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800 | 24,840,368 | This study provides clearer evidence that hypnotherapy has beneficial short-term effects in improving gastrointestinal symptoms of patients with IBS | BACKGROUND / AIMS Hypnotherapy is considered as a promising intervention for irritable bowel syndrome ( IBS ) , but the evidence is still limited .
The aims of this study were to conduct a systematic review and meta- analysis to estimate the efficacy of hypnotherapy for the treatment of IBS . | 33 patients with refractory irritable bowel syndrome were treated with four 40-minute sessions of hypnotherapy over 7 weeks . 20 improved , 11 of whom lost almost all their symptoms . Short-term improvement was maintained for 3 months without further formal treatment . Hypnotherapy in groups of up to 8 patients was as effective as individual therapy OBJECTIVES : Gut-directed hypnotherapy has been found to be effective in irritable bowel syndrome ( IBS ) . However , r and omized , controlled studies are rare and few have been performed outside highly specialized research centers . The objective of this study was to study the effect of gut-directed hypnotherapy in IBS in different clinical setting s outside the traditional research units . METHODS : The study population included IBS patients refractory to st and ard management . In study 1 , patients were r and omized to receive gut-directed hypnotherapy ( 12 sessions , 1 h/week ) in psychology private practice s or supportive therapy , whereas patients were r and omized to receive gut-directed hypnotherapy in a small county hospital or to serve as waiting list controls in study 2 . Gastrointestinal symptom severity and quality of life were evaluated at baseline , at 3 months follow-up and after 1 year . RESULTS : We r and omized 138 IBS patients refractory to st and ard management , 90 in study 1 and 48 in study 2 . In both the studies , IBS-related symptoms were improved at 3 months in the gut-directed hypnotherapy groups ( P<0.05 ) , but not in the control groups ( ns ) . In study 1 , a significantly greater improvement of IBS-related symptom severity could be detected in the gut-directed hypnotherapy group than in the control group ( P<0.05 ) , and a trend in the same direction was seen in study 2 ( P=0.17 ) . The results seen at 3 months were sustained up to 1 year . CONCLUSIONS : Gut-directed hypnotherapy is an effective treatment alternative for patients with refractory IBS , but the effectiveness is lower when the therapy is given outside the highly specialized research centers 30 patients with severe refractory irritable-bowel syndrome were r and omly allocated to treatment with either hypnotherapy or psychotherapy and placebo . The psychotherapy patients showed a small but significant improvement in abdominal pain , abdominal distension , and general well-being but not in bowel habit . The hypnotherapy patients showed a dramatic improvement in all features , the difference between the two groups being highly significant . In the hypnotherapy group no relapses were recorded during the 3-month follow-up period , and no substitution symptoms were observed Background / Aims Irritable bowel syndrome ( IBS ) is one of the most common functional gastrointestinal disorders and when compared to the vast knowledge pertaining to adults with IBS , very little is known about IBS in children and adolescents . We aim ed to explore the prevalence of IBS , identify symptoms and contributing factors and also to examine the efficacy of trimebutine maleate in children and adolescents . Methods The study involved 345 children and adolescents ( 4 - 18 years ) and parents were requested to fill in a question naire , Rome III criteria was used to diagnose IBS . To exclude organic disease , all patients underwent medical investigations . Half of the r and omly selected IBS patients were treated with trimebutine maleate while the rest of IBS patients were not . The IBS patients were reevaluated at the end of 3 weeks . Results The prevalence of IBS according to Rome III criteria in children and adolescents was 22.6 % and IBS with constipation was the predominant subtype . Back pain ( OR , 6.68 ) , headache ( OR , 4.72 ) and chronic fatigue ( OR , 3.74 ) were significantly higher in IBS group . The prevalence of IBS in both parents and depression in mothers was greater for the patient group than the healthy controls ( P < 0.0001 ) . The prevalence of functional dyspepsia in IBS group was 80.8 % and was significantly higher than control group . Clinical recovery was seen in 94.9 % of the trimebutine maleate group versus spontaneous recovery in 20.5 % of the non-medicated group . The difference was significant ( P < 0.0001 ) . Conclusions IBS is a common disorder in children and adolescents . IBS is closely associated with somatic and familial factors . Trimebutine maleate is effective for pediatric IBS patients Previous research from the United Kingdom has shown hypnotherapy to be effective in the treatment of irritable bowel syndrome ( IBS ) . The current study provides a systematic replication of this work in the United States . Six matched pairs of IBS patients were r and omly assigned to either a gut-directed hypnotherapy ( n=6 ) or to a symptom monitoring wait-list control condition ( n=6 ) in a multiple baseline across subjects design . Those assigned to the control condition were later crossed over to the treatment condition . Subjects were matched on concurrent psychiatric diagnoses , susceptibility to hypnosis , and various demographic features . On a composite measure of primary IBS symptoms , treatment was superior ( p=.016 ) to symptom monitoring . Results from the entire treated sample ( n=11 ; one subject was removed from analysis ) indicate that the individual symptoms of abdominal pain , constipation , and flatulence improved significantly . State and trait anxiety scores were also seen to decrease significantly . Results at the 2-month follow-up point indicated good maintenance of treatment gains . No significant correlation was found between initial susceptibility to hypnosis and treatment gain . A positive relationship was found between the incidence of psychiatric diagnosis and overall level of improvement BACKGROUND & AIMS Functional abdominal pain ( FAP ) and irritable bowel syndrome ( IBS ) are highly prevalent in childhood . A substantial proportion of patients continues to experience long-lasting symptoms . Gut-directed hypnotherapy ( HT ) has been shown to be highly effective in the treatment of adult IBS patients . We undertook a r and omized controlled trial and compared clinical effectiveness of HT with st and ard medical therapy ( SMT ) in children with FAP or IBS . METHODS Fifty-three pediatric patients , age 8 - 18 years , with FAP ( n = 31 ) or IBS ( n = 22 ) , were r and omized to either HT or SMT . Hypnotherapy consisted of 6 sessions over a 3-month period . Patients in the SMT group received st and ard medical care and 6 sessions of supportive therapy . Pain intensity , pain frequency , and associated symptoms were scored in weekly st and ardized abdominal pain diaries at baseline , during therapy , and 6 and 12 months after therapy . RESULTS Pain scores decreased significantly in both groups : from baseline to 1 year follow-up , pain intensity scores decreased in the HT group from 13.5 to 1.3 and in the SMT group from 14.1 to 8.0 . Pain frequency scores decreased from 13.5 to 1.1 in the HT group and from 14.4 to 9.3 in the SMT group . Hypnotherapy was highly superior , with a significantly greater reduction in pain scores compared with SMT ( P < .001 ) . At 1 year follow-up , successful treatment was accomplished in 85 % of the HT group and 25 % of the SMT group ( P < .001 ) . CONCLUSIONS Gut-directed HT is highly effective in the treatment of children with longst and ing FAP or IBS OBJECTIVES : Gut-directed hypnotherapy ( GHT ) in individual sessions is highly effective in the treatment of irritable bowel syndrome ( IBS ) . This study aim ed to assess the long-term effect of GHT in group sessions for refractory IBS . METHODS : A total of 164 patients with IBS ( Rome-III- criteria ) were screened , and 100 refractory to usual treatment were r and omized 1:1 either to supportive talks with medical treatment ( SMT ) or to SMT with GHT ( 10 weekly sessions within 12 weeks ) . The primary end point was a clinical ly important improvement on several dimensions of daily life ( assessed by IBS impact scale ) after treatment and 12-month follow-up . The secondary end point was improvement in general quality of life ( QOL ; Medical Outcome Study Short-Form-36 ) , psychological status ( Hospital Anxiety Depression Scale ) and reduction of single IBS symptoms . Analysis was by intention to treat . RESULTS : A total of 90 patients received allocated intervention . After treatment , 28 ( 60.8 % ) out of 46 GHT patients and 18 ( 40.9 % ) out of 44 SMTs improved ( absolute difference 20.0 % ; 95 % confidence interval ( CI ) : 0–40.2 % ; P=0.046 ) ; over 15 months , 54.3 % of GHT patients and 25.0 % of controls improved ( absolute difference 29.4 % ; 95 % CI 10.1–48.6 % ; P=0.004 ) . GHT with SMT improved physical and psychological well being significantly more than SMT alone ( P<0.001 ) . Gender , age , disease duration and IBS type did not have an influence on the long-term success of GHT . CONCLUSIONS : GHT improves IBS-related QOL , is superior to SMT alone , and shows a long-term effect even in refractory IBS Hypnosis improves irritable bowel syndrome ( IBS ) , but the mechanism is unknown . Possible physiological and psychological mechanisms were investigated in two studies . Patients with severe irritable bowel syndrome received seven biweekly hypnosis sessions and used hypnosis audiotapes at home . Rectal pain thresholds and smooth muscle tone were measured with a barostat before and after treatment in 18 patients ( study I ) , and treatment changes in heart rate , blood pressure , skin conductance , finger temperature , and forehead electromyographic activity were assessed in 24 patients ( study II ) . Somatization , anxiety , and depression were also measured . All central IBS symptoms improved substantially from treatment in both studies . Rectal pain thresholds , rectal smooth muscle tone , and autonomic functioning ( except sweat gl and reactivity ) were unaffected by hypnosis treatment . However , somatization and psychological distress showed large decreases . In conclusion , hypnosis improves IBS symptoms through reductions in psychological distress and somatization . Improvements were unrelated to changes in the physiological parameters measured BACKGROUND In western population s irritable bowel syndrome ( IBS ) affects between 10 % and 30 % of the population and has a significant effect on quality of life . It generates a substantial workload in both primary and secondary care and has significant cost implication s. Gut-directed hypnotherapy has been demonstrated to alleviate symptoms and improve quality of life but has not been assessed outside of secondary and tertiary referral centres . AIM To assess the effectiveness of gut-directed hypnotherapy as a complementary therapy in the management of IBS . DESIGN OF STUDY R and omised controlled trial . SETTING Primary care patients aged 18 - 65 years inclusive , with a diagnosis of IBS of greater than 6 weeks ' duration and having failed conventional management , located in South Staffordshire and North Birmingham , UK . METHOD Intervention patients received five sessions of hypnotherapy in addition to their usual management . Control patients received usual management alone . Data regarding symptoms and quality of life were collected at baseline and again 3 , 6 , and 12 months post-r and omisation . RESULTS Both groups demonstrated a significant improvement in all symptom dimensions and quality of life over 12 months . At 3 months the intervention group had significantly greater improvements in pain , diarrhoea and overall symptom scores ( P<0.05 ) . No significant differences between groups in quality of life were identified . No differences were maintained over time . Intervention patients , however , were significantly less likely to require medication , and the majority described an improvement in their condition . CONCLUSIONS Gut-directed hypnotherapy benefits patients via symptom reduction and reduced medication usage , although the lack of significant difference between groups beyond 3 months prohibits its general introduction without additional evidence . A large trial incorporating robust economic analysis is , therefore , urgently recommended Assessment of the physiological effects of physical and emotional stress has been hampered by a lack of suitable laboratory techniques . Since hypnosis can be used safely to induce specific emotional states of considerable intensity , we studied the effect on distal colonic motility of three hypnotically induced emotions ( excitement , anger , and happiness ) in 18 patients aged 20 - 48 years with irritable bowel syndrome . Colonic motility index was reduced by hypnosis on its own ( mean change 19.1 ; 95 % CI 0.8 , 37.3 ; p less than 0.05 ) and this change was accompanied by decreases in both pulse ( 12 ; 8 , 15 ) and respiration ( 6 ; 4 , 8) rates ( p less than 0.001 for both ) . Anger and excitement increased the colonic motility index ( 50.8 ; 29.4 , 72.2 ; and 30.4 ; 8.9 , 51.9 , respectively ; p less than 0.01 for both ) , pulse rate ( 26 ; 22 , 30 ; and 28 ; 24 , 32 ; p less than 0.001 for both ) , and respiration rate ( 14 ; 12 , 16 ; and 12 ; 10 , 14 ; p less than 0.001 for both ) . Happiness further reduced colonic motility although not significantly from that observed during hypnosis alone . Changes in motility were mainly due to alterations in rate than in amplitude of contractions . Our results indicate that hypnosis may help in the investigation of the effects of emotion on physiological functions ; this approach could be useful outside the gastrointestinal system . Our observation that hypnosis strikingly reduces fasting colonic motility may partly explain the beneficial effects of this form of therapy in functional bowel disorders Background and aims : There is now good evidence from several sources that hypnotherapy can relieve the symptoms of irritable bowel syndrome in the short term . However , there is no long term data on its benefits and this information is essential before the technique can be widely recommended . This study aim ed to answer this question . Patients and methods : 204 patients prospect ively completed question naires scoring symptoms , quality of life , anxiety , and depression before , immediately after , and up to six years following hypnotherapy . All subjects also subjectively assessed the effects of hypnotherapy retrospectively in order to define their “ responder status ” . Results : 71 % of patients initially responded to therapy . Of these , 81 % maintained their improvement over time while the majority of the remaining 19 % cl aim ed that deterioration of symptoms had only been slight . With respect to symptom scores , all items at follow up were significantly improved on pre-hypnotherapy levels ( p<0.001 ) and showed little change from post-hypnotherapy values . There were no significant differences in the symptom scores between patients assessed at 1 , 2 , 3 , 4 , or 5 + years following treatment . Quality of life and anxiety or depression scores were similarly still significantly improved at follow up ( p<0.001 ) but did show some deterioration . Patients also reported a reduction in consultation rates and medication use following the completion of hypnotherapy . Conclusion : This study demonstrates that the beneficial effects of hypnotherapy appear to last at least five years . Thus it is a viable therapeutic option for the treatment of irritable bowel syndrome BACKGROUND Stool form scales are a simple method of assessing intestinal transit rate but are not widely used in clinical practice or research , possibly because of the lack of evidence that they are responsive to changes in transit time . We set out to assess the responsiveness of the Bristol stool form scale to change in transit time . METHODS Sixty-six volunteers had their whole-gut transit time ( WGTT ) measured with radiopaque marker pellets and their stools weighed , and they kept a diary of their stool form on a 7-point scale and of their defecatory frequency . WGTT was then altered with senna and loperamide , and the measurements were repeated . RESULTS The base-line WGTT measurements correlated with defecatory frequency ( r = 0.35 , P = 0.005 ) and with stool output ( r = -0.41 , P = 0.001 ) but best with stool form ( r = -0.54 , P < 0.001 ) . When the volunteers took senna ( n = 44 ) , the WGTT decreased , whereas defecatory frequency , stool form score , and stool output increased ( all , P < 0.001 ) . With loperamide ( n = 43 ) all measurements changed in the opposite direction . Change in WGTT from base line correlated with change in defecatory frequency ( r = 0.41 , P < 0.001 ) and with change in stool output ( n = -0.54 , P < 0.001 ) but best with change in stool form ( r = -0.65 , P < 0.001 ) . CONCLUSIONS This study has shown that a stool form scale can be used to monitor change in intestinal function . Such scales have utility in both clinical practice and research |
801 | 20,587,698 | While an intact meniscus or meniscal repair was generally favorable in the ACL-reconstructed knees , meniscal repair of degenerative meniscal tissue was not favorable .
Although r and omized controlled trials are considered to be the gold st and ard in medical research , a multicenter prospect i ve cohort design may be more appropriate in assessing the long-term outcome of meniscal surgery and the role that multiple preoperative and intraoperative variables may play in clinical outcomes . | Knee meniscectomy is the most common procedure performed by orthopaedic surgeons .
While it is generally believed that loss of meniscal tissue leads to osteoarthritis and poor knee function , many variables may significantly influence this outcome . | In this prospect i ve r and omised study two treatments after non-traumatic medial meniscal tear diagnosed with radiological examination and magnetic resonance imaging were compared ; arthroscopic partial meniscectomy followed by supervised exercise or supervised exercise alone . The aim was to evaluate knee function and physical activity . Ninety patients ( mean age 56 years ) were evaluated using the Knee Injury and Osteoarthritis Outcome Score , the Lysholm Knee Scoring Scale , the Tegner Activity Scale and a Visual Analogue Scale for knee pain prior to the intervention , after 8 weeks of exercise and after 6 months . According to the outcome scores arthroscopic partial medial meniscectomy combined with exercise did not lead to greater improvement than exercise alone . After the intervention both groups reported decreased knee pain , improved knee function and a high satisfaction ( P < 0.0001 ) . Forty-one per cent of the patients returned to their pre-injury activity level after 6 months . In conclusion , when evaluated with outcome scores , arthroscopic partial medial meniscectomy followed by supervised exercise was not superior to supervised exercise alone in terms of reduced knee pain , improved knee function and improved quality of life We report the results of a prospect i ve longitudinal study of 147 athletes who had had a meniscectomy for an isolated meniscus injury . The patients were review ed in detail after median periods of 4.5 years and 14.5 years and the results analysed . The frequency of complaints related to the operation increased from 53 % at 4.5 years to 67 % at 14.5 years , while demonstrable knee instability increased from 10 % to 36 % . The incidence of radiographic changes of degeneration rose from 40 % to 89 % and at late review 8 % of patients had definite osteoarthritis by the criteria of Ahlbäck ( 1968 ) . In consequence 46 % had given up or reduced their sporting activity , and 6.5 % had changed their occupation . Radiographic deterioration started after the 4.5-year review in 49 % of the patients and was more frequent after lateral than medial meniscectomy Summary Two hundred patients were r and omly selected for either a partial or a total meniscectomy for a meniscal tear during open operation . They were followed for a median of 7.8 years after operation . After partial meniscectomy , posterior horn tears had the worst outcome , but this was only apparent when more than two-thirds of the meniscus had been removed . The amount of meniscal tissue excised was inversely related to the function of the knee , except with bucket-h and le tears treated by partial meniscectomy . Patients with bucket-h and le , anterior and posterior horn tears had similar functional results after total meniscectomy . Preservation of the peripheral rim of the meniscus following partial meniscectomy produces the best functional results .RésuméDeux cents patients atteints de lésion méniscale ont été répartis en cours d'opération , de façon r and omisée , entre méniscectomie partielle et méniscectomie totale . Ces patients ont été revus , au dernier examen , de 6.3 à 9.8 ans après l'intervention ( à 7.8 ans en moyenne ) . Après méniscectomie partielle c'étaient les lésions de la corne postérieure qui avaient les moins bons résultats fonctionnels , mais les différences de résultat selon les types de lésion n'étaient observées que lorsque plus d'un tiers de la surface méniscale avait été réséquée . La quantité de tissu méniscal enlevé était inversement proportionnelle à la qualité de la fonction du genou , sauf dans les déchirures en anse de seau traitées par méniscectomie partielle . Ces lésions étaient celles où la plus forte proportion de tissu méniscal avait été réséquée , mais do nt les résultats fonctionnels étaient meilleurs que ceux des lésions de la corne postérieure . Les patients présentant des anses de seau , des lésions de la corne antérieure ou de la corne postérieure , avaient des résultats fonctionnels similaires après méniscectomie totale . La conservation de la périphérie du ménisque après méniscectomie partielle est le facteur essentiel d'un bon résultat fonctionnel post-opératoire Two hundred patients with a meniscus lesion were peroperatively allocated to partial or total meniscectomy . The results were compared at one year and at 6.3 - 9.8 years ( median 7.8 ) . After one year , more patients with partial meniscectomy ( 90 % ) than with total meniscectomy ( 80 % ) had no complaints ( p = 0.029 ) . At the late review these figures were 62 % and 52 % respectively ( p = 0.18 ) . However , patients with partial meniscectomy had the highest functional scores . In five percent knee joint function had improved and in 35 % deteriorated , in the latter group without detectable difference between partial and total meniscectomy . The incidence of lateral laxity rose from eight to 47 % , most frequently seen after total meniscectomy . During the observation period radiological signs of knee joint degeneration changed from solely joint line narrowing into additional ridge formation and flattening of the femoral condyle , but unrelated to whether partial or total meniscectomy had been performed . Following partial meniscectomy posterior horn lesions had the poorest functional outcome , but only if more than one third of the meniscal surface had been removed . The amount of meniscal tissue excised was inversely correlated to the level of knee joint function except in bucket h and le lesions treated with partial meniscectomy . These lesions had the largest areas of meniscal tissue removed , but higher functional scores than posterior horn lesions . Preservation of the peripheral rim of the meniscus following partial meniscectomy was essential for the functional outcome after surgery Background Repair of meniscal tears is generally preferred over meniscectomy . Hypothesis Repair of unstable bucket-h and le tears of the medial meniscus leads to better outcomes than partial meniscectomy . Study Design Retrospective review of prospect ively collected data . Methods We review ed the records of 155 patients who had isolated bucket-h and le medial meniscal tears and anterior cruciate ligament tears . Fifty-six menisci were repaired ; 99 that were degenerative and crushed beyond repair were removed . Patients were evaluated at a mean follow-up of 6 to 8 years after surgery with the International Knee Documentation Committee examination and a modified Noyes question naire . Results The mean subjective scores were similar for patients in both the repair ( N = 51 ) and meniscectomy ( N = 87 ) groups . However , in the repair group , the mean subjective score of 93.9 for nondegenerative menisci was significantly better than the 87.1 for degenerative menisci . Objective grade s for 25 patients in the repair group were normal or nearly normal in 22 patients ( 88 % ) and for 51 of 56 patients ( 91 % ) in the removal group . Radiographic subscores for the repair group were normal or nearly normal in 23 patients in the repair group and 49 in the removal group . Conclusion Outcomes from meniscal repair were not superior to those from partial removal . Patients with repaired degenerative tears had significantly lower subjective scores than those with nondegenerative tears We have carried out a prospect i ve , longitudinal 30-year review of 95 adolescents who underwent total meniscectomy in one knee , and have compared the results with those observed 13 years earlier . All the medical records were scrutinised . Of the 63 patients review ed clinical ly , 47 reported decreased sporting activity , although subjective satisfaction rose by 3 % to 71 % . The scores on the WOMAC osteoarthritis index differed significantly between patients grouped by subjective global assessment . Satisfactory function scores increased from 48 % to 60 % . In the 53 patients consenting to bilateral radiography of the knee , the incidence of narrowing of the articular cartilage in the operated knee increased significantly between the review s ( 19 % to 36 % ) . Progression of degenerative change paralleled reduction in activity . Outcome measures were best after medial , intermediate after lateral and worst after double meniscectomy In order to compare partial with total meniscectomy a prospect i ve clinical study of 200 patients was carried out . At arthrotomy 100 patients were allocated to each type of operation . The two groups did not differ in duration of symptoms , age distribution , or sex ratio . The operations were performed as conventional arthrotomies . One hundred and ninety two of the patients were seen at follow up 2 and 12 months after operation . There was no difference in the period off work between the two groups . One year after operation , 6 of the 98 patients treated with partial meniscectomy had undergone further operation . In all posterior tears were found at both procedures . Among the 94 patients undergoing total meniscectomy , 4 required further operation . In each , part of the posterior horn had been left at the primary procedure . One year after operation significantly more patients who had undergone partial meniscectomy had been relieved of symptoms . However , the two groups did not show any difference in the degree of radiological changes present BACKGROUND The efficacy of arthroscopic surgery for the treatment of osteoarthritis of the knee is unknown . METHODS We conducted a single-center , r and omized , controlled trial of arthroscopic surgery in patients with moderate-to-severe osteoarthritis of the knee . Patients were r and omly assigned to surgical lavage and arthroscopic débridement together with optimized physical and medical therapy or to treatment with physical and medical therapy alone . The primary outcome was the total Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) score ( range , 0 to 2400 ; higher scores indicate more severe symptoms ) at 2 years of follow-up . Secondary outcomes included the Short Form-36 ( SF-36 ) Physical Component Summary score ( range , 0 to 100 ; higher scores indicate better quality of life ) . RESULTS Of the 92 patients assigned to surgery , 6 did not undergo surgery . Of the 86 patients assigned to control treatment , all received only physical and medical therapy . After 2 years , the mean ( + /-SD ) WOMAC score for the surgery group was 874+/-624 , as compared with 897+/-583 for the control group ( absolute difference [ surgery-group score minus control-group score ] , -23+/-605 ; 95 % confidence interval [ CI ] , -208 to 161 ; P=0.22 after adjustment for baseline score and grade of severity ) . The SF-36 Physical Component Summary scores were 37.0+/-11.4 and 37.2+/-10.6 , respectively ( absolute difference , -0.2+/-11.1 ; 95 % CI , -3.6 to 3.2 ; P=0.93 ) . Analyses of WOMAC scores at interim visits and other secondary outcomes also failed to show superiority of surgery . CONCLUSIONS Arthroscopic surgery for osteoarthritis of the knee provides no additional benefit to optimized physical and medical therapy . ( Clinical Trials.gov number , NCT00158431 . |
802 | 17,229,239 | Over-the-counter medications are effective in treating symptomatic gastro-oesophageal reflux disease . | BACKGROUND Over-the-counter histamine-2 receptor antagonists , antacids and alginate/antacids are commonly used for gastro-oesophageal reflux disease .
AIM To conduct a systematic review and meta- analysis of related treatment trials . | Abstract Three r and omised groups of 20 patients with gastro-œsophageal reflux were studied using 15-hour recordings of lower œsophageal pH , before and after two weeks ' treatment , either with an alginate/antacid compound ( ' Gaviscon ' ) , antacids alone , or a placebo tablet . Significant reduction in the number of reflux episodes and percentage time during which the lower œsophageal pH was acid was noted in the gaviscon group after treatment , whereas no significant changes occurred in the other two groups . Symptoms reported by patients during the second test were fewer after gaviscon treatment than after antacid alone The symptomatic effect of a 2-week low-dose antacid tablet regimen was assessed in a prospect i ve , double-blind , r and omized , placebo-controlled , crossover trial in 47 patients with endoscopically verified reflux oesophagitis . During treatment with antacid there were lower global symptomatic scores ( p less than 0.05 ) , less acid regurgitation ( p less than 0.05 ) , and fewer days ( p less than 0.01 ) and nights ( p less than 0.05 ) with heartburn than during placebo therapy . Also , significantly more patients preferred antacid than placebo treatment ( p less than 0.05 ) . Thus , a low-dose antacid tablet regimen relieves symptoms significantly better than placebo in patients with reflux oesophagitis Although antacids have been the mainstay of pharmacologic therapy for reflux esophagitis , their effectiveness has not been tested in a placebo-controlled double-blind trial . We report a double-blind comparison of liquid antacid vs placebo in the treatment of reflux esophagitis in 32 patients with chronic heartburn . Entry criteria included the presence of symptomatic gastroesophageal reflux confirmed by both an acid perfusion ( Bernstein ) test and by intraesophageal pH probe . Drug treatment consisted of 15 ml ( 80 mEq ) doses of antacid ( Maalox Therapeutic Concentration , William H. Rorer ) or placebo taken 7 times daily , ie , 1 and 3 hr after meals and at bedtime . Both groups showed significant improvement ( P<0.05 ) in both frequency and severity of heartburn . The time to reproduce heartburn with the timed Bernstein test was increased with both active drug and placebo therapy . The mean increase was 402 % ( 41±20 sec to 169±66 sec ) for the placebo group and 286 % ( 42±16 to 120±57 sec ) in the antacid group . Both the antacid and placebo groups showed improvement in the degree of esophagitis as assessed endoscopically . The current study asked : does regular antacid therapy have a favorable influence on the natural history of symptomatic reflux esophagitis , ie , does therapy heal or otherwise change esophagitis so that painful episodes are either less frequent , less severe , or both ? We found that the natural history of symptomatic reflux esophagitis was to improve with either antacid or placebo . There was no significant difference in antacid or placebo on the ( short-term ) natural history of the disease BACKGROUND Heartburn is frequently associated with overindulgence in food and drink , meal-stimulated gastric acid secretion , and a gastroesophageal reflux with a pH of 4 or lower . Nizatidine is a selective histamine2 receptor antagonist that effectively suppresses gastric acid secretion at lower than prescription doses and has been approved for nonprescription use in the prevention of postpr and ial heartburn . OBJECTIVE To examine the relative effectiveness of 3 dose levels of nizatidine ( 225 mg , 75 mg , and 25 mg ) in preventing postpr and ial heartburn . METHODS Four hundred thirteen subjects with documented moderate to severe heartburn following a st and ard meal that provoked heartburn were r and omized to receive a single dose of nizatidine at 225 mg ( n = 104 ) , 75 mg ( n = 101 ) , or 25 mg ( n = 105 ) , or placebo ( n = 103 ) 30 minutes before the meal , at 30 minutes ( immediately after completing the meal ) , and at 60 , 90 , 120 , 150 , 180 , and 210 minutes ( from beginning the meal ) , subjects assessed the presence or absence of heartburn ( yes or no ) and the severity of heartburn ( 100-mm visual analog scale ) . RESULTS The use of both 225 mg and 75 mg of nizatidine were significantly better than placebo in preventing heartburn in the proportion of subjects with complete prevention of heartburn ( 15 [ 14.4 % ] and 15 [ 14.9 % ] , respectively , vs 3 [ 2.9 % ] ; P < .001 ) ; the effects of nizatidine , 25 mg , in 7 subjects ( 7 % ) were not distinguishable from placebo . Similar results for nizatidine , 225 mg and 75 mg , were seen for longest duration of no heartburn , total duration of no heartburn , the average severity of heartburn , and the peak heartburn severity . All 3 doses of nizatidine were superior to placebo ( P < .001 ) in reducing average and peak heartburn severity and were well tolerated . CONCLUSIONS Single doses of 225 mg and 75 mg of nizatidine administered 30 minutes before a st and ard meal intended to provoke heartburn are significantly more effective than placebo for the prevention and /or reduction of postpr and ial heartburn A double-blind , placebo-controlled , r and omized crossover study was made of 60 patients with chronic heartburn to test the efficacy of foaming antacid in promoting symptom relief . Heartburn was induced by a meal consisting of chili , black coffee , and a spicy tomato drink mix . Of the 60 patients , 40 ( 67 % ) had relief within 15 minutes after taking foaming antacid tablets as compared to only 17 ( 28 % ) after taking a placebo . The difference in response was significant ( P < .05 ) . Foaming antacid appears to be an effective therapy for acute postpr and ial heartburn To compare the effects of ranitidine 75 mg with those of either cimetidine 200 mg or placebo given on dem and for relief of typical symptoms of gastro‐oesophageal reflux disease during a 15‐day period Summary Twenty-eight patients with hiatus hernia and severe symptoms of oesophageal reflux completed a double-blind cross-over trial in which compounds design ed to float on gastric contents were administered . Each patient received an alginate/antacid compound ( ‘ Gaviscon ’ ) , alginate without antacid and ‘ placebo ’ inr and omized order for periods of two weeks . Significant relief of both regurgitation and heartburn was achieved with the alginate I antacid compound despite its low antacid content . The mode of action of alginate is discussed and , as alginate without antacid is only marginally better than placebo , it seems probable that it facilitates placement of antacid in the upper stomach and lower oesophagus . † ‘ Gaviscon ’ is a trade mark of Reckitt and Colman Limited |
803 | 25,623,739 | New evidence -based statements and expert opinion supplement the original guideline published in 2012 , which provided guidance for the diagnosis and overall management of OAB in adults . | PURPOSE The purpose of this guideline amendment , herein referred to as the amendment , is to incorporate relevant newly published literature to better provide a clinical framework for the diagnosis and treatment of patients with non-neurogenic overactive bladder . | Objective To verify whether the combination of transcutaneous electrical neural stimulation ( TENS ) with oxybutynin in the treatment of women with overactive bladder ( OAB ) would be more effective than isolated treatments . Methods We r and omized 75 women with OAB , in three groups : GI—30 min TENS , twice a week ; GII — daily slow release 10 mg oxybutynin ; and GIII — TENS + oxybutynin ( multimodal ) ; all for 12 weeks . Patients were evaluated with vali date d question naires International Consultation on Incontinence-Short Form ( ICIQ-SF ) , International Consultation on Incontinence-OAB ( ICIQ-OAB ) , Symptom bother , and 3-day Voiding diary at weeks 0 , 12 , and 24 . Results The groups were similar before treatment . After treatment , all groups significantly improved in OAB symptoms and quality of life ( QoL ) . At week 12 , ICIQ-OAB scores were 5.9 , 4.6 , and 2.9 , in groups I , II , and III , respectively , p = 0.01 . At week 24 , GI and GIII kept the scores of the end of treatment ( week 12 ) , while GII increased ICIQ-OAB from 4.6 to 9.2 , p = 0.0001 , ICIQ-SF from 9.8 to 13.3 , p = 0.0006 , and Symptom bother score from 3.4 to 7.0 , p = 0.0001 . Conclusions The multimodal treatment was more effective and TENS alone or in association presented longer lasting results for improvement of clinical symptoms of OAB and BACKGROUND Overactive bladder ( OAB ) syndrome with urinary incontinence ( UI ) is prevalent in the population and impairs health-related quality of life ( HRQOL ) . OBJECTIVE To assess the impact on efficacy , safety , and HRQOL of onabotulinumtoxinA ( BOTOX ( ® ) , Allergan , Inc. ) treatment in patients with OAB with UI . DESIGN , SETTING , AND PARTICIPANTS This pivotal , multicentre , double-blind , r and omised , placebo-controlled , phase 3 study enrolled patients with idiopathic OAB with ≥ 3 urgency UI episodes over 3 d and ≥ 8 micturitions per day who were inadequately managed by anticholinergics . INTERVENTION OnabotulinumtoxinA at a 100U dose ( n=277 ) or placebo ( n=271 ) , administered as 20 intradetrusor injections of 0.5 ml . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Co- primary end points were change from baseline in the number of UI episodes per day and proportion of patients reporting positive treatment response on the treatment benefit scale ( TBS ) at week 12 . Additional end points included other OAB symptoms ( episodes of urinary urgency incontinence , micturition , urgency , and nocturia ) and HRQOL ( Incontinence Quality of Life [ I-QOL ] , King 's Health Question naire [ KHQ ] ) . Safety assessment s included adverse events ( AEs ) , postvoid residual ( PVR ) urine volume , and initiation of clean intermittent catheterisation ( CIC ) . RESULTS AND LIMITATIONS OnabotulinumtoxinA significantly decreased UI episodes per day at week 12 ( -2.95 for onabotulinumtoxinA versus -1.03 for placebo ; p<0.001 ) . Reductions from baseline in all other OAB symptoms were also significantly greater following onabotulinumtoxinA compared with placebo ( p ≤ 0.01 ) . Patients perceived a significant improvement in their condition , as measured by patients with a positive treatment response on the TBS ( 62.8 % for onabotulinumtoxinA versus 26.8 % for placebo ; p<0.001 ) . Clinical ly meaningful improvements from baseline in all I-QOL and KHQ multi-item domains ( p<0.001 versus placebo ) indicated positive impact on HRQOL . AEs were mainly localised to the urinary tract . Mean PVR was higher in the onabotulinumtoxinA group ( 46.9 ml versus 10.1 ml at week 2 ; p<0.001 ) ; 6.9 % of onabotulinumtoxinA patients versus 0.7 % of placebo patients initiated CIC . CONCLUSIONS OnabotulinumtoxinA 100 U was well tolerated and demonstrated significant and clinical ly relevant improvements in all OAB symptoms , patient-reported benefit , and HRQOL in patients inadequately managed by anticholinergics . TRIAL REGISTRATION Clinical Trials.gov : NCT00910520 OBJECTIVE To determine the efficacy of intradetrusor injections of botulinum toxin A for non-neurogenic urinary urge incontinence . METHODS We conducted a six-month , r and omized , double-blind controlled trial involving women with urinary urge incontinence . Participants received intradetrusor injections of either botulinum toxin ( 100U in 10 mL ) via cystoscopy or a placebo control ( saline injection ) . The primary outcome was maximum bladder capacity at cystoscopy . Secondary outcomes included quality -of-life measures , 24-hour leakage rate , patients ' subjective assessment , and safety data . RESULTS There were 21 participants : 11 in the botulinum toxin ( treated ) group and 10 in the placebo ( control ) group . There were no significant differences between the groups at baseline . After six months the mean maximum bladder capacity at cystoscopy was 161.6 mL greater in the treated group than in the control group ( P = 0.018 ) . There were no differences in diary data or quality -of-life measures . The 24-hour pad test ( a measure of leakage ) after three months showed significant improvement in the treated group ( difference 272.12 g , P = 0.016 ) ; treated subjects also showed subjective benefit at three months ( difference 1.29 , P = 0.007 ) and at six months ( difference 1.16 , P = 0.01 ) . There was no significant difference in rates of urinary tract infection between groups . There was one serious adverse event ( a perioperative cardiac event ) in the botulinum toxin group . CONCLUSION Botulinum toxin increased bladder capacity at cystoscopy and reduced urinary incontinence on 24-hour pad testing in adult females with urinary urge incontinence . There was one adverse event in the group treated with botulinum toxin Aim : To evaluate the clinical outcomes of two different doses of BTX-A in patients with refractory idiopathic overactive bladder . Patients and Methods : Thirty nine patients with refractory idiopathic overactive bladder from 1/1/2008 till 30/3/2009 were evaluated in a tertiary care hospital . Patients were evaluated using urodynamic studies , voiding diary , UDI-6 and IIQ-7 question naires prior to being prospect ively r and omized ( alternate r and omization ) to the BTX-A applications and three months after treatment . Voiding diary and residual volume were followed two weeks later . All patients received intradetrusorial injections of BTX-A ( Botox , Allergan , Irvine , CA ) of 100u or 200u under cystoscopic control on an outpatient basis . The primary endpoint was assessed for the improvement of urodynamic parameters and adverse events at three months after the initial treatment . Secondary end points included urinary frequency , urgency and UUI episodes as assessed by voiding diary and QoL. Results : Eleven patients were enrolled to each arm of the study . There were no significant differences in demographic characteristics between the two groups . Urodynamic assessment at the end of the third month showed significant improvement in urodynamic variables in both groups . There was no statistically significant difference in urodynamic parameters and in the voiding diary between the two groups . QOL was significantly improved in both groups with no statistically significant difference between the different doses . Only three patients developed acute urinary retention . Conclusion : BTX-A at 100u and 200u appears to improve symptoms , urodynamic parameters and QoL with no statistical significance between the two groups BACKGROUND Patients with urgency urinary incontinence ( UUI ) due to overactive bladder ( OAB ) refractory to oral antimuscarinics have limited therapeutic options . OnabotulinumtoxinA appears to be an effective new treatment . OBJECTIVE Assess disease-specific quality -of-life outcomes and general health-related quality -of-life ( HRQOL ) outcomes following treatment with onabotulinumtoxinA in patients with idiopathic OAB and UUI inadequately managed with antimuscarinics . DESIGN , SETTING , AND PARTICIPANTS A phase 2 , r and omized , double-blind , placebo-controlled , dose-ranging study conducted at 40 sites from July 2005 to June 2008 with 313 patients ( 288 females ) with idiopathic OAB experiencing eight or more UUI episodes per week and eight or more micturitions per day at baseline , with follow-up of 36 wk . INTERVENTION Intradetrusor onabotulinumtoxinA ( 50 U , 100 U , 150 U , 200 U , or 300 U ) or placebo . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS HRQOL was assessed using the urinary Incontinence-Specific Quality -of-Life Instrument ( I-QOL ) , the King 's Health Question naire ( KHQ ) symptom component , and the Medical Outcomes Study 36-Item Short-Form Health Survey . Descriptive statistics were used for absolute scores/changes from baseline . Within-group changes from baseline were assessed using paired t tests . Change from baseline for each onabotulinumtoxinA group compared with placebo was analyzed using an analysis of covariance model . RESULTS AND LIMITATIONS OnabotulinumtoxinA treatment at doses≥100 U produced significantly greater improvements than placebo in the I-QOL total and subscale scores at all follow-up visits from week 2 through week 24 ( p<0.05 ) . OnabotulinumtoxinA doses≥100 U produced significantly greater improvements than placebo in the KHQ symptom score at a majority of follow-up visits . HRQOL instruments demonstrated low to moderate correlations ( Spearman correlation range : 0.01 - 0.51 ) with the symptoms of UUI recorded using daily diary data , with I-QOL demonstrating the highest correlations . A study limitation was that certain quality -of-life measures were exploratory and not vali date d. CONCLUSIONS A single onabotulinumtoxinA treatment with doses≥100 U result ed in statistically significant and clinical ly meaningful improvement in HRQOL by week 2 compared with placebo , and this improvement was sustained for ≤36 wk in patients with idiopathic OAB and UUI who were inadequately managed by oral antimuscarinics . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT00168454 To compare the efficacy of tolterodine plus simplified bladder training ( BT ) with tolterodine alone in patients with an overactive bladder Introduction and hypothesisMirabegron is a potent and selective β3-adrenoceptor agonist that may represent an alternative treatment option in place of antimuscarinics for patients with overactive bladder . Methods Patients completed a single-blinded , 2-week placebo run-in period followed by 12 weeks of r and omized ( n = 928 ) double-blinded treatment with mirabegron oral controlled absorption system ( OCAS ) 25 , 50 , 100 , or 200 mg once-daily ( QD ) , placebo or tolterodine extended release ( ER ) 4 mg QD . The primary endpoint was change from baseline to end-of-treatment in mean number of micturition episodes/24 h. Secondary endpoints included changes in mean volume voided per micturition ; mean number of urinary incontinence , urgency urinary incontinence , and urgency episodes/24 h ; severity of urgency ; nocturia ; and quality of life measures . Safety parameters included vital signs , adverse events , laboratory tests , electrocardiogram measurements and post-void residual volume . Results Mirabegron 25 , 50 , 100 , and 200 mg result ed in dose-dependent reductions ( improvements ) from baseline to end-of-treatment in micturition frequency of 1.9 , 2.1 , 2.1 , and 2.2 micturitions/24 h respectively , versus 1.4 micturitions/24 h with placebo ( p ≤ 0.05 for the mirabegron 50- , 100- , and 200-mg comparisons ) . There was a statistically significant improvement with mirabegron compared with placebo for most secondary endpoints including quality of life variables . While there was a significant ( p < 0.05 ) increase from baseline in pulse rate in the mirabegron 100-mg and 200-mg groups , this was not associated with an increased incidence of cardiovascular adverse events . Conclusions The favorable efficacy and tolerability of mirabegron in this phase II dose-finding study has led to its successful advancement into a phase III clinical development program Objective : The aim of the study was a prospect i ve assessment of patient-reported side effects in an open-label study after intradetrusor botulinum toxin injections for idiopathic overactive bladder ( OAB ) . Patients and Methods : Botulinum toxin A injection was performed in 56 patients with idiopathic OAB . Patients were followed up for 6 months concerning side effects and patients ’ satisfaction . Results : Different types of side effects were assessed such as dry mouth ( 19.6 % ) , arm weakness ( 8.9 % ) , eyelid weakness ( 8.9 % ) , leg weakness ( 7.1 % ) , torso weakness ( 5.4 % ) , impaired vision ( 5.4 % ) and dysphagia ( 5.4 % ) . In all cases , symptoms were mild and transient . Urological complications such as gross hematuria ( 17.9 % ) , acute urinary retention ( 8.9 % ) and acute urinary tract infection ( 7.1 % ) were noticed . In all cases , acute urinary retention was transient and treated with temporary intermittent self-catheterization . There was no statistically significant correlation between dosage and observed side effects . Patients ’ satisfaction rate was high ( 71.4 % ) . Conclusion : Intradetrusor injection of botulinum toxin was associated with a high rate of neurourological side effects . In general , side effects were transient , mild and did not require special treatment PURPOSE We report the long-term efficacy and safety of percutaneous tibial nerve stimulation with the Urgent ® PC Neuromodulation System for overactive bladder after 3 years of therapy . MATERIAL S AND METHODS Fifty participants in the r and omized , double-blind SUmiT ( Sham Effectiveness in Treatment of Overactive Bladder Symptoms ) Trial who met the primary effectiveness end point after 12 weekly percutaneous tibial nerve stimulation treatments were enrolled in this prospect i ve study to assess long-term outcomes with percutaneous tibial nerve stimulation . STEP ( Sustained Therapeutic Effects of Percutaneous Tibial Nerve Stimulation ) Study patients were prescribed a fixed schedule 14-week tapering protocol followed by a personal treatment plan aim ed at sustaining overactive bladder symptom improvement . Overactive bladder and quality of life question naires were completed every 3 months and 3-day voiding diaries were completed every 6 months . RESULTS A total of 29 patients completed the 36-month protocol and received a median of 1.1 treatments per month after a 14-week treatment tapering protocol . A Bayesian model estimated that 77 % ( 95 % CI 64 - 90 ) of patients maintained moderate or marked improvement in overactive bladder symptoms at 3 years . Compared to baseline , median voids per day decreased from 12.0 ( IQR 10.3 - 13.7 ) to 8.7 ( IQR 7.3 - 11.3 ) , nighttime voids per night decreased from 2.7 ( IQR 1.7 - 3.3 ) to 1.7 ( IQR 1.0 - 2.7 ) and urge incontinence episodes per day decreased from 3.3 ( IQR 0.7 - 6.0 ) to 0.3 ( IQR 0.0 - 1.0 ) ( all p < 0.0001 ) . All quality of life parameters remained markedly improved from baseline through 3 years ( all p < 0.0001 ) . One patient experienced 2 mild treatment related adverse events of bleeding at the needle site during followup . CONCLUSIONS Most STEP participants with an initial positive response to 12 weekly percutaneous tibial nerve stimulation treatments safely sustained overactive bladder symptom improvement to 3 years with an average of 1 treatment per month AIMS This prospect i ve , r and omized , multicenter trial evaluated the 6-month success rate of sacral neuromodulation ( SNM ) with InterStim ® Therapy versus st and ard medical therapy ( SMT ) for overactive bladder ( OAB ) . METHODS Enrolled subjects discontinued OAB medications prior to and during baseline data collection and were r and omized 1:1 to SNM or SMT . Subjects had bothersome symptoms of overactive bladder ( OAB ) including urinary urge incontinence ( ≥2 leaks/72 hr ) and /or urgency-frequency ( ≥8 voids/day ) . Subjects failed at least one anticholinergic medication , and had at least one medication not yet attempted . The primary objective was to compare OAB therapeutic success rate at 6 months between SNM and SMT . RESULTS Overall , 147 subjects were r and omized ( 70 to SNM and 77 to SMT ) ; 93 % were female and mean age was 58 . The primary intent to treat analysis showed OAB therapeutic success was significantly greater in the SNM group ( 61 % ) than the SMT group ( 42 % ; P = 0.02 ) . In the as treated analysis , OAB therapeutic success was 76 % for SNM and 49 % for SMT ( P = 0.002 ) . The SNM group showed significant improvements in quality of life versus the SMT group ( all P < 0.001 ) and 86 % of SNM subjects reported improved or greatly improved urinary symptom interference score at 6 months , compared to 44 % for SMT subjects . The device-related adverse event rate was 30.5 % and the medication-related adverse event rate was 27.3 % . CONCLUSIONS This study demonstrates superior objective and subjective success of SNM compared to SMT . SNM is shown to be a safe and effective treatment for OAB patients with mild to moderate symptoms . Neurourol . Urodynam . 34:224 - 230 , 2015 . © 2014 Wiley Periodicals , We compared the effects of bladder training and /or tolterodine as first line treatment in female patients with overactive bladder ( OAB ) . One hundred and thirty-nine female patients with OAB were r and omized to treatment with bladder training ( BT ) , tolterodine ( To , 2 mg twice daily ) or both ( Co ) for 12 weeks . Treatment efficacy was measured by micturition diary , urgency scores and patients ' subjective assessment of their bladder condition . Mean frequency and nocturia significantly decreased in all treatment groups , declining 25.9 % and 56.1 % , respectively , in the BT group ; 30.2 % and 65.4 % , respectively , in the To group ; and 33.5 % and 66.3 % , respectively in the Co group ( p<0.05 for each ) . The decrease in frequency was significantly greater in the Co group than in the BT group ( p<0.05 ) . Mean urgency score decreased by 44.8 % , 62.2 % and 60.2 % in the BT , To , and Co groups , respectively , and the improvement was significantly greater in the To and Co groups than in the BT group ( p<0.05 for each ) . Although BT , To and their combination were all effective in controlling OAB symptoms , combination therapy was more effective than either method alone . Tolterodine alone may be instituted as a first-line therapy , but may be more effective when combined with bladder training PURPOSE We compared 200 U intradetrusor botulinum toxin A vs placebo in women with refractory idiopathic urge incontinence . MATERIAL S AND METHODS This institutional review board approved , multicenter registered trial r and omized women with refractory urge incontinence , detrusor overactivity incontinence and 6 or greater urge incontinence episodes in 3 days to botulinum toxin A or placebo at a 2:1 ratio . Refractory was defined as inadequate symptom control after 2 or more attempts at pharmacotherapy and 1 or more other first line therapies for detrusor overactivity incontinence . The primary outcome measure was time to failure , as evidence d by a Patient Global Impression of Improvement score of 4 or greater at least 2 months after injection , or changes in treatment ( initiation or increase ) at any time after injection . Safety data , including increased post-void residual volume , defined as more than 200 ml irrespective of symptoms , was obtained at specified time points . RESULTS Approximately 60 % of the women who received botulinum toxin A had a clinical response based on the Patient Global Impression of Improvement . The median duration of their responses was 373 days , significantly longer than the 62 days or less for placebo ( p < 0.0001 ) . In the botulinum toxin A group increased post-void residual urine ( 12 of 28 women or 43 % ) and urinary tract infection in those with increased post-void residual urine ( 9 of 12 or 75 % ) exceeded expected ranges . Further injections were stopped after 43 patients were r and omized , including 28 to botulinum toxin A and 15 to placebo . CONCLUSIONS Local injection of 200 U botulinum toxin A was an effective and durable treatment for refractory overactive bladder . However , a transient post-void residual urine increase was experienced in 43 % of patients . Botulinum toxin A for idiopathic overactive bladder is still under investigation AIMS To evaluate the safety , sustained effectiveness , and treatment interval for percutaneous tibial nerve stimulation ( PTNS ) for overactive bladder ( OAB ) therapy through 24 months . METHODS A prospect i ve study following treatment success after 12 weekly PTNS treatments , subjects were prescribed a 14-week tapering protocol , followed by ongoing therapy with a Personal Treatment Plan determined by the investigator and subject to sustain subject OAB symptom improvement . Question naires were completed every 3 months , voiding diaries every 6 months ; adverse events were reported throughout . RESULTS Of 50 subjects enrolled , 35 remained in the study at 24 months . During the 24 months following initial treatment success and a 14-week tapering protocol , mean treatments per month was 1.3 . Voiding diary and OAB-q data demonstrate sustained improvement reported at 13 weeks through 24 months . Improvements in frequency , urge incontinence episodes , night-time voids and moderate-to-severe urgency episodes from voiding diaries at 6 , 12 , 18 , and 24 months were statistically significant compared to baseline ( prior to initial 12 weekly treatments ) . Compared to baseline , OAB-q symptom severity scores and health related quality of life scores were statistically significant for improvement at each tested time point . Five mild adverse events of unknown relation to treatment were reported . CONCLUSION Sustained safety and efficacy of PTNS were demonstrated over 24 months with initial success after 12 weekly treatments , followed by a 14-week prescribed tapering protocol and a Personalized Treatment Plan . With an average of 1.3 treatments per month , PTNS therapy is a safe , durable , and valuable long-term OAB treatment option to sustain clinical ly significant OAB symptom control BACKGROUND In the treatment of patients with idiopathic overactive bladder ( iOAB ) , high doses of botulinum toxin type A ( BoNTA ) were often associated with complications result ing from high postvoid residuals ( PVR ) , leading to clean intermittent catheterisation ( CIC ) and urinary tract infections ( UTI ) . OBJECTIVE Evaluate the efficacy and tolerability of low doses of onabotulinumtoxinA compared to placebo in patients with iOAB . DESIGN , SETTING , AND PARTICIPANTS Between 2005 and 2009 , adults with persistent iOAB were included in a prospect i ve , r and omised , double-blind , placebo-controlled comparative trial . INTERVENTION Patients were r and omised to undergo a single intradetrusor injection procedure of either placebo or onabotulinumtoxinA ( 50 U , 100 U or 150 U ) . MEASUREMENTS The initial evaluations ( ie , clinical and urodynamic variables as well as quality of life [ QoL ] ) were repeated at day 8 and months 1 , 3 , 5 , and 6 . RESULTS AND LIMITATIONS Ninety-nine patients were included in the efficacy analysis . Three months after the procedure , we observed>50 % improvement versus baseline in urgency and urge urinary incontinence ( UUI ) in 65 % and 56 % of patients who respectively received 100 U ( p=0.086 ) and 150 U ( p=0.261 ) BoNTA injections and > 75 % improvement in 40 % of patients of both groups ( 100 U [ p=0.058 ] and 150 U [ p=0.022 ] ) . Complete continence was observed in 55 % and 50 % patients after 100 U and 150 U BoNTA treatment , respectively , at month 3 . Frequency symptoms and QoL improved up to the 6-mo visit . We observed only three patients with a PVR>200 ml in the 150 U group and a few UTIs . CONCLUSIONS 100 U and 150 U BoNTA injections were well tolerated and have both shown to improve symptoms and QoL in patients with iOAB . Nevertheless , 100 U injections showed a reasonable efficacy , with a lower risk of high PVR . TRIAL REGISTRATION Clinical Trials.gov NCT00231491 BACKGROUND Mirabegron , a β(3)-adrenoceptor agonist , has been developed for the treatment of overactive bladder ( OAB ) . OBJECTIVE To assess the efficacy and tolerability of mirabegron versus placebo . DESIGN , SETTING , AND PARTICIPANTS Multicenter r and omised double-blind , parallel-group placebo- and tolterodine-controlled phase 3 trial conducted in 27 countries in Europe and Australia in patients ≥ 18 yr of age with symptoms of OAB for ≥ 3 mo . INTERVENTION After a 2-wk single-blind placebo run-in period , patients were r and omised to receive placebo , mirabegron 50 mg , mirabegron 100 mg , or tolterodine extended release 4 mg orally once daily for 12 wk . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Patients completed a micturition diary and quality -of-life ( QoL ) assessment s. Co- primary efficacy end points were change from baseline to final visit in the mean number of incontinence episodes and micturitions per 24h . The primary comparison was between mirabegron and placebo with a secondary comparison between tolterodine and placebo . Safety parameters included adverse events ( AEs ) , laboratory assessment s , vital signs , electrocardiograms , and postvoid residual volume . RESULTS AND LIMITATIONS A total of 1978 patients were r and omised and received the study drug . Mirabegron 50-mg and 100-mg groups demonstrated statistically significant improvements ( adjusted mean change from baseline [ 95 % confidence intervals ] ) at the final visit in the number of incontinence episodes per 24h ( -1.57 [ -1.79 to -1.35 ] and -1.46 [ -1.68 to -1.23 ] , respectively , vs placebo -1.17 [ -1.39 to -0.95 ] ) and number of micturitions per 24h ( -1.93 [ -2.15 to -1.72 ] and -1.77 [ -1.99 to -1.56 ] , respectively , vs placebo -1.34 [ -1.55 to -1.12 ] ; p<0.05 for all comparisons ) . Statistically significant improvements were also observed in other key efficacy end points and QoL outcomes . The incidence of treatment-emergent AEs was similar across treatment groups . The main limitation of this study was the short ( 12-wk ) duration of treatment . CONCLUSIONS Mirabegron represents a new class of treatment for OAB with proven efficacy and good tolerability . TRIAL IDENTIFICATION : This study is registered at Clinical Trials.gov , identifier NCT00689104 Study Type – Therapy ( RCT ) Level of Evidence To evaluate the efficacy and safety of the β3‐adrenoceptor agonist mirabegron , in a Japanese population with overactive bladder ( OAB ) OBJECTIVES This was a single-center , institutional review board-approved study , conducted in the USA that used a 3 × 3 orthogonal Latin squares crossover design to assess variability in overactive bladder symptoms and adverse events when subjects were exposed to three rate setting s of sacral neuromodulation . METHODS Thirteen female subjects who had urgency frequency and urinary urge incontinence were enrolled into the study . Twelve subjects completed the study . Upon enrollment , each subject was r and omized to one of three rate- setting sequences : 5.2 , 14 , and 25 Hz . Each rate setting was tested for 1 week in every subject . RESULTS When subjects were programmed to 5.2 , 14 , and 25 Hz , they had an average of 3.83 ± 2.27 , 2.37 ± 1.83 , and 2.82 ± 2.1 incontinence episodes per day and an average of 2.61 ± 1.64 , 1.84 ± 1.43 , and 1.94 ± 1.61 pad changes per day , respectively . Rate had a statistically significant effect on the number of incontinent episodes ( P < 0.001 ) and number of pad changes ( P = 0.039 ) with more incontinent episodes in the 5.2-Hz setting compared to the 14- and 25-Hz setting s ( P < 0.04 ) for both measurements . Nine subjects reported 21 adverse events . None of the adverse events was considered either a serious or an unanticipated adverse device effect ( UADE ) . CONCLUSION Rate significantly affected the number of incontinence episodes and pad changes per day . The number of adverse events was similar across the three rate setting s with programming-related adverse events lowest in the 14 Hz group OBJECTIVES To investigate the clinical and urodynamic effects of suburothelial injection of botulinum A toxin on patients with nonneurogenic detrusor overactivity . Intradetrusor injection of botulinum A toxin has been used to treat patients with detrusor overactivity . Suburothelial injection of botulinum A toxin might effectively inhibit the occurrence of detrusor overactivity mediated by sensory nerves . METHODS Twenty patients with nonneurogenic detrusor overactivity refractory to anticholinergics were enrolled and treated with injection of 200 U botulinum A toxin into the suburothelial space . The clinical effects on the lower urinary tract symptoms and urodynamic parameters were assessed . RESULTS At 3 months after treatment , 9 patients had regained continence ( 45 % ) , 8 had improvement ( 40 % ) , and treatment had failed in 3 ( 15 % ) . At 6 months after treatment , 7 patients remained continent , but treatment had failed in 5 . Hematuria developed in 1 patient , urinary tract infection in 7 ( 35 % ) , and a large postvoid residual urine volume requiring catheterization in 6 ( 30 % ) . Hesitancy in initiation and difficult urination was also noted in 15 patients ( 75 % ) . The volume of the first sensation of bladder filling and bladder capacity increased about two times ; however , the voiding efficiency was reduced by 50 % at 2 weeks after treatment . The postvoid residual urine volume was increased by seven times the baseline value at 2 weeks and had decreased to three times greater at 3 and 6 months after treatment . CONCLUSIONS The results of this study have shown that suburothelial injection of 200 U botulinum A toxin impairs bladder sensation and voiding efficiency , but is effective in the treatment of nonneurogenic detrusor overactivity . Transient urinary retention and the development of urinary tract infection should be carefully monitored Objective : To investigate and compare the effectiveness of various treatment protocol s for the treatment of women with idiopathic detrusor overactivity . Design : Prospect i ve , r and omized controlled trial . Setting : Departments of Physiotherapy and Rehabilitation and Obstetrics and Gynaecology , Hacettepe University . Subjects : Forty-six subjects were r and omized to three groups . Interventions : The first group received only pharmacotherapy , the second group received only physiotherapy and in the third group pharmacotherapy was combined with physiotherapy ( combined therapy group ) . Main measures : All patients were evaluated at the beginning and at the end of treatment . Assessment parameters were maximum cystometric capacity , electromyographic activity of pelvic floor muscles , voiding diary parameters , the amount of urine leakage and the quality of life score . Results : The maximum cystometric capacity and the electromyographic activity of pelvic floor muscles increased significantly and the number of voids/day and incontinence episodes/day , and the amount of urine leakage reduced significantly ( P < 0.05 ) in both physiotherapy and combined therapy groups while there was no significant difference in the pharmacotherapy group . After treatment , the number of voids/day increased by 0.3 ± 3.4 in the pharmacotherapy group ( P > 0.05 ) and decreased by 5.1 ± 5.5 and 4.7 ± 5.6 in the physiotherapy and combined therapy groups , respectively ( P < 0.05 ) . Statistically significant improvements were observed in all groups according to the number of voids/night and the quality of life scores at the end of the treatment . Conclusion : The physiotherapy protocol we introduced in the present study with or without anticholinergic therapy has a substantial positive impact on the treatment of female patients with idiopathic detrusor overactivity BACKGROUND Emerging data suggest botulinum toxin is an effective treatment for detrusor overactivity ( DO ) , but large studies confirming efficacy and safety are lacking . OBJECTIVE Study the efficacy and safety of onabotulinumtoxinA ( onaBoNTA ) for the treatment of DO . DESIGN , SETTING , AND PARTICIPANTS A double-blind placebo-controlled r and omised trial in eight UK urogynaecology centres was conducted between 2006 and 2009 . A total of 240 women with refractory DO were r and omised to active or placebo treatment and followed up for 6 mo . INTERVENTION Treatment consisted of 200 IU onaBoNTA or placebo injected into the bladder wall ( 20 sites ; 10 IU per site in 1ml saline ) . MEASUREMENTS Primary outcome was voiding frequency per 24h at 6 mo . Secondary outcomes included urgency and incontinence episodes and quality -of-life data . Intention-to-treat analysis was used with imputation of missing data . RESULTS AND LIMITATIONS A total of 122 women received onaBoNTA and 118 received the placebo . Median ( interquartile range ) voiding frequency was lower after onaBoNTA compared with placebo ( 8.3 [ 6.83 - 10.0 ] vs 9.67 [ 8.37 - 11.67 ] ; difference : 1.34 ; 95 % confidence interval [ CI ] , 1.00 - 2.33 ; p=0.0001 ) . Similar differences were seen in urgency episodes ( 3.83 [ 1.17 - 6.67 ] vs 6.33 [ 4.0 - 8.67 ] ; difference : 2.50 ; 95 % CI , 1.33 - 3.33 ; p<0.0001 ) and leakage episodes ( 1.67 [ 0 - 5.33 ] vs 6.0 [ 1.33 - 8.33 ] ; difference : 4.33 ; 95 % CI , 3.33 - 5.67 ; p<0.0001 ) . Continence was more common after botulinum toxin type A ( BoNTA ; 31 % vs 12 % ; odds ratio [ OR ] : 3.12 ; 95 % CI , 1.49 - 6.52 ; p=0.002 ) . Urinary tract infection ( UTI ; 31 % vs 11 % ; OR : 3.68 ; 95 % CI , 1.72 - 8.25 ; p=0.0003 ) and voiding difficulty requiring self-catheterisation ( 16 % vs 4 % ; OR : 4.87 ; 95 % CI , 1.52 - 20.33 ; p=0.003 ) were more common after onaBoNTA . CONCLUSIONS This r and omised controlled trial of BoNTA for refractory DO , the largest to date , confirms efficacy and safety of the compound . UTI ( 31 % ) and self-catheterisation ( 16 % ) are common . A third of women achieved continence . TRIAL REGISTRATION The study received ethical committee approval from the Scottish Multicentre Research Ethics Committee ( reference : 04/MRE10/67 ) . The trial has a EudraCT number ( 2004 - 002981 - 39 ) , a clinical trial authorisation from the UK Medicines and Healthcare Regulatory Agency , and it was registered on Current Controlled Trials ( IS RCT N26091555 ) on May 26 , 2005 BACKGROUND Despite several antimuscarinic treatment options for overactive bladder ( OAB ) , there is still a need for distinct treatment approaches to manage this condition . Mirabegron , a β(3)-adrenoceptor agonist , has demonstrated efficacy and tolerability for up to 12 wk in phase 3 trials . OBJECTIVE To assess the 12-mo safety and efficacy of mirabegron . DESIGN , SETTING , AND PARTICIPANTS Patients ≥ 18 yr of age with OAB symptoms for ≥ 3 mo . INTERVENTIONS After a 2-wk single-blind placebo run-in , patients with eight or more micturitions per 24h and three or more urgency episodes in a 3-d micturition diary were r and omized 1:1:1 to once-daily mirabegron 50 mg , mirabegron 100 mg , or tolterodine extended release ( ER ) 4 mg for 12 mo . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Primary variable : incidence and severity of treatment-emergent AEs ( TEAEs ) . Secondary variables : change from baseline at months 1 , 3 , 6 , 9 , and 12 in key OAB symptoms . RESULTS AND LIMITATIONS A total of 812 , 820 , and 812 patients received mirabegron 50 mg , mirabegron 100 mg , and tolterodine ER 4 mg , respectively . Baseline demographic and OAB characteristics were similar across groups . TEAEs were reported in 59.7 % , 61.3 % , and 62.6 % of patients , respectively ; most were mild or moderate . Serious TEAEs were reported in 5.2 % , 6.2 % , and 5.4 % of patients , respectively . The most common TEAEs were similar across groups . Dry mouth was reported by 2.8 % , 2.3 % , and 8.6 % of patients , respectively . Adjusted mean changes from baseline to final visit in morning systolic blood pressure were 0.2 , 0.4 , and -0.5 mm Hg for mirabegron 50 mg , 100 mg , and tolterodine ER 4 mg , respectively . Mirabegron and the active control , tolterodine , improved key OAB symptoms from the first measured time point of 4 wk , and efficacy was maintained throughout the 12-mo treatment period . The study was not placebo controlled , which was a limitation . CONCLUSIONS The safety and tolerability of mirabegron was established over 1 yr , with sustained efficacy observed over this treatment period . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT00688688 BACKGROUND Women with urge urinary incontinence are commonly treated with antimuscarinic medications , but many discontinue therapy . OBJECTIVE To determine whether combining antimuscarinic drug therapy with supervised behavioral training , compared with drug therapy alone , improves the ability of women with urge incontinence to achieve clinical ly important reductions in incontinence episodes and to sustain these improvements after discontinuing drug therapy . DESIGN 2-stage , multicenter , r and omized clinical trial conducted from July 2004 to January 2006 . SETTING 9 university-affiliated outpatient clinics . PATIENTS 307 women with urge-predominant incontinence . INTERVENTION 10 weeks of open-label , extended-release tolterodine alone ( n = 153 ) or combined with behavioral training ( n = 154 ) , followed by discontinuation of therapy and follow-up at 8 months . MEASUREMENTS The primary outcome , measured at 8 months , was no receipt of drugs or other therapy for urge incontinence and a 70 % or greater reduction in frequency of incontinence episodes . Secondary outcomes were reduction in incontinence , self-reported satisfaction and improvement , and scores on vali date d question naires measuring symptom distress and bother and health-related quality of life . Study staff who performed outcome evaluations , but not participants and interventionists , were blinded to group assignment . RESULTS 237 participants completed the trial . According to life-table estimates , the rate of successful discontinuation of therapy at 8 months was the same in the combination therapy and drug therapy alone groups ( 41 % in both groups ; difference , 0 percentage points [ 95 % CI , -12 to 12 percentage points ] ) . A higher proportion of participants who received combination therapy than drug therapy alone achieved a 70 % or greater reduction in incontinence at 10 weeks ( 69 % vs. 58 % ; difference , 11 percentage points [ CI , -0.3 to 22.1 percentage points ] ) . Combination therapy yielded better outcomes over time on the Urogenital Distress Inventory and the Overactive Bladder Question naire ( both P < 0.001 ) at both time points for patient satisfaction and perceived improvement but not health-related quality of life . Adverse events were uncommon ( 12 events in 6 participants [ 3 in each group ] ) . LIMITATIONS Behavioral therapy components ( daily bladder diary and recommendations for fluid management ) in the group receiving drug therapy alone may have attenuated between-group differences . Assigned treatment was completed by 68 % of participants , whereas 8-month outcome status was assessed on 77 % . CONCLUSION The addition of behavioral training to drug therapy may reduce incontinence frequency during active treatment but does not improve the ability to discontinue drug therapy and maintain improvement in urinary incontinence . Combination therapy has a beneficial effect on patient satisfaction , perceived improvement , and reduction of other bladder symptoms PURPOSE Treatment options for patients with overactive bladder refractory to anticholinergics are limited . We assessed the dose response across a range of doses of onabotulinumtoxinA ( BOTOX ® ) in patients with idiopathic overactive bladder and urinary urgency incontinence whose symptoms were not adequately managed with anticholinergics . MATERIAL S AND METHODS In a phase 2 , multicenter , r and omized , double-blind study , 313 patients with idiopathic overactive bladder and urinary urgency incontinence experiencing 8 or more urinary urgency incontinence episodes a week and 8 or more micturitions daily at baseline received 50 , 100 , 150 , 200 or 300 U intradetrusor onabotulinumtoxinA , or placebo . Symptoms were recorded using a 7-day bladder diary . The primary efficacy variable was weekly urinary urgency incontinence episodes and the primary end point was week 12 . RESULTS Demographics and baseline characteristics were balanced across the treatment groups . Durable efficacy was observed for all onabotulinumtoxinA dose groups of 100 U or greater for primary and secondary efficacy measures , including the proportion of incontinence-free patients . When the dose response curves were analyzed , doses greater than 150 U contributed minimal additional or clinical ly relevant improvement in symptoms . This finding was also reflected in health related quality of life assessment s. Dose dependent changes in post-void residual urine volume were observed and the use of clean intermittent catheterization was also dose dependent . The only adverse events significantly greater with onabotulinumtoxinA than with placebo were urinary tract infection and urinary retention . CONCLUSIONS OnabotulinumtoxinA at doses of 100 U or greater demonstrated durable efficacy in the management of idiopathic overactive bladder and urinary urgency incontinence . A dose of 100 U may be the dose that appropriately balances the symptom benefits with the post-void residual urine volume related safety profile PURPOSE Many patients with overactive bladder discontinue pharmacotherapy due to suboptimal efficacy or side effects . Mirabegron , a β3-adrenoceptor agonist , may offer an effective and well tolerated alternative treatment for overactive bladder . MATERIAL S AND METHODS A r and omized , double-blind , placebo controlled trial was conducted in the United States and Canada . After a 2-week placebo run-in period , adults with overactive bladder symptoms for 3 or more months were r and omized 1:1:1 to receive placebo , 50 or 100 mg mirabegron once daily for 12 weeks . Efficacy data were collected via patient completed diaries and quality of life assessment s. Co- primary efficacy end points were changes from baseline to final visit in mean number of incontinence episodes per 24 hours and micturitions per 24 hours . Key secondary micturition and incontinence end points were also evaluated . Safety assessment s included treatment emergent adverse events , laboratory assessment s , vital signs , electrocardiograms and post-void residual volume . RESULTS Compared to placebo , 50 and 100 mg mirabegron groups demonstrated statistically significantly greater mean decreases ( 95 % CI ) from baseline for incontinence episodes ( -1.13 [ -1.35 , -0.91 ] , -1.47 [ -1.69 , -1.25 ] and -1.63 [ -1.86 , -1.40 ] ) and micturitions ( -1.05 [ -1.31 , -0.79 ] , -1.66 [ -1.92 , -1.40 ] and -1.75 [ -2.01 , -1.48 ] ) per 24 hours ( p < 0.05 ) . Significant improvements in all key secondary end points were observed for both mirabegron doses vs placebo . The incidence of frequently reported treatment emergent adverse events ( hypertension , urinary tract infection , headache , nasopharyngitis ) was similar in the mirabegron and placebo groups . Dry mouth was reported for 1.5 % , 0.5 % and 2.1 % of patients in the placebo , 50 and 100 mg mirabegron groups , respectively . CONCLUSIONS Once daily mirabegron in a 50 or 100 mg dose is an effective treatment for overactive bladder symptoms with a low occurrence of side effects AIMS To evaluate the potential of mirabegron , a selective β3-adrenoceptor agonist , for treatment of overactive bladder ( OAB ) symptoms . METHODS A multicenter , r and omized , double-blind , double-dummy , parallel group , placebo and active-controlled , Phase 2 , proof-of-concept study was conducted . Eligible patients ( n = 314 ) were enrolled into a single-blind , 2-week placebo run-in period followed by a r and omized , double-blind , placebo-controlled treatment period . Patients received mirabegron 100 or 150 mg twice-daily ( BID ) , placebo or tolterodine 4 mg extended release ( ER ) once-daily for 4 weeks . Primary endpoint was change from baseline to end-of-treatment in mean number of micturition episodes per 24 hr . Secondary endpoints included changes in mean volume voided per micturition ; mean number of urinary incontinence , urgency urinary incontinence , and urgency episodes per 24 hr ; severity of urgency ; nocturia , and quality of life measures . Safety parameters included adverse events , laboratory tests , electrocardiogram parameters and post-void residual volume . RESULTS Mirabegron 100 and 150 mg BID result ed in a statistically significant improvement versus placebo in mean change from baseline to end-of-treatment in the primary endpoint of micturition frequency ( 2.2 micturitions/24 hr vs. 1.2 micturitions/24 hr for both doses , adjusted P ≤ 0.01 for both comparisons ) . Mirabegron had a statistically significant effect versus placebo for most secondary endpoints , including quality of life variables . Despite a small increase in pulse rate , mirabegron demonstrated good safety and tolerability . CONCLUSIONS Mirabegron was efficacious and well tolerated in patients with OAB symptoms and heralds the first of a new class of oral pharmacological therapy for OAB for more than 30 years OBJECTIVE To assess the efficacy and tolerability of mirabegron 25 mg and 50 mg once-daily vs placebo in patients with overactive bladder ( OAB ) . MATERIAL S AND METHODS Patients ≥18 years with OAB symptoms were recruited to a 2-week , single-blind , placebo run-in . Those with ≥8 micturitions per 24 hours and ≥3 urgency episodes were r and omized 1:1:1 to once-daily mirabegron 25 mg or 50 mg , or placebo for 12 weeks . Primary endpoints were changes to final visit in mean number of incontinence episodes and micturitions per 24 hours . Key secondary endpoints were changes to final visit in mean volume voided or micturition , change to week 4 in mean number of incontinence episodes and micturitions per 24 hours , changes to final visit in mean level of urgency , number of urgency incontinence episodes , and urgency ( grade 3 or 4 ) episodes per 24 hours . Patient-reported outcomes were assessed using the OAB- question naire , Patient Perception of Bladder Condition , and Treatment-Satisfaction-Visual Analog Scale . RESULTS Both mirabegron groups demonstrated statistically significant improvements in co primary endpoints vs placebo . Mirabegron 50 mg demonstrated significantly greater improvements vs placebo in the following : change to final visit in mean volume voided per micturition and change to week 4 in mean number of incontinence episodes per 24 hours . Statistically significant improvements vs placebo were demonstrated by mirabegron 50 mg in all patient-reported outcome scales with no increase in the incidence of treatment-emergent adverse events vs placebo . CONCLUSION Mirabegron 25 mg and 50 mg were associated with significant improvements in efficacy measures of incontinence episodes and micturition frequency . Mirabegron was well tolerated vs placebo PURPOSE This is a prospect i ve , double-blind , placebo controlled study , based on an original placebo technique , performed to evaluate the efficacy of percutaneous tibial nerve stimulation in female patients with detrusor overactivity incontinence . MATERIAL S AND METHODS A total of 35 female patients presenting with detrusor overactivity incontinence that did not respond to antimuscarinic therapy were r and omly assigned to percutaneous tibial nerve stimulation or to a control group . The percutaneous tibial nerve stimulation group ( 18 patients ) was treated with 12 percutaneous tibial nerve stimulation sessions . The control group ( 17 patients ) received an original placebo treatment using a 34 gauge needle placed in the medial part of the gastrocnemius muscle . The sessions lasted for 30 minutes and were performed 3 times weekly as percutaneous tibial nerve stimulation sessions . All patients were evaluated with bladder diaries as well as quality of life scores before and after treatment . Patients showing a reduction in urge incontinence episodes greater than 50 % were considered responders . RESULTS Some patients ( 1 in the percutaneous tibial nerve stimulation group and 2 in the placebo group ) did not complete the study for reasons not related to the technique . Of 17 patients in the percutaneous tibial nerve stimulation group 12 ( 71 % ) and of 15 in placebo group 0 were considered responders according to the previously reported definition ( p < 0.001 ) . Improvement in the number of incontinence episodes , number of voids , voided volume and incontinence quality of life score were statistically significant in the percutaneous tibial nerve stimulation group but not in the placebo group . CONCLUSIONS Percutaneous tibial nerve stimulation can be considered an effective treatment for detrusor overactivity incontinence with 71 % of patients considered responders , while none of those treated with placebo was considered a responder . The relevance of a placebo effect seems to be negligible in this patient population |
804 | 25,811,419 | Both G551D phase 3 trials ( n = 219 ) demonstrated a clinical ly relevant impact of the potentiator ivacaftor on outcomes at 24 and 48 weeks , providing evidence for the use of this treatment in adults and children ( over six years of age ) with cystic fibrosis and the G551D mutation ( class III ) . | BACKGROUND Cystic fibrosis is the most common inherited life-shortening illness in Caucasians and caused by a mutation in the gene that codes for the cystic fibrosis transmembrane regulator protein ( CFTR ) , which functions as a salt transporter .
This mutation most notably affects the airways of people with cystic fibrosis .
Excess salt absorption by defective CFTR dehydrates the airway lining and leads to defective mucociliary clearance .
Consequent accumulation of thick , sticky mucus makes the airway prone to chronic infection and progressive inflammation ; respiratory failure often ensues .
Additionally , abnormalities with CFTR lead to systemic complications like malnutrition , diabetes and subfertility .
Since the discovery of the causative gene , our underst and ing of the structure and function of CFTR and the impact of different mutations has increased and allowed pharmaceutical companies to design new mutation-specific therapies targeting the underlying molecular defect .
Therapies targeting mutation classes III and IV ( CFTR potentiators ) aim to normalise airway surface liquid and help re-establish mucociliary clearance , which then has a beneficial impact on the chronic infection and inflammation that characterizes lung disease in people with cystic fibrosis .
These therapies may also affect other mutations .
