little just after operation [ ( 0.51 + /- 0.17 ) U/mL vs. ( 0.57 + /- 0.21 ) U/mL and ( 1.20 + /- 0.46 ) mmol/L vs. ( 1.33 + /- 0.37 ) mmol/L , both P > 0.05 ] and continued to decrease 24 hours after operation [ ( 0.35 + /- 0.19 ) U/mL and ( 0.92 + /- 0.22 ) mmol/L respectively , both P < 0.01 ] . Compared with those of the laparotomy group , the plasma AOPP and MDA levels of the laparoscopy group were both significantly lower ( P < 0.01 and P < 0.05 ) , and the GPx level was significantly higher ( P < 0.01 ) 24 hours after operation , however , the AOA level was not significantly different ( P > 0.05 ) . CONCLUSION Laparoscopic surgery is better than laparotomy . Protein oxidation and lipid hyperoxidation occur during the laparoscopic surgery , however , disappeared after operation . Free radicals are generated by the end of laparoscopic procedure , possibly as a result of an ischemia-reperfusion phenomenon induced by the inflation and deflation of the pneumoperitoneum . AOPP and MDA are induced during laparoscopic procedure and then return to the normal levels finally OBJECTIVE To compare systemic stress responses after laparoscopic and open hernia repair to find out if the laparoscopic approach caused less stress than an open operation . DESIGN Prospect i ve r and omised trial . SETTING Teaching hospital , Sanliurfa , Turkey . SUBJECTS 50 patients who required preperitoneal hernia repair were r and omised to be treated by either the open or laparoscopic approach ( n = 25 in each ) . INTERVENTIONS Sample s of venous blood were taken before operation and at 2 , 24 , and 48 hours afterwards for measurement of the concentrations of : glucose , cortisol , malonyldialdehyde ( MDA ) , C-reactive protein ( CRP ) , creatine phosphokinase ( CPK ) , caeruloplasmin , transferrin , fibrinogen , and albumin , and counts of leucocytes , neutrophils , and lymphocytes . MAIN OUTCOME MEASURES Changes in these indicators of a stress response . RESULTS Concentrations of glucose , cortisol , CRP , MDA , and CPK , and counts of leucocytes and neutrophils increased significantly , and the concentration of albumin decreased significantly , in both groups postoperatively . Lymphocyte counts were lower postoperatively but not significantly so . Concentrations of CRP , MDA , and CPK , and leucocyte counts were significantly lower in the laparoscopic group . CONCLUSION These findings suggest that there is less systemic stress response after laparoscopic than after open hernia repair BACKGROUND Free radicals induced by several diseases can trigger oxidative stress , leading to the production of malondialdehyde ( MDA ) and protein carbonyl content ( CB ) . Volatile agents are able to increase the extent of oxidative status . However , the effects of these agents together with pneumoperitonium ( Pp ) have not been reported . We aim ed to investigate the role of volatile anesthetics and ischemic injury during Pp on free radicals and scavenging enzymes in laparoscopic abdominal surgery . METHODS AND MATERIAL S Forty patients were examined . Patients were r and omly divided into four groups in order to receive sevoflurane-fentanyl ( SF = 10 ) , sevoflurane-N(2)O ( SN = 10 ) , desflurane-fentanyl ( DF = 10 ) , and desflurane-N(2)O ( DN = 10 ) , respectively . Tidal volume and ventilation frequency were kept unchanged during the operation . Intraabdominal pressure was remained constant at 12 mm Hg . Baseline values in venous blood sample s were preoperatively taken and blood was also taken postoperatively at the 6th and the 24th hours . After collection of blood sample s into citrate ( 3.5 mg/mL blood ) containing glass tubes , erythrocyte sediments were prepared for the analyses . Then malondialdehyde levels , protein carbonyl content , and sulfhydryl ( SH ) groups were measured . RESULTS The levels of MDA and protein carbonyl content were significantly higher at the 6th hour rather than the 24th hour postoperatively with desflurane anesthesia . In addition , SH groups were significantly different between the 6th hour and the 24th hour measurements ( P < 0.05 ) . In our study , desflurane caused a statistically significant increase in MDA levels and protein carbonyl content and a decrease in SH groups . When the two groups were compared , in the case of MDA and CB values , a significant increase was observed in the 6th and the 24th hour , where there was a decrease in SH groups in the desflurane group ( P < 0.05 ) . These parameters did not change in the sevoflurane group ( P > 0.05 ) . CONCLUSION We concluded that desflurane was affected by desflurane with low flow anesthesia in patients undergoing laparoscopic abdominal surgery . Significant influence on oxidative stress and antioxidant mechanics was not seen with sevoflurane anesthesia . Our studies support that oxidant and antioxidant defense mechanisms were altered in the desflurane group and this alteration improved after a combination of Objective : To vali date ischemia-reperfusion mechanism during laparoscopic cholecystectomy , and to assess the reduction of oxidative stress by an intermittent sequential pneumatic compression ( ISPC ) device . Summary Background : Increased intraperitoneal pressure during laparoscopic operations may lead to decreased cardiac output and visceral perfusion , and possible ischemia-reperfusion effects . Using the ISPC device was shown to improve cardiac output and visceral perfusion during pneumoperitoneum ( PP ) . Methods : Twenty patients undergoing elective laparoscopic cholecystectomy were enrolled in a r and omized prospect i ve controlled study and divided into 2 groups : 1 ) study group ( 10 patients ) , activation of ISPC together with creation of PP ; and 2 ) control group , without ISPC . Lipid peroxidation and glutathione levels ( as indicators of oxidative stress ) as well as liver and renal function tests , were measured before and at the end of PP , and again at 30 minutes , 4 hours , and 24 hours afterward , together with hemodynamic and respiratory parameters . Results : There was no significant difference between both groups concerning liver enzymes and bilirubin , nor in hemodynamic parameters . In the control group , increased lipid peroxide levels were noted 4 hours after PP termination , in comparison to pre-PP levels ( 590.4–649.2 mmol/L , P = 0.002 ) . In the study group ( ISPC ) , such changes were not inspected . Decreased total glutathione levels were noted in the control group , 30 minutes following CO2 evacuation . Conclusions : Our study vali date s the ischemia-reperfusion mechanism following laparoscopic surgery . The use of an ISPC device decreased the oxidative stress ( secondary to relative ischemia-reperfusion insult ) following PP , probably due to improved cardiac output and visceral perfusion BACKGROUND / PURPOSE Cytokines are inflammatory mediators found in the circulation after surgery . Newborns have less protection against oxidation and are very susceptible to free radical oxidative damage . Melatonin has been reported recently to reduce oxidative stress in neonates with sepsis , asphyxia , and respiratory distress . The aim of this study has been to determine if melatonin would lower interleukin (IL)-6 , IL-8 , tumor necrosis factor alpha ( TNF-alpha ) and nitrite/nitrate ( NOx ) levels and modify serum inflammation parameters , improving the clinical course of surgical neonates . METHODS Ten newborns ( group 1 ) , 5 with surgical malformations and respiratory distress ( group 1a ) and 5 with isolated abdominal surgical malformations ( group 1b ) received a total of 10 doses of melatonin ( 10 mg/kg ) at defined times interval for 72 hours . The treatment was started within 3 hours after the end of surgery . Ten surgical neonates ( group 2 ) , did not receive melatonin . Twenty healthy neonates ( group 3 ) served as control . Blood sample s were collected at the end of operation ; before treatment with the antioxidant ; and 24 hours 72 hours , and 7 days after start of treatment with melatonin or placebo , respectively . RESULTS Postoperative value of cytokines and NOx levels of groups 1 and 2 were significantly higher than group 3 . Compared with group 1b , group 2 displayed significantly higher cytokines and NOx levels at 24 hours , 72 hours , and at 7 days . In group 1a the immediate postoperative values of cytokines were significantly higher than group 1b and group 2 , but a significant improvement was observed after administration of melatonin with significantly lower levels of IL-6 and IL-8 with respect to group 2 . An improvement of clinical outcome was observed by progressive reduction of clinical parameters of inflammation . CONCLUSIONS Melatonin reduces cytokines and NOx levels showing potent antioxidant properties with improvement in clinical outcome . Further studies are warranted to define , on larger numbers , the role of melatonin in surgical patients BACKGROUND Free radical-induced lipid peroxidation that is associated with a decrease in the antioxidant status of plasma occurs in many kinds of surgical procedures . In this study , we aim ed to investigate markers of oxidative stress -- malondialdehyde ( as thiobarbituric acid reactive substances ) , protein carbonyls , and protein sulfhydryls -- in patients undergoing Lichtenstein tension-free hernioplasty ( LH ) or laparoscopic preperitoneal hernia ( LPPH ) repair . METHODS Seventeen patients with unilateral inguinal hernia and no complications or recurrence were included in this study . Ten were r and omized to undergo LH and seven to LPPH repair . Heparinized blood sample s were taken to measure the levels of oxidative stress markers in the patients undergoing hernia repair . Levels of malondialdehyde , protein carbonyls , and protein sulfhydryls were measured preoperatively and at 6 and 24 hours postoperatively in all patients . RESULTS Both types of hernia repair caused a significant increase in the oxidative stress response and a decrease in antioxidant activity . Plasma levels of malondialdehyde and carbonyls ( indicators of oxidant activity ) were significantly higher in the LH than in the LPPH repair group ( P<.05 ) , and plasma sulfhydryl levels ( indicators of antioxidant activity ) were significantly lower in the LH than in the LPPH group ( P<.05 ) . In both groups , significant differences were also found between the preoperative levels and the postoperative levels 6 and 24 hours ( P<.05 ) . CONCLUSIONS These data demonstrate that both LH and LPPH repair cause a significant increase in markers of oxidative stress ; however , the oxidative stress response associated with LH is greater than that associated with LPPH repair |
12,393 | 18,381,234 | In summary , thalidomide appears to improve the overall survival of patients with newly diagnosed myeloma both when it is added to st and ard , non-transplantation therapy , and when it is given as maintenance therapy following ASCT .
However , thalidomide is associated with toxicity , particularly a significantly increased risk of VTE | A systematic review and meta- analysis was performed to determine the efficacy and toxicity of thalidomide in previously untreated patients with myeloma . | BACKGROUND We have previously demonstrated that vincristine , liposomal doxorubicin and dexamethasone ( VAD-doxil ) is equally effective with VAD-bolus yielding objective response rates of 61 % as first-line treatment in multiple myeloma ( MM ) . In a phase II study , the addition of thalidomide to VAD-doxil ( TVAD-doxil ) proved feasible and increased response rate to 74 % . The aim of the present multicenter prospect i ve r and omized clinical trial was to compare the efficacy and toxicity of VAD-doxil and TVAD-doxil in previously untreated MM patients . PATIENTS AND METHODS We enrolled 232 newly diagnosed MM patients aged < 75 years , 115 r and omized to VAD-doxil ( arm A ) and 117 to TVAD-doxil ( arm B ) . Patients in arm A received vincristine 2 mg i.v . and liposomal doxorubicin 40 mg/m(2 ) i.v . , on day 1 and dexamethasone 40 mg p.o . daily on days 1 - 4 , 9 - 12 and 17 - 20 for the first cycle and on days 1 - 4 for the next three cycles . Patients in arm B received additionally thalidomide 200 mg p.o . daily , at bedtime . Treatment was administered every 28 days . RESULTS On an intention-to-treat basis , at least partial response was observed , in 62.6 % and in 81.2 % of patients r and omized to arms A and B , respectively ( P = 0.003 ) . Progression-free survival ( PFS ) at 2 years was 44.8 % in arm A and 58.9 % in arm B ( P = 0.013 ) . Overall survival ( OS ) at 2 years was 64.6 % and 77 % , in arms A and B , respectively ( P = 0.037 ) . Considering overall toxicity , constipation , peripheral neuropathy , dizziness/somnolence , skin rash and edema were significantly higher in arm B compared with arm A ( P < 0.01 ) , but grade 3 - 4 toxicities were low and similar in both arms . CONCLUSIONS The addition of thalidomide to VAD-doxil increases response and PFS rates and probably OS in previously untreated myeloma patients . The superiority of efficacy counterbalances the higher overall toxicity of TVAD-doxil Newer chemotherapeutic protocol s as well as high-dose chemotherapy have increased the response rate in myeloma . However , these treatments are not curative . Effective maintenance strategies are now required to prolong the duration of response . We conducted a r and omized trial of maintenance treatment with thalidomide and pamidronate . Two months after high-dose therapy , 597 patients younger than age 65 years were r and omly assigned to receive no maintenance ( arm A ) , pamidronate ( arm B ) , or pamidronate plus thalidomide ( arm C ) . A complete or very good partial response was achieved by 55 % of patients in arm A , 57 % in arm B , and 67 % in arm C ( P = .03 ) . The 3-year postr and omization probability of event-free survival was 36 % in arm A , 37 % in arm B , and 52 % in arm C ( P < .009 ) . The 4-year postdiagnosis probability of survival was 77 % in arm A , 74 % in arm B , and 87 % in arm C ( P < .04 ) . The proportion of patients who had skeletal events was 24 % in arm A , 21 % in arm B , and 18 % in arm C ( P = .4 ) . Thalidomide is an effective maintenance therapy in patients with multiple myeloma . Maintenance treatment with pamidronate does not decrease the incidence of bone events BACKGROUND In multiple myeloma , combination chemotherapy with melphalan plus prednisone is still regarded as the st and ard of care in elderly patients . We assessed whether the addition of thalidomide to this combination , or reduced-intensity stem cell transplantation , would improve survival . METHODS Between May 22 , 2000 , and Aug 8 , 2005 , 447 previously untreated patients with multiple myeloma , who were aged between 65 and 75 years , were r and omly assigned to receive either melphalan and prednisone ( MP ; n=196 ) , melphalan and prednisone plus thalidomide ( MPT ; n=125 ) , or reduced-intensity stem cell transplantation using melphalan 100 mg/m2 ( MEL100 ; n=126 ) . The primary endpoint was overall survival . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00367185 . FINDINGS After a median follow-up of 51.5 months ( IQR 34.4 - 63.2 ) , median overall survival times were 33.2 months ( 13.8 - 54.8 ) for MP , 51.6 months ( 26.6-not reached ) for MPT , and 38.3 months ( 13.0 - 61.6 ) for MEL100 . The MPT regimen was associated with a significantly better overall survival than was the MP regimen ( hazard ratio 0.59 , 95 % CI 0.46 - 0.81 , p=0.0006 ) or MEL100 regimen ( 0.69 , 0.49 - 0.96 , p=0.027 ) . No difference was seen for MEL100 versus MP ( 0.86 , 0.65 - 1.15 , p=0.32 ) . INTERPRETATION The results of our trial provide strong evidence to indicate that the use of thalidomide in combination with melphalan and prednisone should , at present , be the reference treatment for previously untreated elderly patients with multiple myeloma BACKGROUND Since 1960 , oral melphalan and prednisone ( MP ) has been regarded as the st and ard of care in elderly multiple myeloma patients . This multicentre r and omised trial compared oral MP plus thalidomide ( MPT ) with MP alone in patients aged 60 - 85 years . METHODS Patients with newly diagnosed multiple myeloma were r and omly assigned to receive oral MP for six 4-week cycles plus thalidomide ( n=129 ; 100 mg per day continuously until any sign of relapse or progressive disease ) or MP alone ( n=126 ) . Analysis was intention-to-treat . This study is registered at , number NCT00232934 . RESULTS Patients treated with thalidomide had higher response rates and longer event-free survival ( primary endpoints ) than patients who were not . Combined complete or partial response rates were 76.0 % for MPT and 47.6 % for MP alone ( absolute difference 28.3 % , 95 % CI 16.5 - 39.1 ) , and the near-complete or complete response rates were 27.9 % and 7.2 % , respectively . 2-year event-free survival rates were 54 % for MPT and 27 % for MP ( hazard ratio [ HR ] for MPT 0.51 , 95 % CI 0.35 - 0.75 , p=0.0006 ) . 3-year survival rates were 80 % for MPT and 64 % for MP ( HR for MPT 0.68 , 95 % CI 0.38 - 1.22 , p=0.19 ) . Rates of grade 3 or 4 adverse events were 48 % in MPT patients and 25 % in MP patients ( p=0.0002 ) . Introduction of enoxaparin prophylaxis reduced rate of thromboembolism from 20 % to 3 % ( p=0.005 ) . CONCLUSION Oral MPT is an effective first-line treatment for elderly patients with multiple myeloma . Anticoagulant prophylaxis reduces frequency of thrombosis . Longer follow-up is needed to assess effect on overall survival PURPOSE To determine if thalidomide plus dexamethasone yields superior response rates compared with dexamethasone alone as induction therapy for newly diagnosed multiple myeloma . PATIENTS AND METHODS Patients were r and omly assigned to receive thalidomide plus dexamethasone or dexamethasone alone . Patients in arm A received thalidomide 200 mg orally for 4 weeks ; dexamethasone was administered at a dose of 40 mg orally on days 1 to 4 , 9 to 12 , and 17 to 20 . Cycles were repeated every 4 weeks . Patients in arm B received dexamethasone alone at the same schedule as in arm A. RESULTS Two hundred seven patients were enrolled : 103 were r and omly assigned to thalidomide plus dexamethasone and 104 were r and omly assigned to dexamethasone alone ; eight patients were ineligible . The response rate with thalidomide plus dexamethasone was significantly higher than with dexamethasone alone ( 63 % v 41 % , respectively ; P = .0017 ) . The response rate allowing for use of serum monoclonal protein levels when a measurable urine monoclonal protein was unavailable at follow-up was 72 % v 50 % , respectively . The incidence rates of grade 3 or higher deep vein thrombosis ( DVT ) , rash , bradycardia , neuropathy , and any grade 4 to 5 toxicity in the first 4 months were significantly higher with thalidomide plus dexamethasone compared with dexamethasone alone ( 45 % v 21 % , respectively ; P < .001 ) . DVT was more frequent in arm A than in arm B ( 17 % v 3 % ) ; grade 3 or higher peripheral neuropathy was also more frequent ( 7 % v 4 % , respectively ) . CONCLUSION Thalidomide plus dexamethasone demonstrates significantly superior response rates in newly diagnosed myeloma compared with dexamethasone alone . However , this must be balanced against the greater toxicity seen with the combination PURPOSE To determine whether interferon maintenance therapy improves overall survival and response duration in patients with multiple myeloma who have responded to induction therapy with melphalan and prednisone . PATIENTS AND METHODS In a multicenter trial , patients with symptomatic clinical stage I and stage II and III multiple myeloma were registered at diagnosis and those who responded to melphalan-prednisone ( MP ) were r and omized either to receive interferon ( 2 mU/m2 ) subcutaneously three times per week or no maintenance . MP was discontinued in both groups once a stable response plateau of the monoclonal protein was reached . Interferon was continued until relapse , and then was restarted on subsequent response to MP . Interferon toxicity was recorded using a self-report diary . Survival and response duration were calculated using life-table methods , and were adjusted in the analysis for imbalances in baseline prognostic factors . RESULTS Four hundred two patients were registered and 176 responders were r and omized ( 85 to interferon and 91 to control ) . At a median follow-up time of 43 months , the median survival duration was 43 months for interferon and 35 months for control ( P = .16 ) , but when adjusted for chance imbalances in baseline prognostic factors ( mainly performance status ) , the median survival duration was 44 months and 33 months for interferon and control , respectively ( P = .049 ) . Progression-free survival from r and omization to first relapse also favored interferon ( unadjusted P < .002 ; adjusted P < .003 ) . Interferon toxicity caused 58 % of patients to reduce their dose , of which 84 % were able to return to the initial dose ; 14 % had to discontinue interferon treatment . CONCLUSION Interferon maintenance therapy improves progression-free and overall survival of patients with multiple myeloma who respond to melphalan and prednisone . Toxicity is substantial and must be weighed by patients against the potential benefits in response duration and survival BACKGROUND High-dose therapy with supporting autologous stem-cell transplantation remains a controversial treatment for cancer . In multiple myeloma , first-line regimens incorporating high-dose therapy yield higher remission rates than do conventional-dose treatments , but evidence that this translates into improved survival is limited . METHODS In this multicenter study , the Medical Research Council Myeloma VII Trial , we r and omly assigned 407 patients with previously untreated multiple myeloma who were younger than 65 years of age to receive either st and ard conventional-dose combination chemotherapy or high-dose therapy and an autologous stem-cell transplant . RESULTS Among the 401 patients who could be evaluated , the rates of complete response were higher in the intensive-therapy group than in the st and ard-therapy group ( 44 percent vs. 8 percent , P<0.001 ) . The rates of partial response were similar ( 42 percent and 40 percent , respectively ; P=0.72 ) , and the rates of minimal response were lower in the intensive-therapy group than in the st and ard-therapy group ( 3 percent vs. 18 percent , P<0.001 ) . Intention-to-treat analysis showed a higher rate of overall survival ( P=0.04 by the log-rank test ) and progression-free survival ( P<0.001 ) in the intensive-therapy group than in the st and ard-therapy group . As compared with st and ard therapy , intensive treatment increased median survival by almost 1 year ( 54.1 months [ 95 percent confidence interval , 44.9 to 65.2 ] vs. 42.3 months [ 95 percent confidence interval , 33.1 to 51.6 ] ) . There was a trend toward a greater survival benefit in the group of patients with a poor prognosis , as defined by a high beta2-microglobulin level ( more than 8 mg per liter ) . CONCLUSIONS High-dose therapy with autologous stem-cell rescue is an effective first-line treatment for patients with multiple myeloma who are younger than 65 years of age From April 2003 to December 2006 , 195 patients with de novo symptomatic myeloma and younger than 60 years of age were r and omly assigned to receive either t and em transplantation up front ( arm A , n = 97 ) or one autologous stem-cell transplantation followed by a maintenance therapy with thalidomide ( day + 90 , 100 mg per day during 6 months ) ( arm B , n = 98 ) . Patients included in arm B received a second transplant at disease progression . In both arms , autologous stem-cell transplantation was preceded by first-line therapy with thalidomide-dexamethasone and subsequent collection of peripheral blood stem cells with high-dose cyclophosphamide ( 4 g/m(2 ) ) and granulocyte colony stimulating factor . Data were analyzed on an intent-to-treat basis . With a median follow-up of 33 months ( range , 6 - 46 months ) , the 3-year overall survival was 65 % in arm A and 85 % in arm B ( P = .04 ) . The 3-year progression-free survival was 57 % in arm A and 85 % in arm B ( P = .02 ) . Up-front single autologous transplantation followed by 6 months of maintenance therapy with thalidomide ( with second transplant in reserve for relapse or progression ) is an effective therapeutic strategy to treat multiple myeloma patients and appears superior to t and em transplant in this setting . This study was registered at www . Clinical Trials.gov as ( NCT 00207805 ) |
12,394 | 10,796,283 | Sensitivity analyses did not identify a particular type of anticoagulant regimen or patient characteristic associated with net benefit .
REVIEW ER 'S CONCLUSIONS Immediate anticoagulant therapy in patients with acute ischaemic stroke is not associated with net short- or long-term benefit .
The data from this review do not support the routine use of any type of anticoagulant in acute ischaemic stroke | BACKGROUND Most ischaemic strokes are caused by blood clots blocking an artery in the brain .
Clot prevention with anticoagulant therapy could have a significant impact on patient survival , disability and recurrence of stroke .
OBJECTIVES The objective of this review was to assess the effect of anticoagulant therapy in the early treatment of patients with acute ischaemic stroke . | Eighteen consecutive patients satisfying predefined clinical criteria for embolic strokes were prospect ively studied by sequential computerized tomography ( CT ) . Their findings were compared to CT scans obtained from patients presumed to have suffered thrombotic strokes . Our data reveal that the CT appearance of hemorrhagic infa rct ion is likely to occur twice as frequently ( 22 % ) in CT scans of strokes presumed embolic than in those presumed thrombotic , where hemorrhagic infa rct ion appeared at some time in 10 % of the patients . No patient deteriorated with anticoagulation regardless of the CT appearance . In patients showing hemorrhagic infa rct ion before anticoagulants , follow-up scans obtained after the administration of anticoagulants revealed resolution of the hemorrhagic aspect Background and Purpose — We sought to investigate the apparently high risk of early death after an ischemic stroke among patients with atrial fibrillation ( AF ) , identify the main factors associated with early death , and assess the effect of treatment with different doses of subcutaneous unfractionated heparin ( UFH ) given within 48 hours . Methods — We studied the occurrence of major clinical events within 14 days among 18 451 patients from the International Stroke Trial , first for all treatment groups combined . Then , among patients with AF , we examined the effects of treatment with subcutaneous UFH started within 48 hours and continued until 14 days after stroke onset . Results — A total of 3169 patients ( 17 % ) had AF . Seven hundred eighty-four patients were allocated to UFH 12 500 IU SC BID , 773 to UFH 5000 IU SC BID , and 1612 to no heparin . Within each of these groups , half of the patients were r and omly assigned to aspirin 300 mg once daily . Compared with patients without AF , patients with AF were more likely to be female ( 56 % versus 45 % ) , to be old ( mean age , 78 versus 71 years ) , to have an infa rct on prer and omization CT ( 57 % versus 47 % ) , and to have impaired consciousness ( 37 % versus 20 % ) . The initial ischemic stroke type was more often a large-artery infa rct ( 36 % versus 21 % ) . A lacunar stroke syndrome was less common ( 13 % versus 26 % ) . Death within 14 days was more common in patients with AF ( 17 % versus 8 % ) and more often attributed to neurological damage from the initial stroke ( 10 % versus 4 % ) . The frequency of recurrent ischemic or undefined stroke was not significantly different ( 3.9 % versus 3.3 % ) . The proportion of AF patients with further events within 14 days allocated to UFH 12 500 IU ( n=784 ) , UFH 5000 IU ( n=773 ) , and to no-heparin ( n=1612 ) groups were as follows : ischemic stroke , 2.3 % , 3.4 % , 4.9 % ( P = 0.001 ) ; hemorrhagic stroke , 2.8 % , 1.3 % , 0.4 % ( P < 0.0001 ) ; and any stroke or death , 18.8 % , 19.4 % and 20.7 % ( P = 0.3 ) , respectively . No effect of heparin on the proportion of patients dead or dependent at 6 months was apparent . Conclusions — Acute ischemic stroke patients with AF have a higher risk of early death , which can be explained by older age and larger infa rcts but not by a higher risk of early recurrent ischemic stroke , although slightly more patients with AF died from a fatal recurrent stroke of ischemic or unknown type ( 1.3 % versus 0.9 % ) . In patients with AF the absolute risk of early recurrent stroke is low , and there is no net advantage to treatment with heparin . These data do not support the widespread use of intensive heparin regimens in the acute phase of ischemic stroke associated with AF In a group of 60 patients in the acute phase of an ischemic stroke the assumption that low-molecular-weight heparin Kabi 2165 in the dose of 2 X 2,500 anti-Xa units s.c . could prevent thromboembolic complications was tested using a double-blind , placebo-controlled , r and omized trial design . Thirty patients were allocated to each group . Both treatment groups were comparable with regard to neurological status and general condition . In the Kabi 2165 group there were 6 cases of deep venous thrombosis ( DVT ) compared to 15 in the placebo group ( p = 0.05 ) . In the placebo group there were 4 deaths during the trial versus 9 in the Kabi-2165-treated group ( NS ) . Cerebral bleeding complicated 2 cases in the placebo group versus 4 in the Kabi 2165 group ( NS ) . These results indicate that in ischemic stroke patients Kabi 2165 2 X 2,500 anti-Xa units s.c./24 h reduces the frequency of DVT . Because of the small number of patients it is impossible to evaluate the safety IN A PREVIOUS issue of this journa1,l the details of our national cooperative ControIled study of long-term anticoagulant therapy in cerebral ischemia and cerebral infa rct ion were presented along with an interim report covering some eighteen months . At that time , longterm anticoagulation did not appear to reduce the mortality and there was an added risk due to hemorrhagic complications . The study , embracing 7 clinical centers and extending over a period of forty-two months , was brought to an end in August 1961 , and this is a report of our findings and final conclusions . The important aspects of the study , including selection and classification of cases and method of anticoagulation , were fully covered previously and will not be repeated here . A total of 443 patients were enrolled in the study , each patient being assigned to the anticoagulant or nonanticoagulant therapeutic groups on a statistically r and om basis by means of sealed envelopes . All the patients in the study were divided into 5 diagnostic categories : ( 1 ) transient ischemic attacks , ( 2 ) thrombosis-in-evolution , ( 3 ) thrombosis-completed stroke , ( 4 ) thorem ( thrombosis or embolism ) , and ( 5 ) cerebral embolism . Analysis of the control and treated groups showed that they were remarkably comparable in most respects ( table 1 ) . The number of cases involving the internal carotidmiddle cerebral and vertebral-basilar systems varied from category to category ; in the whole series there were 328 in the carotid and 102 in the vertebral-basilar . In regard to blood pressure , 59.6 per cent of the entire group had an elevated blood pressure . To determine the effect of anticoagulant therapy , the cases were analyzed as to the incidence of ( 1 ) deaths , ( 2 ) progression of cerebral infa rct ion due to either extension of the infa rct ed area or a new infa rct ion , ( 3 ) the advent of extracerebral thrombotic episodes ( ECTE ) , including myocardial infa rct ion , pulmonary embolism , thrombophlebitis , and so forth , and ( 4 ) hemorrhagic complications . Patients whose anticoagulants were stopped within two weeks of death when the patient 's condition was deteriorating were reckoned as deaths while on anticoagulants The clinical features of 49 patients who had sustained small strokes in the internal carotid artery territory , who were normotensive , free from cardiac or other relevant disease , and who each had a normal appropriate single vessel angiogram are presented . These were r and omized into two groups : group A , 25 patients , who received only supportive treatment ; group B , 24 patients who were treated with anticoagulants for an average period of 18 months . There was a reduced incidence of neurological episodes during the administration of anticoagulant therapy but , after treatment was discontinued , there was no significant difference between the two groups . In view of the relatively benign prognosis for this syndrome , unless special facilities exist for the personal control of anticoagulant treatment , the dangers may outweigh the benefits In a non‐r and omized controlled study carried out on 238 hospitalized patients with cerebral infa rct ion , anticoagulant treatment ( AC ) was compared with the natural course in the prevention of transient ischemic attacks ( TIA ) , cerebral infa rct ion , stroke , stroke or death . 137 patients were allocated to AC , mean follow‐up 30.5 months , and 101 patients were allocated to the controls ( untreated group ) , mean follow‐up 25.2 months In a double-blind , placebo-controlled trial , 225 patients with acute partial stable thrombotic stroke were r and omly assigned to receive continuous intravenous heparin therapy or placebo for 7 days for the prevention of stroke progression or death . No statistically significant difference between the two groups was found in degree of neurologic change ; incidence of stroke progression after 7 days ; or functional activity level of survivors at 7 days , 3 months and at 1 year after treatment . Compared with controls , a statistically significant greater number of patients in the group receiving heparin died in the year after the stroke . These deaths occurred 3 to 12 months after the initial stroke and probably were not related to treatment . Results of this study do not support the use of intravenous heparin to treat patients who have had acute partial stroke Deep vein thrombosis ( DVT ) and subsequent pulmonary embolism ( PE ) is a major source of mortality and morbidity in stroke patients . This study was design ed to determine the effectiveness of different prophylactic treatments in the prevention of DVT after a stroke in patients undergoing rehabilitation . An additional objective was the identification of risk factors for DVT in stroke in patients during rehabilitation . Three hundred and sixty patients , over a 3-year period , were r and omly assigned to one of four groups : adjusted dose heparin , intermittent pneumatic compression ( IPC ) , functional electrical stimulation ( FES ) , or control . There was no significant difference in the development of DVT by treatment group . Patients with DVT on admission ( prevalent , n = 61 ) were compared with the study patients ( n = 360 ) . Time interval ( from stroke to admission ) and lactic dehydrogenase ( LDH ) concentration were significant risk factors , as well as predictors , for development of DVT ( p < .000 ) . These results suggest that the longer a patient remains without DVT prophylaxis after a stroke , the greater the risk of developing DVT and this supports early prophylaxis before rehabilitation Venous thrombo-embolism is a major and often unrecognized cause of morbidity and mortality in patients after acute strokes . Three hundred and five elderly patients were r and omly allocated to either control ( 161 ) or treatment ( 144 ) with 5000 units calcium heparin subcutaneously 8-hourly for two weeks . A reduction in deep-vein thrombosis rate from 72.7 % in the control group to 22.2 % in treatment patients was achieved . In patients who died ( 84 ) , post-mortem examination to look for pulmonary emboli was performed in 71 . Comparison between treated and untreated patients showed significantly fewer deaths and pulmonary emboli in the treated group . Most of the beneficial effect on mortality was seen in patients with lighter strokes . When patients with pulmonary emboli at post-mortem were excluded , there was no significant difference in the death rate in treatment ( 17 ) and control ( 14 ) groups . At post-mortem , 9.9 % of the strokes were haemorrhagic ( 4 in the treatment and 3 in the control group ) . Low-dose calcium heparin given subcutaneously following acute stroke reduced the number of deep-vein thromboses , pulmonary emboli and deaths without increasing the number of haemorrhagic strokes in this study We studied the effect of argatroban , a new selective thrombin inhibitor , on the haemostatic system in seven patients with acute ischaemic stroke ( the argatroban group ) . Argatroban was infused continuously at 2.5 mg/h for the first 48 h , and then 10 mg of argatroban was infused over 3 h twice a day on days 3 - 7 . The placebo group consisted of six acute ischaemic stroke patients . As a combination therapy , intravenous administration of glycerol was also performed at the same time in five of the seven patients in the argatroban group and in four of the six patients in the placebo group . D-dimer levels were measured by a latex photometric immunoassay that allowed immediate quantitative assessment . The D-dimer levels of our 13 patients with acute ischaemic stroke were raised at the time of admission ( day 1 ) and 69 % of the values were above the 97th percentile ( > 500 ng/ml ) in healthy subjects . D-dimer levels were significantly reduced in the argatroban group on days 2 and 7 after admission when compared with the placebo group ( day 2 : P = 0.032 ; day 7 : P = 0.046 ) . Thus , haemostatic activation occurred in acute ischaemic stroke was effectively blocked by argatroban A r and omized trial of immediate versus delayed anticoagulation of patients with cardiogenic embolic brain infa rct ion was carried out in a multi-centered study . Patients who were within 48 hours of onset of deficit and who had no evidence of hemorrhage on computed tomography ( CT ) were r and omized to receive either immediate heparinization or no anticoagulants for the initial 14 days following stroke . There were 63 patients with embolic stroke identified during the study period . Eighteen patients were not r and omized because of specific exclusion criteria or delayed identification more than 48 hours after stroke . Of 45 patients who were r and omized , 44 patients ( 98 % ) completed the initial week of the protocol : 24 were immediately heparinized at an average of 32 hours after stroke , 21 received no immediate anticoagulation . Two patients developed delayed hemorrhagic infa rct ion and two patients experienced early recurrent embolism , all among the nonanticoagulated group . Of all patients with embolic stroke who were not receiving coumadin at onset of stroke , only two of 56 ( 4 % ) had hemorrhagic infa rct ion on initial CT . Follow-up CT in 40 of these patients showed late developing hemorrhagic infa rct ion in two additional patients ( 5 % ) . All four hemorrhagic infa rct ions occurred in 18 non-anticoagulated patients with large infa rcts . There were no major complications associated with immediate heparinization of 24 unselected patients with all sizes of embolic infa rct ion . A trend toward reduction of early recurrent embolism was apparent . These data support immediate anticoagulation of nonhypertensive patients with embolic brain infa rct ion who have no evidence of hemorrhage on CT performed 24 - 48 hours after stroke BACKGROUND AND PURPOSE : To test the design and feasibility of a very large r and omised controlled trial assessing the efficacy and safety of antithrombotic therapy started within 48 hours of symptom onset in patients with suspected acute ischaemic stroke . DESIGN : R and omised controlled multicentre open study , with a 3 x 2 factorial design , allocating patients to : medium dose subcutaneous heparin ( 12,500 units twice per day ) , versus low dose subcutaneous heparin ( 5000 units twice per day ) versus no heparin ; and aspirin ( 300 mg daily ) versus no aspirin . Treatment was given for two weeks or until discharge from hospital if sooner . RESULTS : 984 patients were r and omised . CT was performed in 924 ( 94 % ) ( before r and omisation in 622/984 ( 63 % ) . Within 14 days : 97 patients had died ( 10 % ) , 30 ( 3.0 % ) had a fatal or non-fatal recurrent ischaemic stroke , nine ( 0.9 % ) had fatal or non-fatal recurrent stroke due to intracranial haemorrhage , and eight ( 0.8 % ) had a fatal or non-fatal pulmonary embolus . At six months , vital status was known for 975 patients ( 99 % ) , of whom 210 ( 22 % ) were dead , 373 ( 38 % ) were alive but dependent , and 225 ( 23 % ) were independent but not fully recovered . CONCLUSIONS : The trial procedures proved practicable and a wide variety of patients were recruited . Sample size calculation based on the event rates confirmed that reliable evidence on the balance of risk and benefit of early antithrombotic therapy might require a study with more than 20,000 patients . Recruitment rates in the pilot study indicated that if about 200 hospitals participated , recruitment could be completed by 1997 In a double-blind , r and omised trial Org 10172 low-molecular-weight ( LMW ) heparinoid was compared with placebo in the prevention of deep-vein thrombosis in patients with acute thrombotic stroke . Prophylaxis was started within 7 days of the onset of stroke with a loading dose of 1000 anti-factor-Xa units intravenously followed by a fixed dose of 750 anti-factor-Xa units twice a day subcutaneously ; it was continued for 14 days or until hospital discharge , if earlier . 50 patients were r and omised to receive Org 10172 and 25 to receive placebo . All patients underwent surveillance with I125-fibrinogen leg scanning and impedance plethysmography . Venography was carried out if either test became positive . Venous thrombosis occurred in 2 of 50 patients ( 4.0 % ) given Org 10172 and 7 of 25 patients ( 28.0 % ) given placebo ( p = 0.005 ) ; the corresponding rates of proximal-vein thrombosis were 0 % and 16 % , respectively ( p = 0.01 ) . There was one major haemorrhage in the Org 10172 group and one minor bleed in the placebo group An open , r and omized , controlled study including 57 patients with acute cerebral infa rct was performed . All the patients , followed and controlled by the same examiner , received , in the first ten days , 24 mg/die i.v . of dexamethasone . 28 patients were also treated with mesoglycan ( 150 mg/die i.m . for five days and 144 mg/die per os for a further twenty-five days ) . The differences between the basal and final scores in the mesoglycan group and in the controls were not statistically significant as analysed by the Mann-Whitney U test . The mesoglycan influenced only slightly the laboratory values ( PT , PTT , alkaline phosphatase , GOT , GPT , cholesterol and triglycerides , fibrinogen , blood glucose , azotemia and creatinine ) performed before the beginning of the treatment , as their changes after thirty days of therapy were in the normal range . The mesoglycan was very well tolerated and no side-effects were observed during the treatment Desmukh M , Bisignani M , L and au P , Orchard TJ : Deep vein thrombosis in rehabilitating stroke patients : incidence , risk factors and prophylaxis . Am J Phys Med Rehabil 1991;70:313–316.A total of 503 consecutive cases of suspected stroke were examined for potential eligibility based on recent development of a paralyzed limb . Of 123 otherwise eligible subjects , 22 were found by ultrasound to have deep vein thrombosis ( DVT ) on admission . Therefore , 101 patients were assigned r and omly to one of the treatment groups or to the control group . The three treatments were adjusted-dose heparin , external pneumatic compression and functional electrical muscle stimulation . An ultrasound examination of the lower extremities was conducted twice a week on each patient until completion of the study ( 28 days or discharge , whichever came first ) . Electrical muscle stimulation was discontinued after 4 mo of the study because of discomfort , blister formation and high drop-out rate . Ten patients developed DVT during the study period . In 17 of the 32 cases of DVT , venography was performed , which confirmed the ultrasound findings in every case . The 32 cases of DVT differed from those without DVT by having a higher prevalence of hypertension ( P = 0.02 ) , cholesterol ( P = 0.08 ) and a longer time interval between stroke and admission ( P < 0.05 ) . We conclude that ultrasound is effective for DVT detection in the rehabilitation setting , and two-thirds of such cases are detectable on BACKGROUND AND PURPOSE We sought to observe the type , timing , and frequency of complications occurring in hospitalized patients after an acute stroke . METHODS In a single hospital , we prospect ively identified a consecutive cohort of patients who were either admitted after an acute stroke or who suffered a stroke while already an inpatient ( n=613 ) . We retrieved the case notes for 607 ( 99 % ) of these strokes , and a single observer , using predefined diagnostic criteria , review ed the notes and recorded the type , timing , and frequency of complications that occurred during the inpatient period . We also measured the reliability of complication identification from case note review by comparing two observers on a sample of records . RESULTS Complications were recorded after 360 strokes ( 59 % ) ; the most common individual complications were falls ( complicating 22 % of all strokes ) , skin breaks ( 18 % ) , and urinary tract ( 16 % ) or chest ( 12 % ) infections . Miscellaneous " other " complications complicated 32 % of strokes . Seizures and chest infections occurred early , whereas depression and painful shoulder were later problems . Complications were more common in older patients , who were more disabled before their stroke and had suffered more severe strokes . We demonstrated moderate to good agreement between the two observers for most complications . CONCLUSIONS Complications after acute stroke are common , confirming that stroke rehabilitation requires active and knowledgeable medical input . Knowing the nature and timing of complications , together with the identification of high-risk patients , may be useful to those planning stroke services . The differences in our results and those previously reported , most notably for skin breaks , are probably due to the different methods used , in particular patient selection and diagnostic criteria for complications . Although complications may be useful as a measure of outcome in comparative studies ( eg , therapeutic trials and audit ) , the method ological difficulties in accurately and reliably measuring them must be addressed Argatroban is a direct antithrombin agent developed for the first time by Okamoto et al in 1978 . Unlike heparin , it manifests its anticoagulant effect by binding directly to the active site of thrombin . A phase II double-blind comparative study was conducted in 52 facilities with a placebo control . The drug was administered by a slow intravenous infusion at 60 mg/d for the first 2 days and then at 10 mg twice daily for the subsequent 5 days . Glycerol was used concomitantly as a basic therapy for both the argatroban and placebo groups . The results demonstrated superior improvements , particularly in neurological symptoms ( motor paralysis ) and daily living activities ( walking , st and ing up , continuous sitting , and eating ) , in the argatroban group compared with the placebo group . These improvements were observed from the early stage of administration . It was also found that administration of the drug in the early stage of the disease gave better results . In the present study , although a hemorrhagic cerebral infa rct occurred in one case in the argatroban group , this seemed to be no different from a spontaneous incidence , as it also occurred in two cases in the placebo group . Symptoms were not aggravated in any of the cases . These results indicate that argatroban is an effective and safe drug for the treatment of acute cerebral thrombosis A trial of subcutaneous low-dose heparin in the prevention of deep-vein thrombosis was carried out in elderly patients admitted to hospital after an acute stroke . A statistically significant reduction was observed in deep-vein thrombosis as assessed by isotope leg scanning |
12,395 | 18,547,378 | Although the results are inconsistent , the evidence points towards a possible role of the Mediterranean diet in preventing overweight/obesity , and physiological mechanisms can explain this protective effect . | World Health Organization projections estimate that worldwide approximately one-third of adults are overweight and one-tenth are obese .
There is accumulating research into the Mediterranean diet and whether it could prevent or treat obesity .
Therefore , the purpose of this paper was to systematic ally review and analyse the epidemiological evidence on the Mediterranean diet and overweight/obesity . | The influence of the source of dietary fat on postpr and ial thermogenesis and substrate oxidation rates , was examined in twelve postmenopausal women aged 57 - 73 years , with BMI 21.9 - 38.3 kg/m(2 ) . A single blind , r and omised , paired comparison of two high-fat , isoenergetic , mixed test meals was conducted . The major source of fat was either cream ( CREAM ) or extra virgin olive oil ( EVOO ) . RMR , diet-induced thermogenesis ( DIT ) and substrate oxidation rates over 5 h were measured by indirect calorimetry . There were no differences in body weight , RMR , fasting carbohydrate or fat oxidation rates between the two occasions . DIT ( EVOO 97 ( SD 46 ) v. CREAM 76 ( SD 69 ) kJ/5 h and EVOO 5.2 ( SD 2.5 ) v. CREAM 4.1 ( SD 3.7)% energy ) did not differ between the two test meals . The postpr and ial increase in carbohydrate oxidation rates , relative to their respective fasting values ( DeltaCOX ) , was significantly lower following the EVOO meal ( EVOO 10.6 ( SD 8.3 ) v. CREAM 17.5 ( SD 10 ) g/5 h ; paired t test , P=0.023 ) , while postpr and ial fat oxidation rates ( DeltaFOX ) were significantly higher ( EVOO 0.0 ( SD 4.4 ) v. CREAM -3.6 ( sd 4.0 ) g/5 h ; P=0.028 ) . In the eight obese subjects , however , DIT was significantly higher following the EVOO meal ( EVOO 5.1 ( SD 2.0 ) v. CREAM 2.5 ( sd 2.9 ) % ; P=0.01 ) . This was accompanied by a significantly lower DeltaCOX ( EVOO 10.9 ( SD 9.9 ) v. CREAM 17.3 ( SD 10.5 ) g/5 h ; P=0.03 ) and significantly higher DeltaFOX ( EVOO 0.11 ( SD 4.4 ) v. CREAM -4.1 ( SD 4.5 ) g/5 h , P=0.034 ) . The present study showed that olive oil significantly promoted postpr and ial fat oxidation and stimulated DIT in abdominally obese postmenopausal women The aim of this dynamic prospect i ve follow-up study was to assess the association between olive oil consumption and the likelihood of weight gain or the incidence of overweight or obesity in a large Mediterranean cohort of 7,368 male and female Spanish university graduates ( the SUN Project ) who were followed for a median period of 28.5 mon . A vali date d Food Frequency Question naire was administered at baseline , and respondents also completed a follow-up question naire after 28.5 mon . Changes in participants ' consumption of olive oil and their weight were assessed during follow-up . A higher baseline consumption of olive oil was associated with a lower likelihood of weight gain , although the differences were not statistically significant . The adjusted difference in weight gain ( kg ) was −0.16 [ 95 % confidence interval ( C1 ) : −0.42 to + 0.11 ] for participants in the upper quintile of olive oil consumption ( median : 46 g/d ) compared with those in the lowest quintile ( median : 6 g/d ) . For participants with a high baseline consumption of olive oil whose olive oil consumption also increased during follow-up , we found a slightly increased but nonsignificant risk of incidence of over-weight or obesity ( adjusted odds ratio=1.19 , 95 % C1 : 0.73 to 1.95 ) . Our study , carried out in a sample of free-living people , shows that a high amount of olive oil consumption is not associated with higher weight gain or a significantly higher risk of developing overweight or obesity in the context of the Mediterranean food pattern BACKGROUND The effect of dietary fat and carbohydrate on glucose metabolism has been debated for decades . OBJECTIVE The objective was to compare the effect of 3 ad libitum diets , different in type and amount of fat and carbohydrate , on insulin resistance and glucose tolerance subsequent to weight loss . DESIGN Forty-six nondiabetic , obese [ mean ( + /-SEM ) body mass index ( in kg/m(2 ) ) : 31.2 + /- 0.3 ] men ( n = 20 ) and premenopausal women ( n = 26 ) aged 28.0 + /- 0.7 y were r and omly assigned to 1 of 3 diets after > or = 8 % weight loss : 1 ) MUFA diet ( n = 16 ) : moderate in fat ( 35 - 45 % of energy ) and high in monounsaturated fatty acids ( > 20 % of energy ) ; 2 ) LF diet ( n = 18 ) : low-fat diet ( 20 - 30 % of energy ) , and 3 ) control diet ( n = 12 ) : 35 % of energy as fat ( > 15 % of energy as saturated fatty acids ) . Protein accounted for 15 % of energy in all 3 diets . A 2-h oral-glucose-tolerance test ( OGTT ) was performed before and after the 6-mo dietary intervention . All foods were provided by a purpose -built supermarket . RESULTS After 6 mo , the MUFA diet reduced fasting glucose ( -3.0 % ) , insulin ( -9.4 % ) , and the homeostasis model assessment of insulin resistance score ( -12.1 % ) . Compared with the MUFA diet , the control diet increased these variables [ 1.4 % ( P = 0.014 ) , 21.2 % ( P = 0.030 ) , and 22.8 % ( P = 0.015 ) , respectively ] , as did the LF diet [ 1.4 % ( P = 0.090 ) , 13.1 % ( P = 0.078 ) , and 15.5 % ( P = 0.095 ) , respectively ] . No significant group differences were detected in glucose or insulin concentrations during the OGTT , in the Matsudas index , in body weight , or in body composition . CONCLUSION A diet high in monounsaturated fat has a more favorable effect on glucose homeostasis than does the typical Western diet in the short term and may also be more beneficial than the official recommended low-fat diet during a period of weight regain subsequent to weight loss BACKGROUND Adherence to a Mediterranean diet has been reported to increase longevity , but concerns have been expressed that such a diet may promote overweight and obesity . OBJECTIVE The objective was to investigate whether adherence to the traditional Mediterranean diet , as operationalized in a Mediterranean diet score , is associated with body mass index ( BMI ) and waist-to-hip ratio ( WHR ) . DESIGN In a general population sample of 23,597 adult men and women participating in the Greek European Prospect i ve Investigation into Cancer and Nutrition Study , a vali date d food-frequency question naire was interviewer-administered , and anthropometric , sociodemographic , physical activity , and other lifestyle characteristics were recorded . BMI and WHR were regressed on a score that reflects adherence to the traditional Mediterranean diet and potentially confounding variables . RESULTS In models in which total energy intake was included , adherence to the Mediterranean diet was unrelated to BMI in both sexes and was weakly related to WHR only in women . When energy intake was not controlled for , a 2-point increase in the score was found to correspond to increases of approximately 650 and 