OBJECTIVES To evaluate the effects of CFTR potentiators on clinical ly important outcomes in children and adults with cystic fibrosis . | BACKGROUND Ivacaftor has been shown to be a safe , effective treatment for cystic fibrosis in patients aged 6 years or older with a CFTR gating mutation . We aim ed to assess the safety , pharmacokinetics , and pharmacodynamics of ivacaftor in children aged 2 - 5 years . METHODS In the two-part KIWI study , we enrolled children aged 2 - 5 years weighing 8 kg or more with a confirmed diagnosis of cystic fibrosis and a CFTR gating mutation on at least one allele from 15 hospitals in the USA , UK , and Canada . Participants received oral ivacaftor 50 mg ( if bodyweight < 14 kg ) or 75 mg ( if bodyweight ≥14 kg ) every 12 h for 4 days in part A ( to establish the short-term safety of doses for subsequent assessment in part B ) , and then for 24 weeks in part B ( to assess safety and longer-term pharmacodynamics ) . Children could participate in both or just one part of the study . Primary outcomes were pharmacokinetics and safety , analysed in all patients who received at least one dose of ivacaftor . Secondary outcomes were absolute change from baseline in sweat chloride concentrations and bodyweight , body-mass index ( BMI ) , and height Z scores , and pharmacokinetic parameter estimation of ivacaftor . This study is registered with Clinical Trials.gov , number NCT01705145 . FINDINGS Between Jan 8 , 2013 , and March 1 , 2013 , nine patients were enrolled onto part A of the study , all of whom completed the 4 day treatment period , and eight of whom took part in part B. Between June 28 , 2013 , and Sept 26 , 2013 , 34 patients were enrolled in part B , 33 of whom completed the 24 week treatment period . All patients received at least one dose of ivacaftor . Results of ivacaftor pharmacokinetics suggested that exposure was similar to that reported in adults ( median Cmin were 536 ng/mL for the 50 mg dose ; 580 ng/mL for the 75 mg dose ; median ivacaftor AUC values were 9840 ng × h/mL and 10 200 ng × h/mL , respectively ) . Common adverse events in part B included cough ( in 19 [ 56 % ] of 34 patients ) and vomiting ( in ten [ 29 % ] ) . Five ( 15 % ) patients had liver function test ( LFT ) results that were more than eight times higher than the upper limit of normal , four of whom had study drug interrupted , and one of whom had study drug discontinued . Six ( 18 % ) of 34 patients had seven serious adverse events ; a raised concentration of transaminases was the only serious adverse event regarded as related to ivacaftor and the only adverse event that result ed in study treatment discontinuation . At week 24 , in patients for whom we had data , sweat chloride had changed from baseline by a mean of -46·9 mmol/L ( SD 26·2 , p<0·0001 ) , weight Z score by 0·2 ( 0·3 ; p<0·0001 ) , BMI Z score by 0·4 ( 0·4 , p<0·0001 ) , and height Z score by -0·01 ( 0·3 ; p=0·84 ) . INTERPRETATION Ivacaftor at doses of 50 mg and 75 mg seems to be safe in children aged 2 - 5 years with cystic fibrosis with a gating mutation followed up for 24 weeks , although the frequency of elevated LFTs suggests that monitoring should be frequent in young children , particularly those with a history of elevated LFTs . Results of an ongoing extension study assessing durability of these effects and longer-term safety are warranted . FUNDING Vertex Pharmaceuticals Incorporated BACKGROUND We examined data from a Phase 2 trial { NCT00457821 } of ivacaftor , a CFTR potentiator , in cystic fibrosis ( CF ) patients with aG551D mutation to evaluate st and ardized approaches to sweat chloride measurement and to explore the use of sweat chloride and nasal potential difference ( NPD ) to estimate CFTR activity . METHODS Sweat chloride and NPD were secondary endpoints in this placebo-controlled , multicenter trial . St and ardization of sweat collection , processing , and analysis was employed for the first time . Sweat chloride and chloride ion transport ( NPD ) were integrated into a model of CFTR activity . RESULTS Within-patient sweat chloride determinations showed sufficient precision to detect differences between dose-groups and assess ivacaftor treatment effects . Analysis of changes in sweat chloride and NPD demonstrated that patients treated with ivacaftor achieved CFTR activity equivalent to approximately 35%–40 % of normal . CONCLUSIONS Sweat chloride is useful in multicenter trials as a biomarker of CFTR activity and to test the effect of CFTR potentiators Background Cystic fibrosis ( CF ) is an inherited , rare autosomal recessive disease that results in chronically debilitating morbidities and high premature mortality . We evaluated how ivacaftor treatment affected CF symptoms , functioning , and well-being , as measured by the Cystic Fibrosis Question naire-Revised ( CFQ-R ) , a widely-used patient-reported outcome ( PRO ) measure . Methods STRIVE , a double-blind , placebo-controlled r and omized trial , evaluated ivacaftor ( 150 mg ) in CF patients aged 12 + with the G551D-CFTR mutation for 48 weeks . Treatment effect analysis used a mixed-effects repeated measures model . Treatment benefit analyses applied the cumulative distribution function and a categorical analysis of change scores ( “ improvement , ” “ no change , ” or “ decline ” ) . Content-based interpretation examined treatment effect on specific item responses . Results Data from 152 patients with a baseline CFQ-R assessment were analyzed . The treatment effect analysis favored treatment with ivacaftor over placebo on the Body Image , Eating , Health Perceptions , Physical Functioning , Respiratory , Social Functioning , Treatment Burden , and Vitality scales . Findings were supported by the analysis of categorical change . On all CFQ-R scales , the percentage of patients who improved was greater for ivacaftor . In the content-based analysis , the treatment benefit was characterized by better scores across a broad range of domains . Conclusions Results illustrate broad benefits of ivacaftor treatment across many domains : respiratory symptoms , physical and social functioning , health perceptions , and vitality , as measured by the CFQ-R. The breadth of improvements reflects the systemic mechanism of action of ivacaftor compared to other therapies . Findings support the patient-reported value of ivacaftor treatment in this patient population .Trial Registration Clinical Trials.gov BACKGROUND Increasing the activity of defective cystic fibrosis transmembrane conductance regulator ( CFTR ) protein is a potential treatment for cystic fibrosis . METHODS We conducted a r and omized , double-blind , placebo-controlled trial to evaluate ivacaftor ( VX-770 ) , a CFTR potentiator , in subjects 12 years of age or older with cystic fibrosis and at least one G551D-CFTR mutation . Subjects were r and omly assigned to receive 150 mg of ivacaftor every 12 hours ( 84 subjects , of whom 83 received at least one dose ) or placebo ( 83 , of whom 78 received at least one dose ) for 48 weeks . The primary end point was the estimated mean change from baseline through week 24 in the percent of predicted forced expiratory volume in 1 second ( FEV(1 ) ) . RESULTS The change from baseline through week 24 in the percent of predicted FEV(1 ) was greater by 10.6 percentage points in the ivacaftor group than in the placebo group ( P<0.001 ) . Effects on pulmonary function were noted by 2 weeks , and a significant treatment effect was maintained through week 48 . Subjects receiving ivacaftor were 55 % less likely to have a pulmonary exacerbation than were patients receiving placebo , through week 48 ( P<0.001 ) . In addition , through week 48 , subjects in the ivacaftor group scored 8.6 points higher than did subjects in the placebo group on the respiratory-symptoms domain of the Cystic Fibrosis Question naire-revised instrument ( a 100-point scale , with higher numbers indicating a lower effect of symptoms on the patient 's quality of life ) ( P<0.001 ) . By 48 weeks , patients treated with ivacaftor had gained , on average , 2.7 kg more weight than had patients receiving placebo ( P<0.001 ) . The change from baseline through week 48 in the concentration of sweat chloride , a measure of CFTR activity , with ivacaftor as compared with placebo was -48.1 mmol per liter ( P<0.001 ) . The incidence of adverse events was similar with ivacaftor and placebo , with a lower proportion of serious adverse events with ivacaftor than with placebo ( 24 % vs. 42 % ) . CONCLUSIONS Ivacaftor was associated with improvements in lung function at 2 weeks that were sustained through 48 weeks . Substantial improvements were also observed in the risk of pulmonary exacerbations , patient-reported respiratory symptoms , weight , and concentration of sweat chloride . ( Funded by Vertex Pharmaceuticals and others ; VX08 - 770 - 102 Clinical Trials.gov number , NCT00909532 . ) Background The analysis aim ed to examine the impact of pulmonary exacerbations ( PEs ) and lung function on generic measures of HRQL in patients with cystic fibrosis ( CF ) using trial-based data . Methods In a 48-week r and omized , placebo-controlled study of ivacaftor in patients ≥12 years with CF and a G551D-CFTR mutation the relationship between PEs , PE-related hospitalizations and percent predicted forced expiratory volume in one second ( ppFEV1 ) with EQ-5D measures ( index and visual analog scale [ VAS ] ) was examined in post-hoc analyses . Multivariate mixed-effects models were employed to describe the association of PEs , PE-related hospitalizations , and ppFEV1 on EQ-5D measures . Results One hundred sixty one patients ( age : mean 25.5 [ SD 9.5 ] years ; baseline ppFEV1 : 63.6 [ 16.4 ] ) contributed 1,214 observations ( ppFEV1 : no lung dysfunction [ n = 157 ] , mild [ n = 419 ] , moderate [ n = 572 ] , severe [ n = 66 ] ) . Problems were most frequently reported on pain/discomfort , anxiety/depression , and usual activities EQ-5D items . The mean ( SE ) EQ-5D index nominally decreased ( worsened ) with worsening severity of lung dysfunction ( P = 0.070 ) : 0.931 ( 0.023 ) ; mild : 0.923 ( 0.021 ) ; moderate : 0.904 ( 0.018 ) ; severe : 0.870 ( 0.020 ) . 146 PEs were experienced by 72 patients , including 52 PEs ( 35.6 % ) that required hospitalization . Mean EQ-5D index and VAS scores were lowest ( worst ) within 1 week ( before or after PE start ) for PEs requiring hospitalization . Pulmonary exacerbations , PE-related hospitalizations , and ppFEV1 were significant predictors of EQ-5D index and VAS . Conclusions In a clinical study of patients with CF ( ≥12 years of age and a G551D-CFTR mutation ) , PEs , primarily those requiring hospitalization , were associated with low EQ-5D index and VAS scores . The impact of ppFEV1 was relatively smaller . Reducing PEs , in particular those requiring hospitalization , would likely improve HRQL among these patients .Trial registration Clinical Trials.gov , NCT00909532 ; URL : clinical trials.gov , May 26 , CPX ( 8-cyclopentyl-1,3-dipropylxanthine ) is a novel compound currently under development as a potential treatment for cystic fibrosis ( CF ) . The drug has been shown to increase chloride efflux and CFTR trafficking in vitro in CF airway cells . This phase I multicenter , single-dose , placebo-controlled trial was performed at four institutions . Thirty-seven subjects homozygous for the Delta F(508 ) allele were studied in an escalating dose protocol of seven single-dose cohorts ( 1 , 3 , 10 , 30 , 100 , 300 , and 1,000 mg ) to evaluate the safety , pharmacokinetics , and efficacy of CPX . Efficacy was determined using nasal transepithelial potential difference and sweat chloride measurements prior to dosing and at 1 , 2 , and 4 hr postdose . The incidence of adverse events in the treatment group was similar to that with placebo , indicating safety of the single doses studied . One serious adverse event ( an acute pulmonary exacerbation ) occurred 13 days after dosing , and was not considered related to the study drug . The maximal plasma CPX concentration and total amount of CPX absorbed appeared to be linearly related to dose , but was highly variable throughout the dose range studied , suggesting inconsistent absorption . There was no apparent effect of single-dose administration on either nasal transepithelial potential difference or sweat chloride measurements . The positive safety and pharmacokinetic findings of this study support continued development of CPX as a potential therapeutic for CF Background VX-809 , a cystic fibrosis transmembrane conductance regulator ( CFTR ) modulator , has been shown to increase the cell surface density of functional F508del-CFTR in vitro . Methods A r and omised , double-blind , placebo-controlled study evaluated the safety , tolerability and pharmacodynamics of VX-809 in adult patients with cystic fibrosis ( n=89 ) who were homozygous for the F508del-CFTR mutation . Subjects were r and omised to one of four VX-809 28 day dose groups ( 25 , 50 , 100 and 200 mg ) or matching placebo . Results The type and incidence of adverse events were similar among VX-809- and placebo-treated subjects . Respiratory events were the most commonly reported and led to discontinuation by one subject in each active treatment arm . Pharmacokinetic data supported a once-daily oral dosing regimen . Pharmacodynamic data suggested that VX-809 improved CFTR function in at least one organ ( sweat gl and ) . VX-809 reduced elevated sweat chloride values in a dose-dependent manner ( p=0.0013 ) that was statistically significant in the 100 and 200 mg dose groups . There was no statistically significant improvement in CFTR function in the nasal epithelium as measured by nasal potential difference , nor were there statistically significant changes in lung function or patient-reported outcomes . No maturation of immature F508del-CFTR was detected in the subgroup that provided rectal biopsy specimens . Conclusions In this study , VX-809 had a similar adverse event profile to placebo for 28 days in F508del-CFTR homozygous patients , and demonstrated biological activity with positive impact on CFTR function in the sweat gl and . Additional data are needed to determine how improvements detected in CFTR function secondary to VX-809 in the sweat gl and relate to those measurable in the respiratory tract and to long-term measures of clinical benefit . Clinical trial number Background The cystic fibrosis ( CF ) transmembrane conductance regulator ( CFTR ) gating mutation G551D prevents sufficient ion transport due to reduced channel-open probability . Ivacaftor , an oral CFTR potentiator , increases the channel-open probability . Aim To further analyze improvements in weight and body mass index ( BMI ) in two studies of ivacaftor in patients aged ≥6 years with CF and the G551D mutation . Methods Patients were r and omized 1:1 to ivacaftor 150 mg or placebo every 12 h for 48 weeks . Primary end point ( lung function ) was reported previously . Other outcomes included weight and height measurements and CF Question naire-Revised ( CFQ-R ) . Results Studies included 213 patients ( aged ≤ 20 years , n = 105 ; aged > 20 years , n = 108 ) . In patients ≤20 years , adjusted mean change from baseline to week 48 in body weight was 4.9 versus 2.2 kg ( ivacaftor vs. placebo , p = 0.0008 ) . At week 48 , change from baseline in mean weight-for-age z-score was 0.29 versus −0.06 ( p < 0.0001 ) ; change in mean BMI -for-age z-score was 0.26 versus −0.13 ( p < 0.0001 ) . In patients > 20 years , adjusted mean change from baseline to week 48 in body weight was 2.7 versus −0.2 kg ( p = 0.0003 ) . Mean BMI change at week 48 was 0.9 versus −0.1 kg/m2 ( p = 0.0003 ) . There was no linear correlation evident between changes in body weight and improvements in lung function or sweat chloride . Significant CFQ-R improvements were seen in perception of eating , body image , and sense of ability to gain weight . Conclusions Nutritional status improved following treatment with ivacaftor for 48 weeks Nasal potential difference ( NPD ) is used as a biomarker of the cystic fibrosis transmembrane conductance regulator ( CFTR ) and epithelial sodium channel ( ENaC ) activity . We evaluated methods to detect changes in chloride and sodium transport by NPD based on a secondary analysis of a Phase II CFTR-modulator study . Thirty-nine subjects with CF who also had the G551D-CFTR mutation were r and omized to receive ivacaftor ( Kalydeco ™ ; also known as VX-770 ) in four doses or placebo twice daily for at least 14 days . All data were analyzed by a single investigator who was blinded to treatment assignment . We compared three analysis methods to determine the best approach to quantify changes in chloride and sodium transport : ( 1 ) the average of both nostrils ; ( 2 ) the most-polarized nostril at each visit ; and ( 3 ) the most-polarized nostril at screening carried forward . Parameters of ion transport included the PD change with zero chloride plus isoproterenol ( CFTR activity ) , the basal PD , Ringer 's PD , and change in PD with amiloride ( measurements of ENaC activity ) , and the delta NPD ( measuring CFTR and ENaC activity ) . The average and most-polarized nostril at each visit were most sensitive to changes in chloride and sodium transport , whereas the most-polarized nostril at screening carried forward was less discriminatory . Based on our findings , NPD studies should assess both nostrils rather than a single nostril . We also found that changes in CFTR activity were more readily detected than changes in ENaC activity , and that rigorous st and ardization was associated with relatively good within-subject reproducibility in placebo-treated subjects ( ±2.8 mV ) . Therefore , we have confirmed an assay of reasonable reproducibility for detecting chloride-transport improvements in response to CFTR modulation BACKGROUND Ivacaftor has been previously assessed in patients with cystic fibrosis with Gly551Asp-CFTR or other gating mutations . We assessed ivacaftor in patients with Arg117His-CFTR , a residual function mutation . METHODS We did a 24-week , placebo-controlled , double-blind , r and omised clinical trial , which enrolled 69 patients with cystic fibrosis aged 6 years and older with Arg117His-CFTR and percentage of predicted forced expiratory volume in 1 s ( % predicted FEV1 ) of at least 40 . We r and omly assigned eligible patients ( 1:1 ) to receive placebo or ivacaftor 150 mg every 12 h for 24 weeks . R and omisation was stratified by age ( 6 - 11 , 12 - 17 , and ≥18 years ) and % predicted FEV1 ( < 70 , ≥70 to ≤90 , and > 90 ) . The primary outcome was the absolute change from baseline in % predicted FEV1 through week 24 . Secondary outcomes included safety and changes in sweat chloride concentrations and Cystic Fibrosis Question naire-Revised ( CFQ-R ) respiratory domain scores . An open-label extension enrolled 65 of the patients after washout ; after 12 weeks , we did an interim analysis . FINDINGS After 24 weeks , the treatment difference in mean absolute change in % predicted FEV1 between ivacaftor ( n=34 ) and placebo ( n=35 ) was 2·1 percentage points ( 95 % CI -1·13 to 5·35 ; p=0·20 ) . Ivacaftor treatment result ed in significant treatment differences in sweat chloride ( -24·0 mmol/L , 95 % CI -28·01 to -19·93 ; p<0·0001 ) and CFQ-R respiratory domain ( 8·4 , 2·17 to 14·61 ; p=0·009 ) . In prespecified subgroup analyses , % predicted FEV1 significantly improved with ivacaftor in patients aged 18 years or older ( treatment difference vs placebo : 5·0 percentage points , 95 % CI 1·15 to 8·78 ; p=0·01 ) , but not in patients aged 6 - 11 years ( -6·3 percentage points , -11·96 to -0·71 ; p=0·03 ) . In the extension study , both placebo-to-ivacaftor and ivacaftor-to-ivacaftor groups showed % predicted FEV1 improvement ( absolute change from post-washout baseline at week 12 : placebo-to-ivacaftor , 5·0 percentage points [ p=0·0005 ] ; ivacaftor-to-ivacaftor , 6·0 percentage points [ p=0·006 ] ) . We did not identify any new safety concerns . The studies are registered with Clinical Trials.gov ( the r and omised , placebo-controlled study , number NCT01614457 ; the open-label extension study , number NCT01707290 ) . INTERPRETATION Although this study did not show a significant improvement in % predicted FEV1 , ivacaftor did significantly improve sweat chloride and CFQ-R respiratory domain scores and lung function in adult patients with Arg117His-CFTR , indicating that ivacaftor might benefit patients with Arg117His-CFTR who have established disease . FUNDING Vertex Pharmaceuticals Incorporated Most individuals with cystic fibrosis ( CF ) carry one or two mutations that result in a maturation defect of the full-length protein . One such mutation , deltaF508 , results in a mutant membrane glycoprotein that fails to progress to the apical membrane , where the wild-type protein normally functions as a cyclic AMP-regulated chloride channel . 4-Phenylbutyrate ( Buphenyl ) , an orally bioavailable short chain fatty acid , modulates heat shock protein expression and restores maturation of the deltaF508 protein in vitro and in vivo . We performed a r and omized , double-blind , placebo-controlled , dose-escalation and safety study of Buphenyl in 19 adults with CF ( homozygous deltaF508 ) to test the hypothesis that Buphenyl would be safe , well-tolerated , and associated with an increase in chloride transport in nasal epithelia . Three dose levels ( 20 , 30 , or 40 g divided t.i.d . ) of drug or placebo were given for 1 week . Serial measurements of chloride transport by nasal potential difference ( NPD ) testing and metabolic safety testing were performed . A maximum tolerated dose of 20 g was defined based on minimal adverse reactions , the safety profile , and a statistically significant induction of chloride transport that was maximal by day 3 . This short-term phase I/II study demonstrates proof of principle that modulation of deltaF508 CFTR bio synthesis and trafficking is a viable therapeutic approach for cystic fibrosis BACKGROUND Ivacaftor has shown a clinical benefit in patients with cystic fibrosis who have the G551D-CFTR mutation and reduced lung function . Lung clearance index ( LCI ) using multiple-breath washout might be an alternative to and more sensitive method than forced expiratory volume in 1 s ( FEV1 ) to assess treatment response in the growing number of children and young adults with cystic fibrosis who have normal spirometry . The aim of the study was to assess the treatment effects of ivacaftor on LCI in patients with cystic fibrosis , a G551D-CFTR mutation , and an FEV1 > 90 % predicted . METHODS This phase 2 , multicentre , placebo-controlled , double-blind 2 × 2 crossover study of ivacaftor treatment was conducted in patients with cystic fibrosis , at least one G551D-CFTR allele , and an FEV1 > 90 % predicted . Patients also had to have an LCI higher than 7·4 at screening , age of 6 years or older , and a weight higher than or equal to 15 kg . Eligible patients were r and omly allocated to receive one of two treatment sequences ( placebo first followed by ivacaftor 150 mg twice daily [ sequence 1 ] or ivacaftor 150 mg twice daily first followed by placebo [ sequence 2 ] ) of 28 days ' treatment in each period , with a 28-day washout between the two treatment periods . R and omisation ( ratio 1:1 ) was done with block sizes of 4 , and all site personnel including the investigator , the study monitor , and the Vertex study team were masked to treatment assignment . The primary outcome measure was change from baseline in LCI . The study is registered at Clinical Trials.gov , NCT01262352 . FINDINGS Between February and November , 2011 , 21 patients were enrolled , of which 11 were assigned to the sequence 1 group , and 10 to the sequence 2 group . 20 of these patients received treatment and 17 completed the trial ( eight in sequence 1 group and 9 in sequence 2 group ) . Treatment with ivacaftor led to significant improvements compared with placebo in LCI ( difference between groups in the average of mean changes from baseline at days 15 and 29 was -2·16 [ 95 % CI -2·88 to -1·44 ] ; p<0·0001 ) . Adverse events experienced by study participants were similar between treatment groups ; at least one adverse event was reported by 15 ( 79 % ) of 19 patients who received placebo and 13 ( 72 % ) of 18 patients who received ivacaftor . No deaths occurred during study period . INTERPRETATION In patients with cystic fibrosis aged 6 years or older who have at least one G551D-CFTR allele , ivacaftor led to improvements in LCI . LCI might be a more sensitive alternative to FEV1 in detecting response to intervention in these patients with mild lung disease . FUNDING Vertex Pharmaceuticals Incorporated BACKGROUND Ataluren was developed to restore functional protein production in genetic disorders caused by nonsense mutations , which are the cause of cystic fibrosis in 10 % of patients . This trial was design ed to assess the efficacy and safety of ataluren in patients with nonsense-mutation cystic fibrosis . METHODS This r and omised , double-blind , placebo-controlled , phase 3 study enrolled patients from 36 sites in 11 countries in North America and Europe . Eligible patients with nonsense-mutation cystic fibrosis ( aged ≥ 6 years ; abnormal nasal potential difference ; sweat chloride > 40 mmol/L ; forced expiratory volume in 1 s [ FEV1 ] ≥ 40 % and ≤ 90 % ) were r and omly assigned by interactive response technology to receive oral ataluren ( 10 mg/kg in morning , 10 mg/kg midday , and 20 mg/kg in evening ) or matching placebo for 48 weeks . R and omisation used a block size of four , stratified by age , chronic inhaled antibiotic use , and percent-predicted FEV1 . The primary endpoint was relative change in percent-predicted FEV1 from baseline to week 48 , analysed in all patients with a post-baseline spirometry measurement . This study is registered with Clinical Trials.gov , number NCT00803205 . FINDINGS Between Sept 8 , 2009 , and Nov 30 , 2010 , 238 patients were r and omly assigned , of whom 116 in each treatment group had a valid post-baseline spirometry measurement . Relative change from baseline in percent-predicted FEV1 did not differ significantly between ataluren and placebo at week 48 ( -2.5 % vs -5.5 % ; difference 3.0 % [ 95 % CI -0.8 to 6.3 ] ; p=0.12 ) . The number of pulmonary exacerbations did not differ significantly between treatment groups ( rate ratio 0.77 [ 95 % CI 0.57 - 1.05 ] ; p=0.0992 ) . However , post-hoc analysis of the subgroup of patients not using chronic inhaled tobramycin showed a 5.7 % difference ( 95 % CI 1.5 - 10.1 ) in relative change from baseline in percent-predicted FEV1 between the ataluren and placebo groups at week 48 ( -0.7 % [ -4.0 to 2.1 ] vs -6.4 % [ -9.8 to -3.7 ] ; nominal p=0.0082 ) , and fewer pulmonary exacerbations in the ataluern group ( 1.42 events [ 0.9 - 1.9 ] vs 2.18 events [ 1.6 - 2.7 ] ; rate ratio 0.60 [ 0.42 - 0.86 ] ; nominal p=0.0061 ) . Safety profiles were generally similar for ataluren and placebo , except for the occurrence of increased creatinine concentrations ( ie , acute kidney injury ) , which occurred in 18 ( 15 % ) of 118 patients in the ataluren group compared with one ( < 1 % ) of 120 patients in the placebo group . No life-threatening adverse events or deaths were reported in either group . INTERPRETATION Although ataluren did not improve lung function in the overall population of nonsense-mutation cystic fibrosis patients who received this treatment , it might be beneficial for patients not taking chronic inhaled tobramycin . FUNDING PTC Therapeutics , Cystic Fibrosis Foundation , US Food and Drug Administration 's Office of Orphan Products Development , and the National Institutes of Health Clinical studies in patients with cystic fibrosis and G551D-CFTR showed that the group treated with ivacaftor had improved clinical outcomes . To better underst and the effect of ivacaftor therapy across the distribution of individual FEV(1 ) responses , data from Phase 3 studies ( STRIVE/ENVISION ) were re-examined . In this post-hoc analysis of patients ( n = 209 ) who received 48 weeks of ivacaftor or placebo , patients were assigned to tertiles according to FEV(1 ) response . These groups were then used to evaluate response ( FEV(1 ) , sweat chloride , weight , CFQ-R , and pulmonary exacerbation ) . The number needed to treat ( NNT ) was calculated for specific thresholds for each outcome . Across all tertiles , numerical improvements in FEV(1 ) , sweat chloride , CFQ-R and the frequency of pulmonary exacerbations were observed in ivacaftor-treated patients : the treatment difference versus placebo was statistically significant for all outcomes in the upper tertile and for some outcomes in the lower and middle tertiles . The NNT for a ≥ 5 % improvement in % predicted FEV(1 ) was 1.90 , for a ≥ 5 % body weight increase was 5.74 , and to prevent a pulmonary exacerbation was 3.85 . This analysis suggests that the majority of patients with clinical characteristics similar to STRIVE/ENVISION patients have the potential to benefit from ivacaftor therapy BACKGROUND A new approach in the treatment of cystic fibrosis involves improving the function of mutant cystic fibrosis transmembrane conductance regulator ( CFTR ) . VX-770 , a CFTR potentiator , has been shown to increase the activity of wild-type and defective cell-surface CFTR in vitro . METHODS We r and omly assigned 39 adults with cystic fibrosis and at least one G551D-CFTR allele to receive oral VX-770 every 12 hours at a dose of 25 , 75 , or 150 mg or placebo for 14 days ( in part 1 of the study ) or VX-770 every 12 hours at a dose of 150 or 250 mg or placebo for 28 days ( in part 2 of the study ) . RESULTS At day 28 , in the group of subjects who received 150 mg of VX-770 , the median change in the nasal potential difference ( in response to the administration of a chloride-free isoproterenol solution ) from baseline was -3.5 mV ( range , -8.3 to 0.5 ; P=0.02 for the within-subject comparison , P=0.13 vs. placebo ) , and the median change in the level of sweat chloride was -59.5 mmol per liter ( range , -66.0 to -19.0 ; P=0.008 within-subject , P=0.02 vs. placebo ) . The median change from baseline in the percent of predicted forced expiratory volume in 1 second was 8.7 % ( range , 2.3 to 31.3 ; P=0.008 for the within-subject comparison , P=0.56 vs. placebo ) . None of the subjects withdrew from the study . Six severe adverse events occurred in two subjects ( diffuse macular rash in one subject and five incidents of elevated blood and urine glucose levels in one subject with diabetes ) . All severe adverse events resolved without the discontinuation of VX-770 . CONCLUSIONS This study to evaluate the safety and adverse-event profile of VX-770 showed that VX-770 was associated with within-subject improvements in CFTR and lung function . These findings provide support for further studies of pharmacologic potentiation of CFTR as a means to treat cystic fibrosis . ( Funded by Vertex Pharmaceuticals and others ; Clinical Trials.gov number , NCT00457821 . ) BACKGROUND Mutations in the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene containing a premature termination signal cause a deficiency or absence of functional chloride-channel activity . Aminoglycoside antibiotics can suppress premature termination codons , thus permitting translation to continue to the normal end of the transcript . We assessed whether topical administration of gentamicin to the nasal epithelium of patients with cystic fibrosis could result in the expression of functional CFTR channels . METHODS In a double-blind , placebo-controlled , crossover trial , patients with stop mutations in CFTR or patients homozygous for the DeltaF508 mutation received two drops containing gentamicin ( 0.3 percent , or 3 mg per milliliter ) or placebo in each nostril three times daily for two consecutive periods of 14 days . Nasal potential difference was measured at base line and after each treatment period . Nasal epithelial cells were obtained before and after gentamicin treatment from patients carrying stop mutations , and the C-terminal of surface CFTR was stained . RESULTS Gentamicin treatment caused a significant reduction in basal potential difference in the 19 patients carrying stop mutations ( from -45+/-8 to -34+/-11 mV , P=0.005 ) and a significant response to chloride-free isoproterenol solution ( from 0+/-3.6 to -5+/-2.7 mV , P<0.001 ) . This effect of gentamicin on nasal potential difference occurred both in patients who were homozygous for stop mutations and in those who were heterozygous , but not in patients who were homozygous for DeltaF508 . After gentamicin treatment , a significant increase in peripheral and surface staining for CFTR was observed in the nasal epithelial cells of patients carrying stop mutations . CONCLUSIONS In patients with cystic fibrosis who have premature stop codons , gentamicin can cause translational " read through , " result ing in the expression of full-length CFTR protein at the apical cell membrane , and thus can correct the typical electrophysiological abnormalities caused by CFTR dysfunction BACKGROUND Ivacaftor , a cystic fibrosis transmembrane conductance regulator ( CFTR ) potentiator , is approved for the treatment of patients with cystic fibrosis aged 6 years or older with Gly551Asp-CFTR . We assessed the safety and efficacy of ivacaftor during 96 weeks of PERSIST in patients with cystic fibrosis who completed a previous 48-week , placebo-controlled trial of the drug ( STRIVE or ENVISION ) . METHODS In this phase 3 , open-label extension study , patients received ivacaftor 150 mg every 12 h in addition to their prescribed cystic fibrosis therapies . Patients who received placebo in their previous study initiated ivacaftor in this extension study . Patients were eligible if they had a Gly551Asp-CFTR mutation on at least one allele . The primary objective was to assess the long-term safety profile of ivacaftor as assessed by adverse events , clinical laboratory assessment s , electrocardiograms , vital signs , and physical examination ; secondary measures included change in forced expiratory volume in one second ( FEV1 ) , weight , and pulmonary exacerbations . This study is registered with Clinical Trials.gov , number NCT01117012 and EudraCT , number 2009 - 012997 - 11 . FINDINGS Between July 8 , 2010 , and April 8 , 2013 , 144 adolescents/adults ( ≥12 years ) from STRIVE and 48 children ( 6 - 11 years ) from ENVISION were enrolled . Across both trials , 38 ( 20 % ) patients had a serious adverse event during the first 48 weeks and 44 ( 23 % ) during the subsequent 48 weeks . Two adults ( 1 % ) and one child ( < 1 % ) discontinued because of adverse events . The most common adverse events were pulmonary exacerbation , cough , and upper respiratory tract infection . Patients previously treated with ivacaftor had sustained improvements in FEV1 , weight , and rate of pulmonary exacerbations for up to 144 weeks of treatment . Among adolescents/adults and children who previously received ivacaftor , absolute change in FEV1 at week 96 ( 144 weeks ivacaftor ) was 9·4 and 10·3 % points and absolute increase in weight was 4·1 kg and 14·8 kg , respectively . For adolescents/adults only , the pulmonary exacerbation rate remained suppressed compared with that of patients who received placebo in the placebo-controlled study . INTERPRETATION At 144 weeks of treatment , ivacaftor was well tolerated , with no new safety concerns . Ivacaftor also provided durable effects for 144 weeks in patients who had received active treatment in the placebo-controlled study . Those patients who previously received placebo had improvements comparable to those of patients treated with ivacaftor in the placebo-controlled study . FUNDING Vertex Pharmaceuticals Sodium 4-phenylbutyrate ( Buphenyl , 4PBA ) is a new FDA approved drug for management of urea cycle disorders . We have previously presented data suggesting that 4PBA , at clinical ly achievable concentrations , induces CFTR channel function on the plasma membrane of deltaF508-expressing cystic fibrosis ( CF ) airway epithelial cells in vitro ( Rubenstein , R. C. , and P. L. Zeitlin , 1997 . J. Clin . Invest . 100:2457 - 2463 ) . We hypothesized that 4PBA would induce epithelial CFTR function in vivo in individuals homozygous for deltaF508-CFTR . A r and omized , double-blind , placebo-controlled trial in 18 deltaF508-homozygous patients with CF was performed with the maximum approved adult dose of 4PBA , 19 grams p.o . divided t.i.d . , given for 1 wk . Nasal potential difference ( NPD ) response patterns and sweat chloride concentrations were determined before and after study drug treatment , and 4PBA and metabolites were assayed in plasma and urine at the end of study drug treatment . Subjects in the 4PBA group demonstrated small , but statistically significant improvements of the NPD response to perfusion of an isoproterenol/amiloride/chloride-free solution ; this measure reflects epithelial CFTR function and is highly discriminatory between patients with and without CF . Subjects who had received 4PBA did not demonstrate significantly reduced sweat chloride concentrations or alterations in the amiloride-sensitive NPD . Side effects due to drug therapy were minimal and comparable in the two groups . These data are consistent with 4PBA therapy inducing CFTR function in the nasal epithelia of deltaF508-homozygous CF patients BACKGROUND The phe508del CFTR mutation causes cystic fibrosis by limiting the amount of CFTR protein that reaches the epithelial cell surface . We tested combination treatment with lumacaftor , an investigational CFTR corrector that increases trafficking of phe508del CFTR to the cell surface , and ivacaftor , a CFTR potentiator that enhances chloride transport of CFTR on the cell surface . METHODS In this phase 2 clinical trial , we assessed three successive cohorts , with the results of each cohort informing dose selection for the subsequent cohort . We recruited patients from 24 cystic fibrosis centres in Australia , Belgium , Germany , New Zeal and , and the USA . Eligibility criteria were : confirmed diagnosis of cystic fibrosis , age at least 18 years , and a forced expiratory volume in 1 s ( FEV1 ) of 40 % or more than predicted . Cohort 1 included phe508del CFTR homozygous patients r and omly assigned to either lumacaftor 200 mg once per day for 14 days followed by addition of ivacaftor 150 mg or 250 mg every 12 h for 7 days , or 21 days of placebo . Together , cohorts 2 and 3 included phe508del CFTR homozygous and heterozygous patients , r and omly assigned to either 56 days of lumacaftor ( cohort 2 : 200 mg , 400 mg , or 600 mg once per day , cohort 3 : 400 mg every 12 h ) with ivacaftor 250 mg every 12 h added after 28 days , or 56 days of placebo . The primary outcomes for all cohorts were change in sweat chloride concentration during the combination treatment period in the intention-to-treat population and safety ( laboratory measurements and adverse events ) . The study is registered with Clinical Trials.gov , number NCT01225211 , and EudraCT , number 2010 - 020413 - 90 . FINDINGS Cohort 1 included 64 participants . Cohort 2 and 3 combined contained 96 phe508del CFTR homozygous patients and 28 compound heterozygotes . Treatment with lumacaftor 200 mg once daily and ivacaftor 250 mg every 12 h decreased mean sweat chloride concentration by 9.1 mmol/L ( p<0.001 ) during the combination treatment period in cohort 1 . In cohorts 2 and 3 , mean sweat chloride concentration did not decrease significantly during combination treatment in any group . Frequency and nature of adverse events were much the same in the treatment and placebo groups during the combination treatment period ; the most commonly reported events were respiratory . 12 of 97 participants had chest tightness or dyspnoea during treatment with lumacaftor alone . In pre-planned secondary analyses , a significant decrease in sweat chloride concentration occurred in the treatment groups between day 1 and day 56 ( lumacaftor 400 mg once per day group -9.1 mmol/L , p<0.001 ; lumacaftor 600 mg once per day group -8.9 mmol/L , p<0.001 ; lumacaftor 400 mg every 12 h group -10.3 mmol/L , p=0.002 ) . These changes were significantly greater than the change in the placebo group . In cohort 2 , the lumacaftor 600 mg once per day significantly improved FEV1 from day 1 to 56 ( difference compared with placebo group : + 5.6 percentage points , p=0.013 ) , primarily during the combination period . In cohort 3 , FEV1 did not change significantly across the entire study period compared with placebo ( difference + 4.2 percentage points , p=0.132 ) , but did during the combination period ( difference + 7.7 percentage points , p=0·003 ) . Phe508del CFTR heterozygous patients did not have a significant improvement in FEV1 . INTERPRETATION We provide evidence that combination lumacaftor and ivacaftor improves FEV1 for patients with cystic fibrosis who are homozygous for phe508del CFTR , with a modest effect on sweat chloride concentration . These results support the further exploration of combination lumacaftor and ivacaftor as a treatment in this setting . FUNDING Vertex Pharmaceuticals , Cystic Fibrosis Foundation Therapeutics Development Network RATIONALE Nonsense ( premature stop codon ) mutations in mRNA for the cystic fibrosis transmembrane conductance regulator ( CFTR ) cause cystic fibrosis ( CF ) in approximately 10 % of patients . Ataluren ( PTC124 ) is an oral drug that permits ribosomes to readthrough premature stop codons in mRNA to produce functional protein . OBJECTIVES To evaluate ataluren activity , safety , and pharmacokinetics in children with nonsense mutation CF . METHODS Patients were assessed in two 28-day cycles , comprising 14 days on and 14 days off ataluren . Patients took ataluren three times per day ( morning , midday , and evening ) with r and omization to the order of receiving a lower dose ( 4 , 4 , and 8 mg/kg ) and a higher dose ( 10 , 10 , and 20 mg/kg ) in the two cycles . MEASUREMENTS AND MAIN RESULTS The study enrolled 30 patients ( 16 male and 14 female , ages 6 through 18 yr ) with a nonsense mutation in at least one allele of the CFTR gene , a classical CF phenotype , and abnormal baseline nasal epithelial chloride transport . Ataluren induced a nasal chloride transport response ( at least a -5-mV improvement ) or hyperpolarization ( value more electrically negative than -5 mV ) in 50 % and 47 % of patients , respectively , with more hyperpolarizations at the higher dose . Improvements were seen in seven of nine nonsense mutation genotypes represented . Ataluren significantly increased the proportion of nasal epithelial cells expressing apical full-length CFTR protein . Adverse events and laboratory abnormalities were infrequent and usually mild . Ataluren pharmacokinetics were similar to those in adults . CONCLUSIONS In children with nonsense mutation CF , ataluren can induce functional CFTR production and is well tolerated BACKGROUND Ivacaftor ( VX-770 ) is a cystic fibrosis transmembrane conductance regulator ( CFTR ) potentiator that was approved in the United States for the treatment of cystic fibrosis ( CF ) in patients ≥ 6 years of age who have a G551D mutation ; however , the most prevalent disease-causing CFTR mutation , F508del , causes a different functional defect . The objectives of this study were to evaluate the safety of ivacaftor in a larger population and for a longer time period than tested previously and to assess the efficacy of ivacaftor in subjects with CF who are homozygous for F508del-CFTR . METHODS This was a phase 2 study with a 16-week r and omized ( 4:1 ) , double-blind , placebo-controlled period ( part A ) and an open-label extension ( part B ) for subjects who met prespecified criteria . RESULTS Part A : The safety profile of ivacaftor was comparable to that of the placebo . The overall adverse event frequency was similar in the ivacaftor ( 87.5 % ) and placebo ( 89.3 % ) groups through 16 weeks . The difference in the change of FEV₁ % predicted from baseline through week 16 ( primary end point ) between the ivacaftor and placebo groups was 1.7 % ( P = .15 ) . Sweat chloride , a biomarker of CFTR activity , showed a small reduction in the ivacaftor vs placebo groups of -2.9 mmol/L ( P = .04 ) from baseline through week 16 . Part B : No new safety signals were identified . The changes in FEV₁ or sweat chloride in part A were not sustained with ivacaftor treatment from week 16 to week 40 . CONCLUSIONS These results exp and the safety information for ivacaftor and support its continued evaluation . Lack of a clinical effect suggests that a CFTR potentiator alone is not an effective therapeutic approach for patients who have CF and are homozygous for F508del-CFTR . TRIAL REGISTRY Clinical Trials.gov ; No. : NCT00953706 ; URL : www . clinical trials.gov RATIONALE Ivacaftor ( VX-770 ) , a cystic fibrosis transmembrane conductance regulator ( CFTR ) potentiator , has been shown to improve lung function , pulmonary exacerbation rate , respiratory symptoms , and weight gain compared with placebo in patients with cystic fibrosis aged 12 years or older with a G551D-CFTR mutation . OBJECTIVES This r and omized , double-blind , placebo-controlled trial evaluated ivacaftor in patients with cystic fibrosis aged 6 - 11 years with a G551D-CFTR mutation on at least one allele . METHODS Patients were r and omly assigned to receive ivacaftor administered orally at 150 mg ( n = 26 ) or placebo ( n = 26 ) every 12 hours for 48 weeks in addition to existing prescribed cystic fibrosis therapies . MEASUREMENTS AND MAIN RESULTS Despite near-normal mean baseline values in FEV1 , patients receiving ivacaftor had a significant increase in percent predicted FEV1 from baseline through Week 24 versus placebo group ( treatment effect , 12.5 percentage points ; P < 0.001 ) . Effects on pulmonary function were evident by 2 weeks , and a significant treatment effect was maintained through Week 48 . Patients treated with ivacaftor gained , on average , 2.8 kg more than those receiving placebo at Week 48 ( P < 0.001 ) . The change from baseline through Week 48 in the concentration of sweat chloride , a measure of CFTR activity , with ivacaftor was -53.5 mmol/L ( P < 0.001 ) versus placebo . The incidence of adverse events was similar in the two groups . CONCLUSIONS In patients who are younger and healthier than those in previously studied population s , ivacaftor demonstrated a significant improvement in pulmonary function , weight , and CFTR activity compared with placebo . Clinical trial registered with www . clinical trials.gov ( NCT00909727 ) |
805 | 22,592,725 | Although this and other potential sources of bias limited the overall quality , the efficacy of antipsychotic drugs for maintenance treatment in schizophrenia was clear .
The results clearly demonstrate the superiority of antipsychotic drugs compared to placebo in preventing relapse .
This effect must be weighed against the side effects of antipsychotic drugs . | BACKGROUND The symptoms and signs of schizophrenia have been firmly linked to high levels of dopamine in specific areas of the brain ( limbic system ) .
Antipsychotic drugs block the transmission of dopamine in the brain and reduce the acute symptoms of the disorder .
This review examined whether antipsychotic drugs are also effective for relapse prevention .
OBJECTIVES To review the effects of maintaining antipsychotic drugs for people with schizophrenia compared to withdrawing these agents . | 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 The Soteria project ( 1971–1983 ) compared residential treatment in the community and minimal use of antipsychotic medication with “ usual ” hospital treatment for patients with early episode schizophrenia spectrum psychosis . Newly diagnosed DSM-II schizophrenia subjects were assigned consecutively ( 1971 to 1976 , N = 79 ) or r and omly ( 1976 to 1979 , N = 100 ) to the hospital or Soteria and followed for 2 years . Admission diagnoses were subsequently converted to DSM-IV schizophrenia and schizophreniform disorder . Multivariate analyses evaluated hypotheses of equal or better outcomes in Soteria on eight individual outcome measures and a composite outcome scale in three ways : for endpoint subjects ( N = 160 ) , for completing subjects ( N = 129 ) , and for completing subjects corrected for differential attrition ( N = 129 ) . Endpoint subjects exhibited small to medium effect size trends favoring experimental treatment . Completing subjects had significantly better composite outcomes of a medium effect size at Soteria ( + .47 SD , p = .03 ) . Completing subjects with schizophrenia exhibited a large effect size benefit with Soteria treatment ( + .81 SD , p = .02 ) , particularly in domains of psychopathology , work , and social functioning . Soteria treatment result ed in better 2-year outcomes for patients with newly diagnosed schizophrenia spectrum psychoses , particularly for completing subjects and for those with schizophrenia . In addition , only 58 % of Soteria subjects received antipsychotic medications during the follow-up period , and only 19 % were continuously maintained on antipsychotic medications A double-blind withdrawal trial in 41 chronic schizophrenic out patients was carried out during 6 months . Depot neuroleptics ( fluphenazine decanoate or flupenthixol decanoate ) were compared with placebo to evaluate clinical and neurological effects during continued therapy and during withdrawal . The drugs were significantly more effective than placebo in preventing relapse and rehospitalization . In the placebo group 62 % relapsed compared to 27 % in the drug group . There was a weak and nonsignificant tendency to a higher relapse frequency in the flupenthixol group compared to the fluphenazine group . After withdrawal for 6 months , plasma levels for fluphenazine were detectable . Plasma levels for flupenthixol were not detectable after 9 weeks of withdrawal . The differences in the plasma levels may possibly explain the difference in relapse rate between the two depot neuroleptics . Furthermore , it was found that the patients who relapsed during fluphenazine treatment had a significantly lower plasma level of the drug than patients who did not relapse during treatment . The results from this study provide some information on the therapeutic levels of fluphenazine and flupenthixol in schizophrenic patients A six-month evaluation of penfluridol , a long-acting oral preparation , was conducted with 50 severely ill schizophrenic patients . After an initial three-month stabiization period , the patients were divided into two equal groups and a double-blind evaluation of penfluridol versus placebo was conducted . The results of this study indicate that weekly administration of penfluridol ( one oral dose ) provides relatively safe and adequate control of severely ill schizophrenic patients and displays efficacy similar to that of the shorter-acting antipsychotic agents . If these results are confirmed by other clinical investigators , this medication may prove to be of invaluable help in maintaining the schizophrenic patient in his community Out of 253 patients fulfilling criteria for a first episode of schizophrenic illness , 120 entered a r and omised placebo-controlled trial of maintenance neuroleptic medication on discharge ; they were followed to relapse or loss to follow-up , for two years or to the end of the study . Of those on active medication , 46 % relapsed , as did 62 % of those on placebo ; the most important determinant of relapse was duration of illness prior to starting neuroleptic medication . This finding might be because extended duration of symptoms before admission is more likely to be present in illnesses which in any case will have poor prognosis , or because susceptibility to relapse is reduced by early institution of treatment . The study provides no data on which a decision between these alternative explanations can be based BACKGROUND Amisulpride is a substituted benzamide with high selectivity for dopamine D2 and D3 receptors . The purpose of the study was to evaluate the effect of 100 mg amisulpride in patients with predominantly negative symptoms of schizophrenia . METHOD This was a multi-centre , r and omised , parallel-group , double-blind study . Patients received either amisulpride ( 100 mg/day ) or placebo over a six-month treatment period . RESULTS A total of 141 patients were included , 69 received amisulpride , 72 placebo . Fifty-eight patients ( 41 % ) had received neuroleptic treatment prior to inclusion . The percentage of amisulpride patients completing the study ( 55 % ) was significantly higher than that with placebo ( 32 % ) , and drop-out rates due to lack of efficacy were 27 % with amisulpride and 47 % with placebo . All efficacy assessment s were statistically in favour of amisulpride compared with placebo . The overall incidence of extrapyramidal symptoms was comparable in both groups ; only five patients started anti-Parkinsonian treatment during the study ( one in the placebo and four in the amisulpride group ) . CONCLUSION Amisulpride is effective in the medium-term treatment schizophrenic patients with predominantly negative symptoms OBJECTIVE Despite the frequent use of the Positive and Negative Syndrome Scale ( PANSS ) for rating the symptoms of schizophrenia , the clinical meaning of its total score and of the cut-offs that are used to define treatment response ( e.g. at least 20 % or 50 % reduction of the baseline score ) are as yet unclear . We therefore compared the PANSS with simultaneous ratings of Clinical Global Impressions ( CGI ) . METHOD PANSS and CGI ratings at baseline ( n = 4091 ) , and after one , two , four and six weeks of treatment taken from a pooled data base of seven pivotal , multi-center antipsychotic drug trials on olanzapine or amisulpride in patients with exacerbations of schizophrenia were compared using equipercentile linking . RESULTS Being considered " mildly ill " according to the CGI approximately corresponded to a PANSS total score of 58 , " moderately ill " to a PANSS of 75 , " markedly ill " to a PANSS of 95 and severely ill to a PANSS of 116 . To be " minimally improved " according to the CGI score was associated with a mean percentage PANSS reduction of 19 % , 23 % , 26 % and 28 % at weeks 1 , 2 , 4 and 6 , respectively . The corresponding figures for a CGI rating " much improved " were 40 % , 45 % , 51 % and 53 % . CONCLUSIONS The results provide a better framework for underst and ing the clinical meaning of the PANSS total score in drug trials of schizophrenia patients with acute exacerbations . Such studies may ideally use at least a 50 % reduction from baseline cut-off to define response rather than lower thresholds . In treatment resistant population s , however , even a small improvement can be important , so that a 25 % cut-off might be appropriate A double-blind , placebo-controlled trial was carried out to determine the value of maintenance therapy with phenothiazines in a population of out patients who had recently recovered from an acute episode of schizophrenia . The drug was shown to be significantly more effective than the placebo in preventing relapse . The relationship of the trial patients to the population from which they were selected was defined in terms of clinical , historical , and social data . Maintenance therapy seems of little value in patients with a good prognosis and in the severely ill , but it is of value in the indeterminate group between these two extremes Twenty‐seven long‐term psychiatric in patients maintained on neuroleptics with concomitant antiparkinsonian medication were entered into a study in which anticholinergic medication was gradually withdrawn in a r and omized double‐blind within‐subjects design . The extrapyramidal symptoms of each patient were compared when taking their usual anticholinergic medication , when taking placebo and when taking no antiparkinsonian drug . The relapse rate on no medication was 14 % , and if patients relapsed on no medication they also relapsed on placebo . The relapse rate was not significantly different on active medication . Nor were there significant differences in ratings of parkinsonism or dyskinesia . The lack of difference between double‐blind and overt withdrawal does not mean that studies that find a much higher relapse rate are necessarily unaffected by nonspecific factors , as significant unblinding may occur in clinical trials The plasma prolactin ( PRL ) levels of 35 chronic schizophrenic patients undergoing long‐term maintenance treatment with neuroleptic drugs were measured before and after either neuroleptic withdrawal or a switch to a fixed dose of chlorpromazine 900 mg/ day . In both men and women there tended to be a significant correlation between the initial log plasma PRL level while on neuroleptic maintenance treatment and the dosage received converted to chlorpromazine equivalents . Neuroleptic withdrawal in each of 19 cases was followed by a decline in PRL plasma levels . Switching to chlorpromazine 900 mg/day ( 16 cases ) produced either increases or decreases in PRL plasma levels that were significantly correlated with the change in neuroleptic dosage converted to chlorpromazine equivalents . Thus there was no evidence of tolerance to the PRL‐elevating effect of neuroleptics in these patients who had been treated for many years with neuroleptics An earlier study ( Study 1 : 14 months duration ) showed that the PAT ( an auditory attention task ) is sensitive to changes of clinical state in chronic schizophrenia and is able to predict hospital discharge . The newly presented study ( Study 2 : 12 months duration ) investigated the effects of increasing the dose of chlorpromazine ( CPZ ) stepwise ( double-blind ) to between 900 mg and 1800 mg per day , in 10 of the original 20 patients . Measurements were made fortnightly throughout both studies and the data were depicted continuously for each patient . Study 2 showed that a 300 % increase of CPZ dose neither improved nor impaired PAT performance . Also , the addition of orphenadrine 300 mg per day had no significant effect on performance . Four types of relapse were detected . The first was induced by placebo substitution for CPZ and recovered when the drug was reinstated . The remaining types of relapse were all resistant to CPZ and comprised : a long-period pattern with a spontaneous reversal ; unremitting deterioration ; and a short-period pattern of labile relapse and recovery The postulated deficiency of prostagl and in E1 series ( PGE1 ) in schizophrenia has been investigated in a controlled therapeutic trial . Twenty-one in patients with a schizophrenic illness resistant to neuroleptic drug treatments were r and omly assigned to one of three treatment conditions in a blind controlled trial of dihomo-gammalinolenic acid ( DHLA ) , a PGE1 precursor . Patients received depot neuroleptic medication and DHLA capsules , placebo depot medication and DHLA capsules , or placebo depot medication and placebo capsules . No marked treatment effects were noticed on ratings of the patients ' behaviour or symptomatology , though some clinical effects were noted in dyskinetic patients . Abnormalities in red blood cell lipids were observed in the patients entering the trial , suggesting that further investigation of an EFA/prostagl and in deficiency hypothesis in schizophrenia is worth pursuing The dopamine hypothesis of schizophrenia cl aims that increased dopamine activity underlies psychotic behavior . This hypothesis gets major support from the reported d-amphetamine-induced worsening of psychosis , because amphetamine increases dopamine activity in the brain . Dopamine receptor supersensitivity has been shown to be present in animals during the postneuroleptic period . In this study the postulated relationships between psychotic decompensation as observed after d-amphetamine infusion and the dopamine receptor supersensitivity expected to be present during the neuroleptic withdrawal period were examined . Twenty milligrams of d-amphetamine administered intravenously did not cause a stronger psychotogenic effect in 12 schizophrenic patients . One week after discontinuation of pimozide treatment , the d-amphetamine-induced change as indicated by the Brief Psychiatric Rating Scale ( BPRS ) paranoid disturbance cluster score , was not significantly different from the response to a similar infusion during the drug-free state . Unexpectedly , the increase in the BPRS mannerisms and posturing item and in the pulse rate response to d-amphetamine were decreased . These results raise questions about the role of dopamine in d-amphetamine effects and suggest postneuroleptic dopamine receptor subsensitivity . They challenge a simple dopamine hypothesis of schizophrenia Fifty-two " hard core " mental patients who had been receiving psychotropic drugs were assigned to one of four subgroups , equated on descriptive variables , level of functioning , and bizarre behavior . All patients then participated in one of two social-environmental treatment programs , with one subgroup in each program receiving drug continuation in different capsule form , and the other receiving abrupt withdrawal with placebo substitution . Relative and interactional effects of drug conditions were evaluated 17 weeks after drug changes with concomitant exposure to active treatment programs , without patients , treatment staff , or assessors being aware that a drug study was underway . Except in early stages of treatment , where drugs interfered with improvement , continued low-dosage maintenance chemotherapy as prescribed in practice failed to produce direct effects or to contribute to responsiveness to the environmental programs OBJECTIVE In light of the efficacy of newer antipsychotic agents and the possibility that drug withdrawal may negatively affect subsequent drug response , concern has arisen that the use of placebo in schizophrenia research may be unethical . This study examines the effect size of symptom exacerbation during drug washout with placebo and the effects of drug washout on the efficacy of subsequent drug treatment . METHOD Fifty patients with treatment-resistant schizophrenia hospitalized on a research unit participated in a double-blind longitudinal study of the effects of drug washout after chronic treatment with a typical antipsychotic and before prospect i ve treatment with clozapine . Brief Psychiatric Rating Scale ( BPRS ) scores were analyzed to examine drug effects and effect sizes for baseline treatment with a typical antipsychotic ( > 6 months treatment ) , drug washout with placebo ( mean=34 days ) , early treatment with clozapine ( mean=42 days , mean dose=345.0 mg/day ) , and optimal clozapine treatment ( mean=83 days , mean dose=450.5 mg/day ) . RESULTS Patients ' BPRS total , positive , and negative symptom scores significantly increased during placebo washout , compared with baseline treatment , and significantly decreased with administration of clozapine , compared with placebo washout and baseline treatment . However , 30 % of patients showed some symptom improvement during placebo washout . The effect sizes for the BPRS total score were 0.63 for baseline treatment versus placebo washout , 1.10 for optimal clozapine treatment versus placebo washout , and 0.82 for optimal clozapine treatment versus baseline treatment . CONCLUSIONS Symptom exacerbation induced by drug withdrawal in patients with treatment-resistant schizophrenia did not impede subsequent responsiveness to clozapine . The effect size for clozapine , compared with typical antipsychotics , suggests that the drug-washout longitudinal design is useful for establishing a drug-free baseline and for investigating drug response , while requiring relatively few subjects Because the importance of tranquilizing drugs has been difficult to assess precisely , the author undertook a study on the effect of the withdrawal of chlorpromazine and trifluoperazine on hospitalized male schizophrenics in Engl and . Although there were no major relapses among the placebo group , changes occurred that were sometimes disabling Eighty-seven predominantly withdrawn chronic male schizophrenics were r and omly assigned to one of three treatment groups . After a two-week course of placebo administration treatment was started with matching tablets containing either amitriptyline 25 mg.+perphenazine 4 mg . , perphenazine 4 mg . , or placebo . For the first five weeks of the trial the dose was one tablet t.i.d . , and for the second five weeks , 2 tablets t.i.d . Neither the nursing staff nor the doctors concerned knew which tablets were which . Wing Scale Form A ( completed by two psychiatrists independently ) and Form B ( filled in by a senior nurse ) yielded very similar results , rating the effectiveness of the three treatments as amitriptyline/perphenazine > perphenazine > Analysis of variance of overall improvement and of individual symptoms revealed that differences between doctors ' assessment s were insignificant . Patients taking amitriptyline/perphenazine showed a significant weight gain . Regular blood examination revealed no abnormalities . The withdrawn , inert hospitalized male schizophrenic constitutes a difficult problem to many workers in the psychiatric field . The encouraging fact emerged from this clinical trial that symptoms such as flattening and incongruity of affect , sometimes made worse by long-term administration of tranquilizing drugs , could effectively be relieved , bringing a hope that rehabilitation may perhaps be possible in some seemingly hopeless cases The authors estimated components of variance and intraclass correlation coefficients ( ICCs ) to aid in the design of complex surveys and community intervention studies by analyzing data from the Health Survey for Engl and 1994 . This cross-sectional survey of English adults included data on a range of lifestyle risk factors and health outcomes . For the survey , households were sample d in 720 postal code sectors nested within 177 district health authorities and 14 regional health authorities . Study subjects were adults aged 16 years or more . ICCs and components of variance were estimated from a nested r and om-effects analysis of variance . Results are presented at the district health authority , postal code sector , and household levels . Between-cluster variation was evident at each level of clustering . In these data , ICCs were inversely related to cluster size , but design effects could be substantial when the cluster size was large . Most ICCs were below 0.01 at the district health authority level , and they were mostly below 0.05 at the postal code sector level . At the household level , many ICCs were in the range of 0.0 - 0.3 . These data may provide useful information for the design of epidemiologic studies in which the units sample d or allocated range in size from households to large administrative areas Remitted schizophrenic out patients were treated in order to prevent relapse with three doses of haloperidol or propericiazine for 1 year in a double-blind controlled study employing a r and omized design . The drug 's ability to prevent relapse was evaluated by counting the number of symptom-free days for each patient before any sign of relapse or over-dose appeared . Patients were r and omly assinged to the following drugs orally administered once per day at night : placebo ; haloperidol 1 mg , 3 mg , and 6 mg ; propericiazine 10 mg , 30 mg , and 60 mg . Serum prolactin levels in each patient were estimated by radioimmunoassay . All patients treated with placebo relapsed within 1 year and the relapse rate with placebo was significantly higher than with any dose of the two neuroleptics . Haloperidol increased the number of symptom-free days in a dose-dependent manner . Propericiazine at 10 mg and 30 mg also increased the number of symptom-free days dose-dependently but at 60 mg , the number decreased . It appears that propericiazine shows an inverted U-shaped dose-response curve . Prolactin levels were elevated dose-dependently by both drugs but failed to show a significant correlation with the number of symptom-free days . The present results indicate that haloperidol is superior to propericiazine from the viewpoint of the wider “ therapeutic window ” in maintenance treatment and antidopaminergic properties of neuroleptics , wherein it is important to prevent relapse even in remitted schizophrenics Results of studies on intermittent neuroleptic treatment strategies in first episode ( FE ) schizophrenia have not been published . Aims of the present study were to eluci date the comparative efficacy of prodrome-based neuroleptic intervention in first vs multiple episode ( ME ) schizophrenia . As to the methods , three r and omly assigned open neuroleptic treatment strategies were compared over 2 years in 363 schizophrenic out patients ( 115 FE , 248 ME ; ICD-9 , RDC ) : maintenance medication vs two intermittent medication strategies ( prodrome-based intervention and crisis intervention ) . Concerning relapse prevention , the results demonstrate that ME patients seemed to profit most from maintenance medication compared to both intermittent treatments , whereas FE patients did equally well under maintenance medication and prodrome-based intervention treatment . Psychopathology , social adjustment , subjective well-being , and side-effects after two years did not differ significantly between the FE and ME patients irrespective of treatment strategy . Concerning treatment adherence , FE patients complied better with prodrome-based intervention than with maintenance medication . Cumulative neuroleptic dosage was lowest in FE patients under intermittent treatment . In conclusion , maintenance medication is the best strategy for relapse prevention in ME patients . In FE patients , prodrome-based intermittent intervention seems to be equivalent or even better with respect to compliance and dosage applied To test the clinical efficacy of low dose fluphenazine decanoate ( 1.25 mg to 5.0 mg biweekly ) , we carried out two separate experiments : ( 1 ) an open trial in 57 schizophrenic out patients , lasting 6 months ; ( 2 ) a double-blind , placebo-controlled discontinuation study in a subgroup of patients who maintained good remission throughout the entire 6-month open trial . The results suggest that lower doses of fluphenazine decanoate than those usually used may be effective in preventing psychotic relapse while keeping total cumulative dosage to a minimum BACKGROUND Aripiprazole is a novel antipsychotic for the management of schizophrenia . This study investigated the efficacy , safety , and tolerability of aripiprazole in preventing relapse in adult chronic schizophrenia patients experiencing ongoing stable symptomatology . METHOD In this 26-week , r and omized , double-blind , placebo-controlled , parallel-group , multi-center study , 310 patients with DSM-IV schizophrenia ( mean Positive and Negative Syndrome Scale [ PANSS ] total score = 82 ) were r and omly assigned to receive a once-daily fixed dose of aripiprazole , 15 mg , or placebo . The primary outcome measure was time to relapse following r and omization . Secondary objectives were to assess the efficacy , safety , and tolerability of aripiprazole , 15 mg , compared with placebo , in the study population . The study was conducted between Dec. 21 , 2000 , and Aug. 20 , 2001 . RESULTS The time to relapse following r and omization was significantly ( p < .001 ) longer for aripiprazole compared with placebo . More patients relapsed with placebo ( N = 85 ; 57 % ) than aripiprazole ( N = 50 ; 34 % ) ; the relative risk of relapse for the aripiprazole group was 0.59 ( p < .001 ) . Aripiprazole was significantly superior to placebo from baseline to endpoint in PANSS total , PANSS positive , PANSS-derived Brief Psychiatric Rating Scale , and Clinical Global Impressions-Severity of Illness scale ( CGI-S ) scores and demonstrated significantly better mean Clinical Global Impressions-Global Improvement scale scores ( p < or = .01 for all comparisons except CGI-S : .01 < p < or = .05 ) . Aripiprazole was well tolerated , with no evidence of marked sedation and no evidence of hyperprolactinemia or prolonged heart rate-corrected QT interval ( QTc ) . Extrapyramidal symptoms were comparable in the aripiprazole and placebo groups . Modest mean weight loss at endpoint was evident in both groups . CONCLUSION Aripiprazole , 15 mg once daily , is an effective , well-tolerated treatment for prevention of relapse in patients with chronic , stable schizophrenia We examined the effects of chlorpromazine and major role therapy ( MRT ) on the quality of community adjustment of schizophrenic patients during a two-year period following hospital discharge . Among patients in the community , those treated with combined drug and sociotherapy adjust better than those taking the drug alone ; to a greater extent , those receiving placebo alone adjust better than those receiving placebo and sociotherapy . However , only 20 % of those in the placebo group have not relapsed after two years while the comparable percentage for the drug group is 52 % . Effects found on assessment s made by psychiatrists , social workers , family ratings , and self-reports replicate at three clinics . Maximum restorative benefits require both maintenance phenothiazine and psychologic treatment continued for beyond a single year following hospital discharge Abstract . Rationale : Zotepine is an antipsychotic drug with proven efficacy for treatment of acute episodes of schizophrenia . Antipsychotic drugs also require to be effective in prevention of recurrence . Objective : This trial was design ed to compare the effects of zotepine and placebo in the prevention of recurrence of acute episodes in a population of patients with chronic schizophrenia . Methods : The study was a double-blind , parallel group , 26-week comparison of zotepine ( 300 mg daily , with fall back to 150 mg if necessary ) versus placebo in 121 patients with chronic schizophrenia and a history of recurrence in the previous 18 months . The primary outcome measure was the time to recurrence . Other evaluations included the brief psychiatric rating scale ( BPRS ) , the scale for the assessment of negative symptoms ( SANS ) , the clinical global impression ( CGI ) severity and improvement scales , and the Simpson and Angus scale for extrapyramidal symptoms ( EPS ) . Results : Fewer zotepine patients experienced recurrence over 26 weeks than placebo patients ( 4 versus 21 , respectively ) . The estimated 26-week risk of recurrence was six times lower for zotepine than placebo ( 8.7 % versus 52.8 % ; hazard ratio 0.16 , 95 % CI 0.053 , 0.484 ; P<0.001 ) . Scores on the BPRS and CGI supported the efficacy of zotepine . There was no difference between the treatments with respect to EPS . Conclusions : Zotepine is effective in preventing recurrence in patients with chronic schizophrenia . The level of EPS was not different between zotepine and placebo The treatment of schizophrenic patients who fail to respond to adequate trials of neuroleptics is a major challenge . Clozapine , an atypical antipsychotic drug , has long been of scientific interest , but its clinical development has been delayed because of an associated risk of agranulocytosis . This report describes a multicenter clinical trial to assess clozapine 's efficacy in the treatment of patients who are refractory to neuroleptics . DSM-III schizophrenics who had failed to respond to at least three different neuroleptics underwent a prospect i ve , single-blind trial of haloperidol ( mean dosage , 61 + /- 14 mg/d ) for six weeks . Patients whose condition remained unimproved were then r and omly assigned , in a double-blind manner , to clozapine ( up to 900 mg/d ) or chlorpromazine ( up to 1800 mg/d ) for six weeks . Two hundred sixty-eight patients were entered in the double-blind comparison . When a priori criteria were used , 30 % of the clozapine-treated patients were categorized as responders compared with 4 % of chlorpromazine-treated patients . Clozapine produced significantly greater improvement on the Brief Psychiatric Rating Scale , Clinical Global Impression Scale , and Nurses ' Observation Scale for Inpatient Evaluation ; this improvement included " negative " as well as positive symptom areas . Although no cases of agranulocytosis occurred during this relatively brief study , in our view , the apparently increased comparative risk requires that the use of clozapine be limited to selected treatment-resistant patients In a simple remitted , nonpsychotic schizophrenics , the relapse rate within one year was significantly higher for those patients taking placebo as opposed to those taking fluphenazine hydrochloride orally or fluphenazine decanoate . There were no differences in relapse rates between the two active drugs , but there were significantly more terminations due to toxicity from fluphenazine decanoate than from pluphenazine given orally , entirely due to the fact that in 35 % of patients receiving fluphenazine decanoate , severe akinesia developed Benztropine mesylate ( intravenous [ IV ] and oral ) challenge was compared with brief neuroleptic withdrawal on dyskinesia ratings and symptom measures . Thirty-six neuroleptic-treated patients underwent a placebo-controlled acute IV challenge with 2 mg benztropine and a placebo-controlled two-week trial of oral benztropine mesylate ( 2 mg three times a day ) , followed by a double-blind placebo-controlled neuroleptic withdrawal involving four weeks of dose tapering and six weeks of placebo treatment . Benztropine given IV had no significant effect . Orally administered benztropine , however , led to statistically significant increases in dyskinesia and dysphoric mood . The brief neuroleptic withdrawal significantly increased dyskinesia scores and dysphoria and result ed in early termination of therapy in 12 of 36 patients ( 33 % ) due to symptom exacerbation . There was a striking absence of correlation between dyskinesia change measures brought about by benztropine and changes following neuroleptic withdrawal . Therefore anticholinergic challenge does not appear to be a fruitful procedure for identifying patients with covert dyskinesia The clinical promise of penfluridol as a long-acting oral antipsychotic medication has led to a number of controlled studies design ed to verify its usefulness . These studies have been review ed and compared with a controlled study carried out by the authors . The data obtained from this study have tended to confirm the impression of previous investigators that penfluridol , administered in a dosage of 40 to 80 mg on a once-a-week basis in a single dose , compares favorably with the antipsychotic activity of those neuroleptics requiring administration on a daily basis OBJECTIVE Long-term efficacy of asenapine in preventing schizophrenia relapse was assessed in a 26-week double-blind , placebo-controlled trial that followed 26 weeks of open-label treatment . METHOD Stable schizophrenia patients ( DSM-IV-TR criteria ) who were cross-titrated from previous medication to sublingual asenapine and remained stable during 26 weeks of open-label treatment were eligible for 26 weeks of double-blind treatment , with r and omization to continued asenapine or switch to placebo . Time to relapse/impending relapse ( primary endpoint , as usually determined by specific scores on the Positive and Negative Syndrome Scale and the Clinical Global Impressions-Severity of Illness Scale ) and discontinuation for any reason ( key secondary endpoint ) were assessed by survival analyses for asenapine versus placebo . The study was conducted from May 2005 through June 2008 . RESULTS Of 700 enrolled patients treated with open-label asenapine , 386 entered ( asenapine , n = 194 ; placebo , n = 192 ) and 207 completed ( n = 135 ; n = 72 ) the double-blind phase . Times to relapse/impending relapse and discontinuation for any reason were significantly longer with asenapine than with placebo ( both P < .0001 ) . Incidence of relapse/impending relapse was lower with asenapine than placebo ( 12.1 % vs 47.4 % , P < .0001 ) . The modal dosage of asenapine was 10 mg twice daily in both phases . During the double-blind phase , the incidence of adverse events ( AEs ) considered serious with asenapine and placebo was 3.1 % and 9.9 % , respectively ; incidence of extrapyramidal symptom-related AEs was 3.1 % and 4.7 % , respectively . The most frequently reported AEs with asenapine versus placebo were anxiety ( 8.2 % ; 10.9 % ) , increased weight ( 6.7 % ; 3.6 % ) , and insomnia ( 6.2 % ; 13.5 % ) . The incidence of clinical ly significant weight gain ( ≥ 7 % increase from double-blind baseline ) was 3.7 % with asenapine and 0.5 % with placebo . CONCLUSIONS Long-term treatment with asenapine was more effective than placebo in preventing relapse of schizophrenia and appeared to be safe and well tolerated . TRIAL REGISTRATION clinical trials.gov Identifier NCT00150176 The posthospital treatment of 374 schizophrenics was controlled and evaluated for two years . Relapse rates for the first year were recorded . At clinic intake , patients were r and omly assigned to major role therapy ( MRT ; social casework and vocational rehabilitation counseling ) and stabilized through the administration of chlorpromazine . After two months , further assignment to drug or placebo was made . Four groups were studied in each of three aftercare clinics : placebo alone ; placebo and MRT ; drug alone ; drug and MRT . Relapse in the placebo group is twice that of the drug group , but one half of all relapsers ( drug and placebo ) cease medication prior to relapse . The prophylactic action of the drug is established for many remitted schizophrenics . The MRT also lowers relapse rate significantly , but only after six months . Drug and sociotherapy effects are additive rather interactive by 12 months . Results replicate across all clinics OBJECTIVE We assessed efficacy and tolerability of the injectable atypical antipsychotic paliperidone palmitate in delaying time-to-relapse in adults with schizophrenia . METHODS Eligible patients ( Positive and Negative Syndrome Scale [ PANSS ] total score < 120 ) were transitioned from previous antipsychotics to paliperidone palmitate during a 9-week , open-label phase . Patients received the first 2 intramuscular injections of paliperidone palmitate ( 50 mg eq ) one-week apart , then subsequent injections ( 25 , 50 , or 100 mg eq , flexibly-dosed ) , once-monthly . Stable patients ( PANSS total score < or = 75 ) continued into the 24-week maintenance phase . At maintenance phase endpoint , stabilized patients were r and omized ( 1:1 ratio ) to either continue paliperidone palmitate ( at stabilized dose ) or begin placebo in the variable- duration , double-blind phase . RESULTS The preplanned interim analysis ( conducted after 68 relapse events ) included 312 patients : mean age = 40 years , 55 % men , 66 % white , and mean transition baseline PANSS total score ( SD ) : placebo , 69.5 ( 16.89 ) ; paliperidone palmitate , 69.3 ( 17.39 ) . Time-to-relapse ( primary endpoint ) favored paliperidone palmitate ( p<0.0001 , log-rank test ) at interim and final analysis ( n=408 ) . The hazard ratio ( placebo/paliperidone palmitate ) at the final analysis was 3.60 ( 95 % CI : 2.45 , 5.28 ) . Treatment-emergent adverse event rates ( final analysis set ) were : 67 % for transition and maintenance phases , and 45 % ( placebo ) and 44 % ( paliperidone palmitate ) for the double-blind phase . Across phases , the incidence of glucose-related adverse events was low ( < or = 4 % ) , while mean weight increased by 1.9 kg for paliperidone palmitate and remained unchanged for placebo patients . Injection site tolerability was comparable between groups . CONCLUSION Paliperidone palmitate significantly delayed time-to-relapse compared with placebo and presented no new safety signals Abstract Objective . To assess the effect of withdrawal of antipsychotic treatment on relapse risk in remitted first-episode schizophrenia patients . Methods . First-episode 1-year stable and remitted out patients with a schizophrenic disorder were r and omly allocated to continuation of their antipsychotic regimen for at least 6 months ( N = 9 ) , or gradual withdrawal ( N = 11 ) . Primary outcome was the difference in cumulative relapse-free survival at 9 months . Results . Recruitment was terminated prematurely on 26 October 2005 . The cumulative relapse-free survival was 88 % ( SE = 0.12 ) in the continuation and 18 % ( SE = 0.12 ) in the discontinuation group ( P = 0.001 ) at 9 months follow-up . Conclusions . Discontinuation of antipsychotic medication markedly increases the risk of relapse in stable remitted first-episode schizophrenia patients . In future studies the topics of safety monitoring and sampling of patients should receive extra attention A new auditory attention task ( PAT ) is described . The test comprises four different subtest combinations ( diotic/dichotic , slow/fast ) each of 5 min duration . Omission and commission errors are combined by an index of errors ( IE ) . The PAT was given fortnightly to 20 chronic schizophrenic in patients for more than one year . Independent psychiatrists rated the patients according to the Brief Psychiatric Rating Scale and a Global Rating Scale . All measures yielded significant test-retest reliabilities . The patients were stabilized on individualized doses of chlorpromazine ( CPZ ) and r and omized to two groups . Placebo was substituted for CPZ during 10 weeks , according to a double-blind cross-over design . Significant deterioration under placebo was detected by all three methods , but the PAT was the most sensitive to change . The PAT mean score ( M IE ) was correlated with both rating scales . Unlike the rating scales , it also correctly ordered the twenty patients along a dimension which measured the severity of illness and ' predicted ' hospital discharge This secondary report from our 52-week , double-blind , relapse prevention trial tested whether stable patients with schizophrenia who were taken off active drug treatment would experience greater improvements in long-term quality of life than those who were continued on antipsychotic treatment . On average , Heinrichs-Carpenter Quality -of-Life Scale total scores improved by 4.3 ± 10.6 points during treatment with olanzapine ( 10 - 20 mg/d ; n = 212 ) , but decreased by 7.1 ± 14.6 points during treatment with placebo ( n = 92 ; P < 0.001 ) . Mean Quality -of-Life Scale total scores worsened in both treatment groups for the relapsing patient subgroup , whereas for nonrelapsing patients , those treated with olanzapine had significantly improved mean Quality -of-Life Scale total scores compared with those given placebo . For a subset of nonrelapsing patients who were considered " nonexacerbating " on the basis of minimal non clinical ly relevant increases in psychopathology , Quality -of-Life Scale total mean change was no better ( P = 0.066 ) for those given placebo ( 2.7 ± 11.0 ; n = 40 ) than those treated with olanzapine ( 5.7 ± 8.9 ; n = 174 ) . Path analysis indicated a direct effect of treatment ( ~29 % ) on quality of life that was not accounted for by differential changes in psychopathology . In conclusion , stable patients with schizophrenia who were taken off active drug treatment experienced no greater improvements in long-term quality of life than those who were continued on antipsychotic treatment , even in the absence of psychotic symptoms Single dose pharmacokinetics and the antipsychotic effect of 4 weeks treatment with three fixed dose levels of remoxipride ( a selective D2 receptor antagonist ) were studied in chronic , stable schizophrenic in patients . After a placebo washout of 1 month , 15 patients entered the study . Of these , 11 patients received a single 50 mg oral dose of remoxipride for pharmacokinetic evaluations . All 15 patients were r and omly assigned to treatment with oral remoxipride either 25 mg t.i.d . , 50 mg t.i.d . or 100 mg t.i.d . for 4 weeks . Blood sample s for remoxipride and prolactin assays were taken at 0 , 0.33 , 0.5 , 0.66 , 1.0 , 1.5 , 2 , 3 , 4 , 8 , 12 , 24 , 28 , 32 and 48 h after drug intake . The pharmacokinetic characteristics were similar to those previously found in normal healthy volunteers : the mean peak plasma concentration of remoxipride after 50 mg was 3.3 μmol/l , the mean time to reach this was 2.1 h ; the mean area under the plasma concentration/time curve was 27.8 μmol/1.h.1 -1 and the mean elimination half-life of remoxipride was 5.5 h. A significant increase in prolactin levels was detected 2 h after administration of remoxipride but they had reverted to normal 8 h after drug intake in all but one patient . Antipsychotic effects were estimated using the brief psychiatric rating scale ( BPRS ) and the Krawiecka rating scale ( KRS ) at admission , baseline ( end of the 4 week placebo washout period ) and after 7 , 14 and 28 days treatment . Following an increase in mean psychosis ratings for both positive and negative symptoms during the placebo washout period , these decreased during active treatment and at the end of the study were similar to the scores on admission . Thus the possible efficacy of remoxipride in chronic patients with negative symptoms should be further explored in placebo controlled studies . Remoxipride was well tolerated . Sleep disorders occurred in three patients , extrapyramidal symptoms were not aggravated and no clinical ly significant effects were observed on the cardiovascular system , in clinical chemistry or haematology Fifty-six chronic schizophrenic patients were r and omized into haloperidol decanoate ( HD ) or placebo groups for 48 weeks of double-blind treatment . The double-blind trial was preceded by a 15-week single-blind run-in period , during which all patients were treated with 60 mg of HD ( approximately corresponding to 3.6 mg orally/day ) every fourth week ( except for the second injection , which was given after 3 weeks ) . Eight relapses occurred during the run-in period , and seven other patients refused further participation . The remaining 41 patients were then treated double blind , either with HD , 60 mg/4 weeks ( 18 patients ) , or with placebo ( 23 patients ) . Two patients ( 11 % ) in the HD group and 16 ( 69 % ) in the placebo group relapsed during the 48-week double-blind period . The plasma concentrations of haloperidol were measured every fourth week in both groups . Steady state was reached after 11 weeks . The mean steady-state level was 6.3 nmol/L. In the placebo group , a 50 % decrease in the mean haloperidol plasma concentration was seen 8 weeks after withdrawal of haloperidol . The haloperidol plasma concentration was a predictor of relapse . There was no statistical difference between the treatment groups regarding extrapyramidal symptoms . More biperiden , however , was used in the HD group , while the placebo patients took more sedatives . The results of this study show that the relatively low and fixed dose of 60 mg of HD every fourth week was superior to placebo in preventing relapse in schizophrenia . ( ABSTRACT TRUNCATED AT 250 WORDS Maintenance treatment regimens for patients with schizophrenia are often suboptimal . Partial adherence and outright noncompliance are associated with symptom recurrence and increased likelihood of rehospitalization . Long-acting conventional neuroleptics have limited efficacy and are associated with treatment-limiting adverse events , while oral atypical antipsychotics have not improved adherence substantially . A long-acting formulation of risperidone , an atypical antipsychotic with proven efficacy , has been developed . Introduction of long-acting injectable treatment may be appropriate during inpatient hospitalization , when consequences of relapse are most evident . To support this intervention , a sub analysis of patients who were in patients at study initiation was conducted from a 12-week , double-blind , placebo-controlled long-acting risperidone study ( N = 214 ) . Long-acting risperidone was associated with a significant reduction in total Positive and Negative Syndrome Scale ( PANSS ) score ( mean change + /- st and ard error [ S.E. ] at endpoint : long-acting risperidone , -9.27 + /- 1.44 , n = 133 ; placebo , 0.72 + /- 2.59 , n = 41 ; P < 0.001 ) , and a significantly higher rate of treatment response , defined as > or = 20 % reduction in total PANSS score ( 50 % vs. 27 % , P < 0.05 ) . Significantly more long-acting risperidone patients had endpoint Clinical Global Impressions ( CGI ) assessment s of not ill , very mild or mild ( 32 % vs. 5 % ; P < 0.01 ) . Long-acting risperidone was well tolerated . Long-acting risperidone initiated during inpatient treatment may be an important strategy in improving long-term outcomes among patients with schizophrenia Abstract A sample of 85 patients with schizophrenia , of whom 34 later dropped out , received r and omised treatment . There were no significant differences between treatment-takers and drop-outs in the variables assessed . Patients received either st and ard-dose maintenance neuroleptic treatment or targeted maintenance pharmacotherapy and all patients received behavioural family therapy . Measures of psychopathology , social adjustment , side-effects , family burden , and expressed emotion were assessed at baseline and then periodically over an 18-month period . The study was design ed to compare the two alternative pharmacological maintenance approaches , each of them supported by psychosocial intervention . Any evaluation of the impact of behavioural family treatment on relapse rates and other outcome criteria is exclusively descriptive . A significantly higher rate of relapse was observed at 18 months in patients r and omised to targeted treatment compared to those r and omised to st and ard-dose treatment ( 35 % vs 4 % ) . Although patients assigned to the targeted maintenance group received significantly lower mean doses of neuroleptics , there were no significant differences between the two groups with regard to side-effects , global measures of social function , and overall psychopathology . Family burden was higher in the targeted-treatment group at six months , but did not differ at the one-year and eighteen-month time points . However , both groups improved significantly from baseline to 12 or 18 months in almost all variables assessed . Thus , the behavioural family approach did not compensate for the problems associated with the targeted medication strategy In a double blind placebo controlled clinical evaluation of maintenance therapy in chronic schizophrenic female out patients , thiordazine in single daily doses not exceeding 375 mg./day for 6 months was shown to be effective maintenance treatment compared with PL , thereby establishing the sensitivity of the experiment . Pimozide was also shown to be effective in a single oral dose not exceeding 16 mg./day and comparable overall to the st and ard drug . The experimental design was based on the anticipated retrogression of PL treated subjects during the 6-month study period , which was reflected in 5 of 9 ( 56 % ) " treatment failures " in the PL group compared to 2 of 14 ( 14 % ) and 2 of 12 ( 17 % ) in the THI and PIM groups , respectively . In addition , in some instances improvement over baseline evaluations was noted in both drug groups , particularly on global impression . Though some items of the BPRS exhibited Drug : PL differences , the scale in general was felt to be rather insensitive for this kind of study . Social adjustment ratings on a special scale completed by the patients and families alike , were also found to be insensitive to treatment differences . Side effects most often seen with THI were sedation , EKG and liver function abnormalities . Headache and restlessness occurred most often with PIM . Extrapyramidal symptoms and insomnia were seen most often with PIM and PL equally In an attempt to prospect ively vali date the existence of supersensitivity psychosis ( SSP ) , five schizophrenic patients meeting Chouinard 's criteria for SSP and five non-SSP schizophrenic controls had neuroleptic treatment withdrawn for 2 weeks under double-blind conditions . The sudden worsening of psychotic symptoms and tardive dyskinesia postulated in the SSP group was not observed on the Brief Psychiatric Rating Scale , the Clinical Global Impressions scale , and the Abbreviated Dyskinesia Rating Scale . In conclusion , the authors ' pilot data do not seem to support the existence of SSP Prophylactic effects of psychotropic drugs on 55 schizophrenics in remission were evaluated for 3 years in a double-blind controlled study employing a cross-over design . Patients were r and omly assigned to the following drugs orally administered twice a day : placebo ; diazepam 15 mg ; imipramine 50 mg ; chlorpromazine 75 mg ; and haloperidol 3 mg . The number of days of remission for each patient was recorded . Since only two patients received all five drug treatments , the data were analyzed using the number of days allocated to the “ first assigned drugs ” only and the cross-over aspect of the experimental design was disregarded . All patients treated with either the placebo , diazepam or imipramine relapsed within a year . On the other h and , four patients treated with chlorpromazine , or with haloperidol , were in remission for more than 1 year . Fifty percent of the patients relapsed within 16 days with placebo ; 88 days with diazepam ; 30 days with imipramine ; 165 days with chlorpromazine ; and 74 days with haloperidol . Within a year , only chlorpromazine significantly prolonged the remission state as compared to placebo and imipramine . At the end of the 3-year trial , both chlorpromazine and haloperidol significantly prolonged the remission state as compared to the other three drugs . These data suggest that neuroleptic treatment for a longer period is vitally important to prevent relapse even in schizophrenics in remission and that such a trial seems an efficient method for investigating the prophylactic effects of neuroleptics In a seven-hospital collaborative study , 210 chronic schizophrenics were assigned to a placebo for a 24-week period . During that time , 40 per cent . of the patients relapsed and had to be returned to active medication . Probability of relapse was related to two variables : ( 1 ) the hospital conducting the study and ( 2 ) the dose of tranquillizing medication the patient was receiving before being put on placebo . Patients receiving low doses of tranquillizing medication before the study were less likely to relapse than patients receiving moderate to high doses . The practical and theoretical implication s of these findings are discussed Thirty-six remitted schizophrenics who participated in an outpatient study of fluphenazine decanoate or oral fluphenazine vs placebo given for a year were examined for the effect of drug treatment upon social and vocational functioning . Only the period prior to any clinical relapse was evaluated . We found no difference between those on drug or placebo , and conclude that antipsychotic drugs , at least in the context of an aftercare clinic offering a rich spectrum of nonpharmacological services , and when combined with antiparkinson medication , do not interfere with social and vocational functioning The authors prospect ively examined the effects of double-blind , placebo-controlled neuroleptic withdrawal and administration on ratings of negative and positive symptoms in 19 young patients with chronic schizophrenia . Negative symptoms were significantly reduced by neuroleptic treatment , and negative and positive symptoms demonstrated similar patterns of reduction and exacerbation during neuroleptic treatment and withdrawal , respectively . The changes in negative and positive symptoms induced by neuroleptic treatment and withdrawal were not significantly correlated , however . The negative and positive symptom profiles of individual patients were significantly altered by neuroleptic treatment , indicating limitations to the cross-sectional classification of patients on the basis of predominance of one or the other symptom group . The authors discuss implication s for the neurobiological underpinnings of negative and positive symptoms Impaired affect in recovering schizophrenic patients has been viewed as either an integral part of the disease , a postpsychotic depression , or , increasingly , as a pharmacogenically determined effect secondary to the use of antipsychotics . Two months following hospital discharge , operationally defined groups of “ depressed ” and “ not depressed ” drug-treated and nonrelapsed schizophrenic patients were r and omly assigned to chlorpromazine or placebo and followed for 4 months . Among depressed schizophrenic patients , there was no evidence that drug either contributes to the depression or that depressive signs are primarily extrapyramidal symptom phenomena ( akinesia ) . Equal numbers of nondepressed patients on drug and placebo manifested a subsequent postpsychotic depression Twenty‐one female schizophrenics ( age range 34–74 years ) were included in a clinical study assessing the effectiveness of penfluridol as a basic maintenance therapy . At the start of the study , the patients , all of whom had been successfully maintained on penfluridol for at least 6 months , were divided into two comparable groups . Group I ( ten patients ) received penfluridol and Group II(II patients ) placebo under double‐blind conditions for 6 months . Patients were evaluated using a 36‐item question naire , which was completed before and after 1 , 3 , 4 and 6 months of treatment Twenty adult female schizophrenics were included in a double-blind , between-patient trial . Patients received either 20 mg . trifluoperazine or 150 mg . oxypertine daily in capsule form . The dose could be altered to 10 or 30 mg . trifluoperazine ( or 120 to 180 mg . oxypertine ) at the doctor 's discretion , still maintaining the double-blind discipline . The trial drugs were administered for six weeks , after a three-week period of placebo treatment . Ratings were made throughout the trial period and for four subsequent weeks , using the Wing ` A ' and Venables rating scales . Laboratory tests , including S.G.O.T. , S.P.G.T. , alkaline phosphatase , P.C.V. , E.S.R. haemoglobin , and total and differential white cell counts , were also carried out . The results of this trial do not suggest that oxypertine is superior to trifluoperazine in activating withdrawn schizophrenics . Significantly lower values for white cell count and haemoglobin were found in the oxypertine group . Side-effects , which comprised mainly vomiting , diarrhoea , dizziness and tremor , and were not clinical ly significant , were observed more frequently after administration of trifluoperazine than after oxypertine The ability of long-acting fluphenazine decanoate and oral fluphenazine hydrochloride to forestall relapse among newly discharge schizophrenic patients is examined in the context of high and low degrees of social therapy ( ST ) . A total of 105 patients were r and omly assigned to the various treatments and maintained under controlled conditions for two years or until relapse . Relapse rates for all treatments remained traditionally high . Relpase rates for long-acting fluphenazine decanoate and oral fluphenazine hydrochloride are nearly identical in the first year , indicating that drug noncompliance does not adequately explain early schizophrenic relapse . However , patients who received long-acting fluphenazine decanoate and ST have a reduced risk of relapse over time . Relapsers who received long-acting fluphenazine decanoate appeared more affectively disturbed than other relapsers , yet both groups were diagnostically and symptomatically equivalent prior to treatment . Personal discomfort and intrafamilial stress are important predictors Data were collected during a year-long multicenter collaborative trial comparing short-acting fluphenazine hydrochloride with long-acting fluphenazine decanoate in a group of schizophrenic patients being maintained in the community . We examined the emergence and course of depressive symptomatology , operationally defined by the Hamilton Depression Scale total score . Of 211 patients , approximately 25 % had depression develop within five months after discharge . Depressed patients had a more chronic psychiatric history and , contrary to the hypothesis that depression is a favorable prognostic indicator , they were more likely to relapse . There were no differences in incidence of emergent depression between the two drug treatment groups Twenty-eight patients who had recently recovered from an acute-onset , first-episode schizophrenic illness were r and omly given fluphenazine hydrochloride or decanoate or placebo for a one-year period in a double-blind study . Seven of 17 patients ( 14 % ) receiving placebo experienced a psychotic relapse , whereas none of 11 drug-treated patients experienced a relapse . Eighteen ( 69 % ) of the 26 patients available for follow-up ( mean interval , 3.5 years ) experienced a second psychotic relapse either during the study or afterward , and 50 % ( 14/28 ) of the original sample experienced a third episode A double-blind withdrawal trial in 41 chronic schizophrenic out patients was carried out over 6 months . Depot neuroleptics ( fluphenazine decanoate or flupenthixol decanoate ) were compared with placebo to evaluate neurological side effects during continued therapy and during withdrawal . The drugs were significantly more effective than placebo in preventing relapse and rehospitalization . In the placebo group 62 % relapsed compared to 27 % in the drug group . A difference was observed in the occurrence of extrapyramidal symtoms ( EPS ) between the neuroleptics in the study .Akathasia was observed in 9/38 ( 23.7 % ) cases , significantly more frequent in the fluphenazine decanoate group . Tardive dyskinesia ( TD ) was observed in six cases ( 15.8 % ) ; four cases existed at the start of the study and two others were observed after 3–6 weeks of withdrawal . There was no relation between TD symptoms and relapse . There was a significant decrease in the EPS scores during the placebo treatment and also a significant weight decrease The potential for unwanted side effects , particularly tardive dyskinesia , following long-term after care maintenance with antipsychotic medication has led to serious question ing of its continued use for schizophrenic patients . Does the risk of relapse decline with the passage of time ? If so , is the advantage of drug therapy sustained and large enough to justify continued treatment beyond one or two years ? More appropriate methods for analyzing the after care experience of 374 schizophrenic patients treated with drug or placebo reveals that while the risk of relapse does decline substantially , it remains twice as high for placebo-treated patients than drug-treated patients even after two years of treatment . The prophylactic effect of maintenance chemotherapy appears to be one to two times larger than generally estimated by the less precise " cumulative percentage " method Thirty-five schizophrenic out patients over the age of 52 who had been stable on neuroleptic medication were all switched to haloperidol . Ten patients were unable to tolerate the haloperidol and two dropped out of the study . The remaining 23 patients were r and omly and blindly assigned to haloperidol or placebo and then followed for 6 months . Five patients did not complete the study due to medical or administrative reasons . Among the patients who completed the study , five of 10 r and omized to placebo relapsed compared with only one of eight r and omized to haloperidol . However , three of 10 patients r and omized to placebo have remained stable without medication for 2.5 years This collaborative study on the efficacy of high doses of trifluoperazine in chronic schizophrenia showed that treatment response was related to length of hospitalization ; short-term patients benefited most . High doses of trifluoperazine were most effective with those short-term patients who had been on a piperazine phenothiazine prior to the study . Also , most placebo patients who had been receiving low doses of phenothiazines before the study did not suffer deleterious effects while they were off medication . Treatment implication s are discussed BACKGROUND We set out to determine whether and to what degree life events independent of illness increase the risk of relapse in schizophrenia following withdrawal from medication in the previous 6 months , either by triggering a relapse in the following 4 weeks or by acting cumulatively over time . METHOD Seventy-one patients fulfilling DSM-III-R criteria for schizophrenia with chronic illness were followed for 48 weeks and assessed on the LEDS scale . Half were treated with regular neuroleptic medication and half had been recently withdrawn from medication . A subgroup was r and omised double-blind to treatment or placebo . RESULTS A proportional hazards regression model showed that life events made a significant cumulative contribution over time ( P < 0.05 ) to the risks of relapse and that ceasing medication made an independent contribution . The risk of relapse increased in proportion to the number of life events but no interaction between medication status and events could be detected , i.e. life events were not more closely associated with relapse on medication than off medication . For those of the sample exposed to the mean rate of life events during the study period , it was estimated that 23 % of the relapse risk could be attributed to life events , and for those with twice the mean rate of events , 41 % . In contrast , patients who continued on regular medication had 80 % less risk of relapse than those who had been withdrawn from medication either by choice or under double-blind controlled conditions . CONCLUSIONS A contribution of life events to the risk of relapse in schizophrenia was confirmed by this study but the hypothesis that life events trigger relapse was not supported , nor was the hypothesis that life events are more relevant to relapse in patients on maintenance medication than in patients off medication All recently completed controlled two-year studies on intermittent , early neuroleptic intervention treatment have failed to compare favourably with studies on maintenance treatment concerning relapse prevention . The reason for this failure is still unclear . Therefore the implicit , but as yet unproven , hypothesis that a relapse can be predicted from prodromal symptoms was tested from the perspective of our German multicentre study . Results demonstrate that this is not the case . Possible reasons for and clinical implication s of this negative finding are discussed Phenothiazine drugs were withdrawn from 17 chronic schizophrenic in- patients , with a control group of 14 patients remaining on active medication . The trial was conducted under double blind conditions over a period of 42 weeks with weekly assessment of the patients by ward nurses . Of the placebo group 35 % relapsed , relapse being related to the level of previous active medication THIS PAPER is the fourth in a series of investigations into the factors influencing hospitalization of schizophrenic out patients . In the first publication it was shown that chlorpromazine had a marked effect in reducing the incidence of hospitalization among ambulatory chronic schizophrenic Patients .1Further exploration revealed that although chlorpromazine was highly effective early in treatment , its effectiveness diminished progressively over time , suggestingdelayrather thanpreventionof hospitalization . In contrast to phenothiazine-treated patients , the hospitalization rates for groups of patients treated with placebo were similar , regardless of duration of treatment exposure.2A review of the literature found a similar consistency in the hospitalization rates reported for placebo-treated patients ( 25 % to 30%),2suggesting the existence of a finite subgroup of " hospitalization prone " patients in any given group of ambulatory schizophrenic patients . In addition , the consistency in the hospitalization rates of placebo-treated groups We discontinued fluphenazine decanoate using a double-blind , crossover r and om order design , in 12 recent onset clinical ly stable schizophrenics who had been given fluphenazine decanoate 12.5 mg intramuscularly every 2 weeks for at least 1 year prior to drug withdrawal . Each condition ( drug or placebo ) lasted 12 weeks . Using a radioimmunoassay verified by comparison to a gas chromatographic-mass spectrometric method , plasma fluphenazine levels were measured every 2 weeks during drug continuation and drug withdrawal conditions . No patient relapsed over the 24-week period of the study . Mean fluphenazine levels between drug continuation and withdrawal conditions showed a progressively larger difference over time , although significant differences were not seen until week 8 . By week 12 after drug withdrawal , 33 % of subjects still showed notable plasma fluphenazine levels . On the basis of our preliminary findings , we suggest that 2-week intervals between injections may be too short and that wider intervals may achieve similar clinical results A double-blind r and omized investigation compared withdrawal ( placebo ) with continued use of long-acting neuroleptics ( fluphenazine decanoate or flupenthixol decanoate ) in 41 chronic schizophrenic out patients . After 6 weeks there was a tendency toward higher depressive scores in the placebo group , a difference which became statistically significant ( p less than .05 ) at week 24 . These results do not support earlier observations that neuroleptic drugs cause depression . Further analyses of the data indicated that depressive symptomatology could be an early sign of relapse Group psychotherapy and antipsychotic medications were employed in the treatment of 49 outpatient schizophrenics . Two treatment regimens , using thiothixene and chlorpromazine hydrochloride , were divided into group therapy and nongroup therapy subgroups for a duration of six months . Patients ' symptoms were evaluated on a monthly basis through use of a physician 's global assessment , and the Brief Psychiatric Rating Scale . Subtle changes in subjects ' interpersonal emotional adjustment ( a possible positive effect of psychotherapy ) were measured before and after treatment by means of the Interpersonal Test Battery . Results indicated no substantial difference between medications , but a positive change over this time period for both drug regimens . While group therapy did not alter patients ' symptomatology , it did , according to projective test results , deepen the subjects ' awareness and insight into their own behavior A follow-up study of all patients entering the MRC double-blind trial of fluphenazine decanoate in chronic schizophrenic out- patients achieved a trace rate of 94 % . In general , these patients were severely disabled , continued under the care of the maintenance clinic , and their diagnoses remained remarkably consistent ; more than one-fifth were found to be in acute schizophrenic relapse and in over a half of these cases , the relapse was not known to the treatment agency . The maintenance clinic attenders were little different from those who no longer used such a facility A double-blind placebo trial of fluphenazine decanoate , a long-acting phenothiazine , was carried out to determine its value in maintenance therapy of chronic schizophrenic out patients already established on the drug for a minimum period of eight weeks . In low doses it was significantly more effective than placebo in preventing relapse and admission to hospital . Relapse was accompanied by a resurgence of specifically schizophrenic symptoms and by an increase in abnormalities described by the relatives . There was no difference between the experimental and control groups in the treatment required for depression . The group on active medication required more treatment for Parkinsonism , but this difference did not reach statistical significance . In the context of a well-run special clinic for outpatient follow-up of chronic schizophrenic patients these results confirm the usefulness of long-acting fluphenazine . By inference , the benefit of this treatment highlights the need for adequate community services to deal with the residual chronic disabilities which are characteristic of these patients Sustained response to antipsychotic therapy is an important outcome measure for patients with psychotic disorders . Placebo control in studies of relapse prevention contributes valuable information yet provokes much debate . This study , using placebo as a control , evaluated olanzapine ’s efficacy in preventing a psychotic relapse . Participants were stable minimally symptomatic out patients with schizophrenia or schizoaffective disorder . The study included 4 phases : ( 1 ) 4-day to 9-day screening/evaluation ( N = 583 ) , ( 2 ) 6-week conversion to open-label olanzapine ( N = 493 ; 10 - 20 mg/d ) , ( 3 ) 8-week stabilization on olanzapine ( N = 458 ; 10 - 20 mg/d ) , and ( 4 ) 52-week r and omized ( 2:1 ) , double-blind maintenance with olanzapine ( N = 224 ; 10–20 mg/d ) or placebo ( N = 102 ) . Primary relapse criteria were clinical ly significant changes in the Brief Psychiatric Rating Scale ( BPRS ) positive item cluster or rehospitalization due to positive symptoms . Statistical methodology allowed sequential real-time estimation of efficacy across blinded treatment groups and multiple interim analyses , which permitted study termination when efficacy was significantly different between treatments . A significant between-treatment difference emerged 210 days after first patient r and omization to double-blind treatment . Thus , 151 ( 46.3 % ) of the r and omized patients were discontinued early and 34 ( 10.4 % ) of the planned patient enrollment were not required . The olanzapine group had a significantly longer time to relapse ( P < 0.0001 ) than the placebo group . The 6-month cumulative estimated relapse rate ( Kaplan-Meier ) was 5.5 % for olanzapine-treated patients versus 55.2 % for placebo-treated patients . The design of this study enabled appropriate statistical testing of the primary hypothesis while minimizing exposure of patients to a less effective treatment than olanzapine . In remitted stabilized patients with schizophrenia or schizoaffective disorder , olanzapine demonstrated a positive benefit-to-risk profile in relapse prevention Language comprehension , measured by the Luria-Nebraska Relational Concepts Factor Scale , was evaluated twice in 15 male DSM-III-R schizophrenic patients during a controlled double-blind haloperidol maintenance ( without anticholinergics ) and placebo replacement protocol . Fifteen male normal controls were tested once . Patients and controls were matched on age and education . Language comprehension was significantly reduced in patients under both pharmacologic conditions , as compared with controls . Patients ' comprehension accuracy did not differ significantly between neuroleptic-treatment and placebo replacement conditions . Patients ' comprehension accuracy was independent of positive symptoms , anxiety-depression , measures of clinical course , and CSF and plasma monoamines . Comprehension accuracy was also not associated with patients ' educational level or WAIS-R measures of their intellectual and short-term memory functioning . Patients ' comprehension performance was significantly associated only with the negative symptom anhedonia-asociality during haloperidol maintenance . Thus , language comprehension in schizophrenic patients was independent of changes in pharmacologic treatment and the positive symptoms of psychosis . Results suggest language comprehension may represent a stable or trait characteristic in schizophrenia A double‐blind withdrawal trial in 41 chronic schizophrenic out patients on neuroleptics was carried out during 6 months . Long‐acting neuroleptics ( fluphenazine decanoate or flupenthixol decanoate ) were used in comparison with placebo to determine the value in maintenance therapy . Most patients had a rather low maintenance dose , about 12.5‐25 mg fluphenazine decanoate or 20–40 mg flupenthixol decanoate every third week ABSTRACT – Thirty‐two chronic schizophrenics who had relapsed entered a double‐blind r and omised study and were followed‐up for 2 years with the intention of measuring any difference in therapeutic effect and side effects between flupenthixol decanoate and fluphenazine decanoate . No differences could be seen as regards the global effect or the effect on the schizophrenic symptomatology during the first 6 months . After 1 year of treatment flupenthixol decanoate showed a trend towards a better effect on schizophrenic symptomatology . A corresponding result was seen for the depressive symptoms . There There were no differences in the appearance of side effects . The need for additional neuroleptics in the initial phase seemed to be identical for both drugs . A possible slow antipsychotic effect with flupenthixol decanoate is probably due to the administered dose being somewhat low ( in the present study approximately 31 mg flupenthixol corresponding to 27 mg fluphenazine ) . This suggests that flupenthixol should have been given in a somewhat higher dose ( 25 mg fluphenazine decanoate corresponding to 40 mg flupenthixol decanoate ) Functional psychosis is conventionally subdivided into schizophrenia and manic depressive psychosis . Response to treatment is assumed to be a validating criterion for these diagnoses . The efficacy of pimozide ( a dopamine antagonist neuroleptic ) , lithium , and a combination of the two was compared with that of placebo in a 4 week trial in 120 functionally psychotic patients each of whom was assessed for psychotic symptoms , manic symptoms , and depressive symptoms . The sample was subdivided into patients with predominantly elevated mood , predominantly depressed mood , and no consistent mood change . Pimozide reduced psychotic symptoms in all groups of patients . The only significant effect of lithium was to reduce elevated mood . Thus dopamine blockade seems relevant to the resolution of psychotic symptoms in all types of " functional " psychosis but the mode of action of lithium in psychotic patients concerns only mood . Application of st and ardised classifications of functional psychosis to these data did not change this conclusion This study of patients with remitted chronic schizophrenia in an aftercare clinic was design ed to test whether such patients require maintenance antipsychotic medication . A previous report showed that the group receiving active medication , fluphenazine decanoate and oral fluphenazine , had far fewer relapses ; but the former group had a high incidence of akinesia . This present report presents rating scale data substantiating these two findings : ( 1 ) patients terminated on clinical grounds because of a schizophrenic relapse showed rating scale changes consistent with that diagnosis ; and ( 2 ) the patients removed due to severe akinesia showed a worsening on items selected a priori to measure akinesia , and when compared to survivors on the same items , showed significant differences -- thus confirming our clinical judgments This paper reports the social results of a double-blind placebo controlled trial of fluphenazine decanoate . Among patients on placebo there was a deterioration in family relationships , which was due to an increase in aggression , noisiness , talking about delusions , and socially embarrassing behaviour after withdrawal of active drug We have conducted a 6-wk drug withdrawal study in a group of chronic schizophrenic out patients who had been maintained on injectable fluphenazine decanoate for at least 2 yr prior to the study . After two baseline assessment s , patients were r and omly assigned to two groups . The first group ( holiday ) received a placebo injection from a nurse who was not involved in the assessment ( N = 17 ) . The second group continued on their regular medication ( N = 14 ) . The assessment was done in a double-blind fashion at 3 and 6 wk using the Schedule for Affective Disorders and Schizophrenia ( SADS ) and the Global Assessment Scale ( GAS ) inventories to assess symptom status . Tardive dyskinesia was measured using the Abnormal Involuntary Movement Scale ( AIMS ) . Community adjustment was assessed by means of the self-rated Weissman Social Adjustment Scale . We found that there were no relapses of any kind in either group of patients using the instruments mentioned above . The prevalence of tardive dyskinesia as measured by the AIMS was low , with only one patient having severe tardive dyskinesia . There was no significant worsening of the tardive dyskinesia during the drug holiday . Our study concludes that a 6-wk drug holiday was safe in this group of chronic schizophrenic patients maintained on fluphenazine decanoate . In contrast to other studies , no cases of covert tardive dyskinesia were detected during the drug holiday Seven years after the completion of the original trial , over 73 % of patients were maintained on depot neuroleptics , and 70 % had received such medication for over seven years . About 40 % had presented with a problem of compliance at some time , and there was a significant correlation between poor compliance and in-patient admissions and schizophrenic relapses . The prevalence of parkinsonian side-effects , akathisia , and tardive dyskinesia was low . Non-psychotic symptoms were common , even in the absence of acute psychosis . Depression was found in a subgroup of patients ; it was frequently reported as an indication for admission during follow-up period , and seemed to be part of the schizophrenic illness rather than a result of antipsychotic drug treatment A double-blind comparison between benzodiazepines and neuroleptics was carried out for 1 1/2 years on 30 schizophrenics who had hitherto continuously received neuroleptics and remained apparently in full remission for at least 3 - 5 years . The benzodiazepine-group had a significantly higher relapse rate than the neuroleptic-group , meaning that we can not stop neuroleptics for these patients yet . Three possible reasons for this are ( 1 ) dem and of the natural course of the illness , ( 2 ) the fact that the patients agreed to stay in therapy for so long may signify a need for therapy , ( 3 ) some of the relapses on stopping neuroleptics may be ' withdrawal psychosis ' after prolonged neuroleptic therapy . If withdrawal of neuroleptics is really needed , however , it may be considered for a subgroup of female patients whose illness started after the age of 40 Objective To study rates of relapse in remitted patients with first episode psychosis who either continued or discontinued antipsychotic drugs after at least one year of maintenance treatment . Design 12 month r and omised , double blind , placebo controlled trial . Setting Early psychosis outpatient clinics in Hong Kong . Participants 178 patients with first episode psychosis who had received at least one year of antipsychotic drug treatment between September 2003 and July 2006 and had no positive symptoms of psychosis . Interventions Patients received either maintenance treatment with quetiapine ( 400 mg/day ) or placebo and were followed up for the next 12 months or until a relapse occurred . Main outcome measure Relapse assessed monthly and defined as re-emergence of psychotic symptoms ( delusions , conceptual disorganisation , hallucinations , suspiciousness , and unusual thought content ) according to predefined thresholds . Results 178 patients were r and omised ( 89 to quetiapine and 89 to placebo ) . The Kaplan-Meier estimate of the risk of relapse at 12 months was 41 % ( 95 % confidence interval 29 % to 53 % ) for the quetiapine group and 79 % ( 68 % to 90 % ) for the placebo group ( P<0.001 ) . Although quetiapine was generally well tolerated , the rate of discontinuation due to adverse or serious adverse events was greater in the quetiapine group ( 18 % ; 16/89 ) than in the placebo group ( 8 % ; 7/89 ) ( relative risk 2.29 , 95 % confidence interval 0.99 to 5.28 ; χ2=3.20 , df=1 ; P=0.07 ) . Conclusion In a group of asymptomatic patients with first episode psychosis and at least one year of previous antipsychotic drug treatment , maintenance treatment with quetiapine compared with placebo result ed in a substantially lower rate of relapse during the following year . Trial registration Clinical trials NCT00334035 This report focuses on two comparisons between oral and depot fluphenazine specifically FPZ decanoate : 1 ) can equivalent dosages for the two drugs be established and do these equivalencies change over six months of treatment ; 2 ) what are the side effects seen with the two drugs during the early weeks of administration . Patients in the study receive either oral or depot FPZ as the active treatment but in order to preserve double blind conditions , they are also given the other treatment in placebo form . No dosage equivalence is established by the protocol , however , if dosage is adjusted , both forms must be changed and in the same direction . During the first weeks of treatment there is a linear relationship between the two dosage forms but a range of relatively low dosages of the oral compound ( 5 - 20 mg ) is associated with a single dose ( 25 mg/q 3 weeks ) of FPZ decanoate . At higher dosages of the oral drug the relationship is linear . Side effects of some kind are noted in over 60 percent of patients in both treatment groups after four weeks of treatment , while symptoms of at least moderate severity occur in almost 40 percent . Only symptoms involving the extrapyramidal system and sleep disturbance are observed in more than 20 percent of the patients . Benztropine was prescribed only if needed and was administered to 65 % of patients . In general , those receiving benztropine had more side effects than those who did not . These differences reached significance for extrapyramidal symptoms and depression . Based on these data , we conclude that at the dosages used in this study there are no side effect differences between these two forms of fluphenazine in the early weeks of administration . Dosage equivalence between the two drugs can be set within the range of 5 - 60 mg/day oral and 12.5 - 100 mg/three weeks depot A modification of an earlier rating scale for extrapyramidal system disturbance is described , and evidence for the validity and reliability of the scale is presented . The usefulness of the scale in studies of neuroleptic drugs is discussed . By its application it is possible to quantify extrapyramidal side effects and to separate them into four principal factors We evaluated relapse in patients with stable , chronic schizophrenia over a 1-year period ; in patients were r and omized to ziprasidone 40 mg/day ( n = 72 ) , 80 mg/day ( n = 68 ) , 160 mg/day ( n = 67 ) or placebo ( n = 71 ) . The probability of relapse ( Kaplan – Meier ) at 1 year was significantly lower in the ziprasidone 40 , 80 , and 160 mg/day groups ( 43 % , 35 % and 36 % , respectively ) compared to placebo ( 77%;P = 0.002 , P < 0.001 and P < 0.001 , respectively ) . In those patients who remained on treatment for at least 6 months , only 9 % subsequently relapsed on ziprasidone compared to 42 % on placebo ( P = 0.001 ) . All three doses of ziprasidone were significantly superior to placebo on Positive and Negative Syndrome Scale ( PANSS ) efficacy variables ( all P < 0.05 ) . Ziprasidone was associated with a significantly greater mean improvement in the PANSS negative symptom subscale compared to placebo ( P < 0.05 ) . Discontinuation due to adverse events was similar with ziprasidone and placebo . Ziprasidone treatment was indistinguishable from placebo in assessment s of movement disorders and was not associated with weight gain or cardiovascular abnormalities . These results demonstrate that ziprasidone was effective in reducing the frequency of relapse and was associated with long-term improvement in negative symptoms . Ziprasidone was well tolerated in this population of patients with chronic , stable schizophrenia A double‐blind , 6‐month trial of penfluridol and placebo was conducted in 15 chronic psychotic patients in the age range of 25–64 years . The patients , who had been well controlled with penfluridol for several months , were divided into two comparable groups with seven patients receiving penfluridol and eight receiving placebo . Dexetimide and other non‐psychotropic drugs already taken before the trial were continued . Each patient was assessed before and after 1 , 2 , 4 and 6 months of treatment using a 36‐item question naire . At the end of the trial , the weekly dosage of the double‐blind medication was two tablets of 20 mg or placebo in all patients . Whereas penfluridol‐treated patients maintained their improvement , placebo‐treated patients by the end of the trial had significantly deteriorated as regards direct psychotic phenomena and general behaviour BACKGROUND A recent review suggested an association between using unpublished scales in clinical trials and finding significant results . AIMS To determine whether such an association existed in schizophrenia trials . METHOD Three hundred trials were r and omly selected from the Cochrane Schizophrenia Group 's Register . All comparisons between treatment groups and control groups using rating scales were identified . The publication status of each scale was determined and cl aims of a significant treatment effect were recorded . RESULTS Trials were more likely to report that a treatment was superior to control when an unpublished scale was used to make the comparison ( relative risk 1.37 ( 95 % CI 1.12 - 1.68 ) ) . This effect increased when a ' gold-st and ard ' definition of treatment superiority was applied ( RR 1.94 ( 95 % CI 1.35 - 2.79 ) ) . In non-pharmacological trials , one-third of ' gold-st and ard ' cl aims of treatment superiority would not have been made if published scales had been used . CONCLUSIONS Unpublished scales are a source of bias in schizophrenia trials INTRODUCTION This long-term , r and omized , double-blind , placebo-controlled study examined the efficacy of extended release quetiapine fumarate ( quetiapine XR ) in preventing psychotic relapse in schizophrenia . METHODS Three hundred twenty-seven clinical ly stable patients with schizophrenia were switched to open-label quetiapine XR ( 300 mg on Day 1 , 600 mg on Day 2 , followed by flexible dosing [ 400 - 800mg/day ] ) for a 16-week stabilization phase . Thereafter , patients who were clinical ly stable for four months were r and omized to flexible doses of quetiapine XR ( 400 - 800mg/day ) or placebo . Primary endpoint was time to first schizophrenia relapse after r and omization . Secondary endpoints included risk of relapse at six months . Interim analyses were planned after 45 and 60 relapses and final analysis after 90 relapses . Maximal treatment time was one year . RESULTS The study was terminated after the first interim analysis showed a significant difference between r and omized treatment groups . Time to relapse was significantly longer in quetiapine XR-treated patients versus placebo ( hazard ratio 0.16 [ 95 % confidence interval 0.08 , 0.34 ] ; p=0.001 ) . Fewer quetiapine XR-treated patients relapsed versus those receiving placebo ( 10.7 % vs. 41.4 % , respectively ) . Estimated risk of relapse at six months was significantly lower with quetiapine XR ( 14.3 % ) compared with placebo ( 68.2 % ; p=0.0001 ) . The incidence of treatment-related adverse events ( AEs ) was similar between quetiapine XR and placebo groups ( 18 % and 21 % of patients , respectively ) and only one percent of patients in each group withdrew because of AEs . CONCLUSION Once-daily quetiapine XR ( 400 - 800mg/day ) was effective in preventing relapse in patients with clinical ly stable schizophrenia . Quetiapine XR was well tolerated during longer-term use We evaluated the efficacy of paliperidone extended-release ( ER ) , an investigational psychotropic agent , in delaying symptom recurrence in adult patients with schizophrenia and its safety and tolerability . In this r and omized , double-blind , placebo-controlled , multicenter study , patients ' symptoms were stabilized during an 8-week run-in and a 6-week stabilization phases using open-label , flexibly dosed paliperidone ER ( 3 - 15 mg once daily , starting dose = 9 mg ) . The primary efficacy variable was the time of first recurrence of schizophrenia symptoms , which included predefined changes in symptom scores , psychiatric hospitalization , self-injury , and suicidal or aggressive behavior during the double-blind phase ( paliperidone ER or placebo treatment ) . Based on positive efficacy , the study was terminated at the preplanned interim analysis ( 43 recurrence events ) . The interim analysis ( primary analysis ) included 113 patients ( mean age = 41 years ; 51 % men , 85 % white ) . In the intent-to-treat group , 14 paliperidone ER-treated patients ( 25 % ) experienced a recurrence event versus 29 ( 53 % ) for placebo . Time-to-recurrence was significantly different , favoring the paliperidone ER group ( P = 0.005 , log-rank test ) : 25 % quantile of time-to-recurrence was 83 days ( paliperidone ER ) versus 23 days ( placebo ) . Final analyses ( n = 205 ) were confirmatory . During initial open-label treatment with paliperidone ER , symptoms improved significantly . This improvement was maintained with continued treatment , as were functioning and quality -of-life measures . Treatment-emergent adverse events rates were similar : 35 % for paliperidone ER and 40 % for placebo . Paliperidone ER treatment versus placebo significantly delayed time-to-recurrence in patients with schizophrenia , maintained symptom stability and measures of functioning , and was generally well tolerated in this patient population ABSTRACT — Of 49 schizophrenic patients followed up 2 years after their first admission to hospital , 37 % were well , 47 % had been readmitted to hospital at some time over the 2 years , and 18mo showed schizophrenic symptoms at follow‐up . A poor outcome at 2 years was associated with male sex , poor outcome after the first 5 weeks of the first admission , negative schizophrenic symptoms on first admission , and a diagnosis of definite or probable schizophrenia using the Feighner criteria . Only 23 % were in employment . A small double‐blind discontinuation study of maintenance antipsychotic medication during the second year found more relapses in those switched to placebo medication . Repeat psychometric assessment at 2 years confirmed modest improvements found at 12 months ; that is , there was no evidence of intellectual decline . Relatives showed no more psychosocial distress than that found in a normal community sample ; what distress there was correlated with patients ’ schizophrenic symptoms Abstract One of the major biochemical effects of d-amphetamine is the release and uptake inhibition of dopamine ( DA ) . We measured the effect of d-amphetamine upon prolactin release which is inhibited by DA and stimulated by serotonin . d-Amphetamine ( 20 mg i.v . ) significantly raised the serum prolactin levels of drug-free schizophrenic patients over preinfusion levels and levels following a paired placebo lactose infusion . Amphetamine infusions were repeated after both chronic DA blockade with pimozide and after chronic lithium treatment that has been reported to attenuate amphetamine effects . These chronic pretreatments did not prevent significant increases in prolactin following d-amphetamine infusions . Pimozide raised preinfusion prolactin levels but lithium had no effect . Further studies are needed to clarify the d-amphetamine-induced rise in prolactin Ten hospitalized chronic schizophrenic patients were given chlorpromazine alone and chlorpromazine plus high dose propranolol in two 7-week treatment periods according to a r and omized crossover design . In the six patients who completed the whole study , plasma levels of chlorpromazine and chlorpromazine sulphoxide , total serum levels of neuroleptic and serum levels of prolactin were consistently and significantly elevated during treatment with chlorpromazine plus propranolol relative to levels during treatment with chlorpromazine alone . These effects are sufficient to explain previously reported clinical improvement in schizophrenic patients given propranolol in addition to neuroleptics The relapse and admission histories revealed a positive correlation between number of schizophrenic episodes and time on maintenance medication , probably reflecting severity of illness . Relapse rates after drug discontinuation rose to 45 % within 13 months . There were no differences of predictive value between those relapsing on or off medication . The relationship between relapse rates , drug treatment , and social outcome is complex ; antipsychotic drugs may postpone relapse , and frequent relapses might inhibit improvement in social performance long after florid symptoms have been controlled by medication Fluphenazine enanthate and fluphenazine decanoate — two long-acting neuroleptics — were administered in a controlled comparative study to 30 patients with acute psychoses of different character and origin . The study compared the duration of action and affinity for the extrapyramidal system of the two drugs . The decanoate ester acted longer than the enanthate ester and provoked fewer motor side effects . Since these side effects greatly reduce the patient 's motivation to cooperate in taking depot medication , the decanoate ester is to be preferred We tested the role of guaranteed delivery of medication in the prevention of relapse and the enhancement of adjustment in the community in patients with schizophrenia . Two hundred and ninety newly hospitalized patients at four hospitals were r and omly assigned to groups receiving either long-acting injectable fluphenazine decanoate or short-acting oral fluphenazine hydrochloride . After discharge and stabilization , patients were treated in the community for up to one year . By the end of the year , 28 % of all the patients had relapsed . Contrary to hypothesis , differences between the two treatment groups in relapse percentages were not significant . Furthermore , there were no differences between the treatment groups as to development of affective symptomatology or social adjustment . Patients who rated themselves as having more symptom distress at the start of the community-maintenance phase of the study relapsed much earlier while receiving fluphenazine decanoate rather than fluphenazine hydrochloride . The results suggest that compliance is not an important determinant of relapse among newly discharged schizophrenic patients Despite the established efficacy of neuroleptics for maintaining schizophrenics in the community , there are data suggesting that those with very good prognostic signs may do as well without drugs . In testing this , we find no evidence that patients with good signs are not in need of drugs ; instead they profit most from drug treatment . Patients who benefit little ( 1 ) are men whose families were disrupted earlier in their lives , ( 2 ) live alone or with extended families whose attitudes toward the study are not positive , and ( 3 ) are irregular in taking their medication . The practical implication is that the drug nonresponder can be helped by some means to ensure regularity of medication taking , such as a visiting nurse or long-acting medication . A second research question is whether major role therapy ( MRT , a combination of social casework and vocational rehabilitation ) can lengthen the time until relapse . Major role therapy affected time to relapse in a disordinal manner ; asymptomatic patients benefited from MRT , while in patients with greater symptom severity MRT- suprisingly -- hastened relapse . It is hypothesized that symptomatic patients are suffering from an inability to manage an exp and ed and enriched cognitive field ; MRT , a therapy that urges the patient to become more responsible and to exp and his horizons , may actually induce a state with which the patient can not cope . It is recommended that a therapy such as MRT be deferred until the patient is essentially asymptomatic The plasma levels of homovanillic acid ( HVA ) , a major circulating dopamine ( DA ) metabolite , were measured in schizophrenic patients during five weeks each of double-blind placebo-controlled neuroleptic treatment ( N = 16 ) and withdrawal ( N = 11 ) . Both neuroleptic treatment and withdrawal were associated with time-dependent changes in the plasma levels of HVA ; treatment was associated with decreases and withdrawal with increases . The levels of plasma HVA measured longitudinally during both conditions were highly correlated with psychosis ratings . Moreover , changes in individual mean weekly levels of plasma HVA were predictive of treatment response , including changes in both positive and negative symptoms of schizophrenia . These data are consistent with the suggestion that the mechanisms of action of antipsychotic drugs involve , in addition to short-term DA receptor blockade , a slowly developing decrease in presynaptic DA activity Sixty-two chronic schizophrenics in hospital were studied . There were 32 male and 30 female patients ; their mean ages were 53.6 years and 60.4 years respectively . They had all been on regular phenothiazines , principally trifluoperazine , for a mean of 9.4 years . Placebo capsules were substituted r and omly for 32 patients . Within the 16 drug-free weeks that followed , 9 ( 28 per cent ) patients relapsed sufficiently to require reinstatement on active phenothiazines . The mean drug-free period for those 9 patients was 5 weeks . They were significantly younger , had consumed larger quantities of phenothiazines over the years , and were originally receiving larger daily doses of trifluoperazine than the 23 patients who did not relapse . The patients were rated for the three main extra-pyramidal syndromes — motor restlessness parkinsonian rigidity and tremor and oral dyskinesia-tremor , before and after trifluoperazine was withdrawn . The mean drug-free period was 16 weeks . Comparisons were made between before and after ratings , as well as between placebo and control trifluoperazine groups . Parkinsonian rigidity and tremor , and oral-dyskinesia-tremor did not appreciably change in the placebo or control groups . Motor restlessness worsened significantly in the placebo , but not the trifluoperazine group . Of the 23 placebo patients who were without trifluoperazine for 16 weeks , 8 remained free from motor restlessness , 1 patient continued unchanged , 3 patients improved , 6 patients became worse , and 5 patients developed the disorder for the first time . There was no significant difference in any of the variables tested between the patients who deteriorated and those who remained the same or improved . Trifluoperazine withdrawal , in this study , was therefore followed by a psychiatric relapse in 28 per cent of the patients , persistence of parkinsonian rigidity and tremor and oral dyskinesia-tremor , and worsening of motor restlessness . The implication s of these findings are discussed THE EFFICACY of psychoactive drugs in treating psychotic patients is often dependent on maintenance treatment for extended periods . Many psychotropic compounds exhibit short duration s of action , making repeated daily administration necessary . Patients discontinue their medication , with frequent relapses and rehospitalizations for many reasons , including the sense of wellbeing , fear , neglect , lack of insight , poor judgment , delusions , disturbed communication , miscalculation of visits , or expense.1In contrast to the physically ill who maintain treatment because they suffer from their symptoms , psychiatric patients , particularly schizophrenics , may have no such reminder . In the follow-up of one of our recent studies , 2one-fourth of the discharged patients were rehospitalized with active psychotic symptoms within four to eight weeks of a self-induced drug free period . To avoid discontinuation of medication , recurrence of psychosis , and rehospitalization , a longer acting psychotropic compound was needed , similar to depot insulin used in diabetes , and the development of such a compound among the phenothiazines was encouraged |
806 | 29,355,909 | Risperidone was compared to clozapine , olanzapine , perphenazine , quetiapine and ziprasidone .