150 g in the weight of an average-height man and woman , respectively , whereas the WHR was found to increase by approximately 0.001 units in men and 0.004 units in women . CONCLUSIONS Adherence to a Mediterranean diet was essentially unrelated to BMI , with small differences depending on model choice and having no practical consequences . Overweight is a genuine problem in Greece and perhaps other Mediterranean countries , but it is likely to be related to limited physical activity in conjunction with excessive positive energy balance Few studies have prospect ively examined dietary patterns and adult weight change , and results to date are inconsistent . This study examines whether a Mediterranean diet ( MD ) pattern is associated with reduced 3-y incidence of obesity using data from the Spanish cohort of the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC-Spain ) . The sample included 17,238 women and 10,589 men not obese and aged 29 - 65 y at baseline ( 1992 - 96 ) . Height and weight were measured at baseline ; weight was self-reported in a follow-up survey a mean of 3.3 y later . Detailed dietary history data , collected using a vali date d method , were used to construct a MD score . Logistic regression models were used to estimate odds of becoming overweight or obese . Among initially overweight subjects , 7.9 % of women and 6.9 % of men became obese , whereas 13.8 % of normal weight men and 23.0 % women became overweight . High MD adherence was associated with significantly lower likelihood of becoming obese among overweight subjects , with stronger associations after adjusting for underreporting of dietary data . Associations ( odds ratios with 95 % CI ) were similar in women ( 0.69 , 0.54 - 0.89 ) and men ( 0.68 , 0.53 - 0.89 ) . Adjusting for the plausibility of reported dietary intakes increased the magnitude of these associations , which were approximately 0.8 without this adjustment . MD adherence was not associated with incidence of overweight in initially normal-weight subjects . Nonetheless , results suggest that promoting eating habits consistent with MD patterns may be a useful part of efforts to combat obesity A r and omised crossover study of eight overweight or obese men ( aged 24 - 49 years , BMI 25.5 - 31.3 kg/m(2 ) ) , who followed two diets for 4 weeks each , was performed to determine whether substitution of saturated fat with monounsaturated fat affects body weight and composition . Subjects were provided with all food and beverages as modules ( selected ad libitum ) of constant macronutrient composition , but differing energy content . The % total energy from saturated fat , monounsaturated fat and polyunsaturated fat was 24 , 13 and 3 % respectively on the saturated fatty acid (SFA)-rich diet and 11 , 22 and 7 % respectively on the monounsaturated fatty acid (MUFA)-rich diet . MUFA accounted for about 80 % of the unsaturated fats consumed on both diets . Body composition , blood pressure , energy expenditure ( resting and postpr and ial metabolic rates , substrate oxidation rate , physical activity ) , serum lipids , the fatty acid profile of serum cholesteryl esters and plasma glucose and insulin concentrations were measured before and after each diet period . Significant ( P < or = 0.05 ) differences in total cholesterol and the fatty acid composition of serum cholesteryl esters provided evidence of dietary adherence . The men had a lower weight ( -2.1 ( SE 0.4 ) kg , P=0.0015 ) and fat mass ( -2.6 ( SE 0.6 ) kg , P=0.0034 ) at the end of the MUFA-rich diet as compared with values at the end of the SFA-rich diet . No significant differences were detected in energy or fat intake , energy expenditure , substrate oxidation rates or self-reported physical activity . Substituting dietary saturated with unsaturated fat , predominantly MUFA , can induce a small but significant loss of body weight and fat mass without a significant change in total energy or fat intake Context Some experts attribute a low incidence of heart disease in Mediterranean countries to dietary habits . Contribution In this multicenter , 3-group trial , investigators r and omly assigned 772 adults at high risk for cardiovascular disease to a low-fat diet or to a Mediterranean diet supplemented with either virgin olive oil ( 1 L per week ) or nuts ( 30 g per day ) . After 3 months , the Mediterranean diet groups had lower mean plasma glucose level , systolic blood pressure , and total cholesterolhigh-density lipoprotein cholesterol ratio than the low-fat diet group . Caution s The Mediterranean diet groups received more nutritional education than the low-fat diet group . Implication s Mediterranean diets supplemented with olive oil or nuts may improve cardiovascular risk factors . The Editors Cardiovascular disease is the main cause of death in industrialized countries , but incidence rates have marked geographic differences . The low incidence of coronary heart disease ( CHD ) in Mediterranean countries has been partly ascribed to dietary habits ( 1 - 3 ) . Recent findings from large European cohort studies ( 4 - 6 ) suggest that a high degree of adherence to the Mediterranean diet is associated with a reduction in mortality . In small clinical studies , the Mediterranean diet or some of its components have reduced blood pressure ( 7 ) and have improved lipid profiles ( 8 , 9 ) and endothelial function ( 10 ) . Moreover , a recent cross-sectional study ( 11 ) and a 2-year feeding trial ( 12 ) have shown that adherence to the Mediterranean diet is associated with reduced markers of vascular inflammation . These beneficial effects on surrogate markers of cardiovascular risk add biological plausibility to the epidemiologic evidence that supports a protective effect of the Mediterranean diet . Olive oil , a rich source of monounsaturated fatty acids , is a main component of the Mediterranean diet . Virgin olive oil retains all the lipophilic components of the fruit , -tocopherol , and phenolic compounds with strong antioxidant and anti-inflammatory properties ( 13 , 14 ) . Tree nuts , which are also typical in the Mediterranean diet , have a favorable fatty acid profile and are a rich source of nutrients and other bioactive compounds that may beneficially influence the risk for CHD , such as fiber , phytosterols , folic acid , and antioxidants ( 15 ) . Frequent nut intake has been associated with decreased CHD rates in prospect i ve studies ( 15 ) . Walnuts differ from all other nuts through their high content of polyunsaturated fatty acids , particularly -linolenic acid , a plant n-3 fatty acid ( 16 ) , which may confer additional antiatherogenic properties ( 17 ) . Therefore , we design ed a large-scale feeding trial in high-risk participants to assess the effects of 2 Mediterranean diets , one supplemented with virgin olive oil and the other supplemented with mixed nuts , compared with a low-fat diet on cardiovascular outcomes . We report the results of a 3-month intervention on intermediate markers of cardiovascular risk in the first 772 participants who were recruited into the trial . Supplement . Original Version ( PDF ) Methods Study Design The Prevencin con Dieta Mediterrnea ( PREDIMED ) Study is a large , parallel-group , multicenter , r and omized , controlled , 4-year clinical trial that aims to assess the effects of the Mediterranean diet on the primary prevention of cardiovascular disease ( www.predimed.org ) . An estimated 9000 high-risk participants ( > 5000 participants are already recruited ) will be assigned to 3 interventions : Mediterranean diet with virgin olive oil , Mediterranean diet with mixed nuts , or low-fat diet . The main outcome is an aggregate of cardiovascular events ( cardiovascular death , nonfatal myocardial infa rct ion , or nonfatal stroke ) . The anticipated completion date of the trial is December 2010 . We design ed our present study to assess the 3-month effects of the dietary interventions on surrogate markers of cardiovascular risk in participants entering the study during the first 6 months of recruitment . The institutional review boards of the 10 participating centers approved the study protocol . Participants and Recruitment From October 2003 to March 2004 , we selected 930 potential participants in primary care centers affiliated with 10 teaching hospitals across Spain . Eligible participants were community-dwelling men , 55 to 80 years of age , and women , 60 to 80 years of age , who fulfilled at least 1 of 2 criteria : type 2 diabetes or 3 or more CHD risk factors ( current smoking , hypertension [ blood pressure > 140/90 mm Hg or treatment with antihypertensive drugs ] , low-density lipoprotein [ LDL ] cholesterol level 4.14 mmol/L [ 160 mg/dL ] [ or treatment with hypolipidemic drugs ] , high-density lipoprotein [ HDL ] cholesterol level 1.04 mmol/L [ 40 mg/dL ] , body mass index [ BMI ] 25 kg/m2 , or a family history of premature CHD ) . Exclusion criteria were history of cardiovascular disease , any severe chronic illness , drug or alcohol addiction , history of allergy or intolerance to olive oil or nuts , or low predicted likelihood of changing dietary habits according to the stages-of-change model ( 18 ) . The primary care physicians based participants ' eligibility on review of clinical records and a screening visit . They obtained a list of c and i date s from computer-based records of patients who attended each participating center and review ed their clinical records to exclude those who did not meet eligibility criteria . They then invited suitable c and i date s by telephone to attend a screening visit . The visit included an interview with administration of a 26-item question naire to inquire about medical conditions and risk factors related to eligibility . Of the eligible c and i date s who met entry requirements , 95 % agreed to participate and provided informed consent . R and omization and Intervention After the screening visit , each center r and omly assigned eligible participants to 1 of 3 diet groups by using a computer-generated r and om-number sequence . The coordinating center constructed the r and omization table , and participants were r and omly assigned into blocks of 50 participants balanced by center , sex , and age group ( < 70 years and 70 years ) . We concealed allocation into the intervention groups by using closed envelopes with correlative numbers by prespecified subgroups of sex and age . The baseline examination included the administration of a 14-item question naire , an extension of a previously vali date d question naire ( 19 ) , that assessed the degree of adherence to the traditional Mediterranean diet . We assigned values of 0 or 1 to each item ( Appendix Table 1 ) . We also administered a 137-item vali date d food frequency question naire ( 20 ) ; the vali date d Spanish version ( 21 ) of the Minnesota Leisure Time Physical Activity Question naire ; and a 47-item question naire about education , lifestyle , history of illnesses , and medication use . We performed anthropometric and blood pressure measurements and obtained sample s of fasting blood and spot urine . We repeated all examinations at 3 months . The same dietitian delivered the interventions to the 3 r and omized groups in each center . On the basis of the assessment of individual Mediterranean diet scores , the dietitian gave personalized dietary advice during a 30-minute session to each participant , with recommendations on the desired frequency of intake of specific foods . We advised participants who were allocated to the low-fat diet to reduce intake of all types of fat , and we gave them a leaflet with written recommendations according to the American Heart Association guidelines ( 22 ) . For total fat intake , these recommendations were opposite to those given to participants in the 2 Mediterranean diet groups , who received instructions intended to increase the 14-item Mediterranean diet score , including increased consumption of vegetable fats and oils . We did not suggest any energy restriction . While the participants who were allocated to the low-fat diet did not receive further intervention , those assigned the 2 Mediterranean diet groups had access to more intense intervention in 2 ways . First , they were given a free provision of typical Mediterranean fatty foods ( olive oil or nuts ) . Depending on group assignment , participants were given either free virgin olive oil ( 15 L [ 1 L/wk ] for 3 months ) or free sachets of walnuts , hazelnuts , and almonds ( 1350 g of walnuts [ 15 g/d ] , 675 g of hazelnuts [ 7.5 g/d ] , and 675 g of almonds [ 7.5 g/d ] for 3 months ) . To improve adherence and account for family needs , participants in the corresponding Mediterranean diet groups were given excess olive oil or additional 1000-g packets of nuts . We analyzed the nutrient composition of the olive oil and nuts used in the study by st and ard methods in a reference laboratory ( Appendix Table 2 ) ) . Second , 1 week after inclusion , the dietitian delivered a 1-hour group session with up to 20 participants , with separate sessions for each Mediterranean diet group . Each group session consisted of informative talks and provision of written material s with elaborate descriptions of typical Mediterranean foods and seasonal shopping lists , meal plans , and cooking recipes . Throughout the study , all participants had free and continuous access to their center dietitian for advice and consultation . Measurements Trained personnel measured weight and height by using calibrated scales and a wall-mounted stadiometer , respectively ; waist circumference midway between the lowest rib and the iliac crest by using an anthropometric tape ; and blood pressure in triplicate with a vali date d semiautomatic oscillometer ( Omron HEM-705CP , Hoofddorp , the Netherl and s ) . We calculated energy and nutrient intake from Spanish food composition tables ( 23 ) . At the 3-month visit and when consulted by participants , dietitians assessed any adverse effects from the interventions by administering a checklist of symptoms and gave advice on how to remedy them . The checklist included mouth symptoms ; bloating , fullness , or indigestion ; altered bowel OBJECTIVE Few multiple lifestyle behavior change programs have been design ed to reduce the risk of coronary heart disease in postmenopausal women with type 2 diabetes . This study tested the effectiveness of the Mediterranean Lifestyle Program ( MLP ) , a comprehensive lifestyle self-management program ( Mediterranean low-saturated fat diet , stress management training , exercise , group support , and smoking cessation ) , in reducing cardiovascular risk factors in postmenopausal women with type 2 diabetes . RESEARCH DESIGN AND METHODS Postmenopausal women with type 2 diabetes ( n = 279 ) were r and omized to either usual care ( control ) or treatment ( MLP ) conditions . MLP participants took part in an initial 3-day retreat , followed by 6 months of weekly meetings , to learn and practice program components . Biological end points were changes in HbA(1c ) , lipid profiles , BMI , blood pressure , plasma fatty acids , and flexibility . Impact on quality of life was assessed . RESULTS Multivariate ANCOVAs revealed significantly greater improvements in the MLP condition compared with the usual care group on HbA(1c ) , BMI , plasma fatty acids , and quality of life at the 6-month follow-up . Patterns favoring intervention were seen in lipids , blood pressure , and flexibility but did not reach statistical significance . CONCLUSIONS These results demonstrate that postmenopausal women with type 2 diabetes can make comprehensive lifestyle changes that may lead to clinical ly significant improvements in glycemic control , some coronary heart disease risk factors , and quality of life BACKGROUND AND AIM The effect of the quality of dietary fat on body composition is unknown . Our objective was to determine whether body composition is modified by the isocaloric substitution of a diet rich in saturated fat by a diet high in monounsaturated fat ( Mediterranean diet ) or a carbohydrate-rich diet in overweight subjects with hypercholesterolemia . METHODS AND RESULTS The study involved 34 hypercholesterolemic males aged 18 - 63 years with a body mass index ( BMI ) of 28.2 ( 2.6 ) , all of whom consumed a diet rich in saturated fat ( SAT ) for 28 days . They were then r and omly divided into two groups of 17 subjects and underwent two dietary periods of 28 days each in a crossover design : a Mediterranean diet high in monounsaturated fat ( MONO ) and a carbohydrate-rich diet ( CHO ) . The order of the diets was different for the two group . The CHO diet contained 57 % CHO and 28 % total fat ( < 10 % saturated fat , 12 % monounsaturated fat and 6 % polyunsaturated fat ) ; the Mediterranean diet contained 47 % CHO and 38 % fat ( < 10 % saturated fat , 22 % monounsaturated fat--75 % of which was provided by olive oil- and 6 % polyunsaturated fat ) . The variables measured at the end of each dietary intervention period were : 1 ) body composition by means of bioelectrical impedance ; 2 ) plasma lipoproteins using enzymatic techniques ; and 3 ) fatty acids in cholesterol esters by means of gas chromatography . BMI and the waist/hip ratio remained the same during the three dietary periods . A decrease in fat was observed when changing from a saturated fat diet ( 23.3 ( 6.3 ) kg ) to a Mediterranean diet ( 20.8 ( 7.2 ) kg ) ( p < 0.05 ) , or a carbohydrate-rich diet ( 20.6 ( 6.7 ) kg ) ( p < 0.05 ) . Lean mass increased when changing from a SAT diet ( 58.4 ( 7.0 ) kg ) to a CHO diet ( 60.2 ( 7.0 ) kg ) ( p < 0.05 ) . CONCLUSION The isocaloric substitution of a saturated fat-rich diet by a Mediterranean or carbohydrate-rich diet decreases total body fat in hypercholesterolemic males CONTEXT : Long-term success in weight loss with dietary treatment has been elusive . OBJECTIVE : To evaluate a diet moderate in fat based on the Mediterranean diet compared to a st and ard low-fat diet for weight loss when both were controlled for energy . DESIGN : A r and omized , prospect i ve 18 month trial in a free-living population . PATIENTS : A total of 101 overweight men and women ( 26.5–46 kg/m2).INTERVENTION : ( 1 ) Moderate-fat diet ( 35 % of energy ) ; ( 2 ) low-fat diet ( 20 % of energy).MAIN OUTCOME MEASUREMENTS : Change in body weight . RESULTS : After 18 months , 31/50 subjects in the moderate-fat group , and 30/51 in the low fat group were available for measurements . In the moderate-fat group , there were mean decreases in body weight of 4.1 kg , body mass index of 1.6 kg/m2 , and waist circumference of 6.9 cm , compared to increases in the low-fat group of 2.9 kg , 1.4 kg/m2 and 2.6 cm , respectively ; P≤0.001 between the groups . The difference in weight change between the groups was 7.0 kg . ( 95 % CI 5.3 , 8.7 ) . Only 20 % ( 10/51 ) of those in the low-fat group were actively participating in the weight loss program after 18 months compared to 54 % ( 27/50 ) in the moderate-fat group , ( P<0.002 ) . The moderate-fat diet group was continued for an additional year . The mean weight loss after 30 months compared to baseline was 3.5 kg ( n=19 , P=0.03 ) . CONCLUSIONS : A moderate-fat , Mediterranean-style diet , controlled in energy , offers an alternative to a low-fat diet with superior long-term participation and adherence , with consequent improvements in weight loss OBJECTIVE : To assess the factors that could predict a successful completion of a weight loss program . STUDY DESIGN : A single-centered , cross-sectional , prospect i ve study conducted over 4 y . SUBJECTS : Data were obtained on 1018 overweight subjects ( 788 women , 230 men ) aged 14.8–76.3 y ( mean 38.4 ) and body mass index ( BMI ) of 31.7 ( range 25.03–57.1 ) seeking help to lose weight at a specialist obesity clinic . MATERIAL S AND METHODS : A program involving a hypocaloric , Mediterranean diet was prescribed plus recommendations for free-time exercise and day-to-day activity . Follow-up was weekly until the desired weight loss was achieved ( ‘ successful completion ’ ) or the patient dropped-out of the program ( ‘ failure ’ ) . Cox 's regression analysis was used to evaluate success and the variables included were compliance with the program , age , gender , initial BMI , physical activity , alcohol consumption , smoking habit , hypertension , diabetes , hypercholesterolemia , cardiovascular disease , previous dietary programs , cause of obesity , age at which excessive weight was first noted and parental obesity . RESULTS : Factors predictive of completion were : gender ( males responded better ) , previous dietary programs ( predictive of dropout ) , initial BMI ( higher index , lower completion ) , and age ( younger age , poorer outcome ) . There was an interaction between parental obesity and offspring childhood obesity . Absence of parental obesity and adult-onset obesity had a higher probability of program completion . CONCLUSIONS : In a st and ard weight reduction program the recommendations of dietary restriction and moderate exercise seems less effective for women , persons with high BMI , younger age groups and those who have had other attempts at weight loss . Poorest outcomes applied to those subjects with childhood obesity and who had obese parents CONTEXT Obesity is an independent risk factor for cardiovascular disease , which may be mediated by increased secretion of proinflammatory cytokines by adipose tissue . OBJECTIVE To determine the effect of a program of changes in lifestyle design ed to obtain a sustained reduction of body weight on markers of systemic vascular inflammation and insulin resistance . DESIGN AND SETTING R and omized single-blind trial conducted from February 1999 to February 2002 at a university hospital in Italy . PATIENTS One hundred twenty premenopausal obese women ( body mass index > or = 30 ) aged 20 to 46 years without diabetes , hypertension , or hyperlipidemia . INTERVENTIONS The 60 women r and omly assigned to the intervention group received detailed advice about how to achieve a reduction of weight of 10 % or more through a low-energy Mediterranean-style diet and increased physical activity . The control group ( n = 60 ) was given general information about healthy food choices and exercise . MAIN OUTCOME MEASURES Lipid and glucose intake ; blood pressure ; homeostatic model assessment of insulin sensitivity ; and circulating levels of interleukin 6 ( IL-6 ) , interleukin 18 ( IL-18 ) , C-reactive protein ( CRP ) , and adiponectin . RESULTS After 2 years , women in the intervention group consumed more foods rich in complex carbohydrates ( 9 % corrected difference ; P<.001 ) , monounsaturated fat ( 2 % ; P = .009 ) , and fiber ( 7 g/d ; P<.001 ) ; had a lower ratio of omega-6 to omega-3 fatty acids ( -5 ; P<.001 ) ; and had lower energy ( -310 kcal/d ; P<.001 ) , saturated fat ( -3.5 % ; P = .007 ) , and cholesterol intake ( -92 mg/d ; P<.001 ) than controls . Body mass index decreased more in the intervention group than in controls ( -4.2 ; P<.001 ) , as did serum concentrations of IL-6 ( -1.1 pg/mL ; P = .009 ) , IL-18 ( -57 pg/mL ; P = .02 ) , and CRP ( -1.6 mg/L ; P = .008 ) , while adiponectin levels increased significantly ( 2.2 microg/mL ; P = .01 ) . In multivariate analyses , changes in free fatty acids ( P = .008 ) , IL-6 ( P = .02 ) , and adiponectin ( P = .007 ) levels were independently associated with changes in insulin sensitivity . CONCLUSION In this study , a multidisciplinary program aim ed to reduce body weight in obese women through lifestyle changes was associated with a reduction in markers of vascular inflammation and insulin resistance OBJECTIVE We evaluated the prevalence of obesity in relation to adherence to a Mediterranean diet . METHODS We conducted a cross-sectional survey that r and omly enrolled 1514 men ( 18 to 87 y old ) and 1528 women ( 18 to 89 y old ) with no history of cardiovascular disease . Anthropometric indices were measured and frequency of various foods consumed during a usual week was recorded . Adherence to a Mediterranean diet was assessed by a diet score that incorporated the inherent characteristics of this diet . RESULTS Prevalences of overweight and obesity were 53 % and 20 % in men and 31 % and 15 % in women . An inverse relation was observed between diet score , waist-to-hip ratio ( r = -0.31 , P < 0.001 ) , and body mass index ( r = -0.4 , P < 0.001 ) after adjusting for sex and age . Greater adherence to the Mediterranean diet ( i.e. , highest tertile ) was associated with a 51 % lower odds of being obese ( odds ratio 0.49 , 95 % confidence interval 0.42 to 0.56 ) and a 59 % lower odds of having central obesity ( odds ratio 0.41 , 95 % confidence 0.35 to 0.47 ) compared with a non-Mediterranean diet ( i.e. , lowest tertile ) after controlling for age , sex , physical activity status , metabolism , and other variables . CONCLUSION We observed an inverse relation between adherence to a Mediterranean dietary pattern and prevalence of obesity in a free-eating , population -based sample of men and women , irrespective of various potential confounders Diet is a lifestyle factor that contributes to the risk of overweight/obesity and cardiovascular disease . The objective of this study was to examine the hypothesis that a Mediterranean-type dietary pattern ( M ) is associated with healthy body weights in a large suburban municipality in Ontario . A r and om cross-sectional sample of 759 adults , 18 to 65 years of age , participated in a telephone survey , which included questions on the frequency of consumption of 60 food categories . Principal components analysis showed that food categories aggregated into six low-order dietary factors and two high-order dietary patterns . The M pattern reflected higher consumption of fruits and vegetables , olive oil and garlic , and fish and shellfish . The non-M pattern reflected high fat/nutrient poor , meats and poultry , and foods high in added sugars . The M-score was inversely related to body mass index ( BMI ) ( p = 0.027 ) . After adjustment for gender , education , income and marital status , a higher M-score predicted a lower BMI in the 40 to 49 year age group . Heart health promotion strategies aim ed at preventing adult obesity should emphasize components of a Mediterranean-type diet pattern OBJECTIVE Research in industrialised countries has documented a high prevalence of underreported energy intakes associated with characteristics such as obesity . This paper examines the prevalence , patterns and impact of energy under- and overreporting on diet-obesity relationships in a middle-income developing country . DESIGN A 70-item food-frequency question naire was used . Underreporters had reported energy intakes < 1.35 x basal metabolic rate ( BMR ) , overreporters > 2.4 x BMR . Multinomial models were used to identify characteristics associated with implausible reporting . Intakes were compared across reporting groups to assess evidence of bias . Associations between diet and obesity were compared with and without adjustment for implausible reporting . SETTING Spanish Town , neighbouring the capital city of Kingston , Jamaica . SUBJECTS Eight hundred and ninety-one Jamaican adults , aged 25 - 75 years , were r and omly recruited . RESULTS More women than men ( 38.6 % vs. 22.5 % ) underreported , but more men overreported energy ( 23.7 % vs. 16.0 % ) . Underreporting was positively associated with obesity , special diets , smoking and age ; age was inversely associated with overreporting . Underreporters estimated lower energy from potentially socially undesirable food groups ( e.g. snacks ) and higher intakes of ' healthy ' foods ( e.g. fruit ) than did plausible reporters . For some of these food groups , significant differences in intakes among normal-weight versus obese subjects observed among plausible reporters were absent when implausible reporters were included . In models of food group-obesity associations , adjusting for implausible energy yielded more credible results that more closely resembled findings in plausible reporters . CONCLUSIONS Energy under- and overreporting are highly prevalent in Jamaica . Adjusting for implausible reporting may help to reduce bias in diet-health outcome associations |
12,396 | 26,167,962 | R and omized clinical trials around the world have shown that combined diet and physical activity promotion programs could prevent or delay progression to type 2 diabetes among persons at increased risk ( 58 ) .
Studies have also demonstrated the feasibility and effectiveness of such programs when they are implemented in primary care or community setting s ( 9 ) .
In 2014 , a systematic review done for the Community Preventive Services Task Force found that programs implemented in health care or community setting s effectively reduced the risk for diabetes in persons at increased risk ; increased the likelihood of reversion to normoglycemia ; and reduced weight and other risk factors for cardiovascular disease , such as elevated blood pressure and lipid levels ( 10 ) . | Diabetes is a highly prevalent , severe , and costly disease in the United States .
Approximately 29 million Americans ( 9.3 % of the U.S. population ) had diabetes in 2012 , and that number is projected to increase ( 1 , 2 ) .
Diabetes is the leading cause of kidney failure , blindness , and amputation , as well as a major cause of heart disease and stroke ( 2 ) .
In the United States in 2012 , the total medical cost of diagnosed diabetes was estimated at $ 176 billion , and the cost of productivity loss due to diabetes was another $ 69 billion ( 3 ) .
Type 2 diabetes accounts for 90 % to 95 % of all cases of diagnosed diabetes .
Common risk factors for type 2 diabetes include obesity , family history of diabetes , physical inactivity , hypertension , hypercholesterolemia , and elevated glucose level .
In addition , approximately 37 % of the U.S. population aged 20 years or older and 51 % of those aged 65 years or older had prediabetes in 2012 , meaning that they were at increased risk for type 2 diabetes ( 2 ) .
However , only about 10 % of at-risk persons knew their risk status ( 4 ) .
Given the potentially large population that is eligible for diet and physical activity promotion programs and the re sources needed for implementation , information on program cost and cost-effectiveness is critical for policy decisions , such as benefit coverage for payers , as well as planning for program design and implementation .