AUTHORS ' CONCLUSIONS There is not sufficient good- quality evidence available to determine the effects of risperidone compared with other antipsychotics in people with a dual diagnosis . | BACKGROUND Up to 75 % of people with serious mental illness ( SMI ) such as schizophrenia and bipolar disorder have co-occurring substance use disorders ( dual diagnosis ) .
Dual diagnosis can have an adverse effect on treatment and prognosis of SMI .
OBJECTIVES To evaluate the effects of risperidone compared to treatment with other antipsychotics ( first-generation and other second-generation antipsychotics ) used in people with serious mental illness and co-occurring substance misuse . | This study examined substance use among a group of 37 schizophrenia patients participating in a year-long fluphenazine decanoate ( FD ; Prolixin ) dosage reduction study ( Inderbitzin et al. ( 1994 ) Am . J. Psychiatry 151 , 1753 - 1759 ) . Ten ( 50 % ) of the 20 FD dose-reduced patients , and 6 ( 35 % ) of the 17 control group patients were identified as substance users . The dose-reduced and control groups did not differ significantly in substance use . We examine here the 37 patients regrouped by substance users ( n = 16 ) versus non-users ( n = 21 ) to determine the effects of substance use . In addition to identifying substance users and types of substances used , we hypothesize that substance users differ demographically from non-users , have worse symptomatology , worse compliance , higher rates of relapse , and therefore , can confound studies . Clinical and demographic data were obtained . At least half of the substance users were using alcohol or cocaine . The substance use group had a significantly higher severity of illness score on the BPRS at study onset . We found no significant differences between the two groups on other rating scales . The non-use group lived more independently , and the substance use group was younger . The substance use group had nearly twice as many hospitalizations in the 2 years prior to the study , a greater rate of missed appointments in the year before and during the study , and 4 times as many relapses during the year of the study than the non-use group . The key finding was that among 9 of the 37 patients who relapsed in the year of the study , 7 of the 9 had a history of substance use . Substance use was found to be a better predictor of relapse and hospitalization than gradual 50 % dosage reduction of FD in the related study . Substance use among schizophrenia patients is a major complicating factor OBJECTIVE Despite the frequent use of the Positive and Negative Syndrome Scale ( PANSS ) for rating the symptoms of schizophrenia , the clinical meaning of its total score and of the cut-offs that are used to define treatment response ( e.g. at least 20 % or 50 % reduction of the baseline score ) are as yet unclear . We therefore compared the PANSS with simultaneous ratings of Clinical Global Impressions ( CGI ) . METHOD PANSS and CGI ratings at baseline ( n = 4091 ) , and after one , two , four and six weeks of treatment taken from a pooled data base of seven pivotal , multi-center antipsychotic drug trials on olanzapine or amisulpride in patients with exacerbations of schizophrenia were compared using equipercentile linking . RESULTS Being considered " mildly ill " according to the CGI approximately corresponded to a PANSS total score of 58 , " moderately ill " to a PANSS of 75 , " markedly ill " to a PANSS of 95 and severely ill to a PANSS of 116 . To be " minimally improved " according to the CGI score was associated with a mean percentage PANSS reduction of 19 % , 23 % , 26 % and 28 % at weeks 1 , 2 , 4 and 6 , respectively . The corresponding figures for a CGI rating " much improved " were 40 % , 45 % , 51 % and 53 % . CONCLUSIONS The results provide a better framework for underst and ing the clinical meaning of the PANSS total score in drug trials of schizophrenia patients with acute exacerbations . Such studies may ideally use at least a 50 % reduction from baseline cut-off to define response rather than lower thresholds . In treatment resistant population s , however , even a small improvement can be important , so that a 25 % cut-off might be appropriate The purpose of this study is to compare the efficacy of olanzapine and risperidone for the acute treatment of first-episode schizophrenia patients with cannabis use disorders . This secondary analysis of a previously published study included 49 first-episode patients with a diagnosis of schizophrenia , schizophreniform disorder , or schizoaffective disorder and a co-occurring lifetime diagnosis of cannabis use disorders r and omly assigned to treatment with either olanzapine ( n=28 ) or risperidone ( n=21 ) for 16weeks . The olanzapine group did not differ significantly from the risperidone group for initial response rates of positive symptoms , and rates of cannabis use or alcohol use during the study . Positive symptoms and the Scale for Assessment of Negative Symptoms ( SANS ) global asociality-anhedonia scores improved over time but did not differ between study medications . In both groups , cannabis use during the study was higher in patients who used cannabis within three months of the admission . Thus , our results suggest that olanzapine and risperidone had a similar initial efficacy on psychotic symptoms and substance use in first-episode patients with co-occurring cannabis use disorders . If clinicians are choosing between olanzapine versus risperidone treatment for this population , their decision should be based upon factors other than symptom response and short-term substance misuse Psychotic disorders are characterized by significant deficits in attentional control , but the neurobiological mechanisms underlying these deficits early in the course of illness prior to extensive pharmacotherapy are not well understood . Moreover , little is known regarding the symptom and brain changes associated with amelioration of attentional impairments through antipsychotic pharmacotherapy . In this study 14 male patients experiencing a first-episode of psychosis with minimal prior antipsychotic treatment completed an attentional control task while undergoing functional magnetic resonance imaging at the onset of treatment with a second generation antipsychotic ( risperidone or aripiprazole ) in a double blind r and omized clinical trial and then again following approximately 12 weeks of treatment . In addition , 14 age- , and performance-matched healthy male volunteers who were not treated completed the same task at a baseline timepoint and then again following 12 weeks . Patients showed significantly greater activation than healthy volunteers in the right globus pallidus , left thalamus , and right thalamus at the time of the baseline scan . Among patients there was a significant reduction in right globus pallidus blood-oxygen level dependent ( BOLD ) response following antipsychotic treatment that correlated significantly with improvement in response accuracy and reductions in thought disturbance . No changes in globus pallidus activation were observed in healthy volunteers over this time period . These preliminary findings suggest that improvement in attentional control and concomitant reductions in thought disturbance in first-episode psychosis may be associated with reductions in subcortical activity following administration of second-generation antipsychotics early in the course of illness . These findings have implication s for underst and ing how changes in basal ganglia activity may be linked to improvements in attentional control through antipsychotics Background : Second-generation antipsychotics , approved for the treatment of mania , are associated with adverse effects such as weight gain and metabolic disorders . Aripiprazole , a recently introduced second-generation antipsychotic , are thought to account for its low propensity for weight gain , metabolic disturbances and sedation . The purpose of this study was to investigate the effect of risperidone versus aripiprazole in the treatment of acute mania . Material s and Methods : Fifty patients with acute episodes of mania were enrolled in this study , and they were r and omly assigned into a risperidone group of 24 cases and an aripiprazole group of 26 cases . In group A , aripiprazole with a dose of 5 - 30 mg/day and in group B , risperidone with a dose of 2 - 8 mg/day was given to patients . The average dose of aripiprazole was 27 mg/day , and the average dose of risperidone was 6 mg/day . The effects of each drug for the treatment of acute mania were assessed on the 1st day of admission and on days 2 , 4 , 6 , 8 and at weeks 2 , 4 and 6 after therapy using the young mania rating scale ( YMRS ) and at the baseline and on weeks 3 and 6 after admission using the clinical global impression ( CGI ) scale . Results : The mean age of the group of risperidone was 34 ± 8.6 years and in a group of aripiprazole it was 34 ± 9.1 years ( P = 0.83 ) . Comparison of YMRS scores over the period of 6 weeks revealed a statistically significant difference in both groups ( P < 0.0001 ) . There was also a statistically significant difference in YMRS scores between risperidone and aripiprazole at day 8 ( P = 0.026 ) and weeks 2 ( P = 0.035 ) and 4 ( P = 0.042 ) . There was also a statistically significant difference in CGI-Severity scale score at weeks 3 ( P = 0.003 ) and 6 ( P = 0.000 ) and in CGI-Improvement scale score at weeks 3 ( P = 0.005 ) and 6 ( P = 0.002 ) . The most common side-effect observed in both groups was headache ( 0%15/4 in aripiprazole vs. % 16/7 in risperidone ) Conclusion : Aripiprazole that is readily available in our market , could be considered more effective than risperidone in the treatment of acute mania BACKGROUND Many patients recovering from a first psychotic episode will discontinue medication against medical advice , even before a 1-year treatment course is completed . Factors associated with treatment adherence in patients with chronic schizophrenia include beliefs about severity of illness and need for treatment , treatment with typical versus atypical antipsychotic and medication side effects . METHOD In this 2-year prospect i ve study of 254 patients recovering from a first episode of schizophrenia , schizophreniform , or schizoaffective disorder we examined the relationship between antipsychotic medication non-adherence and patient beliefs about : need for treatment , antipsychotic medication benefits , and negative aspects of antipsychotic medication treatment . We also examined the relationship between medication non-adherence and treatment with either haloperidol or olanzapine , and objective measures of symptom response and side effects . RESULTS The likelihood of becoming medication non-adherent for 1 week or longer was greater in subjects whose belief in need for treatment was less ( HR=1.75 , 95 % CI 1.16 , 2.65 , p=0.0077 ) or who believed medications were of low benefit ( HR=2.88 , 95 CI 1.79 - 4.65 , p<0.0001 ) . Subjects r and omized to haloperidol were more likely to become medication non-adherent for > or=1 week than subjects r and omized to olanzapine ( HR-1.51 , 95 % CI 1.01 , 2.27 , p=0.045 ) . CONCLUSION Beliefs about need for treatment and the benefits of antipsychotic medication may be intervention targets to improve likelihood of long-term medication adherence in patients recovering from a first episode of schizophrenia , schizoaffective , or schizophreniform disorder OBJECTIVE This double-blind study compared a second generation ( atypical ) antipsychotic drugs compared to a representative older agent for patients with schizophrenia who use or avoid illicit substances . METHODS Schizophrenic subjects were recruited at 57 U.S. sites and r and omly assigned to olanzapine , perphenazine , quetiapine , risperidone or ziprasidone for up to 18 months . The primary aim of this analysis was to delineate differences between the overall effectiveness of these five treatments among patients who used or did not use illicit substances . RESULTS There were no significant differences between treatment groups in time to all-cause treatment discontinuation among patients who use illicit drugs ( median 3.3 to 6.8 months ) . Among non-users time to treatment discontinuation was significantly longer for patients treated with olanzapine ( median 13.0 months ) than perphenazine ( 5.9 months ) , risperidone ( 5.6 months ) , or quetiapine ( 5.0 months ) ; time to discontinuation for ziprasidone ( 4.3 months ) was even shorter , although the latter difference was not significant . The difference between risperidone and quetiapine , although small , was significant . All remaining differences were non-significant . Similar results were found for discontinuation due to inefficacy . There were no differences between illicit users and non-users in symptom reduction and global improvement , after adjustment for differential duration of treatment . Differences in discontinuation results were attenuated by non-compliance , but the trends persisted after controlling for treatment compliance . CONCLUSIONS Among patients with chronic schizophrenia who avoid use of illicit drugs , olanzapine was more effective than other antipsychotics as reflected by longer time to all-cause discontinuation , but illicit substance abuse attenuated this advantage , reinforcing the need for concurrent substance abuse treatment OBJECTIVE To compare olanzapine and risperidone in the treatment of nonpsychotic acute manic or mixed episodes . METHOD This 3-week , r and omized , controlled , double-blind , parallel multicenter study compared olanzapine ( 5 - 20 mg/day ; N = 165 ) and risperidone ( 1 - 6 mg/day ; N = 164 ) among hospital in patients who met DSM-IV criteria for bipolar I disorder , manic or mixed episode , without psychotic features . The study was conducted at 30 sites in the United States between July 2001 and June 2002 . The primary outcome measure was the mean change in the Young Mania Rating Scale ( YMRS ) total score . Secondary measures included the 21-item Hamilton Rating Scale for Depression ( HAM-D-21 ) , the Montgomery-Asberg Depression Rating Scale ( MADRS ) , the Clinical Global Impressions-Bipolar Version ( CGI-BP ) severity of illness scale , and the Cognitive Test for Delirium ( CTD ) . Quality of life ( Short Form Health Survey [ SF-12 ] ) , psychological well-being ( Psychological General Well-Being [ PGWB ] inventory ) , and sexual functioning were also compared . RESULTS Mean modal doses for olanzapine and risperidone were 14.7 mg/day and 3.9 mg/day , respectively . Between treatments , there was no difference in mean change in the YMRS , MADRS , CTD , PGWB , or SF-12 measures or in remission or response rates . Significantly more olanzapine-treated patients completed the study compared with risperidone patients ( 78.7 % vs. 67.0 % ; p = .019 ) . Olanzapine-treated patients had greater HAM-D-21 ( p = .040 ) and CGI-BP ( p = .026 ) score improvement across the study . Olanzapine-treated patients experienced greater elevations in liver function enzymes ( p < .05 ) and increase in weight ( 2.5 kg vs. 1.6 kg ; p = .004 ) , while risperidone-treated patients were more likely to experience prolactin elevation ( 51.73 ng/mL vs. 8.23 ng/mL ; p < .001 ) and sexual dysfunction ( total score increase of 1.75 vs. 0.64 ; p = .049 ) . CONCLUSION Both olanzapine and risperidone treatment yielded similar improvements in mania . The olanzapine group had significantly greater improvements in secondary measures of severity and depressive symptoms and better study completion rates but experienced more weight gain Objective : To examine the efficacy of atypical neuroleptics for decreasing craving and drug relapses during protracted withdrawal in individuals dually diagnosed with schizophrenia and cocaine dependence . Method : We conducted a 6-week , open-label pilot study comparing risperidone with typical neuroleptics in a sample of withdrawn cocaine-dependent schizophrenia patients . Results : Preliminary results suggest that individuals treated with risperidone had significantly less cue-elicited craving and substance abuse relapses at study completion . Further , they showed a trend toward a greater reduction in negative and global symptoms of schizophrenia . Conclusion : Atypical neuroleptics may help reduce craving and relapses in this population . Future research should include more rigorous double-blind placebo-controlled studies with this class of medications Background No clear recommendations exist regarding which antipsychotic drug should be prescribed first for a patient suffering from psychosis . The primary aims of this naturalistic study were to assess the head-to-head effectiveness of first-line second-generation antipsychotics with regards to time until drug discontinuation , duration of index admission , time until readmission , change of psychopathology scores and tolerability outcomes . Methods Patients ≥ 18 years of age admitted to the emergency ward for symptoms of psychosis were consecutively r and omized to risperidone ( n = 53 ) , olanzapine ( n = 52 ) , quetiapine ( n = 50 ) , or ziprasidone ( n = 58 ) , and followed for up to 2 years . Results A total of 213 patients were included , of which 68 % were males . The sample represented a diverse population suffering from psychosis . At admittance the mean Positive and Negative Syndrome Scale ( PANSS ) total score was 74 points and 44 % were antipsychotic drug naïve . The primary intention-to-treat analyses revealed no substantial differences between the drugs regarding the times until discontinuation of initial drug , until discharge from index admission , or until readmission . Quetiapine was superior to risperidone and olanzapine in reducing the PANSS total score and the positive subscore . Quetiapine was superior to the other drugs in decreasing the PANSS general psychopathology subscore ; in decreasing the Clinical Global Impression - Severity of Illness scale score ( CGI-S ) ; and in increasing the Global Assessment of Functioning - Split version , Functions scale score ( GAF-F ) . Ziprasidone was superior to risperidone in decreasing the PANSS positive symptoms subscore and the CGI-S score , and in increasing the GAF-F score . The drugs performed equally with regards to most tolerability outcomes except a higher increase of hip-circumference per day for olanzapine compared to risperidone , and more galactorrhoea for risperidone compared to the other groups . Conclusions Quetiapine appears to be a good starting drug c and i date in this sample of patients admitted to hospital for symptoms of psychosis . Trial Registration Clinical Trials.gov ID ; URL : http://www . clinical trials.gov/ : Atypical antipsychotic adjunctive therapy to lithium or valproate is effective in treating acute mania . Although continuation of atypical antipsychotic adjunctive therapy after mania remission reduces relapse of mood episodes , the optimal duration is unknown . As many atypical antipsychotics cause weight gain and metabolic syndrome , they should not be continued unless the benefits outweigh the risks . This 52-week double-blind placebo-controlled trial recruited patients with bipolar I disorder ( n=159 ) who recently remitted from a manic episode during treatment with risperidone or olanzapine adjunctive therapy to lithium or valproate . Patients were r and omized to one of three conditions : discontinuation of risperidone or olanzapine and substitution with placebo at ( i ) entry ( ‘ 0-weeks ’ group ) or ( ii ) at 24 weeks after entry ( ‘ 24-weeks ’ group ) or ( iii ) continuation of risperidone or olanzapine for the full duration of the study ( ‘ 52-weeks ’ group ) . The primary outcome measure was time to relapse of any mood episode . Compared with the 0-weeks group , the time to any mood episode was significantly longer in the 24-weeks group ( hazard ratio ( HR ) 0.53 ; 95 % confidence interval ( CI ) : 0.33 , 0.86 ) and nearly so in the 52-weeks group ( HR : 0.63 ; 95 % CI : 0.39 , 1.02 ) . The relapse rate was similar in the 52-weeks group compared with the 24-weeks group ( HR : 1.18 ; 95 % CI : 0.71 , 1.99 ) ; however , sub-group analysis showed discordant results between the two antipsychotics ( HR : 0.48 , 95 % CI : 0.17 ; 1.32 olanzapine patients ; HR : 1.85 , 95 % CI : 1.00 , 3.41 risperidone patients ) . Average weight gain was 3.2 kg in the 52-weeks group compared with a weight loss of 0.2 kg in the 0-weeks and 0.1 kg in the 24-weeks groups . These findings suggest that risperidone or olanzapine adjunctive therapy for 24 weeks is beneficial but continuation of risperidone beyond this period does not reduce the risk of relapse . Whether continuation of olanzapine beyond this period reduces relapse risk remains unclear but the potential benefit needs to be weighed against an increased risk of weight gain Objective : To examine whether subjective well-being and craving for cannabis were different in patients with schizophrenia or related disorders treated with either olanzapine or risperidone . Method : A 6-week , double-blind , r and omized trial of olanzapine and risperidone was carried out in 128 young adults with recent onset schizophrenia or related disorders . Primary efficacy measures were the mean baseline-to-endpoint change in total scores on the Subjective Well-Being under Neuroleptics scale , the Obsessive – Compulsive Drug Use Scale , the Drug Desire Question naire , and the cannabis use self-report . An analysis of covariance was used to test between-group differences . Results : Estimated D2 receptor occupancy did not differ between olanzapine ( n = 63 ) and risperidone ( n = 65 ) . Similar improvements in subjective well-being were found in both groups . In the comorbid cannabis-using group ( n = 41 , 32 % ) , a similar decrease in craving for cannabis was found in both treatment conditions . Conclusions : Both olanzapine and risperidone were associated with improved subjective well-being . No evidence was found for a differential effect of olanzapine or risperidone on subjective experience or on craving for cannabis in dosages leading to comparable dopamine D2 occupancy . Objectif : Examiner si le bien-être subjectif et l'état de manque de cannabis étaient différents chez les patients souffrant de schizophrénie ou de troubles connexes traités à l'olanzapine ou à la rispéridone The authors estimated components of variance and intraclass correlation coefficients ( ICCs ) to aid in the design of complex surveys and community intervention studies by analyzing data from the Health Survey for Engl and 1994 . This cross-sectional survey of English adults included data on a range of lifestyle risk factors and health outcomes . For the survey , households were sample d in 720 postal code sectors nested within 177 district health authorities and 14 regional health authorities . Study subjects were adults aged 16 years or more . ICCs and components of variance were estimated from a nested r and om-effects analysis of variance . Results are presented at the district health authority , postal code sector , and household levels . Between-cluster variation was evident at each level of clustering . In these data , ICCs were inversely related to cluster size , but design effects could be substantial when the cluster size was large . Most ICCs were below 0.01 at the district health authority level , and they were mostly below 0.05 at the postal code sector level . At the household level , many ICCs were in the range of 0.0 - 0.3 . These data may provide useful information for the design of epidemiologic studies in which the units sample d or allocated range in size from households to large administrative areas BACKGROUND Studies in experimental animals have implicated the mesolimbic dopaminergic projections into the ventral striatum in the neural processes underlying behavioral reinforcement and motivated behavior ; however , underst and ing the relationship between subjective emotional experience and ventral striatal dopamine ( DA ) release has awaited human studies . Using positron emission tomography ( PET ) , we correlated the change in endogenous dopamine concentrations following dextroamphetamine ( AMPH ) administration with the associated hedonic response in human subjects and compared the strength of this correlation across striatal subregions . METHODS We obtained PET measures of [(11)C]raclopride specific binding to DA D2/D3 receptors before and after AMPH injection ( 0.3 mg/kg IV ) in seven healthy subjects . The change in [(11)C]raclopride binding potential ( DeltaBP ) induced by AMPH pretreatment and the correlation between DeltaBP and the euphoric response to AMPH were compared between the anteroventral striatum ( AVS ; comprised of accumbens area , ventromedial cau date , and anteroventral putamen ) and the dorsal cau date ( DCA ) using an MRI-based region of interest analysis of the PET data . RESULTS The mean DeltaBP was greater in the AVS than in the DCA ( p < .05 ) . The AMPH-induced changes in euphoria analog scale scores correlated inversely with DeltaBP in the AVS ( r = -.95 ; p < .001 ) , but not in the DCA ( r = .30 , ns ) . Post hoc assessment s showed that changes in tension-anxiety ratings correlated positively with DeltaBP in the AVS ( r = .80 ; p [ uncorrected ] < .05 ) and that similar relationships may exist between DeltaBP and emotion ratings in the ventral putamen ( as were found in the AVS ) . CONCLUSIONS The preferential sensitivity of the ventral striatum to the DA releasing effects of AMPH previously demonstrated in experimental animals extends to humans . The magnitude of ventral striatal DA release correlates positively with the hedonic response to AMPH Background Efficacy studies indicate anti-depressive effects of at least some second generation antipsychotics ( SGAs ) . The Bergen Psychosis Project ( BPP ) is a 24-month , pragmatic , industry-independent , r and omized , head-to-head comparison of olanzapine , quetiapine , risperidone and ziprasidone in patients acutely admitted with psychosis . The aim of the study is to investigate whether differential anti-depressive effectiveness exists among SGAs in a clinical ly relevant sample of patients acutely admitted with psychosis . Methods Adult patients acutely admitted to an emergency ward for psychosis were r and omized to olanzapine , quetiapine , risperidone or ziprasidone and followed for up to 2 years . Participants were assessed repeatedly using the Positive and Negative Syndrome Scale - Depression factor ( PANSS-D ) and the Calgary Depression Scale for Schizophrenia ( CDSS ) . Results A total of 226 patients were included . A significant time-effect showing a steady decline in depressive symptoms in all medication groups was demonstrated . There were no substantial differences among the SGAs in reducing the PANSS-D score or the CDSS sum score . Separate analyses of groups with CDSS sum scores > 6 or ≤6 , respectively , reflecting degree of depressive morbidity , revealed essentially identical results to the primary analyses . There was a high correlation between the PANSS-D and the CDSS sum score ( r = 0.77 ; p < 0.01 ) . Conclusions There was no substantial difference in anti-depressive effectiveness among olanzapine , quetiapine , risperidone or ziprasidone in this clinical ly relevant sample of patients acutely admitted to hospital for symptoms of psychosis . Based on our findings we can make no recommendations concerning choice of any particular SGA for targeting symptoms of depression in a patient acutely admitted with psychosis . Trial Registration Clinical Trials.gov ID ; URL : http://www . clinical trials.gov/ : Thirty-six patients with long-st and ing psychotic illness r and omly selected among attenders at two community centers of Bologna were interviewed as were their therapists , in order to determine prevalence and patterns of substance use , reasons for use and effects on illness . Protocol s were the same as used in previous research carried out in Boulder , Colorado . For all substances , except stimulants and over-the-counter products , prevalence rates were lower in the Bologna sample than in Boulder . Overall lifetime rates of substance use were significantly lower in the Bologna sample . Nevertheless 47.2 % of the Bologna sample had a lifetime moderate to severe drug use and nearly two-thirds of the sample had a current drug use of some severity . Reasons for use equally reflected attempts to alleviate unpleasant emotional states and recreational purpose s. Patients with high degrees of psychopathology had significantly lower scores on severity of drug use The subjects were 62 patients hospitalized for acute exacerbations of schizophrenia and were r and omly assigned to receive risperidone ( mean dose , 7.4 mg/day ) , haloperidol ( 7.6 mg/day ) , or methotrimeprazine ( 100 mg/day ) for 4 weeks . Clinical improvement , defined a priori as a 20 % reduction in total Positive and Negative Syndrome Scale ( PANSS ) scores at end point , was attained by 81 % of the risperidone patients , 60 % of the haloperidol patients , and 52 % of the methotrimeprazine patients ( p < 0.05 ) . The reductions in total PANSS and Clinical Global Impression Scale severity scores from baseline to end point were significantly greater in the risperidone patients than in the other two groups . Reductions in scores on the Psychotic Anxiety Scale were significantly greater in the risperidone patients than the methotrimeprazine patients ; the difference between haloperidol and methotrimeprazine was not significant . Extrapyramidal symptoms ( scores on the Extrapyramidal Symptom Rating Scale ) were more severe in the haloperidol patients than in the other two groups , but few differences were apparent between risperidone and methotrimeprazine patients . It is concluded that risperidone is an effective antipsychotic and anxiolytic agent in schizophrenic patients INTRODUCTION Negative symptoms of schizophrenia often predict an unfavorable clinical outcome . Disturbed dopamine transmission in different brain parts may underlie different aspects of negative symptoms , and the effect of antipsychotics on them may also differ . This pilot study investigated the potentially therapeutic effects of the partial dopamine agonist aripiprazole on different negative symptoms . METHODS This pilot study r and omly assigned patients with schizophrenia ( N=40 ) to either aripiprazole or risperidone . After 6 weeks of treatment , the severity of negative symptoms was determined by the PANSS . Subscales of self-report question naires were used to assess differences in initiative , anhedonia , social functioning and subjective well-being . RESULTS Patients treated with aripiprazole showed a significant improvement on measures for anhedonia and subjective wellbeing . Negative symptoms in general , lack of initiative and social inhibition were also lower in the aripiprazole treated group , but without reaching statistical significance . DISCUSSION According to this pilot study , aripiprazole appears to specifically improve anhedonia and subjective wellbeing compared to risperidone . This may be caused by a specific effect of aripiprazole on the limbic branch of the dopamine system . Future studies should replicate this finding with a larger sample size BACKGROUND Well- design ed prospect i ve studies of substance misuse in first-episode psychosis can improve our underst and ing of the risks associated with comorbid substance misuse and psychosis . AIMS To examine the potential effects of substance misuse on in-patient admission and remission and relapse of positive symptoms in first-episode psychosis . METHOD The study was a prospect i ve 15-month follow-up investigation of 103 patients with first-episode psychosis recruited from three mental health services . RESULTS Substance misuse was independently associated with increased risk of in-patient admission , relapse of positive symptoms and shorter time to relapse of positive symptoms after controlling for potential confounding factors . Substance misuse was not associated with remission or time to remission of positive symptoms . Heavy substance misuse was associated with increased risk of in-patient admission , relapse and shorter time to relapse . CONCLUSIONS Substance misuse is an independent risk factor for a problematic recovery from first-episode psychosis BACKGROUND Cocaine dependence is associated with high rates of relapse . Stress and drug cue exposure are known to increase cocaine craving and stress arousal , but the association between these responses and cocaine relapse has not been previously studied . OBJECTIVE To examine whether stress-induced and drug cue-induced cocaine craving and hypothalamic-pituitary-adrenal axis responses evoked in the laboratory are associated with subsequent cocaine relapse . DESIGN Prospect i ve study design assessing cocaine relapse and drug use during a 90-day follow-up period after discharge from inpatient treatment and research . Data were analyzed by Cox proportional hazards regression and multiple regression . SETTING Inpatient treatment and research unit in a community mental health center . PATIENTS Forty-nine treatment-seeking cocaine-dependent individuals . MAIN OUTCOME MEASURES Time to cocaine relapse , number of days of cocaine use , and amount of cocaine used per occasion in the follow-up phase . RESULTS Greater stress-induced , but not drug cue-induced , cocaine craving was associated with a shorter time to cocaine relapse . Stress-induced corticotropin and cortisol responses predicted higher amounts of cocaine use per occasion in the 90-day follow-up . CONCLUSIONS These results demonstrate that stress-related increases in cocaine craving and hypothalamic-pituitary-adrenal axis responses are each associated with specific cocaine relapse outcomes . The findings support the use of stress-induced drug craving and associated hypothalamic-pituitary-adrenal axis responses to evaluate cocaine relapse propensity . Furthermore , treatments that address stress-induced cocaine craving and hypothalamic-pituitary-adrenal responses could be of benefit in improving relapse outcomes in cocaine dependence BACKGROUND The relative effectiveness of second-generation ( atypical ) antipsychotic drugs as compared with that of older agents has been incompletely addressed , though newer agents are currently used far more commonly . We compared a first-generation antipsychotic , perphenazine , with several newer drugs in a double-blind study . METHODS A total of 1493 patients with schizophrenia were recruited at 57 U.S. sites and r and omly assigned to receive olanzapine ( 7.5 to 30 mg per day ) , perphenazine ( 8 to 32 mg per day ) , quetiapine ( 200 to 800 mg per day ) , or risperidone ( 1.5 to 6.0 mg per day ) for up to 18 months . Ziprasidone ( 40 to 160 mg per day ) was included after its approval by the Food and Drug Administration . The primary aim was to delineate differences in the overall effectiveness of these five treatments . RESULTS Overall , 74 percent of patients discontinued the study medication before 18 months ( 1061 of the 1432 patients who received at least one dose ) : 64 percent of those assigned to olanzapine , 75 percent of those assigned to perphenazine , 82 percent of those assigned to quetiapine , 74 percent of those assigned to risperidone , and 79 percent of those assigned to ziprasidone . The time to the discontinuation of treatment for any cause was significantly longer in the olanzapine group than in the quetiapine ( P<0.001 ) or risperidone ( P=0.002 ) group , but not in the perphenazine ( P=0.021 ) or ziprasidone ( P=0.028 ) group . The times to discontinuation because of intolerable side effects were similar among the groups , but the rates differed ( P=0.04 ) ; olanzapine was associated with more discontinuation for weight gain or metabolic effects , and perphenazine was associated with more discontinuation for extrapyramidal effects . CONCLUSIONS The majority of patients in each group discontinued their assigned treatment owing to inefficacy or intolerable side effects or for other reasons . Olanzapine was the most effective in terms of the rates of discontinuation , and the efficacy of the conventional antipsychotic agent perphenazine appeared similar to that of quetiapine , risperidone , and ziprasidone . Olanzapine was associated with greater weight gain and increases in measures of glucose and lipid metabolism Background : The prevalence of obsessive-compulsive symptoms ( OCS ) in patients with schizophrenia is relatively high . Antipsychotics have been found to influence OCS . Objective : To determine whether induction or severity of OCS differs during treatment with olanzapine or risperidone in young patients with early psychosis . Methods : One hundred twenty-two patients with a Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition diagnosis of schizophrenia , schizoaffective disorder , or schizophreniform disorder were r and omized in a double-blind design to groups of 6 weeks ' treatment with olanzapine ( n = 59 ) or risperidone ( n = 63 ) , with a mean dose of 11.3 mg olanzapine and 3.0 mg risperidone at 6 weeks . Primary outcome measures were the mean baseline-to-endpoint change in total score on the Yale-Brown Obsessive-Compulsive Scale ( Y-BOCS ) . Results : Treatment with olanzapine was associated with greater decreases in Y-BOCS total score than treatment with risperidone in total group ( N = 122 : -2.2 vs -0.3 , z = -2.651 , P < 0.01 ) , in patients with baseline Y-BOCS total score greater than 0 ( n = 58 : -5.1 vs -0.4 , z = -2.717 , P < 0.01 ) , and in patients with baseline Y-BOCS total score greater than 10 ( n = 29 : -7.1 vs -0.6 , z = -2.138 , P = 0.032 ) . Conclusions : In this r and omized , 6-week , double-blind trial , we found a significant and clinical ly relevant difference in decrease in Y-BOCS scores favoring olanzapine compared with risperidone OBJECTIVES This r and omized , open-label trial was design ed to help inform antipsychotic treatment policies . It compared the 1-year cost-effectiveness of initial treatment with olanzapine ( OLZ ) ( n = 229 ) versus a " fail-first " algorithm on conventional antipsychotics ( then olanzapine if indicated ) ( CON ) ( n = 214 ) ; and versus initial treatment with risperidone ( RIS ) ( n = 221 ) . METHODS Individuals with schizophrenia or schizoaffective disorder were recruited from May 1998 to September 2001 . Clinical , functioning , and re source utilization data were collected at baseline and five postbaseline visits . Brief Psychiatric Rating Scale scores defined " clinical effectiveness ; " Lehman Quality of Life Scale social relations scores defined " social effectiveness . " RESULTS Requiring failure on less expensive antipsychotics before use of olanzapine did not result in total cost savings , despite significantly higher antipsychotic costs with OLZ . Total 1-year mean costs were 21,283 dollars for CON ; 20,891 dollars for OLZ ; and 21,347 dollars for RIS ( pair-wise comparisons nonsignificant ) . Intent-to-treat effectiveness comparisons ( nonsignificant ) were augmented by analyses that adjusted for duration on initial antipsychotic treatment , and by comparisons of patients remaining on initial antipsychotic treatment versus those who required switching . When accounting for differential switching rates ( OLZ 0.14 vs. CON 0.53 , P < 0.0001 ; vs. RIS 0.31 , P < 0.0001 ) , OLZ was significantly more effective than CON on clinical ( P = 0.025 ) and social ( P = 0.043 ) measures , and significantly more effective than RIS on the social ( P = 0.002 ) measure . Further , patients initiated on an antipsychotic from which they needed to switch required additional re sources for hospitalization ( P = 0.036 ) and crisis services ( P = 0.029 ) . CONCLUSIONS Approaches that integrate costs , effectiveness , and treatment patterns are important for providing optimal information regarding the value of first-line antipsychotic options for schizophrenia Objective : This study aim ed to compare the efficacy of long-acting risperidone and zuclopenthixol in subjects with schizophrenia and substance abuse . Method : A total of 115 subjects with schizophrenia and substance use disorders were enrolled for an open , r and omized , controlled , 6-month follow-up study . Fifty-seven subjects were selected for treatment with long-acting injectable risperidone , while another 58 were treated with zuclopenthixol-depot . Results : Long-acting risperidone patients presented fewer positive urine tests ( 8.67 compared with 10.36 , P = 0.005 ) , showed improved scores on the Positive and Negative Syndrome Scale , and showed better compliance with the Substance Abuse Management program . The use of long-acting risperidone and less severe dependence explained the outcome at the end of the follow-up . Conclusions : Long-acting injectable risperidone was more effective than zuclopenthixol-depot in improving substance abuse and schizophrenia symptoms in subjects with dual diagnosis OBJECTIVES This study aim ed to prospect ively identify the best single predictor and the best set of predictors of risk for nonadherence with anti-psychotic medication in the treatment of patients with schizophrenia . METHOD We used data from 1579 patients in a 3-year , prospect i ve , naturalistic , nonr and omized , multisite study of schizophrenia patients conducted from July 1997 to September 2003 ( U.S. Schizophrenia Care and Assessment Program ) . Adherence with any oral antipsychotic medication was assessed using patient-reported medication adherence and an indirect adherence measure based on medical record prescription information . Patients who reported poor medication adherence or had a medication possession ratio < or = 80 % ( percentage of days with prescriptions for any oral antipsychotic ) during the first year after enrollment were defined as nonadherent ( N = 296 , 18.8 % ) . Thirty-nine previously reported potential risk factors of nonadherence with antipsychotic medication were assessed at enrollment with valid and reliable measures . Risk factors represented patient- , environment- , and treatment-related domains , including sociodemographics , symptom severity , substance use , threat to safety of self and others , other illness-related factors , need for supervision , medication-related adverse events , and prior medication-utilization patterns . RESULTS The best single predictor of future nonadherence was nonadherence during the 6 months prior to enrollment ( odds ratio = 4.1 , 95 % confidence interval = 3.1 to 5.6 , p < .001 ) . The best set of predictors of nonadherence , ordered by strength of association , included prior non-adherence , recent illicit drug use , recent alcohol use , prior treatment with antidepressants , and greater patient-reported , medication-related cognitive impairment . CONCLUSION Nonadherence with antipsychotic medication is associated with a well-defined set of risk factors that can be used to identify patients who are predisposed to poor adherence Chronic management of schizophrenia and schizoaffective disorders is frequently complicated by symptomatic relapse . An open-label , r and omized , active-controlled , 2-year trial evaluated 710 patients with schizophrenia or related disorders who were switched from stable treatment with oral risperidone , olanzapine , or conventional neuroleptics to risperidone long-acting injectable ( RLAI ) or oral quetiapine . Primary effectiveness evaluation was time-to-relapse . Safety evaluations included adverse events ( AEs ) reported for the duration of the study , Extrapyramidal Symptom Rating Scale ( ESRS ) , clinical laboratory tests , and vital signs . A total of 666 patients ( n=329 RLAI , n=337 quetiapine ) were evaluable for effectiveness measures . Baseline demographics were similar between treatment groups . Kaplan – Meier estimate of time-to-relapse was significantly longer with RLAI ( p<0.0001 ) . Relapse occurred in 16.5 % of patients with RLAI and 31.3 % with quetiapine . RLAI and quetiapine were both safe and well tolerated . Weight gain affected 7 % of patients with RLAI and 6 % with quetiapine , with mean end point increases of 1.25±6.61 and 0±6.55 kg , respectively . There were no significant between-group differences in weight gain . ESRS total scores decreased similarly after r and omization to either RLAI or quetiapine . Extrapyramidal AEs occurred in 10 % of patients with RLAI and 6 % with quetiapine . Treatment-emergent potentially prolactin-related AEs were reported in 15 ( 5 % ) patients with RLAI and 5 ( 2 % ) patients with quetiapine ; hyperprolactinemia was reported in 43 ( 13.1 % ) patients with RLAI and 5 ( 1.5 % ) patients with quetiapine . Somnolence occurred in 2 % of patients with RLAI and 11 % with quetiapine . To our knowledge , this is the first report of a r and omized clinical trial directly comparing relapse prevention with a second-generation long-acting injectable antipsychotic and oral therapy . Time-to-relapse in stable patients with schizophrenia or schizoaffective disorder was significantly longer in patients r and omized to RLAI compared with those r and omized to oral quetiapine . Both antipsychotics were generally well tolerated OBJECTIVE Little is known about the epidemiology of substance use disorders ( SUD ) among psychiatric in patients in the Western Cape , South Africa . Therefore , this study was conducted to examine the prevalence of SUD among acute adult psychiatric in patients at Stikl and Hospital , one of three state acute psychiatric hospitals in the Western Cape . METHOD A prospect i ve descriptive prevalence survey was undertaken over a three-month period . During this period , data was collected on psychiatric patients ( N=298 ) who were hospitalized in the acute psychiatric wards at Stikl and . This included patient demography , psychiatric and substance use history . Urine was also collected and analyzed for substances commonly abused in the Western Cape . RESULTS A co-morbid SUD ( abuse or dependence ) was diagnosed in 51 % of patients . In addition , a diagnosis of a substance-induced psychiatric disorder was made in 8 % of these patients , 1 % of who was diagnosed with a substance-induced mood disorder , while 7 % was diagnosed with a substance induced psychotic disorder . Patients diagnosed with a co-morbid SUD were younger than those without a SUD and more likely to have been involuntary admissions . These patients also displayed more violence prior to admission that contributed to their admission and were more likely to have used cannabis or methamphetamine as their preferred drug of abuse . Only a small group of patients had documented evidence of any prior interventions for their SUD . CONCLUSION SUD are prevalent among psychiatric in patients and contribute to their morbidity . This has implication s for staff training and service development Objective : Cannabis use disorder is the most common co-occurring drug use disorder in people with schizophrenia and is associated with poor outcomes . The authors launched a r and omized controlled trial to assess the impact of clozapine compared with treatment as usual on cannabis use in patients with schizophrenia and co-occurring cannabis use disorder . Methods : Thirty-one patients with schizophrenia and co-occurring cannabis use disorder were r and omly assigned to switch to clozapine or to stay on their current antipsychotic and were then followed weekly for 12 weeks . Blinded raters assessed participants weekly with the Timeline Followback for substance use and the exp and ed Brief Psychiatric Rating Scale for symptoms . Longitudinal r and om effects models were used to investigate the time-varying differences in cannabis use and other outcomes between the treatment as usual and clozapine groups . Results : The two groups differed in average intensity of cannabis use by approximately 4.5 joints/week , with lesser use in the clozapine group ( t = −1.77 ; df = 28.5 ; p = .086 ; effect size ∼ 0.6 ) . Symptoms and functioning were not different between the two groups . Conclusions : Clozapine may reduce cannabis use among patients with schizophrenia and co-occurring cannabis use disorder . Further controlled trials are warranted Cannabis use disorders ( CUDs ) are highly comorbid in patients with schizophrenia and are associated with poor outcome . Clozapine has been put forward as the first choice antipsychotic in this comorbid group . However , little is known about the mechanisms underlying the assumed superiority of clozapine . We compared the effects of clozapine and risperidone on attentional bias , subjective craving and associated regional brain activity in patients with schizophrenia and CUD . Overall , 36 patients with schizophrenia and 19 healthy controls were included . Patients were r and omised to antipsychotic treatment with clozapine or risperidone . At baseline and after 4 weeks of medication use , regional brain responses were measured during a classical Stroop and a cannabis word Stroop using functional magnetic resonance imaging . Clozapine-treated CUD patients showed a larger reduction in craving and in activation of the insula during the cannabis word Stroop , while risperidone-treated patients showed a larger decrease in activation of the right anterior cingulate cortex during the classical Stroop . A significant association was found between decreases in subjective craving and decreases in insula activation during the cannabis word Stroop . These findings strongly suggest that clozapine may be a better treatment choice in patients with schizophrenia and CUD than risperidone BACKGROUND The treatment of psychotic symptoms in patients with mood disorders is a complex challenge . Antipsychotic medications in these individuals may be associated with extrapyramidal symptoms ( EPS ) , worsening of depression , and functional impairment . Atypical antipsychotics such as quetiapine and risperidone are associated with a decreased incidence of adverse events such as EPS . The objective of this study was to compare the efficacy and tolerability of quetiapine and risperidone for the treatment of depressive symptoms in out patients with psychosis . METHOD In this 4-month , multicenter , open-label trial , patients were r and omly assigned in a 3:1 ratio of quetiapine to risperidone , and both drugs were flexibly dosed . Eligible patients had psychoses and demonstrated 1 of several DSM-IV diagnoses , including schizoaffective disorder , bipolar I disorder , major depressive disorder , delusional disorder , Alzheimer 's dementia , schizophreniform disorder , vascular dementia , and substance abuse dementia . Patients were classified as mood disordered if they had bipolar disorder , major depressive disorder , or schizoaffective disorder . Efficacy was assessed using the Positive and Negative Syndrome Scale and the Clinical Global Impressions scale . The Hamilton Rating Scale for Depression ( HAM-D ) was used to assess the level of depressive symptoms . The primary tolerability assessment was presence or absence of substantial EPS , defined as EPS severe enough to require an alteration in treatment . RESULTS A total of 554 patients were r and omly assigned to quetiapine and 175 to risperidone . Mean doses at 16 weeks were 318 mg for quetiapine and 4.4 mg for risperidone . Although both agents produced improvements in mean HAM-D scores , quetiapine produced a greater improvement than risperidone in all patients ( p = .0015 ) . Within the mood-diagnosed population , incidences of both substantial EPS ( p = .001 ) and at least moderate EPS ( p = .0373 ) occurred significantly less frequently among patients taking quetiapine . For patients with non-mood diagnoses , incidences of substantial EPS were fewer for patients taking quetiapine than for those taking risperidone ( p = .062 ) ; however , this was not statistically significant . CONCLUSION These results suggest that quetiapine may be a useful agent in the management of depressive symptoms in patients with psychosis OBJECTIVE Antipsychotic medications differ in their sedative potential , which can affect cognitive performance . The primary objective of this double-blind study was to compare the effects of treatment initiation with risperidone and quetiapine on cognitive function in subjects with stable bipolar disorder . METHOD Subjects had a DSM-IV diagnosis of bipolar I disorder in partial or full remission and a Young Mania Rating Scale score < or= 8 at screening . Subjects were r and omly assigned to 1 of 2 treatment sequences : risperidone-quetiapine or quetiapine-risperidone . Subjects in the risperidone-quetiapine sequence received 2 mg of risperidone with dinner and placebo with breakfast during period 1 and 100 mg of quetiapine with dinner and 100 mg with breakfast during period 2 . Subjects in the quetiapine-risperidone sequence received the same treatments in reverse order . The 2 treatment periods were separated by a 6- to 14-day washout period . Cognitive function , including attention , working memory , declarative memory , processing speed , and executive functions , was measured before and after dosing . The Visual Analog Scale for Fatigue was also completed . The primary endpoint was a neurocognitive composite score ( NCS ) . The study was conducted from November 2004 through August 2005 . RESULTS Thirty subjects were r and omly assigned ; 28 took all doses of study medication and completed a baseline and at least 1 postbase-line assessment in each treatment . On the NCS , significantly better overall cognitive function was seen after risperidone than after quetiapine at each time point after dosing . Subjects performed significantly better after risperidone than after quetiapine ( p < .05 ) on 9 of the 18 individual cognitive outcome measures and significantly better after quetiapine than after risperidone on 1 measure . Sleeping or the need for sleep during the test days was reported in significantly more patients after receiving quetiapine than risperidone . CONCLUSIONS The results indicate that initiation of quetiapine treatment was associated with more immediate adverse cognitive effects and increased somnolence than risperidone treatment . CLINICAL TRIALS REGISTRATION Clinical Trials.gov identifier NCT00097032 OBJECTIVE Alcohol use disorders worsen the course of schizophrenia . Although the atypical antipsychotic clozapine appears to decrease alcohol use in schizophrenia , risperidone does not . We have proposed that risperidone 's relatively potent dopamine D2 receptor blockade may partly underlie its lack of effect on alcohol use . Since long-acting injectable ( LAI ) risperidone both results in lower average steady-state plasma concentrations than oral risperidone ( with lower D2 receptor occupancy ) and encourages adherence , it may be more likely to decrease heavy alcohol use ( days per week of drinking 5 or more drinks per day ) than oral risperidone . METHOD Ninety-five patients with DSM-IV-TR diagnoses of schizophrenia and alcohol use disorder were r and omized to 6 months of oral or LAI risperidone between 2005 and 2008 . Explanatory ( efficacy ) analyses were carried out to evaluate the potential benefits of LAI under suitably controlled conditions ( in contrast to real-world setting s ) , with intent-to-treat analyses being secondary . RESULTS Explanatory analyses showed that heavy drinking in the oral group worsened over time ( P = .024 ) and that there was a statistical trend toward significance in the difference between the changes in heavy drinking days in the oral and LAI groups ( P = .054 ) . Furthermore , the 2 groups differed in the mean number of drinking days per week ( P = .035 ) . The intent-to-treat analyses showed no difference in heavy drinking but did show a difference in average drinking days per week similar to that obtained from the explanatory analyses ( P = .018 ) . Neither explanatory nor intent-to-treat analyses showed any between-group differences in alcohol use as measured by intensity or the Alcohol Use Scale . The plasma concentrations of the active metabolite 9-hydroxyrisperidone were significantly lower in patients taking LAI ( P < .05 ) , despite their significantly ( overall ) better treatment adherence ( P < .005 ) . CONCLUSION For the population considered here , schizophrenia patients with alcohol use disorder appear to continue drinking some alcohol while taking either form of risperidone . Nonetheless , our data suggest that injectable risperidone may be a better choice than the oral form for these dual diagnosis patients . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT00130923 BACKGROUND Alcohol and cannabis use disorders worsen the course of schizophrenia . While the typical antipsychotics are of limited value in controlling substance use in schizophrenic patients , previous studies suggest that the novel antipsychotic clozapine ( CLOZ ) may decrease their substance use . We describe a retrospective study of the effects of the novel antipsychotics risperidone ( RISP ) and clozapine on alcohol and cannabis use in patients with schizophrenia or schizoaffective disorder and comorbid alcohol and /or cannabis use disorder . METHOD This study involved retrospective assessment of abstinence ( cessation of alcohol and cannabis use ) in 41 patients treated with either risperidone ( n=8 ) or clozapine ( n=33 ) for at least 1 year . In 32 of these 41 patients , information was available on whether abstinence occurred during the 1-year period . RESULTS Abstinence rates were significantly higher in patients treated with clozapine than in those treated with risperidone ( 54 % vs. 13 % , p=0.05 ) . The nine patients treated for at least 1 year , but excluded from the analysis because time of cessation of use was not known , had all stopped alcohol/cannabis use during clozapine treatment . DISCUSSION While the limitations of this retrospective study must be recognized , the data suggest that comorbid patients treated with clozapine are more likely to abstain from alcohol and cannabis use than are those treated with risperidone . Further prospect i ve studies will be required to confirm these intriguing results OBJECTIVE The authors compared 4-month treatment outcomes for olanzapine versus risperidone in patients with first-episode schizophrenia spectrum disorders . METHOD One hundred twelve subjects ( 70 % male ; mean age=23.3 years [ SD = 5.1 ] ) with first-episode schizophrenia ( 75 % ) , schizophreniform disorder ( 17 % ) , or schizoaffective disorder ( 8 % ) were r and omly assigned to treatment with olanzapine ( 2.5 - 20 mg/day ) or risperidone ( 1 - 6 mg/day ) . RESULTS Response rates did not significantly differ between olanzapine ( 43.7 % , 95 % CI=28.8%-58.6 % ) and risperidone ( 54.3 % , 95 % CI=39.9%-68.7 % ) . Among those responding to treatment , more subjects in the olanzapine group ( 40.9 % , 95 % CI=16.8%-65.0 % ) than in the risperidone group ( 18.9 % , 95 % CI=0%-39.2 % ) had subsequent ratings not meeting response criteria . Negative symptom outcomes and measures of parkinsonism and akathisia did not differ between medications . Extrapyramidal symptom severity scores were 1.4 ( 95 % CI=1.2 - 1.6 ) with risperidone and 1.2 ( 95 % CI=1.0 - 1.4 ) with olanzapine . Significantly more weight gain occurred with olanzapine than with risperidone : the increase in weight at 4 months relative to baseline weight was 17.3 % ( 95 % CI=14.2%-20.5 % ) with olanzapine and 11.3 % ( 95 % CI=8.4%-14.3 % ) with risperidone . Body mass index at baseline and at 4 months was 24.3 ( 95 % CI=22.8 - 25.7 ) versus 28.2 ( 95 % CI=26.7 - 29.7 ) with olanzapine and 23.9 ( 95 % CI=22.5 - 25.3 ) versus 26.7 ( 95 % CI=25.2 - 28.2 ) with risperidone . CONCLUSIONS Clinical outcomes with risperidone were equal to those with olanzapine , and response may be more stable . Olanzapine may have an advantage for motor side effects . Both medications caused substantial rapid weight gain , but weight gain was greater with olanzapine BACKGROUND The long-term safety and efficacy of long-acting injectable risperidone , the first long-acting second-generation antipsychotic , were evaluated in stable patients with schizophrenia . METHOD After a 2-week run-in period during which patients with DSM-IV schizophrenia received flexible doses of 1 to 6 mg of oral risperidone , patients received injections of 25 mg , 50 mg , or 75 mg of long-acting risperidone every 2 weeks for 12 months . Severity of extrapyramidal symptoms was assessed with the Extrapyramidal Symptom Rating Scale ( ESRS ) , and efficacy was assessed with the Positive and Negative Syndrome Scale ( PANSS ) . This study was conducted from March 29 , 1999 to July 19 , 2000 . RESULTS The subjects were 615 patients with schizophrenia who received at least 1 injection of long-acting risperidone . The 12-month trial was completed by 65 % of patients . Treatment was discontinued because of adverse events in 5 % of patients . Extrapyramidal symptoms as adverse events were reported by 25 % of the patients . Severity of extrapyramidal symptoms ( according to ESRS scores ) was low at baseline and decreased in each of the groups during the 12 months . The other most common adverse events were anxiety in 24 % , insomnia in 21 % , psychosis in 17 % , and depression in 14 % of the patients . Little pain was associated with the injections . Severity of symptoms of schizophrenia was improved in each group , with significant reductions in PANSS total scores ( p < .01 ) and positive ( p < .01 ) and negative ( p < .001 ) factor scores . CONCLUSION In terms of both safety and efficacy , symptomatically stable patients with schizophrenia benefit from being switched to long-acting injectable risperidone In a r and omized , double-blind trial , patients with acute bipolar mania received 1 - 6 mg/day of risperidone , 2 - 12 mg/day of haloperidol , or placebo for 3 weeks , followed by double-blind risperidone or haloperidol for 9 weeks . Of 438 patients , 154 were r and omized to risperidone , 144 to haloperidol , and 140 to placebo . The mean+/-S.D. modal doses were 4.2+/-1.7 mg/day of risperidone and 8.0+/-3.6 mg/day of haloperidol during the initial 3-week phase and 4.1+/-1.8 and 7.4+/-3.7 mg/day during the 12-week period . At week 3 , mean Young Mania Rating Scale ( YMRS ) score reductions from baseline were significantly greater in patients receiving risperidone than placebo ( p<0.001 ) . Differences between risperidone and haloperidol on this efficacy measure were not significant . Further reductions in YMRS scores were seen in patients receiving risperidone or haloperidol during the subsequent 9 weeks . No unexpected adverse events were reported . Extrapyramidal disorder and hyperkinesias , the most commonly reported adverse events with antipsychotic use , occurred less frequently with risperidone than haloperidol . We conclude that risperidone monotherapy was an effective and well-tolerated treatment for bipolar mania and that efficacy was maintained over the long term A modification of an earlier rating scale for extrapyramidal system disturbance is described , and evidence for the validity and reliability of the scale is presented . The usefulness of the scale in studies of neuroleptic drugs is discussed . By its application it is possible to quantify extrapyramidal side effects and to separate them into four principal factors BACKGROUND A recent review suggested an association between using unpublished scales in clinical trials and finding significant results . AIMS To determine whether such an association existed in schizophrenia trials . METHOD Three hundred trials were r and omly selected from the Cochrane Schizophrenia Group 's Register . All comparisons between treatment groups and control groups using rating scales were identified . The publication status of each scale was determined and cl aims of a significant treatment effect were recorded . RESULTS Trials were more likely to report that a treatment was superior to control when an unpublished scale was used to make the comparison ( relative risk 1.37 ( 95 % CI 1.12 - 1.68 ) ) . This effect increased when a ' gold-st and ard ' definition of treatment superiority was applied ( RR 1.94 ( 95 % CI 1.35 - 2.79 ) ) . In non-pharmacological trials , one-third of ' gold-st and ard ' cl aims of treatment superiority would not have been made if published scales had been used . CONCLUSIONS Unpublished scales are a source of bias in schizophrenia trials Objective : This paper reports on a study design ed within the framework of the National Survey of Mental Health and Wellbeing to : estimate the prevalence of psychoses in urban areas of Australia ; identify profiles of symptomatology , impairments and disabilities ; collect information on services received and needed ; and explore quality of life issues in a broadly representative sample of people with psychotic illnesses . Method : The study was conducted over four areas in the Australian Capital Territory , Queensl and , Victoria and Western Australia , as a two-phase survey : ( i ) a census and screening for psychosis of all individuals who made contacts with mental health services during a period of 1 month in 1997 ; and ( ii ) interviews with a stratified r and om sample ( n = 980 ) of the screen-positive individuals ( n = 3800 ) using a st and ardised instrument . Results : The point prevalence ( 1 month ) of psychotic disorders in the urban population aged 18–64 is in the range of 4–7 per 1000 with a weighted mean of 4.7 per 1000 . People with psychotic disorders experience high rates of functional impairments and disability , decreased quality of life , persistent symptoms , substance-use comorbidity and frequent side effects of medication . Although the utilisation of hospital-based and community mental health services , as well as of public and non-governmental helping agencies , is high , the majority live in extreme social isolation and adverse socioeconomic circumstances . Among the many unmet needs , the limited availability of community-based rehabilitation , supported accommodation and employment opportunities is particularly prominent . Conclusions : The so-called ‘ low-prevalence ’ psychotic disorders represent a major and complex public health problem , associated with heavy personal and social costs . There is a need for a broad programmatic approach , involving various sectors of the community , to tackle the multiple dimensions of clinical disorder , personal functioning and socioeconomic environment that influence the course and outcome of psychosis and ultimately determine the effectiveness of service-based intervention The National Institute of Mental Health initiated the Clinical Antipsychotic Trials of Intervention Effectiveness ( CATIE ) program to evaluate the effectiveness of antipsychotic drugs in typical setting s and population s so that the study results will be maximally useful in routine clinical situations . The CATIE schizophrenia trial blends features of efficacy studies and large , simple trials to create a pragmatic trial that will provide extensive information about antipsychotic drug effectiveness over at least 18 months . The protocol allows for subjects who receive a study drug that is not effective to receive subsequent treatments within the context of the study . Medication dosages are adjusted within a defined range according to clinical judgment . The primary outcome is all-cause treatment discontinuation because it represents an important clinical endpoint that reflects both clinician and patient judgments about efficacy and tolerability . Secondary outcomes include symptoms , side effects , neurocognitive functioning , and cost-effectiveness . Approximately 50 clinical sites across the United States are seeking to enroll a total of 1,500 persons with schizophrenia . Phase 1 is a double-blinded r and omized clinical trial comparing treatment with the second generation antipsychotics olanzapine , quetiapine , risperidone , and ziprasidone to perphenazine , a midpotency first generation antipsychotic . If the initially assigned medication is not effective , subjects may choose one of the following phase 2 trials : ( 1 ) r and omization to open-label clozapine or a double-blinded second generation drug that was available but not assigned in phase 1 ; or ( 2 ) double-blinded r and omization to ziprasidone or another second generation drug that was available but not assigned in phase 1 . If the phase 2 study drug is discontinued , subjects may enter phase 3 , in which clinicians help subjects select an open-label treatment based on individuals ' experiences in phases 1 and 2 OBJECTIVE The study assessed the efficacy and safety of risperidone as an adjunctive agent to mood stabilizers in the treatment of acute mania . METHOD This 3-week r and omized , double-blind , placebo-controlled study included 156 bipolar disorder patients with a current manic or mixed episode who received a mood stabilizer ( lithium or divalproex ) and placebo , risperidone , or haloperidol . The primary efficacy measure was the Young Mania Rating Scale . Other assessment s used the Brief Psychiatric Rating Scale , the Clinical Global Impression scale , and safety measures . RESULTS The trial was discontinued by 25 ( 49 % ) of the 51 placebo group patients , 18 ( 35 % ) of the 52 risperidone group patients , and 28 ( 53 % ) of the 53 haloperidol group patients . Mean modal doses were 3.8 mg/day ( SD=1.8 ) of risperidone and 6.2 mg/day ( SD=2.9 ) of haloperidol . Significantly greater reductions in Young Mania Rating Scale scores at endpoint and over time were seen in the risperidone group and in the haloperidol group , compared with the placebo group . Young Mania Rating Scale total scores improved with risperidone and with haloperidol both in patients with psychotic features and in those without psychotic features at baseline . Extrapyramidal Symptom Rating Scale total scores at endpoint were significantly higher in the haloperidol patients than in the placebo patients . Antiparkinsonian medications were received by 8 % , 17 % , and 38 % of patients in the placebo , risperidone , and haloperidol groups , respectively . CONCLUSIONS Risperidone plus a mood stabilizer was more efficacious than a mood stabilizer alone , and as efficacious as haloperidol plus a mood stabilizer , for the rapid control of manic symptoms and was well tolerated The aim of this study was to compare the 12-month effectiveness of several second-generation antipsychotic drugs , with that of haloperidol in never-treated patients with first-episode psychosis . In total , 114 patients without life time exposure to any psychotropic medication were r and omized to haloperidol , olanzapine , risperidone , quetiapine or ziprasidone . Primary outcome was time to all-cause discontinuation . Secondary outcomes included discontinuation rates and symptom change as measured by the Positive and Negative Syndrome Scale ( PANSS ) . The overall discontinuation rate 64 % . At 12 months , the proportion of patients discontinuing treatment was 40.0 % for olanzapine , 56.5 % for quetiapine , 64.0 % for risperidone , 80.0 % for ziprasidone and 85.7 % for haloperidol . Mean time to antipsychotic discontinuation was higher in patients r and omized to second-generation antipsychotics than in those taking haloperidol . Significantly lower discontinuation was noted in patients on olanzapine than on haloperidol , or ziprasidone . Our results suggest that olanzapine might lead to longer treatment continuation in treatment naïve FEP patients than haloperidol and , possibly ziprasidone . Global psychopathology was significantly less reduced by haloperidol than with each individual SGA in this earliest phase of treatment |
807 | 24,888,383 | Furthermore , between-group BNP changes seemed to be a significant modifier to the effects of BNP-guided therapy on clinical outcomes , and BNP-guided therapy may improve the clinical outcomes of CHF patients if substantial reduction of BNP can be achieved .
In addition , BNP-guided therapy was not associated with increased risk for serious adverse events .
BNP-guided therapy may improve the clinical outcomes of CHF patients if substantial reduction of BNP can be achieved . | Abstract The role of B-type natriuretic peptide ( BNP ) in the management of patients with chronic heart failure ( CHF ) was uncertain .
The aim of this meta- analysis was to comprehensively evaluate the effect of BNP-guided therapy in CHF . | OBJECTIVES The purpose of this study was to compare the effects of N-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided therapy with those of intensive clinical management and with usual care ( UC ) on clinical outcomes in chronic symptomatic heart failure . BACKGROUND Initial trial results suggest titration of therapy guided by serial plasma B-type natriuretic peptide levels improves outcomes in patients with chronic heart failure , but the concept has not received widespread acceptance . Accordingly , we conducted a longer-term study comparing the effects of NT-proBNP-guided therapy with those of intensive clinical management and with UC of patients with heart failure . METHODS Three hundred sixty-four patients admitted to a single hospital with heart failure were r and omly allocated 1:1:1 ( stratified by age ) to therapy guided by NT-proBNP levels or by intensive clinical management , or according to UC . Treatment strategies were applied for 2 years with follow-up to 3 years . RESULTS One-year mortality was less in both the hormone- ( 9.1 % ) and clinical ly-guided ( 9.1 % ) groups compared with UC ( 18.9 % ; p = 0.03 ) . Three-year mortality was selectively reduced in patients < or=75 years of age receiving hormone-guided treatment ( 15.5 % ) compared with their peers receiving either clinical ly managed treatment ( 30.9 % ; p = 0.048 ) or UC ( 31.3 % ; p = 0.021 ) . CONCLUSIONS Intensive management of chronic heart failure improves 1-year mortality compared with UC . Compared with clinical ly guided treatment and UC , hormone-guided treatment selectively improves longer-term mortality in patients < or=75 years of age . ( NT-proBNP-Assisted Treatment To Lessen Serial Cardiac Readmissions and Death [ BATTLESCARRED ] ; Australian New Zeal and Clinical Trials Registry 12605000735651 ) OBJECTIVES The aim of this multicenter study was to evaluate the prognostic impact of a therapeutic strategy using plasma brain natriuretic peptide ( BNP ) levels . BACKGROUND The prognosis of chronic heart failure ( CHF ) remains poor , even among patients treated in specialized departments . METHODS A total of 220 New York Heart Association functional class II to III patients considered optimally treated with angiotensin-converting enzyme inhibitors ( ACEIs ) , beta-blockers , and diuretics by CHF specialists were r and omized to medical treatment according to either current guidelines ( clinical group ) or a goal of decreasing BNP plasma levels < 100 pg/ml ( BNP group ) . Outpatient visits were scheduled every month for 3 months , then every 3 months . The primary combined end point was CHF-related death or hospital stay for CHF . RESULTS Both groups were similar for baseline clinical and biological characteristics . Left ventricular ejection fraction was slightly lower in the BNP group than in the clinical group ( 29.9 + /- 7.7 % vs. 31.8 + /- 8.4 % , p = 0.05 ) . At the end of the first 3 months , all types of drugs were changed more frequently in the BNP group . Mean dosages of ACEIs and beta-blockers were significantly higher in the BNP group ( p < 0.05 ) , whereas the mean increase in furosemide dosage was similar in both groups . During follow-up ( median 15 months ) , significantly fewer patients reached the combined end point in the BNP group ( 24 % vs. 52 % , p < 0.001 ) . CONCLUSIONS In optimally treated CHF patients , a BNP-guided strategy reduced the risk of CHF-related death or hospital stay for CHF . The result was mainly obtained through an increase in ACEI and beta-blocker dosages Although previous studies have documented adherence with certain established heart failure ( HF ) quality metrics in outpatient cardiology practice s , the extent to which there is conformity with other evidence -based , guideline -driven quality metrics in out patients with HF is unknown . IMPROVE HF is a prospect i ve cohort study design ed to characterize the current management of patients with chronic HF and left ventricular ejection fraction < or=35 % in outpatient cardiology practice s. We evaluated baseline data for conformity with adjunctive HF therapies including pneumococcal vaccinization , hydralazine/isosorbide dinitrate ( HYD/ISDN ) for Black patients , statin therapy , antiplatelet therapy , smoking-cessation counseling , low-density lipoprotein cholesterol levels ( < 100 mg/dl ) , and systolic blood pressure decrease ( all patients < 140 mm Hg or [ optimal ] < 130 mm Hg ) . Baseline data were available for 15,381 patients attending 167 cardiology practice s. Patient characteristics included a median age 70 years , 71.0 % men , 9.1 % Black patients , 65.2 % with ischemic HF cause , and 61.7 % with a history of hypertension . Mean adherences or documentations of adherence were only 7.3 % for HYD/ISDN and 1.0 % for pneumococcal vaccination . Adherence to other adjunctive therapies ranged from 27.4 % to 82.0 % but none of the adjunctive treatment interventions were associated with high levels of adherence . Conformity with guideline -recommended , adjunctive HF therapies is deficient in the management of out patients with HF . Critical gaps in documentation or delivery of care exist , especially for the use of pneumococcal vaccination and HYD/ISDN . In conclusion , improved processes of care , better documentation , and /or increased measures to promote adherence to all primary and adjunctive therapies for HF are needed OBJECTIVES This study was design ed to investigate whether the addition of N-terminal pro-B-type natriuretic peptide-guided , intensive patient management ( BM ) to multidisciplinary care ( MC ) improves outcome in patients following hospitalization due to heart failure ( HF ) . BACKGROUND Patients hospitalized due to HF experience frequent rehospitalizations and high mortality . METHODS Patients hospitalized due to HF were r and omized to BM , MC , or usual care ( UC ) . Multidisciplinary care included 2 consultations from an HF specialist who provided therapeutic recommendations and home care by a specialized HF nurse . In addition , BM included intensified up-titration of medication by HF specialists in high-risk patients . NT-proBNP was used to define the level of risk and to monitor wall stress . This monitoring allowed for anticipation of cardiac decompensation and adjustment of medication in advance . RESULTS A total of 278 patients were r and omized in 8 Viennese hospitals . After 12 months , the BM group had the highest proportion of antineurohormonal triple-therapy ( difference among all groups ) . Accordingly , BM reduced days of HF hospitalization ( 488 days ) compared with the hospitalization for the MC ( 1,254 days ) and UC ( 1,588 days ) groups ( p < 0.0001 ; significant differences among all groups ) . Using Kaplan-Meier analysis , the first HF rehospitalization ( 28 % ) was lower in the BM versus MC groups ( 40 % ; p = 0.06 ) and the MC versus UC groups ( 61 % ; p = 0.01 ) . Moreover , the combined end point of death or HF rehospitalization was lower in the BM ( 37 % ) than in the MC group ( 50 % ; p < 0.05 ) and in the MC than in the UC group ( 65 % ; p = 0.04 ) . Death rate was similar between the BM ( 22 % ) and MC groups ( 22 % ) , but was lower compared with the UC group ( 39 % ; vs. BM : p < 0.02 ; vs. MC : p < 0.02 ) . CONCLUSIONS Compared with MC alone , additional BM improves clinical outcome in patients after HF hospitalization . ( BNP Guided Care in Addition to Multidisciplinary Care ; NCT00355017 ) Background —Brain natriuretic peptide ( BNP ) and norepinephrine ( NE ) are strongly related to severity of and are independent predictors of outcome in heart failure . The long-term effects of angiotensin receptor blockers on BNP and NE in heart failure patients are not known . Methods and Results —Both BNP and NE were measured in 4284 patients r and omized to valsartan or placebo in the Valsartan Heart Failure Trial ( Val-HeFT ) at baseline and 4 , 12 , and 24 months after r and omization . The effects of valsartan were tested by ANCOVA , controlling for baseline values and concomitant ACE inhibitors and /or & bgr;-blockers . BNP and NE concentrations were similar at baseline in the 2 groups and were decreased by valsartan starting at 4 months and up to 24 months . BNP increased over time in the placebo group . At the end point , least-squares mean ( ±SEM ) BNP increased from baseline by 23±5 pg/mL in the placebo group ( n=1979 ) but decreased by 21±5 pg/mL ( n=1940 ) in the valsartan group ( P < 0.0001 ) . NE increased by 41±6 pg/mL ( n=1979 ) and 12±6 pg/mL ( n=1941 ) for placebo and valsartan , respectively ( P = 0.0003 ) . Concomitant therapy with both ACE inhibitors and & bgr;-blockers significantly reduced the effect of valsartan on BNP but not on NE ( P for interaction=0.0223 and 0.2289 , respectively ) . Conclusions —In Val-HeFT , the largest neurohormone study in patients with symptomatic chronic heart failure , BNP and NE rose over time in the placebo group . Valsartan caused sustained reduction in BNP and attenuated the increase in NE over the course of the study . These neurohormone effects of valsartan are consistent with the clinical benefits reported in Val-HeFT BACKGROUND STARBRITE , a multicenter r and omized pilot trial , tested whether outpatient diuretic management guided by B-type natriuretic peptide ( BNP ) and clinical assessment result ed in more days alive and not hospitalized over 90 days compared with clinical assessment alone . METHODS AND RESULTS A total of 130 patients from 3 sites with left ventricular ejection fraction ≤35 % were enrolled during hospitalization for heart failure ( HF ) and r and omly assigned to therapy guided by BNP and clinical assessment ( BNP strategy ) or clinical assessment alone . The clinical goal was resolution of congestion without hypotension or renal dysfunction . In the BNP arm , therapy was adjusted to achieve optimal fluid status , defined as the BNP level and congestion score obtained at the time of discharge . In the clinical assessment arm , therapy was titrated to achieve optimal fluid status , represented by the patient 's signs and symptoms at the time of discharge . Exclusion criteria were serum creatinine > 3.5 mg/dL and acute coronary syndrome . Follow-up was done in HF clinics . BNP was measured with the use of a rapid assay test . There was no significant difference in number of days alive and not hospitalized ( hazard ratio 0.72 , 95 % confidence interval 0.41 - 1.27 ; P = .25 ) , change in serum creatinine , or change in systolic blood pressure ( SBP ) . BNP strategy was associated with a trend toward a lower blood urea nitrogen ( 24 mg/dL vs 29 mg/dL ; P = .07 ) ; BNP strategy patients received significantly more angiotensin-converting enzyme ( ACE ) inhibitors , beta-blockers , and the combination of ACE inhibitor or angiotensin receptor blocker plus beta-blockers . CONCLUSIONS BNP strategy was not associated with more days alive and not hospitalized , but the strategy appeared to be safe and was associated with increased use of evidence -based medications BACKGROUND Angiotensin-converting enzyme ( ACE ) inhibitors are established as first-line therapy in chronic heart failure ( CHF ) . However , conflicting results exist regarding the dose-effect relation of ACE inhibitors . METHODS We investigated 45 patients ( age 55 + /- 10 years ) with stable CHF who presented with a maintenance dosage of enalapril of either 5 mg given twice daily ( E10 ; n = 16 ) , 10 mg given twice daily ( E20 ; n = 18 ) , or 20 mg given twice daily ( E40 ; n = 11 ) . This dosage was changed 3 times to treat all patients with lower , higher , and the initial dosages for 4 weeks each . Neurohormones ( atrial natriuretic peptide [ ANP ] , brain natriuretic peptide [ BNP ] , and norepinephrine ) and enalaprilat trough levels were measured , and ergospirometry was performed . RESULTS Changes in enalapril dose and enalaprilat level were concordant in 82 % of patients , indicating good compliance . After augmentation of enalapril to 40 mg daily , patients in the E10 group showed an increase in maximal oxygen consumption and a decrease in neurohormonal stimulation , whereas the opposite changes were observed after reduction of enalapril to 10 mg daily in patients in the E20 and E40 groups ( maximal oxygen consumption : Delta1.1 + /- 2.0 vs -1.0 + /- 1.9 mL. kg(-1 ) . min(-1 ) , P < .01 ; ANP : Delta-63 + /- 106 vs 19 + /- 54 pg/mL , P < .01 ; BNP : Delta-62 + /- 104 vs 18 + /- 89 pg/mL , P < .05 ; norepinephrine : Delta-1.3 + /- 2.9 vs 0.6 + /- 1.8 , P < .05 ) . Within-patient comparison showed that neurohormone levels were higher and exercise capacity lower while patients were receiving 10 mg of enalapril per day than when they were receiving 40 mg per day ( ANP : 172 + /- 148 vs 139 + /- 122 pg/mL , P < .01 ; BNP : 193 + /- 244 vs 152 + /- 225 pg/mL , P < .005 ; norepinephrine : 4.2 + /- 2.2 vs 3.5 + /- 1 . 6 nmol/L , P < .05 ; maximal oxygen consumption 22.0 + /- 4.4 vs 21.3 + /- 4.3 mL. kg(-1 ) . min(-1 ) P < .05 ) . Similar differences were observed when comparing these variables , and patients had lowest and highest enalaprilat trough levels . CONCLUSIONS High doses of enalapril result ed in an improvement of exercise capacity and reduction of neurohumoral stimulation , whereas these parameters worsened after reduction of enalapril dose . Thus patients with congestive heart failure may benefit from increasing dosage of ACE inhibitors AIMS This study was design ed to evaluate a new NT-proBNP monitoring concept in out patients with systolic heart failure ( HF ) . METHODS AND RESULTS This was a multicentre , prospect i ve r and omized open-label blinded endpoint study . A total of 407 systolic HF patients were allocated to either clinical management ( n = 208 ) or clinical management + NT-proBNP monitoring ( n = 199 ) and followed for 2.5 years . If NT-proBNP increased > 30 % , a clinical checklist was completed and treatment initiated . The patients were matched at r and omization and were 73 years old , 25 % were females , 85 % were NYHA class I-II , LVEF was 30 % , and NT-proBNP 1955 pg/mL. NT-proBNP monitoring did not improve outcome , the hazard ratio for the primary composite endpoint ( death or a cardiovascular admission ) being 0.96 [ 95 % confidence interval ( CI ) 0.71 - 1.29 , P = 0.766 ] . NT-proBNP monitoring did not induce a significant change in the pharmacological strategy ( P > 0.05 for all comparisons ) . In patients in whom NT-proBNP increased > 30 % ( 25 % of the patients ) during follow-up , a higher frequency of admission ( 69 % vs. 47 % , P = 0.002 ) , a higher number of admission days ( 14 vs. 5 days , P = 0.003 ) and number of admissions ( 2 vs. 1 , P = 0.009 ) , and a lower quality of life ( P = 0.032 ) and a poorer functional class ( 37 % vs. 18 % in NYHA class III-IV , P < 0.001 ) were observed . CONCLUSIONS Adding serial measurements of NT-proBNP to optimal clinical management was not associated with a change in pharmacological strategy and did not improve outcome . However , survivors in whom NT-proBNP increased > 30 % showed a poorer functional class , clinical outcome , and quality of life . TRIAL REGISTRATION www.centerwatch : 173491 ( NorthStar ) B-type natriuretic peptide ( BNP ) is a cardiac neurohormone used as a noninvasive tool for diagnosing and monitoring heart failure . Beta blockers have beneficial effects in patients with heart failure as well as a direct effect on BNP plasma levels . The aim of this study is to compare the efficacy of a BNP-guided approach vs. st and ard care on beta-blocker titration in heart failure patients . Forty-one patients with heart failure were r and omized into a clinical trial . Bisoprolol was started , and the dose was regularly up-titrated . BNP was measured monthly . The clinical group had beta-blocker dosage increased according to st and ard care , whereas the BNP group had beta-blocker dosage up-titrated according to plasma BNP levels plus st and ard care . The primary outcome was mean beta-blocker dose achieved after 3 months . BNP levels , left ventricular ejection fraction , clinical score , quality of life , and hospitalization were collected in all patients . BNP-guided up-titration of beta blocker in ambulatory patients with heart failure did not result in higher doses of beta blocker at the end of 3 months+/-SD ( 5.9+/-4.3 mg vs. 4.4+/-3.4 mg , p=0.22 ) . Left ventricular ejection fraction was significantly improved in both groups by 7.3 % ( 95 % confidence interval , 4.1%-10.4 % ; p<0.0001 ) . A trend toward better quality of life was seen in the BNP group BACKGROUND There is currently no objective practical guide to intensity of drug treatment for individuals with heart failure . We hypothesised that pharmacotherapy guided by plasma concentrations of the cardiac peptide aminoterminal brain natriuretic peptide ( N-BNP ) would produce a superior outcome to empirical trial-based therapy dictated by clinical acumen . METHODS 69 patients with impaired systolic function ( left-ventricular ejection fraction < 40 % ) and symptomatic heart failure ( New York Heart Association class II-IV ) were r and omised to receive treatment guided by either plasma N-BNP concentration ( BNP group ) or st and ardised clinical assessment ( clinical group ) . FINDINGS During follow-up ( minimum 6-months , median 9.5 months ) , there were fewer total cardiovascular events ( death , hospital admission , or heart failure decompensation ) in the BNP group than in the clinical group ( 19 vs 54 , p=0.02 ) . At 6 months , 27 % of patients in the BNP group and 53 % in the clinical group had experienced a first cardiovascular event ( p=0.034 ) . Changes in left-ventricular function , quality of life , renal function , and adverse events were similar in both groups . INTERPRETATION N-BNP-guided treatment of heart failure reduced total cardiovascular events , and delayed time to first event compared with intensive clinical ly guided treatment We prospect ively evaluated whether the N-terminal brain natriuretic peptide ( NT-ProBNP ) reduction percentage , during hospitalization for acutely decompensated heart failure ( HF ) , has a prognostic significance in 6-month follow-up . In 120 patients consecutively admitted for acute HF to an internal medicine unit , plasma NT-ProBNP was measured on admission and at discharge . During a 6-month follow-up 52 ( 43.3 % ) patients had events : 9 ( 7.5 % ) died from cardiovascular causes , and 43 ( 35.8 % ) were readmitted for HF . In patients without events , the mean reduction percentage of NT-ProBNP was greater than in patients with events ( 39.5 ± 7.4 versus 26.3 ± 5.9 % ; P = 0.04 ) . In receiver operating characteristic curve analysis , the mean area under the curve for NT-ProBNP reduction percentage was 0.63 ( 95 % CI , 0.51–0.75 ; P = 0.04 ) for the composite end point ( death or readmission ) , and 0.81 ( 95 % CI , 0.65–0.97 , P = 0.01 ) for cardiovascular mortality . NT-ProBNP reduction percentage less than 30 % was the best cut-off for the identification of patients at risk of events . We suggest that in clinical practice the evaluation of change of NT-ProBNP levels during admission is probably more helpful than predischarge NT-ProBNP absolute value AIMS Treatment of chronic heart failure ( CHF ) guided by natriuretic peptides has been studied in clinical trials with conflicting results . The aim of this study was to investigate if N-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided therapy in symptomatic heart failure patients in primary care would improve clinical outcomes over and above treatment according to guidelines . METHODS AND RESULTS SIGNAL-HF was a 9 month , r and omized , single-blind , parallel group study in patients with CHF in NYHA class II-IV , ejection fraction (EF)<50 % and elevated NT-proBNP levels ( males>800 , females>1000 ng/L ) . All investigators underwent a pre- study educational programme about current CHF guidelines . A control group managed by non-trained investigators was considered not possible for ethical and practical reasons . Patients were r and omized to structured treatment of CHF according to guidelines with or without NT-proBNP monitoring . The choice and dose of therapy for CHF was at the investigator 's discretion . The primary outcome variable was the composite endpoint of days alive , days out of hospital , and symptom score from the Kansas City Cardiomyopathy Question naire . In all , 252 patients were r and omized . The allocation groups were well balanced with regards to age , NT-proBNP , and EF . Treatment doses of beta-blockers and blockers of the renin-angiotensin-aldosterone system were markedly increased towards target doses and to a similar degree in both groups . There were no differences between the groups concerning either the primary endpoint ( P=0.28 ) or its components [ cardiovascular ( CV ) death , P=0.93 ; CV hospitalization , P=0.88 ; or symptom score , P=0.28 ] . CONCLUSION NT-proBNP-guided CHF treatment did not result in important improvements in clinical outcomes in patients with CHF in primary care above and beyond what could be achieved by education and structured CHF treatment according to guidelines AIMS To assess the effects of an NT-proBNP-guided medical management on 18-month outcomes in patients with heart failure ( HF ) and preserved LVEF ( HFpEF ) . METHODS AND RESULTS Patients with HFpEF ( LVEF > 45 % ; n = 123 ) and HF with reduced LVEF ( HFrEF ; LVEF ≤45 % ; n = 499 ) with age ≥60 years , NYHA class ≥ II , and elevated NT-proBNP ( > 400 ng/L or > 800 ng/L depending on age ) were r and omized to medical therapy titrated only to reduce symptoms to NYHA ≤II ( symptom-guided ) or also to reduce NT-proBNP below the inclusion threshold ( NT-proBNP-guided ) during a 6-month period . Patients were followed for an additional 12 months . Despite similar treatment escalation , NT-proBNP reduction and symptom relief were less in HFpEF than in HFrEF . Hospitalization-free survival at 18 months was worse in HFpEF than in HFrEF ( P = 0.02 ) , while survival and HF hospitalization-free survival did not differ . Among HFpEF patients , NT-proBNP reduction and symptom relief were similar in the symptom-guided ( n = 59 ) and NT-proBNP-guided ( n = 64 ) group despite more aggressive treatment in the NT-proBNP-guided group . In contrast to effects in HFrEF , NT-proBNP-guided management tended to worsen 18-month outcomes in HFpEF , with P-values for the interactions between LVEF stratum and management strategy of 0.2 for hospitalization-free survival , 0.03 for survival , and 0.01 for HF hospitalization-free survival . CONCLUSIONS Outcomes in HFpEF were not better than in HFrEF , and opposite effects of NT-proBNP-guided management were observed in HFpEF compared with HFrEF . These preliminary findings suggest that , in contrast to HFrEF , NT-proBNP-guided therapy may not be beneficial in HFpEF . Trial registration IS RCT N43596477 OBJECTIVES The purpose of this study was to assess whether management of heart failure ( HF ) guided by an individualized N-terminal pro-B-type natriuretic peptide ( NT-proBNP ) target would lead to improved outcome compared with HF management guided by clinical assessment alone . BACKGROUND Natriuretic peptides may be attractive biomarkers to guide management of heart failure ( HF ) and help select patients in need of more aggressive therapy . The PRIMA ( Can PRo-brain-natriuretic peptide guided therapy of chronic heart failure IMprove heart fAilure morbidity and mortality ? ) study is , to our knowledge , the first large , prospect i ve r and omized study to address whether management of HF guided by an individualized target NT-proBNP level improves outcome . METHODS A total of 345 patients hospitalized for decompensated , symptomatic HF with elevated NT-proBNP levels at admission were included . After discharge , patients were r and omized to either clinical ly-guided outpatient management ( n = 171 ) , or management guided by an individually set NT-proBNP ( n = 174 ) defined by the lowest level at discharge or 2 weeks thereafter . The primary end point was defined as number of days alive outside the hospital after index admission . RESULTS HF management guided by this individualized NT-proBNP target increased the use of HF medication ( p = 0.006 ) , and 64 % of HF-related events were preceded by an increase in NT-proBNP . Nevertheless , HF management guided by this individualized NT-proBNP target did not significantly improve the primary end point ( 685 vs. 664 days , p = 0.49 ) , nor did it significantly improve any of the secondary end points . In the NT-proBNP-guided group mortality was lower , as 46 patients died ( 26.5 % ) versus 57 ( 33.3 % ) in the clinical ly-guided group , but this was not statistically significant ( p = 0.206 ) . CONCLUSIONS Serial NT-proBNP measurement and targeting to an individual NT-proBNP value did result in advanced detection of HF-related events and importantly influenced HF-therapy , but failed to provide significant clinical improvement in terms of mortality and morbidity . ( Effect of NT-proBNP Guided Treatment of Chronic Heart Failure [ PRIMA ] ; NCT00149422 ) |
808 | 19,846,082 | Analysis of national survey data showed higher prevalences among men aged 55 years and older than for women of the same age .
Prevalences were highest for people aged 70 to 79 years .
Prevalence estimates from the United States indicate that a considerable and increasing proportion of the population at risk has had at least 1 colonoscopy or sigmoidoscopy in their lives , although differences between age and sex groups persist . | BACKGROUND Lower GI endoscopy , such as colonoscopy or sigmoidoscopy , is thought to have a substantial impact on colorectal cancer incidence and mortality through detection and removal of precancerous lesions and early cancers .
We aim ed to review prevalence estimates of history of colonoscopy or sigmoidoscopy in the general population and to analyze recent trends . | Despite recent declines in both incidence and mortality ( 1 ) , colorectal cancer remains the second most common cause of death from cancer in the United States ( 2 ) . Screening for colorectal cancer reduces mortality by allowing physicians to detect cancer at earlier , more treatable stages , as well as to identify and remove adenomatous polyps ( asymptomatic benign precursor lesions that may lead to colorectal cancer ) . Many tests are available for screening , such as fecal occult blood tests ( FOBTs ) , flexible sigmoidoscopy , and colonoscopy . Screening with FOBT ( Hemoccult II , Beckman Coulter , Fullerton , California ) has been shown to reduce colorectal cancer mortality by 15 % to 33 % in r and omized , controlled trials ( 35 ) , and screening with more sensitive FOBTs , flexible sigmoidoscopy , colonoscopy , or combinations of these tests may reduce the burden of colorectal cancer even more ( 6 , 7 ) . In the absence of adequate clinical trial data on several recommended screening strategies , microsimulation modeling can provide guidance on the risks , benefits , and testing re sources required for different screening strategies to reduce the burden of colorectal cancer . In July 2002 , the U.S. Preventive Services Task Force ( USPSTF ) concluded that there was sufficient evidence to recommend strongly that all average-risk adults 50 years of age or older should be offered colorectal cancer screening ( 8) . However , the logistics of screening , such as the type of screening test , screening interval , and age at which to stop screening , were not evaluated in terms of the balance of benefits and potential harms . The USPSTF has again addressed recommendations for colorectal cancer screening with a systematic review of the evidence ( 9 ) on screening tests . For this assessment , the USPSTF requested a decision analysis to project expected outcomes of various strategies for colorectal cancer screening . Two independent microsimulation modeling groups from the Cancer Intervention and Surveillance Modeling Network ( CISNET ) , funded by the National Cancer Institute , used a comparative modeling approach to compare life-years gained relative to re source use of different strategies for colorectal cancer screening . Methods We used 2 microsimulation models , MISCAN ( MIcrosimulation Screening Analysis ) ( 1012 ) and SimCRC ( Simulation Model of Colorectal Cancer ) ( 13 ) , to estimate the life-years gained relative to no screening and the colonoscopies required ( that is , an indicator for re source use and risk for complications ) for different colorectal cancer screening strategies defined by test , age at which to begin screening , age at which to stop screening , and screening interval . We aim ed to identify a set of recommendable strategies with similar clinical benefit and an efficient use of colonoscopy re sources . Using 2 models ( that is , a comparative modeling approach ) adds credibility to the results and serves as a sensitivity analysis on the underlying structural assumptions of the models , particularly pertaining to the unobservable natural history of colorectal cancer . Microsimulation Models The Appendix describes the MISCAN and SimCRC models , and st and ardized model profiles are available at cisnet.cancer.gov/profiles/. In brief , both models simulate the life histories of a large population of individuals from birth to death . As each individual ages , there is a chance that an adenoma will develop . One or more adenomas can occur in an individual , and each adenoma can independently develop into pre clinical ( that is , undiagnosed ) colorectal cancer ( Figure 1 ) . The risk for developing an adenoma depends on age , sex , and baseline individual risk . The models track the location and size of each adenoma ; these characteristics influence disease progression and the chance that the adenoma will be found by screening . The size of adenomas can progress from small ( 5 mm ) to medium ( 6 to 9 mm ) to large ( 10 mm ) . Some adenomas eventually become malignant , transforming to stage I pre clinical cancer . Pre clinical cancer has a chance of progressing through stages I to IV and may be diagnosed by symptoms at any stage . Survivorship after diagnosis depends on the stage of disease . Figure 1 . Natural history of disease as modeled by the Microsimulation Screening Analysis and Simulation Model of Colorectal Cancer models . The opportunity to intervene in the natural history through screening is noted . The natural history component of each model was calibrated to 19751979 clinical incidence data ( 14 ) and adenoma prevalence from autopsy studies in the same period ( 1524 ) . We used this period because incidence rates and adenoma prevalence had not yet been affected by screening . We corrected the adenoma prevalence for studies of non-U.S. population s by using st and ardized colorectal cancer incidence ratios . The models use all-cause mortality estimates from the U.S. life tables and stage-specific data on colorectal cancer survival from the 19961999 Surveillance , Epidemiology , and End Results program ( 14 ) . Table 1 compares outcomes from the natural history components of the models . Table 1 . Comparison of the Natural History Outcomes from the Microsimulation Screening Analysis ( MISCAN ) and Simulation Model of Colorectal Cancer ( SimCRC ) Models The effectiveness of a screening strategy is modeled through a test 's ability to detect lesions ( that is , adenomas or pre clinical cancer ) . Once screening is introduced , a simulated person who has an underlying lesion has a chance of having it detected during a screening round depending on the sensitivity of the test for that lesion and whether the lesion is within the reach of the test . Screened persons without an underlying lesion can have a false-positive test result and undergo unnecessary follow-up colonoscopy . Hyperplastic polyps are not modeled explicitly , but their detection is reflected in the specificity of the screening tests . The models incorporate the risk for fatal complications associated with perforation during colonoscopy . Both models have been vali date d against the long-term reductions in incidence and mortality of colorectal cancer with annual FOBT reported in the Minnesota Colon Cancer Control Study ( 3 , 25 , 26 ) and show good concordance with the trial results . Strategies for Colorectal Cancer Screening In consultation with the USPSTF , we included the following basic strategies : 1 ) no screening , 2 ) colonoscopy , 3 ) FOBT ( Hemoccult II , Hemoccult SENSA [ Beckman Coulter ] , or fecal immunochemical testing ) , 4 ) flexible sigmoidoscopy ( with biopsy ) , and 5 ) flexible sigmoidoscopy combined with Hemoccult SENSA . For each basic strategy , we evaluated start ages of 40 , 50 , and 60 years and stop ages of 75 and 85 years . For the FOBT strategies , we considered screening intervals of 1 , 2 , and 3 years , and for the sigmoidoscopy and colonoscopy strategies , we considered intervals of 5 , 10 , and 20 years . These variations result ed in 145 strategies : 90 single-test strategies , 54 combination-test strategies , and 1 no-screening strategy . The stop age reflects the oldest possible age at which to screen , but the actual stopping age is dictated by the start age and screening interval . In the base case , we assumed 100 % adherence for screening tests , follow-up of positive findings , and surveillance of persons found to have adenomas . Individuals with a positive FOBT result or with an adenoma detected by sigmoidoscopy were referred for follow-up colonoscopy . For years in which both tests were due for the combined strategy , the FOBT was performed first ; if the result was positive , the patient was referred for follow-up colonoscopy . In those years , flexible sigmoidoscopy was done only for patients with a negative FOBT result . If findings on follow-up colonoscopy were negative , the individual was assumed to undergo subsequent screening with colonoscopy with a 10-year interval ( as long as results of the repeated colonoscopy were negative ) and did not return to the initial screening schedule , as is the recommendation of the U.S. Multi-Society Task Force and American Cancer Society ( 7 , 27 ) . All individuals with an adenoma detected were followed with colonoscopy surveillance per the Multi-Society guidelines ( 27 , 28 ) . The surveillance interval depended on the number and size of the adenomas detected on the last colonoscopy ; it ranged from 3 to 5 years and was assumed to continue for the remainder of the person 's lifetime . We estimated the test characteristics of colorectal cancer screening from a review of the available literature ( Table 2 ) ( 29 ) . We conducted this review independently of and parallel in time with the systematic evidence review performed for the USPSTF ( 9 ) . Table 2 . Test Characteristics Used in the Microsimulation Screening Analysis and Simulation Model of Colorectal Cancer Models Evaluation of Outcomes Determination of Efficient Strategies The most effective strategy was defined as the one with the greatest life-years gained relative to no screening . However , it is important to consider the relative intensity of test use required to achieve those gains . The more effective strategies tended to be associated with more colonoscopies on average in a person 's lifetime , which translated into an increased risk for colonoscopy-related complications . We used an approach that mirrors that of cost-effectiveness analysis ( 30 ) to identify the set of efficient , or dominant , strategies within each test category . A strategy was considered dominant when no other strategy or combination of strategies provided more life-years with the same number of colonoscopies . We conducted this analysis separately for each of the 5 basic screening strategies because the number of noncolonoscopy tests differed by strategy . We then ranked the efficient screening strategies by increasing effectiveness and calculated the incremental number of colonoscopies ( COL ) per 1000 , the incremental life-years gained ( LYG ) per 1000 , and the incremental number of colonoscopies necessary to achieve 1 year of life ( Objective : This is the first study to evaluate the association between colonic screening and colorectal cancer risk among Canadians . Methods : A case – control study was conducted . Cases were diagnosed with cancer of the colorectum , between 1997 and 2000 , aged 20 to 74 years , identified through the population -based Ontario Cancer Registry and recruited by the Ontario Familial Colorectal Cancer Registry . Controls were a sex- and age-matched r and om sample of the population of Ontario . 971 cases and 1944 controls completed question naires ( including colorectal screening history and many risk factors ) . Multivariate logistic regression analysis was used to obtain adjusted odds ratios ( OR ) estimates . Results : Having had a fecal occult blood screen was associated with reduced colorectal cancer risk ( OR=0.76 ; 95 % confidence interval ( CI ) : 0.59 , 0.97 ) . Having had a screening sigmoidoscopy was associated with a halving of colorectal cancer risk ( OR = 0.52 ; 95 % CI : 0.34 , 0.80 ) . Having had a screening colonoscopy did not significantly reduce colorectal cancer risk ( OR = 0.69 ; 95 % CI : 0.44 , 1.07 ) ; however , having had either screening endoscopy was associated with a significant reduction in colorectal cancer risk ( OR = 0.62 ; 95 % CI : 0.44 , 0.87 ) . Findings differed slightly by anatomic sub-site ( proximal and distal colorectum ) . Conclusions : We report a reduction in colorectal cancer risk among persons who underwent colorectal cancer screening ; in particular , sigmoidoscopy . Findings are of great importance for the prevention of colorectal cancer OBJECTIVES We compared the effectiveness of a telephone outreach approach versus a direct mail approach in improving rates of colorectal cancer ( CRC ) screening in a predominantly Black population . METHODS A r and omized trial was conducted between 2000 and 2003 that followed 456 participants in the New York metropolitan area who had not had recent CRC screening . The intervention group received tailored telephone outreach , and the control group received mailed printed material s. The primary outcome was medically documented CRC screening 6 months or less after r and omization . RESULTS CRC screening was documented in 61 of 226 ( 27.0 % ) intervention participants and in 14 of 230 ( 6.1 % ) controls ( prevalence rate difference=20.9 % ; 95 % CI = 14.34 , 27.46 ) . Compared with the control group , the intervention group was 4.4 times more likely to receive CRC screening within 6 months of r and omization . CONCLUSIONS Tailored telephone outreach can increase CRC screening in an urban minority population BACKGROUND : National guidelines recommending colorectal cancer ( CRC ) screening for average risk Canadians were released in 2001 . The current study determined rates of CRC screening and predictors of screening 3 yr after the guidelines were released . METHOD : A population -based r and om digit dial telephone survey of 1,808 Alberta men and women aged 50–74 yr assessed awareness about , and self-reported rates of , screening . RESULTS : More average risk women than men reported a recent screening with a home fecal occult blood test ( FOBT ) ( 14.0 % vs 9.8 % , P = 0.013 ) but men had slightly higher rates of screening endoscopy in the past 5 yr ( 4.3 % vs 1.6 % , P = 0.003 ) . Overall , only 14.3 % of average risk adults ( N = 1,476 ) were up-to- date on CRC screening . Multivariable predictors of being up-to- date on CRC screening differed for men and women although a doctor 's recommendation for screening was a strong predictor for both genders ( men OR 5.0 , 2.9–8.3 , women OR 3.8 , 2.3–6.5 ) . Screening for other cancers was also an important predictor in both men and women . CONCLUSION : Three years after the release of national guidelines , rates of screening among average risk adults aged 50–74 yr were very low . Public education programs and primary care interventions to specifically invite average risk adults for screening may be required to increase CRC screening rates Valid and reliable self-report measures of cancer screening behaviors are important for evaluating efforts to improve adherence to guidelines . We evaluated test-retest reliability and validity of self-report of the fecal occult blood test ( FOBT ) , sigmoidoscopy ( SIG ) , colonoscopy ( COL ) , and barium enema ( BE ) using the National Cancer Institute colorectal cancer screening ( CRCS ) question naire . A secondary objective was to evaluate reliability and validity by mail , telephone , and face-to-face survey administration modes . Consenting men and women , 51 to 74 years old , receiving care at a multispecialty clinic for at least 5 years who had not been diagnosed with colorectal cancer were stratified by prior CRCS status and r and omized to survey mode ( n = 857 ) . Within survey mode , respondents were r and omized to complete a second survey at 2 weeks , 3 months , or 6 months . Comparing self-report with administrative and medical records , concordance estimates were 0.91 for COL , 0.85 for FOBT , 0.85 for SIG , and 0.92 for BE . Overall sensitivity estimates were 0.91 for COL , 0.82 for FOBT , 0.76 for SIG , and 0.56 for BE . Specificity estimates were 0.91 for COL , 0.86 for FOBT , 0.89 for SIG , and 0.97 for BE . Sensitivity and specificity varied little by survey mode for any test . Report-to-records ratio showed overreporting for SIG ( 1.1 ) , COL ( 1.15 ) , and FOBT ( 1.57 ) , and underreporting for BE ( 0.82 ) . Reliability at all time intervals was highest for COL ; there was no consistent pattern according to survey mode . This study provides evidence to support the use of the National Cancer Institute CRCS question naire to assess self-report with any of the three survey modes . ( Cancer Epidemiol Biomarkers Prev 2008;17(4):758–67 OBJECTIVES : Socioeconomic status is explored as a predictor of differences between Hispanics and non-Hispanic Whites in cancer prevention behavior . METHODS : In a cross-sectional study , in-person interviews ( n = 1795 ) were conducted in a population -based r and om sample of adults in 20 communities with a high proportion of Hispanics . RESULTS : Hispanics were significantly less likely than non-Hispanic Whites to ever have had cervical ( p < 0.001 ) , breast ( p = 0.007 ) , or colorectal cancer ( FOBT p = 0.008 ; sigmoidoscopy/colonoscopy p < 0.002 ) screening . After adjusting for socioeconomic status ( education and having health insurance ) , only differences in cervical cancer remained significant ( p = 0.024 ) . After adjusting for socioeconomic status , Hispanics had a significantly higher intake of fruits and vegetables per day ( 4.84 servings ) than non-Hispanic Whites ( 3.84 servings ) ( p < 0.001 ) ; and fat behavior score was marginally significant after adjustment for socioeconomic status ( p = 0.053 ) . Significantly fewer Hispanics were current smokers than non-Hispanic Whites ( p < 0.001 ) . CONCLUSIONS : There is only limited support for the hypothesis that socioeconomic status is a major determinant of some cancer-related behaviors ; specifically , socioeconomic status is related to mammography and colorectal screening , but not cervical cancer , dietary behavior , or smoking Although colorectal cancer ( CRC ) is the second leading cause of cancer death in the U.S. , screening rates are low . Underst and ing the predictors of CRC screening is needed . In 2003 , a r and om sample of patients aged 50 and over from three inner-city health centers was surveyed by computer-assisted telephone interview concerning CRC screening . The question naire was based on the Transtheoretical Model and the Theory of Reasoned Action . Factor analysis with Varimax rotation and logistic regression analyses were conducted . Of 319 surveys with data about endoscopy , 148 ( 46 % ) met guidelines ( 19 reported sigmoidoscopy within 5 years , 105 reported colonoscopy within 10 years , and 24 reported both within 5 years ) . Factor analysis identified three factors associated with increased likelihood of lower endoscopy within guidelines : Social Influence for CRC Screening ( Eigenvalue 1.73 ) , Barriers to Lower Endoscopy ( Eigenvalue 2.00 ) , and Lower Endoscopy Benefit/Ease ( Eigenvalue 1.19 ) . Variables in logistic regression associated with a lower rate of endoscopy include being African American ( Odds Ratio ( OR ) = 0.35 , 95 % confidence interval = 0.13–0.96 ) , being a current smoker ( OR = 0.13 , CI = 0.03–0.60 ) , and having a higher score on the Barriers to Lower Endoscopy factor ( i.e. , viewed the inconvenience and unpleasant aspects as more troubling , OR = 0.33 , CI = 0.18–0.60 ) . The perceived inconvenience and unpleasant aspects of lower endoscopy are substantial barriers to screening . Advances in colon preparation procedures and better educational campaigns might lessen this perceived barrier and may be particularly important in disadvantaged and African American communities Background Colorectal cancer ( CRC ) is the second most commonly diagnosed cancer for both sexes in developed countries . This study assessed the knowledge , attitudes , and preventive practice s regarding CRC of adults in Italy . Methods A r and om sample of 1165 adults received a self-administered question naire on socio-demographic characteristics ; knowledge regarding definition , risk factors , and screening ; attitudes regarding perceived risk of contracting CRC and utility of screening tests ; health-related behaviors and health care use ; source of information . Results Only 18.5 % knew the two main modifiable risk factors ( low physical activity , high caloric intake from fat ) and this knowledge was significantly associated with higher educational level , performing physical activity , modification of dietary habits and physical activity for fear of contracting CRC , and lower risk perception of contracting CRC . Half of respondents identified fecal occult blood testing ( FOBT ) as main test for CRC prevention and were more knowledgeable those unmarried , more educated , who knew the main risk factors of CRC , and have received advice by physician of performing FOBT . Personal opinion that screening is useful for CRC prevention was high with a mean score of 8.3 and it was predicted by respondents ' lower education , beliefs that CRC can be prevented , higher personal perceived risk of contracting CRC , and information received by physician about CRC . An appropriate behavior of performing FOBT if eligible or not performing if not eligible was significantly higher in female , younger , more educated , in those who have been recommended by physician for undergo or not undergo FOBT , and who have not personal history of precancerous lesions and familial history of precancerous lesions or CRC . Conclusion Linkages between health care and educational systems are needed to improve the levels of knowledge and to raise CRC screening adherence BACKGROUND Although colorectal cancer screening by using a fecal occult blood test ( FOBT ) , flexible sigmoidoscopy , colonoscopy , or barium enema x-ray reduces the incidence of and death from colorectal cancer , the rate of colorectal cancer screening in the general population is low . We conducted a r and omized trial consisting of direct mailing of FOBT kits to increase colorectal cancer screening among residents of Wright County , Minnesota , a community in which colorectal cancer screening was promoted . METHODS At baseline , we mailed a question naire about colorectal cancer screening to a r and om sample of Wright County residents aged 50 years or older who were r and omly selected from the Minnesota State Driver 's License and Identification Card data base ( estimated N = 1451 ) . The sample was r and omly allocated into three equal subgroups : one group ( control ) received only the question naire , one group received FOBT kits by direct mail with reminders , and one group received FOBT kits by direct mail without reminders . Study participants were sent a follow-up question naire 1 year after baseline . We used the responses to the question naires to estimate the 1-year change in self-reported screening rates in each group and the differences in the changes among the groups , along with the associated bootstrap 95 % confidence intervals ( CIs ) . RESULTS At baseline , the estimated response rate was 86.5 % , self-reported adherence to FOBT guidelines was 21.5 % , and overall adherence to any colorectal cancer screening test guidelines was 55.8 % . The 1-year rate changes in absolute percentage for self-reported adherence to FOBT use were 1.5 % ( 95 % CI = -2.9 % to 5.9 % ) for the control group , 16.9 % ( 95 % CI = 11.5 % to 22.3 % ) for the direct-mail-FOBT-with-no-reminders group , and 23.2 % ( 95 % CI = 17.2 % to 29.3 % ) for the direct-mail-FOBT-with-reminders group . The 1-year rate changes for self-reported adherence to any colorectal cancer screening test were 7.8 % ( 95 % CI = 3.2 % to 12.0 % ) for the control group , 13.2 % ( 95 % CI = 8.4 % to 18.2 % ) for the direct-mail-FOBT-with-no-reminders group , and 14.1 % ( 95 % CI = 9.1 % to 19.1 % ) for the direct-mail-FOBT-with-reminders group . CONCLUSION Direct mailing of FOBT kits combined with follow-up reminders promotes more rapid increases in the use of FOBT and nearly doubles the increase in overall rate of adherence to colorectal cancer screening guidelines in a general population compared with a community-wide screening promotion and awareness campaign OBJECTIVES : The goals of this study were to compare women and men 's underst and ing of screening flexible sigmoidoscopy ( FS ) and to identify predictors of endoscopic colorectal cancer ( CRC ) screening . METHODS : We mailed a 36-item question naire to asymptomatic patients aged 50 years or older who were scheduled for routine health assessment s at a large multispecialty health-care group . Data collection included demographics , health behaviors , psychosocial factors , and CRC screening compliance . We followed participants for 1 year and assessed completion of endoscopic CRC screening . Both cross-sectional results examining previous screening and prospect i ve results examining screening 1 year later were evaluated . RESULTS : 554 ( 54 % ) of 998 patients responded to the survey . Responses of 13 patients were excluded in the analyses due to unverifiable screening outcome . The majority of the respondents were white , and their average age was 62 years . Women reported significantly more embarrassment and fear about having FS than men . Women were more willing to consider having a FS if a female endoscopist performed the procedure . Of the 334 participants who were eligible to have endoscopic CRC screening , 53 ( 16 % ) had the procedure within a year . The odds of having the endoscopic procedures increased with the length of time the patients were under the care of their primary care providers and how strongly patients believed that one should have an FS even without symptoms . CONCLUSIONS : Our findings suggest some unique gender-specific attitudes and beliefs that act as potential barriers for CRC screening and further support the important role of primary care providers in facilitating timely completion of screening OBJECTIVE Colorectal cancer ( CRC ) screening uptake remains poor . Until we underst and patient motivation and preferences for undertaking screening , it is unlikely the uptake will be optimal . Our objective is to examine patient preferences for CRC screening modalities and uptake rates using utility-based methods . METHODS The preference survey was mailed to a r and om sample of Canadian subjects aged 40 to 60 years from a primary care network . A fractional factorial experimental design maximized D-efficiency and included four blocks with 12 choice tasks in a conditional two-step design , two-alternative discrete choice format with five screening attributes ( process , pain , preparation , sensitivity , and specificity ) . Bivariate probit regression analysis was used to estimate patient preferences for attributes , choice probabilities for alternative modalities and expected rates of uptake . RESULTS Five hundred forty-seven of 1047 surveys were returned . Almost 30 % of respondents preferred no screening . The most preferred test attribute levels were noninvasive process ( e.g. , CT ) , no preparation , no pain , 100 % specificity , and 90 % sensitivity . Accuracy-related attributes were more important than test process-related attributes . Virtual colonoscopy was the most preferred , followed by colonoscopy , barium enema , sigmoidoscopy , and fecal DNA testing , based on simulated choice probability estimates . Fecal occult blood testing ( FOBT ) was least preferred . Adjusted screening uptake rate estimates showed the greatest impact ( 42 % increase ) would be achieved if all CRC screening modalities were available rather than FOBT alone . CONCLUSIONS Our findings emphasize the important role of patient preferences for no screening and in selecting alternative CRC screening modalities . CRC screening implementation in Canada should consider patient preferences to optimize uptake CONTEXT Professional organizations have published guidelines for colorectal cancer screening . Defining which patients are currently , or should be , screened is an important clinical and public health issue . OBJECTIVE To document the prevalence of colorectal cancer screening and profile the tests patients have had . DESIGN / POPULATION : A r and om-digit telephone survey of Massachusetts adults , 50 years of age and older . OUTCOME MEASURES Percentage of persons ever and currently tested by fecal occult blood tests , flexible sigmoidoscopy , barium enema , colonoscopy , or some combination of these tests . RESULTS Sixty-five percent of those contacted agreed to the telephone interview . Approximately 29 % of the 1119 respondents had never had any currently accepted test , including 10 % who reported having only a fecal occult blood test done in a provider 's office and 19 % who reported having no tests . At least 51 % were currently tested by one or more tests for screening , diagnosis , or both . Another 10 % were possibly current by colonoscopy or barium enema , both of which can be ordered for screening but are more commonly used to evaluate a problem , such as rectal bleeding , or for surveillance after identification of a polyp or other abnormality . An additional 11 % had been tested at some point but were not current according to guidelines . CONCLUSIONS Accurate assessment of rates of colorectal cancer screening is complex because of the multiple acceptable screening methods , the fact that patients may be tested for screening or diagnostic purpose s , and the lack of adequate systems for tracking such testing . For accurate measurement , all methods must be assessed regardless of whether tests were ordered for screening , diagnosis , or surveillance BACKGROUND This article describes the self-reported colorectal cancer ( CRC ) screening adherence rates of adults , aged 50 years and older , living in five nonurban Minnesota counties . METHODS During the year 2000 , 1693 eligible respondents , aged 50 years and older , from a r and omly selected sample completed a survey assessing CRC screening adherence ( approximately 86.3 % response ) . The survey allowed differentiation between the four CRC screening modalities but did not differentiate between screening and diagnostic testing . Adjustment for nonresponse was performed using a version of Horvitz-Thompson weighting accounting for unknown eligibility . RESULTS 24.5 % of respondents had a fecal occult blood test within 1 year of the survey , 33.8 % had flexible sigmoidoscopy within 5 years , 29.3 % had a colonoscopy within 10 years , and 13.7 % had a barium enema within the last 5 years . Overall , 55.3 % of respondents reported testing by any modality ; thus , 44.7 % were not adherent to screening guidelines . CONCLUSIONS This study improves on previous attempts to characterize CRC screening adherence by assessing all four modalities of screening as recommended by current screening guidelines , by focusing on nonadherence , and by rigorously accounting for nonresponse . This study confirms that nearly half of the population remains unscreened by any method BACKGROUND Developing effective programs to promote colorectal cancer ( CRC ) screening requires underst and ing of the effect of healthcare system factors on access to screening and adherence to guidelines . METHODS This study assessed the role of insurance status , type of plan , the frequency of preventive health visits , and provider recommendation on utilization of CRC screening tests using a cross-sectional , r and om-digit-dial survey of 1002 Massachusetts residents aged > or = 50 . RESULTS A broad definition of CRC screening status included colonoscopy or barium enema ( screening or diagnostic ) within 10 years , flexible sigmoidoscopy ( FSIG ) within 5 years , and fecal occult blood testing ( FOBT ) in the past year as options ; 51.7 % of subjects aged 50 to 64 and 61.5 % of older subjects were current . The uninsured had the lowest current testing rate . Among insured participants , type of insurance had little impact on CRC testing ; older subjects enrolled in HMOs had marginally higher rates , although not statistically significant . Increased frequency of preventive health visits and ever receiving a physician 's recommendation for FSIG or ever receiving FOBT cards were associated with higher rates of CRC screening among both age groups . CONCLUSIONS Even when broad criteria are used to define current CRC screening status , a substantial proportion of the age-eligible population remains underscreened . Obtaining regular preventive care and receiving a physician 's recommendation for screening appear to be potent facilitators of screening that should be considered in design ing promotional efforts OBJECTIVE : Colorectal cancer screening is underutilized . Total colon examination ( TCE ) , such as with colonoscopy , can have a significant effect on the measured compliance with screening , as colonoscopy may be able to be performed as infrequently as once every 10 yr . In a population -based survey we determined the prevalence and vali date d the self-reporting of TCE and assessed its impact on compliance with screening . METHODS : We interviewed an age- and sex-stratified r and om sample of 50- to 79-yr-old residents in two communities in southwestern Pennsylvania . Subjects reported ever having had and duration since last use of fecal occult blood testing ( FOBT ) , flexible sigmoidoscopy ( FS ) , rigid proctoscopy , barium enema , and colonoscopy . Self-reports of colorectal testing were vali date d via retrieval of procedure reports . RESULTS : Out of 1223 individuals sample d , 496 completed a telephone interview ( 40.6 % overall and 58.3 % of eligible contacts ) . In those without personal or family histories of colorectal cancer or personal histories of polyps ( n = 377 ) , 50 % , 19.6 % , 39.8 % , and 17.5 % reported ever having had FOBT , FS , barium enema , and colonoscopy , respectively . Thirty-one percent reported having FOBT within the previous year or FS within the previous 5 yr . Including TCE within the previous 5 yr increased the measured compliance to 39.7 % . Compliance was significantly greater among subjects with family histories of colorectal cancer ( 62.9 % vs 39.7 % , odds ratio = 2.6 , 95 % CI = 1.3–5.2 ) . Self-reports of recent colonoscopy were verified in 29 of 35 instances ( 83 % ) . CONCLUSION : The prevalence of TCE in this population was significant , and including TCE substantially increased measured compliance with colorectal cancer screening . Self-reported use of colonoscopy was vali date d as accurate OBJECTIVES To estimate current rates of use of fecal occult blood testing ( FOBT ) and sigmoidoscopy or colonoscopy ; to determine whether test use varies by demographic factors ; and to compare 1999 rates of use with 1997 rates . STUDY DESIGN The Behavioral Risk Factor Surveillance System is an ongoing , state-based r and om-digit-dialed telephone survey of the US population that collects various health behavior information , including the use of colorectal cancer ( CRC ) screening tests . POPULATION In 1999 , 63,555 persons 50 years of age or older responded to questions regarding FOBT and sigmoidoscopy or colonoscopy . OUTCOMES MEASURED The proportion of survey respondents reporting having had FOBT and sigmoidoscopy/colonoscopy at any time ; and the proportion reporting having had FOBT and sigmoidoscopy/colonoscopy within recommended time intervals . Data were recorded for the years 1997 and 1999 , and analyzed according to various demographic factors . RESULTS In 1999 , 40.3 % of respondents reported having had an FOBT at some time , and 43.8 % reported having had a sigmoidoscopy or colonoscopy . Regarding recent test use , 20.6 % of respondents reported having had an FOBT within the year , and 33.6 % reported having had a sigmoidoscopy or colonoscopy within the past 5 years . Some demographic variation was noted . In 1997 , 19.6 % reported having had an FOBT within the year , and 30.3 % reported having had a sigmoidoscopy or proctoscopy within the past 5 years . CONCLUSIONS Use of CRC screening tests increased only slightly from 1997 to 1999 . Usage remains low , despite consensus that screening for CRC reduces mortality from the disease . Efforts to promote awareness of , and screening for , CRC must intensify OBJECTIVES To characterize self-reported colorectal cancer ( CRC ) screening behavior , and to identify characteristics of CRC screening practice s , stratified by risk . METHODS Using r and om-digit-dial methodology , we conducted telephone surveys in US adults 50 years of age and older . Respondents provided data on utilization of CRC screening tests ; demographic characteristics ; and awareness , concerns , attitudes and beliefs about the tests , CRC , and health care . On the basis of available guidelines , three definitions of adequate screening were considered . RESULTS Among persons reporting having ever had a CRC screening exam , the exam was more likely to have been a fecal occult blood test than a radiologic or endoscopic exam ( p < .0001 ) . Subjects at increased CRC risk were more likely to have met the screening criteria ( p < .001 ) compared with average-risk subjects . Receipt of information or advice about cancer screening tests , male gender , and concern about managed care were positively associated with adequate screening . Smoking , low health self-monitoring , and an average risk for CRC reduced the probability of CRC screening . CONCLUSIONS Lack of awareness about screening remains common , regardless of CRC risk . Providing information and advice about cancer screening may be the single most important tool available to improve screening rates BACKGROUND Even though colorectal cancer ( CRC ) screening tests for persons 50 years of age or over are recommended to reduce colorectal cancer mortality , screening rates remain disturbingly low . METHODS Using r and om digit dialing , 355 telephone interviews were conducted with black and white men and women , 50 - 79 years of age , who resided in Genesee County , Michigan . The Health Belief Model provided the framework to assess attitudes and practice s regarding CRC screening . RESULTS For both endoscopic procedures , significantly higher percentages of whites than blacks were aware of the screening procedure ( P < 0.05 ) . Overall , fewer than 30 % of respondents were adherent to current CRC screening guidelines . Adherence was lowest for black females : 21 % for fecal occult blood test , 20 % for flexible sigmoidoscopy , and 12 % for colonoscopy . Black males compared to black females were about 2.8 times more likely to have had either flexible sigmoidoscopy or colonoscopy ( P < 0.05 ) . Physician recommendation was a powerful motivator to screening . Two consistent barriers to screening were the belief that : ( a ) the test is not needed ; and ( b ) the test is embarrassing . CONCLUSIONS Interventions directed at physicians and patients are essential to enhance CRC screening rates . CRC survival rates may be improved by physician-guided promotion of screening that focuses on identified barriers CONTEXT Colorectal cancer is the second leading cause of cancer death in the United States , yet screening rates are well below target levels . Rural communities may face common and unique barriers to health care , particularly preventive health care . PURPOSE To establish baseline attitudinal , knowledge , belief , and behavior measures on colorectal cancer screening and to identify barriers to or predictors of colorectal cancer screening . METHODS As part of a controlled trial using a quasi-experimental , pretest , post-test design , we conducted a baseline telephone survey of 1,050 rural eastern Colorado residents aged 50 years and older . Smaller counties were over- sample d to ensure a minimum of 30 completed interviews per county . FINDINGS Seventy-seven percent reported they ever had a colorectal cancer screening test and 59 % were up-to- date on at least 1 test . The most important independent predictors of being up-to- date were having visited a doctor or other health care practitioner for a checkup in the past year , having personal or family history of colon polyps or cancer , and having asked for a colorectal cancer screening test . Financial concerns were reported reasons for not obtaining fecal occult blood testing by 18 % and colonoscopy by 21 % . CONCLUSIONS This study suggests that health care providers should be vigilant in counseling their patients 50 and older to have a colorectal cancer test . Community programs design ed to promote colon cancer screening should encourage residents to have regular contact with their primary care physician and ask their doctor for a screening test . Additionally , programs should provide financial assistance for testing for low-income and uninsured patients BACKGROUND Few studies have examined lack of physician recommendation and other reasons for under-utilization of colorectal cancer ( CRC ) screening in the Medicare population . METHODS Data from a telephone survey conducted in 2001 in a r and om sample of Medicare consumers residing in North and South Carolina were used to examine barriers to CRC screening , focusing on consumers ' reports of receiving a physician 's recommendation to obtain CRC screening and reasons for not being screened . Analyses were restricted to respondents with no history of CRC ( n = 1901 ) . Descriptive statistics were used to characterize respondents ' CRC screening status , receipt of a physician 's recommendation for screening , and reasons for not being screened . Logistic regression modeling was used to examine factors associated with receiving a physician recommendation for fecal occult blood test , sigmoidoscopy , colonoscopy , any endoscopy , and any CRC test . RESULTS Thirty-one percent of Medicare consumers had never been tested for CRC , and 18 % had been tested but were not current with Medicare-covered intervals . Overall , 28 % reported not receiving a physician recommendation for screening . Predictors of receiving a physician recommendation included sociodemographic ( younger age , white race , more education ) , health status ( increased CRC risk , comorbidity ) , and healthcare access ( had a routine/preventive care visit in the past 12 months ) factors . Lack of knowledge/awareness and the physician not ordering the test were commonly cited reasons for not having CRC tests . CONCLUSIONS Colorectal cancer screening was under-utilized by Medicare consumers in two states , and lack of physician recommendation was an important contributing factor . Providing a benefit under the Medicare program does not ensure its widespread use by consumers or their physicians Purpose . To determine baseline use rates for health-promoting behaviors of the recently adopted New Jersey Health Wellness Promotion Act and to examine the effects of demographic and socioeconomic factors on the use of preventive services included in the Act . Design . A r and om telephone survey of 3094 households was conducted using questions from the Behavioral Risk Factor Surveillance System supplemented by questions related to provisions of the Act . Setting . All New Jersey households . Subjects . State representative adult sample of 1246 subjects . Measures . Rates for getting timely screening tests , for obtaining influenza immunizations , and engaging in selected health-promoting behaviors . Results . Rates for receiving recommended screening tests ranged from 0.88 for blood pressure testing to 0.29 for osteoporosis screening . According to bivariate analysis , having insurance was the most consistent determinant associated with receiving preventive services but was associated only with sigmoidoscopy , mammography , and Pap smear testing in the multivariate modeling . Reminders were significantly associated with respective screening tests . Age was positively associated with receiving the majority of tests . Gender , ethnicity , education , and income affected receipt sporadically . Half the respondents were overweight and a quarter were current smokers . Conclusions . Receipt of appropriate screening tests and adoption of health-promoting behaviors fell short of desired goals . Having health insurance increased receipt rates , but was not enough to achieve usage goals . Procedure-specific reminders may improve usage rates BACKGROUND : Obesity is associated with a higher incidence of colorectal cancer and increased colorectal cancer mortality . Obese women are less likely to undergo breast and cervical cancer screening than nonobese women . It is not known whether obesity is associated with a lower likelihood of colorectal cancer screening . OBJECTIVE : To evaluate whether there is an association between body mass index ( BMI ) and rates of colorectal cancer screening . To examine whether BMI -related disparities in colorectal cancer screening differ between men and women . DESIGN AND SETTING : The Behavioral Risk Factor Surveillance System , a cross-sectional r and om-digit telephone survey of noninstitutionalized adults conducted by the Centers for Disease Control and Prevention and state health departments in the 50 states and Washington , DC in 1999 . PATIENTS : Survey respondents ( N=52,886 ) between 51 and 80 years of age representing 64,563,332 U.S. adults eligible for colorectal cancer screening . INTERVENTIONS AND MEASURMENTS : Adjusted rates of self-reported colorectal cancer screening with fecal occult blood testing within the past year or endoscopic screening ( sigmoidoscopy or colonoscopy ) within the past 5 years . RESULTS : The colorectal cancer screening rate was 43.8 % overall . The rate of screening by FOBT within the last year or endoscopic screening within the past 5 years was 39.5 % for the morbidly obese group , 45.0 % for the obese group , 44.3 % for the overweight group , and 43.5 % for the normal weight group . The difference in screening rates was entirely attributable to differences in BMI among women . After statistical adjustment for potential confounders , morbidly obese women were less likely than normal weight women to be screened ( adjusted rate difference , −5.6 % ; 95 % confidence interval , −8.5 to −2.6 ) . Screening rates among normal weight , overweight , and obese women , and among men in different weight groups did not differ significantly . CONCLUSIONS : Colorectal cancer screening rates among age-eligible persons in the U.S. are disturbingly low . Morbidly obese women , who are at higher risk than others to develop and to die from colorectal cancer , are less likely to be screened . Efforts to increase colorectal cancer screening are needed for all age-eligible groups , but should also include targeted screening of morbidly obese women since they could reap substantial clinical benefits from screening |
809 | 23,576,227 | There is valuable evidence for paramedic assessing and managing patients autonomously to reduce Emergency Department conveyance which is acceptable to patients and carers .
This review identifies many viable extra skills for paramedics but the evidence is not strong enough to guide policy . | BACKGROUND Increasing dem and on the UK emergency services is creating interest in review ing the structure and content of ambulance services .
Only 10 % of emergency calls have been seen to be life-threatening and , thus , paramedics , as many patients ' first contact with the health service , have the potential to use their skills to reduce the dem and on Emergency Departments .
This systematic literature review aim ed to identify evidence of paramedics trained with extra skills and the impact of this on patient care and interrelating services such as General Practice s or Emergency Departments . | Objective To evaluate the benefits of paramedic practitioners assessing and , when possible , treating older people in the community after minor injury or illness . Paramedic practitioners have been trained with extended skills to assess , treat , and discharge older patients with minor acute conditions in the community . Design Cluster r and omised controlled trial involving 56 clusters . Weeks were r and omised to the paramedic practitioner service being active ( intervention ) or inactive ( control ) when the st and ard 999 service was available . Setting A large urban area in Engl and . Participants 3018 patients aged over 60 who called the emergency services ( n=1549 intervention , n=1469 control ) . Main outcome measures Emergency department attendance or hospital admission between 0 and 28 days ; interval from time of call to time of discharge ; patients ' satisfaction with the service received . Results Overall , patients in the intervention group were less likely to attend an emergency department ( relative risk 0.72 , 95 % confidence interval 0.68 to 0.75 ) or require hospital admission within 28 days ( 0.87 , 0.81 to 0.94 ) and experienced a shorter total episode time ( 235 v 278 minutes , 95 % confidence interval for difference −60 minutes to −25 minutes ) . Patients in the intervention group were more likely to report being highly satisfied with their healthcare episode ( relative risk 1.16 , 1.09 to 1.23 ) . There was no significant difference in 28 day mortality ( 0.87 , 0.63 to 1.21 ) . Conclusions Paramedics with extended skills can provide a clinical ly effective alternative to st and ard ambulance transfer and treatment in an emergency department for elderly patients with acute minor conditions . Trial registration IS RCT N27796329 Background : A scheme to train paramedics to undertake a greater role in the care of older people following a call for an emergency ambulance was developed in a large city in the UK . Objectives : To assess the cost effectiveness of the paramedic practitioner ( PP ) scheme compared with usual emergency care . Methods : A cluster r and omised controlled trial was undertaken of PP compared with usual care . Weeks were allocated to the study group at r and om to the PP scheme either being active ( intervention ) or inactive ( control ) . Re source use data were collected from routine sources , and from patient-completed question naires for events up to 28 days . EQ-5D data were also collected at 28 days . Results : Whereas the intervention group received more PP contact time , it reduced the proportion of emergency department ( ED ) attendances ( 53.3 % vs 84.0 % ) and time in the ED ( 126.6 vs 211.3 minutes ) . There was also some evidence of increased use of health services in the days following the incident for patients in the intervention group . Overall , total costs in the intervention group were £ 140 lower when routine data were considered ( p = 0.63 ) . When the costs and QALY were considered simultaneously , PP had a greater than 95 % chance of being cost effective at £ 20 000 per QALY . Conclusion : Several changes in re source use are associated with the use of PP . Given these economic results in t and em with the clinical , operational and patient-related benefits , the wider implementation and evaluation of similar schemes should be considered OBJECTIVES To evaluate paramedics ' ability to identify elderly at risk and refer them for assessment and service . DESIGN A prospect i ve nonr and omized open trial . SETTING Akron , Ohio , a midsize city with a well-developed advanced life support emergency medical services system . TYPE OF PARTICIPANTS One hundred thirty firefighter paramedics evaluated 6,000 elderly patients . Assessment s were performed by trained geriatric assessors . INTERVENTION Regardless of the reason for the call , paramedics screened all emergency medical services users age 60 and older for medical , mental health , social , and environmental problems . Identified cases were referred to the Area Agency on Aging for assessment and follow-up . MAIN RESULTS Paramedics identified 197 people with possible problems , 124 of whom received an assessment . The remainder could not be assessed due to death , moving , referral , or transfer to a long-term care facility . Assessors confirmed the presence of a problem in 121 of 124 assessed cases , a positive predictive value of 98 % . The program was useful for 94 people , 48 % of those identified and assessed . CONCLUSION Paramedics can serve as case finders for at-risk elderly , and effective linkage to service agencies can occur UNLABELLED Residential carbon monoxide ( CO ) poisoning represents a significant cause of unintentional morbidity and mortality in the United States . Screening by fire departments and utility companies is usually limited to instances in which there are symptoms of CO poisoning or there is activation of a home CO detector . OBJECTIVES To determine whether emergency medical services ( EMS ) personnel can perform routine CO screening during 911 calls . METHODS A prospect i ve observational study was conducted in an urban EMS system using emergency medical technicians ( EMTs ) to screen for elevated CO levels during emergency responses . The EMTs carried h and -held CO meters that detect as little as one part per million of CO . Readings were taken at the patient 's side during indoor patient contacts . If time allowed , a brief question naire was then administered to patients or by-st and ers concerning knowledge about CO poisoning , type of household heating system , and presence of home CO detectors . RESULTS In a three-month convenience sample of emergency responses , there were 264 residential CO readings obtained . There were nine ( 3.4 % ) positive residential readings , all with chief complaints believed to be unrelated to CO toxicity . Two hundred twelve surveys were completed during these emergency responses , with 145 of 212 ( 68 % ) participants familiar with the term " carbon monoxide poisoning . " Only 54 of 145 ( 37 % ) participants could name any signs or symptoms of CO poisoning . Of those surveyed , 133 of 212 ( 63 % ) participants reported an oil- or gas-powered heating system in their residence . Carbon monoxide detectors were absent in 185 of 212 ( 87 % ) residences , including all domiciles in which a positive CO reading was obtained . CONCLUSIONS Emergency medical services personnel can perform routine CO screening and detect occult elevations in CO levels during 911 responses . Public knowledge of CO poisoning is limited and the use of home CO detectors is rare in this study population INTRODUCTION This study evaluates whether a continuing education program for paramedics , focusing on Children with Special Health Care Needs , improved paramedics ' assessment and management . METHODS Emergency Medical Services responses for children , 21 years of age or younger , with a congenital or acquired condition or a chronic physical or mental illness , were identified . The responses before and after the specialized education program were review ed by a multidisciplinary team to evaluate assessment and management of the children . Inter review er agreement between the nurses on the team and between the physicians on the team was assessed . We also evaluated whether there was an improvement in assessment and care by paramedics completing our education program . RESULTS Significant improvement was seen in appropriate assessment and overall care by paramedics who completed our specialized education program . Review ers also noted an appropriate rating for the initial assessment category more often for responses involving paramedics who had the training . Agreement on whether assessment and treatment was appropriate for all five review ers varied considerably , ranging from 32 % to 93 % . Overall there was a high percentage of agreement ( > 70 % ) between the nurses and between the physicians on most items . However , kappa statistics did not generally reflect good agreement except for most of the focused assessment items and some treatment and procedure items . CONCLUSION Most of the documentation on the EMS records indicated appropriate assessment and treatment during all responses for Children with Special Health Care Needs . Nevertheless , the results indicate that paramedics may improve their assessment and management of these children after specialized continuing education The aim of this study was to carry out a critical appraisal to detect the occurrence of publication bias , specifically positive- outcome bias , in Brazilian dental journals . A convenience sample of twenty-eight dental journals published in Brazil between 1994 and 2003 was selected ( 564 issues containing 5,453 articles ) . Each article was classified according to method ological design ; 1,064 were classified as case reports . A simple r and om sample of 435 articles comprised the final study sample and was su bmi tted to a critical appraisal by previously trained raters . Although a great part of case reports achieve proper structural aspects , most authors did not consider important aspects that could help the decision making process , such as discussion of alternative approaches , limitation of the performed procedures , lack of long-term clinical follow-up , possible variations in treatment outcome , and failure to discuss limitations of study design . In addition , unanimous reports of successful outcomes of clinical interventions strongly suggest that publication of case reports was influenced by positive outcome bias , which may influence readers ' clinical decision making process |
810 | 19,225,234 | The correlation with other st and ard screening tests was statistically significant in most studies , but the results were influenced by age , education and language .
In studies that included patients with mild or question able dementia , the CDT had a low sensitivity and variable specificity .
Conclusion : The CDT has the characteristics of a good screening method for moderate and severe dementia . | Background / Aims : The Clock Drawing Test ( CDT ) is used in clinical practice for the screening of cognitive disorders .
This systematic review aims to present and discuss the CDT scoring methods available in the literature , in order to find differences in administration and utility of the CDT . | Forty eight elderly Thai patients , 12 demented , 36 non-demented who consecutively attended a geriatric clinic , at Chulalongkorn University Hospital , with a memory problem were recruited in the study which aim ed to determine the validity of the clock-drawing test ( CDT ) and Chula mental test ( CMT ) . Subjects took the Chula Mental Test ( CMT ) and were asked to draw a clock on a preprinted 12 centimeters circle showing the time of 11:10 . Clocks were scored using the Chula Clock-drawing Scoring System ( CCSS ) . Ten subjects voluntarily participated and completed the WAIS test . The best cutoff score of the CMT and the CDT using diagnosis of dementia as a gold st and ard were 15 and 7 respectively . Sensitivity and specificity for detecting dementia by the CDT were 100 per cent and 94.1 per cent respectively . Sensitivity and specificity for detecting dementia by the CMT were 83.3 per cent 91.7 per cent . The likelihood ratio ( 95 % confidence interval ) of the CMT and the CDT were 10 ( 3.3 - 30.4 ) and 17 ( 4.4 - 65.2 ) respectively . There was a good correlation of the CDT score and the CMT score with the WAIS score . Although the CDT was better than the CMT in literate patients , the CDT had limitation of use among illiterate patients but not the CMT . The benefits of simultaneously application on dementia screening was shown . This study showed that the CDT was a valuable , brief method of dementia screening in elderly Thai patients with memory problems BACKGROUND Subjects with a mild cognitive impairment ( MCI ) have a memory impairment beyond that expected for age and education yet are not demented . These subjects are becoming the focus of many prediction studies and early intervention trials . OBJECTIVE To characterize clinical ly subjects with MCI cross-sectionally and longitudinally . DESIGN A prospect i ve , longitudinal inception cohort . SETTING General community clinic . PARTICIPANTS A sample of 76 consecutively evaluated subjects with MCI were compared with 234 healthy control subjects and 106 patients with mild Alzheimer disease ( AD ) , all from a community setting as part of the Mayo Clinic Alzheimer 's Disease Center/Alzheimer 's Disease Patient Registry , Rochester , Minn. MAIN OUTCOME MEASURES The 3 groups of individuals were compared on demographic factors and measures of cognitive function including the Mini-Mental State Examination , Wechsler Adult Intelligence Scale-Revised , Wechsler Memory Scale-Revised , Dementia Rating Scale , Free and Cued Selective Reminding Test , and Auditory Verbal Learning Test . Clinical classifications of dementia and AD were determined according to the Diagnostic and Statistical Manual of Mental Disorders , Revised Third Edition and the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer 's Disease and Related Disorders Association criteria , respectively . RESULTS The primary distinction between control subjects and subjects with MCI was in the area of memory , while other cognitive functions were comparable . However , when the subjects with MCI were compared with the patients with very mild AD , memory performance was similar , but patients with AD were more impaired in other cognitive domains as well . Longitudinal performance demonstrated that the subjects with MCI declined at a rate greater than that of the controls but less rapidly than the patients with mild AD . CONCLUSIONS Patients who meet the criteria for MCI can be differentiated from healthy control subjects and those with very mild AD . They appear to constitute a clinical entity that can be characterized for treatment interventions OBJECTIVES To assess the usefulness , relative ease of administration , and patient acceptance of the clock drawing test as well as the time and change test for detecting dementia in Chinese elderly adults . DESIGN Prospect i ve case-controlled study . SETTING Memory clinic and geriatric clinic of a district hospital , Hong Kong . PARTICIPANTS A convenient sample of 85 subjects aged 65 years or older attending the two clinics during the period from September 2002 to June 2003 . MAIN OUTCOME MEASURES The clock drawing test scored according to Lam 's method ; the time and change test with modification to the making change task ; and the Chinese version of the Mini-Mental State Examination . RESULTS Demented subjects were matched with non-demented ones with respect to age , sex , educational level , and co-morbidity status . The clock drawing test had a comparable sensitivity ( 89.4 % ) but a lower specificity ( 47.1 % ) when compared with that of the Chinese version of the Mini-Mental State Examination ( 96.0 and 76.5 % , respectively ) . In contrast , the time and change test had a lower sensitivity ( 62.7 % ) but higher specificity ( 94.1 % ) . Both tests took significantly less time to complete than the Chinese version of the Mini-Mental State Examination . All except four subjects completed the clock drawing test while all subjects accepted the time and change test well . CONCLUSIONS The Chinese version of the Mini-Mental State Examination is still the best among the three tests despite the longer time to completion . The clock drawing test may be a good alternative to the Mini-Mental State Examination as an effective screening test for dementia when time does not permit . The time and change test , although time-saving , is not suitable to be used alone because of its low sensitivity BACKGROUND As elderly population s grow , dementia detection in the community is increasingly needed . Existing screens are largely unused because of time and training requirements . We developed the Mini-Cog , a brief dementia screen with high sensitivity , specificity , and acceptability . Here we describe the development of its scoring algorithm , its receiver operating characteristics ( ROC ) , and the generalizability of its clock drawing scoring system . SAMPLE AND METHODS A total of 249 multi-lingual older adults were examined . Scores on the three-item recall task and the clock drawing task ( CDT-CERAD version ) were combined to create an optimal algorithm . Receiver operating characteristics for seven alternatives were compared with those of the MMSE and the CASI using expert raters . To assess the CDT scoring generalizability , 20 naïve raters , without explicit instructions or prior CDT exposure , scored 80 r and omly selected clocks as " normal " or " abnormal " ( 20 from each of four CERAD categories ) . RESULTS An algorithm maximizing sensitivity and correct diagnosis was defined . Its ROC compared favorably with those of the MMSE and CASI . CDT concordance between naïve and trained raters was > 98 % for normal , moderately and severely impaired clocks , but lower ( 60 % ) for mildly impaired clocks . Recalculation of the Mini-Cog 's performance , assuming that naïve raters would score all mildly impaired CDTs in the full sample as normal , retained high sensitivity ( 97 % ) and specificity ( 95 % ) . CONCLUSION The Mini-Cog algorithm performs well with simple clock scoring techniques . The results suggest that the Mini-Cog may be used successfully by relatively untrained raters as a first-stage dementia screen . Further research is needed to characterize the Mini-Cog 's utility when population dementia prevalences are low The ten‐point clock test is administered by tracing an 11·4 cm ( 4 1/2 inch ) diameter circle on a piece of paper and asking the patient to ‘ Write the numbers in the face of a clock ’ . The patient is then asked to ‘ Make the clock say 10 minutes after 11 ’ . The spacing of the numbers and the positions of the h and s are used to score the test . A score of less than eight points identified 71 % of patients with Alzheimer 's disease who had a Mini‐Mental State Examination score of greater than 23 . The specificity measured in elderly controls was 82 % . The test may prove useful in screening for early stage Alzheimer 's disease . Copyright © 1999 John Wiley & Sons , OBJECTIVE To assess the accuracy of clock drawing for detecting dementia in a multicultural , non-English-speaking- background population . DESIGN A prospect i ve cohort study . SETTING A general geriatric medical outpatient clinic in southwest Sydney , Australia . PARTICIPANTS Ninety-three consecutive new patients to the clinic who had a non-English-speaking- background country of birth ( mean age 78.0 years ) . MEASUREMENTS The clock drawing test was conducted at the beginning of each clinic visit by a blinded investigator . Each patient was then assessed by a geriatrician who collected demographic data , administered the Modified Barthel Index , the Geriatric Depression Scale , and the Folstein Mini-Mental State Examination , and categorized each patient as normal or demented , according to DSM-IV criteria . Interpreters were used for participants who spoke a language other than English or who requested them . Each clock drawing was scored according to the 4-point CERAD scale and the previously published methods of Mendez , Shulman , Sunderl and , Watson , and Wolf-Klein . Scoring was evaluated for reliability and predictive accuracy , using receiver operating characteristic ( ROC ) curve analysis . Logistic regression analysis was used to assess the potential interaction between level of education and each of the clock scoring methods . RESULTS Using ROC curve analysis , there was no significant difference between the clock scoring methods ( area under the curve varied from 0.60 to 0.72 ) . The most sensitive was the Mendez scoring method ( 98 % ) , with a specificity of 16 % . Specificity above 50 % was found only for the Wolf-Klein method , with an intermediate sensitivity of 78 % . CONCLUSIONS There were no significant differences in the clock scoring methods used to detect dementia . Performance of the clock drawing test was modest at best with low levels of specificity across all methods . Scored according to these methods , clock drawing was not a useful predictor of dementia in our multicultural population INTRODUCTION The Clock Drawing Test ( CDT ) has been used in recent years as a simple neuropsychological instrument to assess cognitive deterioration associated with dementia , even though uniform operative criteria with respect to its application and scoring have not been established . OBJECTIVE To present application normatives and establish the most relevant psychometric criteria of the CDT in a sample of healthy subjects ( HS ) and patients with Alzheimer 's disease ( AD ) . PATIENTS AND METHODS 56 patients were selected of which 35 were female and 21 were male . The patients ' mean age was 72.7 with a st and ard deviation of 7.64 . All of whom where probable AD patients according to the NINCDS-ADRDA criteria at stage 1 CDR . The group of HS was made up of 56 control subjects ( 34 female , 22 male ) with a mean age of 72.14 and a st and ard deviation of 7.2 . The CDT was applied in both its comm and ( COM ) and copy ( COP ) experimental conditions . RESULTS The main psychometric parameters analysed in the studied series showed the following values : internal consistency ( Cronbach 's alpha coefficient 0.9029 ) ; cut off point CT COM 6 with 92.80 , sensitivity ; false negatives ( FN ) 7.2 with a specificity rating 93.48 ; false positive ( FP ) 6.52 with 93.16 efficacy ; cut off point CT COP 8 with 73.11 sensitivity ; FN 26.89 with 90.58 specificity ; FP 9.42 with 82.49 efficacy . CONCLUSION The CDT can be used to discriminate between HS and those in the initial stages of AD in the given sample using the established application and scoring criteria OBJECTIVE To develop a simple , readily administered and scored screening test for dementia utilizing the clock-drawing task . DESIGN Retrospective analysis of clock-drawing errors and prospect i ve validations . SETTING Hospital-based outpatient geriatric assessment clinic , rehabilitation service , apartment building for older adults , and long-term care facility . PARTICIPANTS Convenience sample of patients attending the geriatric assessment clinic , patients on the rehabilitation service , or residents of the above sites . MEASUREMENTS Sensitivity and specificity of a clock-scoring system in identifying patients with dementia and the comparison of this system with the Short Blessed Test ( SBT ) in the diagnosis of dementia and in the prospect i ve validation of the test . RESULTS Of the 10 clock-drawing errors evaluated , placement of digits in a pre-drawn circle had the greatest sensitivity and specificity in distinguishing patients with irreversible dementia from patients with other disorders who did not meet NINCDS-ADRDA criteria for probable dementia . The derived scoring system had a sensitivity of 87 % and a specificity of 82 % , compared with a sensitivity of 82 % and a specificity of 88 % for the SBT in identifying dementia . Test-retest reliability for the distinction between demented and non-demented was 82 % , with a Kappa of 0.63 for the clock completion , and 82 % , with a Kappa of 0.62 for the SBT . Inter-rater reliability for clock completion was 0.90 to 0.93 . CONCLUSION A simple , completely objective scoring system for a clock completion test has been developed which involves only the number of digits placed in the fourth quadrant of a pre-drawn circle . This readily administered test is as effective in screening for dementia as the longer six-item SBT Causes of cognitive impairment in the elderly include dementia , delirium , toxic effects of medications , trauma , and psychiatric illness . Dementia is the most common cause , and it implies a decline in cognitive function severe enough to interfere with social functioning . The estimated prevalence of dementia is 3 % to 6 % for community-dwelling elderly persons aged 65 years and older [ 1 - 4 ] , but the prevalence of dementia increases with advancing age [ 1 , 2 , 5 , 6 ] and is more common among elderly patients in primary care setting s , hospitals , or nursing homes [ 7 , 8 ] . The annual cost of caring for a patient with Alzheimer disease is estimated to be $ 47 000 [ 9 ] , and total national costs for senile dementia in 1991 were estimated to be more than $ 67 billion [ 10 ] . In addition , patients with dementia have been shown to have greater mortality than elderly patients without dementia [ 5 ] . Given the prevalence , costs , and morbidity of cognitive impairment , and the availability of several brief screening instruments [ 11 - 13 ] , screening for cognitive impairment among elderly patients seen in primary care has been recommended [ 14 - 20 ] . Early recognition and diagnosis of cognitive impairment are believed to be beneficial for at least three reasons . First , a diagnosis provides some comfort to the patient and family by explaining the changes in the patient 's behavior and also allows the practitioner to counsel the patient and family about prognosis . Second , an accurate diagnosis of cognitive impairment and assessment of its functional and social effects may facilitate access to rehabilitative , social , and financial services , as well as help inform decisions about competency and guardianship [ 21 - 23 ] . Third , early recognition may allow an opportunity to alter the course of the cognitive impairment . Physicians may be able to do so if diagnostic evaluations show a reversible or partially reversible cause [ 24 - 26 ] or if the rate of progression of a dementing illness or a comorbid illness can be slowed [ 27 - 29 ] . Indeed , routine diagnostic investigations for reversible causes of dementia have been recommended [ 19 , 20 , 24 ] . However , the prevalence of reversible causes of dementia and the clinical utility of routine diagnostic investigations are still being debated [ 13 , 30 - 35 ] . Thus , although early documentation of cognitive impairment offers many other benefits , clinicians might appropriately choose either an extensive or a limited diagnostic evaluation for any given patient . Our study had four objectives . First , we determined the prevalence of cognitive impairment by screening a group of urban , elderly , primary care patients using the Short Portable Mental Status Question naire ( SPMQ ) . Second , we describe their primary care physicians ' rates of documentation and evaluation of cognitive impairment . Third , we compare use of health services in the year after the patient 's screening examination . Fourth , we compare practice patterns and use of health services among patients with documented and those with undocumented cognitive impairment . Methods Patients Our study was done in the General Medicine Practice of the Regenstrief Health Center , a multispecialty ambulatory care clinic associated with an urban county hospital [ 36 ] . The General Medicine Practice is a university-affiliated primary care practice staffed by 35 general internists on the faculty and 118 internal medicine residents . Beginning in January 1991 , all patients aged 60 years and older were screened for cognitive impairment , depression , and alcoholism during their regularly scheduled visits . We excluded prisoners , patients residing in a nursing home , patients unable to speak English , and patients who had hearing impairment . The screening instruments included the Short Portable Mental Status Question naire [ 37 ] , the Center for Epidemiologic Studies Depression scale ( CES-D ) [ 38 ] , and the CAGE alcoholism question naire [ 39 ] . Professional research assistants administered the screening interview to patients at the time of scheduled office visits . Screening scores on the SPMQ completed for the purpose s of our study were not revealed to the primary care physicians . Patients with 3 to 4 errors on the SPMQ were considered to have mild cognitive impairment , and patients with 5 or more errors were considered to have moderate to severe cognitive impairment . We corrected the SPMQ score for years of education by allowing an additional error for patients with 8 or fewer years of education [ 37 ] , but we did not correct scores for race . When administered to community-dwelling elderly persons , the SPMQ has a specificity of greater than 90 % and a sensitivity of 50 % to 82 % ( cutoff , 3 or more errors ) [ 12 , 40 ] . The positive predictive value of the test in a community-dwelling patient sample was 87 % , and the validity was tested against structured psychiatric assessment s [ 37 ] . We used the st and ard cutoff score of 16 or greater on the CES-D to indicate significant symptoms of depression [ 38 ] . Patients with two or more positive responses on the CAGE question naire were considered to have evidence of alcoholism [ 39 ] . Interview data were merged with information routinely collected and stored in the patients ' electronic medical records [ 41 ] . These data included all outpatient diagnoses as recorded by the patients ' physicians . The ICD-9-CM codes for the individual diagnoses for each patient were collapsed into 1 of 40 unique categories . We report only the 20 most common diagnoses . We also determined whether each patient had ever had any of the following : tests for hemoglobin concentrations , serum chemistries , thyroid function , erythrocyte sedimentation rate , syphilis ( VDRL or fluorescent treponemal antibody absorption or Treponema pallidum microhemagglutination assay ) , serum cobalamin levels , and serum folate levels ; radiograph of the chest ; neuroimaging ( computed tomography or magnetic resonance imaging ) ; lumbar puncture ; or electroencephalography . We determined whether patients had had neurologic evaluation in the year before or in the year after the screening date and whether they had been prescribed any of the major classes of central nervous system-active medications ( anticholinergics , narcotics , antidepressants , benzodiazepines , or major tranquilizers ) in the year after the screening date . We determined whether patients had ever received pneumococcal vaccination and whether they had received influenza vaccination or colon cancer screening ( hemoccult test , barium enema , sigmoidoscopy , or colonoscopy ) in the year after the screening date . We determined whether female patients had had mammography and Papanicolaou smears in the year after the screening date . We also determined whether patients had been prescribed aspirin , a nonsteroidal anti-inflammatory drug , or estrogen replacement in each of the 2 years before the screening date . For use of health services in the year after the screening date , we determined the following : whether patients had been hospitalized or had visited the emergency department and the mean number of these episodes among patients with at least one of these visits ; the mean number of outpatient visits , including those to medical and surgical subspecialty clinics ; and total outpatient charges , including charges for office visits , outpatient diagnostic testing , and pharmacy services . Mortality was determined as of December 1992 using hospital discharge condition , death summaries , autopsy reports , and the Indiana State Board of Health 's death certificate files . Statistical Analysis For dichotomous variables , we used chi-square tests to compare frequencies among patients with no cognitive impairment , mild cognitive impairment , or moderate to severe cognitive impairment . We used analysis of variance to compare the mean log-transformed values for continuous and count variables among these three groups . We also looked for significant differences between those with documented cognitive impairment and those with undocumented impairment . A patient with documented cognitive impairment had an SPMQ score of 5 or greater and had dementia ( or a synonymous term such as the organic brain syndrome or Alzheimer disease ) listed in their outpatient medical record . With moderate to severe cognitive impairment as the dependent variable , we next used logistic regression to determine which variables were independently associated with cognitive impairment . Because the data used in these models are cross-sectional , these analyses can not ascribe causality . The multivariable regression was done to determine whether age , education , and race were independently correlated with cognitive impairment even when we controlled for comorbid conditions . In the first model , we included all comorbid medical illnesses as independent variables . In the second model , we included the significant variables from the first model in addition to the demographic variables , with significant bivariate relations including age , sex , years of education , and low serum albumin level . The calculation of patients ' SPMQ scores for these models did not include corrections for race or education . For these analyses , we r and omly divided the data set in half for derivation and validation sets . We also did logistic regression analyses to determine if cognitive impairment was independently correlated with hospitalization , emergency department visits , outpatient visits , use of preventive health care services , or mortality after we controlled for age , race , and education . Results From January 1991 to May 1993 , we contacted 4413 patients aged 60 years and older during routine visits to the primary care practice ; 3954 ( 90 % ) of these patients completed the SPMQ . One hundred fifteen patients refused the screening examination , 284 were ineligible , and 60 could not complete the SPMQ . Among all patients screened , the mean age was 68 years ( range , 60 to 102 years ) , 68.8 % were women , 63.4 % were black , 43.6 % had 8 or fewer years of education , 10.5 % had evidence of This article presents results of a prospect i ve multivariate study of hospitalized elderly patients at an acute-care Veterans Administration ( VA ) hospital to identify factors on hospital admission predictive of several short- and long-term outcomes : in-hospital and 6-month mortality , immediate and delayed nursing home admission , length of hospital stay , and 6-month rehospitalization . All patients aged 70 years and over admitted to acute-care beds on the medical service wards during a 1-year period were included in the study ( N = 396 ) . Factors most predictive of 6-month mortality ( using logistic regression ) were decreased functional status , admitting diagnosis , and decreased mental status . Factors most predictive of nursing home admission were decreased functional status , living location , and decreased mental status . Functional status was a stronger predictor of length of stay , mortality , and nursing home placement than was principal admitting diagnosis -- of relevance to the current emphasis on diagnosis-related groups ( DRGs ) . These data may be helpful in improving discharge planning , in re source allocation , and in targeting patients for different specialized geriatric programs The current increase in aged individuals in number and proportionof the general population warrants dependable strategies to improve early detection of cognitive impairment . It was the goal of the present study to develop a triage for bedside testing and outpatient ser vices . In a prospect i ve clinical cohort study at the outpatient Memory Clinic , University of Ulm , Germany , 232 subjects were diagnosed with Alzheimer ’s disease [ AD ; NINCDS-ADRDA criteria ; n = 66 ; age 65.9 ± 7.3 years ( mean ± SD ) ; Mini Mental State Examination ( MMSE ) score 23.4 ± 4.1 ] , mild cognitive impairment ( MCI ; criteria of Petersen et al. ; n = 48 ; age 66.4 ± 7.1 years ; MMSE score 28.3 ± 1.5 ) , and major depressive disorder ( DSM-IV criteria ; n = 61 ; age 63.4 ± 8.0 years ; MMSE score 28.6 ± 1.6 ) . Diagnosis was secured with extensive neuropsychological , clinical , radiological , and laboratory investigations . Six brief screening tests including the Memory Impairment Screen ( MIS ) , Letter Sorting Test ( LST ) , Verbal Fluency ( VF ) , and Clock Drawing Test ( CDT ) were assessed independently from the diagnostic procedure . We compared single items and composite scores . LST yielded a diagnostic accuracy of 0.81 and 0.62 for AD and MCI patients versus controls , respectively . With the MIS , diagnostic accuracy was 0.89 and 0.71 , respectively . With a combination of LST , MIS , VF , and CDT , a sensitivity for AD and MCI patients of 1.00 and 0.83 was achieved . Thus , single-item screening ( e.g. LST , VF ) taking little more than 1 min and suitable for bedside testing or brief screening in the general practitioner ’s office yields diagnostic accuracy comparable to st and ard laboratory tests for other diseases . A composite of screening tests suitable for application in general outpatient care in neurological and psychiatric services reliably detects patients with AD and MCI OBJECTIVE To examine the clinical utility of the Clock Test for identifying dementia . DESIGN Group comparisons . SETTING A hospital-based out-patient diagnostic clinic . PATIENTS Volunteer sample of elderly individuals ( normal elderly , NE , n = 62 ) and a referred sample of probable Alzheimer Disease ( AD , n = 58 ) patients meeting NINCDS-ADRDA criteria . MAIN OUTCOME MEASURE The Clock Test is composed of three components : Clock Drawing , Clock Setting , and Clock Reading . A detailed scoring system for qualitative as well as quantitative evaluation of Clock Drawing errors was used . Five time setting s , varying in level of complexity , were used to evaluate Clock Setting and Clock Reading . RESULTS The groups differed significantly on Clock Drawing , Clock Setting , and Clock Reading ( P less than 0.001 ) . On Clock Drawing , the AD group made significantly more errors of omission and misplacement of numbers than the NE group ( P less than 0.001 ) . Using cut-off scores derived to maximize separation between the groups to define deficits in performance , the sensitivity and specificity for the diagnosis of AD of Clock Drawing , Clock Setting , and Clock Reading were 92 % and 86 % , 87 % and 97 % , 92 % and 85 % , respectively . Using a criterion of deficits on two or more of the three components , sensitivity and specificity increased to 94 % and 93 % , respectively . CONCLUSIONS Deficits on clock drawing in AD may be reflective of a generalized disturbance in the conceptualization of time rather than constructional apraxia , per se . The functionally relevant components of Clock Setting and Clock Reading combined with Clock Drawing make the Clock Test particularly useful as a screening and research tool for AD |
811 | 17,712,252 | Interventions generally demonstrated improvement in HRQL .
Conclusions : A variety of interventions can improve HRQL among adults with diabetes , but the magnitude of effects varied with the interventions . | Background : Health-related quality of life ( HRQL ) is increasingly used to measure the outcomes of interventions among people with chronic diseases .