As a companion to the aforementioned effectiveness review , we did this systematic economic review for the Community Preventive Services Task Force to estimate the cost associated with diet and physical activity promotion programs and the cost-effectiveness and costbenefit ratios of these programs . | OBJECTIVE To describe the 1 ) lifestyle intervention used in the Finnish Diabetes Prevention Study , 2 ) short- and long-term changes in diet and exercise behavior , and 3 ) effect of the intervention on glucose and lipid metabolism . RESEARCH DESIGN AND METHODS There were 522 middle-aged , overweight subjects with impaired glucose tolerance who were r and omized to either a usual care control group or an intensive lifestyle intervention group . The control group received general dietary and exercise advice at baseline and had an annual physician 's examination . The subjects in the intervention group received additional individualized dietary counseling from a nutritionist . They were also offered circuit-type resistance training sessions and advised to increase overall physical activity . The intervention was the most intensive during the first year , followed by a maintenance period . The intervention goals were to reduce body weight , reduce dietary and saturated fat , and increase physical activity and dietary fiber . RESULTS The intervention group showed significantly greater improvement in each intervention goal . After 1 and 3 years , weight reductions were 4.5 and 3.5 kg in the intervention group and 1.0 and 0.9 kg in the control group , respectively . Measures of glycemia and lipemia improved more in the intervention group . CONCLUSIONS The intensive lifestyle intervention produced long-term beneficial changes in diet , physical activity , and clinical and biochemical parameters and reduced diabetes risk . This type of intervention is a feasible option to prevent type 2 diabetes and should be implemented in the primary health care system Context A previous Markov modelbased analysis estimated that use of the Diabetes Prevention Program diet and exercise intervention to forestall diabetes in high-risk people would be cost-effective from a societal perspective . Contribution Using a vali date d model design ed to be more complete and realistic than previous models , the authors estimated that the intervention would cost society about $ 62600 per quality -adjusted life-year saved . It would be cost-saving if the annual cost of the intervention decreased from $ 672 to $ 100 . Implication s This model suggests that the Diabetes Prevention Program intervention costs more per quality -adjusted life-year saved than previously estimated , and health plans and insurers may consider it too expensive to cover . The Editors Recent r and omized , controlled studies have shown that diabetes can be prevented or delayed in high-risk individuals by intensive lifestyle modification programs ( 1 , 2 ) or glucose-lowering drugs ( 2 - 4 ) . For example , in the Diabetes Prevention Program ( DPP ) , the relative reductions in the 2.8-year incidence of diabetes were 58 % in the lifestyle modification group and 31 % in the metformin group ( 2 ) . This raises hopes of substantially reducing the morbidity , mortality , and cost of this important disease . However , the trial was too short to observe the effects on microvascular or macrovascular outcomes , and the programs cost several hundred dollars a year ( 5 ) . These findings generate obvious questions : What are the long-term effects of trying to prevent diabetes in high-risk people ? Does lifestyle modification truly prevent or just postpone diabetes ? Is such a prevention program cost-effective ? What is the best strategy ? A previous analysis has suggested that lifestyle modification would be cost-effective over 75 years from a societal perspective ( 6 ) . We used a more thorough , clinical ly realistic , and independently vali date d model to estimate the short- and intermediate-term health and economic effects of different prevention programs for high-risk individuals and health plans , as well as for society . Methods We conducted the analysis by using the Archimedes model , which has been described elsewhere ( 7 - 9 ) . Briefly , it is a simulation model written at a relatively high level of anatomic , physiologic , clinical , and administrative detail . It uses object-oriented programming to create in the model objects that correspond to objects in reality , one-to-one . Among the hundreds of objects are people , pancreases , cells , plasma glucose levels , coronary arteries , plaque , chest pain , emergency departments , electrocardiograms , aspirin , and angioplasties . Helpful analogies might be a flight simulator ( in which the objects include the plane and its wings , airports , runways , buildings , and the wind ) , or the SimCity computer game . In the Archimedes model , each individual is simulated down to the level of hepatic glucose production , insulin resistance , -cell fatigue , and similar biological variables . The core of the model is a set of differential equations that represent the anatomy and physiology pertinent to diseases and their complications . Currently , the model includes diabetes , congestive heart failure , coronary artery disease , stroke , hypertension , and asthma in a single integrated model . The structure and equations of the model pertinent to diabetes and its complications are described elsewhere ( 8 , 9 ) . The Appendix and a technical report available through our Web site ( 10 ) describe additional aspects of the model and its validations that are pertinent to this analysis . Calculations are performed by using a distributed computing network . Clinical Events The model includes the biological variables and outcomes relevant to diabetes and its complications . Examples are basal hepatic glucose production ; insulin amount ; insulin resistance ; fasting plasma glucose ; hemoglobin A1c ( HbA1c ) ; 2-hour oral glucose tolerance ; high-density lipoprotein ( HDL ) cholesterol , low-density lipoprotein ( LDL ) cholesterol , and total cholesterol ; triglycerides ; systolic and diastolic blood pressures and their determinants ( for example , cardiac output , arterial compliance , peripheral resistance ) ; weight and body mass index ( BMI ) ; stenosis of coronary arteries ; retinopathy ( assessed by the Early Treatment of Diabetic Retinopathy scale ) ; urine protein ; creatinine ; peripheral neuropathy ; foot ulcers of varying degrees of severity ; and amputations . The use of differential equations preserves the continuous nature of biological variables as well as the interactions between them . Clinical outcomes are defined in terms of the underlying variables , as occurs in reality . For example , a person is said to have diabetes if his or her fasting plasma glucose level exceeds 6.9375 mmol/L ( 125 mg/dL ) or results on a 2-hour oral glucose tolerance test exceed 11.0445 mmol/L ( 199 mg/dL ) . This enables the model to incorporate different definitions and changes in definitions . The model is continuous : Biological variables are changing and interacting continuously , the natural histories and severity of conditions progress smoothly , any clinical event can occur at any time , and the timing of events is as condensed or drawn out as occurs in reality . The model also includes a detailed representation of the processes and logistics of clinical care and their related costs . Interventions , both to prevent diabetes and to manage it when it occurs , are modeled at the level of the underlying biology . Pertinent to this analysis is that in the model , diet and exercise reduce weight ( 2 ) ; reduce blood pressure ( 11 ) ; improve LDL cholesterol , HDL cholesterol , and total cholesterol levels ( 12 ) ; and decrease fasting plasma glucose levels ( 2 ) . The effects of metformin in the model are to reduce fasting plasma glucose and 2-hour oral glucose tolerance test results ( 2 ) ( by reducing basal hepatic glucose production ) , decrease LDL cholesterol and triglyceride levels ( 13 ) , and retard weight gain . Data used to build the model were derived from basic physiologic studies , surveys , epidemiologic studies , and clinical trials using methods described in the technical report ( 10 ) . Every variable in the model is estimated from at least 1 empirical source ; no variables are simply assumed . We identified specific sources by search ing MEDLINE from 1970 to 28 February 2005 and by consulting textbooks and clinical experts . Because the model includes scores of continuously valued , interacting variables , it does not have simplified states , transitions , or events at discrete time intervals that can be tabulated , as is commonly done for a Markov-type model . The equations themselves are in the technical report ( 10 ) . For nonmathematical readers , we have calculated annualized rates of change of representative biological variables and annualized rates of occurrence of representative clinical events , and compared them with rates for comparable events observed in epidemiologic studies and clinical trials . The Appendix reports those results . Costs The DPP measured the direct medical costs of delivering the lifestyle and metformin interventions ( for example , personnel , health education material s , medications , and laboratory tests ) . Compared with the placebo group 's costs , costs in the lifestyle group were $ 1356 more per person in the first year , with approximately $ 672 in annual costs thereafter ; for the metformin group , costs were $ 977 in the first year and averaged $ 742 per year thereafter ( 5 ) . Following the completion of the DPP , metformin became generic . When this is considered , the cost of the metformin program is reduced to about $ 780 for 3 years , or about $ 260 a year . In the DPP study , costs apply to the year 2000 . To calculate the routine costs of providing health care to high-risk people before they develop diabetes , as well as to people with diabetes and its complications , the model includes a detailed mathematical representation of a health care system , including such elements as facilities , personnel , tests and treatments , protocol s , and provider behaviors . For the base-case analysis , we obtained itemized costs from Kaiser Permanente , a nonprofit , group- practice , integrated managed care organization that provides comprehensive care ( with no deductibles or copayments ) . The facilities , personnel , protocol s , and costs in the model are based on that organization 's records , at the level of detail at which actual accounts are kept ( for example , 37 different kinds of office visits ) . The model calculates costs by keeping track of the occurrence of every event that has cost implication s and adding them up . The costs assigned to any event or item were calculated by Kaiser Permanente 's cost-accounting department using micro-costing methods ( 14 ) , and they represent the real costs to the organization , not charges , reimbursements , or diagnosis-related groups . Because costs vary from setting to setting , the implication s of different cost structures are examined in the sensitivity analysis . Calculation of costs applies to the year 2000 . Indirect costs , such as lost time from work and decreased productivity , are included in the cost-effectiveness analysis through the Quality of Well-Being Index ( 14 ) . We calculated the effects of lifestyle and metformin interventions on quality of life . For people who do not yet have diabetes , we used utility weights reported for the participants of the DPP study ( 15 ) . For people who have diabetes and its complications , we used the results of a published survey by Coffey and colleagues ( 16 ) . Both surveys used the Quality of Well-Being Index . The decrements in quality of life were assumed to be additive for people who have 2 or more complications , with a limit that quality of life could not be less than 0 . Use of an additive rule biases the calculation of cost/ quality -adjusted life-year ( QALY ) in favor of a prevention program , making the program appear more cost-effective than would occur if a multiplicative model were used . We discuss the OBJECTIVES The Finnish Diabetes Prevention Study ( DPS ) was a r and omized intervention program that evaluated the effect of intensive lifestyle modification on the development of diabetes mellitus type 2 in patients with impaired glucose tolerance . As such , a program is dem and ing in terms of re sources ; it is necessary to assess whether it would be money well spent . This determination was the purpose of this study . METHODS We developed a simulation model to assess the economic consequences of an intervention like the one studied in DPS in a Swedish setting . The model used data from the trial itself to assess the effect of intervention on the risk of diabetes and on risk factors for cardiovascular disease . Results from the United Kingdom Prospect i ve Diabetes Study were used to estimate the risk of cardiovascular disease and stroke . Cost data were derived from Swedish studies . The intervention was assumed to be applied to eligible patients from a population -based screening program of 60-year-olds in the County of Stockholm from which the baseline characteristics of the patients was used . RESULTS The model predicted that implementing the program would be cost-saving from the healthcare payers ' perspective . Furthermore , it was associated with an increase in estimated survival of .18 years . Taking into consideration the increased consumption by patients due to their longer survival , the predicted cost-effectiveness ratio was 2,363 euro per quality -adjusted life-year gained . CONCLUSIONS Lifestyle intervention directed toward high-risk subjects would be cost-saving for the healthcare payer and highly cost-effective for society as a whole Aims /hypothesisLifestyle modification helps in the primary prevention of diabetes in multiethnic American , Finnish and Chinese population s. In a prospect i ve community-based study , we tested whether the progression to diabetes could be influenced by interventions in native Asian Indians with IGT who were younger , leaner and more insulin resistant than the above population s. Methods We r and omised 531 ( 421 men 110 women ) subjects with IGT ( mean age 45.9±5.7 years , BMI 25.8±3.5 kg/m2 ) into four groups . Group 1 was the control , Group 2 was given advice on lifestyle modification ( LSM ) , Group 3 was treated with metformin ( MET ) and Group 4 was given LSM plus MET . The primary outcome measure was type 2 diabetes as diagnosed using World Health Organization criteria . Results The median follow-up period was 30 months , and the 3-year cumulative incidences of diabetes were 55.0 % , 39.3 % , 40.5 % and 39.5 % in Groups 1–4 , respectively . The relative risk reduction was 28.5 % with LSM ( 95 % CI 20.5–37.3 , p=0.018 ) , 26.4 % with MET ( 95 % CI 19.1–35.1 , p=0.029 ) and 28.2 % with LSM + MET ( 95 % CI 20.3–37.0 , p=0.022 ) , as compared with the control group . The number needed to treat to prevent one incident case of diabetes was 6.4 for LSM , 6.9 for MET and 6.5 for LSM + MET . Conclusions /interpretationProgression of IGT to diabetes is high in native Asian Indians . Both LSM and MET significantly reduced the incidence of diabetes in Asian Indians with IGT ; there was no added benefit from combining them OBJECTIVE Older adults in the U.S. have high rates of obesity . Despite the demonstrated efficacy of lifestyle interventions among older adults , lifestyle interventions are not widely implemented in community setting s. Program delivery by lay health educators ( LHEs ) might support greater dissemination because of lower delivery cost and greater accessibility . We examined the costs of a LHE-delivered translation of the Diabetes Prevention Program ( DPP ) evidence -based lifestyle intervention for older adults in Arkansas senior centers . METHODS This examination of costs used data from a cluster r and omized control trial ( conducted 2008 - 2010 ) in which 7 senior centers ( 116 participants ) were r and omized to implement a LHE-delivered 12-session translation of the DPP lifestyle intervention . We compiled direct lifestyle intervention implementation costs , including training , recruitment , material s , and ongoing intervention implementation support . Weight loss data ( at 4-month follow-up ) were collected from participants . RESULTS Participant weight loss averaged 3.7 kg at 4-months . The total estimated cost to implement the lifestyle intervention is $ 2731 per senior center , or $ 165 per participant . The implementation cost per kilogram lost is $ 45 . CONCLUSIONS A LHE-delivered DPP translation in senior centers is effective in achieving weight loss at low cost and offers promise for the dissemination of this evidence -based intervention BACKGROUND Although numerous studies have translated the Diabetes Prevention Program lifestyle intervention into various setting s , no study to date has reported a formal cost analysis . PURPOSE To describe costs associated with the Healthy Living Partnerships to Prevent Diabetes ( HELP PD ) trial . DESIGN HELP PD was a 24-month RCT testing the impact of a lifestyle weight-loss intervention administered through a diabetes education program and delivered by community health workers ( CHWs ) on blood glucose and body weight among prediabetics . SETTING / PARTICIPANTS In all , 301 participants with prediabetes were r and omized in Forsyth County NC . Data reported in these analyses were collected in 2007 - 2011 and analyzed in 2011 - 2012 . INTERVENTION The lifestyle weight-loss group had a 7 % weight loss goal achieved and maintained by caloric restriction and increased physical activity . The usual care group received two visits with a registered dietitian and monthly newsletters . MAIN OUTCOME MEASURES Measures are direct medical costs , direct nonmedical costs , and indirect costs over the 2-year study period . Research costs are excluded . RESULTS The direct medical cost ( in 2010 dollars ) to identify one participant was $ 16.85 . Direct medical costs per capita for participants in the usual care group were $ 142 and $ 850 for lifestyle weight-loss participants . Per capita direct costs of care outside the study were $ 7454 for the usual care group and $ 5177 for the lifestyle weight-loss group . Per capita direct nonmedical costs were $ 12,881 for the usual care group and $ 13,836 for the lifestyle weight-loss group . The lifestyle weight-loss group in HELP PD cost $ 850 in direct medical costs for 2 years , compared to $ 2631 in direct medical costs for the first 2 years of DPP . CONCLUSIONS A community-based translation of the DPP can be delivered effectively and with reduced costs OBJECTIVES Previous research has suggested people with impaired fasting glucose ( IFG ) are less likely to develop Type 2 diabetes ( T2DM ) if they receive prolonged structured diet and exercise advice . This study examined the within-trial cost-effectiveness of such lifestyle interventions . METHODS Screen-detected participants with either newly diagnosed T2DM or IFG were r and omized 2:1 to intervention versus control ( usual care ) between February and December 2009 , in Norfolk ( UK ) . The intervention consisted of group based education , physiotherapy and peer support sessions , plus telephone contacts from T2DM volunteers . We monitored healthcare re source use , intervention costs , and quality of life ( EQ-5D ) . The incremental cost per quality -adjusted life-year ( QALY ) gain ( incremental cost effectiveness ratio [ ICER ] ) , and cost effectiveness acceptability curves ( CEAC ) were estimated . RESULTS In total , 177 participants were recruited ( 118 intervention , 59 controls ) , with a mean follow-up of 7 months . Excluding screening and recruitment costs , the mean cost was estimated to be £ 551 per participant in the intervention arm , compared with £ 325 in the control arm . The QALY gains were -0.001 and -0.004 , respectively . The intervention was estimated to have an ICER of £ 67,184 per QALY ( 16 percent probability of being cost-effective at the £ 20,000/QALY threshold ) . Cost-effectiveness estimates were more favorable for IFG participants and those with longer follow-up ( ≥ 4 months ) ( ICERs of £ 20,620 and £ 17,075 per QALY , respectively ) . CONCLUSIONS Group sessions to prevent T2DM were not estimated to be within current limits of cost-effectiveness . However , there was a large degree of uncertainty surrounding these estimates , suggesting the need for further research OBJECTIVE Individuals with impaired glucose tolerance ( IGT ) have a high risk of developing NIDDM . The purpose of this study was to determine whether diet and exercise interventions in those with IGT may delay the development of NIDDM , i.e. , reduce the incidence of NIDDM , and thereby reduce the overall incidence of diabetic complications , such as cardiovascular , renal , and retinal disease , and the excess mortality attributable to these complications . RESEARCH DESIGN AND METHODS In 1986 , 110,660 men and women from 33 health care clinics in the city of Da Qing , China , were screened for IGT and NIDDM . Of these individuals , 577 were classified ( using World Health Organization criteria ) as having IGT . Subjects were r and omized by clinic into a clinical trial , either to a control group or to one of three active treatment groups : diet only , exercise only , or diet plus exercise . Follow-up evaluation examinations were conducted at 2-year intervals over a 6-year period to identify subjects who developed NIDDM . Cox 's proportional hazard analysis was used to determine if the incidence of NIDDM varied by treatment assignment . RESULTS The cumulative incidence of diabetes at 6 years was 67.7 % ( 95 % CI , 59.8–75.2 ) in the control group compared with 43.8 % ( 95 % CI , 35.5–52.3 ) in the diet group , 41.1 % ( 95 % CI , 33.4–49.4 ) in the exercise group , and 46.0 % ( 95 % CI , 37.3–54.7 ) in the diet-plus-exercise group ( P < 0.05 ) . When analyzed by clinic , each of the active intervention groups differed significantly from the control clinics ( P < 0.05 ) . The relative decrease in rate of development of diabetes in the active treatment groups was similar when subjects were stratified as lean or overweight ( BMI < or ≥ 25 kg/m2 ) . In a proportional hazards analysis adjusted for differences in baseline BMI and fasting glucose , the diet , exercise , and diet-plus-exercise interventions were associated with 31 % ( P < 0.03 ) , 46 % ( P < 0.0005 ) , and 42 % ( P < 0.005 ) reductions in risk of developing diabetes , respectively . CONCLUSIONS Diet and /or exercise interventions led to a significant decrease in the incidence of diabetes over a 6-year period among those with IGT BACKGROUND Type 2 diabetes affects approximately 8 percent of adults in the United States . Some risk factors -- elevated plasma glucose concentrations in the fasting state and after an oral glucose load , overweight , and a sedentary lifestyle -- are potentially reversible . We hypothesized that modifying these factors with a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes . METHODS We r and omly assigned 3234 nondiabetic persons with elevated fasting and post-load plasma glucose concentrations to placebo , metformin ( 850 mg twice daily ) , or a lifestyle-modification program with the goals of at least a 7 percent weight loss and at least 150 minutes of physical activity per week . The mean age of the participants was 51 years , and the mean body-mass index ( the weight in kilograms divided by the square of the height in meters ) was 34.0 ; 68 percent were women , and 45 percent were members of minority groups . RESULTS The average follow-up was 2.8 years . The incidence of diabetes was 11.0 , 7.8 , and 4.8 cases per 100 person-years in the placebo , metformin , and lifestyle groups , respectively . The lifestyle intervention reduced the incidence by 58 percent ( 95 percent confidence interval , 48 to 66 percent ) and metformin by 31 percent ( 95 percent confidence interval , 17 to 43 percent ) , as compared with placebo ; the lifestyle intervention was significantly more effective than metformin . To prevent one case of diabetes during a period of three years , 6.9 persons would have to participate in the lifestyle-intervention program , and 13.9 would have to receive metformin . CONCLUSIONS Lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk . The lifestyle intervention was more effective than metformin OBJECTIVES We tested the effectiveness of a community-based , literacy-sensitive , and culturally tailored lifestyle intervention on weight loss and diabetes risk reduction among low-income , Spanish-speaking Latinos at increased diabetes risk . METHODS Three hundred twelve participants from Lawrence , Massachusetts , were r and omly assigned to lifestyle intervention care ( IC ) or usual care ( UC ) between 2004 and 2007 . The intervention was implemented by trained Spanish-speaking individuals from the community . Each participant was followed for 1 year . RESULTS The participants ' mean age was 52 years ; 59 % had less than a high school education . The 1-year retention rate was 94 % . Compared with the UC group , the IC group had a modest but significant weight reduction ( -2.5 vs 0.63 lb ; P = .04 ) and a clinical ly meaningful reduction in hemoglobin A1c ( -0.10 % vs -0.04 % ; P = .009 ) . Likewise , insulin resistance improved significantly in the IC compared with the UC group . The IC group also had greater reductions in percentage of calories from total and saturated fat . CONCLUSIONS We developed an inexpensive , culturally sensitive diabetes prevention program that result ed in weight loss , improved HbA1c , and improved insulin resistance in a high-risk Latino population BACKGROUND The Diabetes Prevention Program ( DPP ) demonstrated that lifestyle intervention reduces risk for type 2 diabetes and the metabolic syndrome . A universal framework for translation of multiple aspects of the DPP intervention , including training , support , and evaluation is needed to enhance treatment fidelity in a variety of setting s. PURPOSE This study aims to develop a comprehensive model for diabetes prevention translation using a modified DPP lifestyle intervention . METHODS The DPP lifestyle intervention was adapted to a 12-session group-based program called Group Lifestyle Balance for implementation in the community setting . A model for training and support mirroring that of the DPP was developed for prevention professionals administering the program . The process of training/support and program implementation was evaluated for feasibility and effectiveness using a nonr and omized prospect i ve design in two phases ( N=51 , Phase 1 : 2005 - 2006 ; N=42 , Phase 2 : 2007 - 2009 ; data analysis completed 2008 - 2009 ) . A total of 93 nondiabetic individuals with BMI > or=25 kg/m(2 ) and the metabolic syndrome or prediabetes participated . Measures were collected at baseline and post-intervention for all and 6 and 12 months post-intervention for Phase 2 . RESULTS Significant decreases in weight , waist circumference , and BMI were noted in both phases from baseline . Participants in Phase 2 also demonstrated decreases in total cholesterol , non-HDL cholesterol , and systolic and diastolic blood pressure that were maintained at 12 months . Average combined weight loss for both groups over the course of the 3-month intervention was 7.4 pounds ( 3.5 % relative loss , p<0.001 ) ; 23.8 % and 52.2 % of those who completed the program reached 7 % and 5 % weight loss , respectively . More than 80 % of those achieving 7 % weight loss in the Phase-2 group maintained their weight loss at 6 months . CONCLUSIONS A comprehensive diabetes prevention model for training , intervention delivery , and support was shown to be successful and was effective in reducing diabetes and cardiovascular disease risk factors in this group of high-risk individuals Purpose With growing numbers of people at risk for diabetes and cardiovascular disease , diabetes educators report increasing referrals for intervention in prevention of these conditions . Diabetes educators have expertise in diabetes self-management education ; however , they are generally not prepared for delivery of chronic disease primary prevention . The purpose of this project was to determine if individuals at risk for diabetes who participate in an intervention delivered by trained diabetes educators in existing diabetes self-management education community-based programs can reduce risk factors for diabetes and cardiovascular disease . Methods Diabetes educators in 3 outpatient-hospital programs ( urban , suburban , and rural ) received training and support for implementation of the Group Lifestyle Balance program , an adaptation of the Diabetes Prevention Program lifestyle intervention , from the Diabetes Prevention Support Center of the University of Pittsburgh . Adults with prediabetes and /or the metabolic syndrome were eligible to enroll in the program with physician referral . With use of existing diabetes educator networks , recruitment was completed via on-site physician in-services , informative letters , and e-mail contact as well as participant-directed newspaper advertisement . Results Eighty-one participants enrolled in the study ( 71 women , 10 men ) . Mean overall weight loss was 11.3 lb ( 5.1 % , P < .001 ) ; in addition , significant decreases were noted in fasting plasma glucose , low-density lipoprotein cholesterol , triglycerides , and blood pressure . Conclusions These results suggest that the Group Lifestyle Balance program delivered by diabetes educators was successful in reducing risk for diabetes and cardiovascular disease in high-risk individuals . Furthermore , diabetes educators , already integrated within the existing health care system , provide yet another re source for delivery of primary prevention programs in the community |
12,397 | 27,317,790 | The liver enzymes , alanine aminotransferase , aspartate aminotransferase and & ggr;-glutamyl transpeptidase , were not significantly altered with exercise .
Conclusions Exercise training reduces intrahepatic fat and FFAs while increasing cardiorespiratory fitness .
An aggregate exercise programme energy expenditure ( > 10 000 kcal ) may be required to promote reductions in intrahepatic fat | Objective Exercise training has been shown to have beneficial effects on liver function in adults overweight or with fatty liver disease .