Objectives : To assess the effect of interventions for adults with diabetes on HRQL , as measured by the Short Form (SF)-36 question naire . | OBJECTIVE To prospect ively examine the effect of weight loss 1 year after laparoscopic adjustable gastric b and surgery on a broad range of health outcomes in 50 diabetic subjects . RESEARCH DESIGN AND METHODS A total of 50 ( 17 men , 33 women ) of 51 patients with type 2 diabetes , from a total of 500 consecutive patients , were studied preoperatively and again 1 year after surgery . RESULTS Preoperative weight and BMI ( means + /- SD ) were 137 + /- 30 kg and 48.2 + /- 8 kg/m(2 ) , respectively ; at 1 year , weight and BMI were 110 + /- 24 kg and 38.7 + /- 6 kg/m(2 ) , respectively . There was significant improvement in all measures of glucose metabolism . Remission of diabetes occurred in 32 patients ( 64 % ) , and major improvement of glucose control occurred in 13 patients ( 26 % ) ; glucose metabolism was unchanged in 5 patients ( 10 % ) . HbA(1c ) was 7.8 + /- 3.2 % preoperatively and 6.2 + /- 2.7 % at 1 year ( P < 0.001 ) . Remission of diabetes was predicted by greater weight loss and a shorter history of diabetes ( pseudo r(2 ) = 0.44 , P < 0.001 ) . Improvement in diabetes was related to increased insulin sensitivity and beta-cell function . Weight loss was associated with significant improvements in fasting triglyceride level , HDL cholesterol level , hypertension , sleep , depression , appearance evaluation , and health-related quality of life . Early complications occurred in 6 % of patients ( wound infections in 4 % , respiratory support in 2 % ) , and late complications occurred in 30 % of patients ( gastric prolapse in 20 % , b and erosion in 6 % , and tubing leaks in 4 % ) . All late complications were successfully revised surgically . CONCLUSIONS Modern laparoscopic weight-loss surgery is effective in managing the broad range of health problems experienced by severely obese individuals with type 2 diabetes . Surgery should be considered as an early intervention Abstract OBJECTIVE : To examine the impact of a nurse-coordinated intervention delivered to patients with non-insulin-dependent diabetes mellitus between office visits to primary care physicians . DESIGN : R and omized , controlled trial . SETTING : Veterans Affairs general medical clinic . PATIENTS : 275 veterans who had NIDDM and were receiving primary care from general internists . INTERVENTION : Nurse-initiated contacts were made by telephone at least monthly to provide patient education ( with special emphasis on regimens and significant signs and symptoms of hyperglycemia and hypoglycemia ) , reinforce compliance with regimens , monitor patients ’ health status , facilitate resolution of identified problems , and facilitate access to primary care . MEASUREMENTS : Glycemic control was assessed using glycosylated hemoglobin ( GHb ) and fasting blood sugar ( FBS ) levels . Health-related quality of life ( HRQOL ) was measured with the Medical Outcomes Study SF-36 , and diabetes-related symptoms were assessed using patients ’ self-reports of signs and symptoms of hyper- and hypoglycemia during the previous month . MAIN RESULTS : At one year , between-group differences favored intervention patients for FBS ( 174.1 mg/dL vs 193.1 mg/dL , p=0.011 ) and GHb ( 10.5 % vs 11.1 % , p=0.046 ) . Statistically significant differences were not observed for either SF-36 scores ( p=0.66 ) or diabetes-related symptoms ( p=0.23 ) . CONCLUSIONS : The intervention , design ed to be a pragmatic , low-intensity adjunct to care delivered by physicians , modestly improved glycemic control but not HRQOL or diabetes-related symptoms OBJECTIVE To assess the efficacy of a lifestyle intervention program that can be readily translated into clinical practice for obese patients with type 2 diabetes . RESEARCH DESIGN AND METHODS The study consisted of a 12-month r and omized controlled trial of 147 health plan members with type 2 diabetes and obesity ( BMI > or=27 kg/m(2 ) ) . Participants were r and omized to lifestyle case management or usual care . Case management entailed individual and group education , support , and referral by registered dietitians ; intervention cost was US dollars 350 per person . Individuals treated with usual care received educational material . Both groups received ongoing primary care . Outcomes were difference between groups for change in weight ( kilograms ) , waist circumference ( centimeters ) , HbA(1c ) , fasting lipid levels , use of prescription medications , and health-related quality of life . RESULTS Case management result ed in greater weight loss ( P < 0.001 ) , reduced waist circumference ( P < 0.001 ) , reduced HbA(1c ) level ( P = 0.02 ) , less use of prescription medications ( P = 0.03 ) , and improved health-related quality of life ( P < 0.001 ) compared with usual care . The 12-month group difference in weight loss and waist circumference was 3.0 kg ( 95 % CI -5.4 to -0.6 ) and -4.2 cm ( -6.8 to -1.6 ) . HbA(1c ) differences were greatest at 4 months ( -0.59 % , P = 0.006 ) but not significant by 12 months ( -0.19 % , P = 0.45 ) . Participants in the case management group lowered their use of medications , primarily diabetes medications , by 0.8 medications per day more than participants treated with usual care ( P = 0.03 ) . In seven of nine quality -of-life domains , the case management group improved compared with usual care ( P < 0.05 ) . CONCLUSIONS Moderate-cost dietitian-led lifestyle case management may improve diverse health indicators among obese patients with type 2 diabetes OBJECTIVE To evaluate the impact of primary care group visits ( chronic care clinics ) on the process and outcome of care for diabetic patients . RESEARCH DESIGN AND METHODS We evaluated the intervention in primary care practice s r and omized to intervention and control groups in a large-staff model health maintenance organization ( HMO ) . Patients included diabetic patients > or = 30 years of age in each participating primary care practice , selected at r and om from an automated diabetes registry . Primary care practice s were r and omized within clinics to either a chronic care clinic ( intervention ) group or a usual care ( control ) group . The intervention group conducted periodic one-half day chronic care clinics for groups of approximately 8 diabetic patients in their respective doctor 's practice . Chronic care clinics consisted of st and ardized assessment s ; visits with the primary care physician , nurse , and clinical pharmacist ; and a group education/peer support meeting . We collected self-report question naires from patients and data from administrative systems . The question naires were mailed , and telephoned interviews were conducted for nonrespondents , at baseline and at 12 and 24 months ; we queried the process of care received , the satisfaction with care , and the health status of each patient . Serum cholesterol and HbA1c levels and health care use and cost data was collected from HMO administrative systems . RESULTS In an intention-to-treat analysis at 24 months , the intervention group had received significantly more recommended preventive procedures and helpful patient education . Of five primary health status indicators examined , two ( SF-36 general health and bed disability days ) were significantly better in the intervention group . Compared with control patients , intervention patients had slightly more primary care visits , but significantly fewer specialty and emergency room visits . Among intervention participants , we found consistently positive associations between the number of chronic care clinics attended and a number of outcomes , including patient satisfaction and HbA1c levels . CONCLUSIONS Periodic primary care sessions organized to meet the complex needs of diabetic patients imrproved the process of diabetes care and were associated with better outcomes OBJECTIVES The current study was conducted to compare the effectiveness of delivering diabetes education in either a group or individual setting using a consistent , evidence -based curriculum . RESEARCH DESIGN AND METHODS A total of 170 subjects with type 2 diabetes were r and omly assigned to either group ( n = 87 ) or individual ( n = 83 ) educational setting s. Subjects received education in four sequential sessions delivered at consistent time intervals over a 6-month period . Outcomes included changes in knowledge , self-management behaviors , weight , BMI , HbA(1c ) , health-related quality of life , patient attitudes , and medication regimen . Changes were assessed at baseline and after the 2-week , 3-month , and 6-month education sessions . RESULTS Both educational setting s had similar improvements in knowledge , BMI , health-related quality of life , attitudes , and all other measured indicators . HbA(1c ) decreased from 8.5 + /- 1.8 % at baseline to 6.5 + /- 0.8 % at 6 months ( P < 0.01 ) in the study population as a whole . Subjects assigned to the individual setting had a 1.7 + /- 1.9 % reduction in HbA(1c ) ( P < 0.01 ) , whereas subjects assigned to the group setting had a 2.5 + /- 1.8 % reduction in HbA(1c ) ( P < 0.01 ) . The difference in HbA(1c ) improvement was marginally greater in subjects assigned to group education versus individualized education ( P = 0.05 ) . CONCLUSIONS This study demonstrates that diabetes education delivered in a group setting , when compared with an individual setting , was equally effective at providing equivalent or slightly greater improvements in glycemic control . Group diabetes education was similarly effective in delivering key educational components and may allow for more efficient and cost-effective methods in the delivery of diabetes education programs AIM The aim of our study was to describe investigate and association between improved glycaemic control on quality of life ( QoL ) during 1 year of treatment in a sample of 94 Type 2 diabetic patients referred for insulin therapy to an outpatient department ( OPD ) . Treatment was aim ed at achieving acceptable glycaemic control by means of maximizing oral therapy , if necessary switching over to insulin therapy , and information and education provided by a diabetes specialist nurse and dietitian . METHODS QoL was measured using a disease-specific ( Diabetes Health Profile ( DHP ) ) and a generic question naire ( R AND -36 ) . After 1 year the medical examination and QoL measurements were repeated . The association between 1-year changes in QoL and achievement of good metabolic control ( final glycosylated haemoglobin ( HbA1c ) < or = 8 % ) , switch to insulin therapy , and presence of hyperglycaemic complaints at baseline was analysed after adjustment for appropriate confounders . RESULTS After 1 year , mean HbA1c was reduced from 10.4 % to 7.8 % . Also QoL improved in the total group . Patients who achieved good glycaemic control after 1 year ( 61 % ) improved in a similar manner as the others . Patients switched over to insulin ( 65 % ) improved in a similar manner as the others , but at the final examination they experienced more problems with social functioning and pain . Patients with hyperglycaemic complaints at baseline ( 49 % ) improved more in QoL than those without , especially in physical functioning , vitality and health change , but at the final examination still scored lower on a majority of the DHP and R AND -36 dimensions . CONCLUSION Symptoms of hyperglycaemia predict the strength of an association between improvements of glycaemic control and OBJECTIVE To compare the efficacy and safety of continuous subcutaneous insulin infusion ( CSII ) and multiple daily injection ( MDI ) in older adults with insulin-treated type 2 diabetes and to assess treatment satisfaction and quality of life . RESEARCH DESIGN AND METHODS Adults ( n = 107 ) > or = 60 years of age ( mean age 66 years ) with insulin-treated type 2 diabetes ( mean duration 16 years , BMI 32 kg/m(2 ) , and HbA(1C ) [ A1C ] 8.2 % ) were r and omized to CSII ( using insulin lispro ) or MDI ( using insulin lispro and insulin glargine ) in a two-center , 12-month , prospect i ve , r and omized , controlled clinical trial . Efficacy was assessed with A1C , safety by frequency of hypoglycemia , and treatment satisfaction and quality of life with the Diabetes Quality of Life Clinical Trial Question naire and the 36-item short-form health survey , version 2 . RESULTS Forty-eight CSII subjects ( 91 % ) and 50 MDI subjects ( 93 % ) completed the study . Mean A1C fell by 1.7 + /- 1.0 % in the CSII group to 6.6 % and by 1.6 + /- 1.2 % in the MDI group to 6.4 % . The difference in A1C between treatment groups was not statistically significant ( P = 0.20 ) . Eighty-one percent of CSII subjects and 90 % of MDI subjects experienced at least one episode of minor ( self-treated ) hypoglycemia ( P = 0.17 ) , and three CSII and six MDI subjects experienced severe hypoglycemia ( P = 0.49 ) . Rates of severe hypoglycemia were similarly low in the two groups ( CSII 0.08 and MDI 0.23 events per person-year , P = 0.61 ) . Weight gain did not differ between groups ( P = 0.70 ) . Treatment satisfaction improved significantly with both CSII and MDI ( P < 0.0001 ) , and the difference between groups was not statistically significant ( P = 0.58 ) . CONCLUSIONS In older subjects with insulin-treated type 2 diabetes , both CSII and MDI achieved excellent glycemic control with good safety and patient satisfaction OBJECTIVE We evaluated the impact of automated telephone disease management ( ATDM ) calls with telephone nurse follow-up as a strategy for improving outcomes such as mental health , self-efficacy , satisfaction with care , and health-related quality of life ( HRQL ) among low-income patients with diabetes mellitus . RESEARCH DESIGN This was a r and omized , controlled trial . SUBJECTS Two hundred forty-eight primarily English- and Spanish-speaking adults with diabetes enrolled at the time of visits to a county health care system . INTERVENTION In addition to usual care , intervention patients received biweekly ATDM calls with telephone follow-up by a diabetes nurse educator . Patients used the ATDM calls to report information about their health and self-care and to access self-care education . The nurse used patients ' ATDM reports to allocate her time according to their needs . MEASURES Patient-centered outcomes were measured at 12 months via telephone interview . RESULTS Compared with patients receiving usual care , intervention patients at follow-up reported fewer symptoms of depression ( P = 0.023 ) , greater self-efficacy to conduct self-care activities ( P = 0.006 ) , and fewer days in bed because of illness ( P = 0.026 ) . Among English-speaking patients , those receiving the intervention reported greater satisfaction with their health care overall and with the technical quality of the services they received , their choice of providers and continuity of care , their communication with providers , and the quality of their health outcomes ( all P < 0.042 ) . Intervention and control patients had roughly equivalent scores for established measures of anxiety , diabetes-specific HRQL , and general HRQL . CONCLUSIONS This intervention had several positive effects on patient-centered outcomes of care but no measurable effects on anxiety or HRQL Background : We implemented a comprehensive intervention program targeting general practice staff , that proved successful in optimizing practice organization and clinical decision-making . In this paper , health-related quality of life ( HRQL ) is investigated as a clinical outcome . Objective : To evaluate the effect of the implementation of an intervention program on the HRQL in patients at high cardiovascular risk . Research design : R and omized controlled trial . Intervention practice s ( n = 62 ) received a comprehensive intervention program ( by means of outreach visitors ) lasting 21 months . HRQL of patients at high cardiovascular risk was assessed by the MOS 36-Item Short-Form Health Survey ( SF-36 ) , at baseline and after intervention . Three patient categories were distinguished : diabetes mellitus , cardiovascular disease and hypertension . Results : HRQL deteriorated in all respondents , but more pronounced in the control group . In diabetes patients the differences between intervention and control group were significant for the Vitality and Mental Health scales , with mean difference in change of 3.93 ( 95 % CI : 1.08–6.78 ) and 3.71 ( 95 % CI : 0.73–6.68 ) , respectively . Patients with cardiovascular disease had significantly different changes on three scales : physical functioning ( 3.57 , 95 % CI : 0.71–6.43 ) , vitality ( 3.01 , 95 % CI : 0.72–5.30 ) and social functioning ( 3.96 , 95 % CI : 0.50–7.42 ) . In patients with hypertension , there were no differences between the intervention and control group . Conclusion : Our comprehensive intervention program result ed in changes in HRQL on several domains , particularly in patients with diabetes and cardiovascular disease Background . There is a need to evaluate empirical disease management programs used in managing chronic diseases such as diabetes mellitus in managed care setting s. Methods . We analyzed data from 252 patients with type 2 diabetes before and 1 year after enrollment in a disease management program . We examined clinical indicators such as HbA1C , HDL , LDL , total cholesterol , diastolic blood pressure , and BMI in addition to self-reported health status measured by SF-36 instrument . Results . All clinical indicators showed statistically and clinical ly significant improvements . Only vitality and mental health showed statistically significant improvements in health status . Weak to moderate significant correlation between clinical indicators and health status was observed . Conclusions . Disease management can be effective at making significant clinical improvements for participants in a mixed-model HMO setting . No strong relationship between clinical indicators and health status was found . Future research is needed using a more specific health status measuring instrument and a r and omized clinical trial design OBJECTIVE To describe the health-related quality of life ( HRQOL ) of patients with insulin-treated diabetes and symptoms of diabetic gastroparesis and to assess the impact of domperidone on HRQOL in these patients . RESEARCH DESIGN AND METHODS This two-phase multicenter study was part of a safety and efficacy investigation . Phase 1 involved 4-week single-blind treatment with domperidone 20 mg q.i.d . ( n = 269 ) . Patients demonstrating significant symptomatic improvement ( n = 208 ) continued to phase II , a 4-week , double-blind , parallel-group study with patients receiving placebo ( n = 103 ) or domperidone ( n = 105 ) . Patients completed the Medical Outcomes Study Short-Form-36 Health Survey at selection and at the end of each phase . Physical component summary ( PCS ) and mental component summary ( MCS ) scores served as primary parameters , and the eight subscales were secondary parameters . RESULTS HRQOL scores of subjects enrolled in the trial were significantly lower than norms from the general population and people with diabetes ( P < 0.001 ) . Subjects experiencing symptomatic improvement after 4 weeks of single-blind treatment demonstrated significant improvement in all HRQOL parameters ( P < 0.001 ) ; PCS , MCS , and six subscale scores of nonresponders did not change . Between-group change score differences were significant for PCS , MCS , and seven subscales ( P < 0.05 to P < 0.001 ) . During phase II , the domperidone group maintained their HRQOL ; the placebo group showed a significant decline in PCS and four subscales ( P < 0.05 ) . The between-group difference in the PCS score change was statistically significant ( −1.77 vs. 0.65 , P = 0.05 ) . CONCLUSIONS Results suggest that patients with symptoms of diabetic gastroparesis experience notable HRQOL impairment and that symptomatic relief with domperidone is accompanied by improvements in HRQOL that can be sustained over 4 weeks of treatment OBJECTIVE An Achilles tendon-lengthening ( ATL ) procedure is effective at reducing ulcer recurrence in patients with diabetes , peripheral neuropathy , and a plantar ulcer , but its effects on functional limitations and perceived disability are unknown . The purpose of this study is to report the effects of an ATL and total contact casting ( TCC ) on the functional limitations and perceived disability of patients with neuropathic plantar ulcers . RESEARCH DESIGN AND METHODS Twenty-eight subjects with a mean age of 55 + /- 10 years and a BMI of 33 + /- 6 kg/m(2 ) participated . All subjects had a history of diabetes , loss of protective sensation , limited ankle motion , and a recurrent forefoot ulcer . Subjects were r and omized into two groups : an ATL group ( n = 14 ) , who received treatment of ATL , and TCC and a TCC group ( n = 14 ) , who received TCC only . Subjects completed a modified physical performance test ( PPT ) and the SF-36 Health Survey before treatment , after primary treatment and healing of the plantar forefoot ulcer , and 8 months after initial ulcer healing . RESULTS There were no significant changes in functional limitations as measured by the PPT between groups or over time . The physical summary score of the SF-36 decreased slightly from before treatment to 8 months after initial ulcer healing in the ATL group ( 35 + /- 7 to 31 + /- 6 ) , whereas the TCC group score increased during this time ( 34 + /- 8 to 39 + /- 11 ; P < 0.05 ) . CONCLUSIONS The ATL result ed in no measurable change in functional limitations , but patients receiving an ATL and TCC reported lower physical functioning at 8 months after initial ulcer healing than subjects receiving TCC alone and may require additional physical therapy to address this perceived disability PURPOSE To describe the incidence of depression and other behavioral disorders in diabetic coronary patients following major cardiac events and to assess the impact of cardiac rehabilitation . PATIENTS 291 consecutive coronary patients ( 70 with diabetes mellitus ) . METHODS Patients were prospect ively enrolled in comprehensive phase II cardiac rehabilitation 4 to 6 weeks following a major cardiac event . Depressive symptoms and other behavioral characteristics ( anxiety , somatization , hostility ) , as well as parameters of quality of life , were assessed by vali date d question naires at entry and upon completion ( 12 weeks , 36 sessions ) of cardiac rehabilitation . RESULTS Diabetic patients made up 24 % of the cohort and were more likely to be female ( P = 0.08 ) , hypertensive ( P = 0.05 ) , and obese ( P = 0.08 ) . Additionally , diabetic patients had a reduced exercise capacity ( P = 0.008 ) , lower high-density lipoprotein cholesterol ( P = 0.008 ) , lower low-density lipoprotein cholesterol ( P = 0.02 ) , and increased triglyceride ( P = 0.04 ) levels . Diabetic patients had a higher incidence of depression ( 26 % versus 14 % ; P < 0.03 ) , demonstrated more symptoms of somatization ( P < 0.06 ) , and exhibited lower scores for components of quality of life . Following cardiac rehabilitation , the incidence of depression was reduced in diabetic patients by 67 % ( P = 0.01 ) and ultimately equaled the 9 % prevalence found in the non-diabetic group . CONCLUSIONS Diabetic coronary patients demonstrate a higher incidence of depression than non-diabetic patients following major cardiac events . In addition to improving traditional cardiac risk factors , cardiac rehabilitation reduces depression in this high-risk group The relationship between glycemic control and health-related quality of life was examined in patients with non-insulin-dependent diabetes mellitus ( NIDDM ) . Within the context of a r and omized controlled trial , 275 patients with NIDDM receiving primary care from a Veteran 's Administration general medical clinic were enrolled and monitored for 1 year . Glycemic control ( glycosylated hemoglobin levels ) and health-related quality of life ( Medical Outcomes Study Short-Form 36-item Health Survey [ SF-36 ] ) were assessed at baseline and at 1 year . Multivariate regression modeling using baseline and change scores during a 1− year period did not find a linear or curvilinear relationship between glycosylated hemoglobin and SF-36 scores ( P = .15 ) ; this was true even after controlling for five covariates identified a priori ( insulin use , number of diabetic complications , duration of diabetes , education , number of hyper- , or hypoglycemic episodes during the preceding month ) . Health services research ers and clinicians alike need to be aware that these two important outcomes may not be directly related . This lack of association could contribute to the high noncompliance rates observed among patients prescribed complex diabetic regimens . Unless patients perceive a benefit from following such regimens , good glycemic control may continue to be an elusive therapeutic goal , especially in patients with long-st and ing disease The effects of insulin therapy on patient well-being , treatment satisfaction and mood , and on carer strain were studied in 30 elderly Type 2 diabetic patients ( age 73 + /- 7 ( SD ) yr ) in poor glycaemic control on tablet therapy . A comparison group of ten poorly controlled patients who remained on oral agents was also studied . After 4 weeks of insulin treatment , there were significant improvements in mental health , role-emotional , role-physical ( all P<0.05 ) and vitality ( P<0.01 ) domains of the short form health survey ( SF-36 ) , and also in the diabetes treatment and satisfaction question naire ( DTSQ ) and geriatric depression scale ( both P<0.01 ) compared to baseline . After 12 weeks , the improvements in mental health , social functioning and vitality ( P<0.01 for all domains ) , and in the DTSQ were sustained . Carer strain was lower at 4 weeks . No changes in outcomes were seen in the comparison group . In selected elderly Type 2 diabetic patients , insulin treatment is associated with significant improvements in well-being , treatment satisfaction and mood , even without significant improvements in glycaemic control and without increase in carer strain . The SF-36 and DTSQ are sensitive to the benefits of the changes in the treatment for these patients We evaluated a Veterans Health Administration ( VHA ) care coordination/ hometelehealth ( CC/HT ) programon the utilization of health care services and health-related quality of life ( HRQL ) in veterans with diabetes . Administrative records of 445 veterans with diabetes were review ed to compare health care service utilization in the 1-year period before and 1-year period postenrollment and also examined self-reported HRQL at enrollment and 1 year later . Multivariate analyses indicated a statistically significant reduction in the proportion of patients who were hospitalized ( 50 % reduction ) , emergency room use ( 11 % reduction ) , reduction in the average number of bed days of care ( decreased an average of 3.0 days ) , and improvement in the HRQL role-physical functioning , bodily pain , and social functioning . The results need to be interpreted with caution because we used a single-group study design that may be influenced by regression to the mean . Ideally , future research should use a r and omized controlled trial design OBJECTIVE To examine the effects of patient choice between two education curriculums that emphasized either the st and ard or nutritional management of type 2 diabetes on class attendance and other outcomes among a mostly Hispanic patient population . RESEARCH DESIGN AND METHODS A total of 596 patients with type 2 diabetes were r and omly assigned to either a choice or no choice condition . Patients in the choice condition were allowed to choose their curriculum , while patients in the no choice condition were r and omly assigned to one of the two curriculums . Outcomes were assessed at baseline and at a 6-month follow-up . RESULTS When given a choice , patients chose the nutrition curriculum almost four times more frequently than the st and ard curriculum . Contrary to our hypothesis , however , patients who had a choice did not significantly increase their attendance rates or demonstrate improvements in other diabetes outcomes compared with patients who were r and omly assigned to the two curriculums . Patients in the nutrition curriculum had significantly lower serum cholesterol at a 6-month follow-up , whereas patients in the st and ard curriculum had significant improvements in glycemic control . Of the r and omized patients , 30 % never attended any classes ; the most frequently cited reasons for nonattendance were socioeconomic . Hispanic patients , however , were just as likely as non-Hispanic patients to attend classes and participate at the follow-up . Patients who attended all five classes of either curriculum significantly increased their diabetes knowledge , gained less weight , and reported improved physical functioning compared with patients who did not attend any classes . CONCLUSIONS Although providing patients with a choice in curriculums at the introductory level did not improve outcomes , differential improvements were noted between patients who attended curriculums with different content emphasis . We suggest that diabetes education programs should provide the opportunity for long-term , repetitive contacts to exp and on the modest gains achieved at the introductory level , as well as provide more options to match individual needs and interests and to address socioeconomic barriers to participation OBJECTIVES The aim of the study was to assess the change in health related quality of life ( HRQoL ) after infrageniculate bypass grafting in patients with critical limb ischaemia ( CLI ) . DESIGN Observational , prospect i ve clinical study . MATERIAL S AND METHODS In total , 86 patients ( 72 % male ; age 71 ( IQR , 64 - 78 ) years ) undergoing infrageniculate bypass grafting for limb salvage were assessed by the short form (SF)-36 question naire before and 6 months after surgery . In subgroup analysis , the influence of diabetes mellitus , age , gender , and stage of peripheral arterial occlusive disease on HRQoL- outcome were assessed . RESULTS Following revascularization HRQoL significantly improved in all eight dimensions of the SF-36 . While baseline HRQoL-values of diabetic and non-diabetic patients did not differ significantly , postoperative improvement was significantly less in the diabetes group . CONCLUSIONS An aggressive approach towards infrageniculate bypass surgery for limb salvage is justified by quality of life improvement . However , this improvement tends to be less in patients with diabetes mellitus Pain is the most disturbing symptom of diabetic neuropathy . Traditionally this type of pain was treated with tricyclic antidepressants which frequently have many side effects . In the study reported here , gabapentin was administered in escalating doses up to 3600 mg per day to eligible patients with moderate to severe diabetic neuropathy pain in a double blind placebo controlled fashion . Gabapentin provided superior and significant pain relief over placebo . In addition , patients taking gabapentin had improvement of sleep scores and a number of items on mood and quality of life question naires . Gabapentin was tolerated well with mild and tolerable side effects OBJECTIVE To evaluate the effect of intensive diabetes treatment on patient quality of life assessed by the Diabetes Quality -of-Life Measure , the Symptom Checklist-90R , the Medical Outcome Study 36-Item Short Form Survey , and intercurrent psychosocial events in the Diabetes Control and Complications Trial ( DCCT ) . RESEARCH DESIGN AND METHODS The DCCT was a 29-center prospect i ve controlled clinical trial that demonstrated the beneficial effect of intensive diabetes treatment on retinopathy , nephropathy , and neuropathy . The 1,441 volunteers with IDDM , aged 13–39 years , were r and omly assigned to intensive or conventional diabetes therapy . The volunteers were followed for a mean of 6.5 years ( range 3–9 years ) . Quality -of-life data were collected during annual visits . Of the volunteers , 99 % completed the study , and > 95 % of scheduled tests were completed . RESULTS All analyses of quality of life , psychiatric symptom indexes , and psychosocial event data showed no differences between intensive and conventional diabetes treatment . CONCLUSION Under careful treatment conditions , such as those followed in the DCCT , patients undergoing intensive diabetes treatment do not face deterioration in the quality of their lives , even while the rigor of their diabetes care is increased The aim of this study is to determine effects and the role of facilitators of empowerment of a Multidisciplinary Intensive Education Programme ( MIEP ) for diabetic patients with prolonged self-management difficulties . Glycemic control ( HbA1c ) , health-related quality of life ( HR-QoL ) and facilitators of empowerment ( health locus of control and coping ) were measured in 99 participants of MIEP at baseline ( T0 ) , 3 ( T1 ) and 12 months ( T2 ) follow-up and in 231 non-referred consecutive out patients . HbA1c improved at T2 , although initial improvement was partially lost . Patients improved in most HR-QoL domains , without any relapse at T2 . At T2 , participants no longer differed from the average out patients in any outcome . Initially , the HbA1c of men and women improved equally , but at T2 women consoli date d improvement , whereas men relapsed . After MIEP , patients became more empowered ( both at T1 and T2 ) , explaining additional variance in HR-QoL improvement . The aim of MIEP to empower patients , rather than trying to solve problems for them seems effective |
812 | 18,646,082 | Home participants underwent fewer investigations than hospital participants ( P < 0.002 ) and general activity was higher in the home group .
No significant differences were found for clinical outcomes , adverse events , complications or change of intravenous lines , or time to next admission .
Home participants received less low-dose home maintenance antibiotic .
Quality of life measures showed no significant differences for dyspnoea and emotional state , but fatigue and mastery were worse for home participants , possibly due to a higher general activity and need of support .
Personal , family , sleeping and eating disruptions were less important for home than hospital admissions .
Home therapy was cheaper for families and the hospital .
It suggests that , in the short term , home therapy does not harm individuals , entails fewer investigations , reduces social disruptions and can be cost-effective .
There were both advantages and disadvantages in terms of quality of life . | BACKGROUND Recurrent endobronchial infection in cystic fibrosis ( CF ) requires treatment with intravenous antibiotics for several weeks usually in hospital , affecting health costs and quality of life for patients and their families .
OBJECTIVES To determine whether home intravenous antibiotic therapy in CF is as effective as inpatient intravenous antibiotic therapy and if it is preferred by individuals or families or both . | Many cystic fibrosis patients with Pseudomonas lung infections receive intravenous ( IV ) antibiotics and chest physiotherapy ( CPT ) at home . Previous studies have suggested that home care , in the setting of a clinical study , is as efficacious as hospital care . This report compares the outcomes of home care with minimal supervision to outcomes of hospital care . We compared two groups of similar age and severity of lung impairment . Patients met strict definitions for home or hospital treatment ( 27 home care courses/33 hospital care courses ) . Five patients completed six courses of both home care and hospital treatment . Treatment in both groups included intravenous antibiotics and CPT . Primary outcome measures included changes in pulmonary function between the start of treatment and after 2 weeks of therapy , duration of treatment , and intervals between antibiotic courses . In hospitalized patients , forced vital capacity ( FVC ) increased by 17.4 + /- 3.1 % ( mean + /- SEM ) , and forced expiratory volume in one second ( FEV1 ) increased by 23.3 + /- 4.1 % , both significant at P < 0.001 . The FVC and FEV1 of patients treated at home increased by 10.2 + /- 2.0 % and 13.7 + /- 2.6 % respectively , neither of which was a significant improvement . Similar results were found in the five patients completing both home and hospital courses . The average duration of treatment was twice as long and time between IV antibiotic courses only two-thirds as long for those treated at home compared with the hospitalized patients . Previous reports have cl aim ed that home care in the setting of a prospect i ve study is as efficacious as hospital care . Our experience indicates that routine home care with minimal supervision of patients is less effective than hospital care . Furthermore , home care as delivered to patients in this report increased the overall cost of care by as much as 30 % because of longer and more frequent courses of antibiotic therapy Abstract . Background : Home intravenous antibiotic treatment has added to therapeutic options against Pseudomonas aeruginosa in cystic fibrosis ( CF ) patients leading to increased flexibility . A prospect i ve clinical study was carried out to compare home and hospital iv antibiotic treatment in CF patients with chronic P. aeruginosa infection . Patients and Methods : Treatment courses were planned selectively , exacerbations were excluded . 28 consecutive hospital courses ( group 1 ) were compared with 30 home care courses ( group 2 ) . Chest physiotherapy and nutrition therapy were carried on in both groups . Antibiotic treatment in both groups consisted of tobramycin and ceftazidime , with equal dosage and application . Groups were compared using clinical , inflammatory and microbiological parameters . Results : There was a significant difference ( p ≤ 0.05 ) in peripheral leukocyte counts before and after therapy in both groups . The same was true for forced expiratory volume in 1 sec ( FEV1 ; p ≤ 0.05 ) , weight for height ( p ≤ 0.005 ) and for Pseudomonas counts ( p ≤ 0.005 ) in sputa . There was no statistical difference between the two groups for any of the parameters tested . Conclusion : It is concluded that , when exacerbations are excluded , home iv therapy is an effective therapeutic option in CF . Long-term comparison is still needed to effectively evaluate the pros and cons of home and hospital antibiotic treatment in CF In this study , we set out to determine if home intravenous ( i.v . ) antibiotic therapy in adult patients with cystic fibrosis ( CF ) is a feasible , effective and less costly alternative to hospitalization , and to assess the impact of home therapy on quality of life . The study was a prospect i ve , r and omized , two-factor mixed design involving adults presenting with respiratory exacerbations of CF . Patients were r and omized such that they were discharged home after 2 - 4 days , or remained in hospital . Seventeen patients had 31 admissions ( 13 home and 18 hospital ) . Following 10 days of therapy , there were no significant differences between home or hospital arms with respect to body weight , 12 minute walking distance , sputum weight , pulse oximetry , or improvement in lung function ( forced expiratory volume in one second ( FEV1 ) , or forced vital capacity ( FVC ) ) . Patients who remained in hospital were less fatigued and noted a greater degree of mastery . Patients discharged early noted less disruption to their family life , personal life and sleeping pattern . The total cost for the home therapy arm was approximately half that of the hospital therapy arm . Home intravenous antibiotic therapy in patients with cystic fibrosis was a feasible , cost-effective alternative to receiving therapy in hospital . Although there was no clinical compromise associated with home therapy , there were advantages and disadvantages in terms of quality of life METHODS 14 patients with cystic fibrosis and chronic pulmonary pseudomonas infection received four courses of two-week intravenous antibiotic therapy at home and during hospitalisation over an 18-month period . Following a controlled , intra-individual cross-over design , two courses of home therapy were followed by two courses of hospital treatment or vice versa . Parameters for inflammation , lung function , and body mass index were obtained at the beginning and end of each intravenous antibiotic therapy . Health-related quality of life , i.e. physical , emotional , social and functional components as well as happiness and medical care , was assessed at the end of each course . RESULTS There was a trend towards better reduction of infection ( p = 0.20 for leukocyte reduction ) and improvement of lung function ( p = 0.20 for FEV1 improvement ) with hospital intravenous antibiotic therapy , although the differences did not attain statistical significance . Quality of life during therapy was significantly higher with home therapy regarding social ( p < 0.01 ) , functional and emotional subscales and happiness ( all p < 0.05 ) . The necessity for professional help and support from family and /or partner was emphasised . Individual answers showed that home therapy has the advantage of self-determination and continuity of daily life . Parents and partners felt impaired by day and night intravenous therapy at home . CONCLUSION From our data we conclude that home intravenous antibiotic therapy is a useful option for a selected subgroup of patients with cystic fibrosis , but professional support and family aid is important to gain an effect similar to hospital treatment In a prospect i ve , r and omised , cross-over study including cystic fibrosis patients with indications for HIVAT ( home intravenous antibiotic treatment ) the prospect of pharmaceutical intervention was investigated . A comparison between the use of disposable infusion devices with antibiotics from the pharmacy and when the patients prepared the drugs themselves was performed . During a first treatment course the patients received either infusion devices during 5 days or reconstituted the drugs themselves during 5 days , or vice versa . During a second treatment course the order was the reversed . Eight patients were included , out of which six completed the original design as a cross-over study , yielding a total of 550 doses of antibiotics . The patients preferred infusion devices from the pharmacy prepared according to GMP ( Good Manufacturing Practice ) as opposed to reconstituting the antibiotics themselves . Points of view presented included no anxiety over the correct dosage of drugs and less disruption of family and social life . In a practical sense , portable devices are more expensive than the preparation of the drugs by the patients themselves . However , when comparing with in-hospital treatment the direct costs for a hospital stay exceed that of the devices . Another part of the study evaluated the quality of life using a modified form of SEIQoL-DW ( Schedule for the Evaluation of Individual Quality of Life - Direct Weighting ) . Twenty patients took part in the study and the overall quality of life scores increased significantly when patients received infusion devices compared to reconstituting the drugs themselves Methods for combining data from several studies exist and appear to be quite useful . None satisfactorily addresses the question of what studies should be combined . This issue is the most serious method ological limitation . Even studies with statistically significant interaction might still be combined if the effect were in the same direction . Thus , substantial scientific input is required as to what criteria must be met by each potential study . Much can be learned from combining or pooling data but it must be done cautiously . Pooling exercises do not replace well design ed prospect i ve clinical trials . Efforts for establishing basic design criteria to allow for multicentre and multicountry trials to be more easily combined might be useful . OBJECTIVE Despite widespread adoption of home care services , few r and omised trials have compared health outcomes in the hospital and at home . We report a prospect i ve , r and omised trial of home versus hospital therapy in adults receiving intravenous ( IV ) antibiotics . Our objective was to show that home care is a feasible alternative to hospitalisation over a broad range of infections , without compromise to quality of life ( QOL ) or clinical outcomes . METHODS Consenting adults requiring IV antibiotics were r and omised to complete therapy at home or in hospital . Short Form 36 and Perceived Health Competence Scale ( PHCS ) were used for assessment of QOL . Statistical analysis used unpaired t-tests , Mann-Whitney tests and ANOVA . RESULTS One hundred and twenty-nine admissions were referred . Recruitment was hampered by patient preference for one therapy over another . 82 ( 62 % ) were included and r and omised : 44 to home , 38 to hospital ; the two groups had comparable characteristics . There were no differences in improvements in QOL and PHCS scores between the two groups after treatment . Treatment duration was median 11.5 days ( range 3 - 57 ) and 11 days ( range 4 - 126 ) for home and hospital groups , respectively . Home therapy costs , approximately , half that of hospital therapy . Time to readmission was longer after hospital therapy . CONCLUSION Out study showed that home IV therapy is well tolerated , is less costly , is not associated with any major disadvantage to QOL or clinical outcomes compared to hospital therapy , and is an appropriate treatment option for selected patients A controlled prospect i ve study was undertaken to compare the efficacy and benefits of home and hospital treatment for patients with exacerbations of pulmonary disease caused by cystic fibrosis . A total of 41 home and 41 hospital treatments were analyzed . Home and hospital patients were matched according to sex , age , pulmonary function tests , and arterial blood gas values . Both home and hospital treatments result ed in statistically significant improvement in pulmonary function . A comparison of these values did not show any statistically significant difference between groups at admission or discharge . Furthermore , the mean number of treatment days for both groups , individually determined by the primary physician , was equivalent ( home 17.7 + /- 1.1 days , hospital 18.1 + /- 4.1 ) . The mean charge for a home treatment was approximately $ 10,000 , and for a hospital treatment $ 18,000 . Sixty-five percent of home care patients and 68 % of hospital patients required retreatment for pulmonary exacerbations within the study period ; the interval between pulmonary exacerbations for the two groups was not significantly different . In addition , 85 % of patients receiving treatment at home were able to maintain at least some of their school or work activities . These data indicate that home therapy for cystic fibrosis patients with pulmonary exacerbations is less costly and is as effective as in-hospital therapy |
813 | 30,341,113 | There was little evidence of inconsistency between direct and indirect evidence .
Conclusion The comparison of different treatment strategies for HCC indicated that RES is associated with longer survival . | Objective Hepatocellular carcinoma ( HCC ) is the third leading cause of cancer death worldwide .
We conducted network meta-regression within a Bayesian framework to compare and rank different treatment strategies for HCC through direct and indirect evidence from international studies . | BACKGROUND To compare the results of radiofrequency ablation ( RFA ) with hepatic resection in the treatment of hepatocellular carcinoma ( HCC ) within the Milan criteria . METHODS A nonr and omized comparative study was performed with 111 consecutive patients who underwent laparoscopic RFA ( n = 31 ) or curative hepatic resection ( n = 80 ) for HCC within Milan criteria . RESULTS Procedure related complications were less often and severe after RFA than resection ( 3.2 % vs. 25 % ) . There was no significant difference in hospital mortality ( 0 % vs. 3.8 % ) . Hospital stay was significantly shorter in the RFA group than in the resection group ( mean , 3.8 vs. 6.8 days ) . The 1- , 3- , and 5-year disease-free survival rates for the RFA group and the resection group were 76 % , 40 % , 40 % and 76 % , 60 % , 60 % , respectively . Disease-free survival was significantly lower in the RFA group than in the resection group . The corresponding 1- , 3- , and 5-year overall survival rates for the RFA group and the resection group were 100 % , 92 % , 84 % , and 92 % , 75 % , 71 % , respectively . The overall survival for RFA and resection were not significantly different . CONCLUSIONS Our result showed comparable overall survival between RFA and surgery , although RFA was associated with a significantly higher tumor recurrence rate . RFA had the advantages over surgical resection in being less invasive and having lower morbidity Abstract Background Hepatocellular carcinoma ( HCC ) is a primary tumor of the liver with poor prognosis . For early stage HCC , treatment options include surgical resection , liver transplantation , and percutaneous ablation . Percutaneous ablative techniques ( radiofrequency and microwave techniques ) emerged as best therapeutic options for nonsurgical patients . Aims We aim ed to determine the safety and efficacy of radiofrequency and microwave procedures for ablation of early stage HCC lesions and prospect ively follow up our patients for survival analysis . Patients and methods One Hundred and 11 patients with early HCC are managed in our multidisciplinary clinic using either radiofrequency or microwave ablation . Patients are assessed for efficacy and safety . Complete ablation rate , local recurrence , and overall survival analysis are compared between both procedures . Results Radiofrequency ablation group ( n = 45 ) and microwave ablation group ( n = 66 ) were nearly comparable as regards the tumor and patients characteristics . Complete ablation was achieved in 94.2 and 96.1 % of patients managed by radiofrequency and microwave ablation techniques , respectively ( p value 0.6 ) with a low rate of minor complications ( 11.1 and 3.2 , respectively ) including subcapsular hematoma , thigh burn , abdominal wall skin burn , and pleural effusion . Ablation rates did not differ between ablated lesions ≤3 and 3–5 cm . A lower incidence of local recurrence was observed in microwave group ( 3.9 vs. 13.5 % in radiofrequency group , p value 0.04 ) . No difference between both groups as regards de novo lesions , portal vein thrombosis , and abdominal lymphadenopathy . The overall actuarial probability of survival was 91.6 % at 1 year and 86.1 % at 2 years with a higher survival rates noticed in microwave group but still without significant difference ( p value 0.49 ) . Conclusion Radiofrequency and microwave ablations led to safe and equivalent ablation and survival rates ( with superiority for microwave ablation as regards the incidence of local recurrence ) Background R and omized trials suggest that radiofrequency ablation ( RFA ) may be more effective than percutaneous ethanol injection ( PEI ) in the treatment of hepatocellular carcinoma ( HCC ) . However , the survival advantage of RFA needs confirmation in daily practice . Methods We conducted a population -based cohort study using the Taiwan Cancer Registry , National Health Insurance cl aim data base and National Death Registry data from 2004 through 2009 . Patients receiving PEI or RFA as first-line treatment for newly-diagnosed stage I-II HCC were enrolled . Results A total of 658 patients receiving RFA and 378 patients receiving PEI treatment were included for final analysis . The overall survival ( OS ) rates of patients in the RFA and PEI groups at 5-year were 55 % and 42 % , respectively ( p < 0.01 ) . Compared to patients that received PEI , those that received RFA had lower risks of overall mortality and first-line treatment failure ( FTF ) , with adjusted hazard ratios ( HRs ) [ 95 % confidence interval ( CI ) ] of 0.60 ( 0.50 - 0.73 ) for OS and 0.54 ( 0.46 - 0.64 ) for FTF . The favorable outcomes for the RFA group were consistently significant for patients with tumors > 2 cm as well as for those with tumors < 2 cm . Consistent results were also observed in other subgroup analyses defined by gender , age , tumor stage , and co-morbidity status . Conclusion RFA provides better survival benefits than PEI for patients with unresectable stage I-II HCC , irrespective of tumors > 2 cm or ≤ 2 cm , in contemporary clinical practice Evidence of relative effectiveness of local treatments for hepatocellular carcinoma ( HCC ) is scanty . We investigated , in a retrospective cohort study , whether surgical resection , radiofrequency ablation ( RFA ) , percutaneous ethanol injection ( PEI ) , and transarterial embolization with ( TACE ) or without ( TAE ) chemotherapy result ed in different survival in clinical practice . All patients first diagnosed with HCC and treated with any locoregional therapy from 1998 to 2002 in twelve Italian hospitals were eligible . Overall survival ( OS ) was the unique endpoint . Three main comparisons were planned : RFA versus PEI , surgical resection versus RFA/PEI ( combined ) , TACE/TAE versus RFA/PEI ( combined ) . Propensity score method was used to minimize bias related to non r and om treatment assignment . Overall 425 subjects were analyzed , with 385 ( 91 % ) deaths after a median followup of 7.7 years . OS did not significantly differ between RFA and PEI ( HR 1.11 , 95 % CI 0.79 - 1.57 ) , between surgery and RFA/PEI ( HR 0.95 , 95 % CI 0.64 - 1.41 ) and between TACE/TAE and RFA/PEI ( HR 0.88 , 95 % CI 0.66 - 1.17 ) . 5-year OS probabilities were 0.14 for RFA , 0.18 for PEI , 0.27 for surgery , and 0.15 for TACE/TAE . No locoregional treatment for HCC was found to be more effective than the comparator . Adequately powered r and omized clinical trials are still needed to definitely assess relative effectiveness of locoregional HCC treatment BACKGROUND AND STUDY AIMS Hepatocellular carcinoma ( HCC ) is a major burden on health-care systems worldwide . Although radiofrequency ablation ( RFA ) is currently considered the best technique for coagulative necrosis , the superiority of concomitant use of RFA and percutaneous ethanol injection ( PEI ) needs to be determined . The study was design ed to compare efficacy , safety and rate of survival of patients with HCC assigned to receive combined PEI-RFA versus RFA alone and versus PEI alone . PATIENTS AND METHODS This 3-year study enrolled 90 cirrhotic patients with HCC ( Child 's class A or B , but not class C ) . They were r and omly assigned for either PEI-RFA ( group I ) , RFA alone ( group II ) or PEI alone ( group III ) . The primary end point was ablation of the tumour . The secondary end point was rate of survival and recurrence . RESULTS After the first session , complete ablation was significantly higher in the combination group ( 87.9 % ) compared with the RFA group ( 54.54 % ) . After the second session , complete ablation was achieved in 97.0 % of the combination group and in 84.8 % of the RFA group . Regarding the PEI group , 75 % had complete ablation , whereas 25 % had partial ablation after multiple sessions . The survival rate , 1.5 years later , was significantly higher in group I ( 86.7 % ) compared with group III ( 63.3 % ) . The overall incidence of serious adverse events was nil . CONCLUSION Combined treatment is superior to RFA alone and to PEI alone , in safety and efficacy in patients with HCC Purpose Although there are several prospect i ve clinical studies comparing radiofrequency ablation ( RFA ) and hepatic resection ( HR ) for the treatment of hepatocellular carcinoma , there are few trials that have been performed in strictly homogeneous patients . Methods Patients who were newly diagnosed with a solitary hepatocellular carcinoma were r and omized to the HR or RFA group . Inclusion criteria were as follows : age ≥ 20 years but ≤ 70 years , Child-Pugh class A , maximal diameter of the tumor ≥ 2 cm but ≤ 4 cm , no previous treatment history , and platelet count > 80,000/mm3 . Results Although the study was early terminated , 29 and 34 patients were enrolled in the HR and RFA groups , respectively , and prospect ively followed on an intention-to-treat basis . The 5-year overall survival rates were 83.4 % and 86.2 % in the HR and RFA groups , respectively , which were not significantly different ( P = 0.812 by log-rank , P = 0.990 by Breslow ) . The 3- and 5-year disease-free survival rates in the HR group were significantly superior to those in the RFA group ( 66.7 % , 44.4 % vs. 44.1 % , 31.2 % , P = 0.071 by log-rank , P = 0.023 by Breslow ) . Intrahepatic local recurrence tended to develop more frequently in the RFA group ( P = 0.042 ) , while the frequency of intrahepatic distant and extrahepatic recurrence was similar bet ween the 2 groups . There were no significant differences in the frequency and severity of complications between the 2 groups . Conclusion HR was significantly superior to RFA in terms of disease-free survival ; however , the overall survival was excellent in both groups Objective : To compare the results of percutaneous local ablative therapy ( PLAT ) with surgical resection in the treatment of solitary and small hepatocellular carcinoma ( HCC ) . Summary Background Data : PLAT is effective in small HCC . Whether it is as effective as surgical resection in the long-term survivals remains unknown . Methods : We conducted a prospect i ve r and omized trial on 180 patients with a solitary HCC ≦5 cm to receive either PLAT or surgical resection . The patients were regularly followed up after treatment with physical examination , blood , and radiologic tests . Results : Of the 90 patients who were r and omized to PLAT , only 71 received PLAT because 19 withdrew their consent . Of the 90 patients who were r and omized to surgical resection , a single Couinaud liver segment resection was carried out in 69 patients , 2 segments in 16 patients , and 3 or more segments in 3 patients . Ethanol injection was given during open surgery in 2 patients . Only 1 patient died after surgical resection within the same hospital admission . Posttreatment complications were more often and severe after surgery than PLAT . The 1- , 2- , 3- , and 4-year overall survival rates after PLAT and surgery were 95.8 % , 82.1 % , 71.4 % , 67.9 % and 93.3 % , 82.3 % , 73.4 % , 64.0 % , respectively . The corresponding disease-free survival rates were 85.9 % , 69.3 % , 64.1 % , 46.4 % and 86.6 % , 76.8 % , 69 % , 51.6 % , respectively . Statistically , there was no difference between these 2 treatments . Conclusion : PLAT was as effective as surgical resection in the treatment of solitary and small HCC . PLAT had the advantage over surgical resection in being less invasive The effect of percutaneous microwave ablation and laparoscopic resection on the prognosis of liver cancer was investigated . Ninety patients with liver cancer treated at our hospital from March 2010 to March 2012 were divided into group A and group B ( n=45 ) by using a r and om number table , and the surgical conditions and the prognosis were compared . The surgical conditions of patients in group A were significantly better than those in group B ( P<0.05 ) . The incidence of complications in group A was 6.67 % , which was obviously lower than that of group B ( P<0.05 ) . The local recurrence rate of group A was 20.00 % , and that of group B was 8.89 % , which showed a significant difference ( P<0.05 ) . The two groups did not differ significantly in terms of either total recurrence rate ( P>0.05 ) or 1-year , 2-year and 3-year survival ( P>0.05 ) . Both percutaneous microwave ablation and laparoscopic resection had a good long-term efficacy in liver cancer . However , percutaneous microwave ablation was superior as it caused less invasiveness , reduced the incidence of complications and improved prognosis of liver cancer PURPOSE To prospect ively compare combined radiofrequency ablation and transcatheter arterial chemoembolization ( TACE ) with radiofrequency ablation alone for the treatment of small ( < or =3 cm ) hepatocellular carcinomas ( HCCs ) . MATERIAL S AND METHODS The ethics committee of the study institution approved the study protocol . Written informed consent was obtained from all patients at enrollment . Eighty-nine patients with 93 HCC nodules 0.8 - 3.0 cm ( mean + /- st and ard deviation , 1.7 cm + /- 0.5 ) in diameter were r and omly treated with combined radiofrequency ablation and TACE ( 46 patients with 49 nodules ) or with radiofrequency ablation alone ( 43 patients with 44 nodules ) . The patients were followed up for 9 - 68 months ( mean + /- st and ard deviation , 30.4 months + /- 14.0 ) . Rates of local tumor progression , overall survival , local progression-free survival , and event-free survival were evaluated by using the Kaplan-Meier method . RESULTS The 1- , 2- , 3- , and 4-year rates of local tumor progression , overall survival , local progression-free survival , and recurrence-free survival were as follows : Local tumor progression rates were 14.4 % , 17.6 % , 17.6 % , and 17.6 % , respectively , in the combined treatment group and 11.4 % , 14.4 % , 14.4 % , and 14.4 % , respectively , in the radiofrequency ablation group ( P = .797 ) . Overall survival rates were 100 % , 100 % , 84.8 % , and 72.7 % , respectively , in the combined treatment group and 100 % , 88.8 % , 84.5 % , and 74.0 % , respectively , in the radiofrequency ablation group ( P = .515 ) . Local progression-free survival rates were 84.6 % , 81.1 % , 69.7 % , and 55.8 % , respectively , in the combined treatment group and 88.4 % , 74.1 % , 74.1 % , and 61.7 % , respectively , in the radiofrequency ablation group ( P = .934 ) . Event-free survival rates were 71.3 % , 59.9 % , 48.8 % , and 36.6 % , respectively , in the combined treatment group and 74.3 % , 52.4 % , 29.7 % , and 29.7 % , respectively , in the radiofrequency ablation group ( P = .365 ) . CONCLUSION Combined radiofrequency ablation plus TACE and radiofrequency ablation alone have equivalent effectiveness for the treatment of small ( < or =3 cm ) HCCs , so the combination treatment may not be necessary Aims : The aim of this study was to compare the outcomes of radiofrequency thermal ablation ( RFTA ) , percutaneous ethanol injection ( PEI ) , and percutaneous acetic acid injection ( PAI ) in the treatment of hepatocellular carcinoma ( HCC ) . Patients and methods : A total of 187 patients with HCCs of 3 cm or less were r and omly assigned to RFTA ( n = 62 ) , PEI ( n = 62 ) , or PAI ( n = 63 ) . Tumour recurrence and survival rates were assessed . Results : One , two , and three year local recurrence rates were 10 % , 14 % , and 14 % in the RFTA group , 16 % , 34 % , and 34 % in the PEI group , and 14 % , 31 % , and 31 % in the PAI group ( RFTA v PEI , p = 0.012 ; RFTA v PAI , p = 0.017 ) . One , two , and three year survival rates were 93 % , 81 % , and 74 % in the RFTA group , 88 % , 66 % , and 51 % in the PEI group , and 90 % , 67 % , and 53 % in the PAI group ( RFTA v PEI , p = 0.031 ; RFTA v PAI , p = 0.038 ) . One , two , and three year cancer free survival rates were 74 % , 60 % , and 43 % in the RFTA group , 70 % , 41 % , and 21 % in the PEI group , and 71 % , 43 % , and 23 % in the PAI group ( RFTA v PEI , p = 0.038 ; RFTA v PAI , p = 0.041 ) . Tumour size , tumour differentiation , and treatment methods ( RFTA v PEI and PAI ) were significant factors for local recurrence , overall survival , and cancer free survival . Major complications occurred in 4.8 % of patients ( two with haemothorax , one gastric perforation ) in the RFTA group and in none in two other groups ( RFTA v PEI and PAI , p = 0.035 ) . Conclusions : RFTA was superior to PEI and PAI with respect to local recurrence , overall survival , and cancer free survival rates , but RFTA also caused more major complications BACKGROUND & AIMS The aim of this study was to compare the clinical outcome of percutaneous radiofrequency ( RF ) ablation , conventional percutaneous ethanol injection ( PEI ) , and higher-dose PEI in treating hepatocellular carcinoma ( HCC ) 4 cm or less . METHODS A total of 157 patients with 186 HCCs 4 cm or less were r and omly assigned to 3 groups ( 52 patients in the conventional PEI group , 53 in the higher-dose PEI group , and 52 in the RF group ) . Clinical outcomes in terms of complete tumor necrosis , overall survival , local tumor progression , additional new tumors , and cancer-free survival were compared across 3 groups . RESULTS The rate of complete tumor necrosis was 88 % in the conventional PEI group , 92 % in the higher-dose PEI group , and 96 % in the RF group . Significantly fewer sessions were required to achieve complete tumor necrosis in the RF group than in the other 2 groups ( P < .01 ) . The local tumor progression rate was lowest in the RF group ( vs the conventional PEI group , P = .012 ; vs the higher-dose PEI group , P = .037 ) . The overall survival rate was highest in the RF group ( vs the conventional PEI group , P = .014 ; vs the higher-dose PEI group , P = .023 ) . The cancer-free survival rate was highest in the RF group ( vs the conventional PEI group , P = .019 ; vs the higher-dose PEI group , P = .024 ) . Multivariate analysis determined that tumor size , tumor differentiation , and the method of treatment ( RF vs both methods of PEI ) were significant factors in relation to local tumor progression , overall survival , and cancer-free survival . CONCLUSIONS The results show that RF ablation yielded better clinical outcomes than conventional and higher-dose PEI in treating HCC 4 cm or less Hepatic resection is still considered the treatment of choice for hepatocellular carcinoma in patients with liver cirrhosis . Radiofrequency ablation is a new emerging modality . The aim of this study was to compare two homogeneous groups of patients who underwent either surgical resection or laparoscopic radiofrequency , analyzing the factors predicting survival and intrahepatic recurrences with use of a multivariate analysis . From February 1997 to April 2003 , 98 patients were enrolled in this prospect i ve study . Inclusion criteria were a single nodule of less than 5 cm , Child A-B class of liver function , and no previous treatment : 40 patients were in the surgical group and 58 patients were in the radiofrequency group . The two groups were homogeneous as far as preoperative characteristics were concerned . Operative mortality was zero , and the rates of operative morbidity were similar . Actuarial survival at 4 years was not significantly different ( 61 % after resection and 45 % after radiofrequency ) . There was a significant higher incidence of intrahepatic recurrences after radiofrequency than after resection ( 53 % versus 30 % ; P = 0.018 ) . This was mainly due to local recurrences , whereas those appearing in other liver segments were similar in both groups . A multivariate analysis showed that the significant factors predictive of an intrahepatic recurrence were the level of α-fetoprotein , the etiology of cirrhosis , and the type of the treatment . On the other h and , multivariate analysis of the survival showed that only the level of α-fetoprotein was an independent predictor of survival . The results of our study showed a significant lower incidence of intrahepatic recurrences after resection compared with after radiofrequency . This seems not to significantly influence the overall survival , probably because of a prompt and effective treatment of the recurrences themselves BACKGROUND & AIMS The aim of this study was to compare the efficacy of radiofrequency ablation ( RFA ) with surgical resection ( RES ) in the treatment of small hepatocellular carcinoma ( HCC ) . METHODS A total of 168 patients with small HCC with nodular diameters of less than 4 cm and up to two nodules were r and omly divided into RES ( n=84 ) and RFA groups ( n=84 ) . Outcomes were carefully monitored and evaluated during the 3-year follow-up period . RESULTS The 1- , 2- , and 3-year survival rates for the RES and RFA groups were 96.0 % , 87.6 % , 74.8 % and 93.1 % , 83.1 % , 67.2 % , respectively . The corresponding recurrence-free survival rates for the two groups were 90.6 % , 76.7 % , 61.1 % and 86.2 % , 66.6 % , 49.6 % , respectively . There were no statistically significant differences between the two groups in overall survival rate ( p=0.342 ) or recurrence-free survival rate ( p=0.122 ) . Multivariate analysis demonstrated that the independent risk factors associated with survival were multiple occurrences of tumors at different hepatic locations ( relative risk of 2.696 ; 95 % CI : 1.189 - 6.117 ; p=0.018 ) and preoperative indocyanine green retention rate at 15 min ( ICG-15 ) ( relative risk of 3.853 ; 95 % CI : 1.647 - 9.015 ; p=0.002 ) . CONCLUSIONS In patients with small hepatocellular carcinomas , percutaneous RFA may provide therapeutic effects similar to those of RES . However , percutaneous RFA is more likely to be incomplete for the treatment of small HCCs located at specific sites of the liver , and open or laparoscopic surgery may be the better choice AIM To compare 5-year survival of patients with a single hepatocellular carcinoma≤3 cm r and omly assigned to receive percutaneous ethanol injection or radiofrequency ablation . PATIENTS AND METHODS A total of 285 patients ( 192 males , mean age 70 years ) , with a single hepatocellular carcinoma ( mean diameter 2.2 cm ) were r and omly assigned to receive percutaneous ethanol injection ( n=143 ) or radiofrequency ablation ( n=142 ) . The primary endpoint of the study was 5-year survival . RESULTS Overall 143 patients underwent percutaneous ethanol injection and 128 radiofrequency ablation . In consideration of segmental location , in fact , 14 patients with 14 hepatocellular carcinomas could not be treated with established radiofrequency and were treated with percutaneous ethanol injection ; these patients were not included in the survival evaluation . In the percutaneous ethanol injection and in the radiofrequency ablation groups , 3- and 5-year survival rates of 74 % and 68 % , and 78 % and 68 % , and 79 % and 70 % [ corrected ] respectively , were observed ( p = n.s ) . In the percutaneous ethanol injection group , 3- and 5-year local recurrence rates were 9.4 % and 12.8 % respectively ; in the radiofrequency group , the 3 and 5 years local recurrence rates were 7.8 % and 11.7 % , respectively ( p = n.s . ) . The overall costs of percutaneous ethanol injection and radiofrequency ablation were 1359 Euros and 171.000 Euros , respectively ( p<0.0001 ) CONCLUSION Percutaneous ethanol injection and radiofrequency ablation conferred similar 5-year survival . Feasibility is not the same for both procedures . Percutaneous ethanol injection is much cheaper than radiofrequency ablation and should be considered whether in poor and rich countries PURPOSE To compare radiofrequency ablation ( RFA ) with or without transcatheter arterial chemoembolization ( TACE ) in the treatment of hepatocellular carcinoma ( HCC ) . PATIENTS AND METHODS A r and omized controlled trial was conducted on 189 patients with HCC less than 7 cm at a single tertiary referral center between October 2006 and June 2009 . Patients were r and omly asssigned to receive TACE combined with RFA ( TACE-RFA ; n = 94 ) or RFA alone ( n = 95 ) . The primary end point was overall survival . The secondary end point was recurrence-free survival , and the tertiary end point was adverse effects . RESULTS At a follow-up of 7 to 62 months , 34 patients in the TACE-RFA group and 48 patients in the RFA group had died . Thirty-three patients and 52 patients had developed recurrence in the TACE-RFA group and RFA group , respectively . The 1- , 3- , and 4-year overall survivals for the TACE-RFA group and the RFA group were 92.6 % , 66.6 % , and 61.8 % and 85.3 % , 59 % , and 45.0 % , respectively . The corresponding recurrence-free survivals were 79.4 % , 60.6 % , and 54.8 % and 66.7 % , 44.2 % , and 38.9 % , respectively . Patients in the TACE-RFA group had better overall survival and recurrence-free survival than patients in the RFA group ( hazard ratio , 0.525 ; 95 % CI , 0.335 to 0.822 ; P = .002 ; hazard ratio , 0.575 ; 95 % CI , 0.374 to 0.897 ; P = .009 , respectively ) . There were no treatment-related deaths . On logistic regression analyses , treatment allocation , tumor size , and tumor number were significant prognostic factors for overall survival , whereas treatment allocation and tumor number were significant prognostic factors for recurrence-free survival . CONCLUSION TACE-RFA was superior to RFA alone in improving survival for patients with HCC less than 7 cm OBJECTIVE To compare the clinical results of surgical resection ( SR ) and percutaneous thermal ablation ( PTA ) for early-stage hepatocellular carcinoma ( HCC ) ( single tumor nodule < or= 5 cm in diameter , or < or= 3 nodules with < or= 3 cm in diameter ) . METHODS One hundred and five patients with 114 HCC nodules were r and omly allocated to SR ( n = 54 ) and ultrasound-guided PTA with microwave or radiofrequency energy ( n = 51 ) . RESULTS The complete tumor elimination rates in SR and PTA groups were similar ( 100 % vs 94.7 % ) and the local recurrence rates were both 0 . There were no significant differences in distance recurrence rate ( 16.7 % vs 27.5 % , P = 0.182 ) and time to the first recurrence ( 4.9 month vs 9.6 month , P = 0.130 ) between the SR and PTA groups . One , 2- , and 3-year disease-free survival rates were 82.4 % , 82.4 % and 82.4 % , respectively , in SR group , whereas they were 78.5 % , 61.5 % and 51.3 % in PTA group , respectively . The difference between these two groups was statistically not significant ( P = 0.128 ) . The overall survival rates in SR group were 91.3 % , 86.4 % and 86.4 % at 1 , 2 , and 3 years , respectively , and those in PTA group were 93.5 % , 87.1 % and 87.1 % , respectively . There was no significant difference between these two groups ( P = 0.808 ) . Compared with SR , PTA required less treatment time ( 27 min vs 145 min , P < 0.005 ) , less necessity for blood transfusion ( 0 patient vs 7 patients , P = 0.013 ) and less hospital-stay ( 5.2 d vs 19.1 , P < 0.005 ) . There was no significant difference in the rate of treatment-related complication between the two groups ( 11.1 % for SR vs 7.8 % for PTA , P = 0.742 ) . At day 7 and day 30 after treatment , the numbers of patient with physical status ( WHO Performance Status grade s ) of grade 0 - 1 were 32 and 44 in PTA group , respectively , significantly more than 16 and 33 in SR group ( P = 0.001 and P = 0.004 , respectively ) . CONCLUSION Besides minimal invasiveness , easy to access and cost saving , PTA achieved equivalent local therapeutical effectiveness and 3-year survival outcomes as SR did , and may be considered as a one of the first-choice treatment modality for treatment of early-stage HCC PURPOSE To compare prospect ively the effects of radiofrequency ( RF ) ablation after transcatheter arterial chemoembolization ( TACE ) with those of RF ablation alone in the treatment of recurrent hepatocellular carcinoma ( HCC ) . MATERIAL S AND METHODS This study was approved by the institutional ethics committee , and all patients gave written informed consent . From January 2002 to December 2006 , 139 patients with recurrent HCC measuring 5 cm in diameter or smaller were r and omized to receive either sequential TACE and RF ablation ( sequential treatment group , n=69 ) or RF ablation alone ( RF ablation group , n=70 ) . The survival curves were constructed with the Kaplan-Meier method and compared by using the log-rank test . Bonferroni correction was applied when multiple comparisons were performed . P<.0083 ( .05÷6 ) was considered indicative of a statistically significant difference . RESULTS The 1- , 3- , and 5-year overall survival rates were 94 % , 69 % , and 46 % , respectively , for the sequential treatment group and 82 % , 47 % , and 36 % for the RF ablation group ( P=.037 ) . The corresponding recurrence-free survival rates were 80 % , 45 % , and 40 % for the sequential treatment group and 64 % , 18 % , and 18 % for the ablation group ( P=.005 ) . At subgroup analyses , the overall survival for the sequential treatment group was better than that for the RF ablation group for patients with tumor recurrence 1 year or less after initial treatment ( P=.004 ) and those with tumors measuring 3.1 - 5.0 cm ( P=.002 ) but not for those with tumor recurrence more than 1 year after initial treatment ( P=.421 ) and those with tumors 3.0 cm or smaller ( P=.478 ) . The recurrence-free survival in the sequential treatment group was better than that in the RF ablation group for patients with tumors measuring 3.1 - 5.0 cm ( P<.001 ) but not for those with tumors 3.0 cm or smaller ( P=.204 ) . For recurrence-free survival , there was no significant difference between the two groups for patients with tumor recurrence 1 year or less or more than 1 year after initial treatment ( P=.020 and P=.111 , respectively ) . Logistic regression analysis showed that treatment allocation and the interval between initial treatment and tumor recurrence were significant prognostic factors for overall survival , whereas the interval between initial treatment and tumor recurrence , treatment allocation , and tumor size were significant prognostic factors for recurrence-free survival . CONCLUSION The efficacy of sequential TACE-RF ablation is better than that of RF ablation alone for recurrent HCC BACKGROUND Several surgical and non-surgical therapeutic modalities have been used for the treatment of hepatocellular carcinoma ( HCC ) . There have been several studies comparing hepatic resection ( HR ) and percutaneous ethanol injection ( PEI ) for the treatment of HCC . However , there is still disagreement about the best treatment modality . METHODS From 130 patients undergoing HR , 116 patients were individually matched to 116 controls from 249 patients undergoing PEI using propensity score matching to overcome possible biases in non-r and omized study . Survival analyses were undertaken to compare these propensity score-matched groups . RESULTS After matching by propensity score , the major clinical outcomes in the HR ( n = 116 ) and the PEI ( n = 116 ) groups were found to be similar . The 1- , 3- and 5-year overall survival rates were higher in the HR group ( 94.8 % , 76.5 % and 65.6 % ) compared to the PEI group ( 95.7 % , 73.5 % and 49.3 % ) ( P = 0.059 ) . The cumulative 1- , 3- and 5-year disease-free survival rates showed the same trend ( HR : 76.1 % , 50.6 % and 40.6 % ; PEI : 62.6 % , 25.5 % and 19.1 % ) ( P < 0.001 ) . However , when stratified by Child-Pugh classification , it was no longer the case in the Child B patients . Single intrahepatic recurrence was the most common pattern of tumor recurrence after both treatments . CONCLUSIONS Patients undergoing HR had a better survival profile than those undergoing PEI . However , when considering which technique to use for optimal HCC management , the individual patient 's hepatic function must be considered Objective : To compare the long-term outcomes of surgical resection and radiofrequency ablation for the treatment of small hepatocellular carcinoma ( HCC ) . Summary Background Data : Radiofrequency ablation ( RFA ) is a promising , emerging therapy for small HCC . Whether it is as effective as surgical resection ( RES ) for long-term outcomes is still indefinite . Methods : Two hundred thirty HCC patients who met the Milan criteria and were suitable to be treated by either RES or RFA entered into a r and omized controlled trial . The patients were regularly followed up after treatment for 5years ( except for those who died ) . The primary end point was overall survival ; the secondary end points were recurrence-free survival , overall recurrence , and early-stage recurrence . Results : The 1- , 2- , 3- , 4- and 5-year overall survival rates for the RFA group and the RES group were 86.96 % , 76.52 % , 69.57 % , 66.09 % , 54.78 % and 98.26 % , 96.52 % , 92.17 % , 82.60 % , 75.65 % , respectively . The corresponding recurrence-free survival rates for the 2 groups were 81.74 % , 59.13 % , 46.08 % , 33.91 % , 28.69 % and 85.22 % , 73.92 % , 60.87 % , 54.78 % , 51.30 % , respectively . Overall survival and recurrence-free survival were significantly lower in the RFA group than in the RES group ( P = 0.001 and P = 0.017 ) . The 1- , 2- , 3- , 4- , and 5-year overall recurrence rates were 16.52 % , 38.26 % , 49.57 % , 59.13 % , and 63.48 % for the RFA group and 12.17 % , 22.60 % , 33.91 % , 39.13 % , and 41.74 % for the RES group . The overall recurrence was higher in the RFA group than in the RES group ( P = 0.024 ) . Conclusions : Surgical resection may provide better survival and lower recurrence rates than RFA for patients with HCC to the Milan criteria Objective . To compare percutaneous ethanol injection ( PEI ) , the st and ard approach which has been used for many years to treat early non-surgical hepatocellular carcinoma ( HCC ) in cirrhotic patients , and radiofrequency ablation ( RFA ) , which has become an interesting alternative . Material and methods . A r and omized trial was carried out on 139 cirrhotic patients in Child-Pugh classes A/B with 1–3 nodes of HCC ( diameter 15–30 mm ) , for a total of 177 lesions . Patients were r and omized to receive RFA ( n=70 ) or PEI ( n=69 ) . The primary end-point was complete response ( CR ) 1 year after the percutaneous ablation of all HCC nodes identified at baseline . Secondary end-points were : early ( 30–50 days ) CR , complications , survival and costs . Results . In an intention-to-treat analysis , 1-year CR was achieved in 46/70 ( 65.7 % ) and in 25/69 ( 36.2 % ) patients treated by RFA and PEI , respectively ( p=0.0005 ) . For lesions > 20 mm in diameter , there was a larger CR rate in the RFA group ( 68.1 % versus 26.3 % ) . An early CR was obtained in 67/70 ( 95.7 % ) patients treated by RFA compared with 42/64 ( 65.6 % ) patients treated by PEI ( p=0.0001 ) . Complications occurred in 10 and 12 patients treated by RFA and PEI , respectively . The overall survival rate was not significantly different in the RFA versus PEI arm ( adjusted hazard ratio=0.88 , 95 % CI : 0.50–1.53 ) . There was an incremental health-care cost of 8286 € for each additional patient successfully treated by RFA . Conclusions . The 1-year CR rate after percutaneous treatment of early HCC was significantly better with RFA than with PEI but did not provide a clear survival advantage in cirrhotic patients Background The aim of this study was to compare the results of percutaneous radiofrequency ablation ( RFA ) with those of partial hepatectomy ( PH ) in the treatment of multicentric small hepatocellular carcinomas ( HCCs ) . With advances in RFA , it is not known whether the minimally invasive approach with percutaneous RFA could attain comparable survival outcomes but with a lower morbidity in patients with multicentric HCCs . Methods From January 2002 and December 2007 , 159 patients who had two or three HCCs , with the largest tumor no more than 5 cm in diameter , had no major vascular invasion or extrahepatic metastases , and were treated with either PH ( n = 73 ) or RFA ( n = 86 ) were included in the study . Results There was no procedure-related mortality in both groups of patients . Major complications happened significantly more often after PH than after RFA ( 19.2 vs. 8.1 % ) . The hospital stay was significantly longer after PH than after RFA ( median = 9 vs. 3 days ) . The 1- , 3- , and 5-year overall survival rates for the PH and RFA groups were 91.8 , 68.7 , 44.5 % and 94.2 , 64.4 , 21.2 % , respectively . The corresponding disease-free survival rates for the two groups were 62.1 , 33.6 , 3.6 % and 29.4 , 2.7 , 0 % , respectively . The PH group had significantly longer overall survival and disease-free survival than the RFA group . Conclusions PH result ed in better survival outcomes than RFA for patients with multicentric small HCCs . However , RFA had the benefits of lower procedure-related morbidity and shorter hospital stay PURPOSE To compare the effectiveness of radio-frequency ( RF ) thermal ablation with that of percutaneous ethanol injection ( PEI ) for the treatment of small hepatocellular carcinoma ( HCC ) in patients with cirrhosis . MATERIAL S AND METHODS A series of 102 patients with hepatic cirrhosis and either single HCC 5 cm in diameter or smaller or as many as three HCCs each 3 cm or smaller ( overall number of lesions , 142 ) r and omly received either RF ablation ( n = 52 ) or PEI ( n = 50 ) as the sole first-line anticancer treatment . Mean follow-up was 22.9 months + /- 9.4 ( SD ) in the RF group and 22.4 months + /- 8.6 in the PEI group . Prognostic value of treatment techniques was assessed with univariate and multivariate Cox proportional hazards regression models . RESULTS One- and 2-year survival rates were 100 % and 98 % in the RF group and 96 % and 88 % in the PEI group , respectively ( univariate relative risk [ RR ] = 0.20 ; 95 % CI : 0.02 , 1.69 ; P = .138 ) . One- and 2-year local recurrence-free survival rates were 98 % and 96 % in the RF group and 83 % and 62 % in the PEI group , respectively ( univariate RR = 0.17 ; 95 % CI : 0.06 , 0.51 ; P = .002 ) . One- and 2-year event-free survival rates were 86 % and 64 % for the RF group and 77 % and 43 % for the PEI group , respectively ( univariate RR = 0.48 ; 95 % CI : 0.27 , 0.85 ; P = .012 ) . RF treatment was confirmed as an independent prognostic factor for local recurrence-free survival rates with multivariate analysis ( adjusted RR = 0.20 ; 95 % CI : 0.05 , 0.73 ; P = .015 ) . CONCLUSION RF ablation is superior to PEI with respect to local recurrence-free survival rates OBJECTIVE To compare the transcatheter arterial chemoembolization ( TACE ) alone or plus radiofrequency ablation ( RFA ) in the treatment of single branch portal vein tumor thrombus(PVTT)in patients with hepatocellular carcinoma ( HCC ) so as to evaluate the safety , control rate , prognostic factors and overall survival . METHODS From January 2004 to December 2007 , 50 HCC patients ( < 5 cm in diameter and 3 parenchymal lesions ) with concurrent PVTT were enrolled and treated by TACE alone or TACE plus RFA r and omly ( TACE , n = 25 ; TACE-RFA , n = 25 ) . In TACE group , the intra-hepatic lesions received TACE sequentially with RFA ; in TACE-RFA group , PVTT and intra-hepatic lesions were treated with TACE sequentially with RFA separately . Strict follow-up was conducted by computed tomography and alpha-fetoprotein ( AFP ) assay . The survival time was analyzed by the Kaplan-Meier method and Cox regression analysis was performed to evaluate the prognostic factors . RESULTS Of all 50 HCC patients with single branch PVTT with TACE or RFA , 47 patients ( TACE , n = 24 ; TACE-RFA , n = 23 ) received all the scheduled procedures and completed the follow-up . Two patients ( 8.3 % ) in TACE group had liver dysfunction versus none in TACE-RFA group , 2 patients ( 8.7 % ) developed bile duct injury in TACE-RFA group related with the RFA procedure . The OR ( overall response ) for PVTT was 54.2 % ( complete response ( CR ) 8.3 % , partial response ( PR ) 45.8 % ) in TACE group while 87.0 % ( CR 60.9 % , PR 26.1 % ) in TACE-RFA group during the follow-up . From the definite diagnosis of HCC , the median survival was 8 months . And the 1- , 2- & 3-year survival rates were 33.3 % , 12.5 % , 8.3 % in TACE group . And 26 months , 65.2 % , 47.8 % , 30.4 % in TACE-RFA group respectively . The difference between two groups was significant . From the definite diagnosis of PVTT , the respective data were 7 months , 12.5 % and 4.2 % , 0 in TACE group versus 22 months , 52.2 % , 34.8 % , and 8.7 % in TACE-RFA group with a significant P value . In multivariate analysis , only therapy ( TACE or TACE-RFA ) showed a protective value ( hazard rate 0.430 vs 0.345 , P < 0.05 ) . Survival was not correlated with age , intra-hepatic tumor status , liver functions and AFP level for all patients . CONCLUSION RFA is both safe and efficacious to prolong survival in the treatment of single branch PVTT plus TACE in selected HCC patients . It may provide rationale s for further studies of evaluating the outcome of RFA plus other therapies in the treatment of HCC with single branch PVTT Objective : To compare disease recurrence and survival among patients with small hepatocellular carcinoma after surgical resection or percutaneous ethanol injection therapy , 2 treatments that have not been evaluated with a prospect i ve study . Methods : A total of 76 patients were r and omly assigned to 2 groups based on treatment ; all had one or 2 tumors with diameter ≤3 cm , with hepatitis without cirrhosis or Child class A or B cirrhosis without evident ascites or bleeding tendency . Results : Follow-up ranged from 12 to 59 months . Among percutaneous injection patients , 18 had recurrence 1 to 37 months after treatment ( true recurrence , 11 ; original safety margin inadequate , 3 ; limitation of imaging technology to detect tiny tumors , 4 ) . Three injection therapy patients died of cancer 25 , 37 , and 57 months after treatment . For the surgical resection group , 15 had recurrence 2 to 54 months after treatment ( true recurrence , 12 ; limitation of imaging , 2 ; neck metastasis , 1 ) . Five resection patients died of cancer at 11 , 20 , 23 , 26 , and 52 months , respectively . By Cox regression model and Kaplan-Meier survival analysis , there is no statistical significance for recurrence and survival between treatment groups . However , tumor size larger than 2 cm and alpha-fetoprotein over 200 ng/mL correlated with higher recurrence rate , and Child class B liver cirrhosis correlated with shorter survival . Conclusions : Percutaneous ethanol injection therapy appears to be as safe and effective as resection , and both treatments can be considered first-line options for small hepatocellular carcinoma BACKGROUND & AIMS Percutaneous radiofrequency ablation is a recently introduced treatment for hepatocellular carcinoma , whereas ethanol injection is now a st and ard therapy . We compared their long-term outcomes . METHODS Two hundred thirty-two patients with hepatocellular carcinoma who had 3 or fewer lesions , each 3 cm or less in diameter , and liver function of Child-Pugh class A or B were entered onto a r and omized controlled trial . The primary end point was survival , and the secondary end points were overall recurrence and local tumor progression . RESULTS One hundred eighteen patients were assigned to radiofrequency ablation and 114 to ethanol injection . The number of treatment sessions was smaller ( 2.1 times vs 6.4 times , respectively , P < .0001 ) and the length of hospitalization was shorter ( 10.8 days vs 26.1 days , respectively , P < .0001 ) in radiofrequency ablation than in ethanol injection . Four-year survival rate was 74 % ( 95 % CI : 65%-84 % ) in radiofrequency ablation and 57 % ( 95 % CI : 45%-71 % ) in ethanol injection . Radiofrequency ablation had a 46 % smaller risk of death ( adjusted relative risk , 0.54 [ 95 % CI : 0.33 - 0.89 ] , P = .02 ) , a 43 % smaller risk of overall recurrence ( adjusted relative risk 0.57 [ 95 % CI : 0.41 - 0.80 ] , P = .0009 ) , and an 88 % smaller risk of local tumor progression ( relative risk , 0.12 [ 95 % CI : 0.03 - 0.55 ] , P = .006 ) than ethanol injection . The incidence of adverse events was not different between the 2 therapies . CONCLUSIONS Judging from higher survival but similar adverse events , radiofrequency ablation is superior to ethanol injection for small hepatocellular carcinoma Aim The aim of our study was to compare the short-term and long-term outcomes of resection and radiofrequency ablation ( RFA ) in cases of very early hepatocellular carcinoma ( HCC ) ( tumors<2 cm in diameter ) . Patients and methods Between July 2003 and August 2008 , 52 patients were diagnosed as very early HCC ( ⩽2 cm ) , of whom 21 received a liver resection and 31 underwent RFA . We compared the baseline characteristics , the intraoperative data , and the recovery metrics between these two groups including postoperative complications and the 1- , 3- , and 5-year overall and tumor-free survival rates . Results No statistically significant differences were observed in the baseline characteristics between very early HCC patients allocated to the liver resection group and those in the RFA group . The liver function in the liver resection group was better than that of the RFA group with respect to the Child score ( P=0.004 ) , but not the model for end-stage liver disease score ( P=0.066 ) . More tumor targets were located in the center of the liver ( compared with the periphery ) in the RFA group ( P=0.003 ) . The RFA patients showed much shorter operative times , less blood loss , and had shorter hospital stays than the resection group but had a much higher overall cost ( all P=0.000 ) . The 1- , 3- , and 5-year overall survival rates were 95.2 , 85.7 , and 81.0 % , respectively , for the liver resection group , and 93.5 , 90.3 , and 80.6 % , respectively , for the RFA group ( P=0.976 ) . The 1- , 3- , and 5-year tumor-free survival rates were 90.5 , 81.0 , and 76.2 % , respectively , in the resection group and 90.3 , 83.9 , and 71.0 % , respectively , in the RFA group ( P=0.830 ) . Conclusion With comparable short-term and long-term effects on overall survival and tumor recurrence rate and with a shorter operative time , less blood loss , and a shorter hospital stay , RFA should be considered as the first choice for the treatment for very early HCCs as it presents an efficacious and economic option |
814 | 30,349,793 | Conclusion : The literature on STSG donor-site dressings has not yet identified an ideal dressing . | Background : Many types of split-thickness skin graft ( STSG ) donor-site dressings are available with little consensus from the literature on the optimal dressing type .
The purpose of this systematic review was to analyze the most recent outcomes regarding moist and nonmoist dressings for STSG donor sites . | BACKGROUND Split- thickness skin graft is one of the most common operations in plastic surgery . It is always painful and patient discomfort from donor site often is more significant than recipient site . There is not still a st and ard method for treatment of the donor site . The purpose of this study was to determine the best method of dressing the donor site among three different methods with respect to the rate of healing , pain , secretion , infection and cost . METHODS The study includes 60 patients that were r and omly divided into three groups . Donor site and thickness of the graft was the same and were dressed with one of the methods including Method A : Paraffin fine mesh gauze , Method B : Nitrofurazone soaked fine mesh gauze and Method C : Dry fine mesh gauze . Each method included an intermediate layer of sterile plastic sheet witch was covered with 10 layers of dry gauze . Comparison with respect to the rate of healing , pain , secretion , infection and cost was done . RESULTS Thirty seven patients were men and 23 were women . The mean age of the patients was 27.2 years . There was a significant difference between three methods in average time of repair and superiority of dressing with Method B was noted . Pain severity was the least in Method B and difference between the methods was significant . Dressing with Method B had the least secretion and there was a statistically significant difference between three methods . There was no statistically significant difference in cost of the management . CONCLUSION This study showed that dressing the donor site with nitrofurazone ointment soaked gauze used as the first layer of dressing and intermediate layer of sterile plastic sheet which was covered with 10 layers of dry gauze was the best method of dressing and had the least complications Accelerating the healing process and reducing pain during healing are beneficial for the following reasons : faster return to work , lower risk of wound infection , improved quality of life , and possibly reduced need for analgesia . This clinical study assessed the effectiveness of a new oxygen-diffusion dressing ( OxyB and ; Oxyb and Technologies , St. Louis , MO ) compared with st and ard Xeroform gauze dressings ( Convidien , Mansfield , MA ) , in the care of skin-graft donor sites in burn patients . Time to healing was the primary endpoint , and pain scores and cosmetic outcome were also assessed . This was a prospect i ve , r and omized , controlled study of burn patients undergoing harvesting of two donor sites . Patients were followed at predetermined time points for 30 to 45 days to determine the time to reepithelialization , cosmetic appearance , and pain . Subjects were adult burn patients with less than 30 % TBSA burns admitted to the burn center , who required excision and grafting . Twenty patients were enrolled , of whom 17 completed the study . Average age was 35 years . Average burn size was 9.2 % TBSA . Patients underwent harvesting of split-thickness skin grafts with one donor wound dressed with OxyB and and the other dressed in Xeroform gauze . Wounds were inspected and photographed on postoperative days 4 and 8 , and then every 2 days until the donor wounds were healed . Pain scores at each site were also collected at these visits ( rated by patients on a scale from 0 to 10 ) . Mean time to wound healing for OxyB and was 9.3 ± 1.7 days ; for Xeroform , 12.4 ± 2.7 days ( P < .001 ) . Pain scores were lower ( P < .01 ) at the OxyB and site compared with the Xeroform site at all time points during postoperative days 4 to 12 . There was no difference in the cosmetic outcome of the wounds at 30 to 45 days postoperatively . This study revealed a decrease in the time to healing and in pain at donor sites dressed with an oxygen-diffusion dressing An ongoing objective of burn research is to evaluate wound dressings and develop new treatments to expedite wound healing . This was a single-center , prospect i ve , r and omized , controlled study to evaluate the effectiveness of Aquacel Ag as a dressing for autogenous skin donor sites compared with Xeroform . We hypothesized that donor sites treated with Aquacel Ag would heal faster . Patients were considered for enrollment if they required skin grafting with two donor sites > 100 cm2 at least 2 inches apart . Dressings were observed daily starting on post-op day # 2 until discharge and then weekly in the outpatient burn clinic . Assessment s evaluated pain , infection , and reapplication . Photographs were taken on post-op day # 2 , upon “ 90 % re-epithelialization , ” and at post-op day # 30–45 . Scar assessment s and blinded photographic review s were completed to assess cosmetic healing . Twenty-nine patients completed the study . Re-epithelialization occurred faster with Xeroform ( 15.2 days vs 17.6 days ) . Daily pain scores were higher with Xeroform ( 6.72 vs 5.68 ) and Aquacel Ag needed to be replaced more often ( 1.72 times vs 0.10 times ) . Three patients developed donor site infections with Aquacel Ag . Scar scores between the donor sites were not statistically significant . The blinded photo review concluded that Xeroform had a better cosmetic outcome ( 24 vs 10 % ) . Although patients complained of more pain with Xeroform , it demonstrated shorter healing times and better cosmetic outcomes . Aquacel Ag needed to be replaced more often and represented the only three donor site infections The present study was performed in China to compare the efficacy and safety of an advanced wound dressing made of crystalline cellulose ( Veloderm ® ) to a conventional treatment of three Vaseline gauzes in the management of skin donor sites of burns or reconstructive plastic surgery . In this prospect i ve , multicenter , open-labeled , r and omized clinical trial performed in three Chinese burn centers in China , 96 patients who required autologous split skin graft were r and omized into either the test ( Veloderm ® ) group or the control ( Vaseline gauze ) group . Average healing times in the test group and in the control group were 8.40±2.90 and 8.92±2.58 days , respectively , with median values of 7.00 and 8.00 days , respectively : the difference between two groups was statistically significant ( P=.045 ) . Scores for exu date s , pain intensity , and peripheral erythema showed no difference between the groups ; however , composite scores of three variables on day 10 postoperatively was significantly lower in the test group ( 0.00±0.00 vs 0.13±0.49 ; P = .043 ) . The need for a dressing change was also significantly lower in the test group ( 12.5 vs 31.25 % ; P = .036 ) . Veloderm ® is a safe and effective dressing that may offer some advantages over the traditional application of Vaseline gauze in the management of donor sites in burn or reconstructive plastic surgery patients Skin graft is a st and ard therapeutic technique in patients with deep ulcers , but managing donor site after grafting is very important . Although several modern dressings are available to enhance the comfort of donor site , using techniques that accelerate wound healing may enhance patient satisfaction . Low-level laser therapy ( LLLT ) has been used in several medical fields , including healing of diabetic , surgical , and pressure ulcers , but there is not any report of using this method for healing of donor site in burn patients . The protocol s and informed consent were review ed according to Medical Ethics Board of Shahid Beheshti University of Medical Sciences ( IR.SBMU.REC.1394.363 ) and Iranian Registry of Clinical Trials ( I RCT 2016020226069N2 ) . Eighteen donor sites in 11 patients with grade 3 burn ulcer were selected . Donor areas were divided into 2 parts , for laser irradiation and control r and omly . Laser area was irradiated by a red , 655-nm laser light , 150 mW , 2 J/cm2 , on days 0 ( immediately after surgery ) , 3 , 5 , and 7 . Dressing and other therapeutic care for both sites were the same . The patients and the person who analyzed the results were blinded . The size of donor site reduced in both groups during the 7-day study period ( P < 0.01 ) and this reduction was significantly greater in the laser group ( P = 0.01 ) . In the present study , for the first time , we evaluate the effects of LLLT on the healing process of donor site in burn patients . The results showed that local irradiation of red laser accelerates wound healing process significantly This study aim ed to investigate whether previous findings from a small retrospective study could be replicated prospect ively . The previous study showed that patients with an existing diagnosis of psychosis or depression , admitted to a burns service , had longer hospital stays and longer wound healing times when compared with controls matched for burn injury but without a pre-existing psychiatric condition [ 1 ] . In this study it was hypothesised that those patients without pre-existing psychiatric diagnosis , but with high levels of psychological distress after burn would also show a similar pattern of delayed recovery to those with a pre-existing psychiatric illness . In addition , we examined potential mechanisms for slowed recovery , including ; adherence with treatment ; delayed discharge on social grounds and psychological distress . It was hypothesised that patients with pre-existing psychiatric diagnosis would exhibit poorer adherence and delayed placement due to social reasons , compared to patients without pre-existing psychiatric diagnoses . 107 consecutive admissions to a burns service over a seven-month period were included in the study . Psychiatric history and level of psychological distress post-burn were collected for all patients as part of routine psychological screening . Patients were compared on the following outcome variables : number of days spent in hospital and number of procedures required . 24 % ( n=27 ) were found to have a pre-existing psychiatric diagnosis . This group were also found to have significantly longer hospital stays ( Mann-Whitney U=585.50 , p<0.01 ) and required more surgical procedures than the group without a psychiatric history ( Mann-Whitney U=569.00 , p=<0.001 ) . The pattern of results for the group with high psychological distress but without pre-existing psychiatric diagnoses mirrored that of the group with pre-existing psychiatric diagnoses , suggesting that heightened psychological distress alone , has a significant delaying effect upon the rate of recovery ( Kruskal-Wallis X=24.75 , p<0.01 ) . An exploratory model entering all the variables stepwise at the same stage identified poor adherence and delayed discharge issues as making significant contributions to the final model ( r=0.81 adjusted r(2)=62.9 , F ( 4 , 42)=20.48 , p<0.001 ) . In conclusion , this study supports the role of psychosocial factors , such as pre-existing psychiatric diagnosis and in hospital psychological distress , in contributing the recovery of survivors of burns . This suggests that identifying and working with these difficulties may impact not only on psychosocial , but also physical aspects of recovery OBJECTIVES : To compare postoperative healing of split-thickness skin graft ( STSG ) donor sites using traditional dressings ( paraffin gauze ) or modern wound dressings ( alginate dressing and polyurethane film ) in a r and omized controlled trial . METHOD : Thirty patients were r and omly assigned to treatment of an STSG donor site with an alginate dressing and a polyurethane film or nonadherent paraffin gauze . Outcome variables were pain ( measured with a visual analog scale ) , amount of dressing changes , healing time , cosmetic outcome , treatment costs , and overall satisfaction with the procedure . RESULTS : There was no significant difference in pain ( postoperative day 1 : 2.1 vs 1.2 , P = .26 ; postoperative days 5–7 : 1.0 vs 0.9 , P = .47 ; final removal : 1.9 vs 1.0 , P = .19 ) and time to healing ( 18.1 vs 15.4 days , P = .29 ) between alginate/polyurethane film dressing and nonadherent paraffin gauze . The semiocclusive dressings with polyurethane film required multiple dressing changes , whereas the nonadherent paraffin gauze could be left in place until complete epithelialization . Treatment costs were substantially lower for paraffin gauze . CONCLUSIONS : Semiocclusive dressings with alginate dressings and polyurethane film showed no advantages over treatment with paraffin gauze . With lower costs and better patient acceptance , paraffin gauze dressings were the preferred treatment for STSG donor sites BACKGROUND This paper presents the results of the first part of the clinical study of temporary biosynthetic dermal skin substitute based a on collagen and hyaluronic acid , named Coladerm H/HM . The aim of this study was to evaluate safety and effects of Coladerm H/HM in covering the split-thickness skin graft donor sites in humans . This membrane was applied to a part of the split-thickness skin graft donor site ; its effects and properties were compared to st and ard dressing used for covering the split-thickness skin graft donor sites at the Department of Burns and Reconstructive Surgery , University Hospital Bratislava , Slovakia , Dermazin ® ( Lek ) + Acidum Aceticum 1 % ( magistraliter ) , which were applied together to the rest of the donor site . MATERIAL AND METHODS Twenty patients were r and omly selected with the following criteria : age of 18 - 65 years , no severe accompanying diseases such as diabetes , renal failure , immune disorders , severe arteriosclerosis , severe allergic conditions . Evaluation was done according to the evaluation protocol . RESULTS Primary assessment showed that Coladerm H/HM does not influence the rate of epithelization from a long term point of view , but the initial faster epithelization contributes to the reduction of the risk of complications , which may arise from a long term open wounds . Secondary assessment showed the effect of Coladerm H/HM to the secretion of the wounds in the second inspection interval when the wound was dry in the whole group . Next , Coladerm H/HM contributed to the temporarily statistically significant positive effect to the color of donor area in the third inspection interval . Positive bacteriological finding occurred in one patient secondary . Analgetic effect of Coladerm H/HM assessed by a doctor was expressed as good in 70 % . 95 % of patients reported only mild pain after application of Coladerm H/HM . There were no significant side effects recorded , only 1 patient stated itching , which disappeared spontaneously . Application of Coladerm H/HM has positive properties for treating the split-thickness skin graft donor sites in humans . CONCLUSION Coladerm H/HM showed positive results covering the split-thickness skin graft donor sites in the first part of the clinical trial . Production of the Coladerm H/HM and its introduction into the clinical practice is planned after successful completion of all the parts of clinical trial The use of paraffin-impregnated gauze for burns and skin graft donor sites is commonly associated with wound adherence with consequent pain and trauma upon removal . This prospect i ve clinical study was performed to evaluate a new class of lipido-colloid dressings ( Urgotul ) in promoting healing and in reducing tissue adherence . In a 6-month period , 25 consecutive patients were recruited . Two separate burn or donor sites on each patient were dressed with tulle-gras ( TG ) or Urgotul and covered with st and ard secondary dressings . Objective assessment of wounds by two review ers , and patients ' subjective assessment s were recorded . Twenty-three ( 92 % ) patients were followed up for a mean of 3 months . Mean time to complete epithelialisation was 9.6 and 11.9 days for the Urgotul and TG sites respectively ( P < 0.05 ) . Bleeding was seen in 52 % of Urgotul sites compared with 100 % of the TG sites at first dressing change ( P < 0.05 ) . Patients reported ' moderate pain ' during dressing change in 22 % and 57 % in the Urgotul and TG groups respectively ( P < 0.05 ) , with 35 % of TG sites being ' very painful ' requiring extra analgesia . We found that compared with TG , Urgotul was associated with faster epithelialisation , less pain and trauma ( bleeding ) during dressing changes ABSTRACT Purpose An ethyl alcohol-precipitated silk sericin/PVA scaffold that controlled the release of silk sericin was previously developed and applied for the treatment of full-thickness wounds in rats and demonstrated efficient healing . In this study , we aim ed to further evaluate the clinical potential of this scaffold , hereafter called “ silk sericin-releasing wound dressing ” , for the treatment of split-thickness skin graft donor sites by comparison with the clinical ly available wound dressing known as “ Bactigras ® ” . Methods In vitro characterization and in vivo evaluation for safety of the wound dressings were performed . A clinical trial of the wound dressings was conducted according to st and ard protocol s. Results The sericin released from the wound dressing was not toxic to HaCat human keratinocytes . A peel test indicated that the silk sericin-releasing wound dressing was less adhesive than Bactigras ® , potentially reducing trauma and the risk of repeated injury upon removal . There was no evidence of skin irritation upon treatment with either wound dressing . When tested in patients with split-thickness skin graft donor sites , the wounds treated with the silk sericin-releasing wound dressing exhibited complete healing at 12 ± 5.0 days , whereas those treated with Bactigras ® were completely healed at 14 ± 5.2 days ( p = 1.99 × 10−4 ) . In addition , treatment with the silk sericin-releasing wound dressing significantly reduced pain compared with Bactigras ® particularly during the first 4 postoperative days ( p = 2.70 × 10−5 on day 1 ) . Conclusion We introduce this novel silk sericin-releasing wound dressing as an alternative treatment for split-thickness skin graft donor sites The Bactigras ® paraffin tulle coated with chlorhexidine is normally used for the treatment of donor-site wounds in burn patients who received split-thickness skin grafts in several centers . It has some disadvantages , such as adhesion to wound surfaces and pain from the irritation caused by this dressing . The Telfa AMD ® , a non-adherent wound dressing which consists of absorbent cotton fibers impregnated with polyhexamethylene biguanide enclosed in a sleeve of thermoplastic polymers , is a new option for donor-site wound care which causes less adherence to the wound . The purpose of this study was to compare clinical efficacy of these two dressings for the management of donor-site wounds . Thirty-two patients who received split-thickness skin grafts by donor site harvesting from the thigh were enrolled in this study and r and omized into two groups receiving either the Bactigras ® or the Telfa AMD ® wound treatment . Re-epithelialization , pain , infection and cost-effectiveness analyses were compared between both groups . The results showed that there was no significant difference in age , area of donor sites or length of hospital stays between the groups ( p > 0.05 ) . However , the day of re-epithelialization ( ≥90 % ) was significantly shorter in patients treated with the Telfa AMD ® compared to the Bactigras ® group ( 14.00 ± 3.05 vs. 9.25 ± 1.88 days for Bactigras ® and Telfa AMD ® groups , respectively , p < 0.001 ) . The average pain score was also significantly lower in the Telfa AMD ® group ( 1.57 ± 0.55 vs. 4.70 ± 1.16 , p < 0.001 ) . There was no difference in the cost of treatment between the groups ( 4.64 ± 1.97 vs. 5.72 ± 2.54 USD , p = 0.19 ) . This study indicated that the Telfa AMD ® was an effective dressing for the treatment of donor-site wounds Many new dressings have been introduced for use on split-thickness skin graft donor sites in an effort to reduce pain at the donor site and decrease healing time , while maintaining a low infection rate and cost . To assess these factors in two such dressings , Biobrane ( temporary wound dressing ) ( Winthrop ) and Duoderm ( hydrocolloid dressing ) ( Convatec ) , we compared them with a conventional fine mesh gauze dressing , xeroform , in a prospect i ve , r and omized study of 30 donor sites in the same number of patients . Wounds were considered healed when they were 100 per cent re-epithelialized and required no further dressings . Patient self- assessment of pain was quantified on a scale of zero to ten , with ten being the most severe pain . Donor sites dressed with xeroform had a healing time of 10.5 days , which was significantly better ( p less than 0.05 ) than Duoderm ( 15.3 days ) or Biobrane ( 19.0 days ) , although the protocol for Duoderm use ( wound visualization at seven day intervals ) extended the apparent healing times in this group . Duoderm was the most comfortable dressing ( 0.53 grade ) when compared with Biobrane ( 1.44 ) and xeroform ( 2.41 , p less than 0.05 ) . No infections occurred in donor sites dressed with xeroform , but two developed in patients using Biobrane . One patient with a Duoderm dressing had a donor site infection during a drug-related neutropenic reaction . Xeroform was the least expensive dressing to use ( $ 1.16 per patient ) , followed by Duoderm ( $ 54.88 per patient ) and Biobrane ( $ 102.57 per patient ) . The results of our study confirm the usefulness of xeroform as a donor site dressing as it promotes relatively rapid healing , is easy to use and is inexpensive . We found Duoderm to be ideal for smaller donor sites when pain could be significantly reduced with minimal increase in cost . Biobrane is too costly and the infection rate too high for it to be used routinely as a skin graft donor site dressing Donor-site wound healing was tested with a nonadherent petrolatum- and hydrocolloid-impregnated polyester , a lipid-colloid dressing , and a nonadherent polyester dressing , supplemented with petrolatum manually by a physician onsite . Ten patients , 1 woman and 9 men ( 22 to 79 years old ; average 58.4 ± 17.54 years ) , were enrolled in this prospect i ve comparison study . The split-thickness skin graft was 14.5 ± 7.49 cm long × 8.2 ± 4.07 cm wide ( 5.5 - 27 cm long and 4.0 - 14.0 wide ) and 14/1000 inches ( 0.356 mm ) deep . The degree of reepithelialization in lipid-colloid dressing was significantly better than that in polyester mesh dressing , with 1.7 ± 1.00 and 2.8 ± 0.83 for the lipid-colloid dressing and polyester mesh dressing , respectively ( P < .05 ) , and degree of pain was significantly lower in lipid-colloid dressing than that in polyester dressing , 1.7 ± 1.11 and 2.9 ± 1.12 for the lipid-colloid dressing and polyester mesh dressing , respectively ( P < .01 ) . In moisture meter analyses , the values of effective contact coefficient and corneal thickness in lipid-colloid at wound healing was significantly smaller than those in polyester mesh ( effective contact coefficient : 11.7 ± 1.87 % and 15.6 ± 3.09 % for lipid-colloid and polyester mesh , respectively , P < .05 ; corneal thickness : 31.1 ± 6.65 µm and 40.7 ± 8.69 µm for lipid-colloid and polyester mesh , respectively , P < .05 ) . No significant difference was observed at 1 month after healing . The nonadherent lipid-colloid polyester dressing has superior wound healing and pain relief and demonstrates better corneal barrier function delineated by effective contact coefficient and corneal thickness at healing in split-thickness donors Background : An ideal topical formulation for wound therapy does not exist . The aim of this study was to develop a novel improved therapeutic option for the treatment of acute and chronic wounds . Methods : A transparent wound gel which is in a liquid state below and in a gel state at or above room temperature was developed . Forty-four patients were included in this open r and omized controlled single-center study . Flammazine ™ served as control in the treatment of skin graft donor sites . Wounds were assessed for time of dressing change and overall satisfaction of patients and health care providers . The data were analyzed using the nonparametric Mann-Whitney test . Results : The wound gel proved to be superior in comparison with Flammazine with respect to wound assessment ( p = 0.002 ) , staining ( p = 0.007 ) , leaking ( p = 0.032 ) and smell ( p = 0.034 ) . Flammazine showed favorable results regarding the parameters dehydration of the dressings ( p = 0.012 ) and wound adherence ( p = 0.005 ) . The evaluation of the overall dressing change process showed no significant differences . Conclusion : The thermoreversible wound gel containing polyhexanide allows for good h and ling and wound assessment . This study demonstrated a high satisfaction level of patient and health care providers , and the wound gel proved an effective alternative to commonly used treatments Although the recipient site in burn wounds is dressed with universally accepted material s , the ideal management of split-thickness skin donor sites remains controversial . The aim of our study is to compare two methods of wound dressing in donor sites of split-thickness skin graft in patients undergoing burn wound reconstructive surgery . Forty-two consecutive patients with second- and third-degree burns with a total body surface area between 20 and 40 % were enrolled in this r and omized clinical trial conducted in Motahari Burn Hospital in Tehran , Iran . In each patient , two anatomic areas with similar features were r and omly selected as intervention and control donor sites . The intervention site was dressed with amniotic membrane , whereas the control site was treated with Vaseline-impregnated gauze . Wounds were examined daily by expert surgeons to measure the clinical outcomes including duration of healing , severity of pain , and infection rate . The mean ± SD age of patients was 31.17 ± 13.72 years ; furthermore , burn percentage had a mean ± SD of 31.19 ± 10.56 . The mean ± SD of patients ' cooperation score was 1.6 ± 0.79 in the intervention group compared with 2.93 ± 0.71 in the control group , revealing a statistically significant difference ( P < 0.05 ) . Duration of wound healing was significantly shorter ( P < 0.05 ) in the intervention group ( 17.61 ± 2.56 days ) compared with the control group ( 21.16 ± 3.45 days ) . However , there was no significant difference in terms of wound infection rate between donor sites in the control and intervention groups ( P > 0.05 ) . Amniotic membrane as an alternative for dressing of skin graft donor sites provides significant benefits by increasing patients ' comfort via diminishing the number of dressing changes and facilitating the process of wound healing Background : Pain at split skin graft donor sites is common . Fibrin sealant has been demonstrated to reduce time to hemostasis at wound sites , and patients receiving this treatment were incidentally noted to report less pain . This study aim ed to evaluate pain and incapacity in split skin graft donor sites treated with and without fibrin sealant . Methods : Fifty patients requiring thigh donor-site split skin grafts were prospect ively r and omized to receive either a self-adhesive fabric dressing alone or fibrin sealant plus the self-adhesive fabric dressing as primary donor-site dressings . External secondary dressings were the same . Patients were blinded with regard to treatment group . Using visual analogue scales ( scored 0 to 5 ) , patients rated their donor-site pain and incapacity for 14 days postoperatively . Secondary endpoints were length of hospital stay and duration of requirement for dressings . Results : Forty patients were included in the study analysis and completed self-reported pain and incapacity scores . Twenty received the fibrin sealant plus self-adhesive fabric dressing and 20 received the fabric dressing only ( controls ) . Patients using the fibrin sealant plus the dressing reported significantly less pain ( mean score , 0.42 versus 1.60 , p < 0.001 ) and significantly less incapacity ( mean score , 0.48 versus 1.71 , p < 0.001 ) . Patients allocated to the fibrin sealant group recorded shorter lengths of stay and faster time to discontinuation of dressing , though statistical significance was not achieved . Conclusion : Patients whose split skin graft donor sites were dressed with fibrin sealant plus self-adhesive fabric dressing experienced significantly less pain and incapacity than patients with self-adhesive fabric dressings alone , allowing a more rapid return to normal activity . CLINICAL QUESTION /LEVEL OF EVIDENCE : Therapeutic , II PURPOSE : A review of the literature reveals a lack of consensus regarding local management of skin graft donor sites . This study was undertaken to determine the effects of 3 different dressings on healing of donor sites and patient discomfort related to donor sites . DESIGN : This study is a comparison cohort study . SUBJECTS AND SETTING : We recruited 34 burn patients scheduled for partial-thickness skin grafts ; their mean age was 36 ± 18 years ( mean ± SD , range 20 to 54 years ) , and 63 % were male . All subjects were managed at Burn Unity Care , located in Sao Paulo , Brazil . MATERIAL S AND METHODS : Subjects were r and omly allocated to 1 of 3 groups : ( 1 ) a study group ( group A ) whose donor sites were dressed with a bovine collagen calcium-alginate dressing covered with transparent polyurethane film ; ( 2 ) a second intervention group ( group B ) , whose donor sites were dressed only with transparent polyurethane film dressing ; and ( 3 ) a control group whose donor sites were dressed with rayon soaked in 0.9 % saline ( group C ) . Two independent observers assessed donor site wounds for epithelialization , scabbing , quantity and characteristics of exu date , and complications . Pain was measured using the visual analog scale , the brief pain inventory , and Index of Pain Management . RESULTS : Subjects managed with the bovine collagen calcium-alginate dressing covered with transparent polyurethane film ( group A ) achieved the greatest epithelialization ( 6.3 vs 8.2 for thin film dressing only P < .02 and 6.3 vs 11.7 days for control group P < .01 ) . Patients managed with the bovine collagen calcium-alginate dressing covered with transparent polyurethane film also reported less pain that subjects allocated to the control ( group C ) or thin film only group ( group B ) , ( P < .05 ) . Ninety percent of subjects allocated to the calcium alginate covered with thin film dressing reported mild pain intensity on the Visual Analog Scale , 85 % of did not report pain localized to the donor site on the brief pain inventory , and scores on the Index of Pain Management ranged from 23 to 11 . CONCLUSION : Study findings suggest that use of a collagen calcium-alginate dressing with a transparent film covering reduces the time for complete epithelialization and may reduce pain related to skin graft donor sites BACKGROUND The authors investigated the possible effect of ibuprofen when included in polyurethane dressing foam in the management of pain and healing related to split-thickness skin graft ( STSG ) donor sites . The study focused on the use of a foam dressing , Biatain-Ibu , the combination of an absorbent hydrophilic polyurethane foam , Biatain , and the active ingredient ibuprofen as an integral part of the matrix . PATIENTS AND METHODS A prospect i ve study was conducted from October 2006 to April 2007 and included 40 patients undergoing surgery for any reconstructive purpose s with the use of STSG . The patients were divided into two groups in a r and omized fashion . In the first group of 20 patients , the donor sites were covered using Biatain-Ibu foam dressing . In the second group of 20 patients , the donor sites were closed intra-operatively with a st and ard dressing which did not contain any known healing promoting agent . To evaluate the extent and quality of the pain experienced by the patients and to score pain over time , the patients in the study were asked to complete a form containing a visual analogue scale and answer questions on the quality of pain and the way normal daily activities were affected . RESULTS The combined use of ibuprofen with bio-occlusive dressings accelerated wound healing compared to fine-mesh gauze dressings and almost eliminated pain and discomfort in all patients treated . In patients receiving topical ibuprofen , itch did not present a major problem . DISCUSSION This study demonstrates that the Biatain-Ibu dressing is a useful tool in the management of STSG donor sites by providing an optimal environment for wound healing due to its bio-occlusive properties and by minimizing pain and discomfort INTRODUCTION Preservation of human amniotic membrane ( HAM ) in glycerol 85 % has been used clinical ly but the use of glycerol 98 % can give the maximum virucidal activity and increases the safety of HAM . OBJECTIVE To determine the degree of clinical efficacy of HAM preserved in glycerol 98 % as a biological dressing in management of donor site of split thickness skin graft ( STSG ) . PATIENTS AND METHODS 40 subjects were enrolled in this r and omized , controlled study conducted in Al-Azhar University Hospitals from August 2013 to June 2014 . We compared HAM preserved in glycerol 98 % to vaseline gauze . Patients were r and omly allocated to STSG donor site dressing with one of these material s. Outcome measures included pain scores at postoperative days 2 , 6 and 10 , time to re-epithelialization , and incidence of infection . RESULTS Both groups were homogenous regarding age , gender , cause of burn and size . The HAM group showed significantly less pain on postoperative days 2 and 6 ( 4 and 2.7 vs. 5.6 and 4.2 respectively with p value < 0.05 ) . Shorter time to re-epithelialization was also found in the HAM group ( 11.7 vs. 15.4 with p value < 0.05 ) . No significant difference was found between both groups in the incidence of infection . CONCLUSION HAM preserved in glycerol 98 % is clinical ly effective as a biological dressing . The higher glycerol concentration increases the safety of HAM with retaining the clinical effect at the same time The aim of this study was to compare the effectiveness of a hemicellulose dressing with that of rayon dressing in the healing of split-thickness skin graft donor sites . Twenty-eight patients were selected from five different hospitals and r and omized into two groups : hemicellulose dressing group and rayon dressing group . All patients underwent split-thickness skin grafting for various reasons , and the skin graft donor site wounds were covered with hemicellulose dressing ( n=14 ) or rayon dressing ( n=14 ) . The donor site was assessed on postoperative days 1 , 7 , 14 , 21 , and 28 for hyperemia , pruritus , pain , exu date level , and adherence of the wound dressing . At the 60-day follow-up visit , the donor site was assessed again for pruritus and pain . Touch-pressure , thermal , and pain sensibility tests were performed preoperatively and on postoperative day 60 together with the assessment of color and texture of the re-epithelialized area . In all patients , re-epithelialization was completed between 14 and 21 days after surgery . There were no significant differences between the two groups with regard to pain , hyperemia , pruritus , exu date , and final appearance ( color and texture ) of the skin graft donor site . The rayon dressing provided significantly better adherence than the hemicellulose dressing , and both dressings showed similar results with regard to the parameters evaluated when used in the treatment of split-thickness skin graft donor sites INTRODUCTION Split-thickness skin grafting ( STSG ) is a frequently used reconstructive technique but is associated with a large variation regarding the management of the donor site . The aim of this study is to compare five different dressings for management of the STSG donor site in a prospect i ve trial . PATIENTS AND METHODS 100 consecutive patients , in whom reconstruction with STSG was performed , were included into the study . The grafts are harvested in a st and ard manner and the donor sites were dressed with one of the following material s : Aquacel ® Ag , Bactigras ® with Melolin ® , Comfeel ® Plus Transparent , Opsite ® Flexigrid and Adaptic ® . The material s are compared regarding to the time required for complete epithelialization , pain sensed by the patients , incidence of infection , scar formation , ease of application and the cost . RESULTS The earliest complete epithelialization was observed for Aquacel ® Ag and the latest for Bactigras ® with Melolin ® ·Comfeel ® Plus Transparent was the most painless dressing and Bactigras ® with Melolin ® was the most painful . The incidence of infection was highest for Bactigras ® with Melolin ® ·Opsite ® Flexigrid was the most economical dressing and Aquacel ® Ag was the most expensive one . CONCLUSION The aim is to provide the earliest complete epithelialization with minimal patient discomfort and lower cost in management of the STSG donor sites . None of the tested material s were ideal regarding these criteria , but Comfeel ® Plus Transparent , as the least painful and one of the most economical material s , may be offered as the dressing of choice among the tested material Intention of the study ( EudraCT No 2009 - 017418 - 56 ) is a proof of aesthetic benefit of triterpene treatment in superficial wounds . In an open , prospect i ve , controlled , r and omized , blindly evaluated multicentre phase II clinical trial a triterpene ointment ( OG-S10 ) is compared intra individually with a state-of-the-art moist wound healing dressing ( Mepilex ( ® ) ) in split thickness skin graft donor sites . The graft wound areas at the upper leg were divided into two equal halves , one proximal and one distal site . Decided by r and omization the one site was treated with triterpene and the other in comparison with moist dressing . Triterpene treatment went on for 14 days as covering the wound at every change of wound dressing with the ointment ( 100 mg/cm(2 ) ) . The comparative treatment went on as covering the site by this dressing alone . The outcome of these different treatments was evaluated by two blindly observing distant experts on the basis of photographs of the wound healing progress . Photographs were taken day 14 , 3 month and 1 year after treatment . The only criterion for evaluation of the two sites was similarity of the wound area to the surrounding skin in terms of colour and texture : which of the two sites , the proximal or the distal , was aesthetically superior in normal skin appearance after 14 days at the end of treatment , after 3 month of follow up and 1 year after treatment ? The descriptive comparison is demonstrating quite a remarkable advantage of the ointment versus the moist wound dressing in promoting wound healing : even having in mind the small number of 24 patients within the protocol , the superiority of aesthetic benefit by triterpene treatment after 14 days ( 22 out of 24 patients ) , after 3 month ( 15 out of 19 patients ) and after 1 year ( 8 out of 10 patients ) is obvious The split-thickness skin graft ( STSG ) donor site dressing has been an inconclusive topic . Each of the Hydrofiber ( Aquacel , ConvaTec A Bristol-Myers Squibb Company , Deeside , UK ) and silver dressings have applied in many types of wound care with favorable outcomes . Our study compared the ionic silver-containing Hydrofiber dressing and paraffin gauze dressing . The subjects were r and omized into group A : ionic silver-containing Hydrofiber and group B : paraffin gauze . From February 2006 to 2007 , 20 donor sites were recorded . The mean donor site surface area was 145.5 cm2 ( group A ) and 135.8 cm2 ( group B ) . The completed re-epithelization day was 7.90 and 11.20 days , respectively ( P = 0.031 ) . The average pain score at rest were 0.74 and 0.80 , respectively ( P = 0.894 ) . The average pain score on dressing removal were 3.12 and 4.70 , respectively ( P = 0.027 ) . There was no infection or seroma in both groups . In conclusion , ionic silver-containing Hydrofiber dressing can reduce STSG donor site pain and promote re-epithelization compared to paraffin gauze dressing This prospect i ve , r and omised study compares a new transforming methacrylate dressing ( TMD ) with a silver-containing carboxymethylcellulose dressing ( CMC-Ag ) after application to split-thickness skin graft ( STSG ) donor sites . This was an unblinded , non-inferiority , between-patient , comparison study that involved patients admitted to a single-centre burn unit who required two skin graft donor sites . Each patient 's donor sites were covered immediately after surgery : one donor site with TMD and the other with CMC-Ag . The donor sites were evaluated until healing or until 24 days post-application , whichever came first . Study endpoints were time to healing , daily pain scores , number of dressing changes , patient comfort and physicians ' and patients ' willingness to use the dressings in the future . Nineteen patients had both the dressings applied . No statistically significant difference was noted in time to healing between the two dressings ( 14·2 days using TMD compared with 13·2 days using CMC-Ag ) . When pain scores were compared , TMD result ed in statistically significantly less pain at three different time periods ( 2 - 5 days , 6 - 10 days and 11 - 15 days ; P < 0·001 at all time periods ) . Patients also reported greater comfort with TMD ( P < 0·001 ) . Users rated TMD as being less easy to use because of the time and technique required for application . Reductions in pain and increased patient comfort with the use of the TMD dressing , compared with CMC-Ag , were seen as clinical benefits as these are the major issues in donor site management |
815 | 31,208,420 | Conclusions DDP-4i effectively reduced serum CRP levels and showed no stronger effect than traditional oral antidiabetic agents . | Background Dipeptidyl peptidase-4 inhibitors ( DPP-4i ) are emerging glucose-lowering agents through interacting with DPP-4 substrate , impact of which on systemic inflammation in type 2 diabetes mellitus ( T2DM ) remains unknown .
This study aim ed to evaluate the effect of DPP-4i on modulating serum levels of C-reactive protein ( CRP ) in T2DM . | Background Blood glucose control is fundamental albeit not enough to prevent diabetic macrovascular complications . Dipeptidyl peptidase-4 ( DPP-4 ) inhibitors are effective in improving metabolic parameters in patients with type 2 diabetes mellitus ( T2DM ) but little is known about its cardiovascular effects . We compared the DPP-4 inhibitor sitagliptin with bedtime NPH insulin ( NPH ) as add-on therapy in patients with T2DM , aim ing to ascertain which drug would have additional cardioprotective effects . Methods Thirty-five T2DM patients inadequately controlled with metformin plus glyburide were r and omized to receive sitagliptin ( n = 18 ) or NPH ( n = 17 ) for 24 weeks . Fasting plasma glucose , HbA1c , lipid profile , C-reactive protein , active glucagon-like peptide ( aGLP-1 ) levels , 24-hour ambulatory blood pressure measurement and comprehensive 2-dimensional echocardiogram were determined before and after treatments . Results Both sitagliptin and NPH therapies decreased HbA1c levels after 24 weeks . Fasting plasma glucose and triglyceride levels decreased in the NPH group whereas only sitagliptin increased aGLP-1 levels . Left ventricular diastolic dysfunction ( LVDD ) was detected in 58.6 % of twenty-nine patients evaluated . Beneficial effects in LVDD were observed in 75 % and 11 % of patients treated with sitagliptin and NPH , respectively ( p = 0.015 ) . Neither therapy changed C-reactive protein or blood pressure . Conclusions Sitagliptin and bedtime NPH were similarly effective on glucose control . Improvement in LVDD in T2DM patients treated with sitagliptin was suggested , probably related to the increase of aGLP-1 levels . Therefore , DPP-4 inhibitor seems to have cardioprotective effects independent of glucose control and may have a role in the prevention of diabetic cardiomyopathy Abstract Background Diabetes is associated closely with an increased risk of cardiovascular events , including diastolic dysfunction and heart failure that leads to a shortening of life expectancy . It is therefore extremely valuable to evaluate the impact of antidiabetic agents on cardiac function . However , the influence of dipeptidyl peptidase 4 inhibitors on cardiac function is controversial and a major matter of clinical concern . We therefore evaluated the effect of sitagliptin on echocardiographic parameters of diastolic function in patients with type 2 diabetes as a sub- analysis of the PROLOGUE study . Methods Patients in the PROLOGUE study were assigned r and omly to either add-on sitagliptin treatment or conventional antidiabetic treatment . Of the 463 patients in the overall study , 115 patients ( 55 in the sitagliptin group and 60 in the conventional group ) who had complete echocardiographic data of the ratio of peak early diastolic transmitral flow velocity ( E ) to peak early diastolic mitral annular velocity ( e′ ) at baseline and after 12 and 24 months were included in this study . The primary endpoint of this post hoc sub- analysis was a comparison of the changes in the ratio of E to e′ ( E/e′ ) between the two groups from baseline to 24 months . Results The baseline-adjusted change in E/e′ during 24 months was significantly lower in the sitagliptin group than in the conventional group ( −0.18 ± 0.55 vs. 1.91 ± 0.53 , p = 0.008 ) , irrespective of a higher E/e′ value at baseline in the sitagliptin group . In analysis of covariance , sitagliptin treatment was significantly associated with change in E/e′ over 24 months ( β = −9.959 , p = 0.001 ) , independent of other clinical variables at baseline such as blood pressure , HbA1c , and medications for diabetes . Changes in other clinical variables including blood pressure and glycemic parameters , and echocardiographic parameters , such as cardiac structure and systolic function , were comparable between the two groups . There was also no significant difference in the serum levels of N-terminal-pro brain natriuretic peptide and high-sensitive C-reactive protein between the two groups during the study period . Conclusions Adding sitagliptin to conventional antidiabetic regimens in patients with T2DM for 24 months attenuated the annual exacerbation in the echocardiographic parameter of diastolic dysfunction ( E/e′ ) independent of other clinical variables such as blood pressure and glycemic control . Trial registration UMIN000004490 ( University Hospital Medical Information Network Clinical Trials ) . https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000005356 ; registered November 1 , Background Glycemic variability is associated with the development of diabetic complications through the activation of oxidative stress . This study aim ed to evaluate the effects of a dipeptidyl peptidase 4 inhibitor , vildagliptin , or a thiazolidinedione , pioglitazone , on glycemic variability and oxidative stress in patients with type 2 diabetes . Methods In this open label , r and omised , active-controlled , pilot trial , individuals who were inadequately controlled with metformin monotherapy were assigned to either vildagliptin ( 50 mg twice daily , n=17 ) or pioglitazone ( 15 mg once daily , n=14 ) treatment groups for 16 weeks . Glycemic variability was assessed by calculating the mean amplitude of glycemic excursions ( MAGE ) , which was obtained from continuous glucose monitoring . Urinary 8-iso prostagl and in F2α , serum oxidised low density lipoprotein , and high-sensitivity C-reactive protein were used as markers of oxidative stress or inflammation . Results Both vildagliptin and pioglitazone significantly reduced glycated hemoglobin and mean plasma glucose levels during the 16-week treatment . Vildagliptin also significantly reduced the MAGE ( from 93.8±38.0 to 70.8±19.2 mg/dL , P=0.046 ) , and mean st and ard deviation of 24 hours glucose ( from 38±17.3 to 27.7±6.9 , P=0.026 ) ; however , pioglitazone did not , although the magnitude of decline was similar in both groups . Markers of oxidative stress or inflammation including urinary 8-iso prostagl and in F2α did not change after treatment in both groups . Conclusion In this 16-week treatment trial , vildagliptin , but not pioglitazone , reduced glycemic variability in individuals with type 2 diabetes who was inadequately controlled with metformin monotherapy , although a reduction of oxidative stress markers was not observed The aim of the study was to compare the effects of the addition of sitagliptin or metformin to pioglitazone monotherapy in poorly controlled type 2 diabetes mellitus patients on body weight , glycemic control , beta-cell function , insulin resistance , and inflammatory state parameters . One hundred fifty-one patients with uncontrolled type 2 diabetes mellitus ( glycated hemoglobin [ HbA(1c ) ] > 7.5 % ) in therapy with pioglitazone 30 mg/d were enrolled in this study . We r and omized patients to take pioglitazone 30 mg plus sitagliptin 100 mg once a day , or pioglitazone 15 mg plus metformin 850 mg twice a day . We evaluated at baseline and after 3 , 6 , 9 , and 12 months these parameters : body weight , body mass index , HbA(1c ) , fasting plasma glucose ( FPG ) , postpr and ial plasma glucose ( PPG ) , fasting plasma insulin ( FPI ) , homeostasis model assessment insulin resistance index ( HOMA-IR ) , homeostasis model assessment beta-cell function index , fasting plasma proinsulin ( Pr ) , Pr/FPI ratio , adiponectin , resistin ( R ) , tumor necrosis factor-alpha ( TNF-alpha ) , and high-sensitivity C-reactive protein . A decrease of body weight and body mass index was observed with metformin , but not with sitagliptin , at the end of the study . We observed a comparable significant decrease of HbA(1c ) , FPG , and PPG and a significant increase of homeostasis model assessment beta-cell function index compared with baseline in both groups without any significant differences between the 2 groups . Fasting plasma insulin , fasting plasma Pr , Pr/FPI ratio , and HOMA-IR values were decreased in both groups even if the values obtained with metformin were significantly lower than the values obtained with sitagliptin . There were no significant variations of ADN , R , or TNF-alpha with sitagliptin , whereas a significant increase of ADN and a significant decrease of R and TNF-alpha values were recorded with metformin . A significant decrease of high-sensitivity C-reactive protein value was obtained in both groups without any significant differences between the 2 groups . There was a significant correlation between HOMA-IR decrease and ADN increase , and between HOMA-IR decrease and R and TNF-alpha decrease in pioglitazone plus metformin group after the treatment . The addition of both sitagliptin or metformin to pioglitazone gave an improvement of HbA(1c ) , FPG , and PPG ; but metformin led also to a decrease of body weight and to a faster and better improvement of insulin resistance and inflammatory state parameters , even if sitagliptin produced a better protection of beta-cell function OBJECTIVE : To evaluate the effect of dipeptidyl-peptidase-4 ( DPP-4 ) inhibitor vildagliptin on high sensitivity C-reactive protein ( hsCRP ) and arterial stiffness ( AS ) in patients with type 2 diabetes ( T2DM ) . DESIGN : Sixty-four drug-naive diabetic patients , with inadequate glycemic control , participated in this r and omized , open-label study . Half of the patients received metformin 1700 mg/d and the other half of them received metformin 1700 mg/d plus vildagliptin 100 mg/d . AS was measured by carotid-femoral Pulse Wave Velocity ( cfPWV ) . Body weight ( BW ) , body mass index ( BMI ) , blood pressure ( BP ) , hsCRP , glycosylated hemoglobin ( HbA1c ) , fasting plasma glucose ( FPG ) , lipid profile , albumin/creatinine ratio ( ACR ) , fasting insulin , C-peptide , homeostasis model assessment of insulin resistance ( HOMA-IR ) and homeostasis model assessment of β-cell function ( HOMA-β ) were also assessed at baseline and after 6 months . RESULTS : Vildagliptin in combination with metformin had a beneficial influence on hsCRP , HbA1c , C-peptide and HOMA-β index ( p < 0.05 ) but had no effect on cfPWV , BP , BW , BMI , lipid profile , ACR and HOMA-IR compared with metformin alone ( p = NS ) . CONCLUSIONS : We have found that the addition of vildagliptin to metformin for a period of six months decreased hsCRP , improved glycemic control and β-cell function but had no effect on AS in drug-naive patients with T2DM OBJECTIVE Recent experimental studies have shown that dipeptidyl peptidase 4 ( DPP-4 ) inhibitors have antiatherosclerotic benefits in glucagon-like peptide 1–dependent and –independent manners . The current study investigated the effects of alogliptin , a DPP-4 inhibitor , on the progression of carotid atherosclerosis in patients with type 2 diabetes mellitus ( T2DM ) . RESEARCH DESIGN AND METHODS This prospect i ve , r and omized , open-label , blinded-end point , multicenter , parallel-group , comparative study included 341 patients with T2DM free of a history of apparent cardiovascular diseases recruited at 11 clinical units and r and omly allocated to treatment with alogliptin ( n = 172 ) or conventional treatment ( n = 169 ) . Primary outcomes were changes in mean common and maximum intima-media thickness ( IMT ) of the carotid artery measured by carotid arterial echography during a 24-month treatment period . RESULTS Alogliptin treatment had a more potent glucose-lowering effect than the conventional treatment ( −0.3 ± 0.7 % vs. −0.1 ± 0.8 % , P = 0.004 ) without an increase of hypoglycemia . Changes in the mean common and the right and left maximum IMT of the carotid arteries were significantly greater after alogliptin treatment than after conventional treatment ( −0.026 mm [ SE 0.009 ] vs. 0.005 mm [ SE 0.009 ] , P = 0.022 ; −0.045 mm [ SE 0.018 ] vs. 0.011 mm [ SE 0.017 ] , P = 0.025 , and −0.079 mm [ SE 0.018 ] vs. −0.015 mm [ SE 0.018 ] , P = 0.013 , respectively ) . CONCLUSIONS Alogliptin treatment attenuated the progression of carotid IMT in patients with T2DM free of apparent cardiovascular disease compared with the conventional treatment Background Alpha glucosidase inhibitor ( GI ) attenuates postpr and ial hyperglycemia ( PPH ) and reduces the risk of cardiovascular events in patients with impaired glucose tolerance or type 2 diabetes . Dipeptidyl peptidase 4 ( DPP-4 ) inhibitors also attenuate PPH . PPH is one of the factors leading to endothelial dysfunction which is an early event in the pathogenesis of atherosclerosis . Furthermore , DPP-4 inhibitors protect endothelial function through a GLP-1-dependent mechanism . However , the impact of these two types of drugs on endothelial dysfunction in patients with type 2 diabetes has not been fully eluci date d. We compared the effects of sitagliptin , a DPP-4 inhibitor , and voglibose , an alpha GI , on endothelial function in patients with diabetes . Methods We conducted a r and omized prospect i ve multicenter study in 66 patients with type 2 diabetes who did not achieve the treatment goal with sulfonylurea , metformin or pioglitazone treatment ; 31 patients received sitagliptin treatment and 35 patients , voglibose treatment . The flow-mediated dilatation ( FMD ) of the brachial artery was measured in the fasting state at baseline and after 12 weeks of treatment . The primary endpoint was a change in FMD ( ΔFMD ) from the baseline to the end of follow-up . The effects of sitagliptin and voglibose on FMD were assessed by ANCOVA after adjustment for the baseline FMD , age , sex , current smoking , diabetes duration and body mass index . Secondary efficacy measures included changes in HbA1c , GIP , GLP-1 , C-peptide , CD34 , lipid profile , oxidative stress markers , inflammatory markers and eGFR and any adverse events . Results ΔFMD was significantly improved after 12 weeks of treatment in both groups , and there was no significant difference in ΔFMD between the two groups . There were no significant differences in changes in HbA1c , GIP , GLP-1 , C-peptide , lipid profile , oxidative stress marker , inflammatory marker and eGFR between the two groups . Compared with voglibose , sitagliptin significantly increased the circulating CD34 , a marker of endothelial progenitor cells . Adverse events were observed in 5 patients in only the voglibose group ( diarrhea 1 , nausea 1 , edema 2 and abdominal fullness 1 ) . Conclusions Sitagliptin improved endothelial dysfunction just as well as voglibose in patients with type 2 diabetes . Sitagliptin had protective effects on endothelial function without adverse events . Trial registration registered at http://www.umin.ac.jp/ctrj/ under AIM This study evaluated the effect of sitagliptin versus glibenclamide on arterial stiffness , blood pressure , lipid profile , oxidative stress , and high-sensitivity C-reactive protein ( hsCRP ) in type 2 diabetes mellitus patients . SUBJECTS AND METHODS Forty diabetes patients , inadequately controlled on metformin , were r and omly assigned to either sitagliptin ( 100 mg/day ) or glibenclamide ( 5 mg/day ) for 3 months . Following a 1-month washout period , a crossover switch from glibenclamide to sitagliptin and vice versa was performed for an additional 3 months . Arterial stiffness , 24-h ambulatory blood pressure monitoring , lipids , hsCRP , glycated hemoglobin , fasting glucose , STAT-8-isoprostane ( a measure of oxidative stress ) , body mass index ( BMI ) , and waist circumference were measured at baseline and at 3 months with each of the study drugs . RESULTS Thirty-four patients completed the study . Glibenclamide had a better glucose-lowering effect than sitagliptin , but this was associated with more hypoglycemic events . BMI increased following glibenclamide treatment , whereas sitagliptin proved weight-neutral . Mean BMI gain was + 0.5±1.0 kg/m(2 ) for glibenclamide versus -0.01±0.9 kg/m(2 ) for sitagliptin ( P<0.001 ) . Triglyceride levels significantly dropped following sitagliptin , although they remained unaltered after glibenclamide treatment . Mean triglyceride decrease was -18.4±45 mg/mL after sitagliptin but -0.2±57 mg/dL following glibenclamide treatment ( P=0.018 ) . There was no change in low-density lipoprotein , high-density lipoprotein , arterial stiffness , blood pressure monitoring , hsCRP , or STAT-8-isoprostane with each of the study drugs . CONCLUSIONS Sitagliptin , but not glibenclamide , demonstrated a significant beneficial effect on BMI and triglyceride levels . However , arterial stiffness , blood pressure , oxidative stress , and inflammatory status were not significantly affected by adding sitagliptin or glibenclamide to metformin-treated type 2 diabetes patients BACKGROUND To assess the efficacy of a vildagliptin and metformin combination therapy to a metformin monotherapy in type 2 diabetes mellitus patients . METHODS Sixty-one patients with diabetes inadequately controlled by a metformin monotherapy were r and omized to treatment with a combination therapy of vildagliptin 100 mg and a metformin versus metformin monotherapy . This was a 12-week r and omized parallel group study . During the study we assessed parameters of glycemic and lipid metabolism as well as the treatment effects on the release of proinflammatory and antiinflammatory cytokines . RESULTS Compared with baseline values we observed a significant improvement of glycaemic parameters such as HbA1c , FPG , PPG , FPI , HOMA-IR and HOMA-β index as well as decrease of TCh , TG and LDL and an increase of HDL with the greatest extent of vildagliptin plus a low-dose metformin therapy group . A metformin combination therapy significantly decreased such inflamation parameters as hs-CRP , ox-LDL , TNF-α and IL-1β levels relative to monotherapies . All treatments were well tolerated and there was no incidence of hypoglycaemia . CONCLUSIONS Vildagliptin added to an ongoing metformin therapy allows to achieve better metabolic control parameters in comparison with a metformin monotherapy and the combination treatment is well tolerated and has a low risk of serious adverse effects AIMS To evaluate the impact on glycemic control , insulin resistance , and insulin secretion of sitagliptin+metformin compared to metformin in type 2 diabetic patients . METHODS Patients were instructed to take metformin for 8 ± 2 months , then they were r and omly assigned to sitaglipin 100 mg or placebo for 12 months . We evaluated at 3 , 6 , 9 , and 12 months : body mass index ( BMI ) , glycemic control , fasting plasma insulin ( FPI ) , HOMA-IR , HOMA-β , fasting plasma proinsulin ( FPPr ) , proinsulin/fasting plasma insulin ratio ( Pr/FPI ratio ) , C-peptide , glucagon , adiponectin ( ADN ) , and high sensitivity-C reactive protein ( Hs-CRP ) . Before , and after 12 months since the addition of sitagliptin , patients underwent a combined euglycemic hyperinsulinemic and hyperglycemic clamp , with subsequent arginine stimulation . RESULTS Both treatments similarly decreased body weight , and BMI ; on the other h and , they both improved glycemic control , glucagon and HOMA-IR , but sitagliptin+metformin were more effective in reducing these parameters . Sitagliptin+metformin , but not placebo+metformin , decreased FPPr , FPPR/FPI ratio , and increased C-peptide values , even if no differences between the groups were recorded . Sitaglitin+metformin gave also a greater increase of HOMA-β , M value , C-peptide response to arginine and disposition index compared to placebo+metformin group . CONCLUSIONS Other than improving glycemic control , sitagliptin+metformin also improved β-cell function better than metformin alone Abstract Objective : To determine the relation between exposure to glycaemia over time and the risk of macrovascular or microvascular complications in patients with type 2 diabetes . Design : Prospect i ve observational study . Setting : 23 hospital based clinics in Engl and , Scotl and , and Northern Irel and . Participants : 4585 white , Asian Indian , and Afro-Caribbean UKPDS patients , whether r and omised or not to treatment , were included in analyses of incidence ; of these , 3642 were included in analyses of relative risk . Outcome measures : Primary predefined aggregate clinical outcomes : any end point or deaths related to diabetes and all cause mortality . Secondary aggregate outcomes : myocardial infa rct ion , stroke , amputation ( including death from peripheral vascular disease ) , and microvascular disease ( predominantly retinal photo-coagulation ) . Single end points : non-fatal heart failure and cataract extraction . Risk reduction associated with a 1 % reduction in up date d mean HbA1c adjusted for possible confounders at diagnosis of diabetes . Results : The incidence of clinical complications was significantly associated with glycaemia . Each 1 % reduction in up date d mean HbA1c was associated with reductions in risk of 21 % for any end point related to diabetes ( 95 % confidence interval 17 % to 24 % , P<0.0001 ) , 21 % for deaths related to diabetes ( 15 % to 27 % , P<0.0001 ) , 14 % for myocardial infa rct ion ( 8 % to 21 % , P<0.0001 ) , and 37 % for microvascular complications ( 33 % to 41 % , P<0.0001 ) . No threshold of risk was observed for any end point . Conclusions : In patients with type 2 diabetes the risk of diabetic complications was strongly associated with previous hyperglycaemia . Any reduction in HbA1c is likely to reduce the risk of complications , with the lowest risk being in those with HbA1c values in the normal range ( < 6.0 % ) AIM The aim of this study was to assess the effect of sitagliptin , a dipeptidyl peptidase-4 inhibitor , on 24-h glucose control when added to the regimen of patients with type 2 diabetes who had inadequate glycaemic control on metformin therapy . METHODS In a double-blind , r and omized , placebo-controlled , two-period crossover study , patients with type 2 diabetes with inadequate glycaemic control on metformin monotherapy ( i.e. on a stable dose of > or = 1500 mg/day for > or = 6 weeks prior to the screening visit and an haemoglobin A(1c ) ( HbA(1c ) ) > or = 6.5 % and < 10 % and fasting plasma glucose ( FPG ) < or = 240 mg/dl ) were recruited for participation . A total of 28 patients ( baseline HbA(1c ) range = 6.5 - 9.6 % ) receiving metformin were r and omized into one of two treatment sequences : the addition of placebo for 4 weeks followed by the addition of sitagliptin 50 mg twice daily ( b.i.d . ) for 4 weeks , or vice versa . At the end of each treatment period , patients were domiciled for frequent blood sampling over 24 h. The primary endpoint was 24-h weighted mean glucose ( WMG ) and secondary endpoints included change in FPG , mean of 7 daily self-blood glucose measurements ( MDG ) and fructosamine . beta-cell function was assessed from glucose and C-peptide concentrations were measured during the 5-h period after a st and ard breakfast meal by using the C-peptide minimal model . RESULTS Despite a carryover effect from period 1 to period 2 , the combined period 1 and period 2 results for glycaemic endpoints were statistically significant for sitagliptin relative to placebo when added to ongoing metformin therapy . To account for the carryover effect , the period 1 results were also compared between the groups . Following period 1 , there were significant least-squares ( LS ) mean reductions in 24-h WMG of 32.8 mg/dl , significant LS mean reduction from baseline in MDG of 28 mg/dl , FPG of 20.3 mg/dl and fructosamine of 33.7 mmol/l in patients treated with sitagliptin relative to placebo ( p < 0.05 ) . When added to ongoing metformin therapy , parameters of beta-cell function were significantly improved with sitagliptin compared with placebo . No weight gain or increases in gastrointestinal adverse events or hypoglycaemia events were observed with sitagliptin relative to placebo during this study . CONCLUSIONS In this study , the addition of sitagliptin 50 mg b.i.d . to ongoing metformin therapy improved 24-h glycaemic control and beta-cell function , and was generally well tolerated in patients with type 2 diabetes BACKGROUND This study evaluated the effect of vildagliptin + metformin on glycemic control and β-cell function in type 2 diabetes patients . SUBJECTS AND METHODS One hundred seventy-one type 2 diabetes patients , naive to antidiabetes therapy and with poor glycemic control , were instructed to take metformin for 8±2 months up to a mean dosage of 2,500±500 mg/day ; then they were r and omly assigned to add vildaglipin 50 mg twice a day or placebo for 12 months . We evaluated at 3 , 6 , 9 , and 12 months : body mass index , glycemic control , fasting plasma insulin , homeostasis model assessment insulin resistance index ( HOMA-IR ) , homeostasis model assessment β-cell function index ( HOMA-β ) , fasting plasma proinsulin , proinsulin/fasting plasma insulin ratio , C-peptide , glucagon , adiponectin , and high-sensitivity C-reactive protein . Before and at 12 months after the addition of vildagliptin , patients underwent a combined euglycemic hyperinsulinemic and hyperglycemic clamp , with subsequent arginine stimulation , to assess insulin sensitivity and insulin secretion . RESULTS After 12 months of treatment , vildagliptin + metformin gave a better decrease of body weight , glycemic control , HOMA-IR , and glucagon and a better increase of HOMA-β compared with placebo + metformin . Regarding the measures of β-cell function , treatment-induced changes in M-value , first- and second-phase C-peptide response to glucose , and C-peptide response to arginine were significantly higher in the vildagliptin + metformin group compared with the placebo + metformin group . CONCLUSION The addition of vildagliptin to metformin gave a better improvement of glycemic control , insulin resistance , and β-cell function compared with metformin alone AIM To compare the efficacy and safety of sitagliptin vs. glipizide in patients with type 2 diabetes and inadequate glycaemic control [ haemoglobin A(1c ) ( HbA(1c ) ) > or = 6.5 and < or = 10 % ] on metformin monotherapy . METHODS After a metformin dose titration/stabilization period ( > or = 1500 mg/day ) , 1172 patients were r and omized to the addition of sitagliptin 100 mg q.d . ( N = 588 ) or glipizide 5 mg/day ( uptitrated to a potential maximum 20 mg/day ) ( N = 584 ) for 52 weeks . The primary analysis assessed whether sitagliptin was non-inferior to glipizide regarding HbA(1c ) changes from baseline at Week 52 using a per- protocol approach . RESULTS From a mean baseline of 7.5 % , HbA(1c ) changes from baseline were -0.67 % at Week 52 in both groups , confirming non-inferiority . The proportions achieving an HbA(1c ) < 7 % were 63 % ( sitagliptin ) and 59 % ( glipizide ) . Fasting plasma glucose changes from baseline were -0.56 mmol/l ( -10.0 mg/dl ) and -0.42 mmol/l ( -7.5 mg/dl ) for sitagliptin and glipizide , respectively . The proportion of patients experiencing hypoglycaemia episodes was significantly ( p < 0.001 ) higher with glipizide ( 32 % ) than with sitagliptin ( 5 % ) , with 657 events in glipizide-treated patients compared with 50 events in sitagliptin-treated patients . Sitagliptin led to weight loss ( change from baseline = -1.5 kg ) compared with weight gain ( + 1.1 kg ) with glipizide [ between-treatment difference ( 95 % confidence interval ) = -2.5 kg ( -3.1 , -2.0 ) ; p < 0.001 ] . CONCLUSIONS In this study , the addition of sitagliptin compared with glipizide provided similar HbA(1c)-lowering efficacy over 52 weeks in patients on ongoing metformin therapy . Sitagliptin was generally well tolerated , with a lower risk of hypoglycaemia relative to glipizide and with weight loss compared with weight gain with glipizide CONTEXT Sitagliptin is an inhibitor of the enzyme dipeptidyl peptidase-IV ( DPP-IV ) , which de grade s the incretins , glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide , and thus , sitagliptin increases their bioavailability . The stimulation of insulin and the suppression of glucagon secretion that follow exert a glucose lowering effect and hence its use as an antidiabetic drug . Because DPP-IV is expressed as CD26 on cell membranes and because CD26 mediates proinflammatory signals , we hypothesized that sitagliptin may exert an antiinflammatory effect . PATIENTS AND METHODS Twenty-two patients with type 2 diabetes were r and omized to receive either 100 mg daily of sitagliptin or placebo for 12 wk . Fasting blood sample s were obtained at baseline and at 2 , 4 , and 6 hours after a single dose of sitagliptin and at 2 , 4 , 8 , and 12 wk of treatment . RESULTS Glycosylated hemoglobin fell significantly from 7.6 ± 0.4 to 6.9 ± 3 % in patients treated with sitagliptin . Fasting glucagon-like peptide-1 concentrations increased significantly , whereas the mRNA expression in mononuclear cell of CD26 , the proinflammatory cytokine , TNFα , the receptor for endotoxin , Toll-like receptor (TLR)-4 , TLR-2 , and proinflammatory kinases , c-Jun N-terminal kinase-1 and inhibitory-κB kinase ( IKKβ ) , and that of the chemokine receptor CCR-2 fell significantly after 12 wk of sitagliptin . TLR-2 , IKKβ , CCR-2 , and CD26 expression and nuclear factor-κB binding also fell after a single dose of sitagliptin . There was a fall in protein expression of c-Jun N-terminal kinase-1 , IKKβ , and TLR-4 and in plasma concentrations of C-reactive protein , IL-6 , and free fatty acids after 12 wk of sitagliptin . CONCLUSIONS These effects are consistent with a potent and rapid antiinflammatory effect of sitagliptin and may potentially contribute to the inhibition of atherosclerosis . The suppression of CD26 expression suggests that sitagliptin may inhibit the synthesis of DPP-IV in addition to inhibiting its action We have recently demonstrated a potent antiinflammatory effect of troglitazone , an agonist of peroxisome proliferator-activated receptor gamma ( PPARgamma ) and a partial agonist of PPARalpha in both the nondiabetic obese and diabetic obese subjects . We have now investigated the antiinflammatory actions of rosiglitazone , a selective PPARgamma agonist . Eleven nondiabetic obese subjects and 11 obese diabetic subjects were each given 4 mg of rosiglitazone daily for a period of 6 wk . Fasting blood sample s were obtained at 0 , 1 , 2 , 4 , 6 , and 12 wk ( 6 wk after the cessation of rosiglitazone ) . Eight obese subjects and five obese diabetic subjects were also included in the study as control groups . Fasting blood sample s were obtained from the control groups at 0 , 1 , 2 , 4 , and 6 wk only . Nuclear factor kappaB (NFkappaB)-binding activity in mononuclear cells , plasma monocyte chemoattractant protein-1 ( MCP-1 ) , TNF-alpha , soluble intercellular adhesion molecule-1 , C-reactive protein ( CRP ) , and serum amyloid A ( SAA ) were measured . Blood glucose concentration changed significantly at 6 wk only in the obese diabetic subjects after rosiglitazone treatment for 6 wk , whereas insulin concentration decreased significantly at 6 wk in both groups . NFkappaB-binding activity in mononuclear cell nuclear extract fell in both obese and obese diabetic subjects ( P < 0.02 ) . Rosiglitazone treatment result ed in a reduction in plasma MCP-1 and CRP in both groups ( P < 0.05 ) . Plasma TNF-alpha and SAA concentrations were inhibited significantly in the obese group ( P < 0.05 ) but not in the obese diabetic subjects . NFkappaB-binding activity and plasma MCP-1 , CRP , SAA , and TNF-alpha did not change in the obese and obese diabetic control groups . We conclude that rosiglitazone , a selective PPARgamma agonist , exerts an antiinflammatory effect at the cellular and molecular level , and in plasma . These observations may have implication s for atherogenesis in the long term in subjects treated with rosiglitazone and possibly other thiazolidinediones AIMS To evaluate the effects of the dipeptidyl peptidase-4 ( DPP-4 ) inhibitor linagliptin on aortic pulse wave velocity ( PWV ) as a surrogate marker of arterial stiffness and early atherosclerosis in people with early type 2 diabetes . METHODS A total of 45 people with type 2 diabetes ( median [ interquartile range ] age 63 [ 54 - 66 ] years , 61 % men , mean ± st and ard deviation glycated haemoglobin [ HbA1c ] 6.3 % ± 0.4 % [ 45 ± 4.6 mmol/mol ] ) , without cardiovascular disease and naïve to antidiabetic treatment , were r and omized ( 1:1 ) to treatment with linagliptin 5 mg once daily or placebo for 26 weeks in a double-blind fashion . PWV was assessed at baseline , 4 and 26 weeks of treatment , and again at 30 , 4 weeks after treatment . The primary endpoint was between-group difference in PWV ( corrected for systolic blood pressure [ SBP ] ) at week 26 . Secondary endpoints included differences in central SBP and augmentation index ( AIx ) . RESULTS Compared with placebo , 26 weeks of linagliptin decreased PWV by an average of 0.91 m/s ( 95 % confidence interval -1.76 to -0.06 ; P = .035 ) . PWV returned to baseline after 4 weeks washout . Differences in central SBP and AIx were not different between linagliptin and placebo . Linagliptin decreased HbA1c ( -0.4 % ; P < .001 ) , fasting plasma glucose ( -0.7 mmol/L ; P = .002 ) and triglycerides ( -0.49 mmol/L ; P = .019 ) as compared with placebo . The changes in body weight , cholesterol and high-sensitivity C-reactive protein did not differ between groups . CONCLUSIONS Linagliptin decreased aortic PWV in people with early-stage type 2 diabetes as compared with placebo after 26 weeks of treatment . These results suggest that linagliptin has a favourable effect on arterial stiffness OBJECTIVE To evaluate the efficacy and safety of add-on pioglitazone versus sitagliptin in patients with type 2 diabetes inadequately controlled on metformin and a sulfonylurea ( SU ) . METHODS This 24-week , r and omized , open-label study compared pioglitazone ( 30 mg daily , n = 59 ) and sitagliptin ( 100 mg daily , n = 60 ) in patients with inadequate glycemic control ( glycosylated hemoglobin [ HbA1c ] ≥7.0 % to < 11.0 % ) while receiving a stable dose of metformin ( ≥1,500 mg daily ) and an SU ( ≥half-maximal dose ) . RESULTS The mean changes in HbA1c from baseline was -0.94 ± 0.12 % with pioglitazone and -0.71 ± 0.12 % with sitagliptin , for a between-groups difference of -0.23 ± 0.16 % ( P = .16 ) . The mean change in fasting plasma glucose ( FPG ) were -35.7 ± 4.0 mg/dL with pioglitazone and -22.8 ± 4.0 mg/dL with sitagliptin , for a between-groups difference of -12.9 ± 5.7 mg/dL ( P = .02 ) . Pioglitazone was associated with a significant decrease in high-sensitive C-reactive protein ( hs-CRP ) , but sitagliptin did not . The mean weight gain was higher in the pioglitazone group , with a between-group difference of 1.6 kg ( P<.01 ) . Overall adverse events ( AEs ) were similar in both groups . However , the incidence of edema was higher with pioglitazone , and the incidence of gastrointestinal AEs was higher with sitagliptin . CONCLUSION Pioglitazone and sitagliptin achieved similar improvements in overall glycemic control in patients with type 2 diabetes inadequately controlled with metformin and an SU . However there were some differences in terms of FPG , hs-CRP , lipids , body-weight change , and AEs |
816 | 25,815,707 | The undisputable results of the INIS trial , which enrolled 3493 infants , and our meta-analyses ( n = 3973 ) showed no reduction in mortality during hospital stay , or death or major disability at two years of age in infants with suspected or proven infection .
Although based on a small sample size ( n = 266 ) , this up date provides additional evidence that IgM-enriched IVIG does not significantly reduce mortality during hospital stay in infants with suspected infection . | BACKGROUND Neonates are at higher risk of infection due to immuno-incompetence .
Maternal transport of immunoglobulins to the fetus mainly occurs after 32 weeks ' gestation , and endogenous synthesis begins several months after birth .
Administration of intravenous immunoglobulin ( IVIG ) provides immunoglobulin G ( IgG ) that can bind to cell surface receptors , provide opsonic activity , activate complement , promote antibody-dependent cytotoxicity and improve neutrophilic chemo-luminescence .
Theoretically , infectious morbidity and mortality could be reduced by the administration of IVIG .
OBJECTIVES To assess the effects of IVIG on mortality and morbidity caused by suspected or proven infection at study entry in neonates .
To assess in a subgroup analysis the effects of IgM-enriched IVIG on mortality from suspected infection . | Background Sepsis is an important cause of neonatal death and perinatal brain damage , particularly in preterm infants . While effective antibiotic treatment is essential treatment for sepsis , resistance to antibiotics is increasing . Adjuvant therapies , such as intravenous immunoglobulin , therefore offer an important additional strategy . Three Cochrane systematic review s of r and omised controlled trials in nearly 6,000 patients suggest that non-specific , polyclonal intravenous immunoglobulin is safe and reduces sepsis by about 15 % when used as prophylaxis but does not reduce mortality in this situation . When intravenous immunoglobulin is used in the acute treatment of neonatal sepsis , however , there is a suggestion that it may reduce mortality by 45 % . However , the existing trials of treatment were small and lacked long-term follow-up data . This study will assess reliably whether treatment of neonatal sepsis with intravenous immunoglobulin reduces mortality and adverse neuro-developmental outcome . Methods and design A r and omised , placebo controlled , double blind trial . Babies with suspected or proven neonatal sepsis will be r and omised to receive intravenous immunoglobulin therapy or placebo . Eligibility criteria Babies must be receiving antibiotics and have proven or suspected serious infection AND have at least one of the following : birthweight less than 1500 g OR evidence of infection in blood culture , cerebrospinal fluid or usually sterile body fluid OR be receiving respiratory support via an endotracheal tube AND there is substantial uncertainty that intravenous immunoglobulin is indicated . Exclusion criteria Babies are excluded if intravenous immunoglobulin has already been given OR intravenous immunoglobulin is thought to be needed OR contra-indicated . Trial treatment Babies will be given either 10 ml/kg of intravenous immunoglobulin or identical placebo solution over 4–6 hours , repeated 48 hours later . Primary outcome Mortality or major disability at two years , corrected for gestational age . Data collection Data will be collected at discharge from hospital and at 2 years of age ( corrected for gestation ) using a parental question naire and a health status question naire completed during a face-to-face follow-up appointment with the child 's paediatrician . Trial registration Current Controlled Trials ISCRTN94984750 In a prospect i ve double‐blind study , st and ard intravenous immunoglobulin ( IVIG ) was compared with an IgM‐enriched IVIG in the treatment of neonatal sepsis . The two treatment groups were also compared with matched controls . One hundred and thirty babies ( 65 in each group ) ranging from 0 to 24 days old , 480 to 4200 g in weight and born between 24 and 42 weeks of gestation who had , or were suspected of having , sepsis were given either st and ard IVIG or IgM‐enriched IVIG ( 250 mg/kg per day ) for 4 days in addition to supportive and antibiotic therapy . A further 65 babies who received similar supportive , antibiotic and fluids but not IVIG were used as matched controls . Mortality from infection in ‘ culture proven sepsis ’ was 3/44 ( 6·8 % ) in the IgM‐enriched IVIG group , 6/42 ( 14·2 % ) in the st and ard IVIG group , and 11/43 ( 25·5 % ) in the control group ( P = 0·017 , IgM versus control , P = 019 st and ard IVIG versus control ) . There was no statistical difference in the outcome between the two immunoglobulin therapy groups ( P = 0·25 ) . The study indicates that IVIG improves outcome in neonatal sepsis when used as an adjunct to supportive and antibiotic therapy , but larger studies are required to confirm this OBJECTIVE To evaluate the effect of pentaglobin treatment on clinical and laboratory parametres and the major morbidities in very low birthweight neonates with nosocomial sepsis before and after pentaglobin treatment . METHODS The prospect i ve interventional study was conducted from January 1 to December 31 , 2010 , at the neonatal intensive care unit ( NICU ) of the Bakirköy Dr. Sadi Konuk Training and Research Hospital , Istanbul , Turkey . Pentaglobin was initiated on the day of diagnosis of nosocomial sepsis to 13 pre-term neonates as a support therapy in addition to antibiotics ; 5 ml/kg per day of pentaglobin was infused over a 4-hour period on 3 consecutive days . Clinical and laboratory parametres and major morbidities were recorded before and after pentaglobin treatment and compared using NCSS software . RESULTS Of the total , 8 ( 66 % ) were females and 5 ( 40 % ) males . Following pentaglobin therapy , the immature-to-total neutrophil ratio and C-reactive protein levels were significantly decreased , and the capillary pH and base excess were significantly increased ( p < 0.05 ) . The axillary temperature , non-invasive blood pressure , haemoglobin , leukocyte , and thrombocyte values did not significantly differ before and after treatment ( p > 0.05 ) . Coagulase-negative staphylococci ( n = 3 ; 23 % ) , Klebsiella pneumoniae ( n = 2 ; 15.3 % ) , and Pseudomonas aeruginosa ( n = 1 ; 7.7 % ) were identified in blood cultures . The presence of intraventricular haemorrhages , necrotising enterocolitis , periventricular leukomalacia , and patent ductus arteriosus was not changed following the treatment . Adverse effects and mortality were not observed during or after the therapy . CONCLUSION Pentaglobin treatment of nosocomial sepsis could be used as an adjunct therapy without any adverse short-term reactions , even in very low birthweight pre-term infants Thirty-seven neonates with confirmed septicemia through hemoculture were studied . Of them , 18 were treated with antibiotic and the other 19 were given 500 mg/kg of intravenous immunoglobin with a pH of 4.25 ( IGIV ) . The greater part of the neonates in this study were full-term or near full-term . There were no differences in age , gestational age and weight , nor in mortality , the bacterias found and the clinical manifestations which were seen in both groups . Yet , the hospitalary stay was shorter for those in the group treated with IGIV ( 13.9 + /- 5.7 days ) than in the trial group ( 24.4 + /- 10.3 days ) ; as well as some clinical manifestations like diarrhea and splenomegalia ( P < 0.05 ) . The serum of the neonates from the IGIV group showed a greater capacity of opsonization and inhibition of bacterial growth than those in the trial group ( P < 0.001 ) , coinciding with an increase of 300 mg/dL in the serum levels of IgG of the group treated with IGIV from the 3rd day of the study and the C4 and B-Properdine factor serum levels from the 7th day of the study , while in the trial group , there were no changes in these factors ( P < 0.001 ) . Even though no differences were seen in the mortality rate due to septicemia , the results suggest a much shorter evolution of the illness in patients treated with IGIV . In addition , the serum of those patients treated with IGIV showed in in vitro studies , a better bacteriostatic activity and a better capacity to opsonize the bacterias isolated in the hemocultures . ( ABSTRACT TRUNCATED AT 250 WORDS Despite the development of newer generation of antibiotics , mortality from neonatal sepsis remains high . In a prospect i ve , r and omized study , we investigated the use of IgM-enriched immunoglobulin therapy in neonatal sepsis . Two groups of 30 infants each ( matched for gestational age , sex , weight , and other variables ) were r and omly allocated to receive either antibiotics alone ( control group ) or antibiotics plus 5 mL/kg/d for four days of IgM-enriched immunoglobulin intravenously ( immunotherapy group ) . Mortality from sepsis in the control group was 20 % ( 6/30 ) , while in the immunotherapy group it was 3.3 % ( 1/30 ) . We conclude that IgM-enriched immunoglobulin therapy in conjunction with antibiotic therapy significantly reduces mortality from neonatal sepsis OBJECTIVE Early-onset sepsis ( occurring within 72 hours of birth ) is included in the differential diagnosis of most very low birth weight ( VLBW ) neonates . To determine the current incidence of early-onset sepsis , risk factors for disease , and the impact of early-onset sepsis on subsequent hospital course , we studied a cohort of 7861 VLBW neonates ( 401 to 1500 gm ) admitted to the 12 National Institute of Child Health and Human Development ( NICHD ) Neonatal Research Network centers during a 32-month period ( 1991 - 1993 ) . METHODS The NICHD Neonatal Research Network maintains a prospect ively collected registry on all VLBW neonates born or cared for at participating centers . Data from this registry were analyzed retrospectively . RESULTS Blood culture-proven early-onset sepsis was uncommon , occurring in only 1.9 % of VLBW neonates . Group B streptococcus was the most frequent pathogen associated with early-onset sepsis ( 31 % ) , followed by Escherichia coli ( 16 % ) and Haemophilus influenzae ( 12 % ) . Decreasing gestational age was associated with increased rates of infection . Antibiotic therapy for suspected sepsis is frequently initiated at birth in VLBW neonates . Almost half of the infants in this cohort were considered to have clinical sepsis and continued to receive antibiotics for 5 or more days , despite a negative blood culture result in 98 % of cases . These findings underscore the difficulty of ruling out sepsis in the symptomatic immature neonate and the special concern for culture-negative clinical sepsis in the face of maternal antibiotic use . Neonates with early-onset sepsis were significantly more likely to have subsequent comorbidities , including severe intraventricular hemorrhage , patent ductus arteriosus , and prolonged assisted ventilation . Although 26 % of VLBW neonates with early-onset sepsis died , only 4 % of the 950 deaths that occurred in the first 72 hours of life were attributed to infection . For those infants discharged alive , early-onset sepsis was associated with a significantly prolonged hospital stay ( 86 vs 69 days ; p < 0.02 ) . CONCLUSIONS Early-onset sepsis remains an important but uncommon problem among VLBW preterm infants . Improved diagnostic strategies are needed to enable the clinician to distinguish between the infected and the uninfected VLBW neonate with symptoms and to target continued antibiotic therapy to those who are truly infected Newborn infants may have IgG deficiencies that increase their susceptibility to bacterial infection . To determine whether intravenous immune globulin ( IVIG ) therapy improves survival rates in early-onset sepsis , we prospect ively entered 753 neonates ( birth weight 500 to 2000 gm , gestation less than or equal to 34 weeks , age less than or equal to 12 hours ) into a multicenter , double-blind , controlled trial . Blood culture specimens were obtained and infants r and omly assigned to receive 10 ml ( per kilogram ) intravenously of a selected IVIG ( 500 mg/kg ) or albumin ( 5 mg/kg ) preparation . Maternal and neonatal risk factors were not different between groups . Thirty-one babies ( 4.2 % ) had early-onset sepsis ; the causative organisms were group B streptococcus ( 12 babies ) , Escherichia coli ( 6 ) , and others ( 13 ) . Of these 31 neonates , 7 ( 23 % ) died . Total serum IgG was higher for 7 days after IVIG therapy than after albumin treatment ( p less than 0.05 ) . During these 7 days , 5 ( 30 % ) of 17 albumin-treated and none of 14 IVIG-treated patients died ( p less than 0.05 ) . The survival rate at 56 days of age , however , was not significantly improved . Group B streptococcus type-specific IgG antibody was significantly increased after IVIG treatment and appeared to be related to the amount of IVIG specific antibody . Infusion-related adverse reactions were less frequent in patients receiving IVIG therapy ( 0.5 % ) than in those receiving albumin . The IVIG therapy in neonates with early-onset sepsis , while reducing the early mortality rate , did not significantly affect the overall survival rate . Further studies are necessary to confirm these findings and to determine more effective therapeutic regimens The therapeutic effect of a polyvalent immunoglobulin preparation for intravenous use was tested in 82 newborns with bacterial infections . 35 of the children had neonatal sepsis , whereas in the other 47 bacteremia was not detectable . Treatment consisted either of antibiotics only or of antibiotics combined wih immunoglobulin SRK on an alternating basis for the first six days . Immunoglobulin substitution was tolerated without complications . In the group of infants with neonatal sepsis , two of 20 ( 10 % ) who were substituted with immunoglobulin and four of 15 ( 26 % ) who received no immunoglobulin died . Likewise , in the group of patients without detectable bacteremia , two of 21 on immunoglobulin substitution ( 10 % ) and four of the 26 who were not substituted ( 15 % ) died . The low mortality observed in the present study was attributed to efforts at early diagnosis and conventional early treatment on the one h and , and to immunoglobulin substitution on the other . To detect possible late sequelae of immunoglobulin therapy , particularly in hypogammaglobulinemic premature newborns , clinical and immunological investigations were performed in the septic patient group at the age of one to four years . There were no indications that administration of immunoglobulins during the neonatal period might have had an adverse effect on psychomotor and somatic development or on the immunological maturation of the infants OBJECTIVE To investigate the effectivity of pentoxifylline ( PTX ) and immunoglobulin M (IgM)-enriched intravenous immunoglobulin ( IVIG ) therapy in the treatment of neonatal sepsis ( NS ) , alone or in combination . STUDY DESIGN This was a prospect i ve , double-blind , controlled study . Newborns with suspicion of sepsis were enrolled in the study . The patients were separated into four groups according to treatment protocol : Group 1 = placebo , Group 2 = pentoxifylline , Group 3 = IgM-enriched IVIG , and Group 4 = pentoxifylline + IgM-enriched IVIG . Blood sample s were taken for C-reactive protein , interleukin-6 , neutrophil CD64 expression , and tumor necrosis factor-alfa measurements immediately before treatment ( 1st day ) , and measurements were repeated on the 2nd and 4th days of the therapy . RESULTS A total of 204 patients , 51 in each group , were recruited into the study . There were no significant differences for symptoms of sepsis among groups , except lethargy . No significant differences were observed among the groups according to laboratory data . Overall mortality rate was 8.8 % . The rates of morbidities and mortality among study groups were similar . CONCLUSION PTX and IgM-enriched IVIG therapies , either alone or in combination , did not reduce the rates of morbidities and mortality in NS OBJECTIVE To determine whether therapy with intravenous immunoglobulin G ( IVIG ) would decrease mortality in neonatal sepsis . SETTING Three tertiary care neonatal intensive care units in the city of Bangalore . METHODS All neonates admitted to the Neonatal Intensive Care Units with the clinical diagnosis of sepsis and having at least C-reactive protein and one other rapid diagnostic criteria positive were enrolled . Neonates with a birth weight of less than 1000 g and those with any major congenital malformation were excluded . The neonates were r and omized to receive 1 g/kg of IVIG on three consecutive days or an equivalent amount of placebo . The rest of the treatment including antibiotics and supportive care was as per the treating physician 's decision . The main outcome variable was survival . RESULTS The trial was carried out over a period of 8 months and recruited 58 neonates . Seven neonates who qualified but did not receive either IVIG or placebo were taken into a separate control group , and one baby who received only one dose of IVIG was excluded from the analysis . Twenty-five neonates were enrolled into the IVIG arm and 25 in the placebo arm . The neonates in the therapy and placebo groups were comparable in terms of birth weight ( 2144+/-675 g vs. 2072+/-682 g ) , gestation ( 37.0+/-3.56 vs. 35.8+/-3.52 weeks ) , sex distribution , duration of stay , and number requiring ventilation . The placebo group had a significantly higher number of babies with positive blood culture . Seven babies in each group died ( p>0.05 ) . There was no significant benefit in using IVIG ( OR 1.0 ; 95 % CI 0.25 - 4.07 ) ( p = 0.74 ) . CONCLUSION In the sample studied therapy with IVIG did not reduce mortality in neonatal The value of IgM-enriched immunoglobulin therapy in 44 preterm infants with neonatal sepsis was evaluated in a prospect i ve r and omized study . All infants received antibiotic therapy and fresh plasma and /or whole blood transfusions . Twenty r and omly-chosen infants were allocated to receive 5 ml/kg/d of IgM-enriched immunoglobulin intravenously for three days . Although the mortality rate in preterm infants whose gestational ages were 31 - 34 weeks in the immunotherapy group was slightly lower than in the control group , the general mortality rate from sepsis in the control group ( 9/24 ) and in the immunotherapy group ( 6/20 ) showed no statistically significant difference ( 37.5 % vs 30.0 % , p < 0.05 ) This study was design ed to test the hypothesis that administration of immune globulin to human neonates with early-onset bacterial sepsis would ( 1 ) facilitate neutrophil egress from the marrow , ( 2 ) improve serum opsonic capacity , and ( 3 ) facilitate recovery from the infectious illness . Twenty-two newborn infants with clinical signs of early-onset sepsis were given an intravenous infusion of either 750 mg of immune globulin ( IVIG ) per kilogram of body weight or the same volume of a vehicle control ( albumin ) . All 22 infants survived , but significant hematologic , immunologic , and respiratory differences were observed after the IVIG and not after the control infusion . Eleven of the patients had neutropenia ; 24 hours after the infusions , the neutropenia had resolved in all six IVIG recipients but persisted in all five control recipients ( p less than 0.001 ) . Ten patients had I/T neutrophil ratios ( a measure of immature neutrophils to total neutrophils on the leukocyte differential count ) of less than 0.2 . One hour after completion of the infusions , all five IVIG recipients had elevated I/T ratios ( mean + /- SEM:0.10 + /- 0.05 before vs 0.43 + /- 0.03 after infusion ; p less than 0.001 ) , suggesting a prompt release of neutrophils from the marrow neutrophil storage pool into the circulation ; no increase in the I/T ratio was observed in the control recipients . Six hours after the IVIG infusions , the ratio of arterial oxygen tension to fraction of inspired oxygen increased ; no increase was observed after control infusions . Serum concentrations of IgG , IgG1 , IgG2 , IgG3 , IgG4 , and total hemolytic complement and the capacity of serum to support opsonophagocytosis of type II and type III group B streptococci increased markedly in the IVIG recipients but not in the control subjects . We conclude that administration of 750 mg IVIG per kilogram to neonates with clinical signs of early-onset sepsis was associated with immunologic , hematologic , and physiologic improvement BACKGROUND Neonatal sepsis is a major cause of death and complications despite antibiotic treatment . Effective adjunctive treatments are needed . Newborn infants are relatively deficient in endogenous immunoglobulin . Meta-analyses of trials of intravenous immune globulin for suspected or proven neonatal sepsis suggest a reduced rate of death from any cause , but the trials have been small and have varied in quality . METHODS At 113 hospitals in nine countries , we enrolled 3493 infants receiving antibiotics for suspected or proven serious infection and r and omly assigned them to receive two infusions of either polyvalent IgG immune globulin ( at a dose of 500 mg per kilogram of body weight ) or matching placebo 48 hours apart . The primary outcome was death or major disability at the age of 2 years . RESULTS There was no significant between-group difference in the rates of the primary outcome , which occurred in 686 of 1759 infants ( 39.0 % ) who received intravenous immune globulin and in 677 of 1734 infants ( 39.0 % ) who received placebo ( relative risk , 1.00 ; 95 % confidence interval , 0.92 to 1.08 ) . Similarly , there were no significant differences in the rates of secondary outcomes , including the incidence of subsequent sepsis episodes . In follow-up of 2-year-old infants , there were no significant differences in the rates of major or nonmajor disability or of adverse events . CONCLUSIONS Therapy with intravenous immune globulin had no effect on the outcomes of suspected or proven neonatal sepsis |
817 | 28,485,636 | RESULTS This review found medium to high quality evidence supporting the use of narrative exposure therapy ( NET ) .
A lack of culturally adapted treatments was apparent and there was less evidence to support st and ard cognitive behavioural therapy ( CBT ) , Eye Movement Desensitisation and Reprocessing ( EMDR ) and multidisciplinary treatments .
CONCLUSION NET produced positive outcomes in refugees from a diverse range of background s and trauma types . | BACKGROUND Europe is in the midst of the largest refugee migration since the Second World War ; there is an urgent need to provide an up date d systematic review of the current best evidence for managing mental distress in refugee population s. AIMS The aim of this review is to provide an exhaustive summary of the current literature on psychosocial interventions , both trauma- and non-trauma-focused , for refugee population s experiencing post-traumatic stress disorder ( PTSD ) , depressive or anxiety symptoms .
To produce recommendations for future research and current clinical practice . | Traumatic stress due to conflict and war causes major mental health problems in many re source -poor countries . The objective of this study was to examine whether trained lay counselors can carry out effective treatment of posttraumatic stress disorder ( PTSD ) in a refugee settlement . In a r and omized controlled dissemination trial in Ug and a with 277 Rw and an and Somalian refugees who were diagnosed with PTSD the authors investigated the effectiveness of psychotherapy administered by lay counselors . Strictly manualized narrative exposure therapy ( NET ) was compared with more flexible trauma counseling ( TC ) and a no-treatment monitoring group ( MG ) . Fewer participants ( 4 % ) dropped out of NET treatment than TC ( 21 % ) . Both active treatment groups were statistically and clinical ly superior to MG on PTSD symptoms and physical health but did not differ from each other . At follow-up , a PTSD diagnosis could not be established anymore in 70 % of NET and 65 % TC participants , whereas only 37 % in MG did not meet PTSD criteria anymore . Short-term psychotherapy carried out by lay counselors with limited training can be effective to treat war-related PTSD in a refugee settlement OBJECTIVE Becoming a refugee is a potent risk factor for indicators of psychological distress such as depression , generalized stress , and posttraumatic stress disorder ( PTSD ) , though research into this vulnerable population has been scant , with even less work focusing on interventions . The current study applied principles from self-determination theory ( SDT ; Ryan & Deci , 2000 ) to develop and test an intervention aim ed at increasing need-satisfying experiences in refugees of Syrian civil unrest . METHOD Forty-one refugees who fled Syria during the past 24 months and resettled in Jordan participated in the study and were r and omly assigned to receive the intervention or a neutral comparison . RESULTS The 1-week-long intervention alleviated some of the need frustration likely associated with refugee status , a major aim of the intervention , and also lowered refugees ' self-reported symptoms of depression and generalized stress as compared to the comparison condition , though it did not reduce symptoms of PTSD . CONCLUSIONS Discussion focuses on how these findings speak to the universal importance of need satisfaction for mental health , and how need-satisfying experiences can help buffer against the profound stress of being a refugee . Avenues for longer-term or more intensive interventions that may target more severe outcomes of refugee experiences , such as PTSD symptoms , are also discussed . ( PsycINFO Data base OBJECTIVE There has been uncertainty about whether refugees and asylum seekers with PTSD can be treated effectively in st and ard psychiatric setting s in industrialized countries . In this study , Narrative Exposure Therapy ( NET ) was compared to Treatment As Usual ( TAU ) in 11 general psychiatric health care units in Norway . The focus was on changes in symptom severity and in the diagnostic status for PTSD and depression . METHOD Refugees and asylum seekers fulfilling the DSM-IV criteria for PTSD ( N = 81 ) were r and omized with an a-priori probability of 2:1 to either NET ( N = 51 ) or TAU ( N = 30 ) . The patients were assessed with Clinician Administered PTSD Scale , Hamilton rating scale for depression and the MINI Neuropsychiatric Interview before treatment , and again at one and six months after the completion . RESULTS Both NET and TAU gave clinical ly relevant symptom reduction both in PTSD and in depression . NET gave significantly more symptom reduction compared to TAU as well as significantly more reduction in participants with PTSD diagnoses . No difference in treatment efficacy was found between refugees and asylum seekers . CONCLUSIONS The study indicated that refugees and asylum seekers can be treated successfully for PTSD and depression in the general psychiatric health care system ; NET appeared to be a promising treatment for both groups We examined the feasibility , acceptability , and therapeutic efficacy of a culturally adapted cognitive – behavior therapy ( CBT ) for twelve Vietnamese refugees with treatment-resistant posttraumatic stress disorder ( PTSD ) and panic attacks . These patients were treated in two separate cohorts of six with staggered onset of treatment . Repeated measures Group × Time ANOVAs and between-group comparisons indicated significant improvements , with large effect sizes ( Cohen 's d ) for all outcome measures : Harvard Trauma Question naire ( HTQ ; d=2.5 ) ; Anxiety Sensitivity Index ( ASI ; d=4.3 ) ; Hopkins Symptom Checklist-25 ( HSCL-25 ) , anxiety subscale ( d=2.2 ) ; and Hopkins Symptom Checklist-25 , depression subscale ( d=2.0 ) scores . Likewise , the severity of ( culturally related ) headache- and orthostasis-cued panic attacks improved significantly across Little is known about the usefulness of psychotherapeutic approaches for traumatized refugees who continue to live in dangerous conditions . Narrative exposure therapy ( NET ) is a short-term approach based on cognitive-behavioral therapy and testimony therapy . The efficacy of narrative exposure therapy was evaluated in a r and omized controlled trial . Sudanese refugees living in a Ug and an refugee settlement ( N = 43 ) who were diagnosed as suffering from posttraumatic stress disorder ( PTSD ) either received 4 sessions of NET , 4 sessions of supportive counseling ( SC ) , or psychoeducation ( PE ) completed in 1 session . One year after treatment , only 29 % of the NET participants but 79 % of the SC group and 80 % of the PE group still fulfilled PTSD criteria . These results indicate that NET is a promising approach for the treatment of PTSD for refugees living in unsafe conditions BACKGROUND Previous research indicates a high prevalence of post-traumatic stress disorder ( PTSD ) and depression among refugees . Eye movement desensitization and reprocessing ( EMDR ) is an effective treatment for PTSD for victims of natural disasters , car accidents or other traumatic events . The current study examined the effect of EMDR on symptoms of PTSD and depression by comparing the treatment with a wait-list control condition in Syrian refugees . METHOD Adult refugees located in Kilis Refugee Camp at the Turkish-Syrian border with a PTSD diagnosis were r and omly allocated to either EMDR ( n = 37 ) or wait-list control ( n = 33 ) conditions . All participants were assessed with the Mini-International Neuropsychiatric Interview Plus at pre-intervention , at 1 week after finishing the intervention and at 5 weeks after finishing the intervention . The main outcome measures were the Harvard Trauma Question naire ( HTQ ) and the Impact of Event Scale-Revised . The Beck Depression Inventory and the Hopkins Symptoms Checklist-25 were included as secondary outcome measures . The Trial Registration no. is NCT01847742 . RESULTS Mixed-model analyses adjusted for the baseline scores indicated a significant effect of group at post-treatment indicating that the EMDR therapy group showed a significantly larger reduction of PTSD symptoms as assessed with the HTQ . Similar findings were found on the other outcome measures . There was no effect of time or group × time interaction on any measure , showing that the difference between the groups at the post-treatment was maintained to the 5-week follow-up . CONCLUSIONS EMDR may be effective in reducing PTSD and depression symptoms among Syrian refugees with PTSD located in a refugee camp Background Traumatised asylum seekers and refugees are clinical ly considered a complex population . Discussion exists on whether with this population treatment guidelines for post-traumatic stress disorder ( PTSD ) should be followed and Trauma-Focused Cognitive-Behavioural Therapy ( TF-CBT ) or Eye Movement Desensitisation and Reprocessing ( EMDR ) should be applied , or whether a phased model starting with stabilisation is preferable . Some clinicians fear that trauma-focused interventions may lead to unmanageable distress or may be ineffective . While cognitive-behavioural interventions have been found to be effective with traumatised refugees , no studies concerning the efficacy of EMDR with this population have been conducted as yet . Objective In preparation for a r and omised trial comparing EMDR and stabilisation with traumatised refugees , a pilot study with 20 participants was conducted . The objective was to examine feasibility of participation in a r and omised trial for this complex population and to examine acceptability and preliminary efficacy of EMDR . Design Participants were r and omly allocated to 11 sessions of either EMDR or stabilisation . Symptoms of PTSD ( SCID-I , HTQ ) , depression and anxiety ( HSCL-25 ) , and quality of life ( WHOQOL-BREF ) were assessed at pre- and post-treatment and 3-month follow-up . Results Participation of traumatised refugees in the study was found feasible , although issues associated with complex traumatisation led to a high pre-treatment attrition and challenges in assessment s. Acceptability of EMDR was found equal to that of stabilisation with a high drop-out for both conditions . No participants dropped out of the EMDR condition because of unmanageable distress . While improvement for EMDR participants was small , EMDR was found to be no less efficacious than stabilisation . Different symptom courses between the two conditions , with EMDR showing some improvement and stabilisation showing some deterioration between pre-treatment and post-treatment , justify the conduct of a full trial . Conclusion With some adaptations in study design , inclusion of a greater sample is justifiable to determine which treatment is more suitable for this complex population . For the abstract or full text in other language s , please see Supplementary files under Reading Tools BACKGROUND Little evidence exists on the treatment of traumatised refugees . AIMS To estimate treatment effects of flexible cognitive-behavioural therapy ( CBT ) and antidepressants ( sertraline and mianserin ) in traumatised refugees . METHOD R and omised controlled clinical trial with 2 × 2 factorial design ( registered with Clinical trials.gov , NCT00917397 , EUDRACT no. 2008 - 006714 - 15 ) . Participants were refugees with war-related traumatic experiences , post-traumatic stress disorder ( PTSD ) and without psychotic disorder . Treatment was weekly sessions with a physician and /or psychologist over 6 months . RESULTS A total of 217 of 280 patients completed treatment ( 78 % ) . There was no effect on PTSD symptoms , no effect of psychotherapy and no interaction between psychotherapy and medicine . A small but significant effect of treatment with antidepressants was found on depression . CONCLUSIONS In a pragmatic clinical setting , there was no effect of flexible CBT and antidepressants on PTSD , and there was a small-to-moderate effect of antidepressants and psychoeducation on depression in traumatised refugees Background The most common mental health problems among refugees are depression and posttraumatic stress disorder ( PTSD ) . Eye movement desensitization and reprocessing ( EMDR ) is an effective treatment for PTSD . However , no previous r and omized controlled trial ( RCT ) has been published on treating PTSD symptoms in a refugee camp population . Objective Examining the effect of EMDR to reduce the PTSD and depression symptoms compared to a wait-list condition among Syrian refugees . Method Twenty-nine adult participants with PTSD symptoms were r and omly allocated to either EMDR sessions ( n=15 ) or wait-list control ( n=14 ) . The main outcome measures were Impact of Event Scale-Revised ( IES-R ) and Beck Depression Inventory ( BDI-II ) at posttreatment and 4-week follow-up . Results Analysis of covariance showed that the EMDR group had significantly lower trauma scores at posttreatment as compared with the wait-list group ( d=1.78 , 95 % CI : 0.92–2.64 ) . The EMDR group also had a lower depression score after treatment as compared with the wait-list group ( d=1.14 , 95 % CI : 0.35–1.92 ) . Conclusion The pilot RCT indicated that EMDR may be effective in reducing PTSD and depression symptoms among Syrian refugees located in a camp . Larger RCTs to verify the ( cost- ) effectiveness of EMDR in similar population s are needed Background Little is known about the neurobiological foundations of psychotherapy for Posttraumatic Stress Disorder ( PTSD ) . Prior studies have shown that PTSD is associated with altered processing of threatening and aversive stimuli . It remains unclear whether this functional abnormality can be changed by psychotherapy . This is the first r and omized controlled treatment trial that examines whether narrative exposure therapy ( NET ) causes changes in affective stimulus processing in patients with chronic PTSD . Methods 34 refugees with PTSD were r and omly assigned to a NET group or to a waitlist control ( WLC ) group . At pre-test and at four-months follow-up , the diagnostics included the assessment of clinical variables and measurements of neuromagnetic oscillatory brain activity ( steady-state visual evoked fields , ssVEF ) result ing from exposure to aversive pictures compared to neutral pictures . Results PTSD as well as depressive symptom severity scores declined in the NET group , whereas symptoms persisted in the WLC group . Only in the NET group , parietal and occipital activity towards threatening pictures increased significantly after therapy . Conclusions Our results indicate that NET causes an increase of activity associated with cortical top-down regulation of attention towards aversive pictures . The increase of attention allocation to potential threat cues might allow treated patients to re-appraise the actual danger of the current situation and , thereby , reducing PTSD symptoms . Registration of the clinical trialNumber : NCT00563888Name : " Change of Neural Network Indicators Through Narrative Treatment of PTSD in Torture Victims " ULR : http://www . clinical This study tested the effectiveness of Imagery Rescripting ( ImRs ) for complicated war-related PTSD in refugees . Ten adult patients in long-term supportive care with a primary diagnosis of war-related PTSD and Posttraumatic Symptom Scale ( PSS ) score > 20 participated . A concurrent multiple baseline design was used with baseline varying from 6 to 10weeks , with weekly supportive sessions . After baseline , a 5-week exploration phase followed with weekly sessions during which traumas were explored , without trauma-focused treatment . Then 10 weekly ImRs sessions were given followed by 5-week follow-up without treatment . Participants were r and omly assigned to baseline length , and filled out the PSS and the BDI on a weekly basis . Data were analyzed with mixed regression . Results revealed significant linear trends during ImRs ( reductions of PSS and BDI scores ) , but not during the other conditions . The scores during follow-up were stable and significantly lower compared to baseline , with very high effect sizes ( Cohen 's d = 2.87 ( PSS ) and 1.29 ( BDI ) ) . One patient did clearly not respond positively , and revealed that his actual problem was his sexual identity that he could n't accept . There were no dropouts . In conclusion , results indicate that ImRs is a highly acceptable and effective treatment for this difficult group of patients Background : The aim of the present r and omized controlled trial was to compare the outcome of 2 active treatments for posttraumatic stress disorder ( PTSD ) as a consequence of war and torture : narrative exposure therapy ( NET ) and stress inoculation training ( SIT ) . Methods : Twenty-eight PTSD patients who had experienced war and torture , most of them asylum seekers , received 10 treatment sessions of either NET or SIT at the Outpatient Clinic for Refugees , University of Konstanz , Germany . Posttests were carried out 4 weeks after treatment , and follow-up tests were performed 6 months and 1 year after treatment . The main outcome measure was the PTSD severity score according to the Clinician-Administered PTSD Scale ( CAPS ) at each time point . Results : A significant reduction in PTSD severity was found for NET , but not for SIT . A symptom reduction in the NET group occurred between pretest and the 6-month follow-up examination , the effect size being d = 1.42 ( for SIT : d = 0.12 ) , and between pretest and the 1-year follow-up , the effect size being d = 1.59 ( for SIT : d = 0.19 ) . The rates and scores of major depression and other comorbid disorders did not decrease significantly over time in either of the 2 treatment groups . Conclusions : The results indicate that exposure treatments like NET lead to a significant PTSD symptom reduction even in severely traumatized refugees and asylum seekers The treatment of torture survivors from diverse cultures has been a difficult task involving issues of loss , massive trauma , cultural style , and adjusting to a new country . Research on treatment outcomes has shown inconsistent results . This report presents a prospect i ve one year treatment outcome of 22 severely tortured patients from Ethiopia , Somalia , Iran and Afghanistan . Treatment was provided by psychiatrists and counselors with interpreters from each culture involved . The specific treatment included psychiatric evaluation , medicine , education , supportive psychotherapy and assisting some social needs . All 22 were diagnosed with depression and 17 of these also had posttraumatic stress disorder ( PTSD ) . Twenty of 22 patients showed marked significant improvement on all of the scales for depression , PTSD , disability , and quality of life . Medicine was particularly useful in treating depression and the symptoms of flashbacks , nightmares and irritability . St and ard psychiatric treatment with evaluation , diagnosis , appropriate medicine , supportive psychotherapy and counseling by ethnic counselors provided good outcomes This matched single-blind pilot study tested the effect of Transcendental Meditation ® ( TM ) practice on symptoms of posttraumatic stress ( PTS ) in Congolese refugees . Urban refugees ( N = 102 ) staying around Kampala , Ug and a attended introductory meetings . After initial r and om assignment to the TM group , 30 refugees who revealed that they were unable to attend all meetings and were eliminated from the study . The remaining 21 TM group participants were then instructed in TM and matched with refugees in the control group on age , sex , and baseline scores on the Post-traumatic Stress Disorder Checklist-Civilian ( PCL-C ) . All participants completed the PCL-C measure of PTS symptoms at baseline , and 30-day and 135-day posttests . The PCL-C scores in the control group trended upward . In contrast , the PCL-C scores in the TM group went from 65 on average at baseline indicating severe PTS symptoms to below 30 on average after 30 days of TM practice , and remained low at 135 days . Effect size was high ( d > 1.0 ) . Compliance with TM practice was good ; most reported regular practice throughout the study . There were no adverse events . All refugees who learned TM completed the study and were able to practice TM successfully , with subsequent substantial reduction in PTS symptoms A consensus in Europe about asylum seekers Violent conflicts between groups often generate large numbers of noncombatant refugees . Bansak et al. surveyed western European attitudes toward such asylum seekers . They found that voters favor applicants who will contribute to the recipient country 's economy , who have suffered severe physical or mental distress rather than economic hardship , and who are Christian rather than Muslim . These preferences are similar across countries and independent of the voters ' personal characteristics . Science , this issue p. 217 Choices about which refugees to host are the same for the rich and poor , old and young , and Nordic and Mediterranean . What types of asylum seekers are Europeans willing to accept ? We conducted a conjoint experiment asking 18,000 eligible voters in 15 European countries to evaluate 180,000 profiles of asylum seekers that r and omly varied on nine attributes . Asylum seekers who have higher employability , have more consistent asylum testimonies and severe vulnerabilities , and are Christian rather than Muslim received the greatest public support . These results suggest that public preferences over asylum seekers are shaped by sociotropic evaluations of their potential economic contributions , humanitarian concerns about the deservingness of their cl aims , and anti-Muslim bias . These preferences are similar across respondents of different ages , education levels , incomes , and political ideologies , as well as across the surveyed countries . This public consensus on what types of asylum seekers to accept has important implication s for theory and policy Concentration camp survivors from Bosnia-Herzegovina , now refugees in the Netherl and s , were given early outpatient treatment for posttraumatic stress disorder ( PTSD ) for 6 months . They were tested with the Watson Question naire before entering therapy , after 6 months and 3 years later when a structured interview design ed to obtain information on psychosocial status was administered . Data were analyzed with PCA-STAT 1.1 statistical package . The treatment was effective on a short-term basis with some long-term effects . Elderly people were no more vulnerable to the onset of PTSD than younger ones but were more resistant to therapy . Psychosocial factors had neither protective nor risk value for the development of PTSD in this group Abstract Studies on group treatment of posttraumatic stress disorder ( PTSD ) in asylum seekers and refugees are scarce . The aim of this study was to evaluate the effectiveness of three different trauma-focused day-treatment group programs for treatment of PTSD in male asylum seekers and refugees . Three treatment groups ( n = 56 ) and a waitlisted control group ( n = 16 ) of help-seeking Iranian and Afghani patients were assessed with a set of self-rated symptom checklists for PTSD , anxiety , depression , and psychoticism 1 week before and 2 weeks after treatment . There are no indications that the 2 days ’ group program with three nonverbal and two group psychotherapy sessions per week is less effective in reducing symptoms than the program with the same amount of sessions spread over 3 days per week . The trauma-focused day-treatment group seems a promising approach for treatment of PTSD among asylum seekers and refugees in industrialized setting Context Worldwide , the number of refugees and asylum seekers is estimated to be about 11.5 million plus a much larger number of former refugees who have obtained a residence permit in a new country . Although asylum seekers have been coming to the Netherl and s since the 1980s , very few epidemiological studies have focused on this group of inhabitants or on the refugees who have resettled in this country . Objectives The objectives of this study were to estimate the prevalence rates of physical and mental health problems and to identify the risk factors for these complaints . Design , Setting , and Participants A population -based study was conducted in the Netherl and s from June 2003 to April 2004 among adult refugees and asylum seekers from Afghanistan , Iran and Somalia . Asylum seekers were living in 14 r and omly selected reception centres , and r and om sample s of refugees were obtained from the population registers of three municipalities ( Arnhem , Leiden and Zaanstad ) . A total of 178 refugees and 232 asylum seekers participated ( response rates of 59 and 89 % , respectively).Main Outcome Measures General health and physical health were measured with the Short-Form 36 and a list of 19 chronic conditions , respectively ; symptoms of post-traumatic stress disorder ( PTSD ) , depression and anxiety , were measured with the Harvard Trauma Question naire and the Hopkins Symptoms Checklist-25 . Results More asylum seekers ( 59.1 % ) than refugees ( 42.0 % ) considered their health to be poor ( P=0.001 ) . In both groups , approximately half of the respondents suffered from more than one chronic condition . More asylum seekers than refugees had symptoms of PTSD ( 28.1 and 10.6 % , respectively ; P=0.000 ) and depression/anxiety ( 68.1 and 39.4 , respectively ; P=0.000 ) . Respondents from Afghanistan and , in particular , from Iran had a higher risk for PTSD and depression/anxiety . Female gender was associated with chronic conditions , PTSD and depression/anxiety , and higher age was associated with poor general health and chronic conditions . A greater number of traumatic events was associated with all health outcomes , and more post-migration stress and less social support were associated with PTSD and depression/anxiety symptoms . Conclusions Both physical and mental health problems are highly prevalent among refugees and asylum seekers in the Netherl and s. Although higher prevalence rates for most health outcomes were found among asylum seekers , both the specific health services for asylum seekers and the general health services in the municipalities should be aware of these problems Rates of posttraumatic stress disorder ( PTSD ) are exceptionally high among asylum-seekers . Reportedly , stressors caused by the asylum procedure and psychological consequences of torture contribute to the maintenance of symptoms and interfere with treatment . In a pilot r and omized controlled trial , the authors examined the efficacy of trauma-focused treatment in 32 asylum-seekers with PTSD result ing from state-sponsored violence and other traumatic events . Narrative exposure therapy ( NET ) was compared with treatment as usual ( TAU ) , with a focus on stabilization and psychoactive medication . Six months after treatment , a significant reduction of posttraumatic stress symptoms was found in the NET participants but not in the TAU group . Although treatment gains were moderate , these results indicate that NET is a promising approach for the treatment of PTSD in asylum-seekers living in unstable conditions The present study investigated the efficacy of cognitive-behavior therapy ( CBT ) and exposure therapy ( E ) in the treatment of post-traumatic stress disorder ( PTSD ) in refugees . Sixteen out patients fulfilling the DSM-IV criteria for PTSD were r and omized to one of the two treatments . Assessor and self-report measures of PTSD-symptoms , generalized anxiety , depression , quality of life and cognitive schemas were administered before and after treatment , and at a 6-month follow-up . The patients were treated individually for 16 - 20 weekly sessions . The results showed that both treatments result ed in large improvements on all the measures , which were maintained at the follow-up . There was no difference between E and CBT on any measure . E and CBT led to a 48 and 53 % reduction on PTSD-symptoms , respectively , a 49 and 50 % reduction on generalized anxiety , and a 54 and 57 % reduction on depression . The results were maintained at the 6-month follow-up . The conclusion that can be drawn is that both E and CBT can be effective treatments for PTSD in refugees Based on the results of a r and omized controlled trial , we examined a model of the mechanisms of efficacy of culturally adapted cognitive‐behavior therapy ( CBT ) for Cambodian refugees with pharmacology‐resistant posttraumatic stress disorder ( PTSD ) and comordid orthostatic panic attacks ( PAs ) . Twelve patients were in the initial treatment condition , 12 in the delayed treatment condition . The patients r and omized to CBT had much greater improvement than patients in the waitlist condition on all psychometric measures and on one physiological measure — the systolic blood pressure response to orthostasis ( d = 1.31)—as evaluated by repeated‐ measures MANOVA and planned contrasts . After receiving CBT , the Delayed Treatment Group improved on all measures , including the systolic blood pressure response to orthostasis . The CBT treatment 's reduction of PTSD severity was significantly mediated by improvement in orthostatic panic and emotion regulation ability . The current study supports our model of the generation of PTSD in the Cambodian population , and suggests a key role of decreased vagal tone in the generation of orthostatic panic and PTSD in this population . It also suggests that vagal tone is involved in emotion regulation , and that both vagal tone and emotion regulation improve across treatment The aim of this study was to examine long-term changes in symptoms of post-traumatic stress disorder , depression , anxiety , and in health-related quality of life in traumatized refugees 23 months after admission to multidisciplinary treatment . The study group comprised 45 persons admitted to the Rehabilitation and Research Centre for Torture Victims in 2001 to 2002 . Data on background , trauma , present social situation , mental symptoms ( Hopkins Symptom Checklist-25 , Hamilton Depression Scale , Harvard Trauma Question naire ) , and on health-related quality of life ( World Health Organization Quality of Life-Bref ) were collected before treatment and after 9 and 23 months . No substantial changes in mental health were observed at the 9-month follow-up , and the minor decrease in some symptoms observed between the 9 and 23 months may reflect regression toward the mean or the natural course of symptoms in this cohort . Thus , no clinical ly significant improvement was observed , but there is a need for further studies , in particular r and omized trials evaluating the efficacy of various health-related and social interventions among severely traumatized refugees Cambodian refugees with posttraumatic stress disorder ( PTSD ) represent a cohort in severe need of treatment , but little information is available to guide treatment choices . We selected a sample of pharmacotherapy-refractory individuals to test the efficacy of combination treatment with sertraline and cognitive-behavior therapy ( CBT ) for treating PTSD . Participants in this pilot study were ten Khmer-speaking women who had been at a mean age of 22 - 26 years during the Pol Pot period ( 1975 - 1979 ) . These patients were r and omly assigned to either sertraline alone or combined treatment . We found that combined treatment offered additional benefit in the range of medium to large effect sizes for PTSD and associated symptoms . Our findings indicate that substantial gains can be achieved by adding CBT to pharmacotherapy for PTSD , and that a program of CBT emphasizing information , exposure , and cognitive-restructuring can be successfully modified for Khmer-speaking refugees Many Iraqi refugees suffer from posttraumatic stress . Efficient , culturally sensitive interventions are needed , and so we adapted narrative exposure therapy into a brief version ( brief NET ) and tested its effects in a sample of traumatized Iraqi refugees . Iraqi refugees in the United States reporting elevated posttraumatic stress ( N = 63 ) were r and omized to brief NET or waitlist control conditions in a 2:1 ratio ; brief NET was 3 sessions , conducted individually , in Arabic . Positive indicators ( posttraumatic growth and well-being ) and symptoms ( posttraumatic stress , depressive , and somatic ) were assessed at baseline and 2- and 4-month follow-up . Treatment participation ( 95.1 % completion ) and study retention ( 98.4 % provided follow-up data ) were very high . Significant condition by time interactions showed that those receiving brief NET had greater posttraumatic growth ( d = 0.83 ) and well-being ( d = 0.54 ) through 4 months than controls . Brief NET reduced symptoms of posttraumatic stress ( d = -0.48 ) and depression ( d = -0.46 ) more , but only at 2 months ; symptoms of controls also decreased from 2 to 4 months , eliminating condition differences at 4 months . Three sessions of brief NET increased growth and well-being and led to symptom reduction in highly traumatized Iraqi refugees . This preliminary study suggests that brief NET is both acceptable and potentially efficacious in traumatized Iraqi refugees |
818 | 32,185,552 | The other four secondary outcomes were in the favor of the conventional group but with no statistically significant difference .