To establish which exercise programme characteristics were likely to elicit optimal improvements . | OBJECTIVE Physical fitness is inversely related to mortality in the general population and in subjects with type 2 diabetes . Here , we present data concerning the relationship between changes in physical fitness and modifiable cardiovascular risk factors in subjects with type 2 diabetes from the Italian Diabetes and Exercise Study . RESEARCH DESIGN AND METHODS Sedentary patients with type 2 diabetes ( n = 606 ) were enrolled in 22 outpatient diabetes clinics and r and omized to twice-a-week supervised aerobic and resistance training plus exercise counseling versus counseling alone for 12 months . Baseline to end-of- study changes in cardiorespiratory fitness , strength , and flexibility , as assessed by Vo2max estimation , a 5–8 maximal repetition test , and a hip/trunk flexibility test , respectively , were calculated in the whole cohort , and multiple regression analyses were applied to assess the relationship with cardiovascular risk factors . RESULTS Changes in Vo2max , upper and lower body strength , and flexibility were significantly associated with the variation in the volume of physical activity , HbA1c , BMI , waist circumference , high-sensitivity C-reactive protein ( hs-CRP ) , coronary heart disease ( CHD ) risk score , and inversely , HDL cholesterol . Changes in fitness predicted improvements in HbA1c , waist circumference , HDL cholesterol , hs-CRP , and CHD risk score , independent of study arm , BMI , and in case of strength , also waist circumference . CONCLUSIONS Physical activity/exercise-induced increases in fitness , particularly muscular , predict improvements in cardiovascular risk factors in subjects with type 2 diabetes independently of weight loss , thus indicating the need for targeting fitness in these individuals , particularly in subjects who struggle to lose weight 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 The optimal exercise modality for reductions of abdominal obesity and risk factors for type 2 diabetes in youth is unknown . We examined the effects of aerobic exercise ( AE ) versus resistance exercise ( RE ) without caloric restriction on abdominal adiposity , ectopic fat , and insulin sensitivity and secretion in youth . Forty-five obese adolescent boys were r and omly assigned to one of three 3-month interventions : AE , RE , or a nonexercising control . Abdominal fat was assessed by magnetic resonance imaging , and intrahepatic lipid and intramyocellular lipid were assessed by proton magnetic resonance spectroscopy . Insulin sensitivity and secretion were evaluated by a 3-h hyperinsulinemic-euglycemic clamp and a 2-h hyperglycemic clamp . Both AE and RE prevented the significant weight gain that was observed in controls . Compared with controls , significant reductions in total and visceral fat and intrahepatic lipid were observed in both exercise groups . Compared with controls , a significant improvement in insulin sensitivity ( 27 % ) was observed in the RE group . Collapsed across groups , changes in visceral fat were associated with changes in intrahepatic lipid ( r = 0.72 ) and insulin sensitivity ( r = −0.47 ) . Both AE and RE alone are effective for reducing abdominal fat and intrahepatic lipid in obese adolescent boys . RE but not AE is also associated with significant improvements in insulin sensitivity 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 Nonalcoholic fatty liver disease ( NAFLD ) and its association with insulin resistance are increasingly recognized as major health burdens . The main objectives of this study were to assess the relation between liver lipid content and serum lipids , markers of liver function and inflammation in healthy overweight subjects , and to determine whether caloric restriction ( CR ) ( which improves insulin resistance ) reduces liver lipids in association with these same measures . METHODS AND PROCEDURES Forty-six white and black overweight men and women ( BMI = 24.7 - 31.3 kg/m(2 ) ) were r and omized to " control ( CO ) " = 100 % energy requirements ; " CR " = 25 % ; " caloric restriction and increased structured exercise (CR+EX)"= 12.5 % CR + 12.5 % increase in energy expenditure through exercise ; or " low-calorie diet ( LCD ) " = 15 % weight loss by liquid diet followed by weight-maintenance , for 6 months . Liver lipid content was assessed by magnetic resonance spectroscopy ( MRS ) and computed tomography ( CT ) . Lipid concentrations , markers of liver function ( alanine aminotransferase ( ALT ) , alkaline phosphatase ( ALK ) ) , and whole-body inflammation ( tumor necrosis factor-alpha ( TNF-alpha ) , interleukin-6 ( IL-6 ) , high-sensitivity C-reactive protein ( hsCRP ) ) were measured in fasting blood . RESULTS At baseline , increased liver lipid content ( by MRS ) correlated ( P < 0.05 ) with elevated fasting triglyceride ( r = 0.52 ) , ALT ( r = 0.42 ) , and hsCRP ( r = 0.33 ) concentrations after adjusting for sex , race , and alcohol consumption . With CR , liver lipid content was significantly lowered by CR , CR+EX , and LCD ( detected by MRS only ) . The reduction in liver lipid content , however , was not significantly correlated with the reduction in triglycerides ( r = 0.26 ; P = 0.11 ) or with the changes in ALT , high-density lipoprotein (HDL)-cholesterol , or markers of whole-body inflammation . DISCUSSION CR may be beneficial for reducing liver lipid and lowering triglycerides in overweight subjects without known NAFLD Background : To investigate the effects of varied therapeutic lifestyle programs on patients with ultrasound‐diagnosed nonalcoholic fatty liver disease ( NAFLD ) . Methods : A prospect i ve , case‐controlled study was conducted . A total of 54 subjects with NAFLD were subdivided into 3 groups : ( 1 ) diet plus exercise group ( DPE group , n = 16 ) ; ( 2 ) exercise group ( E group , n = 23 ) ; and ( 3 ) control group ( C group , n = 15 ) . The DPE group received a low‐calorie balanced diet and regular high‐intensity stationary bicycle exercise program for 10 weeks , while the E group received the same exercise protocol as the DPE group but without any changes in diet . Anthropometric indices , biochemical data , physical fitness data and liver ultrasound findings were recorded . A generalized estimating equation method was used to determine the differences among groups . Results : Compared with the C group , the DPE group demonstrated significant improvements in anthropometric indices , total cholesterol , insulin sensitivity , liver biochemistry , ultrasound finding and physical fitness , while the E group showed significant improvements in anthropometric indices , insulin sensitivity status , ultrasound finding and physical fitness but not liver biochemistry . Compared with the E group , the DPE group showed greater reduction in anthropometric indices ( body mass index , body weight , abdominal circumference , hip circumference ) , total cholesterol , alanine aminotransferase , and γ‐glutamyltransferase . Conclusion : Our data suggest that both 10‐week diet‐plus‐exercise and exercise‐only therapeutic lifestyle programs are effective for improving anthropometric indices , insulin sensitivity , ultrasound findings and physical fitness in ultrasound‐diagnosed NAFLD patients . However , the range of improvement in patients on the diet‐plus‐exercise program is more obvious than that in patients on the exercise‐only program . Moreover , the diet‐plus‐exercise program result ed in significant improvement in liver biochemistry , but the exercise‐only program did not . In summary , diet plus exercise is more efficacious than exercise alone in the lifestyle modification treatment of NAFLD BACKGROUND & AIMS Aerobic exercise reduces liver fat and visceral adipose tissue ( VAT ) . However , there is limited data from r and omized trials to inform exercise programming recommendations . This study examined the efficacy of commonly prescribed exercise doses for reducing liver fat and VAT using a r and omized placebo-controlled design . METHODS Inactive and overweight/obese adults received 8 weeks of either ; i ) low to moderate intensity , high volume aerobic exercise ( LO : HI , 50 % VO 2peak , 60 min , 4d/week ) ; ii ) high intensity , low volume aerobic exercise ( HI : LO , 70 % VO 2peak , 45 min , 3d/week ) ; iii ) low to moderate intensity , low volume aerobic exercise ( LO : LO , 50 % VO 2peak , 45 min , 3d/week ) ; or iv ) placebo ( PLA ) . Liver fat ( spectroscopy ) and VAT ( magnetic resonance imaging ) were measured before and after intervention . RESULTS Forty-seven of the 48 ( n = 12 in each group ) participants completed the trial . There were no serious adverse events . There was a significant change in group × time interaction in liver fat , which reduced in HI : LO by 2.38 ± 0.73 % , in LO : HI by 2.62 ± 1.00 % , and in LO : LO by 0.84 ± 0.47 % but not in PLA ( increase of 1.10 ± 0.62 % ) ( p = 0.04 ) . There was a significant reduction in VAT in HI : LO ( -258.38 ± 87.78 cm(3 ) ) , in LO : HI ( -386.80 ± 119.5 cm(3 ) ) , and in LO : LO ( -212.96 ± 105.54 cm(3 ) ) , but not in PLA ( 92.64 ± 83.46 cm(3 ) ) ( p = 0.03 ) . There were no significant differences between the dose or intensity of the exercise regimen and reductions in liver fat or VAT ( p > 0.05 ) . CONCLUSION The study found no difference in efficacy of liver fat reduction by either aerobic exercise dose or intensity . All of the aerobic exercise regimens employed reduced liver fat and VAT by a small amount without clinical ly significant weight loss OBJECTIVE Weight loss through lifestyle changes is recommended for nonalcoholic fatty liver disease ( NAFLD ) . However , its efficacy in patients with type 2 diabetes is unproven . RESEARCH DESIGN AND METHODS Look AHEAD ( Action for Health in Diabetes ) is a 16-center clinical trial with 5,145 overweight or obese adults with type 2 diabetes , who were r and omly assigned to an intensive lifestyle intervention ( ILI ) to induce a minimum weight loss of 7 % or a control group who received diabetes support and education ( DSE ) . In the Fatty Liver Ancillary Study , 96 participants completed proton magnetic resonance spectroscopy to quantify hepatic steatosis and tests to exclude other causes of liver disease at baseline and 12 months . We defined steatosis > 5.5 % as NAFLD . RESULTS Participants were 49 % women and 68 % white . The mean age was 61 years , mean BMI was 35 kg/m2 , mean steatosis was 8.0 % , and mean aspartate aminotransferase ( AST ) and alanine aminotransferase ( ALT ) were 20.5 and 24.2 units/l , respectively . After 12 months , participants assigned to ILI ( n = 46 ) lost more weight ( −8.5 vs. −0.05 % ; P < 0.01 ) than those assigned to DSE and had a greater decline in steatosis ( −50.8 vs. −22.8 % ; P = 0.04 ) and in A1C ( −0.7 vs. −0.2 % ; P = 0.04 ) . There were no significant 12-month changes in AST or ALT levels . At 12 months , 26 % of DSE participants and 3 % ( 1 of 31 ) of ILI participants without NAFLD at baseline developed NAFLD ( P < 0.05 ) . CONCLUSIONS A 12-month intensive lifestyle intervention in patients with type 2 diabetes reduces steatosis and incident NAFLD OBJECTIVE To evaluate the effects of qualitative dietary changes and the interaction with aerobic exercise training on liver fat content independent of weight loss in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS With use of a factorial 2 × 2 r and omized parallel-group design , 37 men and 8 women , aged 35–70 years , with type 2 diabetes in satisfactory blood glucose control on diet or diet plus metformin treatment were assigned to one of the following groups for an 8-week period : 1 ) high-carbohydrate/high-fiber/low – glycemic index diet ( CHO/fiber group ) , 2 ) high-MUFA diet ( MUFA group ) , 3 ) high-carbohydrate/high-fiber/low – glycemic index diet plus physical activity program ( CHO/fiber+Ex group ) , and 4 ) high-MUFA diet plus physical activity program ( MUFA+Ex group ) . Before and after intervention , hepatic fat content was measured by 1H NMR . RESULTS Dietary compliance was optimal and body weight remained stable in all groups . Liver fat content decreased more in MUFA ( −29 % ) and MUFA+Ex ( −25 % ) groups than in CHO/fiber ( −4 % ) and CHO/fiber+Ex groups ( −6 % ) . Two-way repeated- measures ANOVA , including baseline values as covariate , showed a significant effect on liver fat content for diet ( P = 0.006 ) , with no effects for exercise training ( P = 0.789 ) or diet-exercise interaction ( P = 0.712 ) . CONCLUSIONS An isocaloric diet enriched in MUFA compared with a diet higher in carbohydrate and fiber was associated with a clinical ly relevant reduction of hepatic fat content in type 2 diabetic patients independent of an aerobic training program and should be considered for the nutritional management of hepatic steatosis in people with type 2 diabetes ABSTRACT Objectives Postmenopausal women are particularly inclined to an increased risk of developing non-alcoholic hepatic steatosis . The purpose of this study was to investigate whether adding isoflavone supplementation to exercise training could reduce the risk . Methods In a 6-month , double-blind , r and omized , controlled trial , 54 healthy overweight-to-obese ( body mass index 28–40 kg/m2 ) postmenopausal women were r and omly assigned to one of the following groups : ( 1 ) exercise and isoflavones ( Ex-Iso ; n = 26 ) , ( 2 ) exercise and placebo ( Ex-Pla ; n = 28 ) . Exercise training consisted of three weekly sessions of mixed training . We examined the plasma level of specific hepatic enzymes ( alanine aminotransferase , aspartate aminotransferase , γ-glutamyltransferase , and alkaline phosphatase ) as a reflection of fatty liver along with the calculation of the fatty liver index . All measures were obtained at baseline and after the 6-month intervention . Results Following the intervention , a lower fatty liver index ( p < 0.01 ; 29 % in Ex-Iso , 18 % in Ex-Pla ) and plasma γ-glutamyltransferase ( p < 0.01 ; 22 % in Ex-Iso , 16 % in Ex-Pla ) were observed in both groups , with a higher reduction in the Ex-Iso group . On the other h and , for all other hepatic enzymes , there was no change . Conclusions Our results show that exercise training appears to bring favorable changes in the plasma level of hepatic enzymes , possibly due to the lowering of liver fat content . While postmenopausal women can benefit from this intervention to decrease the risk of developing non-alcoholic hepatic steatosis , it seems that the addition of isoflavones to exercise training provides some additional effects to those provided by exercise alone INTRODUCTION Nonalcoholic fatty liver disease ( NAFLD ) is characterized by high intrahepatic triglyceride level . It is associated with an increased prevalence of cardiovascular disease , independently of underlying cardiometabolic risk factors . Metformin is used as a pharmacological treatment ; the adherence is low because of the presence of adverse effects . Aerobic exercise could be an alternative therapy , but its effectiveness compared with metformin has not been established in the treatment of NAFLD . The aim of this study was to establish the effectiveness of aerobic exercise and its influence in reducing cardiovascular risk in overweight or obese women with NAFLD . MATERIAL AND METHODS Sedentary women 25 - 60 years old with body mass index ( BMI ) > 24.9 kg/m2 and liver fat content < 50 HU , were r and omly divided into two parallel groups : exercise group ( EG ) or metformin group ( MG ) . The EG performed an aerobic exercise program of 60 min/5 days/ week at 60 - 85 % of heart rate reserve ; the MG took 1 g/day of metformin each morning . The duration of the intervention was 12 weeks . The liver fat content , metabolic and cardiorespiratory- fitness parameters were evaluated at the beginning and end of the program . The study complied with the Helsinki ethics codes for human research . RESULTS The study included a sample of 16 women , with 8 per group . The treatments modified the liver fat content by 14.6 % ( CI95 % 0.92 , 28.36 ) and 10.37 % ( CI95 % -1.74 , 22.48 ) for the EG and MG , respectively . In the EG , the insulin levels and HOMA-IR decreased ( P < 0.05 ) , and the cardiovascular fitness improved . CONCLUSIONS An aerobic exercise program of 12 weeks with a volume training of 300 min/week and a moderate to vigorous intensity ( 60 - 85 % VO2peak ) modified the liver fat content and improved cardiovascular risk factors during the intervention . Exercise contributed to a holistic approach by modifying a number of the components of metabolic syndrome , cardiorespiratory-fitness , and cardiovascular risk OBJECTIVE The objective of the study was to examine the effects of an exercise/diet lifestyle intervention on free fatty acid (FFA)-induced hepatic insulin resistance in obese humans . RESEARCH DESIGN AND METHODS Obese men and women ( n = 23 ) with impaired glucose tolerance were r and omly assigned to either exercise training with a eucaloric ( EU ; approximately 1800 kcal ; n = 11 ) or hypocaloric ( HYPO ; approximately 1300 kcal ; n = 12 ) diet for 12 wk . Hepatic glucose production ( HGP ; milligrams per kilogram fat-free mass(-1 ) per minute(-1 ) ) and hepatic insulin resistance were determined using a two-stage sequential hyperinsulinemic ( 40 mU/m(2 ) . min(-1 ) ) euglycemic ( 5.0 mm ) clamp with [3-(3)H]glucose . Measures were obtained at basal , during insulin infusion ( INS ; 120 min ) , and insulin plus intralipid/heparin infusion ( INS/FFA ; 300 min ) . RESULTS At baseline , basal HGP was similar between groups ; hyperinsulinemia alone did not completely suppress HGP , whereas INS/FFA exhibited less suppression than INS ( EU , 4.6 + /- 0.8 , 2.0 + /- 0.5 , and 2.6 + /- 0.4 ; HYPO , 3.8 + /- 0.5 , 1.2 + /- 0.3 , and 2.3 + /- 0.4 , respectively ) . After the intervention the HYPO group lost more body weight ( P < 0.05 ) and fat mass ( P < 0.05 ) . However , both lifestyle interventions reduced hepatic insulin resistance during basal ( P = 0.005 ) and INS ( P = 0.001 ) conditions , and insulin-mediated suppression of HGP during INS was equally improved in both groups ( EU : -42 + /- 22 % ; HYPO : -50 + /- 20 % , before vs. after , P = 0.02 ) . In contrast , the ability of insulin to overcome FFA-induced hepatic insulin resistance and HGP was improved only in the HYPO group ( EU : -15 + /- 24 % vs. HYPO : -58 + /- 19 % , P = 0.02 ) . CONCLUSIONS Both lifestyle interventions are effective in reducing hepatic insulin resistance under basal and hyperinsulinemic conditions . However , the reversal of FFA-induced hepatic insulin resistance is best achieved with a combined exercise/caloric-restriction intervention Objective To compare the effects of aerobic training ( AT ) with aerobic plus resistance training ( AT+RT ) in nonalcoholic fatty liver disease ( NAFLD ) obese adolescents . Design Long-term interdisciplinary weight-loss therapy ( 1 year of clinical , nutritional , psychological , and exercise-related intervention ) . Participants Fifty-eight postpubertal obese adolescents were r and omized to AT or AT+RT according to NAFLD diagnosis . Adipokine and neuropeptide concentrations were measured by enzyme-linked immunosorbent assay , visceral fat by ultrasound , and body composition by plethysmography . Results The NAFLD group that followed the AT+RT protocol presented lower insulin , homeostasis model assessment -insulin resistance ( HOMA-IR ) , and alanine transaminase ( ALT ) values after intervention compared with AT . It was verified that there was a higher magnitude of change in the subcutaneous fat , glycemia , total cholesterol ( TC ) , low-density lipoprotein-cholesterol , ALT , and adiponectin in response to AT+RT than in the control group ( AT ) . All patients who underwent the AT+RT exhibited significantly higher adiponectin , leptin , and & Dgr;adiponectin and lower melanin-concentrating hormone ( MCH ) concentrations after therapy compared with the AT group . In the simple linear regression analysis , changes in glycemia , insulin , and HOMA-IR were independent predictors of significant improvement in adiponectin concentration . Indeed , & Dgr;AST ( aspartate transaminase ) and & Dgr;GGT ( & ggr;-glutamyl transpeptidase ) were independent predictors of & Dgr;ALT , while & Dgr;fat mass and & Dgr;AgRP ( agouti-related protein ) were independent predictors of & Dgr;MCH . Although the number of patients was limited , we showed for the first time the positive effects of AT+RT protocol in a long-term interdisciplinary therapy to improve inflammatory biomarkers and to reduce orexigenic neuropeptide concentrations in NAFLD obese adolescents . Conclusion The long-term interdisciplinary therapy with AT+RT protocol was more effective in significantly improving noninvasive biomarkers of NAFLD that are associated with the highest risk of disease progression in the pediatric population The leading causes of mortality in nonalcoholic fatty liver disease ( NAFLD ) relate to cardiovascular disease ( CVD ) . The contribution of nitric oxide ( NO ) to endothelial function , a surrogate of CVD risk , is currently unknown in NAFLD . We hypothesize that NO-mediated cutaneous microvessel function would be impaired in NAFLD compared with controls and that exercise would enhance microvessel function compared with conventional care . Thirteen NAFLD patients ( aged 50 ± 3 yr , BMI 31 ± 1 kg/m² ) and seven controls ( 48 ± 4 yr , 30 ± 2 kg/m² ) were studied . NAFLD patients were r and omized to either 16 wk of exercise or conventional care . Cutaneous microvessel function was examined using laser Doppler flowmetry combined with intradermal microdialysis of N(G)-monomethyl-l-arginine to assay the NO dilator response to local forearm heating . Magnetic resonance imaging and spectroscopy quantified abdominal and liver fat , respectively , and cardiorespiratory fitness was assessed . Differences in NO contribution to cutaneous blood flow between NAFLD and control individuals and between interventions were analyzed using general linear modeling . NO contribution to cutaneous blood flow was similar between NAFLD and controls ( P = 0.47 ) . Cardiorespiratory fitness was greater following exercise training compared with conventional care . NO contribution to cutaneous blood flow in response to heating at 42 ° C was 20.4 % CVCmax ( 95 % CI = 4.4 , 36.4 ) greater following exercise training compared with conventional care ( P = 0.02 ) . Exercise training improves cutaneous microvascular NO function in NAFLD patients . The benefit of exercise training compared with conventional care strongly supports a role for exercise in the prevention of CVD in NAFLD UNLABELLED Although lifestyle interventions are considered the first-line therapy for nonalcoholic fatty liver disease ( NAFLD ) , which is extremely common in people with type 2 diabetes , no intervention studies have compared the effects of aerobic ( AER ) or resistance ( RES ) training on hepatic fat content in type 2 diabetic subjects with NAFLD . In this r and omized controlled trial , we compared the 4-month effects of either AER or RES training on insulin sensitivity ( by hyperinsulinemic euglycemic clamp ) , body composition ( by dual-energy X-ray absorptiometry ) , as well as hepatic fat content and visceral ( VAT ) , superficial ( SSAT ) , and deep ( DSAT ) subcutaneous abdominal adipose tissue ( all quantified by an in-opposed-phase magnetic resonance imaging technique ) in 31 sedentary adults with type 2 diabetes and NAFLD . After training , hepatic fat content was markedly reduced ( P < 0.001 ) , to a similar extent , in both the AER and the RES training groups ( mean relative reduction from baseline [ 95 % confidence interval ] -32.8 % [ -58.20 to -7.52 ] versus -25.9 % [ -50.92 to -0.94 ] , respectively ) . Additionally , hepatic steatosis ( defined as hepatic fat content > 5.56 % ) disappeared in about one-quarter of the patients in each intervention group ( 23.1 % in the AER group and 23.5 % in the RES group ) . Insulin sensitivity during euglycemic clamp was increased , whereas total body fat mass , VAT , SSAT , and hemoglobin A1c were reduced comparably in both intervention groups . CONCLUSION This is the first r and omized controlled study to demonstrate that resistance training and aerobic training are equally effective in reducing hepatic fat content among type 2 diabetic patients with NAFLD UNLABELLED Nonalcoholic fatty liver disease ( NAFLD ) and alterations in hepatic lipoprotein kinetics are common metabolic complications associated with obesity . Lifestyle modification involving diet-induced weight loss and regular exercise decreases intrahepatic triglyceride ( IHTG ) content and very low density lipoprotein ( VLDL ) triglyceride ( TG ) secretion rate . The aim of this study was to evaluate the weight loss-independent effect of following the physical activity guidelines recommended by the Department of Health and Human Services on IHTG content and VLDL kinetics in obese persons with NAFLD . Eighteen obese people ( body mass index [ BMI ] : 38.1 ± 4.6 kg/m(2 ) ) with NAFLD were r and omized to 16 weeks of exercise training ( 45%-55 % VO(2peak ) , 30 - 60 minutes × 5 days/week ; n = 12 ) or observation ( control ; n = 6 ) . Magnetic resonance spectroscopy and stable isotope tracer infusions in conjunction with compartmental modeling were used to evaluate IHTG content and hepatic VLDL-TG and apolipoprotein B-100 ( apoB-100 ) secretion rates . Exercise training result ed in a 10.3 % ± 4.6 % decrease in IHTG content ( P < 0.05 ) , but did not change total body weight ( 103.1 ± 4.2 kg before and 102.9 ± 4.2 kg after training ) or percent body fat ( 38.9 % ± 2.1 % before and 39.2 % ± 2.1 % after training ) . Exercise training did not change the hepatic VLDL-TG secretion rate ( 17.7 ± 3.9 μmol/min before and 16.8 ± 5.4 μmol/min after training ) or VLDL-apoB-100 secretion rate ( 1.5 ± 0.5 nmol/min before and 1.6 ± 0.6 nmol/min after training ) . CONCLUSION Following the Department of Health and Human Services recommended physical activity guidelines has small but beneficial effects on IHTG content , but does not improve hepatic lipoprotein kinetics in obese persons with NAFLD AIM To evaluate the effect of resistance training ( RT ) on non alcoholic liver disease ( NAFLD ) patients . METHODS A r and omized clinical trial enrolling NAFLD patients without secondary liver disease ( e.g. , without hepatitis B virus , hepatitis C virus or excessive alcohol consumption ) . Patients were r and omly allocated either to RT , three times weekly , for 3 mo or a control arm consisting of home stretching . The RT included leg press , chest press , seated rowing , latissimus pull down etc . with 8 - 12 repetitions , 3 sets for each exercise , for a total duration of 40 min . Hepatic ultrasound , fasting blood tests , anthropometrics and body composition by dual energy X-ray absorptiometry were assessed . At baseline and follow-up , patients filled out a detailed semi-quantitative food frequency question naire reporting their habitual nutritional intake . Steatosis was quantified by the hepatorenal-ultrasound index ( HRI ) representing the ratio between the brightness level of the liver and the right kidney . The HRI has been previously demonstrated to be highly reproducible and was vali date d against liver biopsy and proton magnetic resonance spectroscopy . RESULTS Eighty two patients with primary NAFLD were r and omized to receive 3 mo of either RT or stretching . After dropout or exclusion from analysis because of protocol violation ( weight change > 3 kg ) , thirty three patients in the RT arm and 31 in the stretching arm completed the study per protocol . All baseline characteristics were similar for the two treatment groups with respect to demographics , anthropometrics and body composition , blood tests and liver steatosis on imaging . HRI score was reduced significantly in the RT arm as compared to the stretching arm ( -0.25 ± 0.37 vs -0.05 ± 0.28 , P = 0.017 ) . The RT arm had a significantly higher reduction in total , trunk and and roid fat with increase in lean body mass . There was no correlation between the reduction in HRI in the RT arm and weight change during the study , but it was positively correlated with the change in trunk fat ( r = 0.37 , P = 0.048 ) . The RT arm had a significant reduction in serum ferritin and total cholesterol . There was no significant difference between arms in dietary changes and these did not correlate with HRI change . CONCLUSION Three months RT improves hepatic fat content accompanied by favorable changes in body composition and ferritin . RT may serve as a complement to treatment of NAFLD Both obesity and aging increase intrahepatic fat ( IHF ) content , which leads to nonalcoholic fatty liver disease ( NAFLD ) and metabolic abnormalities such as insulin resistance . We evaluated the effects of diet and diet in conjunction with exercise on IHF content and associated metabolic abnormalities in obese older adults . Eighteen obese ( BMI > or=30 kg/m(2 ) ) older ( > or=65 years old ) adults completed a 6-month clinical trial . Participants were r and omized to diet ( D group ; n = 9 ) or diet + exercise ( D+E group ; n = 9 ) . Primary outcome was IHF quantified by magnetic resonance spectroscopy ( MRS ) . Secondary outcomes included insulin sensitivity ( assessed by oral glucose tolerance ) , body composition ( assessed by dual-energy X-ray absorptiometry ) , physical function ( VO(2 peak ) and strength ) , glucose , lipids , and blood pressure ( BP ) . Body weight ( D : -9 + /- 1 % , D+E : -10 + /- 2 % , both P < 0.05 ) and fat mass ( D : -13 + /- 3 % , D+E -16 + /- 3 % , both P < 0.05 ) decreased in both groups but there was no difference between groups . IHF decreased to a similar extent in both groups ( D : -46 + /- 11 % , D+E : -45 + /- 8 % , both P < 0.05 ) , which was accompanied by comparable improvements in insulin sensitivity ( D : 66 + /- 25 % , D+E : 68 + /- 28 % , both P < 0.05 ) . The relative decreases in IHF correlated directly with relative increases in insulin sensitivity index ( ISI ) ( r = -0.52 ; P < 0.05 ) . Improvements in VO(2 peak ) , strength , plasma triglyceride ( TG ) , and low-density lipoprotein-cholesterol concentration , and diastolic BP occurred in the D+E group ( all P < 0.05 ) but not in the D group . Diet with or without exercise results in significant decreases in IHF content accompanied by considerable improvements in insulin sensitivity in obese older adults . The addition of exercise to diet therapy improves physical function and other obesity- and aging-related metabolic abnormalities While the benefits of exercise are clear , many unresolved issues surround the optimal exercise prescription . Many organizations recommend aerobic training ( AT ) and resistance training ( RT ) , yet few studies have compared their effects alone or in combination . The purpose of this study , part of Studies Targeting Risk Reduction Interventions Through Defined Exercise-Aerobic Training and /or Resistance Training ( STRRIDE/AT/RT ) , was to compare the effects of AT , RT , and the full combination ( AT/RT ) on central ectopic fat , liver enzymes , and fasting insulin resistance [ homeostatic model assessment ( HOMA ) ] . In a r and omized trial , 249 subjects [ 18 - 70 yr old , overweight , sedentary , with moderate dyslipidemia ( LDL cholesterol 130 - 190 mg/dl or HDL cholesterol ≤ 40 mg/dl for men or ≤ 45 mg/dl for women ) ] performed an initial 4-mo run-in period . Of these , 196 finished the run-in and were r and omized into one of the following 8-mo exercise-training groups : 1 ) RT , which comprised 3 days/wk , 8 exercises , 3 sets/exercise , 8 - 12 repetitions/set , 2 ) AT , which was equivalent to ∼19.2 km/wk ( 12 miles/wk ) at 75 % peak O(2 ) uptake , and 3 ) full AT + full RT ( AT/RT ) , with 155 subjects completing the intervention . The primary outcome variables were as follows : visceral and liver fat via CT , plasma liver enzymes , and HOMA . AT led to significant reductions in liver fat , visceral fat , alanine aminotransferase , HOMA , and total and subcutaneous abdominal fat ( all P < 0.05 ) . RT result ed in a decrease in subcutaneous abdominal fat ( P < 0.05 ) but did not significantly improve the other variables . AT was more effective than RT at improving visceral fat , liver-to-spleen ratio , and total abdominal fat ( all P < 0.05 ) and trended toward a greater reduction in liver fat score ( P < 0.10 ) . The effects of AT/RT were statistically indistinguishable from the effects of AT . These data show that , for overweight and obese individuals who want to reduce measures of visceral fat and fatty liver infiltration and improve HOMA and alanine aminotransferase , a moderate amount of aerobic exercise is the most time-efficient and effective exercise mode UNLABELLED Nonalcoholic steatohepatitis ( NASH ) is a chronic progressive liver disease that is strongly associated with obesity . Currently , there is no approved therapy for NASH . Weight reduction is typically recommended , but efficacy data are lacking . We performed a r and omized controlled trial to examine the effects of lifestyle intervention using a combination of diet , exercise , and behavior modification , with a goal of 7 % to 10 % weight reduction , on clinical parameters of NASH . The primary outcome measure was the change in NASH histological activity score ( NAS ) after 48 weeks of intervention . Thirty-one overweight or obese individuals ( body mass index [ BMI ] , 25 - 40 kg/m(2 ) ) with biopsy-proven NASH were r and omized in a 2:1 ratio to receive intensive lifestyle intervention ( LS ) or structured education ( control ) . After 48 weeks of intervention , participants assigned to LS lost an average of 9.3 % of their weight versus 0.2 % in the control group ( P = 0.003 ) . A higher proportion of participants in the LS group had a reduction of NAS of at least 3 points or had posttreatment NAS of 2 or less as compared with the control group ( 72 % versus 30 % , P = 0.03 ) . NAS improved significantly in the LS group ( from 4.4 to 2.0 ) in comparison with the control group ( from 4.9 to 3.5 ) ( P = 0.05 ) . Percent weight reduction correlated significantly with improvement in NAS ( r = 0.497 , P = 0.007 ) . Participants who achieved the study weight loss goal ( > or=7 % ) , compared with those who lost less than 7 % , had significant improvements in steatosis ( -1.36 versus -0.41 , P < 0.001 ) , lobular inflammation ( -0.82 versus -0.24 , P = 0.03 ) , ballooning injury ( -1.27 versus -0.53 , P = 0.03 ) and NAS ( -3.45 versus -1.18 , P < 0.001 ) . CONCLUSION Weight reduction achieved through lifestyle intervention leads to improvements in liver histology in NASH |
12,398 | 31,560,864 | Overall , animal research has shown very promising results in potentiating cognition , both physiologically and behaviourally .