AMH-based stimulation has the same results of pregnancy rate and risk of OHSS and can reduce the dose of rFSH and duration of stimulation | Anti-Müllerian hormone ( AMH ) used to establish patient profiles and predict ovarian response to stimulation , its role in assisted reproductive technology techniques is crucial .
To evaluate the evidence from published RCTs about the efficacy and safety of AMH-based ovarian stimulation versus conventional ovarian stimulation . | OBJECTIVE To compare antimüllerian hormone ( AMH ) and antral follicle count ( AFC ) as predictors of ovarian response to controlled ovarian stimulation at individual fertility clinics . DESIGN Retrospective analysis of individual study center data in two multicenter trials . Centers that provided > 10 patients were included in the analysis . SETTING A total of 19 ( n = 519 patients ) and 18 study centers ( n = 686 patients ) participating in a long GnRH agonist trial ( MERIT ) and a GnRH antagonist trial ( MEGASET ) , respectively . PATIENT(S ) Infertile women of good prognosis . INTERVENTION(S ) Long GnRH agonist or GnRH antagonist cycles . MAIN OUTCOME MEASURE(S ) Correlation between AMH and AFC , and oocyte yield by each study center for each trial . RESULTS ( S ) Antimüllerian hormone was more strongly correlated with oocyte yield than AFC : r = 0.56 vs. r = 0.28 in the GnRH agonist cohort , and r = 0.55 vs. r = 0.33 in the GnRH antagonist cohort . The correlation was numerically higher for AMH than for AFC at a significantly higher proportion of study centers : 17 ( 89 % ) and 15 ( 83 % ) centers in the long GnRH agonist and GnRH antagonist trial , respectively . Assessment of the relative capacity of AMH and AFC for predicting oocyte yield demonstrated that AMH dominated the model : AMH , R(2 ) = 0.29 and 0.23 ; AFC : R(2 ) = 0.07 and 0.07 ; AMH + AFC : R(2 ) = 0.30 and 0.23 for long GnRH agonist and GnRH antagonist trials , respectively . CONCLUSIONS ( S ) Antimüllerian hormone was a stronger predictor of ovarian response to gonadotropin therapy than AFC at the study center level in both r and omized trials utilizing GnRH agonist and GnRH antagonist protocol s. Antral follicle count provided no added predictive value beyond AMH Background : Assessment of ovarian reserve before an in vitro fertilization cycle ( IVF ) is one among the many factors that predicts a successful cycle . Individualized protocol based on ovarian reserve is design ed to optimize the pregnancy outcome without compromising the patient safety . Although authors have shown that anti-Mullerian hormone-tailored ( AMH ) protocol s have reduced the treatment burden and improved pregnancy rates , a few others have question ed its efficacy . Aims : The aim of this study was to decide whether the AMH-tailored protocol or the conventional protocol better decides IVF outcomes . Setting and Design : Prospect i ve r and omized controlled trial conducted at a tertiary level university hospital . Material s and Methods : Patients undergoing their first IVF cycle who fulfilled the inclusion criteria were recruited and r and omized to each group . Serum follicle-stimulating hormone was done for the patients on day 2 or 3 of a prior menstrual cycle , and serum AMH was done in the preceding cycle . Statistical Analysis : Analysis was performed using SPSS software version 16 . Results and Conclusion : There were 100 patients in each group . A total of 83 patients underwent embryo transfer in the conventional group and 78 patients in the AMH group . The clinical pregnancy rates per initiated cycle ( 36.4 % vs. 33.3 % ) and per embryo transfer ( 45.1 % vs. 41.3 % ) were similar in both the groups . There was no statistical difference in the number of cycles cancelled due to poor response or the risk of ovarian hyperstimulation syndrome in both the groups . Hence , this study showed the similar effectiveness of AMH-tailored protocol and conventional protocol in women undergoing IVF 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 The initial dose of recombinant Follicle Stimulating Hormone [ rFSH ] to be used in assisted reproduction treatment depends on several factors , mainly the cause of the infertility and the patient ’s age . For young patients [ ≤35 years ] usually an initial dose of around 150 IU of rFSH is recommended , but there are no studies proving that this should actually be the st and ard initial dose . We aim ed to report the experience of a low-cost Human Reproduction Center where a dose of 100 IU of rFSH was used for controlled ovarian hyperstimulation [ COH ] . Findings An observational prospect i ve study was performed on 212 women aged ≤38 years old that underwent high-complexity assisted reproduction treatments . The patients ’ infertility was mainly caused by tuboperitoneal , idiopathic or male factors . Controlled ovarian stimulation was performed using 100 IU of rFSH . Regarding the COH , 53.8 % of the patients presented a satisfactory response , 25.9 % low response , 14.2 % hyper-response , and 6.1 % developed ovarian hyperstimulation syndrome . Of the 55 patients with poor response , 20 started a new cycle with an initial dose of 200 IU of rFSH ; 65 % showed a satisfactory response , 10 % a poor response , 20 % a hyper-response , and 5 % developed OHSS . Conclusion The initial dose of 100 IU of rFSH was considered adequate for controlled ovarian hyperstimulation , meeting the aim to reduce the costs of the assisted reproduction treatment OBJECTIVE To compare the efficacy and safety of follitropin delta , a new human recombinant FSH with individualized dosing based on serum antimüllerian hormone ( AMH ) and body weight , with conventional follitropin alfa dosing for ovarian stimulation in women undergoing IVF . DESIGN R and omized , multicenter , assessor-blinded , noninferiority trial ( ESTHER-1 ) . SETTING Reproductive medicine clinics . PATIENT(S ) A total of 1,329 women ( aged 18 - 40 years ) . INTERVENTION(S ) Follitropin delta ( AMH < 15 pmol/L : 12 μg/d ; AMH ≥15 pmol/L : 0.10 - 0.19 μg/kg/d ; maximum 12 μg/d ) , or follitropin alfa ( 150 IU/d for 5 days , potential subsequent dose adjustments ; maximum 450 IU/d ) . MAIN OUTCOMES MEASURE(S ) Ongoing pregnancy and ongoing implantation rates ; noninferiority margins -8.0 % . RESULT ( S ) Ongoing pregnancy ( 30.7 % vs. 31.6 % ; difference -0.9 % [ 95 % confidence interval ( CI ) -5.9 % to 4.1 % ] ) , ongoing implantation ( 35.2 % vs. 35.8 % ; -0.6 % [ 95 % CI -6.1 % to 4.8 % ] ) , and live birth ( 29.8 % vs. 30.7 % ; -0.9 % [ 95 % CI -5.8 % to 4.0 % ] ) rates were similar for individualized follitropin delta and conventional follitropin alfa . Individualized follitropin delta result ed in more women with target response ( 8 - 14 oocytes ) ( 43.3 % vs. 38.4 % ) , fewer poor responses ( fewer than four oocytes in patients with AMH < 15 pmol/L ) ( 11.8 % vs. 17.9 % ) , fewer excessive responses ( ≥15 or ≥20 oocytes in patients with AMH ≥15 pmol/L ) ( 27.9 % vs. 35.1 % and 10.1 % vs. 15.6 % , respectively ) , and fewer measures taken to prevent ovarian hyperstimulation syndrome ( 2.3 % vs. 4.5 % ) , despite similar oocyte yield ( 10.0 ± 5.6 vs. 10.4 ± 6.5 ) and similar blastocyst numbers ( 3.3 ± 2.8 vs. 3.5 ± 3.2 ) , and less gonadotropin use ( 90.0 ± 25.3 vs. 103.7 ± 33.6 μg ) . CONCLUSION ( S ) Optimizing ovarian response in IVF by individualized dosing according to pretreatment patient characteristics results in similar efficacy and improved safety compared with conventional ovarian stimulation . CLINICAL TRIAL REGISTRATION NUMBER NCT01956110 BACKGROUND Anti-Müllerian hormone ( AMH ) , secreted by the granulosa cells of preantral and small antral follicles , has been described as a potential marker of the ovarian reserve . The aim of this prospect i ve study is to investigate the variations of AMH during the menstrual cycle in a young selected population of normo-ovulatory women and to analyse the correlation with other cyclic hormones . METHODS Twenty healthy volunteers from 19 to 35 years old , with regular menstrual cycles ( 26 - 31 days ) , normal ovulation ( day 10 - 16 ) , normal hormonal profile and normal body mass index ( 18 - 26 kg/m2 ) were recruited . AMH , inhibin B , LH , FSH , estradiol and progesterone were measured on days 3 , 7 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 18 , 21 and 25 of a spontaneous cycle . RESULTS AMH serum levels , either expressed by cycle day or aligned according to the ovulation day , did not show any significant variations during the menstrual cycle . CONCLUSIONS No significant fluctuation of the AMH level during the menstrual cycle was observed . Therefore , this hormone is particularly interesting for clinical evaluation of the ovarian reserve as it may be used at any time during the cycle This pilot study compared the efficacy and safety of two simple dosing algorithms , one based on anti-Müllerian Hormone ( AMH ) and the other on the antral follicle count ( AFC ) , to determine the starting dose of recombinant FSH ( rFSH ) for ovarian stimulation in 348 women . Patients were r and omized to a predefined AMH- or AFC-based algorithm . The proportion of cycles with the desired response was similar when rFSH dose was determined using AMH or AFC ( 35.2 % versus 28.4 % ) . There was a significant difference between the groups in the proportion of cycles with a hyperresponse ( 8.6 % and 17.4 % , but the incidence of ovarian hyperstimulation syndrome was similar ( 1.1 % and 4.6 % ) . There were no significant differences between two groups in outcomes , including implantation ( 19.3 % versus 19.0 % ) , clinical pregnancy ( 38.0 % versus 46.9 % ) , multiple pregnancy ( 16.5 % versus 15.2 % ) and miscarriage ( 7.0 % versus 8.3 % ) . However , statistically significant differences in ovarian response were evident among the AMH and AFC subgroups : for AMH , Desired and Hypo ; for AFC , Hypo and Hyper . This pilot study provides information for developing protocol s to further vali date the use of either AMH or AFC to guide the starting dose of rFSH in ovarian stimulation . The ideal outcome for couples undergoing IVF treatment is the birth of a healthy baby . One factor that might influence this is retrieving an adequate number of eggs , which are obtained using various treatment protocol s. A group of drugs called gonadotrophins have been used for more than 20years to stimulate the ovaries to produce eggs . However , the dose to start treatment has not been clearly defined . A few studies have looked at ways to use the best gonadotrophin dose for each woman , but to be useful in the clinic any approach needs to be simple and easy to use . This study compared the effectiveness and safety of two simple approaches to determining the starting dose of recombinant FSH ( rFSH ) for ovarian stimulation in women undergoing IVF . One was based on the concentration of a hormone secreted by developing eggs ( anti-Müllerian hormone ; AMH ) and the other on the number of developing follicles ( antral follicle count ; AFC ) . The number of cycles achieving the desired response in terms of number of eggs was similar when rFSH dose was guided using AMH or AFC , and the incidence of ovarian hyperstimulation syndrome was also similar . In addition , rates of clinical pregnancy , multiple pregnancy and miscarriage did not differ between the two groups . However , patients with low AMH concentrations or low AFC had a poor response to ovarian stimulation . This pilot study provides useful information from which new studies can further assess these approaches to personalizing treatment during IVF CONTEXT Anti-Müllerian hormone ( AMH ) , a quantitative marker for ovarian reserve , has been suggested to be independent of the classical endocrine fluctuations of the menstrual cycle . OBJECTIVE The objective of the study was to determine whether AMH levels are constant throughout the menstrual cycle , compared with those of FSH , LH , and estradiol . DESIGN / PATIENTS Frequent blood sampling was performed in 44 fertile , regularly cycling , female volunteers during one full menstrual cycle . SETTING The study was conducted at a university hospital . MAIN OUTCOME MEASURES AMH , FSH , LH , and estradiol measurements were allocated to one of seven cycle phases , and a multilevel analysis was performed . Consistent fluctuation patterns were tested by fitting sine patterns to the data . Finally , the frequency in which r and omly selected individual sample s would remain in one of five preset level categories ( quintiles ) for each of the variables was studied . RESULTS A sine pattern fitted to the AMH data was not statistically significant ( P = 0.40 ) . In contrast , sine patterns for FSH , LH , and estradiol were highly significant . Comparing the seven cycle phases , no significant differences could be observed between phase-specific AMH levels ( P = 0.06 ) . Repeated selection of AMH sample s for each individual showed that in 71.5 % of selection s , AMH values remained in the same quintile , whereas in 27.9 % values fell in an adjacent quintile . CONCLUSIONS AMH levels measured through a full menstrual cycle did not show consistent fluctuation patterns in contrast to levels of FSH , LH , and estradiol . Furthermore , r and om fluctuations were small , indicating that AMH can be relied on as a cycle-independent marker for ovarian reserve Abstract STUDY QUESTION Does an individualized serum anti-Müllerian hormone ( AMH ) based FSH dosing algorithm used in a GnRH antagonist protocol increase the proportion of patients with an intended number of oocytes ( 5–14 ) retrieved compared with a st and ard regimen ? SUMMARY ANSWER The AMH-based individualized algorithm did not increase the proportion of patients with an intended oocyte retrieval . WHAT IS KNOWN ALREADY Individualizing treatment for ovarian stimulation by serum AMH or antral follicle count can theoretically improve the ratio between benefits and risks . Current data suggest that there may be a reduced risk of ovarian hyperstimulation syndrome ( OHSS ) , but without improved pregnancy or live birth rates . Only two r and omized controlled trials ( RCTs ) have examined the potential of AMH-based algorithms to optimize the FSH dosing in ovarian stimulation . STUDY DESIGN , SIZE , DURATION A dual-center open-label investigator-driven RCT was conducted between January 2013 and November 2016 . Eligibility was assessed in 269 women and 221 were r and omized 2:1 between individualized and st and ard dosing groups . Women with pretreatment serum AMH > 24 pmol/L had 100 IU/day of recombinant FSH ( rFSH ) ; AMH 12–24 pmol/L had 150 IU/day of rFSH , and AMH < 12 pmol/L had maximal stimulation with corifollitropin 100 or 150 mg depending on bodyweight ±60 kg . The st and ard group had 150 IU/day of rFSH irrespective of pretreatment AMH . All patients followed the GnRH-antagonist protocol . The sample size calculation assumed that individualized dosing by AMH would reduce the proportion of unintended oocyte yield ( outside the 5–14 range ) by 50 % , from 35 to 17.5 % . In a 2:1 r and omization this required 216 patients : 144 in the individualized and 72 patients in the st and ard group ( 80 % power , 5 % significance ) . PARTICIPANTS / MATERIAL S , SETTING , METHODS All women had a presumed ovulatory normal menstrual cycle , were aged 25–38 years , weighed < 75 kg , had pretreatment AMH 4–40 pmol/L , did their first IVF or ICSI cycle and had two ovaries accessible to oocyte retrieval . Recruitment was conducted from both participating sites . Women were excluded if diagnosed with anovulatory polycystic ovary syndrome , endometriosis grade III/IV , hydrosalpings on ultrasound , recurrent miscarriages ( ≥3 ) , FSH > 12 IU/L or major medical disorders . MAIN RESULTS AND THE ROLE OF CHANCE After r and omization 149 women were allocated to the individualized group and 72 to the st and ard group . The primary outcome of women with an intended ( 5–14 ) number of oocytes retrieved was similar in the individualized ( n = 105 ) versus the st and ard ( n = 55 ) rFSH treatment group ( 72 % [ 95 % CI 64–79 % ] versus 78 % [ 95 % CI 67–86 % ] , respectively , P = 0.68 , between group st and ardized mean difference ( SMD ) −6 % , 95 % CI : −19–8 % ) . In the high AMH stratum of the individualized group , significantly more women ( n = 13 ) had an unintended low number of oocytes ( < 5 ) retrieved ( 38 % [ 95 % CI : 23–55 % ] ) compared with the st and ard group ( 6 % [ 95 % CI 0.3–24 % ] , P = 0.029 , between group SMD 32 % , 95 % CI : 9–56 % ) . Conversely , in the low pretreatment AMH stratum , individualized dosing using corifollitropin reduced the proportion of unintended low responders to 24 % ( 95 % CI : 12–40 % ) compared with 47 % ( 95 % CI : 26–69 % ) in the st and ard group , P = 0.10 , between group SMD −23 % ( 95 % CI : −54–8 % ) . OHSS was diagnosed in four women ( two in each study arm ) , and all cases were mild . Daily luteal phase question naire reporting showed similar wellbeing in terms of abdominal distention , abdominal pain , dyspnea and occurrence of bleeding between groups . The cumulative live birth rate per started cycle was similar ( 32 and 35 % ) comparing the individualized with the st and ard group . LIMITATIONS , REASONS FOR CAUTION This study was powered for showing differences only in the distribution of oocyte retrieval when comparing individualized and st and ard groups , therefore additional results should be viewed with caution . In addition , there was a change of AMH assay halfway through the study period and the possibility that corifollitropin being introduced to a subgroup of the intervention has introduced confounding can not be ruled out . WIDER IMPLICATION S OF FINDINGS In the expected high responder AMH stratum , 100 IU/day is an insufficient rFSH dose in a high proportion of patients . Further research might explore the 125 IU/day dose for the high AMH segment . STUDY FUNDING /COMPETING INTEREST(S ) None for the su bmi tted work . ICMJE declared personal interests for two of the authors . TRIAL REGISTRATION NUMBER EUDRACT registration number : 2012 - 004969 - 40 . TRIAL REGISTRATION DATE 27 November 2012 . DATE OF FIRST PATIENT ’S ENROLLMENT 10 January 2013 |
819 | 32,240,668 | Overall , studies consistently show that placebo and nocebo effects can be induced by various methods ( e.g. , suggestions , conditioning and social cues ) , despite high heterogeneity across studies .
Effects of suggestions were found consistently across subjective and behavioral parameters ( e.g. , itch and scratching in humans ) , whereas conditioning was likely to impact physiological parameters under certain conditions ( e.g. , conditioning of histamine levels in stressed rodents ) .
Brain areas responsible for itch processing were associated with nocebo effects . | Placebo and nocebo effects can influence somatic symptoms such as pain .
For itch and other dermatological symptoms these effects have been far less investigated . | Background Placebo treatment can significantly influence subjective symptoms . However , it is widely believed that response to placebo requires concealment or deception . We tested whether open-label placebo ( non-deceptive and non-concealed administration ) is superior to a no-treatment control with matched patient-provider interactions in the treatment of irritable bowel syndrome ( IBS ) . Methods Two-group , r and omized , controlled three week trial ( August 2009-April 2010 ) conducted at a single academic center , involving 80 primarily female ( 70 % ) patients , mean age 47±18 with IBS diagnosed by Rome III criteria and with a score ≥150 on the IBS Symptom Severity Scale ( IBS-SSS ) . Patients were r and omized to either open-label placebo pills presented as “ placebo pills made of an inert substance , like sugar pills , that have been shown in clinical studies to produce significant improvement in IBS symptoms through mind-body self-healing processes ” or no-treatment controls with the same quality of interaction with providers . The primary outcome was IBS Global Improvement Scale ( IBS-GIS ) . Secondary measures were IBS Symptom Severity Scale ( IBS-SSS ) , IBS Adequate Relief ( IBS-AR ) and IBS Quality of Life ( IBS-QoL ) . Findings Open-label placebo produced significantly higher mean ( ±SD ) global improvement scores ( IBS-GIS ) at both 11-day midpoint ( 5.2±1.0 vs. 4.0±1.1 , p<.001 ) and at 21-day endpoint ( 5.0±1.5 vs. 3.9±1.3 , p = .002 ) . Significant results were also observed at both time points for reduced symptom severity ( IBS-SSS , p = .008 and p = .03 ) and adequate relief ( IBS-AR , p = .02 and p = .03 ) ; and a trend favoring open-label placebo was observed for quality of life ( IBS-QoL ) at the 21-day endpoint ( p = .08 ) . Conclusion Placebos administered without deception may be an effective treatment for IBS . Further research is warranted in IBS , and perhaps other conditions , to eluci date whether physicians can benefit patients using placebos consistent with informed consent . Trial Registration Clinical Trials.gov Background Several studies demonstrated that placebo treatment may have a significant impact on many different symptoms . While in the traditional view concealment of the placebo is essential , recent studies report intriguing evidence that placebos may work even without deception . For example , it has been demonstrated that open-label placebos can improve symptoms in allergic rhinitis . However , the mechanisms of how placebos without concealment work remain unknown . Trial design In order to examine expectancy effects we conducted a r and omized controlled trial ( N = 46 ) , in which patients with allergic symptoms received either placebos without deception or no pills at all . In half of those patients we induced positive expectations about the placebo effect . After two weeks we tested whether symptoms and quality of life had changed . Results Results revealed that open-label placebos improved allergic symptoms more than the control group . Inducing positive expectations had no effects on the improvement of allergic symptoms ( the primary and more objective outcome ) , but on mental sum scores of the quality of life question naire . Conclusions Placebos without deception can improve symptoms in allergic rhinitis . Positive expectations do not contribute to the efficacy of open-label placebos , but seem to have an effect on more global and subjective well-being ( mental or emotional quality of life ) . Clinical trial registration number German Clinical Trials Register , Research into placebo effects has convincingly shown that inducing positive outcome expectations can reduce pain and other physical sensations . However , the comparative effects of different expectation inductions , such as verbal suggestion or mental imagery , and their generic effects on physical sensitivity , to different sensations such as pain , itch , and fatigue , are still largely unknown . In the current study , we assessed the individual and combined effects of verbal suggestion and imagery on pain , itch , and fatigue as indicators of physical sensitivity in a r and omized study design . Healthy participants ( n = 116 ) were given an inert ( placebo ) capsule that was said to be effective for reducing physical sensitivity in either the majority ( positive verbal suggestion ) or the minority ( control verbal suggestion ) of users . Subsequently , they imagined either their best possible health ( positive imagery ) or a typical day ( control imagery ) . Sensitivity to pain , itch , and fatigue was tested using a cold pressor test , histamine iontophoresis , and a bicycle test , respectively . Heart rate and skin conductance were recorded continuously . Results showed that positive verbal suggestion and imagery successfully induced positive expectations , but they did not affect physical sensitivity , as indicated by sensitivity to pain , itch , or fatigue , or concurrent physiological responses . These results could indicate that the specificity and concreteness of expectation inductions might be important for their applicability in the treatment of physical symptoms . Trial Registration Nederl and s Trial Register PURPOSE To investigate suggestion-induced placebo effects in inflammatory skin reactions . METHODS A healthy sample of volunteers ( N = 48 ) attended two laboratory sessions . In each , a local short term inflammatory skin reaction was induced with histamine . Participants were told that one session was a control session and the other was a treatment session in which an antihistamine cream would be applied to the arm to reduce the size of the weal and the experience of itch . Inert aqueous cream was applied in both sessions . Participants were r and omly allocated to undergo either the control or the treatment session first . RESULTS The placebo manipulation successfully reduced self-reported itch from the control to the placebo treatment session , but no placebo effect was demonstrated in weal size . Order effects were observed such that only those who underwent control procedures first had a smaller weal in the placebo treatment session as compared to the control session . The same order effect was seen for reported itch at one minute post histamine administration , but this disappeared at the three and five minute measures . CONCLUSION Findings suggest that explicit verbal suggestion can reduce the experience of itch . In addition to conscious awareness , a concrete representation of the suggested changes gained from prior experience to the stimulus may be an important component of placebo effects on inflammatory skin reactions Cutaneous reactivity to challenge with dinitrochlorobenzene ( DNCB ) and diphenylcyclopropenone ( DCP ) was studied in 16 volunteers following hypnotic suggestions to increase and decrease response during sensitization . The immunoreactivity to DNCB and DCP was modulated by direct suggestions and guided imagery under hypnosis . The volunteers were highly susceptible subjects selected by means of the Harvard Group Scale of Hypnotic Susceptibility . Form A. Measurement of skin reactions to the challenge I month after sensitization was performed double blindly . Results showed a significant ( P<0.01 ) difference in visually scored reactions to DCP and DNCB between the group instructed to increase reaction to DCP and decrease reaction to DNCB and the group given the opposite instructions . A non‐significant difference ( P= 0.055 ) in skin thickness measured by ultrasound was found between the two groups . The study supports previous reports of experimental modulation of immunoreactivity and indicates that the specific immunnnological processes involved in the development of allergic reactions may be susceptible to psychological factors The therapeutic results of hypnosis with relaxation therapy were evaluated in 15 patients with chronic urticaria of 7.8 years ' average duration . Compared with baseline and control session values , the hypnosis session provided relief of pruritus as measured by three self-report parameters . There was no change in the number of hives . All subjects were given a st and ard test for hypnotizability . Assuming that the results were not biased by their preceding relaxation sessions , we determined that six subjects were hypnotizable and nine were nonhypnotizable . Subjects in both groups improved symptomatically , but hypnotizable subjects had fewer hives and became more symptomatic during the control ( testing and history taking ) session . Hypnotizable subjects also more frequently related stress as a causative factor . At a follow-up examination five to 14 months after the completion of the experimental sessions , six patients were free of hives and an additional seven reported improvement We conducted r and omized clinical trials to examine the impact of direct-to-consumer advertisements on the efficacy of a br and ed drug . We compared the objective ly measured , physiological effect of Claritin ( Merck & Co. ) , a leading antihistamine medication , across subjects r and omized to watch a movie spliced with advertisements for Claritin or advertisements for Zyrtec ( McNeil ) , a competitor antihistamine . Among subjects who test negative for common allergies , exposure to Claritin advertisements rather than Zyrtec advertisements increases the efficacy of Claritin . We conclude that br and ed drugs can interact with exposure to television advertisements Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Objective : To test the hypothesize that psoriasis patients treated under a partial schedule of pharmacologic ( corticosteroid ) reinforcement would show less severe symptoms and relapse than those given the same amount of drug under st and ard conditions . Behavioral conditioning as an inherent component of many pharmacotherapeutic protocol s has never been examined . Methods : A double-blind , simple r and omization intervention was conducted with 46 patients from California and New York . Initially , lesions were treated with 0.1 % acetonide triamcinolone under st and ard treatment conditions . Thereafter , a St and ard Therapy group continued on continuous reinforcement ( active drug every treatment ) with 100 % of the initial dose ; Partial Reinforcement patients received a full dose 25 % to 50 % of the time and placebo medication other times ; Dose Control patients received continuous reinforcement with 25 % to 50 % of the initial dose . Results : Severity of disease scores in California neither supported nor refuted the hypothesis . In New York , where there was no difference between Partial Reinforcement and Dose Control groups at baseline , partial reinforcement effected a greater reduction in lesion severity than Dose Control conditions and did not differ from St and ard Therapy patients receiving two to four times more drug . For the entire population , the frequency of relapse under partial reinforcement ( 26.7 % ) was lower than in Dose Control patients ( 61.5 % ) and did not differ from full-dose treatment ( 22.2 % ) . Conclusions : A partial schedule of pharmacotherapeutic reinforcement could maintain psoriasis patients with a cumulative amount of corticosteroid that was relatively ineffective when administered under st and ard treatment conditions . Conceivably , corticosteroid administration only one quarter or half as frequently as currently prescribed is sufficient to treat psoriasis . We posit , however , that these preliminary observations implicate conditioning processes in— and for the design of — regimens of pharmacotherapy . PSS = Psoriasis Severity Scale ; CS = conditioned stimulus ; UCS = unconditioned stimulus To clarify the contribution of stress to classical conditioning-associated asthmatic responses , the effect of fasting stress on conditioned histamine release was investigated in a guinea pig model of asthma . The animals were r and omly divided into 2 groups for Experiment 1 and 2 , and received a conditioning procedure in which ovalbumin ( OA ) as an unconditioned stimulus ( US ) and dimethylsulfide ( DMS , sulfur smelling ) as a conditioned stimulus ( CS ) were simultaneously inhaled after fasting for 16 h. Then , one group was given food as a reward for respiratory distress , and the other group was denied it for more than 3 h , while being placed in front of the feeding group . After this procedure was repeated 5 times , the plasma histamine levels in response to the CS were measured in half of each group in Experiment 1 , and the respiratory resistance ( Rrs ) was assessed similarly in the other half of each group in Experiment 2 . The same experiments were again performed after exchanging assignments of feeding group or fasting group in both experiments . The control groups in both experiments received the CS and the US 10 times separately in a r and om order under 16 h fasting conditions and were provided food after the exposures . After these pseudo-conditioning presentations , the plasma histamine levels or the Rrs in response to the CS were measured . In Experiment 1 , the plasma histamine levels in the fasting stress group after the first conditioning sessions were significantly higher than those of the other groups . This difference was not observed when the groups were exchanged . In Experiment 2 , the fasting stress group showed higher values in the Rrs compared to the other groups , irrespective of the first or second conditionings ; however , they were not significant . The present study indicates that fasting stress after the conditioning procedures exacerbates the following conditioned histamine release , although the stress effect on bronchoconstriction was not confirmed Abstract This r and omized controlled trial was performed to investigate whether placebo effects in chronic low back pain could be harnessed ethically by adding open-label placebo ( OLP ) treatment to treatment as usual ( TAU ) for 3 weeks . Pain severity was assessed on three 0- to 10-point Numeric Rating Scales , scoring maximum pain , minimum pain , and usual pain , and a composite , primary outcome , total pain score . Our other primary outcome was back-related dysfunction , assessed on the Rol and –Morris Disability Question naire . In an exploratory follow-up , participants on TAU received placebo pills for 3 additional weeks . We r and omized 97 adults reporting persistent low back pain for more than 3 months ' duration and diagnosed by a board-certified pain specialist . Eighty-three adults completed the trial . Compared to TAU , OLP elicited greater pain reduction on each of the three 0- to 10-point Numeric Rating Scales and on the 0- to 10-point composite pain scale ( P < 0.001 ) , with moderate to large effect sizes . Pain reduction on the composite Numeric Rating Scales was 1.5 ( 95 % confidence interval : 1.0 - 2.0 ) in the OLP group and 0.2 ( −0.3 to 0.8 ) in the TAU group . Open-label placebo treatment also reduced disability compared to TAU ( P < 0.001 ) , with a large effect size . Improvement in disability scores was 2.9 ( 1.7 - 4.0 ) in the OLP group and 0.0 ( −1.1 to 1.2 ) in the TAU group . After being switched to OLP , the TAU group showed significant reductions in both pain ( 1.5 , 0.8 - 2.3 ) and disability ( 3.4 , 2.2 - 4.5 ) . Our findings suggest that OLP pills presented in a positive context may be helpful in chronic low back pain Background Placebo effects have been reported in type I allergic reactions . However the neuropsychological mechanisms steering placebo responses in allergies are largely unknown . The study analyzed whether and to what extend a conditioned placebo response is affecting type I allergic reactions and whether this response can be reproduced at multiple occasions . Methods 62 patients with house dust mite allergy were r and omly allocated to either a conditioned ( n = 25 ) , sham-conditioned ( n = 25 ) or natural history ( n = 12 ) group . During the learning phase ( acquisition ) , patients in the conditioned group received the H1-receptor antagonist desloratadine ( 5 mg ) ( unconditioned stimulus/US ) together with a novel tasting gustatory stimulus ( conditioned stimulus/CS ) . Patients in the sham-conditioned control group received the CS together with a placebo pill . After a wash out time of 9 days patients in the conditioned and sham-conditioned group received placebo pills together with the CS during evocation . Allergic responses documented by wheal size after skin prick test and symptom scores after nasal provocation were analyzed at baseline , after last desloratadine treatment and after the 1st and 5th CS re-exposure . Results Both conditioned and sham-conditioned patients showed significantly decreased wheal sizes after the 1st CS-evocation and significantly decreased symptom scores after the 1st as well as after the 5th evocation compared to the natural history control group . Conclusions These results indicate that placebo responses in type I allergy are not primarily mediated by learning processes , but seemed to be induced by cognitive factors such as patients ’ expectation , with these effects not restricted to a single evocation A classical Pavlovian paradigm pairing an olfactory cue with allergen challenge for a single training trial was used to produce conditioned histamine release and conditioned nasal airflow decrease in seasonal allergic rhinitis sufferers . There was no conditioned increase in subjective symptoms . Histamine release and airflow decrease showed evidence of extinction by a second test trial . A second study comparing the effects of the number of training trials showed that three training trials produced greater histamine release and airflow decrease than a single training trial , suggesting stronger effects with additional training OBJECTIVE This study investigated the placebo effect on experimentally induced skin reactions via the manipulation of expectation . METHODS Fifty-eight healthy volunteers were r and omised into either expectancy or control groups . All participants received a baseline administration of histamine on one arm ( Time 1 ) , then a second administration on the other arm , approximately 30 minutes later ( Time 2 ) . Prior to the second administration , the expectancy group was told that an antihistamine cream ( the placebo ) had been applied that would reduce their skin reaction to the histamine . Expected wheal area , actual wheal area , heart rate , and heart rate variability were measured at each time point . RESULTS There was a positive relationship between expected and actual wheal area at Time 1 . While the expectancy group expected a smaller skin reaction on the second arm they did not experience a greater reduction in wheal area , compared to control . The expectancy group had a greater reduction in heart rate during the second skin reaction , after the manipulation of expectation ( p<.05 ) . CONCLUSION While wheal area was not modulated , it may be worth further investigating this possibility , with modifications to the protocol . The reduction of heart rate appears to be an expectation effect and future research could eluci date mechanisms involved . There is an indication that expectations and inflammatory skin reactions are associated . Further study might aim to clarify the direction and nature of this relationship Classical conditioning of immune responsiveness has been extensively investigated in animals , but few successful studies have been reported with humans . We report the results of a study in which an attempt was made to demonstrate conditioned alteration to an allergic skin test response in humans . For 8 of 10 trials , allergic skin tests were administered to one forearm of volunteer subjects , and saline was administered to the other forearm . For the other two trials , the test substances were covertly switched between arms , but no changes in response result ed from this maneuver that could be ascribed to conditioning Background : Many people suffer from hay fever symptoms . Hypnosis has proved to be a useful adjunct in the treatment of conditions where allergic phenomena have an important role . Methods : R and omised parallel group study over an observation period of two consecutive pollen seasons . Outcome data include nasal flow under hypnosis , pollinosis symptoms from diaries and retrospective assessment s , restrictions in well-being and use of anti-allergic medication . We investigated 79 patients with a mean age of 34 years ( range 19–54 years ; 41 males ) , with moderate to severe allergic rhinitis to grass or birch pollen of at least 2 years duration and mild allergic asthma . The intervention consisted of teaching self-hypnosis during a mean of 2.4 sessions ( SD 1.7 ; range 2–5 sessions ) and continuation of st and ard anti-allergic pharmacological treatment . Results : Of 79 r and omised patients , 66 completed one , and 52 completed two seasons . Retrospective VAS scores yielded significant improvements in year 1 in patients who had learned self-hypnosis : pollinosis symptoms –29.2 ( VAS score , range 0–100 ; SD 25.4 ; p < 0.001 ) , restriction of well-being –26.2 ( VAS score , range 0–100 ; SD 28.7 ; p < 0.001 . In year 2 , the control group improved significantly having learned self-hypnosis as well : pollinosis symptoms –24.8 ( SD 29.1 ; p < 0.001 ) , restriction of well-being –23.7 ( SD 30.0 ; p < 0.001 ) . Daily self-reports of subjects who learnt self-hypnosis do not show a significant improvement . The hazard ratio of reaching a critical flow of 70 % in nasal provocation tests was 0.333 ( 95 % CI 0.157–0.741 ) after having learnt and applied self-hypnosis OBJECTIVE To determine whether individuals selected for good general health , high hypnotizability , and the ability to alter skin temperature under hypnotic suggestion can influence the delayed-type hypersensitivity ( DTH ) response to varicella-zoster ( VZ ) antigen under hypnotic suggestion . DESIGN A blinded clinical trial using a repeated measures design with subjects serving as their own controls . Subjects were r and omly assigned to undergo a predetermined sequence of four different experimental conditions , occurring at weekly intervals , with each condition including VZ skin testing : ( 1 ) hypnosis with suggestions to enhance the DTH response to VZ antigen ; ( 2 ) hypnosis with suggestions to suppress the DTH response ; ( 3 ) hypnosis with suggestions for relaxation only ; and ( 4 ) skin testing without hypnosis . SETTING A National Institutes of Health-supported clinical research center in a teaching hospital . SUBJECTS A stratified sample of 24 ambulatory , healthy , highly hypnotizable , volunteer college students selected for their above-average ability to alter skin temperature after hypnotic suggestions and their positive baseline responses to VZ antigen . There were 11 males and 13 females with a mean + /- SD age of 22 + /- 6 years . The mean + /- SD hypnotizability score ( Harvard Group Scale of Hypnotic Susceptibility ) was 11 + /- 1 . INTERVENTIONS Intradermal skin testing with VZ antigen ( Mantoux method ) and hypnotic suggestion . MAIN OUTCOME MEASURES Areas of in duration of the DTH response measured at 24 and 48 hours after injection of antigen . RESULTS The area of the DTH response was not affected by the experimental interventions . The area of erythema was likewise unaffected . CONCLUSIONS Our subjects were unable to alter their DTH responses using hypnotic suggestion Summary The effect of psychological pain reduction on the cutaneous inflammatory process was investigated by study ing the effect of hypnotically induced analgesia on the flare reaction of cutaneous histamine prick tests . Ten highly hypnotically susceptible volunteers had their cutaneous reactivity against histamine prick tests on both arms measured before hypnosis . Their pain-related brain potentials were measured on the basis of eight argon laser stimulations . These measurements were repeated in the hypnotic condition , where subjects were given repeated suggestions of analgesia in one arm . Final measurements were performed in the post-hypnotic condition . Subjectively felt pain was measured on a visual analogue scale . Results showed a mean reduction in subjectively felt pain of 71.7 % compared to the baseline condition . A significant ( P<0.01 ) mean reduction of the evoked potentials was found in the hypnotic analgesic condition compared to both the pre-hypnotic ( 49.9 % ) and the post-hypnotic condition ( 36.9 % ) . A significant difference was measured in the histamine flare area between the pre-hypnotic and the hypnotic analgesic condition ( P=0.01−0.02 ) and between the hypnotic analgesic and the post-hypnotic condition when compared with the control arm . The mean ratio of flare area between the analgesic arm and the control arm was 1.04 ( SD , 0.16 ) in the pre-hypnotic condition , 0.78 ( SD , 0.22 ) in the hypnotic analgesic condition , and 1.37 ( SD , 0.49 ) in the post-hypnotic condition . The results support the hypothesis that higher cortical processes can be involved in the interaction of inflammatory and pain processes Objective : This study examined if pairing a placebo with stimulant medication produces a placebo response that allows children with attention-deficit hyperactivity disorder ( ADHD ) to be maintained on a lower dose of stimulant medication . The primary aim was to determine the efficacy , side effects , and acceptability of a novel conditioned placebo dose reduction procedure . Method : Participants included 99 children ages 6 to 12 years with ADHD . After an initial double-blind dose finding to identify optimal dose of mixed amphetamine salts , subjects were r and omly assigned to 1 of 3 treatments of 8-week duration : ( a ) conditioned placebo dose reduction condition ( 50 % reduced dose/placebo [ RD/P ] ) or ( b ) a dose reduction only condition ( RD ) or ( c ) a no reduction condition ( full dose ) . The innovative conditioned placebo dose reduction procedure involved daily pairing of mixed amphetamine salts dose with a visually distinctive placebo capsule administered in open label , with full disclosure of placebo use to subjects and parents . Results : Seventy children completed the study . There were no differences in subject retention among the 3 groups . Most subjects in the RD/P group remained stable during the treatment phase , whereas most in the RD group deteriorated . There was no difference in control of ADHD symptoms between the RD/P group and the full dose group , and both RD/P and full dose groups showed better ADHD control than the RD group . Treatment emergent side effects were lowest in the RD/P group . Conclusion : Pairing placebos with stimulant medication elicits a placebo response that allows children with ADHD to be effectively treated on 50 % of their optimal stimulant dose Hypnosis has been used to ameliorate skin test reactivity in studies dating back to the 1930s . This study using modern methodology and statistical analyses sets out to test the hypothesis that it was possible to decrease reactions to histamine by hypnotic suggestion . Five subjects , all asthmatic and untrained in hypnosis , were given three hypnotic sessions where they were asked to control their reactions to histamine administered by the Pepys technique to forearm skin . These sessions were to be compared with three non-hypnotic sessions . The flare sizes but not wheal sizes were found to be significantly reduced after the hypnosis sessions , compared to sessions without hypnosis . Skin temperature was correlated with the size of reactions . The day upon which the sessions took place contributed significant amounts of the remaining unexplained variance , giving rise to questions about what could cause these day to day changes Background : The use of psychological therapies for patients with psoriasis has been proposed based on observations that the severity of their disease may correlate with emotional stress . The aim of this pilot study was to evaluate the effect of hypnosis as a treatment modality for patients with psoriasis . Methods : We performed a 3-month r and omized , single-blind , controlled trial of the use of hypnosis in adults with stable , chronic , plaque-type psoriasis . Highly or moderately hypnotizable subjects were r and omized to receive either hypnosis with active suggestions of improvement ( 5 patients ) or neutral hypnosis with no mention of their disease process ( 6 patients ) . After this period , the study was unblinded , and all the patients were treated for an additional 3 months with hypnosis with active suggestions of improvement . Results : Highly hypnotizable subjects showed significantly greater improvement than did moderately hypnotizable subjects , independent of treatment group assignment ( active suggestion or neutral hypnosis ) . Conclusion : Although this study included a very limited number of patients , the results suggest that hypnosis may be a useful therapeutic modality for highly hypnotizable subjects with psoriasis , and merits further testing in a larger patient population Male guinea pigs were either h and led ( ' stressed ' ) or not disturbed ( ' non-stressed ' ) for four weeks prior to conditioning with a classical discrimination conditioning design . Animals were sensitized to bovine serum albumin ( BSA ) and four weeks later presented with either an odor ( the CS+ ) paired with BSA or a second odor ( the CS- ) paired with saline . These pairs were presented in a r and om order for ten trials . Weekly blood sample s were assayed for histamine and cortisol levels . Following the conditioning trials , animals were subjected to extinction trials during which the CS+ odor was presented but not paired with the BSA . The animals h and led prior to the conditioning procedures learned the association between the odor and the BSA as indicated by increased histamine levels when exposed to the conditioned odor alone . The non-h and led group did not learn . Additionally , the cortisol levels were significantly higher for the h and led group vs. the non-h and led group when the CS+ was presented during extinction . The role of stress in both learning and immunomodulation is discussed Placebo effects are positive outcomes that are not due to active treatment components , which may be elicited even when patients are aware of receiving an inert substance ( open-label ) . This proof-of-principle study investigated for the first time whether open-label placebo effects on itch can be induced by verbal suggestions alone . Ninety-two healthy volunteers were r and omized to experimental ( open-label suggestions ) or control ( no suggestions ) groups . Self-reported itch evoked by histamine iontophoresis was the primary study outcome . In addition , itch expectations , skin condition and affect were assessed . The experimental group expected lower itch than the control group , which was , in turn , related to less experienced itch in this group only , although no significantly different itch levels were reported between groups . The results illustrate a potential role for open-label placebo effects in itch , and suggest that further study of verbal suggestions through an extensive explanation of placebo effects might be promising for clinical practice Background : Chronic pruritus is a multifactorial , challenging symptom of global relevance . Objective : The European Academy of Dermatology and Venereology Network on Assessment of Severity and Burden of Pruritus ( PruNet ) investigation aim ed to analyze the severity and humanistic burden of chronic pruritus in patients suffering from inflammatory dermatoses across Europe . Methods : Prospect ively collected routine data on 552 patients ( with atopic dermatitis , contact dermatitis , prurigo nodularis , psoriasis vulgaris , lichen planus , or mycosis fungoides [ pruritus numeric rating scale score ≥3 ] ) from 9 European centers ( in Austria , France , Germany , Italy , Pol and , Russia , Spain , Switzerl and , and Turkey ) were analyzed by univariate and multivariate variance analyses of various itch characteristics and quality of life ( as measured by the Dermatology Life Quality Index and the ItchyQoL ) . Results : Duration , frequency , and intensity of pruritus ( according to a numeric rating scale and visual analog scale ) and related impairment of quality of life differed between European centers and dermatologic diagnoses ( P < .05 ) . The country in which the center was located had a greater impact on how patients evaluated pruritus intensity and quality of life than diagnosis did ( P < .001 ) . Limitations : One center per country was included . Conclusion : The humanistic burden of chronic pruritus in patients with inflammatory dermatoses is high . European cross-cultural factors may have a stronger influence than a specific dermatologic diagnosis on how patients rate intensity of pruritus and quality of life Placebo and nocebo effects have been shown to influence subjective symptoms such as itch . These effects can be induced by influencing outcome expectations through , for example , combining the application of an inert substance ( e.g. , a cream ) with verbal suggestions on the anticipated effects of this substance . Interestingly , placebo effects also occur when it is known that a treatment is inert ( i.e. , open-label placebo ) . However , no study to date has examined the efficacy of negative and positive verbal suggestions under similar open-label and closed-label ( i.e. , concealed placebo/nocebo ) conditions in itch . A r and omized controlled between-subjects study design was applied in which healthy volunteers ( n = 92 ) were r and omized to 1 ) an open-label positive verbal suggestion group , 2 ) a closed-label positive verbal suggestion group , 3 ) an open-label negative verbal suggestion group , or 4 ) a closed-label negative verbal suggestion group . Verbal suggestions were made regarding the topical application of an inert substance . Itch was evoked experimentally by histamine iontophoresis at baseline and again following suggestions . Itch expectations , self-reported itch during and following iontophoresis , and skin response parameters were measured . Positive suggestions were found to result in significantly lower expected itch than were negative suggestions in both open- and closed-label conditions . No effects of the suggestions on itch during iontophoresis were found , but significantly lower itch was reported in the 4 min following iontophoresis in the ( combined open- and closed-label ) positive compared with negative verbal suggestion groups . In addition , a smaller increase in skin temperature was found in the positive compared with negative suggestion groups . The findings illustrate a potential role of ( open- and closed-label ) placebo for optimizing expectations and treatment effects for itch in clinical practice . Clinical Trial Registration : Netherl and s Trial Register , trial number : NTR6530 Supplemental digital content is available in the text . ABSTRACT Objective Allergic rhinitis symptoms can be reduced by behaviorally conditioning antihistamine . It is unclear whether these findings extend to histamine-induced itch or work when participants are informed about the conditioning procedure ( open-label conditioning ) . The current study aims to investigate the efficacy of ( open-label ) antipruritic behavioral conditioning for histamine-induced itch . Methods Healthy participants ( n = 92 ; 84 % female ) were r and omized to I ) an open-label conditioned , II ) closed-label conditioned , III ) conditioned-not-evoked control , or IV ) nonconditioned control group . A two-phase conditioning paradigm was used . During acquisition , a conditioned stimulus ( CS ; distinctively tasting beverage ) was repeatedly paired with the H1-antihistamine levocetirizine ( groups I – III ) . During evocation , the CS was paired with placebo ( I , II ) , or instead of the CS , water was paired with placebo ( III ) . The nonconditioned control group ( IV ) received CS with placebo in both phases . Itch after histamine iontophoresis and physiological data ( i.e. , spirometry , heart rate , skin conductance ) were assessed . Combined conditioned and combined control groups were first compared , and analyses were repeated for separate groups . Results Marginally lower itch was reported in the combined conditioned compared with the control groups ( F(1,88 ) = 2.10 , p = .076 , η2partial = 0.02 ) ; no differences between separate groups were found . No effects on physiological data were found , except for heart rate , which reduced significantly and consistently for control groups , and less consistently for conditioned groups ( group by time interaction : F(7,80 ) = 2.35 , p = .031 , η2partial = 0.17 ) . Conclusion Limited support was found for the efficacy of antipruritic behavioral conditioning , regardless of whether participants were informed about the conditioning procedure . The application of open-label conditioning in patient population s should be further research ed . Trial Registration : www.trialregister.nl ; ID NTR5544 BACKGROUND This study examined short-term efficacy , side effects and acceptability of a placebo treatment procedure design ed to maintain children with attention deficit hyperactivity disorder ( ADHD ) on 50 % of their usual stimulant dose . METHODS An open-label prospect i ve crossover trial was conducted in 26 children with ADHD , ages 7 - 15 years , stable on stimulant therapy , followed at a community-based developmental paediatrics ADHD clinic . Subjects were r and omly assigned to one of two orders of experimental conditions : ( 1 ) baseline ( 100 % ) dose ( 1 week ) , then 50 % dose ( 1 week ) , then 50 % dose + placebo ( 1 week ) , or ( 2 ) baseline ( 100 % ) , then 50 % dose + placebo , then 50 % dose . The inert nature of the placebo was fully disclosed to parent and child . Treatment was open-label for child , parents and physician , but single blind for teachers . Main outcome measures included weekly IOWA Conners parent and teacher rating scales , the Pittsburgh side effects rating scale ( PSERS ) and the Clinical Global Impressions ( CGI ) scale . RESULTS Parent IOWA showed ADHD behaviour tended to remain the same when the dose of stimulant medication was reduced with placebo but to deteriorate when the dose was reduced without placebo . There were no significant differences between conditions on the Teacher IOWA . PSERS scores were higher at baseline than on 50 % dose . On the CGI , there was a significant difference ( P = 0.004 ) between the 50 % dose and the 50 % + placebo conditions . Individual subject analysis showed that eight subjects met criteria for responder . CONCLUSIONS Results indicate that the open-label placebo treatment was acceptable and efficacious in the short term for some children Background Systematic Review s ( SRs ) of experimental animal studies are not yet common practice , but awareness of the merits of conducting such SRs is steadily increasing . As animal intervention studies differ from r and omized clinical trials ( RCT ) in many aspects , the methodology for SRs of clinical trials needs to be adapted and optimized for animal intervention studies . The Cochrane Collaboration developed a Risk of Bias ( RoB ) tool to establish consistency and avoid discrepancies in assessing the method ological quality of RCTs . A similar initiative is warranted in the field of animal experimentation . Methods We provide an RoB tool for animal intervention studies ( SYRCLE ’s RoB tool ) . This tool is based on the Cochrane RoB tool and has been adjusted for aspects of bias that play a specific role in animal intervention studies . To enhance transparency and applicability , we formulated signalling questions to facilitate judgment . Results The result ing RoB tool for animal studies contains 10 entries . These entries are related to selection bias , performance bias , detection bias , attrition bias , reporting bias and other biases . Half these items are in agreement with the items in the Cochrane RoB tool . Most of the variations between the two tools are due to differences in design between RCTs and animal studies . Shortcomings in , or unfamiliarity with , specific aspects of experimental design of animal studies compared to clinical studies also play a role . Conclusions SYRCLE ’s RoB tool is an adapted version of the Cochrane RoB tool . Widespread adoption and implementation of this tool will facilitate and improve critical appraisal of evidence from animal studies . This may subsequently enhance the efficiency of translating animal research into clinical practice and increase awareness of the necessity of improving the method ological quality of animal studies Nocebo effects , i.e. , adverse treatment effects which are induced by patients ’ expectations , are known to contribute to the experience of physical symptoms such as pain and itch . A better underst and ing of how to minimize nocebo responses might eventually contribute to enhanced treatment effects . However , little is known about how to reduce nocebo effects . In the current r and omized controlled study , we tested whether nocebo effects can be minimized by positive expectation induction with respect to electrical and histaminic itch stimuli . First , negative expectations about electrical itch stimuli were induced by verbal suggestion and conditioning ( part 1 : induction of nocebo effect ) . Second , participants were r and omized to either the experimental group or one of the control groups ( part 2 : reversing nocebo effect ) . In the experimental group , positive expectations were induced by conditioning with verbal suggestion . In the control groups either the negative expectation induction was continued or an extinction procedure was applied . Afterwards , a histamine application test was conducted . Positive expectation induction result ed in a significantly smaller nocebo effect in comparison with both control groups . Mean change itch NRS scores showed that the nocebo effect was even reversed , indicating a placebo effect . Comparable effects were also found for histamine application . This study is the first to demonstrate that nocebo effects can be minimized and even reversed by conditioning with verbal suggestion . The results of the current study indicate that learning via counterconditioning and verbal suggestion represents a promising strategy for diminishing nocebo responses |
820 | 28,356,771 | Ongoing trials are investigating nab-P/Gem with or without other agents across disease setting s. Discussion Studies conducted after MPACT have demonstrated that nab-P/Gem is an effective regimen for the first-line treatment of MPC for a wide range of patients .
Ongoing studies will yield valuable insights on the utility of nab-P – containing regimens to improve patient outcomes in PC in both earlier-stage and advanced disease | Background Nanoparticle albumin-bound paclitaxel ( nab-P ) plus gemcitabine ( Gem ) became a st and ard treatment option for metastatic pancreatic cancer ( MPC ) following positive results from a global phase III trial ( MPACT ) .
A large number of studies have now published results on the use of nab-P/Gem to treat advanced and early-stage disease , warranting a comprehensive review .
The main goal of this systematic review is to summarize the efficacy and safety data of nab-P/Gem for the treatment of pancreatic cancer ( PC ) . | ABSTRACT Aim : Gemcitabine ( GEM ) and nab-paclitaxel ( nab-P ) significantly improved overall survival over GEM in metastatic pancreatic adenocarcinoma ( PA ) . Given the synergism of taxanes with platinum compounds and fluoropyrimidines , we determined the recommended phase 2 dose ( RP2D ) of nab-P in combination with cisplatin , capecitabine , and GEM ( PAXG regimen ) in a phase Ib trial in patients ( pts ) with stage III PA ( NCT01730222 ) . Methods : GEM , cisplatin and capecitabine were given at fixed dose ( 800 , 30 , and 1250 mg/m2 , respectively ) q 2 weeks . Doses of nab-P were escalated in cohorts of 3 to 6 pts from 100 ( level 1 ) , to 125 ( level 2 ) and 150 mg/m2 ( level 3 ) q 2 weeks . The maximum tolerated dose ( MTD ) was defined as the dose at which > 2 out of 3 - 6 pts developed dose-limiting toxicity ( DLT ) during the first month of therapy . DLT was defined as G ≥ 4 neutropenia lasting ≥ 7 days ; G ≥ 3 febrile neutropenia , fever ≥38.5 ° C , thrombocytopenia , diarrhea , nausea or vomiting ; G ≥ 2 neurological toxicity or failure to recover to grade ≤ 1 toxicity ( except alopecia ) or to baseline values after delaying the initiation of next cycle by > 2 weeks . Results : Between Dec 2012 and Mar 2014 , 23 pts ( 16 males ; median age 63 years ) with unresectable ( according to a surgical team performing > 100 duodenocephalopancreasectomy/year ) stage III PA , were enrolled at a single institution ( 3 at level 1 , 5 at level 2 , 15 at level 3 ) . To date , 197 cycles of PAXG were administered . Therapy is ongoing in 5 pts at level 3 . No DLT has occurred . Worse per patient toxicity was G3/4 neutropenia 29/29 % ; G3 fatigue 14 % ; G3 neuropathy , anemia , nausea , diarrhea 7 % . After 123 cycles at 150 mg/m2 the nab-P dose-intensity was 90 % . To date , a partial response ( PR ) was observed in 15 pts ( 65 % ) and stable disease ( SD ) in 8 pts ; among 20 pts with positive PET scan a complete response was observed in 8 ( 40 % ) , PR in 10 ( 50 % ) , SD in 2 ; 19 pts had elevated basal CA19 - 9 which was reduced by > 50 % in 18 ( 95 % ) ; 15/16 ( 94 % ) pts with mature follow-up were progression-free at 6 months from therapy start . Conclusions : The RP2D of nab-P in the PAXG regimen was 150 mg/m2 every 2 weeks . Preliminary results are promising and a phase II r and omized trial with this regimen is ongoing . Disclosure : M. Reni : Participation in an Advisory Board : Merck ; Celgene ; CLOVIS ; Genentech ; Boehringer L. Gianni : advisory board Celgene . All other authors have declared no conflicts of interest Purpose Addition of either nab-paclitaxel or erlotinib to gemcitabine to treat advanced pancreatic cancer has demonstrated overall survival benefit . This study was conducted to evaluate the tolerability and safety of combining all three drugs and assess preliminary evidence of efficacy . Methods In this open-label , phase 1b study , patients with previously untreated , advanced pancreatic cancer were treated in 28-day cycles with intravenous gemcitabine/nab-paclitaxel on days 1 , 8 , and 15 , and once daily oral erlotinib . A st and ard “ 3 + 3 ” design was used . Dose level 1 ( DL1 ) for gemcitabine (mg/m2)/nab-paclitaxel (mg/m2)/erlotinib ( mg ) was 1000/125/100 , respectively , with de-escalation to DL−1 ( 1000/100/100 ) , DL−2b ( 1000/75/100 ) , and DL−3 ( 1000/75/75 ) . The maximum tolerated dose ( MTD ) was defined by occurrence of dose-limiting toxicity ( DLT ) in ≤1 of six patients within the first cycle . Efficacy was assessed with CT scans performed at two-cycle intervals . Results Nineteen patients were enrolled . DLTs occurred in two patients at DL1 , three patients at DL−1 , two patients at DL−2b , and one patient at DL−3 . The MTD for the combination of gemcitabine/nab-paclitaxel/erlotinib was DL−3 ( 1000/75/75 ) . In analyses of efficacy among 14 evaluable patients , partial responses were observed in four of six patients at DL1 , one of two patients at DL−2b , and two of six patients at DL−3 . Conclusion The addition of erlotinib to gemcitabine and nab-paclitaxel is not tolerable at st and ard single-agent dosing of all drugs . However , significant clinical activity was noted , even at DL−3 . Further study of the combination will need to incorporate reduced dosing PURPOSE To provide evidence -based recommendations to oncologists and others for treatment of patients with locally advanced , unresectable pancreatic cancer . METHODS American Society of Clinical Oncology convened an Expert Panel of medical oncology , radiation oncology , surgical oncology , gastroenterology , palliative care , and advocacy experts and conducted a systematic review of the literature from January 2002 to June 2015 . Outcomes included overall survival , disease-free survival , progression-free survival , and adverse events . RESULTS Twenty-six r and omized controlled trials met the systematic review criteria . RECOMMENDATIONS A multiphase computed tomography scan of the chest , abdomen , and pelvis should be performed . Baseline performance status and comorbidity profile should be evaluated . The goals of care , patient preferences , psychological status , support systems , and symptoms should guide decisions for treatments . A palliative care referral should occur at first visit . Initial systemic chemotherapy ( 6 months ) with a combination regimen is recommended for most patients ( for some patients radiation therapy may be offered up front ) with Eastern Cooperative Oncology Group performance status 0 or 1 and a favorable comorbidity profile . There is no clear evidence to support one regimen over another . The gemcitabine-based combinations and treatments recommended in the metastatic setting ( eg , fluorouracil , leucovorin , irinotecan , and oxaliplatin and gemcitabine plus nanoparticle albumin-bound paclitaxel ) have not been evaluated in r and omized controlled trials involving locally advanced , unresectable pancreatic cancer . If there is local disease progression after induction chemotherapy , without metastasis , then radiation therapy or stereotactic body radiotherapy may be offered also with an Eastern Cooperative Oncology Group performance status ≤ 2 and an adequate comorbidity profile . If there is stable disease after 6 months of induction chemotherapy but unacceptable toxicities , radiation therapy may be offered as an alternative . Patients with disease progression should be offered treatment per the ASCO Metastatic Pancreatic Cancer Treatment Guideline . Follow-up visits every 3 to 4 months are recommended . Additional information is available at www.asco.org/ guidelines /LAPC and www.asco.org/ guidelines /MetPC and www.asco.org/ guidelines wiki PURPOSE The trial objectives were to identify the maximum-tolerated dose ( MTD ) of first-line gemcitabine plus nab-paclitaxel in metastatic pancreatic adenocarcinoma and to provide efficacy and safety data . Additional objectives were to evaluate positron emission tomography ( PET ) scan response , secreted protein acidic and rich in cysteine ( SPARC ) , and CA19 - 9 levels in relation to efficacy . Subsequent pre clinical studies investigated the changes involving the pancreatic stroma and drug uptake . PATIENTS AND METHODS Patients with previously untreated advanced pancreatic cancer were treated with 100 , 125 , or 150 mg/m(2 ) nab-paclitaxel followed by gemcitabine 1,000 mg/m(2 ) on days 1 , 8 , and 15 every 28 days . In the pre clinical study , mice were implanted with human pancreatic cancers and treated with study agents . RESULTS A total of 20 , 44 , and three patients received nab-paclitaxel at 100 , 125 , and 150 mg/m(2 ) , respectively . The MTD was 1,000 mg/m(2 ) of gemcitabine plus 125 mg/m(2 ) of nab-paclitaxel once a week for 3 weeks , every 28 days . Dose-limiting toxicities were sepsis and neutropenia . At the MTD , the response rate was 48 % , with 12.2 median months of overall survival ( OS ) and 48 % 1-year survival . Improved OS was observed in patients who had a complete metabolic response on [(18)F]fluorodeoxyglucose PET . Decreases in CA19 - 9 levels were correlated with increased response rate , progression-free survival , and OS . SPARC in the stroma , but not in the tumor , was correlated with improved survival . In mice with human pancreatic cancer xenografts , nab-paclitaxel alone and in combination with gemcitabine depleted the desmoplastic stroma . The intratumoral concentration of gemcitabine was increased by 2.8-fold in mice receiving nab-paclitaxel plus gemcitabine versus those receiving gemcitabine alone . CONCLUSION The regimen of nab-paclitaxel plus gemcitabine has tolerable adverse effects with substantial antitumor activity , warranting phase III evaluation |
821 | 24,522,377 | Axillary lymphatic drainage concordance between superficial and deep sentinel node mapping material in breast cancer patients is fairly high and clinical ly acceptable .
However , both injection techniques can complement each other and the combined superficial/deep injection technique seems to be more successful clinical ly and can decrease the overall false negative rate | It is still unclear whether the deep and superficial lymphatics of the breast always drain into the same nodes and which route best simulates the spread of breast cancer .
In the current study , we systematic ally search ed the available literature to find the studies evaluated the sentinel node locations of deep and superficial injections in the same patients simultaneously or serially . | Background : Radiotracer and blue dye mapping of sentinel lymph nodes ( SLN ) have been advocated as accurate methods to stage the clinical ly negative axilla in breast cancer patients . The technical aspects of SLN biopsy are not fully characterized . In this study we compare the results of intraparenchymal ( IP ) and intradermal ( ID ) injection of Tc-99 m sulfur colloid , to establish an optimal method for SLN localization . Methods : 200 consecutive patients had SLN biopsy performed by a single surgeon . Of these , 100 ( Group I ) had IP injection and 100 ( Group II ) had ID injection of Tc-99 m sulfur colloid . All patients had IP injection of blue dye as well . Endpoints included ( 1 ) successful SLN localization by lymphoscintigraphy , ( 2 ) successful SLN localization at surgery , and ( 3 ) blue dye – isotope concordance ( uptake of dye and isotope by the same SLN ) . Results : Isotope SLN localization was successful in 78 % of Group I and 97 % of group II patients ( P < .001 ) . When isotope was combined with blue dye , SLN were found in 92 % of group I and 100 % of Group II ( P < .01 ) . In cases where both dye and isotope were found in the axilla , dye mapped the same SLN as radiotracer in 97 % of Group I and 95 % of Group II patients . Conclusions : The dermal and parenchymal lymphatics of the breast drain to the same SLN in most patients . Because ID injection is easier to perform and more effective , this technique may simplify and optimize SLN localization BACKGROUND AND OBJECTIVE We performed a pilot study on 30 consecutive patients undergoing sentinel node ( sN ) biopsy by radioguided surgery and vital blue dye mapping to determine whether there is a single sN for each breast independent of tumor site or an sN specifically related to the site of the breast neoplasm . METHODS There were 6 groups of 5 patients ; each patient had a subdermal injection of radiotracer on the tumor site plus a second injection of radiotracer that was changed in every subset of patients to test whether modifying the site or the route of injection could have impaired the proper detection of the sN. RESULTS " False " sN were detected only in patients who had a second injection of radiotracer away from the tumor site ; this occurred in 2 of 5 patients ( 40 % ) in group I , in 3 of 5 patients ( 60 % ) in group II , in all patients in group III , and in 3 of 5 patients ( 60 % ) in group IV . The different route of injection ( peritumoral or subdermal ) always on the tumor site that was tested in groups V and VI did not impair the proper detection of the sN. CONCLUSIONS Our findings support the hypothesis of a precise topographic correspondence between the primary tumor and its specific sN more than the existence of a first sN in the axillary basin , which indiscriminately drains all quadrants of the breast , like " a neck of a bottle . " This should be considered for the proper selection of the injection site of either vital blue dye or radiopharmaceuticals Background Sentinel lymph node ( SLN ) mapping with radioisotope and blue dye is rapidly becoming the st and ard of care for breast cancer . The optimal location for injection of radioisotope and blue dye is still being investigated . The goal of this study was to determine whether blue dye injection into the subareolar ( SA ) location localized the same sentinel nodes as the peritumoral ( PT ) location for patients with breast cancer . Methods Three hundred thirty-two patients with biopsy-proven operable breast cancer or ductal carcinoma in situ at two institutions underwent SLN mapping . Eighty-three patients had PT injection of blue dye ( group 1 ) , and 249 patients had SA injection of blue dye ( group 2 ) . All patients underwent PT injection of99mTc-labeled sulfur colloid . Results The two groups were similar in age , previous biopsy type , and tumor size , location , and histology . The mean number of SLNs identified was 2.4 ( range , 0–9 ) in group 1 and 2.5 ( range , 0–11 ) in group 2 . The SLN identification rate was 95 % for group 1 and 97 % for group 2 . The isotope success rate was 94 % for both groups . The blue dye success rate was 84 % for group 1 and 90 % for group 2 . The isotope/blue dye concordance rate was 87 % for group 1 and 90 % for group 2 . At a median follow-up of 28 months ( range , 14 to 40 ) , there were no axillary recurrences in any of the 332 patients . Conclusions These data suggest that delivery of mapping reagents in the SA and PT locations identifies similar lymph nodes . Because of simplicity and the similarity in node identification between SA and PT injection , further investigation of the SA site for delivery of SLN mapping reagents for breast cancer is warranted Background Preoperative parenchymal or peritumoral ( PT ) injection of 99mTc-labeled sulfur colloid ( TcSC ) is the st and ard method for sentinel lymph node ( SLN ) identification in patients with breast cancer . Limitations of this method include variable identification rates , slow transit times , and painful injections . We hypothesize that TcSC will travel to the SLN within minutes after injection into the subareolar ( SA ) lymphatics , thus making an intraoperative injection technique feasible . Methods One hundred twenty-two women with invasive breast cancer were enrolled onto this prospect i ve study . Immediately after the induction of general anesthesia , patients were injected with 1 to 2 mCi of filtered TcSC in the SA location . Then , 5 mL of 1 % isosulfan blue dye was injected into the PT location . The SLN or SLNs were identified as radioactive , blue , or both and removed for pathologic evaluation . Results The mean patient age was 56 years . The mean tumor size was 1.5 cm . In 86.1 % of patients , a transcutaneous axillary “ hot spot ” was identified by h and held gamma probe . The mean time from TcSC injection to axillary incision was 17.6 minutes . At least one SLN was identified in 99.2 % of patients . The mean number of SLNs identified per patient was 1.83 . The mean count of radioactive SLNs was 2715 cps . In 97.2 % of patients , blue SLNs were also radioactive . Conclusions TcSC injected into the SA lymphatics rapidly drains to the SLN . The radioactive SLN is easily and quickly identified after an intraoperative SA TcSC injection . The simplicity of this method eliminates the inherent problems associated with st and ard PT injection First published in 1996 , the CONSORT guidelines were created to address inadequate reporting of clinical trials , especially individually r and omized , two-group , parallel trials . The original guidelines were developed by a team of statisticians , epidemiologists , and biomedical editors and were revised in 2001 and again in 2010 ( Moher , Schultz , & Altman , 2001 ; Schulz , Altman , & Moher , 2010 ) . The intent of the CONSORT checklist and flow diagram was to provide a template for authors to fully and accurately describe research methodology . Moher and colleagues ( 2001 ) asserted that whereas inadequate reporting hinders interpretation , it also “ borders on unethical practice when biased results receive false credibility ” ( p. 4 ) . The latest CONSORT statement , checklist , flow diagram , and explanation and elaboration document are available on the website ( http://www.consort-statement.org ) or from one of several publications such as Schulz and colleagues ( 2010 ) . The CONSORT guidelines can be useful whether or not the study was design ed as a r and omized controlled trial ( RCT ) . Although most applicable to an RCT , the author of a quantitative study who chooses only the relevant checklist elements will still benefit from prompts to include the appropriate information in the introduction , methods , results , and discussion sections . Fuzzy reporting and omission of critical information comprise the majority of review ers ’ comments and queries back to authors of manuscripts su bmi tted for peer review . For example , authors frequently omit adequate description of the “ setting s and locations where the data were collected ” and have a tendency to gloss over limitations that should include “ sources of potential bias , imprecision , and , if relevant , multiplicity of analyses ” ( Schulz et al. , 2010 , p. 2 ) . PRISMA : PREFERRED REPORTING ITEMS FOR SYSTEMATIC REVIEW S AND AIMS Identification of sentinel lymph nodes ( SLN ) may depend on the tissue plane of tracer injection . To explore this , we developed a dual-isotope technique to compare the lymphatic drainage basins accessed by intradermal and parenchymal injections . METHODS Fifteen breast cancer patients had simultaneous parenchymal and intradermal injections of (99m)Tc-labelled human immunoglobulin G ( HIG ) and (111)In-HIG , respectively , 2 - 4h before axillary lymph node clearance surgery . All 228 freshly dissected nodes were assayed by well counting and examined for metastatic disease by haematoxylin/eosin staining and immuno-histochemistry . RESULTS Total nodal uptake following intradermal injection was 10 times more than after parenchymal injection . Tracer uptake within the first three draining nodes divided patients into three groups ; four ( group 1 ) had identical 1st , 2nd and 3rd echelon nodes , six ( group 2 ) had identical 1st and 2nd echelon nodes and five ( group 3 ) had different 1st echelon nodes . With respect to the first , second and third groups , there was close , moderate and poor correlation ( Pearson ) , respectively , between individual nodal counts accumulated from the two injection sites . Of eight patients with nodal disease , the SLN identified by intradermal and parenchymal injections contained disease in seven and four patients , respectively . CONCLUSIONS Comparison of nodal tracer distributions from the two injection planes allows a functional model to be developed with two possible routes of drainage from the parenchymal plane , one joining the tract from the areolar plexus and the other passing independently to the axilla which builds upon Sappey 's original anatomical model . This may explain the variable uptake , discordance and false negative SLN identification BACKGROUND Sentinel lymph node ( SLN ) biopsy is fast becoming the st and ard for testing lymph node involvement in many institutions . However , questions remain as to the best method of injection . The authors hypothesized that a subareolar injection of material would drain to the same lymph node as a peritumoral injection , regardless of the location of the tumor . METHODS To test this theory , 68 patients with 69 operable invasive breast carcinomas and clinical ly node-negative disease were enrolled in this single-institution Institutional Review Board-approved trial . Patients were injected with 1.0 mCi of technetium-99 sulfur colloid ( unfiltered ) in the subareolar area of the tumor-bearing breast . Each patient received an injection of 2 to 5 cc of isosulfan blue around the tumor . Radioactive SLNs were identified using a h and -held gamma detector probe . RESULTS The average age of patients entered into this trial was 55.2 + /- 13.4 years . The average size of the tumors was 1.48 + /- 1.0 cm . Thirty-two percent of the patients had undergone previous excisional breast biopsies . Of the 69 lesions , 62 ( 89.9 % ) had SLNs located with the blue dye and 65 ( 94.2 % ) with the technetium . In four patients , the SLN was not located with either method . All blue SLNs were also radioactive . All located SLNs were in the axilla . Of the 62 patients in which the SLNs were located with both methods , an average of 1.5 + /- 0.7 SLNs were found per patient , of which 23.2 % had metastatic disease . All four patients in which no SLN was located with either method had undergone prior excisional biopsies . CONCLUSIONS The results of this study suggest that subareolar injection of technetium is as accurate as peritumoral injection of blue dye . Central injection is easy and avoids the necessity for image-guided injection of nonpalpable breast lesions . Finally , subareolar injection of technetium avoids the problem of overlap of the radioactive zone of diffusion of the injection site with the radioactive sentinel lymph node , particularly in medial and upper outer quadrant lesions UNLABELLED AIM of this study was to determine whether the sentinel lymph nodes ( SLNs ) can be accurately identified in breast cancer patients with intradermal injection of the radiotracer above the primary tumour in comparison to peritumoural injection . METHODS In 45 women with breast cancer we performed lymphoscintigraphy on two separate days . We injected Tc-99 m nanocolloid on the first day peritumourally , and on a separate day intradermally . The results of both investigations using different injection sites were compared in order to determine the number and location of SLNs . RESULTS The SLN identification rate using peritumoural injection was 71 % ( 32 of 45 patients ) and 96 % ( 43 out of 45 patients ) using intradermal injection . In 62 % ( 28 of 45 patients ) the number and location of the SLNs were identical . In 97 % ( 31 of 32 patients ) in whom a SLN was detected using peritumoural injection , the same SLNs reappeared with intradermal injection . There were no false negative findings with the peritumoural administration of tracer whereas the intradermal administration approach result ed in a false negative rate of 13 % . CONCLUSION In women with breast cancer the reproducibility of lymphoscintigraphy using peritumoural and intradermal injection sites was 62 % . The intradermal injection modality enables the detection of a SLN in patients where the peritumoural injection failed but it has the disadvantage of a higher false negative rate in comparison to the peritumoural injection technique BACKGROUND Numerous techniques and material s show accuracy in localizing the sentinel lymph node ( SLN ) . We hypothesized that subareolar injection of material would localize the SLN as effectively as peritumoral injection . METHODS Thirty-eight patients were injected with technetium-99 sulfur colloid either peritumorally or subareolarly in addition to the injection of blue dye around the tumor . Radioactive SLNs were localized using a h and -held gamma probe . RESULTS Nineteen patients were included in each of the two groups , peritumoral and subareolar . SLNs were found in all patients injected subareolarly and in 18 of 19 injected peritumorally . The false-negative rate was 20 % for peritumoral injection and 0 % for subareolar injection . CONCLUSION The results suggest that subareolar injection was as accurate , if not more accurate , than peritumoral injection for localizing the SLN . This technique is simpler than peritumoral injection and does not require injection under image guidance for nonpalpable lesions |
822 | 28,177,886 | TACE-S with PVTT had better outcomes in the first-order portal vein branch and lower-order portal vein branches than in the main portal vein and upper branches to superior mesenteric vein .
CONCLUSIONS TACE-S may improve OS , ORR , TTP and DCR for HCC patients with PVTT compared to TACE | BACKGROUND The benefits of transarterial chemoembolization plus sorafenib ( TACE-S ) in hepatocellular carcinoma ( HCC ) with portal vein tumor thrombus ( PVTT ) remain controversial .
We compared the effectiveness and safety of TACE-S and TACE for HCC with PVTT . | PURPOSE This phase II study of sorafenib , an oral multikinase inhibitor that targets Raf kinase and receptor tyrosine kinases , assessed efficacy , toxicity , pharmacokinetics , and biomarkers in advanced hepatocellular carcinoma ( HCC ) patients . METHODS Patients with inoperable HCC , no prior systemic treatment , and Child-Pugh ( CP ) A or B , received continuous , oral sorafenib 400 mg bid in 4-week cycles . Tumor response was assessed every two cycles using modified WHO criteria . Sorafenib pharmacokinetics were measured in plasma sample s. Biomarker analysis included phosphorylated extracellular signal regulated kinase ( pERK ) in pretreatment biopsies ( immunohistochemistry ) and blood-cell RNA expression patterns in selected patients . RESULTS Of 137 patients treated ( male , 71 % ; median age , 69 years ) , 72 % had CP A , and 28 % had CP B. On the basis of independent assessment , three ( 2.2 % ) patients achieved a partial response , eight ( 5.8 % ) had a minor response , and 46 ( 33.6 % ) had stable disease for at least 16 weeks . Investigator-assessed median time to progression ( TTP ) was 4.2 months , and median overall survival was 9.2 months . Grade 3/4 drug-related toxicities included fatigue ( 9.5 % ) , diarrhea ( 8.0 % ) , and h and -foot skin reaction ( 5.1 % ) . There were no significant pharmacokinetic differences between CP A and B patients . Pretreatment tumor pERK levels correlated with TTP . A panel of 18 expressed genes was identified that distinguished " nonprogressors " from " progressors " with an estimated 100 % accuracy . CONCLUSION Although single-agent sorafenib has modest efficacy in HCC , the manageable toxicity and mechanisms of action support a role for combination regimens with other anticancer agents BACKGROUND Assessment of the change in tumour burden is an important feature of the clinical evaluation of cancer therapeutics : both tumour shrinkage ( objective response ) and disease progression are useful endpoints in clinical trials . Since RECIST was published in 2000 , many investigators , cooperative groups , industry and government authorities have adopted these criteria in the assessment of treatment outcomes . However , a number of questions and issues have arisen which have led to the development of a revised RECIST guideline ( version 1.1 ) . Evidence for changes , summarised in separate papers in this special issue , has come from assessment of a large data warehouse ( > 6500 patients ) , simulation studies and literature review s. HIGHLIGHTS OF REVISED RECIST 1.1 : Major changes include : Number of lesions to be assessed : based on evidence from numerous trial data bases merged into a data warehouse for analysis purpose s , the number of lesions required to assess tumour burden for response determination has been reduced from a maximum of 10 to a maximum of five total ( and from five to two per organ , maximum ) . Assessment of pathological lymph nodes is now incorporated : nodes with a short axis of 15 mm are considered measurable and assessable as target lesions . The short axis measurement should be included in the sum of lesions in calculation of tumour response . Nodes that shrink to < 10 mm short axis are considered normal . Confirmation of response is required for trials with response primary endpoint but is no longer required in r and omised studies since the control arm serves as appropriate means of interpretation of data . Disease progression is clarified in several aspects : in addition to the previous definition of progression in target disease of 20 % increase in sum , a 5 mm absolute increase is now required as well to guard against over calling PD when the total sum is very small . Furthermore , there is guidance offered on what constitutes ' unequivocal progression ' of non-measurable/non-target disease , a source of confusion in the original RECIST guideline . Finally , a section on detection of new lesions , including the interpretation of FDG-PET scan assessment is included . Imaging guidance : the revised RECIST includes a new imaging appendix with up date d recommendations on the optimal anatomical assessment of lesions . FUTURE WORK A key question considered by the RECIST Working Group in developing RECIST 1.1 was whether it was appropriate to move from anatomic unidimensional assessment of tumour burden to either volumetric anatomical assessment or to functional assessment with PET or MRI . It was concluded that , at present , there is not sufficient st and ardisation or evidence to ab and on anatomical assessment of tumour burden . The only exception to this is in the use of FDG-PET imaging as an adjunct to determination of progression . As is detailed in the final paper in this special issue , the use of these promising newer approaches requires appropriate clinical validation studies Objectives The aim of this single , r and omized study was to explore the efficacy of postoperative transarterial chemoembolization ( TACE ) and portal vein chemotherapy ( PVC ) for patients with hepatocellular carcinoma ( HCC ) complicated by portal vein tumor thrombosis ( PVTT ) and to evaluate prognostic factors . Methods The study cohort consisted of 112 patients with HCC and PVTT r and omly divided into three groups : Group A ( 37 patients ) , operation only ; Group B ( 35 patients ) , operation plus TACE ; Group C ( 40 patients ) , operation plus TACE and PVC . Disease-free survival rates and prognostic factors were analyzed . Results Most of the side effects and complications were related to the operation , catheters , and local chemotherapy and included liver decompensation ( 15.0 % ) , catheter obstruction ( 11.6 % ) , and nausea and loss of appetite ( 22.1 % ) . The disease-free survival curve was significantly different among the three groups , as estimated by the Kaplan-Meier method ( both P < 0.05 ) . Group C showed a significantly higher disease-free survival rate than Group A ( P < 0.05 ) , but no statistical differences were found between group A and group B , and group B and group C ( both P > 0.05 ) . Tumor size , tumor number , PVTT location , and treatment modalities were independent prognostic factors ( P < 0.05 ) . Conclusion Postoperative TACE combined with PVC may benefit the survival of patients with HCC complicated by PVTT in the short-term ( less than 60 months ) , but long-term efficacy is not yet certain and needs to be confirmed by further studies Sorafenib , an oral multikinase inhibitor , shows efficacy in renal cell and hepatocellular carcinoma ( HCC ) and is well tolerated when combined with doxorubicin in other solid tumours . Eighteen patients with inoperable HCC received doxorubicin 60 mg/m(2 ) IV for up to six 3-week cycles . Sorafenib 400 mg bid was administered continuously starting day 4 . Patients discontinuing doxorubicin were eligible for sorafenib monotherapy . The most frequent grade 3 - 4 drug-related adverse events were neutropaenia ( 61 % ) , leukopaenia ( 45 % ) and diarrhoea ( 17 % , grade 3 ) . Seven of eight patients who completed six cycles of doxorubicin continued treatment with sorafenib for at least 3 months . Doxorubicin moderately increased AUC ( 21 % ) and C(max ) ( 33 % ) when administered with sorafenib . The disease control rate for 16 evaluable patients was 69 % . Sorafenib plus doxorubicin appears to be well tolerated and more effective in the treatment of HCC than doxorubicin alone . Follow-up with single-agent sorafenib in these patients also appears to be well tolerated Purpose The BCLC staging classification has been widely endorsed to predict the prognosis of patients with HCC . However , its validity as a means of therapeutic instructions needs to be challenged . This study aim ed to evaluate perioperative and long-term outcomes of surgical resection in patients with advanced hepatocellular carcinoma ( HCC ) according to the Barcelona Clinic Liver Cancer ( BCLC ) staging . Methods This study used a prospect ively maintained data base consisting of a consecutive series of 511 Chinese patients with advanced HCC who underwent surgical resection in a hepatobiliary surgical center from 2001 to 2007 . Mortality , morbidity , long-term overall survival ( OS ) and disease-free survival ( DFS ) were evaluated . Results Hospital mortality was 2.3 % , and overall morbidity was 31.3 % . After a median follow-up period of 27.8 months ( range , 0–112 months ) , the 1- , 3- and 5-year OS rate was 69.9 , 41.2 and 30.5 % , and the 1- , 3- and 5-year DFS rate was 48.2 , 30.3 and 24.0 % , respectively . The 1- , 3- and 5-year OS and DFS rates were significantly poorer in patients with vascular invasion and /or extrahepatic spread than those in patients without ( both P < 0.001 ) , and also poorer in patients with biliary invasion than those in patients without ( both P < 0.05 ) . Conclusions Surgical resection could be considered in part of patients with advanced HCC ( BCLC stage C ) , with low mortality , acceptable morbidity and favorable survival benefits . These results imply that BCLC recommendations for treatment schedules of advanced HCC need to be re-evaluated PURPOSE To determine the safety and efficacy of transarterial chemoembolization ( TACE ) combined with sorafenib ( hereafter , TACE-sorafenib ) in patients with hepatocellular carcinoma ( HCC ) and portal vein tumor thrombus ( PVTT ) . MATERIAL S AND METHODS This study was approved by the institutional review board , and the requirement for informed consent was waived . The medical records of consecutive patients with HCC and PVTT who underwent TACE-sorafenib or TACE alone from January 2010 to December 2012 were retrospectively evaluated . Sorafenib ( 400 mg ) was administered twice daily . Outcomes of patients who underwent TACE-sorafenib were compared with outcomes of patients who underwent TACE by using the Kaplan-Meier method according to types of PVTT : PVTT in the main portal vein ( type A ) , PVTT in the first-order portal vein branch ( type B ) , and PVTT in second- or lower-order portal vein branches ( type C ) . RESULTS Ninety-one patients were included in the analysis ; 46 patients underwent TACE-sorafenib and 45 underwent TACE . TACE-sorafenib showed significant survival benefits compared with TACE in patients with type B ( median survival , 13 months vs 6 months ; P = .002 ) or type C ( median survival , 15 months vs 10 months ; P = .003 ) PVTT . TACE-sorafenib and main PVTT were the independent prognostic factors for survival at uni- and multivariate analysis . Liver function after TACE-sorafenib worsened only in patients with main PVTT . Sorafenib-related adverse events of grade 3 or higher occurred in 16 patients ( 35 % ) . CONCLUSION TACE-sorafenib side effects were acceptable , and this treatment may improve overall survival in patients with HCC with first-order or lower-branch PVTT when compared with patients who underwent TACE alone BACKGROUND The survival benefit of combining sorafenib and transarterial chemoembolization ( TACE ) therapy compared with sorafenib monotherapy for patients with advanced hepatocellular carcinoma ( HCC ) and main portal vein tumor thrombosis ( MPVTT ) is unclear . METHODS Between January 2009 and June 2013 , 183 consecutive patients with advanced HCC ( Barcelona Clinic Liver Cancer stage C ) and MPVTT were retrospectively review ed . Of these , 89 patients with advanced HCC and MPVTT were enrolled in this study : 45 were treated with combination therapy ( sorafenib-TACE group ) , and the other 44 treated with sorafenib monotherapy ( sorafenib group ) . RESULTS The mean number of TACE sessions per patient was 2.6 ( range : 1 - 5 ) . The median duration of sorafenib in the sorafenib-TACE group and sorafenib group was 5.6 months and 5.4 months , respectively . The disease control rate was similar between the two groups . Median time to progression was 3.0 months ( 95 % confidence interval [ CI ] : 2.2 , 3.7 ) in the sorafenib-TACE group , and 3.0 months ( 95 % CI : 2.1 , 3.8 ) in the sorafenib group ( p = .924 ) . Median overall survival was 7.0 months ( 95 % CI : 6.1 , 7.8 ) and 6.0 months ( 95 % CI : 4.7 , 7.3 ) in the sorafenib-TACE group and the sorafenib group , respectively ( p = .544 ) . The adverse events related to sorafenib were comparable between the two groups . Twenty-one adverse events of grade 3 - 4 related to TACE occurred in 12 patients ( 26.7 % ) , and 2 of them died ( 4.4 % ) . CONCLUSION This study demonstrated no advantage of combination therapy over sorafenib monotherapy . Considering the patients ' morbidity after TACE , sorafenib monotherapy is appropriate for managing patients with advanced HCC and MPVTT |
823 | 12,804,474 | REVIEW ER 'S CONCLUSIONS Acupuncture and hypnosis may be beneficial for the management of pain during labour . | BACKGROUND Many women would like to avoid pharmacological or invasive methods of pain management in labour and this may contribute towards the popularity of complementary methods of pain management .
This review examined currently available evidence supporting the use of alternative and complementary therapies for pain management in labour .