Taking into account measurements of important inflammatory and antioxidant biomarkers , optimal dosages of curcumin , food interactions , and duration of treatment would increase our underst and ing on curcumin 's promising effects on cognition . | Alzheimer 's disease constitutes a growing cause of cognitive impairment in aging population .
Given that current treatments do not produce the desired therapeutic effects , the need for finding alternative biological and pharmacological approaches is critical .
Accumulating evidence suggests inflammatory and oxidative stress responses as potential causal factors of cognitive impairments in Alzheimer 's disease and healthy aging .
Curcumin has received increased interest due to its unique molecular structure that targets inflammatory and antioxidant pathways as well as ( directly ) amyloid aggregation ; one of the major hallmarks of Alzheimer 's disease .
Therefore , this review summarizes pre clinical and clinical findings on curcumin as a potential cognitive enhancer in Alzheimer 's disease and normal aging . | Introduction Curcumin is a polyphenolic compound derived from the plant Curcuma Long Lin that has been demonstrated to have antioxidant and anti-inflammatory effects as well as effects on reducing beta-amyloid aggregation . It reduces pathology in transgenic models of Alzheimer 's disease ( AD ) and is a promising c and i date for treating human AD . The purpose of the current study is to generate tolerability and preliminary clinical and biomarker efficacy data on curcumin in persons with AD . Methods We performed a 24-week r and omized , double blind , placebo-controlled study of Curcumin C3 Complex ® with an open-label extension to 48 weeks . Thirty-six persons with mild-to-moderate AD were r and omized to receive placebo , 2 grams/day , or 4 grams/day of oral curcumin for 24 weeks . For weeks 24 through 48 , subjects that were receiving curcumin continued with the same dose , while subjects previously receiving placebo were r and omized in a 1:1 ratio to 2 grams/day or 4 grams/day . The primary outcome measures were incidence of adverse events , changes in clinical laboratory tests and the Alzheimer 's Disease Assessment Scale - Cognitive Subscale ( ADAS-Cog ) at 24 weeks in those completing the study . Secondary outcome measures included the Neuropsychiatric Inventory ( NPI ) , the Alzheimer 's Disease Cooperative Study - Activities of Daily Living ( ADCS-ADL ) scale , levels of Aβ1 - 40 and Aβ1 - 42 in plasma and levels of Aβ1 - 42 , t-tau , p-tau181 and F2-isoprostanes in cerebrospinal fluid . Plasma levels of curcumin and its metabolites up to four hours after drug administration were also measured . Results Mean age of completers ( n = 30 ) was 73.5 years and mean Mini-Mental Status Examination ( MMSE ) score was 22.5 . One subject withdrew in the placebo ( 8 % , worsened memory ) and 5/24 subjects withdrew in the curcumin group ( 21 % , 3 due to gastrointestinal symptoms ) . Curcumin C3 Complex ® was associated with lowered hematocrit and increased glucose levels that were clinical ly insignificant . There were no differences between treatment groups in clinical or biomarker efficacy measures . The levels of native curcumin measured in plasma were low ( 7.32 ng/mL ) . Conclusions Curcumin was generally well-tolerated although three subjects on curcumin withdrew due to gastrointestinal symptoms . We were unable to demonstrate clinical or biochemical evidence of efficacy of Curcumin C3 Complex ® in AD in this 24-week placebo-controlled trial although preliminary data suggest limited bioavailability of this compound . Trial registration Clinical Trials.gov Identifier : NCT00099710 OBJECTIVE Because curcumin 's anti-inflammatory properties may protect the brain from neurodegeneration , we studied its effect on memory in non-demented adults and explored its impact on brain amyloid and tau accumulation using 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile positron emission tomography ( FDDNP-PET ) . METHODS Forty subjects ( age 51 - 84 years ) were r and omized to a bioavailable form of curcumin ( Theracurmin ® containing 90 mg of curcumin twice daily [ N = 21 ] ) or placebo ( N = 19 ) for 18 months . Primary outcomes were verbal ( Buschke Selective Reminding Test [ SRT ] ) and visual ( Brief Visual Memory Test-Revised [ BVMT-R ] ) memory , and attention ( Trail Making A ) was a secondary outcome . FDDNP-PET signals ( 15 curcumin , 15 placebo ) were determined in amygdala , hypothalamus , medial and lateral temporal , posterior cingulate , parietal , frontal , and motor ( reference ) regions . Mixed effects general linear models controlling for age and education , and effect sizes ( ES ; Cohen 's d ) were estimated . RESULTS SRT Consistent Long-Term Retrieval improved with curcumin ( ES = 0.63 , p = 0.002 ) but not with placebo ( ES = 0.06 , p = 0.8 ; between-group : ES = 0.68 , p = 0.05 ) . Curcumin also improved SRT Total ( ES = 0.53 , p = 0.002 ) , visual memory ( BVMT-R Recall : ES = 0.50 , p = 0.01 ; BVMT-R Delay : ES = 0.51 , p = 0.006 ) , and attention ( ES = 0.96 , p < 0.0001 ) compared with placebo ( ES = 0.28 , p = 0.1 ; between-group : ES = 0.67 , p = 0.04 ) . FDDNP binding decreased significantly in the amygdala with curcumin ( ES = -0.41 , p = 0.04 ) compared with placebo ( ES = 0.08 , p = 0.6 ; between-group : ES = 0.48 , p = 0.07 ) . In the hypothalamus , FDDNP binding did not change with curcumin ( ES = -0.30 , p = 0.2 ) , but increased with placebo ( ES = 0.26 , p = 0.05 ; between-group : ES = 0.55 , p = 0.02 ) . CONCLUSIONS Daily oral Theracurmin may lead to improved memory and attention in non-demented adults . The FDDNP-PET findings suggest that symptom benefits are associated with decreases in amyloid and tau accumulation in brain regions modulating mood and memory Curcumin therapy in animals has produced positive cognitive and behavioural outcomes ; results of human trials , however , have been inconsistent . In this study , we report the results of a 12-month , r and omised , placebo-controlled , double-blind study that investigated the ability of a curcumin formulation to prevent cognitive decline in a population of community-dwelling older adults . Individuals ( n 96 ) ingested either placebo or 1500 mg/d BiocurcumaxTM for 12 months . A battery of clinical and cognitive measures was administered at baseline and at the 6-month and 12-month follow-up assessment s. A significant time × treatment group interaction was observed for the Montreal Cognitive Assessment ( repeated- measures analysis ; time × treatment ; F=3·85 , P<0·05 ) . Subsequent analysis revealed that this association was driven by a decline in function of the placebo group at 6 months that was not observed in the curcumin treatment group . No differences were observed between the groups for all other clinical and cognitive measures . Our findings suggest that further longitudinal assessment is required to investigate changes in cognitive outcome measures , ideally in conjunction with biological markers of neurodegeneration Factors that modify onset of Alzheimer 's disease ( AD ) may be revealed by comparing environmental exposures in affected and unaffected members of discordant twin pairs or sibships . Among siblings at high risk of AD , sustained use of nonsteroidal anti-inflammatory drugs ( NSAIDs ) was associated with delayed onset and reduced risk of AD . After adjustment for use of NSAIDs , there was minimal effect on onset with reported history of any of three common illnesses ( arthritis , diabetes , or acid-peptic disease ) . However , independent of exposure to NSAIDs , onset was unexpectedly delayed in those reporting extended use of histamine H2 blocking drugs . R and omized clinical trials will be needed to affirm the utility of these drugs for prevention , but the present findings may have implication s for pathogenesis : because NSAIDs block the calcium-dependent postsynaptic cascade that induces excitotoxic cell death in NMDA-reactive neurons , and because histamine potentiates such events , excitotoxicity may deserve additional investigation in AD SCOPE Curcumin revealed various health-beneficial properties in numerous studies . However its bioavailability is low due to its limited intestinal uptake and rapid metabolism . The aim of our project was to develop novel curcumin formulations with improved oral bioavailability and to study their safety as well as potential sex-differences . METHODS AND RESULTS In this crossover study , healthy subjects ( 13 women , 10 men ) took , in r and om order , a single oral dose of 500 mg curcuminoids as native powder , micronized powder , or liquid micelles . Blood and urine sample s were collected for 24 h and total curcuminoids and safety parameters were quantified . Based on the area under the plasma concentration-time curve ( AUC ) , the micronized curcumin was 14- , 5- , and 9-fold and micellar curcumin 277- , 114- , and 185-fold better bioavailable than native curcumin in women , men , and all subjects , respectively . Thus , women absorbed curcumin more efficiently than men . All safety parameters remained within the reference ranges following the consumption of all formulations . CONCLUSION Both , the micronized powder and in particular the liquid micellar formulation of curcumin significantly improved its oral bioavailability without altering safety parameters and may thus be ideally suited to deliver curcumin in human intervention trials . The observed sex differences in curcumin absorption warrant further investigation The senescence-accelerated mouse prone 8 ( SAMP8 mice ) is known as a neurodegenerative model and may show age-related deficits of cognition . Curcumin , a major active component of spic turmeric , could increase the capacity of learning and memory in the aged rat . However , it is not known whether curcumin could improve cognitive deficits in SAMP8 mice . The present study was undertaken to evaluate the effect of curcumin on the learning and memory of SAMP8 mice and its possible mechanisms . Subjects were r and omly divided into four groups : SAMR1 mice , SAMP8 mice and two SAMP8 mice groups treated , intragastrically , with curcumin at the dose of 20 and 50mg/kg per day , respectively . After 25days , spatial memory , superoxide dismutase ( SOD ) activity , malondialdehyde ( MDA ) content , p-calcium/calmodulin-dependent kinase II ( p-CaMKII ) and p-N-methyl-d-aspartate receptor subunit 1 ( p-NMDAR1 ) expression in the hippocampus of mice were examined by using the Morris water maze , biochemical analysis , immunohistochemistry and Western blot . Compared with SAMR1 mice , SAMP8 mice had longer escape latency , higher MDA content , lower SOD activity in the hippocampus , and lower intensity of p-CaMKII in the stratum lucidum of hippocampal CA3 and p-NMDAR1 expression in the hippocampal membrane fraction . Both 20 and 50mg/kg curcumin administration significantly shortened the escape latencies and decreased the hippocampal MDA content in the SAMP8 mice . 50mg/kg curcumin administration significantly ameliorated the hippocampal SOD activity , and increased the intensity of p-CaMKII in the stratum lucidum of hippocampal CA3 and p-NMDAR1 expression in the hippocampal membrane fraction of the SAMP8 mice . The present study demonstrated that curcumin treatment could attenuate cognitive deficits of SAMP8 mice in a dose-dependent manner by decreasing the oxidative stress and improving the expression of p-CaMKII and p-NMDAR1 in the hippocampus . Thus treatment with curcumin may have a potential therapeutic agent for aging-related cognitive dysfunctions Background More and more pre clinical studies support the idea that curcumin , a plant-derived natural polyphenol , could be a promising anticancer drug . However , poor bioavailability has limited its efficacy in clinical trials , and plasma curcumin levels remain low despite patients taking gram doses of curcumin . Methods This study aim ed to evaluate the safety and pharmacokinetics of newly developed nanoparticle curcumin with increased water solubility ( named THERACURMIN ) . Six healthy human volunteers were recruited and received THERACURMIN at a single oral dose of 150 mg . After an interval of 2 weeks , the same subjects then received THERACURMIN at a single dose of 210 mg . Plasma curcumin levels were measured at 0 , 1 , 2 , 4 , 6 , and 24 h after THERACURMIN intake using high-performance liquid chromatography ( HPLC ) . Results One subject reported grade 1 diarrhea after intake of 150 mg THERACURMIN . No other toxicities were observed in this study . Cmax for THERACURMIN at 150 and 210 mg was 189 ± 48 and 275 ± 67 ng/ml ( mean ± SEM ) , respectively , and the area under the curve for 24 h was estimated to be 2,649 ± 350 and 3,649 ± 430 ng/ml × h ( mean ± SEM ) , respectively . The t1/2 was estimated to be 9.7 ± 2.1 h for 150 mg and 13.0 ± 3.3 h for 210 mg . Conclusion THERACURMIN can safely increase plasma curcumin levels in a dose-dependent manner at least up to 210 mg without saturating the absorption system . To the best of our knowledge , THERACURMIN is the first nanoparticle formulation of curcumin that demonstrates improved bioavailability in human subjects . We believe this compound could be a promising tool when testing the potential anticancer effects of curcumin in clinical trials Aging induced cognitive impairment has been well documented for many years and several antioxidant strategies have been developed against this impairment . Curcumin is the active component of curcuma longa and has shown antioxidant , antiinflamatory and neuroprotective properties . We hypothesized that curcumin would have an influence on cognitive functions in aged female rats . The purpose of the present study was to investigate the effects of curcumin supplementation on cognitive impairment evaluated by Morris water maze ( MWM ) as well as the oxidative stress induced by aging in female rats . Rats were r and omly divided into either control or curcumin-supplemented groups . Curcumin or vehicle ( corn oil ) were given once daily for a period of 12 days , beginning 7 days prior to and 5 days during the behavioral tests . Behavioral assessment was performed in MWM . At the end of the behavioral test , blood sample s and brain tissues were taken for the analysis of malondialdeyde ( MDA ) , protein carbonyl and glutathione levels . During the training session , curcumin supplementation decreased latency to reach to the platform and the total distance traveled . During the probe trial , curcumin supplementation increased the number of platform crossings . In addition to the behavioral testing , biochemical results showed that MDA levels decreased in brain tissue by curcumin supplementation . It may be concluded that , curcumin supplementation improves cognitive functions by decreasing the lipid peroxidation in brain tissue of aged female rats Background Curcumin is the major yellow pigment extracted from turmeric , a commonly-used spice in India and Southeast Asia that has broad anticarcinogenic and cancer chemopreventive potential . However , few systematic studies of curcumin 's pharmacology and toxicology in humans have been performed . Methods A dose escalation study was conducted to determine the maximum tolerated dose and safety of a single dose of st and ardized powder extract , uniformly milled curcumin ( C3Complex ™ , Sabinsa Corporation ) . Healthy volunteers were administered escalating doses from 500 to 12,000 mg . Results Seven of twenty-four subjects ( 30 % ) experienced only minimal toxicity that did not appear to be dose-related . No curcumin was detected in the serum of subjects administered 500 , 1,000 , 2,000 , 4,000 , 6,000 or 8,000 mg . Low levels of curcumin were detected in two subjects administered 10,000 or 12,000 mg . Conclusion The tolerance of curcumin in high single oral doses appears to be excellent . Given that achieving systemic bioavailability of curcumin or its metabolites may not be essential for colorectal cancer chemoprevention , these findings warrant further investigation for its utility as a long-term chemopreventive agent Article abstract -In a longitudinal study of 1,686 participants in the Baltimore Longitudinal Study of Aging , we examined whether the risk of Alzheimer 's disease ( AD ) was reduced among reported users of aspirin or other nonsteroidal anti-inflammatory drugs ( NSAIDs ) . In addition , we examined use of acetaminophen , a pain-relief medication with little or no anti-inflammatory activity , to assess the specificity of the association between AD risk and self-reported medications . Information on use of medications was collected during each biennial examination between 1980 and 1995 . The relative risk ( RR ) for AD decreased with increasing duration of NSAID use . Among those with 2 or more years of reported NSAID use , the RR was 0.40 ( 95 % confidence interval [ CI ] : 0.19 - 0.84 ) compared with 0.65 ( 95 % CI : 0.33 - 1.29 ) for those with less than 2 years of NSAID use . The overall RR for AD among aspirin users was 0.74 ( 95 % CI : 0.46 - 1.18 ) , and no trend of decreasing risk of AD was observed with increasing duration of aspirin use . No association was found between AD risk and use of acetaminophen ( RR = 1.35 ; 95 % CI : 0.79 - 2.30 ) , and there was no trend of decreasing risk with increasing duration of use . These findings are consistent with evidence from cross-sectional studies indicating protection against AD risk among NSAID users and with evidence suggesting that one stage of the pathophysiology leading to AD is characterized by an inflammatory process . NEUROLOGY 1997;48 : 626 - Curcumin possesses many properties which may prevent or ameliorate pathological processes underlying age-related cognitive decline , dementia or mood disorders . These benefits in pre clinical studies have not been established in humans . This r and omized , double-blind , placebo-controlled trial examined the acute ( 1 and 3 h after a single dose ) , chronic ( 4 weeks ) and acute-on-chronic ( 1 and 3 h after single dose following chronic treatment ) effects of solid lipid curcumin formulation ( 400 mg as Longvida ® ) on cognitive function , mood and blood biomarkers in 60 healthy adults aged 60–85 . One hour after administration curcumin significantly improved performance on sustained attention and working memory tasks , compared with placebo . Working memory and mood ( general fatigue and change in state calmness , contentedness and fatigue induced by psychological stress ) were significantly better following chronic treatment . A significant acute-on-chronic treatment effect on alertness and contentedness was also observed . Curcumin was associated with significantly reduced total and LDL cholesterol and had no effect on hematological safety measures . To our knowledge this is the first study to examine the effects of curcumin on cognition and mood in a healthy older population or to examine any acute behavioral effects in humans . Results highlight the need for further investigation of the potential psychological and cognitive benefits of curcumin in an older population BACKGROUND Proton magnetic resonance spectroscopic imaging ( 1H-MRSI ) studies have reported reductions of N-acetyl aspartate ( NAA ) , a marker of neuronal integrity , in the hippocampal region ( HIPPO ) and dorsolateral prefrontal cortex ( DLPFC ) of pharmacologically treated patients with schizophrenia . The purpose of the present study was twofold : to exclude drug treatment as a source of the previous findings and to examine NAA relative concentrations in a unique sample of chronically untreated patients . METHODS We studied 12 medication-free patients , 5 of whom were " drug naive " and symptomatic for a mean of 12 years , and 12 control subjects . Ratios of areas under the metabolite peaks of the proton spectra were determined [ i.e. , NAA/creatine ( CRE ) , NAA/choline ( CHO ) , CHO/CRE ] for multiple cortical and subcortical regions . Hippocampal formation and frontal lobe volumes were also measured to test for correlations with 1H-MRSI data . RESULTS Significant reductions of NAA/CRE and NAA/CHO were found bilaterally in HIPPO and DLPFC . There were no significant changes in CHO/CRE or in NAA ratios in any other area sample d. No significant correlation was found between metabolite ratios , length of illness , and volumes of the hippocampal region and frontal lobe . Mean ratios and effect sizes were not different in chronically ill but still medication-naive patients in comparison with subacute patients and previously studied chronic patients receiving medications . CONCLUSIONS Bilateral reductions of NAA ratios in HIPPO and DLPFC are reliable findings . The findings implicate a relatively localized pattern of neurochemical pathology that does not appear to change with prolonged illness whether medicated or unmedicated |
12,399 | 22,081,246 | Analysis of confounding factors showed that the intensity of ovarian stimulation is the most important determining factor to explain serum progesterone elevation at the time of hCG administration , CONCLUSIONS This systematic review shows that providing LH activity supplementation in combination with FSH during ovarian stimulation does not have a consistent effect on serum progesterone concentrations at the time of hCG administration .
However , these data also suggest that , in accordance with physiological concept , the timing of LH activity administration could influence the impact on serum progesterone changes | BACKGROUND The influence of LH on serum progesterone rise during gonadotrophin stimulation is a matter of debate .
The purpose of this analysis was to assess the impact of supplementation with ' LH activity ' products on serum progesterone changes before hCG administration in GnRH analog-treated women . | OBJECTIVE To assess if low-dose hCG is similar to hMG and to rFSH in the late follicular phase . STUDY DESIGN In a prospect i ve r and omized controlled trial , 51 patients undergoing controlled ovarian stimulation received ovarian priming with rFSH and then received hCG ( 200 IU/day ) ( hCG group , n=17 ) , hMG ( 225 IU/day ) ( hMG group , n=17 ) or rFSH ( 200 IU/day ) ( FSH group , n=17 ) in the late stage of follicular development . Parameters of follicular response and serum estradiol , progesterone and testosterone levels were assessed . RESULTS Pre-ovulatory ovarian follicle occurrence and length of treatment were similar among the three treatment groups . Serum progesterone level on the day of pre-ovulatory hCG was significantly higher in the hCG group than in the hMG or rFSH group . Clinical pregnancy rates were similar for all groups . The total cost of treatment was significantly lower for the hCG group than for the groups supplemented with hMG or rFSH . CONCLUSIONS LH in the form of low-dose hCG during the late follicular phase induced the same follicular pattern as hMG and rFSH after ovulation induction . The procedure using hCG produced pregnancy rates similar to those obtained using hMG and rFSH , even though the patients showed higher serum progesterone levels on the hCG day The advent of recombinant DNA technology will soon produce for the market a product that has pure follicle-stimulating hormone ( pFSH ) but no luteinizing hormone . A prospect i ve r and omized study was performed to see if pFSH ( Metrodin ) was able to stimulate the same in vitro fertilization parameters as human menopausal gonadotropin when preceded by gonadotropin suppression by leuprolide acetate . The results showed similar parameters between the two drugs , i.e. , number of oocytes , number of embryos , endometrial thickness at time of human chorionic gonadotropin , fertilization rates and pregnancy rates in a protocol purpose ly design ed to stimulate as many follicles as safely as possible because of a shared oocyte and successful cryopreservation program BACKGROUND To test the effects of progressively decreasing dosages of exogenous LH we combined various amounts of HMG , containing FSH , LH and HCG , and highly purified ( HP ) FSH to treat 120 GnRH agonist-suppressed infertile female patients as c and i date s for controlled ovarian stimulation ( COS ) . METHODS Subjects were r and omly assigned to four treatment groups that received the following daily i.m . gonadotrophin regimens : A , FSH 150 IU only ; B , FSH 150 IU and LH activity 37.5 IU ; C , FSH 150 IU and LH activity 75 IU ; D , FSH 150 IU and LH activity 150 IU . FSH dose adjustments were allowed only after the 14th treatment day . Monitoring included transvaginal ultrasound at 2-day intervals and daily determinations of LH , FSH , estradiol ( E(2 ) ) , progesterone , testosterone and HCG . RESULTS Duration of COS was significantly shortened in patients receiving at least 75 IU daily of LH activity . Small ( < 10 mm diameter ) pre-ovulatory ovarian follicle occurrence was inversely correlated with LH activity dose administered ( r = -0.648 , P < 0.0001 ) and serum HCG levels ( r = -0.272 , P < 0.01 ) but not to serum LH levels . Serum testosterone levels were positively correlated to the LH activity dose administered ( r = 0.313 , P < 0.001 ) , while serum progesterone levels were positively correlated to the FSH dose administered ( r = 0.447 , P < 0.00001 ) but not to the LH activity dose administered . CONCLUSIONS Firstly , HCG content considerably contributes to HMG activity ; secondly , menotrophin LH activity content can reduce in a dose-dependent manner the occurrence of small pre-ovulatory follicles ; and finally , contrary to common belief , enhanced FSH stimulation rather than LH activity appears to cause premature follicle luteinization during COS Although FSH is essential to stimulate ovarian folliculogenesis , increasing physiological and clinical evidence suggests that moderate LH stimulation may also be critical for optimal follicle and oocyte development . Conversely , a clinical trend exists toward conducting controlled ovarian hyperstimulation ( COH ) in a LH-depleted environment , as recently developed gonadotropin preparations are devoid of LH activity , and endogenous LH is suppressed with GnRH analogs in most COH cycles . To investigate the role of LH activity during COH we supplemented highly purified ( HP ) FSH with low dose hCG in GnRH agonist-suppressed women . Twenty normoovulatory women were pretreated with a GnRH agonist and after 2 weeks were r and omly assigned to receive HP FSH ( 150 IU/day ) alone ( group A ; 10 patients ) or combined with hCG ( 50 IU/day ; group B ; 10 patients ) . The HP FSH dose was increased after 14 days only in cases of inadequate response . Treatment was monitored with pelvic ultrasound and daily hormone determinations . None of the patients of group B and 8 of group A required more than 14 days of treatment and increments of the FSH dose . Folliculogenesis and 17beta-estradiol ( E2 ) secretion progressed more rapidly and evenly in group B. Although preovulatory follicle number and E2 concentrations were comparable , patients in group B required a shorter stimulation time ( 12.5+/-0.6 vs. 17.3+/-0.7 days in group A ; P < 0.0001 ) and a lower HP FSH dose ( 1725+/-84 vs. 2670+/-164 IU in group A ; P < 0.0001 ) . Serum levels of LH , E2 , progesterone , and testosterone did not differ between the 2 groups ; serum FSH was higher in group A. We conclude that LH activity promotes folliculogenesis in synergy with FSH in the mid- to late follicular phase and that low dose hCG coadministration optimizes COH by 1 ) enhancing FSH action , 2 ) accelerating ovarian follicle development , 3 ) shortening COH duration , 4 ) lowering HP FSH requirements , and 5 ) reducing COH cost . Thus , moderate LH activity in the follicular phase plays a positive physiological and clinical role in folliculogenesis and ovulation induction OBJECTIVES To clarify the endocrine mechanisms underlying the outcome of different ovulation induction regimens with gonadotropins and GnRH agonists ( GnRH-a ) . DESIGN Prospect i ve study . SETTING Reproductive Endocrinology Center , University of Bologna . PATIENTS Forty eumenorrheic women r and omly assigned to four groups of 10 subjects each . INTERVENTIONS Ovulation induction regimens : group A , purified FSH only ; group B , purified FSH and flare-up GnRH-a ; group C , purified FSH and long GnRH-a ; and group D , hMG and long GnRH-a . MAIN OUTCOME MEASURES Pelvic ultrasound and hormone levels in daily serum sample s and in follicular fluid drawn immediately before hCG administration . RESULTS Exogenous gonadotropin dose did not differ among groups . Group B had fewer preovulatory follicles than group C. Group B had higher serum LH , FSH , E2 , P , T , and follicular fluid LH , E2 , T , and alpha-inhibin than groups C and /or D. Groups C and D did not differ . CONCLUSIONS Long GnRH-a regimens improved follicle yield and the endocrine milieu in spite of comparable exogenous gonadotropin dose and lower serum FSH and thus appear to be preferable in assisted reproduction . Reduced folliculogenesis found in flare-up GnRH-a regimens could be mediated by the atretic effects of high intraovarian and rogens . Efficacy of purified FSH and hMG was comparable BACKGROUND LH activity may influence treatment response and outcome in IVF cycles . METHODS A r and omized , assessor-blind , multinational trial compared ongoing pregnancy rates ( primary end-point ) in 731 women undergoing IVF after stimulation with highly purified menotrophin ( HP-hMG ) ( n = 363 ) or recombinant FSH ( rFSH ) ( n = 368 ) following a long GnRH agonist protocol . Patients received identical pre- and post-r and omization interventions . One or two embryos were transferred on day 3 . RESULTS More oocytes were retrieved ( P < 0.001 ) after rFSH treatment ( 11.8 ) compared with HP-hMG treatment ( 10.0 ) , but a higher proportion developed into top- quality embryos ( P = 0.044 ) with HP-hMG ( 11.3 % ) than with rFSH ( 9.0 % ) . At the end of stimulation , lower estradiol ( E(2 ) ) ( P = 0.031 ) and higher progesterone ( P < 0.001 ) levels were found with rFSH , even after adjusting for follicular response . The distribution of hypo- , iso- and hyper-echogenic endometrium showed a significant ( P = 0.023 ) shift towards the hyperechogenic pattern after rFSH treatment . The ongoing pregnancy rate per cycle was 27 % with HP-hMG and 22 % with rFSH [ odds ratio ( 95 % confidence interval ) : 1.25 ( 0.89 - 1.75 ) ] . CONCLUSION Superiority of HP-hMG over rFSH in ongoing pregnancy rate could not be concluded from this study , but non-inferiority was established . Pharmacodynamic differences in follicular development , oocyte/embryo quality , endocrine response and endometrial echogenicity exist between HP-hMG and rFSH preparations , which may be relevant for treatment outcome The effects of treatment of patients with gonadotrophin-releasing hormone analogue ( GnRHa ) combined with purified follicle stimulating hormone ( FSH ) for in-vitro fertilization ( IVF ) were investigated in detail to determine the influences of different administration routes and the degree of suppression of luteinizing hormone ( LH ) . Responses to exogenous gonadotrophins were studied in infertile women ( n = 60 ) with normal menstrual rhythm whose endogenous gonadotrophin activity was suppressed using a GnRHa in a long protocol . They were r and omized to receive i.m . administration of human menopausal gonadotrophins ( HMGim , Pergonal ) or purified follicle stimulating hormone ( FSH , Metrodin High Purity ) administered either i.m . ( MHPim ) or s.c . ( MHPsc ) . Responses were assessed by measuring plasma FSH , LH , oestradiol , testosterone and progesterone . After stimulation day 4 , the MHPsc group showed significantly higher circulating concentrations of FSH than either the MHPim or HMGim group . However , the HMG group showed significantly higher oestradiol concentrations after stimulation day 5 than either MHP group . The differences in circulating oestradiol concentrations in the MHP-treated patients appeared to be strongly influenced by the mean circulating concentrations of LH in the follicular phase . The patients who showed mean follicular phase LH concentrations of < 1 IU/l showed longer follicular phases , lower circulating oestradiol and testosterone concentrations and also lower follicular fluid concentrations of oestradiol and testosterone , indicating a reduction in the normal follicular metabolism of progesterone to and rogens and oestrogens under these conditions . This group of patients also showed longer follicular phases , which may have consequences for future clinical management BACKGROUND Elevated serum progesterone levels at the end of the follicular phase in controlled ovarian stimulation ( COS ) leads to a poorer ongoing pregnancy rate in IVF cycles due to reduced endometrial receptivity . The objective of this study was to use microarray technology to compare endometrial gene expression profiles at the window of implantation according to the levels of circulating progesterone . METHODS For this prospect i ve cohort study , microarray data were obtained from endometrial biopsies from 12 young healthy oocyte donors undergoing COS with pituitary suppression by either gonadotrophin-releasing hormone ( GnRH ) agonists or antagonists , and recombinant FSH . On the day of recombinant chorionic gonadotrophin ( rCG ) administration , six women had serum progesterone levels ( P ) > 1.5 ng/ml ( study group ) and six had serum P levels < 1.5 ng/ml ( control group ) . Endometrial sample s were collected using a Pipelle catheter 7 days after the rCG injection . RESULTS Using the parametric test , we identified 140 genes significantly dysregulated ( 64 up- and 76 down-regulated ) in the study group endometria compared with the control endometria , regardless of the GnRH analogue employed . These genes are related to cell adhesion , developmental processes , the immune system and others , which are all required for normal endometrial function development . Of the 25 gene targets previously proposed as markers for endometrial receptivity , 13 appeared over-regulated in the study group . CONCLUSIONS Our results reveal that elevated progesterone levels on the day of rCG administration can induce significant alterations in the gene expression profile of the endometrium BACKGROUND When administered in the late follicular phase to prevent an LH surge , GnRH antagonists induce a sharp decrease in serum LH levels that may be detrimental for assisted reproductive technology cycle outcome . Therefore , a prospect i ve study was design ed to assess the effects of recombinant human (r)LH supplementation during GnRH antagonist ( cetrorelix ) administration . METHODS The protocol consisted of cycle programming with oral contraceptive pill , ovarian stimulation with rFSH and flexible administration of a single dose of cetrorelix ( 3 mg ) . A total of 218 patients from three IVF centres were r and omized ( by sealed envelopes or according to woman 's birth date ) to receive ( n = 114 ) or not ( n = 104 ) a daily injection of rLH 75 IU from GnRH antagonist initiation to hCG injection . RESULTS The only significant difference was a higher serum peak E2 level in patients treated with rLH ( 1476 + /- 787 versus 1012 + /- 659 pg/ml , P < 0.001 ) whereas the numbers of oocytes and embryos as well as the delivery rate ( 25.2 versus 24 % ) and the implantation rate per embryo ( 19.1 versus 17.4 % ) were similar in both groups . CONCLUSIONS These results show that in an unselected group of patients , there is no evident benefit to supplement GnRH antagonist-treated cycles with rLH OBJECTIVE To carefully examine the features of controlled ovarian stimulation performed with recombinant FSH-alpha or hMG . DESIGN Controlled , prospect i ve , r and omized comparison of fixed gonadotropin regimens . SETTING Academic research institution . PATIENT(S ) Fifty infertile patients who were c and i date s for IUI . INTERVENTION(S ) Patients were r and omized to receive a fixed regimen of recombinant FSH-alpha ( 150 IU/day , 25 patients ) or hMG ( 150 IU/day , 25 patients ) , after GnRH-agonist suppression ( long regimen ) . MAIN OUTCOME MEASURES Daily measurements of serum LH , immunoreactive FSH , hCG , E(2 ) , P , and T. Transvaginal pelvic ultrasound every 2 days . Pregnancy and abortion rates . Cost of medications . Two recombinant FSH-alpha-treated patients did not respond . Despite matched daily FSH dose , duration of treatment ( hMG 10.8 + /- 0.4 vs. recombinant FSH-alpha 12.4 + /- 0.5 days ) , gonadotropin dose ( 21.7 + /- 0.8 vs. 25.3 + /- 1.3 ampoules ) , gonadotropin cost ( 288 + /- 10 vs. 1,299 + /- 66 /cycle ) , serum P levels , and small preovulatory follicle number were significantly lower , and LH , hCG , immunoreactive FSH levels , and larger follicles on day 8 were significantly higher in hMG-treated patients . The pregnancy , abortion , and twin pregnancy rates did not differ . CONCLUSION The hMG administration was associated with : [ 1 ] . increased serum LH activity and immunoreactive FSH levels during treatment ; [ 2 ] . reduced signs of premature luteinization ; [ 3 ] . differential modulation of folliculogenesis ; [ 4 ] . lower treatment duration , gonadotropin dose , and cost ; and [ 5 ] . clinical outcome comparable to recombinant FSH-alpha The aim of the present study was to investigate whether reducing the amount of luteinizing hormone ( LH ) in gonadotrophic preparations impairs follicular growth in in-vitro fertilization ( IVF ) cycles during suppression of endogenous LH levels . A selected group of 20 IVF patients was r and omly divided into two groups . One group was treated with Org 31338 [ follicle stimulating hormone (FSH)/LH 3:1 ] , the other group with Metrodin ( purified FSH ) , both during pituitary down-regulation with buserelin . A fixed daily dose of 150 IU FSH i.m . was given . Serum concentrations of FSH , LH , oestradiol and progesterone were determined frequently and serial ultrasound examinations were performed . Multiple follicular growth with concomitant rise of oestradiol levels was observed in all cycles . The duration of the stimulation phase was shorter in the group treated with Org 31338 than in the group treated with Metrodin . The number of follicles and oocytes and the fertilization rate was larger and the mean embryo quality was higher in the Org 31338 group , but the differences did not reach statistical significance . No significant differences were found in hormonal values . In women with normal endocrine profiles , lowering of the LH activity in gonadotrophic preparations during gonadotrophin-releasing hormone agonist treatment results in adequate ovarian stimulation . However , a preparation with some LH needed a shorter stimulation than a purified FSH preparation . Whether the other beneficial effects of Org 31338 also occur in a larger population needs further investigation OBJECTIVE To determine the prevalence and the effect of premature luteinization in GnRH antagonist IVF-ET cycles . DESIGN Prospect i ve observational study . SETTING In vitro fertilization-embryo transfer ( IVF-ET ) program at the Instituto Valenciano de Infertilidad . PATIENT(S ) Eighty-one infertile patients undergoing controlled ovarian hyperstimulation with gonadotropins and GnRH antagonist for IVF-ET . INTERVENTION(S ) Gonadotropin-releasing hormone ( GnRH ) antagonist was administered from stimulation day 6 . Serum P , E(2 ) , and LH were determined on the day of hCG administration . MAIN OUTCOME MEASURE(S ) Cycles were grouped according to serum P level on the day of hCG administration ( < 1.2 ng/mL or > or = 1.2 ng/mL ) . Clinical pregnancy and implantation rates were determined . RESULT ( S ) The incidence of premature luteinization was 38.3 % . Total recombinant FSH dose and stimulation days differed significantly between the groups . Pregnancy rate ( 25.8 % vs. 54.0 % ) and implantation rate ( 13.8 % vs. 32.0 % ) were significantly lower in the premature luteinization group . CONCLUSION ( S ) Premature luteinization during GnRH antagonist IVF-ET cycles is a frequent event that is associated with lower pregnancy and implantation rates . Progesterone elevations are not related to serum LH levels and may reflect the mature granulosa cell response to high FSH exposure Although the role that LH plays in folliculogenesis is still controversial , recent evidence points toward facilitatory actions of LH activity in ovulation induction . Thus , we compared the response to either highly purified FSH ( 75 IU FSH/ampoule ; group A , 25 subjects ) or human menopausal gonadotropin ( 75 IU FSH and 75 IU LH/ampoule ; group B , 25 subjects ) in normoovulatory GnRH agonist-suppressed women , c and i date s for intrauterine insemination . A fixed regimen of 2 daily ampoules of highly purified FSH or human menopausal gonadotropin was administered in the initial 14 days of treatment ; menotropin dose adjustments were allowed thereafter . Treatment was monitored with daily blood sample s for the measurement of LH , FSH , 17beta-estradiol ( E(2 ) ) , progesterone , testosterone , hCG , inhibin A , and inhibin B , and transvaginal pelvic ultrasound was performed at 2-day intervals . Although preovulatory E(2 ) levels were similar , both the duration of treatment ( 16.1 + /- 0.8 vs. 12.6 + /- 0.5 days ; P < 0.005 ) and the per cycle menotropin dose ( 33.6 + /- 2.4 vs. 23.6 + /- 1.1 ampoules ; P < 0.005 ) were lower in group B. In the initial 14 treatment days the area under the curve of FSH , progesterone , testosterone , inhibin A , and inhibin B did not differ between the 2 groups , whereas LH , hCG , and E(2 ) areas under the curve were higher in group B. The occurrence of small follicles ( < 10 mm ) and the inhibin B/A ratio in the late follicular phase were significantly reduced in group B. A nonsignificant trend toward a higher multiple gestation rate was present in group A ( 60 % vs. 17 % ) . We conclude that ovulation induction with LH activity-containing menotropins is associated with 1 ) shorter treatment duration , 2 ) lower menotropin consumption , and 3 ) reduced development of small ovarian follicles . These features can be exploited to develop regimens that optimize treatment outcome , lower costs , and reduce occurrence of complications such as multiple gestation and ovarian hyperstimulation OBJECTIVE To determine whether the late follicular phase increase in circulating P concentrations during controlled ovarian stimulation with GnRH-a and FSH can be influenced by addition of LH to the stimulating gonadotropin during the final 2 days . DESIGN R and omization of patients to receive either FSH alone or FSH with LH ( hMG ) for the final 2 days before hCG , after follicular phase stimulation with purified FSH . SETTING A.C.S. Unit at the Royal Infirmary , Glasgow , U.K. PATIENT(S ) Patients were unselected and were undergoing IVF . INTERVENTION(S ) Patients received stimulation with purified FSH ( 300 IU/d ) until a follicle of 15 mm was observed ; the regimen was then changed to either 225 IU of FSH or 225 IU of hMG . MAIN OUTCOME MEASURE(S ) Estradiol and P in the peripheral circulation . RESULT ( S ) Significant increases in E2 concentration were observed , but there were no changes in the circulating progesterone . CONCLUSION ( S ) The late follicular phase increase in P is unrelated to any luteinizing process attributable to effects in the circulation or sensitization of follicular cells to LH OBJECTIVE To prove that low-dose hCG alone can be clinical ly used to replace FSH-containing gonadotropins to complete controlled ovarian hyperstimulation ( COH ) . DESIGN Controlled , prospect i ve , r and omized study . SETTING Academic center . PATIENT(S ) Infertile patients who are c and i date s for assisted reproduction . INTERVENTION(S ) Patients received [ 1 ] recombinant FSH or hMG throughout COH ( group A ) ; [ 2 ] ovarian priming with recombinant FSH/hMG followed by low-dose hCG ( 200 IU/day ) alone ( group B ) . MAIN OUTCOME MEASURE(S ) Medication consumption ; daily serum and follicular fluid ( FF ) measurements of LH , FSH , hCG , E2 , P , T , and and rostenedione ( A ) ; number and size of follicles ; intracytoplasmic sperm injection ( ICSI ) outcome . RESULT ( S ) In group B : [ 1 ] duration and dose of recombinant FSH/hMG administration were reduced ; [ 2 ] preovulatory serum hCG , E2 , and T were higher , whereas FSH was lower ; [ 3 ] FF hCG , E2 , T levels , and E2/T , E2/A , and E2/P ratios were higher , whereas A was lower ; [ 4 ] small but not large preovulatory follicles were reduced ; [ 5 ] fertilization rates were higher ; and [ 6 ] serum and FF P levels , and ICSI outcome did not differ . CONCLUSION ( S ) Low-dose hCG alone in the late COH stages : [ 1 ] reduced recombinant FSH/hMG consumption whereas ICSI outcome was comparable to traditional COH regimens ; [ 2 ] stimulated follicle growth and maturation independent of FSH administration ; [ 3 ] was associated with a reduced number of small preovulatory follicles ; [ 4 ] did not cause premature luteinization ; [ 5 ] result ed in a more estrogenic intrafollicular environment OBJECTIVE To analyze the impact of LH administration on cycle outcome in ovarian stimulation with GnRH antagonists . DESIGN R and omized , open-label , controlled trial performed in two age subgroups . Recombinant ( r ) FSH versus rFSH + rLH administration was compared . SETTING University-affiliated private infertility clinic . PATIENT(S ) Up to 35 years old ( n = 380 ) and aged 36 to 39 years ( n = 340 ) , undergoing their first or second IVF cycle . INTERVENTION(S ) Recombinant LH administration since stimulation day 1 . MAIN OUTCOME MEASURE(S ) Implantation rate , ongoing pregnancy rate . RESULT ( S ) In the young population , implantation rates were similar : 27.8 % versus 28.6 % , odds ratio ( OR ) 1.03 ( 95 % confidence interval [ CI ] 0.73 - 1.47 ) , as was the ongoing pregnancy rate per started cycle : 37.4 % versus 37.4 % , OR 1.0 ( 95 % CI 0.66 - 1.52 ) . In older patients , the implantation rate was significantly higher in the rFSH + rLH group : 26.7 % versus 18.6 % , OR 1.56 ( 95 % CI 1.04 - 2.33 ) . Ongoing pregnancy rates per started cycle were 33.5 % versus 25.3 % , OR 1.49 ( 95 % CI 0.93 - 2.38 ) . CONCLUSION ( S ) Recombinant LH administration significantly increased the implantation rate in patients aged 36 to 39 years . A clinical ly relevant better ongoing pregnancy rate per started cycle was observed , although the difference was not statistically significant . Patients younger than 36 years do not obtain any benefit from rLH administration BACKGROUND To assess the clinical profile and efficacy in assisted reproductive treatment of a new human-derived highly purified ( HP ) menotropin , we compared HP hMG and recombinant ( r ) FSHalpha use in ICSI within a prospect i ve , r and omized , controlled study . METHODS 100 infertile women were treated with HP hMG ( 50 patients ) or rFSHalpha ( 50 patients ) . All patients received the same daily gonadotrophin dose ( 150 IU ) following GnRH agonist suppression ( long regimen ) until more than three follicles > 17 mm and estradiol ( E(2 ) ) levels > 600 pg/ml were reached . Patients were monitored with daily LH , FSH , hCG , estradiol ( E(2 ) ) , progesterone , and testosterone measurements ; and alternate day pelvic ultrasound . RESULTS Treatment duration ( 11.1 + /- 0.4 versus 12.9 + /- 0.5 days , P < 0.05 ) and gonadotrophin dose ( 22.4 + /- 1.0 versus 27.0 + /- 1.5 ampoules , P < 0.05 ) were lower in the HP hMG group . Conversely , peak pre-ovulatory E(2 ) ( 1342 + /- 127 versus 933 + /- 109 pg/ml , P < 0.005 ) ; and area under the curve of E(2 ) ( 3491 + /- 350 versus 2602 + /- 349 pg/ml.day , P < 0.05 ) , immunoreactive serum FSH ( 65.9 + /- 2.1 versus 48.8 + /- 1.8 IU/l.day , P < 0.001 ) . and hCG ( 1.7 + /- 0.3 versus 0.0 + /- 0.0 IU/l/day , P < 0.001 ) during treatment were higher in the HP hMG group . Cycle cancellation rates , transferred embryo number , pregnancy rates per started cycle ( 30 versus 28 % ) and per embryo transfer ( 35 versus 35 % ) and miscarriage rates ( 6 versus 6 % ) were not significantly different . CONCLUSIONS HP hMG treatment was associated with : ( i ) a more efficient patient response , as reflected by reduced treatment duration and gonadotrophin requirements ; ( ii ) increased serum levels of hCG , E(2 ) , and immunoreactive FSH during treatment ; ( iii ) an ICSI outcome indistinguishable from rFSHalpha OBJECTIVE Evaluate the effectiveness of a new ovarian stimulation ( OS ) protocol before IVF . DESIGN Prospect i ve clinical r and omized trial . SETTING Private centers . PATIENT(S ) Three hundred and twenty-three intended-to-treat women c and i date s for IVF . INTERVENTION(S ) Patients were divided into three groups and administered the following treatments : group A , recombinant hFSH from day 3 until follicles reached 13 - 14 mm , when recombinant hFSH was lowered to 75 IU daily and daily injections of 200 IU of hCG and a GnRH antagonist were administered until final maturation ; group B , recombinant hFSH and a GnRH antagonist ; group C , recombinant hFSH and a GnRH agonist . MAIN OUTCOME MEASURE(S ) Primary outcome was the number of mature oocytes . Secondary outcomes included average initial and total recombinant hFSH dosage , serum E2 level on day of ovulation , number of oocytes retrieved , fertilization , number of top- quality embryos , endometrial thickness , implantation rate , pregnancy rate ( PR ) , and incidence of ovarian hyperstimulation syndrome ( OHSS ) . RESULT ( S ) The numbers of oocytes retrieved , mature oocytes , fertilization , top- quality embryos , and embryos transferred were comparable in all groups . Implantation rate , PR , and incidence of OHSS were also comparable . The total dose of recombinant hFSH was significantly lower in group A ( 1,674.7 + /- 59.4 IU , vs. 2,197.9 + /- 77.8 IU in group B and 2,156.7 + /- 80.9 IU in group C ) . CONCLUSION ( S ) This new OS protocol permits follicles and oocytes to fully develop , helps generate top- quality embryos , avoids premature ovulation , establishes clinical pregnancies , reduces administration of recombinant hFSH , minimizes costs , and does not increase the chances of OHSS An open label , r and omized , multi-centre study was performed to compare cetrorelix and leuprolide acetate for prevention of premature LH surge and to assess whether patients treated with cetrorelix benefit from addition of recombinant human (r-h)LH . Normo-ovulatory women ( n = 74 ) undergoing ovarian stimulation prior to intracytoplasmic sperm injection were treated with leuprolide acetate ( n = 25 ) before ovarian stimulation with recombinant human FSH ( r-hFSH ) or with cetrorelix 3 mg on stimulation day 7 ( with ( n = 25 ) or without ( n = 24 ) r-hLH 150 IU on days 7 - 10 ) . The main outcome measures were the number of metaphase II ( MII ) oocytes retrieved ; secondary efficacy end-points ; adverse events ( AE ) and other safety measures . There were no significant differences between groups for MII oocytes retrieved , duration of stimulation , total r-hFSH dose and pregnancy rates . The group treated with cetrorelix alone had a significantly lower concentration of oestradiol per follicle compared with the other groups . The majority of AE were mild to moderate in severity . Cetrorelix and leuprolide acetate appear to have comparable efficacy and safety , although cetrorelix has the advantage of typically requiring only one injection The efficacy of recombinant human LH ( rhLH ) for supporting human (rhFSH)-induced follicular development was investigated in hypogonadotropic hypogonadal women ( WHO group I anovulation ) . Patients ( n = 38 ) were r and omized to receive rhLH ( 0 , 25 , 75 , or 225 IU/day ) in addition to a fixed dose of rhFSH ( 150 IU/day ) . rhLH was found 1 ) to promote dose-related increases in estradiol ( E2 ) and and rostenedione secretion by rhFSH-induced follicles , i.e. serum concentrations on the last day of FSH administration were 65 + /- 4 , 195 + /- 94 , 1392 + /- 585 , and 2441 + /- 904 pmol/L for E2 and 3.6 + /- 0.9 , 5.1 + /- 1.3 , 6.4 + /- 1.3 , and 6.7 + /- 1.3 nmol/L for and rostenedione for patients treated with 0 , 25 , 75 , and 225 IU rhLH , respectively ; 2 ) to increase ovarian sensitivity to FSH , as demonstrated by the proportion of patients who developed follicles after the administration of a fixed dose of FSH , i.e. 1 of 8 , 3 of 7 , 7 of 9 , and 8 of 10 in patients treated with 0 , 25 , 75 , and 225 IU rhLH , respectively ; and 3 ) to enhance the ability of these follicles to luteinize when exposed to hCG . A daily dose of 75 IU rhLH was effective in the majority of women in promoting optimal follicular development ( defined as > or = 1 follicle > or = 17 mm ; E2 , > or = 400 pmol/L ; midluteal phase progesterone , > or = 25 nmol/L ) and maximal endometrial growth . A minority of patients may require up to 225 IU/day . rhLH , given sc at a dose up to 225 IU/day , was not immunogenic and was well tolerated OBJECTIVE To assess the effect of ovarian stimulation with recombinant FSH , GnRH antagonists , and hCG on endometrial maturation on the day of oocyte pick-up . DESIGN Prospect i ve study . SETTING Tertiary referral center . PATIENT(S ) Fifty-five women undergoing controlled ovarian hyperstimulation for IVF/intracytoplasmic sperm injection ( ICSI ) . INTERVENTION(S ) [ 1 ] Ovarian stimulation with recombinant FSH , starting on day 2 of the cycle and GnRH antagonist , starting after a median of 6 days of recombinant FSH stimulation ( range , 5 - 12 days ) ; [ 2 ] hCG administration for ovulation induction ; and [ 3 ] aspirational biopsy of endometrium at oocyte pick-up . MAIN OUTCOME MEASURE(S ) Endometrial histology at oocyte pick-up by Noyes criteria . RESULT ( S ) Advancement of endometrial maturation ( 2.5 + /- 0.1 days ) as compared to the expected chronological date was observed in all antagonist cycles at oocyte retrieval . Endometrial advancement at oocyte pick-up increased in line with values of LH at initiation of stimulation and the duration of recombinant FSH treatment before the antagonist was started . CONCLUSION ( S ) The higher the values of LH at initiation of stimulation and the longer the duration of recombinant FSH treatment before the antagonist is started , the more advanced the endometrial maturation at oocyte pick-up OBJECTIVE To investigate the role of exogenous LH in controlled ovarian hyperstimulation for assisted reproductive technologies . DESIGN Prospect i ve r and omized study . SETTING SISMER fertility unit . PATIENT(S ) Women showing a hyporesponsiveness to FSH under GnRH agonist down-regulation were r and omized into three groups : group A ( n = 54 ) received an increased dosage of FSH ; group B ( n = 54 ) was administered recombinant LH in addition to the increased dose of FSH ; group C ( n = 22 ) was given additional FSH and LH using hMG as a combined drug . Fifty-four age-matched women with no need to increase the FSH dose were included as a control group ( D ) . INTERVENTION(S ) None . MAIN OUTCOME MEASURE(S ) Implantation and live birth rate per started cycles . RESULT ( S ) In group B , the pregnancy and implantation rates were statistically higher when compared with groups A and C and did not differ from the control group for normal response . The live birth rate was similar in groups B and D but was half as high in groups A and C. CONCLUSION ( S ) Hyporesponsiveness to FSH could be related to iatrogenic LH deficiency that , in turn , could affect oocyte competence . Addition of a small amount of recombinant LH is able to rescue oocyte competence to produce viable embryos OBJECTIVE To determine the effect of exogenous LH dosage on IVF outcome . DESIGN Single-blinded ( assessor-blinded ) study with r and om assignment of treatment groups . SETTING Human Assisted Reproduction Unit , Rotunda Hospital , Dublin , Irel and . PATIENT(S ) Infertile normogonadotropic women undergoing their first cycle of IVF were studied . INTERVENTION(S ) Patients were r and omized to gonadotropin drugs with varying doses of LH per ampule : recombinant FSH containing no LH ( group 0 , n = 39 ) , urinary FSH containing < 1 IU of LH per ampule ( group 1 , n = 30 ) , hMG containing 25 IU of LH per ampule ( group 25 , n = 30 ) , and hMG containing 75 IU of LH per ampule ( group 75 , n = 29 ) . The FSH dose was kept constant at 75 IU per ampule . A long- protocol GnRH-analog regimen was used . MAIN OUTCOME MEASURE(S ) Dose and duration of gonadotropin stimulation , follicle and oocyte numbers , implantation rate , and pregnancy rate . RESULT ( S ) The median duration of ovarian stimulation ; median number of gonadotropin ampules used ; serum E2 levels ; and numbers of follicles , oocytes , and embryos were similar among the four groups . Median LH levels on the day of hCG administration , however , differed significantly . Live birth rates per cycle differed markedly , but statistical significance was not achieved ( 23 % , 7 % , 20 % , and 31 % for groups 0 , 1 , 25 , and 75 , respectively ) . A significant trend in implantation rates was noted with increasing LH dosage of the urinary preparations ( 19 % , 10 % , 18 % , and 28 % for groups 0 , 1 , 25 , and 75 , respectively ) . CONCLUSION ( S ) In the present study , although the residual endogenous LH after down-regulation was adequate for ovarian response and E2 synthesis , the addition of exogenous LH improved implantation . An FSH/LH ratio of 75/75 IU per ampule appeared to be the optimum dose BACKGROUND Temporary exposure of follicles to increased levels of and rogens may augment follicular responsiveness . The present study tested whether short-term and rogen priming by aromatase inhibitor and human chorionic gonadotrophin ( hCG ) before controlled ovarian stimulation ( COS ) increases the number of top- quality embryos after IVF/ICSI . METHODS Patients were r and omized to and rogen priming ( n = 53 ) : anastrozole 1 mg cycle day ( c.d . ) 2 , 3 and 4 , hCG 1250 IU and cetrorelix 3 mg on c.d . 2 , rFSH 150 IU from c.d . 5 following a flexible antagonist protocol ; or control ( n = 50 ) : flexible antagonist protocol . RESULTS The mean ( confidence interval ) number of top- quality embryos was 1.08 ( 0.83,1.40 ) and 1.43 ( 1.12,1.81 ) in the priming and control group , respectively , being 32 % ( -7 % , 89 % ) higher in the control compared to priming group ( P = 0.120 ) . Stimulation duration was longer in the priming group ( P < 0.001 ) . On the day of hCG administration , the proportion of c.d . 2 antral follicles reaching > or=14 mm was higher in the priming group ( P = 0.014 ) , as were serum estradiol ( E(2 ) ) ( P < 0.001 ) and E(2 ) per follicle > or=14 mm ( P = 0.005 ) . Pre-ovulatory follicular fluid levels of E(2 ) ( P = 0.007 ) and testosterone ( P = 0.014 ) were higher in the priming group . The number of oocytes retrieved was similar . The fertilization rate was lower in the priming group ( P = 0.007 ) . Ongoing pregnancy rates in priming and control group were 30 and 36 % ( P = 0.531 ) . CONCLUSIONS Administration of aromatase inhibitor and hCG before COS for IVF/ICSI failed to improve the number of top- quality embryos OBJECTIVE To determine if premature luteinization can occur in GnRH agonist ( GnRH-a ) and FSH ( recombinant FSH and human urinary FSH ) IVF cycles and whether premature luteinization affects IVF and clinical outcome . DESIGN Retrospective evaluation of 171 IVF-ET cycles . The cycles were divided into two groups according to the P level on the day of hCG : group I ( serum P < /= 0.9 ng/mL [ conversion factor to SI unit , 3.180 ] ) and group II ( serum P > /= 1.1 ng/mL ) . MAIN OUTCOME MEASURES Comparison of cycles characteristics and of cumulative exposure of follicular serum E2 , FSH , LH , and P as well as of IVF and clinical outcome were made between the study groups . RESULTS Twenty-three of the 171 cycles ( 13.4 % ) demonstrated premature luteinization . The age of the patients , the E2 , and LH exposure were similar between the groups . The number of the ampules of gonadotropins ( recombinant FSH and urinary FSH ) used and the area under FSH and P curve were higher in cycles with premature luteinization . The area under the FSH curve correlated with the area under the P curve . Similar IVF and clinical outcomes were observed in cycles with and without premature luteinization . CONCLUSION The greater FSH exposure and its correlation with the P exposure suggest that one of the possible factors inducing premature luteinization is the increased FSH-induced LH receptivity in granulosa cells . No adverse effects of premature luteinization on the IVF and clinical outcome were observed BACKGROUND Suppression of endogenous LH production by mid-follicular phase GnRH-antagonist administration in controlled ovarian hyperstimulation protocol using recombinant ( rec ) FSH preparations void of LH activity may potentially affect ovarian response and the outcome of IVF treatment . The present study prospect ively assessed the effect of using a combination of recFSH and recLH on ovarian stimulation parameters and treatment outcome in a fixed GnRH-antagonist multiple dose protocol . METHODS 127 infertile patients with an indication for IVF or ICSI were recruited and r and omized ( using sealed envelopes ) to receive a starting dose of either 150 IU recFSH ( follitropin alpha ) or 150 IU recFSH plus 75 IU recLH ( lutropin alpha ) for ovarian hyperstimulation . GnRH-antagonist ( Cetrorelix ) 0.25 mg was administered daily from stimulation day 6 onwards up to and including the day of the administration of recombinant HCG ( chorion gonadotropin alpha ) . Gonadotropin dose adjustments were allowed from stimulation day 6 onwards , HCG was administered as soon as three follicles > or = 18 mm were present . The primary outcome parameter was treatment duration until administration of HCG . RESULTS Exogenous LH did not shorten the time necessary to reach ovulation induction criteria . Serum estradiol ( E(2 ) ) and LH levels were significantly higher on the day of HCG administration in the recLH-supplemented group ( 1924.7 + /- 1256.4 vs 1488.3 + /- 824.0 pg/ml , P < 0.03 ) , and 2.1 + /- 1.4 vs 1.4 + /- 1.5 IU/l , P < 0.01 , respectively ) . CONCLUSIONS Except for higher E(2 ) and LH levels on the day of HCG administration , no positive trend in favour of additional LH was found as defined by treatment outcome parameters OBJECTIVE To investigate the association between the probability of pregnancy and hormone exposure between the end of menstruation and the day of triggering final oocyte maturation ( menstruation-free interval ) . DESIGN Prospect i ve study . SETTING University . PATIENT(S ) One hundred women ( aged ≤ 39 years ) stimulated with a fixed dose of recombinant follicle-stimulating hormone ( 200 IU ) . INTERVENTION(S ) Daily gonadotropin-releasing hormone antagonist ( GnRH , 0.25 mg ) used from day 6 of stimulation onward , final oocyte maturation triggered by administration of 10,000 IU of human chorionic gonadotropin ( hCG ) as soon as ≥ 3 follicles ≥ 17 mm were present , and hormone assessment performed at initiation of stimulation , on the first day after menstruation had stopped , on the day of antagonist initiation , and on the day of hCG administration . MAIN OUTCOME MEASURE(S ) The association between hormone exposure during the menstruation-free interval and the probability of ongoing pregnancy . RESULT ( S ) The exposure to progesterone during the menstruation-free interval was statistically significantly higher in patients who did not become pregnant compared with those who did ( 4.20 ± 2.54 vs. 3.13 ± 1.14 , respectively ) . Binary logistic regression confirmed the adverse effect of the increased exposure to progesterone for the achievement of pregnancy . CONCLUSION ( S ) In recombinant follicle-stimulating hormone/gonadotropin-releasing hormone antagonist in vitro fertilization/intracytoplasmic sperm injection cycles , a lower probability of pregnancy is associated with a higher exposure to progesterone during the menstruation-free interval BACKGROUND Highly purified menotrophin ( HP-hMG ) has been associated with fewer oocytes retrieved and a higher proportion of top- quality embryos compared with recombinant FSH ( rFSH ) . METHODS A r and omized , assessor-blind , multinational trial in 731 women undergoing IVF after stimulation with HP-hMG ( MENOPUR ) ( n = 363 ) or rFSH ( GONAL-F ) ( n = 368 ) following a long GnRH agonist protocol was conducted . Blood was collected before , during and after stimulation . Fluid was collected from follicles > or = 17 mm . RESULTS Serum and rostenedione , total testosterone and free and rogen index ( FAI ) were higher ( P < 0.001 ) with HP-hMG than with rFSH after starting stimulation . At the end of stimulation , serum estradiol was higher ( P = 0.031 ) with HP-hMG , whereas progesterone was higher ( P < 0.001 ) with rFSH , even after adjusting for ovarian response . Serum LH was not different between treatments . Mean mid- and end-follicular hCG levels in the HP-hMG group were 2.5 and 2.9 IU/l , respectively . Follicular fluid levels of FSH , LH , hCG , and rostenedione , testosterone , FAI and estradiol and ratios of estradiol : and rostenedione , estradiol : total testosterone and estradiol : progesterone were higher ( P < 0.001 ) with HP-hMG , whereas progesterone was higher ( P < 0.001 ) with rFSH . CONCLUSION Major differences in serum and follicular fluid endocrine profile exist after stimulation with HP-hMG or rFSH . Exogenous LH activity induces a differential endocrine environment influencing oocyte quantity and quality , which may be of relevance for clinical outcome OBJECTIVE To identify if there are certain cutoff levels for P and or the P/E(2 ) ratio on the day of hCG that would be defined as detrimental for occurrence of pregnancy in women with normal ovarian reserve undergoing cleavage-stage embryo transfer ( ET ) . Secondarily , to determine if these same cutoffs might have the same potential negative effect in women undergoing blastocyst ET . DESIGN Prospect i ve cohort study including two r and omized cohorts . SETTING Private and university fertility centers . PARTICIPANT(S ) A total of 240 women undergoing long agonist protocol with at least four grade 1 day 3 embryos . INTERVENTION(S ) Women were r and omized in a 1:1 ratio to undergo day 3 or day 5 embryo transfer . MAIN OUTCOME MEASURE(S ) Clinical pregnancy rate ( CPR ) was the primary outcome . RESULT ( S ) Using receiver operator characteristics , cutoffs for P and P/E(2 ) ratio were 1.5 ng/mL and 0.55 , respectively . Patients with P ≤ 1.5 ng/mL and P/E(2 ) ≤ 0.55 undergoing cleavage-stage ET had higher CPR . Using multiple regression , P/E(2 ) ratio was the only independent predictor for pregnancy . The P and P/E(2 ) cutoffs were not correlated with CPR in blastocyst transfers . CONCLUSION ( S ) Progesterone > 1.5 ng/mL and P/E(2 ) > 0.55 affect the CPR in women undergoing cleavage-stage , but not blastocyst ET . P/E(2 ) ratio is the only independent prognosticator for cycle outcome in women undergoing cleavage-stage ET Using data from a large prospect i ve r and omized controlled trial that evaluated the effect of recombinant LH (rLH)co-administration for ovarian stimulation , the present study assessed whether progesterone concentration on the day of human chorionic gonadotrophin ( HCG ) administration was associated with pregnancy outcome . Progesterone concentration was measured on stimulation day 1 and on the day of HCG administration in 475 patients who underwent IVF/intracytoplasmic sperm injection treatment following ovarian stimulation with gonadotrophin-releasing hormone ( GnRH ) agonist and recombinant FSH with or without rLH administration from day 6 of stimulation . There was no significant association between the late-follicular-phase progesterone concentration and the clinical pregnancy rate . However , progesterone concentration was strongly associated with the number of follicles and retrieved oocytes . Late-follicular-phase LH concentration also showed a significant positive association with progesterone concentration ( P = 0.018 ) . Administration of rLH during ovarian stimulation did not affect progesterone concentration . The present study does not support an association between progesterone concentration on the day of HCG administration and the probability of clinical pregnancy in women undergoing ovarian stimulation with GnRH agonists and gonadotrophins for assisted reproduction treatment . Instead , late-follicular-phase progesterone concentration appears to be governed by the number of preovulatory follicles and LH concentration The relationship of the circulating level of progesterone ( P ) on the day of human chorionic gonadotropin ( hCG ) injection to occurrence of clinical pregnancy was examined in 133 leuprolide acetate human menopausal gonadotropin ( hMG ) in vitro fertilization cycles in women having at least three embryos transferred . Progesterone concentrations greater than 0.5 ng/mL were associated with a significantly lower rate of pregnancy ( 12/59 , 20 % ) compared with less than 0.5 ng/mL ( 40/74 , 54 % , P less than 0.005 ) . The higher P cycles were associated with greater patient age and hMG dose , although these relationships appeared to be indirect . Luteinizing hormone ( LH ) concentrations remained suppressed . Ovarian stimulation may cause excessive luteinization and an adverse cycle outcome even in the presence of low LH levels . Prospect i ve use of P levels may be helpful to determine optimal hCG timing Twenty patients entered a r and omized , crossover study of purified follicle-stimulating hormone ( pure-FSH ) or human menopausal gonadotropin ( hMG ) superovulation , 2 ampules per day after pituitary desensitization with the luteinizing hormone-releasing hormone ( LH-RH ) analogue Buserelin ( D-Ser tBu6 LH-RH 1 - 9 ethylamide ) nasal spray . There were no cycles cancelled . Six patients conceived ( five on pure-FSH , one on hMG ) . There were 24.2 + /- 2.5 ( mean + /- st and ard error of the mean [ SEM ] ) ampules of pure-FSH and 24.3 + /- 3.6 ampules of hMG stimulation required . There were similar numbers of preoperation follicles : 6.9 + /- 1.0 on hMG and 6.6 + /- 1.1 on pure-FSH , of oocytes collected ; 8.5 + /- 1.4 on hMG and 5.8 + /- 1.4 on pure-FSH , and of pre-embryos achieved ; 5.1 + /- 0.9 on hMG and 3.4 + /- 1.0 on pure-FSH ; on either treatment . The fertilization rate on hMG was 60 % and on pure-FSH was 55 % . Pre-embryo transfer rates were 3.2 + /- 0.3 in the hMG group and 2.7 + /- 0.4 in the pure-FSH group . There were no differences in serum FSH , LH , estradiol , or progesterone levels between the hMG and pure-FSH groups . Mean + /- SEM luteal phase length was 10.6 + /- 0.4 days in the nonpregnant cycles OBJECTIVE To study the effect of early follicular phase recombinant LH supplementation on stimulation outcome among women undergoing IVF using the GnRHa long protocol and recombinant FSH . DESIGN R and omized , controlled trial . SETTING Private IVF unit . PATIENT(S ) Women under the age of 40 with normal ovarian function undergoing their first or second IVF cycle . INTERVENTION(S ) All stimulations followed the st and ard luteal long GnRHa down-regulation protocol . At suppression , patients in the experimental group received 75 IU of rLH daily for 4 days , and recombinant FSH at a fixed starting dose of 150 IU for the first 5 days was started a day later , on day 2 of rLH . In the control group , patients started rFSH at a fixed dose of 150 IU for the first 5 days at suppression . MAIN OUTCOME MEASURE(S ) Baseline , stimulation , embryology parameters , and treatment outcome were compared . Of primary interest , recombinant FSH need during stimulation was assessed . RESULT ( S ) Stimulation , embryology parameters , and treatment outcome were comparable . The amount of gonadotropins used and medication expense were similar in the two groups . CONCLUSION ( S ) Early follicular phase recombinant LH supplementation at a daily dose of 75 IU does not improve response to stimulation among normal responder women undergoing IVF OBJECTIVE To compare the efficacy of three different gonadotropin regimens in an oocyte donation program . The analysis of cost minimization also was evaluated . DESIGN Prospect i ve , r and omized , controlled study . SETTING Instituto Universitario-IVI , Valencia , Spain . PATIENT(S ) One thous and twenty-eight donors undergoing a GnRH agonist protocol were assigned r and omly to one of three groups : group 1 ( n=346 ) , only recombinant FSH ( rFSH ) ; group 2 ( n=333 ) , only highly purified menotropin ( HP-hMG ) ; and group 3 ( n=349 ) , rFSH plus HP-hMG . One thous and seventy-nine oocyte recipients . INTERVENTION(S ) Controlled ovarian stimulation . MAIN OUTCOME MEASURE(S ) Controlled ovarian stimulation parameters , IVF outcome , and cost analysis . RESULT ( S ) No differences were found among the groups with respect to days of stimulation , gonadotropin dose , final E2 and P levels , number of oocytes retrieved , and cancellation rate . Similarly , there were no differences among the groups in terms of embryo development parameters . Moreover , implantation , pregnancy , and miscarriage rates with the three regimens were similar . However , the cost of rFSH was greater than that of the other protocol s. CONCLUSION ( S ) This study suggests that in the GnRH agonist protocol the three different gonadotropin regimens evaluated herein are equally effective . Protocol s using HP-hMG would appear to be the best in terms of cost-effectiveness in an oocyte donation program BACKGROUND The purpose of this prospect i ve observational study was to evaluate the association between estradiol ( E(2 ) ) levels on the day of human chorionic gonadotrophin ( hCG ) administration and pregnancy rates in a recombinant FSH ( rec-FSH ) antagonist fixed protocol . METHODS A group of 207 patients ( < or=39 years of age ) , treated by IVF/ICSI , received 200 IU/day rec-FSH from Day 2 of the cycle and daily GnRH antagonist starting on Day 6 of stimulation . The criteria for hCG administration included only the presence of > or=3 follicles of > or=17 mm diameter . One to two embryos were transferred on Day 3 after oocyte retrieval . RESULTS The area under the curve ( AUC ) for E(2 ) on the day of hCG could not distinguish between pregnant and non-pregnant women ( AUC:0.5 ; 95 % confidence interval ( CI ) : 0.42 - 0.59 ) . No significant difference was observed between the three percentile groups of E(2 ) values on the day of hCG administration [ group 1 , lower 25th percentile ( < 1142 pg/ml ) ; group 2 , medium 50th percentile ( 1142 - 2446 pg/ml ) and group 3 , higher 75th percentile ( > 2446 pg/ml ) ] for the ongoing pregnancy rates ( P = 0.52 ) . On the contrary , the linear regression model showed that higher E(2 ) values on the day of hCG administration significantly improved the scores of transferred embryos ( P = 0.01 ) as well as the total embryo score ( P = 0.02 ) . Yet subgroup analysis only in this high responders group revealed lower E(2 ) and progesterone levels on the day of hCG in pregnant women compared with the non-pregnant ( P = 0.01 ) . CONCLUSIONS E(2 ) concentrations on the day of hCG administration in GnRH antagonist cycles are not associated with pregnancy rates . A potential deleterious impact of estradiol on endometrial receptivity is shown for the high responders who have high E(2 ) levels and improved embryo quality without a concomitant rise in pregnancy rate Objective . To assess if the luteinizing hormone / human chorionic gonadotropin present in some gonadotropin formulations may be of benefit in protocol s with GnRH antagonists . Methods . Open , quasi-experimental , multicenter , prospect i ve , parallel-controlled study compared 136 women undergoing in vitro fertilization – intracytoplasmic sperm injection after stimulation with highly purified human menopausal gonadotropin ( hp-hMG ) ( n = 44 ) , recombinant-follicle stimulating hormone ( r-FSH ) ( n = 46 ) , or a combination of both ( r FSH + hp-hMG ) ( n = 46 ) following an antagonist protocol . Blood determinations were made on day 6 of stimulation and on the day of ovulation induction , with central ized analysis . Results . No differences were found in the ongoing pregnancy rates between groups [ 37.0 % versus 29.5 % ( hp-hMG ) and 23.9 % ( r-FSH ) ; p = 0.688 ] . However , the ratio top- quality embryos / retrieved oocytes ( TQE/RO ) was higher in the combined therapy group ( 19.6 % ) – reaching significance versus the r-FSH group ( 6.5 % ) ( p = 0.008 ) , but not versus hp-hMG ( 12.3 % ) ( p = 0.137 ) . Conclusions . An improved TQE/RO ratio was obtained together with a greater percentage of frozen embryos in the patients that incorporated hp-hMG to their stimulation protocol . Despite good results of adding hp-hMG , non statistical differences were found in terms of ongoing pregnancy rate |
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