OBJECTIVES To examine the effectiveness of complementary and alternative therapies for pain management in labour on maternal and perinatal morbidity . | Matched groups of primigravid women received one of three antenatal training programmes : normal antenatal classes , normal classes plus electromyography biofeedback relaxation training , or normal classes plus skin-conductance biofeedback relaxation training . Myographic training was found to be effective within conventional antenatal constraints , whereas skin-conductance training was not . The women reported use of biofeedback training and related skills to be of some benefit during early labour . However , no difference between effectively trained electromyographic , ineffectively trained skin-conductance and control groups was found on labour and delivery performance measures Two studies were conducted to examine the effects of music on analogued labor pain using volunteer nulliparous subjects who were r and omly assigned to treatment groups ( n = 10 per group ) . Assessment s of the treatments were made in a 1-hour session involving twenty 80-second exposures to a laboratory pain stimulus patterned to resemble labor contractions . In the first experiment , it was hypothesized that subjects listening to easy-listening music would report lower pain ratings and cardiovascular responses than subjects listening to rock music , self-selected music , or a dissertation ( placebo-attention ) and subjects in a no-treatment control group . No significant group effects were found ; significant time effects were found for heart rate , systolic and diastolic blood pressure . Subjects spontaneously reported using imagery as a pain reduction technique . In the second study a combination of music and imagery was examined by r and omly assigning subjects to one of five groups : self-generated imagery with music ( SIM ) , guided imagery with music ( GIM ) , self-generated imagery without music ( SI ) , guided imagery without music ( GI ) , or no-treatment control . Again , no significant group effects were obtained . Significant time effects were obtained for heart rate , systolic and diastolic blood pressure British physician , Dr. Grantly Dick-Read , was the first to suggest the “ fear-tension-pain ” cycle in his work Natural Childbirth ( 1933 ) . As a result of his underst and ing of how this cycle affected birthing , he recommended women prepare for childbirth . Research studies from around the world have shown that the use of hypnosis for childbirth results in : ∗ shorter labors ∗ reduced use of pain medication ∗ higher Apgar scores ∗ reduced cesarean and forceps A study of the effects of biofeedback on the pain of childbirth was conducted . Forty primigravidae were r and omly assigned to either an experimental group or a control group . The experimental group was given a series of training sessions in biofeedback and used biofeedback equipment during labor . All subjects were monitored during the labor and delivery period for their reports of pain using a visual analogue scale ( VAS ) and a verbal descriptor scale ( VDS ) . Results showed that women using biofeedback during childbirth reported significantly lower pain : from admission to labor and delivery ( p less than 0.05:VDS ; p less than 0.01:VAS ) , at delivery ( p less than 0.005:VDS ) , and 24-hr postpartum ( p less than 0.01:VDS ) . Also , women in the biofeedback group labored an average of 2 hr less and used 30 % fewer medications . The results of this study suggest that EMG biofeedback may be effective in reducing levels of acute pain experienced by childbearing women CONTEXT A prior national survey documented the high prevalence and costs of alternative medicine use in the United States in 1990 . OBJECTIVE To document trends in alternative medicine use in the United States between 1990 and 1997 . DESIGN Nationally representative r and om household telephone surveys using comparable key questions were conducted in 1991 and 1997 measuring utilization in 1990 and 1997 , respectively . PARTICIPANTS A total of 1539 adults in 1991 and 2055 in 1997 . MAIN OUTCOMES MEASURES Prevalence , estimated costs , and disclosure of alternative therapies to physicians . RESULTS Use of at least 1 of 16 alternative therapies during the previous year increased from 33.8 % in 1990 to 42.1 % in 1997 ( P < or = .001 ) . The therapies increasing the most included herbal medicine , massage , megavitamins , self-help groups , folk remedies , energy healing , and homeopathy . The probability of users visiting an alternative medicine practitioner increased from 36.3 % to 46.3 % ( P = .002 ) . In both surveys alternative therapies were used most frequently for chronic conditions , including back problems , anxiety , depression , and headaches . There was no significant change in disclosure rates between the 2 survey years ; 39.8 % of alternative therapies were disclosed to physicians in 1990 vs 38.5 % in 1997 . The percentage of users paying entirely out-of-pocket for services provided by alternative medicine practitioners did not change significantly between 1990 ( 64.0 % ) and 1997 ( 58.3 % ) ( P=.36 ) . Extrapolations to the US population suggest a 47.3 % increase in total visits to alternative medicine practitioners , from 427 million in 1990 to 629 million in 1997 , thereby exceeding total visits to all US primary care physicians . An estimated 15 million adults in 1997 took prescription medications concurrently with herbal remedies and /or high-dose vitamins ( 18.4 % of all prescription users ) . Estimated expenditures for alternative medicine professional services increased 45.2 % between 1990 and 1997 and were conservatively estimated at $ 21.2 billion in 1997 , with at least $ 12.2 billion paid out-of-pocket . This exceeds the 1997 out-of-pocket expenditures for all US hospitalizations . Total 1997 out-of-pocket expenditures relating to alternative therapies were conservatively estimated at $ 27.0 billion , which is comparable with the projected 1997 out-of-pocket expenditures for all US physician services . CONCLUSIONS Alternative medicine use and expenditures increased substantially between 1990 and 1997 , attributable primarily to an increase in the proportion of the population seeking alternative therapies , rather than increased visits per patient Objective To investigate acupuncture treatment during labour with regard to pain intensity , degree of relaxation and outcome of the delivery Objective To evaluate the effectiveness of acupuncture as an analgesic during labor . Design A r and omized , unblinded , controlled study . Setting A labor ward in a University Hospital . Patients Parturients at term . Interventions One group received acupuncture ( N = 106 ) ; another did not ( N = 92 ) . A second control group ( N = 92 ) , drawn from the labor ward protocol , consisted of patients who met the eligibility criteria for the study and were matched to the “ no acupuncture ” group by parity , but who had not been offered the opportunity to take part . Outcome measure “ effectiveness of acupuncture ” was measured by the requirement for use of meperidine . Results Meperidine was given to 11 % of the acupuncture group , 37 % of the no acupuncture group ( P < 0.0001 ) , and 29 % of the control group . The use of other analgesics was also lower in the acupuncture group . Patient satisfaction was high : 89 of 103 patients asked said they would want acupuncture during another labor . Conclusions Acupuncture during labor reduced the requirement for other painkillers and has high patient satisfaction in this r and omized , unblinded , controlled study The benefits of hypnotic analgesia as an adjunct to childbirth education were studied in 60 nulliparous women . Subjects were divided into high and low hypnotic susceptibility groups before receiving 6 sessions of childbirth education and skill mastery using an ischemic pain task . Half of the Ss in each group received a hypnotic induction at the beginning of each session ; the remaining control Ss received relaxation and breathing exercises typically used in childbirth education . Both hypnotic Ss and highly susceptible Ss reported reduced pain . Hypnotically prepared births had shorter Stage 1 labors , less medication , higher Apgar scores , and more frequent spontaneous deliveries than control Ss ' births . Highly susceptible , hypnotically treated women had lower depression scores after birth than women in the other 3 groups . We propose that repeated skill mastery facilitated the effectiveness of hypnosis in our study OBJECTIVE To determine the effect of breathing techniques and nurse-administered massage on the pain perception of pregnant woman during labour . SETTING AND PARTICIPANTS The present study was conducted among pregnant women ( 75 % primiparous ) admitted to the SSK Bakirkoy Women and Children 's Hospital ( Istanbul , Turkey ) between January 1 , and September 1 , 2000 . The patients were in their 38th to 42nd week of pregnancy , not at high risk and expected to have normal vaginal delivery . They were selected from volunteers by nonr and om sampling . STUDY DESIGN The present study involved 40 cases , with 20 in the experimental group and 20 in the control group . Data were obtained through the visual analogue scale , inspection form , observation form and postnatal interview form . The study investigators provided information about labour , breathing techniques and massage to the pregnant women assigned to the experimental group at the beginning of labour ( latent phase ) . A study investigator also accompanied them during labour . These women received nurse-administered massage and were encouraged to breathe and perform self-administered massage . They were also instructed to change their positions and to relax . RESULTS AND CONCLUSION Study results demonstrated that nursing support and patient-directed education concerning labour and nonpharmacological pain control methods ( eg , breathing and cutaneous stimulation techniques ) were effective in reducing the perception of pain by pregnant women ( when provided in the latent labour phase before delivery ) , leading to a more satisfactory birth experience Acupuncture treatment and control group interventions in parallel-group r and omised trials of acupuncture are not always precisely reported . In an attempt to improve st and ards , an international group of experienced acupuncturists and research ers devised a set of recommendations , design ating them STRICTA : ST and ards for Reporting Interventions in Controlled Trials of Acupuncture . In a further consensus-building round , the editors of several journals helped redraft the recommendations . These follow the Consoli date d St and ards for Reporting Trials ( CONSORT ) format , acting as an extension of the CONSORT guidelines for the specific requirements of acupuncture studies . Participating journal editors are publishing the STRICTA recommendations and requesting prospect i ve authors to adhere to them when preparing reports for publication . Other journals are invited to adopt these recommendations . The intended outcome is that interventions in controlled trials of acupuncture will be more adequately reported , thereby facilitating an improvement in critical appraisal , analysis and replication of trials Labor pain is often severe , and analgesic medication may not be indicated . In this r and omized controlled trial we examined the effects of music on sensation and distress of pain in Thai primiparous women during the active phase of labor . The gate control theory of pain was the theoretical framework for this study . R and omization with a computerized minimization program was used to assign women to a music group ( n = 55 ) or a control group ( n = 55 ) . Women in the intervention group listened to soft music without lyrics for 3 hours starting early in the active phase of labor . Dual visual analog scales were used to measure sensation and distress of pain before starting the study and at three hourly posttests . While controlling for pretest scores , one-way repeated measures analysis of covariance indicated that those in the music group had significantly less sensation and distress of pain than did the control group ( F ( 1 , 107 ) = 18.69 , p < .001 , effect size = .15 , and F ( 1 , 107 ) = 14.87 , p < .001 , effect size = .12 ) , respectively . Sensation and distress significantly increased across the 3 hours in both groups ( p < .001 ) , except for distress in the music group during the first hour . Distress was significantly lower than sensation in both groups ( p < .05 ) . In this controlled study , music -- a mild to moderate strength intervention -- consistently provided significant relief of severe pain across 3 hours of labor and delayed the increase of affective pain for 1 hour . Nurses can provide soft music to laboring women for greater pain relief during the active phase when contractions are strong and women suffer OBJECTIVE The purpose of this study was to evaluate the effects of SP6 acupressure on labor pain and delivery time in women in labor . DESIGN R and omized clinical trial . SETTING /LOCATION Delivery room in a university hospital . PARTICIPANTS Seventy-five ( 75 ) women in labor were r and omly assigned to either the SP6 acupressure ( n = 36 ) or SP6 touch control ( n = 39 ) group . The participants were matched according to parity , cervical dilation , labor stage , rupture of amniotic membrane , and husb and 's presence during labor . There were no additional oxytocin augmentation or administration of analgesics during the study period . INTERVENTION The 30-minute acupressure or touch on SP6 acupoint was performed . OUTCOME MEASURES Labor pain was measured four times using a structured question naire , a subjective labor pain scale ( visual-analogue scale [ VAS ] ) : before intervention , immediately after the intervention , and 30 and 60 minutes after the intervention . Length of delivery time was calculated in two stages : from 3 cm cervical dilation to full cervical dilatation , and full cervical dilatation to the delivery . RESULTS There were significant differences between the groups in subjective labor pain scores at all time points following the intervention : immediately after the intervention ( p = 0.012 ) ; 30 minutes after the intervention ( p = 0.021 ) ; and 60 minutes after the intervention ( p = 0.012 ) . The total labor time ( 3 cm dilatation to delivery ) was significantly shorter in the SP6 acupressure intervention group than in the control group ( p = 0.006 ) . CONCLUSIONS These findings showed that SP6 acupressure was effective for decreasing labor pain and shortening the length of delivery time . SP6 acupressure can be an effective nursing management for women in labor BACKGROUND There are few studies on acupuncture in childbirth despite the generally established analgesic effect of acupuncture treatment . METHODS The analgesic effect of acupuncture during childbirth was assessed by comparing the need for other pain treatments ( epidural analgesia using bupivacaine , pudendal nerve block , intramuscular meperidine , nitrous oxide/oxygen , intracutaneous sterile water injections ) in 90 women given acupuncture ( acupuncture group ) with that in 90 women not given acupuncture ( control group ) . RESULTS 52 women ( 58 % ) in the acupuncture group and 13 ( 14 % ) in the control group managed their deliveries without further pain treatment ( p < 0.001 ) . The groups were similar with respect to age , pariety , duration of delivery , use of oxytocine and incidence of Caesarean section . Acupuncture treatment was found to have no major side effects , and 85 women ( 94 % ) given acupuncture reported that they would reconsider acupuncture in future deliveries . CONCLUSION Acupuncture reduces the need for other methods of analgesia in childbirth Background . To assess if acupuncture could be a reasonable option for pain relief in labor and to look at possible effects of acupuncture on the progress of labor Acupressure is said to promote the circulation of blood and qi , the harmony of yin and yang , and the secretion of neurotransmitters , thus maintaining the normal functions of the human body and providing comfort . However , there has been little research -based evidence to support the positive effects of acupressure in the area of obstetric nursing . The purpose of this study is to determine the effect of LI4 and BL67 acupressure on labor pain and uterine contractions during the first stage of labor . An experimental study with a pretest and posttest control group design was utilized . A total of 127 parturient women were r and omly assigned to three groups . Each group received only one of the following treatments , LI4 and BL67 acupressure , light skin stroking , or no treatment/conversation only . Data collected from the VAS and external fetal monitoring strips were used for analysis . Findings indicated that there was a significant difference in decreased labor pain during the active phase of the first stage of labor among the three groups . There was no significant difference in effectiveness of uterine contractions during the first stage of labor among the three groups . Results of the study confirmed the effect of LI4 and BL67 acupressure in lessening labor pain during the active phase of the first stage of labor . There were no verified effects on uterine contractions Abstract Prior research by the author showed that psychosocial factors distinguished complicated from uncomplicated birth outcome . The purpose of this study was to determine if prenatal hypnosis could facilitate uncomplicated birth . Following a psychosocial assessment , 520 pregnant women in their first or second trimester of pregnancy were r and omized to receiving prenatal hypnosis or attention-only groups . The author provided all of the hypnosis in a manner similar to that taught by David Cheek . The goal was to reduce fear of birth and parenthood ; to reduce anxiety ; to reduce stress ; to identify specific fears that might complicate the labor process ( addressing them whenever possible ) ; and to prepare women for the experience of labor . The attention-only group was matched to a no-contact comparison group . Women receiving prenatal hypnosis had significantly better outcomes than women who did not . Further assessment suggested that hypnosis worked by preventing negative emotional factors from leading to an complicated birth outcome . Attention only was associated with minimal differences in outcome over the no-contact group . The routine prenatal use of hypnosis could improve obstetric outcome Comparaison de 29 primipares preparees avec un entrainement d'auto-hypnose et 36 preparees de facon traditionnelle . Les result ats indiquent que l'hypnose n'est pas significativement efficace en tant que method e d'analgesie , qu'elle donne cependant une amelioration de l'experience de l'accouchement , et qu'elle est peut-etre une cause de prolongement de la Twenty-eight women were recruited from prenatal classes and r and omly assigned to receive massage in addition to coaching in breathing from their partners during labor , or to receive coaching in breathing alone ( a technique learned during prenatal classes ) . The massaged mothers reported a decrease in depressed mood , anxiety and pain , and showed less agitated activity and anxiety and more positive affect following the first massage during labor . In addition , the massaged mothers had significantly shorter labors , a shorter hospital stay and less postpartum depression AIMS To investigate the effects of massage on pain reaction and anxiety during labour . BACKGROUND Labour pain is a challenging issue for nurses design ing intervention protocol s. Massage is an ancient technique that has been widely employed during labour , however , relatively little study has been undertaken examining the effects of massage on women in labour . METHODS A r and omized controlled study was conducted between September 1999 and January 2000 . Sixty primiparous women expected to have a normal childbirth at a regional hospital in southern Taiwan were r and omly assigned to either the experimental ( n=30 ) or the control ( n=30 ) group . The experimental group received massage intervention whereas the control group did not . The nurse-rated present behavioural intensity ( PBI ) was used as a measure of labour pain . Anxiety was measured with the visual analogue scale for anxiety ( VASA ) . The intensity of pain and anxiety between the two groups was compared in the latent phase ( cervix dilated 3 - 4 cm ) , active phase ( 5 - 7 cm ) and transitional phase ( 8 - 10 cm ) . RESULTS In both groups , there was a relatively steady increase in pain intensity and anxiety level as labour progressed . A t-test demonstrated that the experimental group had significantly lower pain reactions in the latent , active and transitional phases . Anxiety levels were only significantly different between the two groups in the latent phase . Twenty-six of the 30 ( 87 % ) experimental group subjects reported that massage was helpful , providing pain relief and psychological support during labour . CONCLUSIONS Findings suggest that massage is a cost-effective nursing intervention that can decrease pain and anxiety during labour , and partners ' participation in massage can positively influence the quality of women 's birth experiences The addition of self-selected music as a conditioning aid during prepared childbirth education and subsequent family performance in labor within a musical environment were examined . Thirty primigravida couples received the same psychoprophylactic instruction , with 15 r and omly selected couples receiving the added musical conditioning aid . Medication use remained minimal , without significant difference , for couples who did and couples who did not use music . However , the value of music to both the family and the health care staff is felt to be of enough subjective significance to warrant its use as a normal component of prepared childbirth education The purpose s of this study were to determine factors affecting the use of music by women during childbirth and to compare the frequency of actual music use during childbirth by women who heard music during prenatal labor rehearsal vs those who did not hear music in rehearsal . Fifty-four women attending Lamaze childbirth classes were r and omly assigned to music-rehearsal or nonmusic-rehearsal groups . After delivery , all subjects completed question naires about music use and subjective responses to music . Eleven factors involved in determination of actual music use were identified . No significant differences in music use by rehearsal group assignment were found . Results demonstrate that music provides an adjunct to childbirth that is highly desirable for some women , while unappealing or inconvenient for others . Suggestions for utilization of findings by maternity care providers are presented |
824 | 27,542,586 | Active and passive exposure to smoke are associated with increased AD prevalence | BACKGROUND Tobacco exposure might be a modifiable risk factor for atopic dermatitis ( AD ) .
OBJECTIVE We examine the association between AD and exposure to tobacco smoke . | BACKGROUND Atopic dermatitis ( AD ) often develops in infancy as the first manifestation of the atopic phenotype . Wheezing is also common in infancy , but it is less clear whether infant wheezing should be considered as an atopic phenotype . If infant wheeze and AD share a common aetiology , this would indicate that infant wheezing is an atopic phenotype . OBJECTIVE To investigate whether potential risk factors for infant wheeze and AD have similar effects on these 2 phenotypes , indicating a common etiology . METHODS A total of 34.793 mother-child pairs enrolled in the Danish National Birth Cohort were followed prospect ively . Information on wheezing episodes , AD , and prenatal , perinatal , and postnatal risk factors was collected by interview at 12 and 30 weeks of gestation , at 6 and 18 months of age , and by linkage to the Danish Medical Birth Register . Data were analyzed by binary and polytomous logistic regression models . RESULTS The following variables had significantly differential effects on infant wheezing and AD : parental hay fever , parental asthma , parental AD , sex , maternal age , maternal occupation , smoking during pregnancy , season of birth , birth weight , gestational age , head circumference , breast-feeding , number of older siblings , day care attendance , and pets in the home . CONCLUSION The majority of risk factors had differential effects on infant wheeze and AD indicative of a different etiology . Infant wheezing does not seem to be etiologically linked to the epidemic of atopic disease , and infant wheezing should not be used as an indicator of the atopic phenotype BACKGROUND AND METHODS Phase III of the International Study of Asthma and Allergies in Childhood ( ISAAC ) was conducted in eight Pacific countries , five of which ( Samoa , Fiji , Tokelau , French Polynesia and New Caledonia ) collected environmental question naire ( EQ ) data . We report the findings of the EQ analyses below . RESULTS The major factors associated with current wheeze were regular margarine consumption ( prevalence odds ratio [ POR ] 1.19 , 95%CI 1.01 - 1.40 ) , paracetamol use ( POR 1.35 , 95%CI 1.11 - 1.64 ) , electric cooking ( POR 1.42 , 95%CI 1.11 - 1.80 ) , regular exercise ( POR 1.44 , 95%CI 1.18 - 1.75 ) and maternal smoking ( POR 1.16 , 95%CI 1.01 - 1.33 ) . Protective factors included having older siblings ( two or more POR 0.69 , 95%CI 0.58 - 0.82 ; one POR 0.86 , 95%CI 0.71 - 1.05 ) , and being born in the country of the survey ( POR 0.74 , 95%CI 0.63 - 0.87 ) . Risk factors for rhinoconjunctivitis included regular consumption of meat , butter , margarine and nuts , regular exercise , regular television viewing , paracetamol use and passive smoking . Eczema was associated with regular meat , pasta and butter consumption , regular television viewing , paracetamol use and passive smoking . CONCLUSIONS Regular meat and margarine consumption , paracetamol use , electric cooking and passive smoking are risk factors for symptoms of asthma , rhinoconjunctivitis and eczema in the Pacific . However , most of these associations were weak , and account for only a small proportion of cases Background : Several cross‐sectional population ‐based studies have reported a negative association between smoking and allergic sensitization to aeroallergens . In a prospect i ve study , we investigated the association between smoking and the development ( incidence ) of allergic sensitization as reflected by skin prick test ( SPT ) positivity and specific IgE positivity The present study aim ed to investigate the prevalence of atopic dermatitis in primary schoolchildren in Denizli , Turkey , and to determine the possible risk factors for atopic dermatitis in home environment . A self-administered question naire was h and led to the parents of 2,100 children aged 7 to 15 years , from three r and omized primary schools and 1,644 ( 78.9 % ) completed and returned the question naire . The question naire included the United Kingdom Working Party diagnostic criteria and asked about conditions that could affect the course of atopic dermatitis . The prevalence of atopic dermatitis and coexisting factors that may affect the course of the disease were evaluated in 1,644 children ( 825 girls and 819 boys ) . The prevalence of atopic dermatitis was detected as 4.9 % . Passive smoking , heating systems either in the house or in the child 's bedroom , and the number of people living in the house had no significant effect ( p > 0.005 ) . The difference in prevalence of atopic dermatitis between developed and developing countries is striking . The determination of the factors that have an influence in this issue will probably enable us to change the course and frequency of atopic dermatitis |
825 | 22,287,821 | With regard to CI in elderly patients , the selected studies document an improvement of the quality of life and perceptive abilities after CI , even if the benefits were found to be inferior in patients over 70 years at the time of surgery .
Thus , from the results of the studies included in the review , advanced age is not a contraindication for the CI procedure .
With respect to unilateral CI , bilateral CI offers advantages in hearing in noise , in sound localization and less during hearing in a silent environment .
However , high interindividual variability is reported in terms of benefits from the second implant .
With regard to CI in prelingually deaf adults , the selected studies document benefits deriving from the CI procedure in terms of improvement of perceptive abilities and in the quality of life after CI , as well as subjectively perceived benefits . | SUMMARY The aim of this systematic review was to summarize the results of scientific publications on the clinical effectiveness of the cochlear implant ( CI ) procedure in adults . | Objective : Compare results of cochlear implantation in younger and older adults in the domains of disability and h and icap , as well as in tests of word recognition and localization , across unilateral implant ( CI ) , bilateral ( CI + CI ) , and CI with an acoustic hearing aid in the nonimplanted ear ( CI + HA ) . Design : Three parts : retrospective ( postimplant only ) analysis ; prospect i ve ( preimplant versus postimplant ) ; correlation between age and benefit from CI versus CI + CI . Two age groups , older and younger than 60 years , for the first 2 analyses ; age is a continuous variable for the third analysis . Setting : Tertiary referral hospital clinic . Patients : Postlingually severely-to-profoundly hearing-impaired adults : Totals of 68 CI , 36 CI + CI , and 38 CI + HA in the retrospective part of the study ; totals of 30 CI , 18 CI + CI , and 16 CI + HA in the prospect i ve parts . Numbers vary from these totals on individual measures . Interventions : Patients receive either 1 or 2 cochlear implants ; some with 1 CI opt to retain a hearing aid in the nonimplanted ear . Outcome Measures : Principal measures : Hearing H and icap Inventory for the Elderly , Hearing H and icap Question naire , Speech , Spatial and Qualities of Hearing Scale , word recognition test , and soundfield localization test . The study is exploratory , but proceeding from a null hypothesis of no expected contrast as a function of patient age . Results : All patient groups show significant benefit after implantation . No significant age-related differences are observed in patients with unilateral implant , nor in CI + HA group . In the CI + CI group , the younger cohort showed very substantial increases in both performance and self-rated abilities ; the older cohort provides more mixed outcomes . Conclusion : Results for the CI group confirm and extend earlier research . The result for the younger group of CI + CI patients demonstrates the consistent incremental benefit obtained from a bilateral procedure . The mixed outcome observed in the older CI + CI group might be due to individual differences in interaction between effects of aging and the ability to integrate binaural cues Objective : The purpose of the study was to investigate sound localization with bilateral and unilateral cochlear implants . Design : Sound localization tests were performed on 20 bilaterally implanted MED-EL COMBI 40/40 + users . All subjects were bilaterally implanted during adolescence or later . Sound localization was tested in the frontal horizontal plane by using 9 equally spaced loudspeakers and speech-shaped noise bursts at r and omized levels . Results : The group of subjects who were bilaterally deafened after 5 to 6 yr of age ( 18 subjects ) showed a statistically significant improvement in sound localization when using both implants , compared with when using only one . The mean deviation between the presentation azimuth and the response azimuth was 16.6 ° when using both implants , which was on average 37.1 ° smaller than when using one implant only . When adjusted for the localization error that was constant across loudspeakers , the mean deviation was 15.9 ° for bilateral implant use , representing an improvement of 30.1 ° over unilateral implant use . Statistical analysis showed that in this group , performance measures were not correlated with subject details such as age at onset of deafness or duration of unilateral implant use . In contrast , subjects who were bilaterally deafened before 6 yr of age ( 2 subjects ) did not show a benefit in sound localization from bilateral implants . Conclusions : Bilateral cochlear implants offer a substantial benefit in sound localization to late-deafened , late-implanted subjects . The very limited data from early-deafened subjects implanted at a later age could suggest that these subjects may not benefit in sound localization from bilateral cochlear implants . It is possible that early implantation for early deafened subjects might allow better acquisition of spatial hearing , thus leading to improved localization performance OBJECTIVES To evaluate sound and speech perception and quality of life in prelingually deafened adults implanted with state of the art devices . To investigate which patient factors influence postoperative performance . STUDY DESIGN Prospect i ve intervention study . METHODS Eight prelingually deafened subjects ( with onset of severe hearing impairment before the age of 4 years and functioning in an oral-aural setting ) participated in this study . Subjects were implanted at a mean age of 36 ( range , 21 - 55 ) years with a CII or 90 K cochlear implant ( Advanced Bionics Corp. ) . All subjects completed st and ard speech perception tests as well as quality of life measures ( Health Utility Index Mark-II , Nijmegen Cochlear Implant Question naire , visual analogue scale for subject 's hearing and health ) at different points in time . Postoperative scores were compared with each other and with the baseline preoperative scores . The relationship between nine patient variables and the postoperative consonant-vowel-consonant ( CVC ) phoneme score was also investigated . RESULTS Significant improvement was measured for CVC word and phoneme scores and several quality of life measures . Postoperative speech perception correlated with a new and promising factor named quality of a patient 's own speech production ( QoSP ) . CONCLUSION With state of the art implants , speech perception and quality of life do improve in prelingually deafened adults . More importantly , the prognostic value of QoSP should be investigated further Objective : Preliminary studies show that bilateral cochlear implantation improves speech-recognition ability in many subjects ; however , the magnitude of this improvement has been variable . The objective of our research was to explore means to better differentiate the binaural benefit that many patients who receive bilateral cochlear implants ( CIs ) describe . Hypothesis : Binaural improvements in speech-perception performance will be consistently evident across patients when they are tested in more challenging listening situations . Design : This was a prospect i ve clinical study . Speech-perception performance was compared between the unilateral and bilateral cochlear implant conditions . Because the purpose was to investigate testing parameters that would demonstrate binaural benefit , word- and sentence-recognition tests were administered under several stimulation conditions : with and without noise and at three presentation levels . In addition , all subjects completed the Abbreviated Profile of Hearing Aid Benefit as a measure of subjective benefit . Subjects were adult cochlear implant recipients . Three device manufacturers were represented ( Advanced Bionics Corporation , Cochlear Americas , and the Med-El Corporation ) ; three patients received simultaneous implantation , and the other four patients received sequential CIs . The setting was a comprehensive cochlear implant program/tertiary referral center . The main outcomes measures were speech-recognition scores in percent correct , mean score difference for unilateral versus bilateral conditions , and subjective benefit scores . Results : The most significant improvements in binaural cochlear implant use were found when subjects were tested with sentence material presented at 60 dB SPL with a + 8 dB signal-to-noise ratio . Six of seven subjects showed significant binaural improvement , with a mean improvement score of 12.43 % ( SD = 5.32 ) . All subjects preferred the binaural listening condition . Measured improvements in quality of life were seen . Conclusions : Preliminary study findings suggest that significant cochlear implant binaural benefit in speech perception may be observed when testing in more difficult listening situations ( i.e. , lower presentation levels and in noise ) . According to the outcome of our study , testing the binaural benefit of CIs requires consideration of suitable test material s and stimulation parameters OBJECTIVE To present the results of a survey administered to a group of early-deafened cochlear implants adults and to report the level of perceived benefit . DESIGN Prospect i ve . SETTING Large tertiary referral centre . METHOD A 47-item question naire design ed to evaluate cochlear implant use and benefit was sent to 42 early-deafened adult cochlear implant users . The question naire can be divided into seven subcategories : time of use , associated symptoms , communication , employment status and function , socialization , perceived benefit , and the impact on quality of life . Responses from 30 patients were received . RESULTS The majority of our patients use their cochlear implant all of their waking hours . The majority of patients continue to depend on lip-reading and hearing as their main mode of communication , although they reported improved lip-reading skills with their cochlear implant . Twenty-three patients ( 76.7 % ) were employed . Eleven patients had a change in employment subsequent to cochlear implantation , nine ( 81.8 % ) of whom attributed this to their cochlear implant . Our patients als reported greater independence , a greater sense of safety in their environment , and an improved social life . Twenty-nine patients ( 96.7 % ) said that they were satisfied with their implant , 28 ( 93.3 % ) said that they would go through the same process again , and 27 ( 90 % ) said that they would recommend it to a friend in a similar situation . Twenty-nine patients ( 96.7 % ) stated that the cochlear implant has had a positive effect on their quality of life . Family and peer support , prior auditory-verbal therapy , and a positive attitude were the most commonly cited factors in successful cochlear implant use . CONCLUSIONS Early-deafened adult cochlear implant users perceive significant benefit from cochlear implantation . Importantly , family and peer support , prior auditory-verbal therapy , and a positive attitude are considered important factors in maximizing this benefit Cochlear implants are indicated for elderly patients with severe-to-profound hearing loss ( sensorineural hearing loss ≥ 70 dB ) . Their use has been limited , possibly by the misconception that elderly patients will perform poorly . To document the performance of older adults ( ≥65 years old ) , we undertook a retrospective analysis of our postlingually deafened adult patients who underwent implantation with the CLARION Multi- Strategy Cochlear Implant and underwent formal audiologic analysis ( sentence recognition [ Central Institute for the Deaf , CID ] and monosyllabic word recognition [ consonant-noun-consonant , CNC ] ) . Both younger ( n = 20 ; mean age = 46.9 years ) and older ( n = 16 ; mean age = 71.5 years ) adults showed statistically significant increases in CID and CNC scores after cochlear implantation . No statistically significant difference could be detected in operative time , anesthesia time , length of hospitalization , or CID or CNC scores between the two age groups . We conclude that age should not be a criterion for deciding who should receive cochlear implants . ( Otolaryngol Head Neck Surg 2000;123:419 - 24 . Objective : The purpose of this 4-year longitudinal study was to assess the stability of the binaural benefits of head shadow , summation , and squelch for bilateral cochlear implant recipients and to quantify these benefits for the underst and ing of speech in noise . Design : This is a prospect i ve study of 9 patients who received simultaneous bilateral insertion of MED-EL COMBI + 40 cochlear implants in a single-stage operation at the University of North Carolina , Chapel Hill , NC . Each patient had postlingual deafness of short duration before insertion of the device . Each year , the patients were tested for word recognition using consonant-nucleus-consonant words in quiet and speech perception in noise using City University of New York sentences . These tests were administered using direct audio input to the implants . Head-related transfer functions were used to simulate speech in noise testing in a spatial environment . Speech was always presented at midline ( 0 ° ) , and the noise masker was presented at either side or midline ( −90 , 0 , + 90 degrees ) . Results : The binaural benefits of head shadow and summation effects developed early in the postoperative period and remained stable throughout the follow-up period . Squelch developed more slowly and was first demonstrated at 12 months after implantation but continued to increase beyond the first year of follow-up . Conclusion : Benefits of head shadow and summation emerge early and remain stable . However , squelch has the most protracted period of development , with increasing benefit after a year or more of implant experience . These data support the idea that binaural integration continues several years after insertion of bilateral cochlear implant devices Objective : To evaluate speech performance , in quiet and noise , and localization ability in adult patients who had undergone bilateral and simultaneous implantation . Study Design : Prospect i ve multi-center study . Methods : Twenty-seven adult patients with profound or total hearing loss were bilaterally implanted in a single-stage procedure , and simultaneously activated ( Med-El , Combi 40/40 + ) . Subjects were assessed before implantation and at 3 , 6 and 12 months after switch-on . Speech perception tests in monaural and binaural conditions were performed in quiet and in noise using disyllabic words , with speech coming from the front and a cocktail party background noise coming from 5 loudspeakers . Sound localization measurements were also performed in background noise coming from 5 loudspeakers positioned from –90 ° to + 90 ° azimuth in the horizontal plane , and using a speech stimulus . Results : There was a bilateral advantage at 12 months in quiet ( 77 ± 5.0 % in bilateral condition , 67 ± 5.3 % for the better ear , p < 0.005 ) and in noise ( signal-to-noise ratio + 15 dB : 63 ± 5.9 % in bilateral condition , 55 ± 6.9 % for the better ear , p < 0.05 ) . Considering unilateral speech scores recorded in quiet at 12 months , subjects were categorized as ‘ good performers ’ ( speech comprehension score ≥60 % for the better ear , n = 19 ) and ‘ poor performers ’ ( n = 8) . Subjects were also categorized as ‘ asymmetrical ’ ( difference between their 2 unilateral speech scores ≥20 % , n = 11 ) or ‘ symmetrical ’ ( n = 16 ) . The largest advantage ( bilateral compared to the better ear ) was obtained in poor performers : + 19 % compared to + 7 % in good performers ( p < 0.05 ) . In the group of good performers , there was a bilateral advantage only in cases of symmetrical results between the 2 ears ( n = 10 ) . In the group of poor performers , the bilateral advantage was shown in both patients with symmetrical ( n = 6 ) and asymmetrical results ( n = 2 ) . In bilateral conditions , the sound localization ability in noise was improved compared to monaural conditions in patients with symmetrical and asymmetrical performance between the 2 ears . No preoperative factor ( age , duration of deafness , use of hearing aids , etiology , etc . ) could predict the asymmetrical performance , nor which ear would be the best . Conclusion : This study demonstrates a bilateral advantage ( at 12 months after the implantation ) in speech intelligibility and sound localization in a complex noisy environment . In quiet , this bilateral advantage is shown in cases of poor performance of both ears , and in cases of good performance with symmetrical results between the 2 ears . No preoperative factor can predict the best c and i date s for a simultaneous bilateral implantation Objective : To evaluate the benefits of bilateral electrical stimulation for hearing-impaired adult subjects using the Nucleus 24 cochlear implant in a multicenter study , and to compare and quantify performance on speech perception measures in quiet and in noise and localization ability for unilateral and bilateral cochlear implant use . Design : Repeated single subject measures were carried out for each subject , with each subject serving as their own control . Assessment of unilateral and bilateral listening conditions for performance on tests of speech comprehension and sound localization were performed . Speech comprehension measures were performed in quiet at 0 degree azimuth and in the presence of background noise simultaneously presented from the same speaker and spatially separated by 90 degrees , at S+45 ° N45 ° and at S−45 ° N+45 ° . Test material s included Freiburger monosyllabic words , Oldenburger sentences , and the Hochmair-Schulz-Moser sentences . Tests of localization were performed in the horizontal plane with 12 speaker locations 30 degrees apart using a shortened sentence stimulus from the Hochmair-Schulz-Moser sentences at two possible presentation levels of 55 and 70 dB sound pressure level for assessment of directionality . The binaural advantage provided by bilateral stimulation was calculated with respect to each ear separately , classified as either the better or poorer performing ear for each speech material in quiet and in noise test conditions . For localization of sound , the binaural advantage was compared with left and right ears separately . Paired comparisons for performance data in all conditions were carried out by considering measurements for each subject in different conditions as paired observations and applying the Student ’s t test to determine the statistical difference between the data sets . Setting : Tertiary referral centers with a cochlear implant program . Patients : Thirty-seven profoundly hearing-impaired adults were enrolled in the study , 22 simultaneously and 15 sequentially bilaterally implanted . All patients received the Nucleus 24 cochlear implant and used the Nucleus SPrint or ESPrit 3 G speech processor , with the vast majority using the ACE speech coding strategy . Results : For spatially separated speech in noise conditions , an interaural performance advantage for the ear closest to the speech source ( i.e. , with a superior signal to noise ratio ) compared with that for the ear closest to the noise source ( i.e. , with an inferior signal to noise ratio ) is consistently demonstrated regardless of whether it is the better or poorer performing ear closest to the speech signal . This is referred to as a significant binaural head-shadow benefit , result ing in a mean improvement between −10 dB and −11.4 dB in the critical signal to noise ratio required for 50 % speech comprehension for the Olden-burger sentences and a mean improvement in the maximum score of 42 % to 55 % for the ear closest to the speech signal over the ear farthest away for the Hochmair-Schulz-Moser sentences . Bilateral stimulation is always observed to provide a performance advantage over the unilateral listening condition for either ear when ipsilateral to the noise source . In addition , as demonstrated by approximately half the subjects tested in noise with the Hochmair-Schulz-Moser sentences , a performance advantage of bilateral stimulation may be observed over the better ear alone when positioned ipsilateral to the speech signal , which is referred to as a binaural squelch effect . On average , for the group , this result ed in a statistically significant improvement in speech comprehension scores of 8 % in the bilateral listening condition compared with the scores for the better ear alone . Through assessment of comprehension of coincidental speech in noise and speech in quiet , a significant benefit of binaural redundancy was noted for the group for Oldenburger sentence scores in noise and in quiet compared with unilateral scores for either ear and for the Freiburger monosyllabic words in quiet in comparison with the better ear alone scores . Binaural stimulation also led to a significant improvement in localization ability over either monaural condition , with the root mean square degrees of error reduced by 38 degrees compared with that observed for unilateral stimulation . Conclusion : Similar to what has been observed for bilateral acoustic stimulation in the past , bilateral electrical stimulation provides the foundation for the potential advantages of the head-shadow effect , providing a binaural head-shadow benefit and binaural auditory processing such as binaural redundancy and binaural squelch effects , all of which combine to lead to improved speech comprehension over unilateral listening conditions . The combination of improved speech comprehension and improved localization ability made available through bilateral electrical stimulation provides the necessary foundation to further assist the hearing-impaired listener to better cope with communication in the everyday listening situation both in noise and in quiet |
826 | 28,878,172 | This meta- analysis shows that total protein and animal protein could increase the risk of T2DM in both males and females , and plant protein decreases the risk of T2DM in females .
The association between high-protein food types and T2DM are also different .
Red meat and processed meat are risk factors of T2DM , and soy , dairy and dairy products are the protective factors of T2DM .
Egg and fish intake are not associated with a decreased risk of T2DM . | Recently , some studies have focused on the relationship between dietary protein intake and the risk of type 2 diabetes mellitus ( T2DM ) , but the conclusions have been inconsistent .
Therefore , in this paper , a systematic review and meta- analysis of cohort studies regarding protein consumption and T2DM risk are conducted in order to present the association between them . | BACKGROUND Despite their beneficial effects on weight loss and blood lipids , high-protein ( HP ) diets have been shown to increase insulin resistance and diabetes risk , whereas high-cereal-fiber ( HCF ) diets have shown the opposite effects on these outcomes . OBJECTIVE We compared the effects of isoenergetic HP and HCF diets and a diet with moderate increases in both cereal fibers and dietary protein ( Mix diet ) on insulin sensitivity , as measured by using euglycemic-hyperinsulinemic clamps with infusion of [6,6-(2)H(2)]glucose . DESIGN We r and omly assigned 111 overweight adults with features of the metabolic syndrome to 1 of 4 two-phased , 18-wk isoenergetic diets by group-matching . Per 3-d food protocol s , the percentages of energy derived from protein and carbohydrates and the intake of cereal fiber per day , respectively , were as follows-after 6 wk : 17 % , 52 % , and 14 g ( control ) ; 17 % , 52 % , and 43 g ( HCF ) ; 28 % , 43 % , and 13 g ( HP ) ; 23 % , 44 % , and 26 g ( Mix ) ; after 18 wk : 17 % , 51 % , and 15 g ( control ) ; 17 % , 51 % , and 41 g ( HCF ) ; 26 % , 45 % , and 14 g ( HP ) ; and 22 % , 46 % , and 26 g ( Mix ) . Eighty-four participants completed the study successfully and were included in the final analyses . Adherence was supported by the provision of tailored dietary supplements twice daily in all groups . RESULTS Insulin sensitivity expressed as an M value was 25 % higher after 6 wk of the HCF diet than after 6 wk of the HP diet ( subgroup analysis : 4.61 ± 0.38 compared with 3.71 ± 0.36 mg · kg(-1 ) · min(-1 ) , P = 0.008 ; treatment × time interaction : P = 0.005 ) . Effects were attenuated after 18 wk ( treatment × time interaction : P = 0.054 ) , which was likely explained by lower adherence to the HP diet . HP intake was associated with a tendency to increased protein expression in adipose tissue of the translation initiation factor serine-kinase-6 - 1 , which is known to mediate amino acid-induced insulin resistance . Biomarkers of protein intake indicated interference of cereal fibers with dietary protein absorption . CONCLUSION Greater changes in insulin sensitivity after intake of an isoenergetic HCF than after intake of an HP diet might help to explain the diverse effects of these diets on diabetes risk . This trial is registered at clinical trials.gov as NCT00579657 OBJECTIVE Phytoestrogen consumption has been shown to reduce risk factors for cardiovascular disease . Type 2 diabetes confers an adverse cardiovascular risk profile particularly in women after menopause . The aim of this study was to determine whether a dietary supplement with soy protein and isoflavones affected insulin resistance , glycemic control , and cardiovascular risk markers in postmenopausal women with type 2 diabetes . RESEARCH DESIGN AND METHODS A total of 32 postmenopausal women with diet-controlled type 2 diabetes completed a r and omized , double blind , cross-over trial of dietary supplementation with phytoestrogens ( soy protein 30 g/day , isoflavones 132 mg/day ) versus placebo ( cellulose 30 g/day ) for 12 weeks , separated by a 2-week washout period . RESULTS Compliance with the dietary supplementation was > 90 % for both treatment phases . When compared with the mean percentage change from baseline seen after 12 weeks of placebo , phytoestrogen supplementation demonstrated significantly lower mean values for fasting insulin ( mean + /- SD 8.09 + /- 21.9 % , P = 0.006 ) , insulin resistance ( 6.47 + /- 27.7 % , P = 0.003 ) , HbA(1c ) ( 0.64 + /- 3.19 % , P = 0.048 ) , total cholesterol ( 4.07 + /- 8.13 % , P = 0.004 ) , LDL cholesterol ( 7.09 + /- 12.7 % , P = 0.001 ) , cholesterol/HDL cholesterol ratio ( 3.89 + /- 11.7 % , P = 0.015 ) , and free thyroxine ( 2.50 + /- 8.47 % , P = 0.004 ) . No significant change occurred in HDL cholesterol , triglycerides , weight , blood pressure , creatinine , dehydroepi and rosterone sulfate , and rostenedione , and the hypothalamic-pituitary-ovarian axis hormones . CONCLUSIONS These results show that dietary supplementation with soy phytoestrogens favorably alters insulin resistance , glycemic control , and serum lipoproteins in postmenopausal women with type 2 diabetes , thereby improving their cardiovascular risk profile BACKGROUND Red meat consumption has been associated with an increased risk of chronic diseases . However , its relationship with mortality remains uncertain . METHODS We prospect ively observed 37 698 men from the Health Professionals Follow-up Study ( 1986 - 2008 ) and 83 644 women from the Nurses ' Health Study ( 1980 - 2008 ) who were free of cardiovascular disease ( CVD ) and cancer at baseline . Diet was assessed by vali date d food frequency question naires and up date d every 4 years . RESULTS We documented 23 926 deaths ( including 5910 CVD and 9464 cancer deaths ) during 2.96 million person-years of follow-up . After multivariate adjustment for major lifestyle and dietary risk factors , the pooled hazard ratio ( HR ) ( 95 % CI ) of total mortality for a 1-serving-per-day increase was 1.13 ( 1.07 - 1.20 ) for unprocessed red meat and 1.20 ( 1.15 - 1.24 ) for processed red meat . The corresponding HRs ( 95 % CIs ) were 1.18 ( 1.13 - 1.23 ) and 1.21 ( 1.13 - 1.31 ) for CVD mortality and 1.10 ( 1.06 - 1.14 ) and 1.16 ( 1.09 - 1.23 ) for cancer mortality . We estimated that substitutions of 1 serving per day of other foods ( including fish , poultry , nuts , legumes , low-fat dairy , and whole grains ) for 1 serving per day of red meat were associated with a 7 % to 19 % lower mortality risk . We also estimated that 9.3 % of deaths in men and 7.6 % in women in these cohorts could be prevented at the end of follow-up if all the individuals consumed fewer than 0.5 servings per day ( approximately 42 g/d ) of red meat . CONCLUSIONS Red meat consumption is associated with an increased risk of total , CVD , and cancer mortality . Substitution of other healthy protein sources for red meat is associated with a lower mortality risk BACKGROUND & AIMS Type 2 diabetes ( DM ) disproportionally affects African Americans . Data on the association between egg consumption and risk of DM are sparse . We sought to examine whether egg consumption is associated with the prevalence and incidence of DM among African Americans . METHODS We analyzed baseline data from 4568 participants of the Jackson Heart Study . Egg consumption was obtained using a food frequency question naire design ed for this population . We used generalized estimating equations to calculate adjusted prevalence ratios of DM and Cox regression to estimate hazard ratios of DM with corresponding 95 % confidence intervals ( CI ) . RESULTS The average age was 55 ± 13 years and 64 % of subjects were women . The median frequency of egg consumption was 2/week for men and 1/week for women . The prevalence of DM was 22 % overall ( 21 % of men and 23 % of women ) . Multivariable adjusted prevalence ratio [ PR ( 95 % CI ) ] for DM were : 1.00 ( ref ) , 1.14 ( 0.90 - 1.44 ) , 1.33 ( 1.04 - 1.70 ) , 1.33 ( 1.06 - 1.68 ) , 1.26 ( 0.99 - 1.61 ) , and 1.52 ( 1.17 - 1.97 ) for egg consumption of < 1/month , 1 - 3/month , 1/week , 2/week , 3 - 4/week , and 5+/week , respectively , p for linear trend 0.0024 . Corresponding multivariable adjusted hazard ratios were 1.00 ( ref ) , 0.88 ( 0.65 - 1.19 ) , 0.94 ( 0.68 - 1.30 ) , 0.91 ( 0.66 - 1.25 ) , 1.11 ( 0.81 - 1.52 ) , and 1.17 ( 0.81 - 1.70 ) , respectively , during a mean follow up of 7.3 years ( p for linear trend 0.22 ) . CONCLUSIONS While egg consumption was positively associated with prevalent DM , prospect i ve analysis did not show an association of egg intake with incidence of DM among African Americans BACKGROUND & AIMS The effect of total dairy products , milk , and calcium intake on risk of type 2 diabetes ( T2D ) is uncertain , particularly in the Chinese population . METHODS The present study was based on a prospect i ve cohort of 63,257 Chinese men and women aged 45 - 74 years during enrollment ( 1993 - 1998 ) in Singapore . Dietary information was obtained using a vali date d 165-item semi-quantitative food-frequency question naire . Information about newly diagnosed T2D was collected by self-report during two follow-up interviews in 1999 - 2004 and 2006 - 2010 . Cox proportional hazard regression method was used to estimate hazard ratios ( HRs ) and their 95 % confidence intervals ( CIs ) in 45,411 eligible participants . RESULTS Incidence rate ( 95 % CI ) of T2D was 10.5 ( 10.2 - 10.8 ) per 1000 person-years . Intake of dairy food was significantly associated with reduced T2D risk ; compared with the lowest quartile , HRs ( 95 % CI ) for the second , third and fourth quartiles of dairy intake were 0.98 ( 0.91 - 1.06 ) , 0.96 ( 0.89 - 1.03 ) and 0.90 ( 0.83 - 0.98 ) , respectively , after adjustment for potential confounders at baseline ( P-trend = 0.01 ) . Daily drinkers of milk had a significant 12 % reduction in T2D risk compared with non-drinkers . While dairy calcium was associated with a decreased risk of T2D ( HR comparing extreme quartiles 0.84 ; 95 % CI 0.76 - 0.93 ; P-trend = 0.001 ) , no association was found for non-dairy calcium ( HR 1.02 ; 95 % CI 0.92 - 1.14 ; P-trend = 0.61 ) . CONCLUSIONS In this large cohort study of Chinese adults , dairy product intake and daily milk consumption was associated with a statistically significant , although modest , decrease in risk of developing T2D , which may be independent of its calcium content Objective To examine relationships between fish consumption and plasma selenium ( Se ) and red blood-cell fatty acid ( RBC FA ) profile in aged subjects . We hypothesised that the importance of Se has been underestimated when interpreting the beneficial effect of fish consumption on health . Design Cross-sectional analysis of data from a prospect i ve cohort study . Setting The EVA study in Nantes , France (1991–2002).Subjects200 subjects aged 69 y with information on RBC FAs , plasma Se and completed food frequency question naires . Methods We examined correlations between the most abundant FAs , Se and number of fish meals per week . Linear regression models were used . Results Plasma Se was negatively correlated with RBC 6 poly-unsaturated FA ( PUFAs ) and positively with 3 PUFAs . Plasma Se , RBC 3 PUFAs , docosahexaenoic acid ( DHA ) and eicosapentaenoic acid ( EPA ) increased with fish consumption . Conversely , levels of 6 PUFAs were lower in the highest fish consumption group . All associations between plasma Se and fish consumption remained significant when adjusting for 6 PUFAs alone or additionally for age , sex , education , diabetes , hypertension , dyslipidemia , cardiovascular diseases , and broad food categories ( meat , eggs , dairy products , cereals , fruit and vegetable ) . Associations between 3 PUFAs and fish also remained significant in the same model independently of Se . In linear regression models adjusted for demographic indicators , fish consumption explained only 2.6 % of the variance in RBC 3 FAs ( 6.2 % for 6 ) but as much as 15 % of the variance in plasma selenium . Conclusions The observed health benefits of fish consumption in the elderly could be related not only to the increase in 3 FA intake but also to other nutrients such as selenium . It is important to consider this observation when interpreting associations between fish consumption and health status in the elderly , particularly with regard to brain function OBJECTIVE —Whereas limited and inconsistent findings have been reported on the relation between dietary cholesterol or egg consumption and fasting glucose , no previous study has examined the association between egg consumption and type 2 diabetes . This project sought to examine the relation between egg intake and the risk of type 2 diabetes in two large prospect i ve cohorts . RESEARCH DESIGN AND METHODS —In this prospect i ve study , we used data from two completed r and omized trials : 20,703 men from the Physicians ' Health Study I ( 1982–2007 ) and 36,295 women from the Women 's Health Study ( 1992–2007 ) . Egg consumption was ascertained using question naires , and we used the Cox proportional hazard model to estimate relative risks of type 2 diabetes . RESULTS —During mean follow-up of 20.0 years in men and 11.7 years in women , 1,921 men and 2,112 women developed type 2 diabetes . Compared with no egg consumption , multivariable adjusted hazard ratios for type 2 diabetes were 1.09 ( 95 % CI 0.87–1.37 ) , 1.09 ( 0.88–1.34 ) , 1.18 ( 0.95–1.45 ) , 1.46 ( 1.14–1.86 ) , and 1.58 ( 1.25–2.01 ) for consumption of < 1 , 1 , 2–4 , 5–6 , and ≥7 eggs/week , respectively , in men ( P for trend < 0.0001 ) . Corresponding multivariable hazard ratios for women were 1.06 ( 0.92–1.22 ) , 0.97 ( 0.83–1.12 ) , 1.19 ( 1.03–1.38 ) , 1.18 ( 0.88–1.58 ) , and 1.77 ( 1.28–2.43 ) , respectively ( P for trend < 0.0001 ) . CONCLUSIONS —These data suggest that high levels of egg consumption ( daily ) are associated with an increased risk of type 2 diabetes in men and women . Confirmation of these findings in other population s is warranted Aim : To investigate the association between meat intake and incidence of type 2 diabetes ( type 2 DM ) in a large cohort of middle-aged women . Design , subjects and methods : Incident cases of type 2 DM were identified during an average of 4.6 years of follow-up in a prospect i ve cohort study of 74,493 middle-aged , Chinese women ( mean age ± SD = 51.7± 8.97 years ) . Participants completed in-person interviews that collected information on type 2 DM risk factors such as dietary factors and physical activity in adulthood . Anthropometric indices were measured . Dietary intake was assessed using a vali date d food frequency question naire ( FFQ ) . We included in the current analysis 70,609 women who had no prior history of type 2 DM at study recruitment and who had valid dietary data . The association of type 2 DM with unprocessed meat intake ( g/day ) and the frequency of consumption of processed meat was evaluated using the Cox model with adjustment for age , kcals/day , body mass index ( BMI ) , waist to hip ratio ( WHR ) , vegetable intake , smoking , alcohol consumption , physical activity , income level , education level , occupation status , and history of hypertension and chronic disease at baseline . Principal results : We identified 1972 incident cases of type 2 DM during a total of 326,581 person-years of follow up . Intake of unprocessed meat , particularly poultry , was associated with a decrease in the risk of type 2 DM in this cohort . The fully adjusted relative risks ( RRs ) for quintiles of total unprocessed meat intake were 1.00 , 0.78 , 0.83 , 0.74 , and 0.83 ( P for trend : < 0.01 ) . When the joint effect between meat intake and BMI categories was evaluated , high intake of total unprocessed meat appeared to be associated with an increased risk of type 2 DM among obese women but a reduced risk among lean women ( P value for the interaction tests = 0.05 ) . Processed meat consumption was positively associated with the risk of type 2 DM . The adjusted RR was 1.15 ( 95 % 1.01 - 1.32 ) in women consuming processed meats compared to those who did not consume processed meats ( P=0.04 ) . Conclusions : Processed meat intake was positively associated with the risk of type 2 DM . There was an indication that the effect of unprocessed meat intake on type 2 DM may be modified by BMI Background and Purpose — Few dietary protein sources have been studied prospect ively in relation to stroke . We examined the relation between foods that are major protein sources and risk of stroke . Methods — We prospect ively followed 84 010 women aged 30 to 55 years at baseline and 43 150 men aged 40 to 75 years at baseline without diagnosed cancer , diabetes , or cardiovascular disease . Diet was assessed repeatedly by a st and ardized and vali date d question naire . We examined the association between protein sources and incidence of stroke using a proportional hazard model adjusted for stroke risk factors . Results — During 26 and 22 years of follow-up in women and men , respectively , we documented 2633 and 1397 strokes , respectively . In multivariable analyses , higher intake of red meat was associated with an elevated risk of stroke , whereas a higher intake of poultry was associated with a lower risk . In models estimating the effects of exchanging different protein sources , compared with 1 serving/day of red meat , 1 serving/day of poultry was associated with a 27 % ( 95 % CI , 12%–39 % ) lower risk of stroke , nuts with a 17 % ( 95 % CI . 4%–27 % ) lower risk , fish with a 17 % ( 95 % CI , 0%–30 % ) lower risk , low-fat dairy with an 11 % ( 95 % CI , 5%–17 % ) lower risk , and whole-fat dairy with a 10 % ( 95 % CI , 4%–16 % ) lower risk . We did not see significant associations with exchanging legumes or eggs for red meat . Conclusions — These data suggest that stroke risk may be reduced by replacing red meat with other dietary sources of protein OBJECTIVE To determine , for individuals with type 2 diabetes and microalbuminuria , the effects of 6 weeks of meals containing plant-based protein ( PP ) versus meals with predominantly animal-based protein ( AP ) on renal function and secondarily on glycemia , lipid levels , and blood pressure . RESEARCH DESIGN AND METHODS In a r and omized crossover trial , we compared 6 weeks of meals containing only PP with meals containing primarily AP ( 60 % animal , 40 % plant ) in 17 subjects with type 2 diabetes and microalbuminuria treated with diet and /or oral antidiabetic agents . Protein content was equivalent to the average American diet , and calories provided weight maintenance . Nutrients were equivalent between the two diets . Meals were prepared and packaged by a metabolic kitchen staff and were sent home weekly . At the beginning and end of each 6-week period , subjects were studied for 36 h on a metabolic unit . RESULTS There were no significant differences between diets for glomerular filtration rate , renal plasma flow , albumin excretion rate , total cholesterol , HDL cholesterol , triglyceride area under the curve ( AUC ) , glucose and insulin AUC , HbA(1c , ) blood pressure , or serum amino acids . For both diets , at the end of the treatment periods as compared with baseline , total cholesterol was significantly lower ( PP and AP : from 4.75 to 4.34 mmol/l , P < 0.01 ) , HbA(1c ) had significantly improved ( PP : from 8.1 to 7.5 % , P < 0.01 ; AP : from 7.9 to 7.4 % , P < 0.01 ) , and diastolic blood pressure was significantly lower ( PP : from 83 to 80 mmHg , P < 0.02 ; AP : from 82 to 78 , P < 0.02 ) . CONCLUSIONS There is no clear advantage for the recommendation of diets containing only PP rather than diets containing protein that is primarily animal-based for individuals with type 2 diabetes and microalbuminuria . There are , however , potential lipid , glycemic , and blood pressure benefits for following a carefully constructed , weight-maintaining , healthy diet , regardless of protein source OBJECTIVE Several studies have suggested that dairy food may reduce the risk of obesity and metabolic abnormalities but few have been able to conclusively demonstrate that it reduces the risk of diabetes . The aim of the present analysis was to investigate if dairy food intake independently reduces the risk of diabetes . DESIGN The Australian Diabetes Obesity and Lifestyle Study ( AusDiab ) is a national , population -based , prospect i ve survey conducted over 5 years . Baseline measurements included a 121-item FFQ , anthropometrics and an oral glucose tolerance test . SETTING Forty-two r and omly selected clusters across Australia . SUBJECTS Adults aged ≥25 years who participated in the baseline survey and returned to follow-up 5 years later . RESULTS A total of 5582 participants with complete data were eligible for analysis , 209 of whom had incident diabetes . Compared with men in the first tertile of dairy food intake , men in the third tertile had a significantly reduced risk of developing diabetes after adjustment for age , sex , total energy intake , family history of diabetes , education , physical activity , smoking status , fasting serum TAG and HDL cholesterol , systolic blood pressure , waist circumference and hip circumference ( OR = 0·53 , 95 % CI 0·29 , 0·96 ; P = 0·033 ) . A similar non-significant association was observed in women . CONCLUSIONS Dietary patterns that incorporate high intakes of dairy food may reduce the risk of diabetes among men . Further investigation into the relationship between dairy food intake and diabetes needs to be undertaken to fully underst and the potential mechanism of this observation BACKGROUND Type 2 diabetes ( T2D ) remains an important public health issue in the United States . There are limited and inconsistent data on the association between egg consumption and fasting glucose or incident diabetes . OBJECTIVES We assessed the association between egg intake and incident diabetes in older adults . DESIGN In this prospect i ve study of 3898 men and women from the Cardiovascular Health Study ( 1989 - 2007 ) , we assessed egg consumption by using a picture-sorted food question naire and ascertained incident T2D annually by using information on hypoglycemic agents and plasma glucose . We used Cox proportional hazards models to estimate adjusted relative risks . RESULTS During a mean follow-up of 11.3 y , 313 new cases of T2D occurred . Crude incidence rates of T2D were 7.39 , 6.83 , 7.00 , 6.72 , and 12.20 per 1000 person-years in people who reported egg consumption of never , < 1 egg/mo , 1 - 3 eggs/mo , 1 - 4 eggs/wk , and almost daily , respectively . In multivariable-adjusted models , there was no association between egg consumption and increased risk of T2D in either sex and overall . In a secondary analysis , dietary cholesterol was not associated with incident diabetes ( P for trend = 0.47 ) . In addition , egg consumption was not associated with clinical ly meaningful differences in fasting glucose , fasting insulin , or measures of insulin resistance despite small absolute analytic differences that were significant . CONCLUSION In this cohort of older adults with limited egg intake , there was no association between egg consumption or dietary cholesterol and increased risk of incident T2D BACKGROUND Although dietary omega-3 ( n-3 ) fatty acids may confer some cardiovascular benefits , it is unclear whether these nutrients may also unfavorably affect risk of type 2 diabetes ( T2D ) . OBJECTIVE We evaluated whether dietary omega-3 fatty acids and fish consumption were associated with increased risk of T2D . DESIGN This was a prospect i ve study of 36,328 women ( mean age : 54.6 y ) who participated in the Women 's Health Study and who were followed from 1992 to 2008 . Incident T2D was self-reported and vali date d primarily through the collection of supplementary information from participants . Information on omega-3 and fish intakes was obtained by using a vali date d food-frequency question naire . We used Cox proportional hazard models to estimate adjusted relative risks . RESULTS During an average follow-up of 12.4 y , 2370 women developed T2D . Marine but not plant-based omega-3 fatty acids were positively associated with incident T2D . From the lowest to highest quintiles of marine omega-3 intake , the multivariable-adjusted hazard ratios ( 95 % CIs ) for T2D were 1.0 ( referent ) , 1.17 ( 1.03 , 1.33 ) , 1.20 ( 1.05 , 1.38 ) , 1.46 ( 1.28 , 1.66 ) , and 1.44 ( 1.25 , 1.65 ) , respectively ( P for trend < 0.0001 ) . A similar association was observed with fish intake , but additional adjustment for docosahexaenoic acid led to the elimination of the association . The relation between marine omega-3 fatty acids and T2D was observed in hypertensive and nonhypertensive subjects and in women who reported infrequent fish consumption . CONCLUSION Our data suggest an increased risk of T2D with the intake of long-chain omega-3 fatty acids , especially with higher intakes ( ≥ 0.20 g omega-3/d or ≥ 2 servings of fish/d ) . The Women 's Health Study was registered at clinical trials.gov as NCT00000479 Aim /hypothesisThe aim of this study was to investigate the association between processed and other meat intake and incidence of Type 2 diabetes in a large cohort of women . Methods Incident cases of Type 2 diabetes were identified during 8 years of follow-up in a prospect i ve cohort study of 91246 U.S. women aged 26 to 46 years and being free of diabetes and other major chronic diseases at baseline in 1991 . Results We identified 741 incident cases of confirmed Type 2 diabetes during 716276 person-years of follow-up . The relative risk adjusted for potential non-dietary confounders was 1.91 ( 95 % CI : 1.42–2.57 ) in women consuming processed meat five times or more a week compared with those consuming processed meat less than once a week ( p<0.001 for trend ) . Further adjustment for intakes of magnesium , cereal fibre , glycaemic index , and caffeine or for a Western dietary pattern did not appreciably change the results and associations remained strong after further adjustment for fatty acid and cholesterol intake . Frequent consumption of bacon , hot dogs , and sausage was each associated with an increased risk of diabetes . While total red meat ( beef or lamb as main dish , pork as main dish , hamburger , beef , pork or lamb as s and wich or mixed dish ) intake was associated with an increased risk of diabetes , this association was attenuated after adjustment for magnesium , cereal fiber , glycaemic index , and caffeine ( relative risk : 1.44 ; 95 % CI : 0.92–2.24 ) . Conclusion /interpretationOur data suggest that diets high in processed meats could increase the risk for developing Type 2 diabetes BACKGROUND It has been postulated that a diet high in legumes may be beneficial for the prevention of type 2 diabetes mellitus ( type 2 DM ) . However , data linking type 2 DM risk and legume intake are limited . OBJECTIVE The objective of the study was to examine the association between legume and soy food consumption and self-reported type 2 DM . DESIGN The study was conducted in a population -based prospect i ve cohort of middle-aged Chinese women . We followed 64,227 women with no history of type 2 DM , cancer , or cardiovascular disease at study recruitment for an average of 4.6 y. Participants completed in-person interviews that collected information on diabetes risk factors , including dietary intake and physical activity in adulthood . Anthropometric measurements were taken . Dietary intake was assessed with a vali date d food-frequency question naire at the baseline survey and at the first follow-up survey administered 2 - 3 y after study recruitment . RESULTS We observed an inverse association between quintiles of total legume intake and 3 mutually exclusive legume groups ( peanuts , soybeans , and other legumes ) and type 2 DM incidence . The multivariate-adjusted relative risk of type 2 DM for the upper quintile compared with the lower quintile was 0.62 ( 95 % CI : 0.51 , 0.74 ) for total legumes and 0.53 ( 95 % CI : 0.45 , 0.62 ) for soybeans . The association between soy products ( other than soy milk ) and soy protein consumption ( protein derived from soy beans and their products ) with type 2 DM was not significant . CONCLUSIONS Consumption of legumes , soybeans in particular , was inversely associated with the risk type 2 DM OBJECTIVE The aim of this study was to prospect ively assess the relation between red meat intake and incidence of type 2 diabetes . RESEARCH DESIGN AND METHODS Over an average of 8.8 years , we evaluated 37,309 participants in the Women 's Health Study aged > /=45 years who were free of cardiovascular disease , cancer , and type 2 diabetes and completed vali date d semiquantitative food frequency question naires in 1993 . RESULTS During 326,876 person-years of follow-up , we documented 1,558 incident cases of type 2 diabetes . After adjusting for age , BMI , total energy intake , exercise , alcohol intake , cigarette smoking , and family history of diabetes , we found positive associations between intakes of red meat and processed meat and risk of type 2 diabetes . Comparing women in the highest quintile with those in the lowest quintile , the multivariate-adjusted relative risks ( RRs ) of type 2 diabetes were 1.28 for red meat ( 95 % CI 1.07 - 1.53 , P < 0.001 for trend ) and 1.23 for processed meat intake ( 1.05 - 1.45 , P = 0.001 for trend ) . Furthermore , the significantly increased diabetes risk appeared to be most pronounced for frequent consumption of total processed meat ( RR 1.43 , 95 % CI 1.17 - 1.75 for > /=5/week vs. < 1/month , P < 0.001 for trend ) and two major subtypes , which were bacon ( 1.21 , 1.06 - 1.39 for > /=2/week vs. < 1/week , P = 0.004 for trend ) and hot dogs ( 1.28 , 1.09 - 1.50 for > /=2/week vs. < 1/week , P = 0.003 for trend ) . These results remained significant after further adjustment for intakes of dietary fiber , magnesium , glycemic load , and total fat . Intakes of total cholesterol , animal protein , and heme iron were also significantly associated with a higher risk of type 2 diabetes . CONCLUSIONS Our data indicate that higher consumption of total red meat , especially various processed meats , may increase risk of developing type 2 diabetes in women OBJECTIVE —Several short-term trials on the effect of soy consumption on cardiovascular risks are available , but little evidence exists regarding the impact of long-term soy protein consumption among type 2 diabetic patients with nephropathy . To determine the effects of long-term soy consumption on cardiovascular risks , we measured C-reactive protein ( CRP ) and kidney function indexes among type 2 diabetic patients with nephropathy . RESEARCH DESIGN AND METHODS —This longitudinal r and omized clinical trial was conducted among 41 type 2 diabetic patients with nephropathy ( 18 men and 23 women ) . Twenty patients in the soy protein group consumed a diet containing 0.8 g protein/kg body weight ( 35 % animal proteins , 35 % textured soy protein , and 30 % vegetable proteins ) and 21 patients in the control group consumed a similar diet containing 70 % animal proteins and 30 % vegetable proteins for 4 years . RESULTS —Soy protein consumption significantly affected cardiovascular risks such as fasting plasma glucose ( mean change in the soy protein versus control groups : −18 ± 3 vs. 11 ± 2 mg/dl ; P = 0.03 ) , total cholesterol ( −23 ± 5 vs. 10 ± 3 mg/dl ; P = 0.01 ) , LDL cholesterol ( −20 ± 5 vs. 6 ± 2 mg/dl ; P = 0.01 ) , and serum triglyceride ( −24 ± 6 vs. −5 ± 2 mg/dl ; P = 0.01 ) concentrations . Serum CRP levels were significantly decreased by soy protein intake compared with those in the control group ( 1.31 ± 0.6 vs. 0.33 ± 0.1 mg/l ; P = 0.02 ) . Significant improvements were also seen in proteinuria ( −0.15 ± 0.03 vs. 0.02 ± 0.01 g/day ; P = 0.001 ) and urinary creatinine ( −1.5 ± 0.9 vs. 0.6 ± 0.3 mg/dl , P = 0.01 ) by consumption of soy protein . CONCLUSIONS —Longitudinal soy protein consumption significantly affected cardiovascular risk factors and kidney-related biomarkers among type 2 diabetic patients with nephropathy There has been interest in the effect of various types and amounts of dietary carbohydrates and proteins on blood glucose . On the basis of our previous data , we design ed a high-protein/low-carbohydrate , weight-maintaining , nonketogenic diet . Its effect on glucose control in people with untreated type 2 diabetes was determined . We refer to this as a low-biologically-available-glucose ( LoBAG ) diet . Eight men were studied using a r and omized 5-week crossover design with a 5-week washout period . The carbohydrate : protein : fat ratio of the control diet was 55:15:30 . The test diet ratio was 20:30:50 . Plasma and urinary beta-hydroxybutyrate were similar on both diets . The mean 24-h integrated serum glucose at the end of the control and LoBAG diets was 198 and 126 mg/dl , respectively . The percentage of glycohemoglobin was 9.8 + /- 0.5 and 7.6 + /- 0.3 , respectively . It was still decreasing at the end of the LoBAG diet . Thus , the final calculated glycohemoglobin was estimated to be approximately 6.3 - 5.4 % . Serum insulin was decreased , and plasma glucagon was increased . Serum cholesterol was unchanged . Thus , a LoBAG diet ingested for 5 weeks dramatically reduced the circulating glucose concentration in people with untreated type 2 diabetes . Potentially , this could be a patient-empowering way to ameliorate hyperglycemia without pharmacological intervention . The long-term effects of such a diet remain to be determined Objective Evidence is sparse and contradictory regarding the association between low-carbohydrate diet score and type 2 diabetes risk , and no prospect i ve study examined the association among Asians , who consume greater amount of carbohydrate . We prospect ively investigated the association of low-carbohydrate diet score with type 2 diabetes risk . Methods Participants were 27,799 men and 36,875 women aged 45–75 years who participated in the second survey of the Japan Public Health Center-Based Prospect i ve Study and who had no history of diabetes . Dietary intake was ascertained by using a vali date d food-frequency question naire , and low-carbohydrate diet score was calculated from total carbohydrate , fat , and protein intake . The scores for high animal protein and fat or for high plant protein and fat were also calculated . Odds ratios of self-reported , physician-diagnosed type 2 diabetes over 5-year were estimated by using logistic regression . Results During the 5-year period , 1191 new cases of type 2 diabetes were self-reported . Low-carbohydrate diet score for high total protein and fat was significantly associated with a decreased risk of type 2 diabetes in women ( P for trend < 0.001 ) ; the multivariable-adjusted odds ratio of type 2 diabetes for the highest quintile of the score were 0.63 ( 95 % confidence interval 0.46–0.84 ) , compared with those for the lowest quintile . Additional adjustment for dietary glycemic load attenuated the association ( odds ratio 0.75 , 95 % confidence interval 0.45–1.25 ) . When the score separated for animal and for plant protein and fat , the score for high animal protein and fat was inversely associated with type 2 diabetes in women , whereas the score for high plant protein and fat was not associated in both men and women . Discussion Low-carbohydrate diet was associated with decreased risk of type 2 diabetes in Japanese women and this association may be partly attributable to high intake of white rice . The association for animal-based and plant-based low-carbohydrate diet warrants further investigation The authors investigated the association of dietary patterns and type 2 diabetes in a 4-year prospect i ve study of 36,787 adults in the Melbourne Collaborative Cohort Study ( 1990 - 1994 ) . A total of 31,641 ( 86 % ) participants completed follow-up , and 365 cases were identified . Four factors with eigenvalues of greater than 2 were identified using the principal factor method with 124 foods/beverages , followed by orthogonal rotation . Variables with factor loadings having absolute values of 0.3 or greater were used in interpreting the factors . Odds ratios for diabetes incidence across quintiles of factor scores were computed by use of logistic regression , adjusting for age , energy intake , family history of diabetes , country of birth , and other factor scores . Factor 1 , characterized by olive oil , salad vegetables , and legumes and by avoidance of sweet bakery items , margarine , and tea , was associated with country of birth but not with diabetes . Factor 2 , characterized by salad and cooked vegetables , was inversely associated with diabetes . Factor 3 , characterized by meats and fatty foods , was associated with increased diabetes risk . A range of fruits loaded strongly on factor 4 , which showed little association with diabetes . Avoidance of a dietary pattern including meats and fatty foods , as well as adherence to a pattern including salad and cooked vegetables , is recommended OBJECTIVE The long-term association between dietary protein and type 2 diabetes incidence is uncertain . We aim ed to investigate the association between total , animal , and plant protein intake and the incidence of type 2 diabetes . RESEARCH DESIGN AND METHODS The prospect i ve European Prospect i ve Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study consists of 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,154 individuals from eight European countries , with an average follow-up time of 12.0 years . Pooled country-specific hazard ratios ( HRs ) and 95 % CI of prentice-weighted Cox regression analyses were used to estimate type 2 diabetes incidence according to protein intake . RESULTS After adjustment for important diabetes risk factors and dietary factors , the incidence of type 2 diabetes was higher in those with high intake of total protein ( per 10 g : HR 1.06 [ 95 % CI 1.02–1.09 ] , Ptrend < 0.001 ) and animal protein ( per 10 g : 1.05 [ 1.02–1.08 ] , Ptrend = 0.001 ) . Effect modification by sex ( P < 0.001 ) and BMI among women ( P < 0.001 ) was observed . Compared with the overall analyses , associations were stronger in women , more specifically obese women with a BMI > 30 kg/m2 ( per 10 g animal protein : 1.19 [ 1.09–1.32 ] ) , and nonsignificant in men . Plant protein intake was not associated with type 2 diabetes ( per 10 g : 1.04 [ 0.93–1.16 ] , Ptrend = 0.098 ) . CONCLUSIONS High total and animal protein intake was associated with a modest elevated risk of type 2 diabetes in a large cohort of European adults . In view of the rapidly increasing prevalence of type 2 diabetes , limiting iso-energetic diets high in dietary proteins , particularly from animal sources , should be considered BACKGROUND Diet and lifestyle modifications can substantially reduce the risk of type 2 diabetes . While a strong inverse association has been reported between dairy consumption and the insulin resistance syndrome among young obese adults , the relation between dairy intake and type 2 diabetes is unknown . METHODS We prospect ively examined the relation between dairy intake and incident cases of type 2 diabetes in 41,254 male participants with no history of diabetes , cardiovascular disease , and cancer at baseline in the Health Professionals Follow-up Study . RESULTS During 12 years of follow-up , we documented 1243 incident cases of type 2 diabetes . Dairy intake was associated with a modestly lower risk of type 2 diabetes . After adjusting for potential confounders , including body mass index , physical activity , and dietary factors , the relative risk for type 2 diabetes in men in the top quintile of dairy intake was 0.77 ( 95 % confidence interval [ CI ] , 0.62 - 0.95 ; P for trend , .003 ) compared with those in the lowest quintile . Each serving-per-day increase in total dairy intake was associated with a 9 % lower risk for type 2 diabetes ( multivariate relative risk , 0.91 ; 95 % CI , 0.85 - 0.97 ) . The corresponding relative risk was 0.88 ( 95 % CI , 0.81 - 0.94 ) for low-fat dairy intake and 0.99 ( 95 % CI , 0.91 - 1.07 ) for high-fat dairy intake . The association did not vary significantly according to body mass index ( < 25 vs > or = 25 kg/m(2 ) ; P for interaction , .57 ) . CONCLUSION Dietary patterns characterized by higher dairy intake , especially low-fat dairy intake , may lower the risk of type 2 diabetes in men OBJECTIVE Dietary recommendations are focused mainly on relative dietary fat and carbohydrate content in relation to diabetes risk . Meanwhile , high-protein diets may contribute to disturbance of glucose metabolism , but evidence from prospect i ve studies is scarce . We examined the association among dietary total , vegetable , and animal protein intake and diabetes incidence and whether consuming 5 energy % from protein at the expense of 5 energy % from either carbohydrates or fat was associated with diabetes risk . RESEARCH DESIGN AND METHODS A prospect i ve cohort study was conducted among 38,094 participants of the European Prospect i ve Investigation into Cancer and Nutrition (EPIC)-NL study . Dietary protein intake was measured with a vali date d food frequency question naire . Incident diabetes was verified against medical records . RESULTS During 10 years of follow-up , 918 incident cases of diabetes were documented . Diabetes risk increased with higher total protein ( hazard ratio 2.15 [ 95 % CI 1.77–2.60 ] highest vs. lowest quartile ) and animal protein ( 2.18 [ 1.80–2.63 ] ) intake . Adjustment for confounders did not material ly change these results . Further adjustment for adiposity measures attenuated the associations . Vegetable protein was not related to diabetes . Consuming 5 energy % from total or animal protein at the expense of 5 energy % from carbohydrates or fat increased diabetes risk . CONCLUSIONS Diets high in animal protein are associated with an increased diabetes risk . Our findings also suggest a similar association for total protein itself instead of only animal sources . Consumption of energy from protein at the expense of energy from either carbohydrates or fat may similarly increase diabetes risk . This finding indicates that accounting for protein content in dietary recommendations for diabetes prevention may be useful The roles of different dietary proteins in the aetiology of type 2 diabetes ( T2D ) remain unclear . We investigated the associations of dietary proteins with the risk of incident T2D in Finnish men from the prospect i ve Kuopio Ischaemic Heart Disease Risk Factor Study . The study included 2332 men aged 42 - 60 years at the baseline examinations in 1984 - 1989 . Protein intakes were calculated from 4-d dietary records . Incident T2D was determined by self-administered question naires , fasting blood glucose measurements , 2-h oral glucose tolerance tests , and with national registers . The multivariable-adjusted risk of T2D on the basis of protein intakes was compared by the Cox proportional hazard ratios ( HR ) . During the mean follow-up of 19·3 years , 432 incident T2D cases were identified . Total , animal , meat or dairy product protein intakes were not associated with risk of T2D when the potential confounders were accounted for . Plant ( multivariable-adjusted extreme-quartile HR 0·65 ; 95 % CI 0·42 , 1·00 ; P trend 0·04 ) and egg ( HR 0·67 ; 95 % CI 0·44 , 1·00 ; P trend 0·03 ) protein intakes were associated with a decreased risk of T2D . Adjustments for BMI , plasma glucose and serum insulin slightly attenuated associations . Replacing 1 % energy from carbohydrates with energy from protein was associated with a 5 % ( 95 % CI 0 , 11 ) increased risk of T2D , but adjustment for fibre intake attenuated the association . Replacing 1 % of energy from animal protein with energy from plant protein was associated with 18 % ( 95 % CI 0 , 32 ) decreased risk of T2D . This association remained after adjusting for BMI . In conclusion , favouring plant and egg proteins appeared to be beneficial in preventing T2D BACKGROUND Type 2 diabetes mellitus is increasingly common , primarily because of increases in the prevalence of a sedentary lifestyle and obesity . Whether type 2 diabetes can be prevented by interventions that affect the lifestyles of subjects at high risk for the disease is not known . METHODS We r and omly assigned 522 middle-aged , overweight subjects ( 172 men and 350 women ; mean age , 55 years ; mean body-mass index [ weight in kilograms divided by the square of the height in meters ] , 31 ) with impaired glucose tolerance to either the intervention group or the control group . Each subject in the intervention group received individualized counseling aim ed at reducing weight , total intake of fat , and intake of saturated fat and increasing intake of fiber and physical activity . An oral glucose-tolerance test was performed annually ; the diagnosis of diabetes was confirmed by a second test . The mean duration of follow-up was 3.2 years . RESULTS The mean ( + /-SD ) amount of weight lost between base line and the end of year 1 was 4.2+/-5.1 kg in the intervention group and 0.8+/-3.7 kg in the control group ; the net loss by the end of year 2 was 3.5+/-5.5 kg in the intervention group and 0.8+/-4.4 kg in the control group ( P<0.001 for both comparisons between the groups ) . The cumulative incidence of diabetes after four years was 11 percent ( 95 percent confidence interval , 6 to 15 percent ) in the intervention group and 23 percent ( 95 percent confidence interval , 17 to 29 percent ) in the control group . During the trial , the risk of diabetes was reduced by 58 percent ( P<0.001 ) in the intervention group . The reduction in the incidence of diabetes was directly associated with changes in lifestyle . CONCLUSIONS Type 2 diabetes can be prevented by changes in the lifestyles of high-risk subjects OBJECTIVE We aim ed to develop a precise risk score for the screening of large population s for individuals at high risk of developing type 2 diabetes based on noninvasive measurements of major risk factors in German study population s. RESEARCH DESIGN AND METHODS A prospect i ve cohort study ( European Prospect i ve Investigation into Cancer and Nutrition [EPIC]-Potsdam study ) of 9,729 men and 15,438 women aged 35 - 65 years was used to derive a risk score predicting incident type 2 diabetes . Multivariate Cox regression model coefficients were used to weigh each variable in the calculation of the score . Data from the EPIC-Heidelberg , the Tübingen Family Study for Type 2 Diabetes ( TUF ) , and the Metabolic Syndrome Berlin Potsdam ( MeSyBePo ) study were used to vali date this score . RESULTS Information on age , waist circumference , height , history of hypertension , physical activity , smoking , and consumption of red meat , whole-grain bread , coffee , and alcohol formed the German Diabetes Risk Score ( mean 446 points [ range 118 - 983 ] ) . The probability of developing diabetes within 5 years in the EPIC-Potsdam study increased from 0.3 % for 300 to 23.2 % for 750 score points . The area under the receiver-operator characteristic ( ROC ) curve was 0.84 in the EPIC-Potsdam and 0.82 in the EPIC-Heidelberg studies . Correlation coefficients between the German Diabetes Risk Score and insulin sensitivity in nondiabetic individuals were -0.56 in the TUF and -0.45 in the MeSyBePo studies . ROC values for undiagnosed diabetes were 0.83 in the TUF and 0.75 in the MeSyBePo studies . CONCLUSIONS The German Diabetes Risk Score ( available at www.dife.de ) is an accurate tool to identify individuals at high risk for or with undiagnosed type 2 diabetes BACKGROUND Diet is a key component of a healthy lifestyle in the prevention of type 2 diabetes mellitus ( T2DM ) . The role of long-chain omega-3 ( n-3 ) fatty acids ( LCFAs ) in the development of T2DM remains unresolved . OBJECTIVE We examined the association between dietary LCFAs and incidence of T2DM in 3 prospect i ve cohorts of women and men . DESIGN We followed 195,204 US adults ( 152,700 women and 42,504 men ) without preexisting chronic disease at baseline for 14 to 18 y. Fish and LCFA intakes were assessed at baseline and up date d at 4-y intervals by using a vali date d food-frequency question naire . RESULTS During nearly 3 million person-years of follow-up , 9380 new cases of T2DM were documented . After adjustment for other dietary and lifestyle risk factors , LCFA intake was positively related to incidence of T2DM . The pooled multivariate relative risks in 3 cohorts across increasing quintiles of LCFAs were as follows : 1 ( reference ) , 1.00 ( 95 % CI : 0.91 , 1.09 ) , 1.05 ( 95 % CI : 0.97 , 1.13 ) , 1.17 ( 95 % CI : 1.07 , 1.28 ) , and 1.24 ( 95 % CI : 1.09 , 1.40 ) ( P for trend < 0.001 ) . Compared with those who consumed fish less than once per month , the relative risk of T2DM was 1.22 ( 95 % CI : 1.08 , 1.39 ) for women who consumed > or = 5 servings fish/wk ( P for trend < 0.001 ) . CONCLUSIONS We found no evidence that higher consumption of LCFAs and fish reduces the risk of T2DM . Instead , higher intakes may modestly increase the incidence of this disease . Given the beneficial effects of LCFA intake on many cardiovascular disease risk factors , the clinical relevance of this relation and its possible mechanisms require further investigation Aims /hypothesisThe aim of this study was to examine the association between baseline body iron stores and new-onset diabetes . Subjects and methods We studied the association between baseline serum ferritin concentration and type 2 diabetes in 360 clinical ly incident diabetes cases and 758 controls nested within the EPIC ( European Prospect i ve Investigation of Cancer)-Norfolk Cohort Study . Serum ferritin levels were categorised into five groups : sex-specific quartiles of the normal range of ferritin and a group with clinical ly raised ferritin below levels indicative of haemochromatosis . Results Baseline serum ferritin was higher among cases than control participants ( geometric mean : men 96.6 vs 67.8 ng/ml , respectively , p < 0.001 ; women 45.9 vs 34.8 ng/ml , respectively , p = 0.005 ) . In analyses adjusted for known risk factors ( age , BMI , sex , family history , physical activity , smoking habit ) and dietary factors measured by 7-day food diary , the risk of diabetes was markedly elevated in participants with clinical ly raised ferritin compared with the lowest quartile ( odds ratio [ OR ] 7.4 , 95 % CI 3.5–15.4 ) . Further adjustment for potential confounding by inflammation ( C-reactive protein , IL-6 and fibrinogen ) had no material impact on the observed association , while adjustment for hepatic enzymes ( alanine aminotransferase and γ glutamyl transferase ) and adiponectin attenuated the magnitude of association , but it remained statistically significant ( OR 3.2 [ 1.3–7.6 ] ) . Conclusions /interpretationSerum ferritin is an important and independent predictor of the development of diabetes . This finding may have important implication s for underst and ing the aetiology of diabetes Aims /hypothesisCalcium and vitamin D have been implicated in the development of type 2 diabetes , but epidemiological evidence is limited . We examined prospect ively the relation of calcium and vitamin D intake to type 2 diabetes risk in a Japanese cohort . Methods Participants were 59,796 middle-aged and older men and women , who participated in the Japan Public Health Center-based Prospect i ve Study and had no history of type 2 diabetes or other serious diseases . Dietary intake of calcium and vitamin D were estimated using a vali date d food frequency question naire . Logistic regression was used to assess the association between intake of these nutrients and self-reported newly diagnosed type 2 diabetes . Results During a 5 year follow-up , 1,114 cases of type 2 diabetes were documented . Overall , calcium intake was not associated with a significantly lower risk of type 2 diabetes ; the multivariable odds ratio for the highest vs lowest quartiles was 0.93 ( 95 % CI 0.71–1.22 ) in men and 0.76 ( 95 % CI 0.56–1.03 ) in women . However , among participants with a higher vitamin D intake , calcium intake was inversely associated with diabetes risk ; the odds ratio for the highest vs lowest intake categories was 0.62 ( 95 % CI 0.41–0.94 ) in men and 0.59 ( 95 % CI 0.38–0.91 ) in women . Dairy food intake was significantly associated with a lower risk of type 2 diabetes in women only . Conclusions /interpretationCalcium and vitamin D may not be independently associated with type 2 diabetes risk . Our finding suggesting a joint action of these nutrients against type 2 diabetes warrants further investigation Aim : To examine the relation between meat intake and diabetes occurrence in adults . Methods : In a prospect i ve cohort study we examined the relation between diet and incident diabetes recorded among 8,401 cohort members ( ages 45–88 years ) of the Adventist Mortality Study and Adventist Health Study ( California , USA ) who were non-diabetic at baseline . During the 17-year follow-up , we identified 543 incident diabetes cases . Results : ( 1 ) Subjects who were weekly consumers of all meats were 29 % ( OR = 1.29 ; 95 % CI 1.08 , 1.55 ) more likely ( relative to zero meat intake ) to develop diabetes . ( 2 ) Subjects who consumed any processed meats ( salted fish and frankfurters ) were 38 % ( OR = 1.38 ; 95 % CI 1.05–1.82 ) more likely to develop diabetes . ( 3 ) Long-term adherence ( over a 17-year interval ) to a diet that included at least weekly meat intake was associated with a 74 % increase ( OR = 1.74 ; 95 % CI 1.36–2.22 ) in odds of diabetes relative to long-term adherence to a vegetarian diet ( zero meat intake ) . Further analyses indicated that some of this risk may be attributable to obesity and /or weight gain – both of which were strong risk factors in this cohort . It is noteworthy that even after control for weight and weight change , weekly meat intake remained an important risk factor ( OR = 1.38 ; 95 % CI 1.06–1.08 ) for diabetes . Conclusions : Our findings raise the possibility that meat intake , particularly processed meats , is a dietary risk factor for diabetes BACKGROUND Available data have indicated independent direct relations of dietary animal protein and meat to the blood pressure ( BP ) of individuals . OBJECTIVE In this study , we aim ed to assess whether BP is associated with the intake of dietary amino acids higher relatively in animal than in vegetable protein ( alanine , arginine , aspartic acid , glycine , histidine , lysine , methionine , and threonine ) . DESIGN The study was a cross-sectional epidemiologic study that involved 4680 persons aged 40 - 59 y from 17 r and om population sample s in the People 's Republic of China , Japan , the United Kingdom , and the United States . BP was measured 8 times at 4 visits ; dietary data ( 83 nutrients and 18 amino acids ) were from four 24-h dietary recalls and two 24-h urine collection s. RESULTS Dietary glycine and alanine ( the percentage of total protein intake ) were considered singly related directly to BP ; with these 2 amino acids together in regression models ( from model 1 , which was controlled for age , sex , and sample , to model 5 , which was controlled for 16 possible confounders ) , glycine , but not alanine , was significantly related to BP . Estimated average BP differences associated with a 2-SD higher glycine intake ( 0.71 g/24 h ) were 2.0 - 3.0-mm Hg systolic BP ( z = 2.97 - 4.32 ) stronger in Western than in East Asian participants . In Westerners , meat was the main dietary source of glycine but not in East Asians ( Chinese : grains/flour and rice/noodles ; Japanese : fish/shellfish and rice/noodles ) . CONCLUSION Dietary glycine may have an independent adverse effect on BP , which possibly contributes to direct relations of animal protein and meat to BP OBJECTIVE To examine dietary fat and meat intake in relation to risk of type 2 diabetes . RESEARCH DESIGN AND METHODS We prospect ively followed 42,504 male participants of the Health Professionals Follow-Up Study who were aged 40 - 75 years and free of diagnosed diabetes , cardiovascular disease , and cancer in 1986 . Diet was assessed by a vali date d food frequency question naire and up date d in 1990 and 1994 . During 12 years of follow-up , we ascertained 1,321 incident cases of type 2 diabetes . RESULTS Intakes of total fat ( multivariate RR for extreme quintiles 1.27 , CI 1.04 - 1.55 , P for trend=0.02 ) and saturated fat ( 1.34 , 1.09 - 1.66 , P for trend=0.01 ) were associated with a higher risk of type 2 diabetes . However , these associations disappeared after additional adjustment for BMI ( total fat RR 0.97 , CI 0.79 - 1.18 ; saturated fat 0.97 , 0.79 - 1.20 ) . Intakes of oleic acid , trans-fat , long-chain n-3 fat , and alpha-linolenic acid were not associated with diabetes risk after multivariate adjustment . Linoleic acid was associated with a lower risk of type 2 diabetes in men < 65 years of age ( RR 0.74 , CI 0.60 - 0.92 , P for trend=0.01 ) and in men with a BMI < 25 kg/m(2 ) ( 0.53 , 0.33 - 0.85 , P for trend=0.006 ) but not in older and obese men . Frequent consumption of processed meat was associated with a higher risk for type 2 diabetes ( RR 1.46 , CI 1.14 - 1.86 for > or = 5/week vs. < 1/month , P for trend < 0.0001 ) . CONCLUSIONS Total and saturated fat intake were associated with a higher risk of type 2 diabetes , but these associations were not independent of BMI . Frequent consumption of processed meats may increase risk of type 2 diabetes Aims /hypothesisRecently , a clear biological link between iron metabolism and diabetes has emerged from epidemiological and experimental studies . We carried out a prospect i ve study of dietary iron intake and incidence of Type 2 diabetes . Methods 35,698 postmenopausal women initially aged 55 to 69 years were followed for 11 years . Diet was assessed with a food frequency question naire at baseline . Results Intake of heme iron showed a positive association with incident Type 2 diabetes ; the relative risks were 1.0 , 1.07 , 1.12 , 1.14 , and 1.28 across quintiles of heme iron ( p trend = 0.02 ) after adjustment for non-dietary and dietary risk factors . Heme iron showed a weak positive association among non-drinkers , but the association appeared to be stronger among subjects who consumed more alcohol . For example , in a model restricted to those who drank alcohol at least 15 g/day , adjusted relative risks across quintiles of heme iron were 1.0 , 2.26 , 3.22 , 1.92 , and 4.42 ( p trend = 0.05 ) ; and consumers of 30 g/day of more of supplemental iron had an adjusted relative risk equal to 3.03 ( 95 % CI , 1.29–7.12 ) ] , compared to those who took no iron supplement . Non-heme iron was inversely associated with incidence of Type 2 diabetes . Amongst non-drinkers adjusted relative risks were 1.0 , 0.83 , 0.87 , 0.72 , and 0.67 across quintiles ( p trend < 0.01 ) . This inverse association was lost among drinkers , in whom there was no association of diabetes incidence with non-heme iron . Conclusions /interpretationGreater dietary heme-iron intake and /or supplemental iron were associated with an increased risk of Type 2 diabetes , especially amongst those who drink alcohol BACKGROUND Although obesity is the most important risk factor for type 2 diabetes , evidence is emerging that certain foods and dietary factors may be associated with diabetes . To examine the association between major dietary patterns and risk of type 2 diabetes mellitus in a cohort of women . METHODS We prospect ively assessed the associations between major dietary patterns and risk of type 2 diabetes in women . Dietary information was collected in 1984 , 1986 , 1990 , and 1994 from 69,554 women aged 38 to 63 years without a history of diabetes , cardiovascular disease , or cancer in 1984 . We conducted factor analysis and identified 2 major dietary patterns : " prudent " and " Western . " We then calculated pattern scores for each participant and examined prospect ively the associations between dietary pattern scores and type 2 diabetes risks . RESULTS The prudent pattern was characterized by higher intakes of fruits , vegetables , legumes , fish , poultry , and whole grains , while the Western pattern included higher intakes of red and processed meats , sweets and desserts , french fries , and refined grains . During 14 years of follow-up , we identified 2699 incident cases of type 2 diabetes . After adjusting for potential confounders , we observed a relative risk for diabetes of 1.49 ( 95 % confidence interval [ CI ] , 1.26 - 1.76 , P for trend , < .001 ) when comparing the highest to lowest quintiles of the Western pattern . Positive associations were also observed between type 2 diabetes and red meat and other processed meats . The relative risk for diabetes for every 1-serving increase in intake is 1.26 ( 95 % CI , 1.21 - 1.42 ) for red meat , 1.38 ( 95 % CI , 1.23 - 1.56 ) for total processed meats , 1.73 ( 95 % CI , 1.39 - 2.16 ) for bacon , 1.49 ( 95 % CI , 1.04 - 2.11 ) for hot dogs , and 1.43 ( 95 % CI , 1.22 - 1.69 ) for processed meats . CONCLUSION The Western pattern , especially a diet higher in processed meats , may increase the risk of type 2 diabetes in women Diets high in protein have shown positive effects on short-term weight reduction and glycaemic control . However , the underst and ing of how dietary macronutrient composition relates to long-term risk of type 2 diabetes is limited . The aim of the present study was to examine intakes of macronutrients , fibre and protein sources in relation to incident type 2 diabetes . In total , 27 140 individuals , aged 45 - 74 years , from the population -based Malmö Diet and Cancer cohort , were included . Dietary data were collected with a modified diet history method , including registration of cooked meals . During 12 years of follow-up , 1709 incident type 2 diabetes cases were identified . High protein intake was associated with increased risk of type 2 diabetes ( hazard ratio ( HR ) 1.27 for highest compared with lowest quintile ; 95 % CI 1.08 , 1.49 ; P for trend = 0.01 ) . When protein consumption increased by 5 % of energy at the expense of carbohydrates ( HR 1.20 ; 95 % CI 1.09 , 1.33 ) or fat ( HR 1.21 ; 95 % CI 1.09 , 1.33 ) , increased diabetes risk was observed . Intakes in the highest quintiles of processed meat ( HR 1.16 ; 95 % CI 1.00 , 1.36 ; P for trend = 0.01 ) and eggs ( HR 1.21 ; 95 % CI 1.04 , 1.41 ; P for trend = 0.02 ) were associated with increased risk . Intake of fibre-rich bread and cereals was inversely associated with type 2 diabetes ( HR 0.84 ; 95 % CI 0.73 , 0.98 ; P for trend = 0.004 ) . In conclusion , results from the present large population -based prospect i ve study indicate that high protein intake is associated with increased risk of type 2 diabetes . Replacing protein with carbohydrates may be favourable , especially if fibre-rich breads and cereals are chosen as carbohydrate sources BACKGROUND The prevalence of type 2 diabetes ( T2D ) is increasing around the world . Eggs are a major source of cholesterol , which has been associated with elevated blood glucose and an increased risk of T2D . However , there are limited and conflicting data from prospect i ve population studies on the association between egg consumption and risk of T2D . OBJECTIVE We investigated the association between egg consumption and risk of incident T2D in middle-aged and older men from eastern Finl and . DESIGN The study included 2332 men aged 42 - 60 y in 1984 - 1989 at the baseline examinations of the prospect i ve , population -based Kuopio Ischaemic Heart Disease Risk Factor Study . Dietary intakes were assessed with 4-d food records at baseline . Incident T2D was assessed by self-administered question naires ; by fasting and 2-h oral-glucose-tolerance-test blood glucose measurement at re-examination rounds 4 , 11 , and 20 y after baseline ; and by record linkage to a hospital discharge registry and reimbursement register of diabetes medication expenses . Cox proportional hazards regression analyses were used to estimate associations with the risk of incident T2D . Associations with the metabolic risk markers at baseline and at the 4-y examinations were analyzed by ANCOVA . RESULTS During an average follow-up of 19.3 y , 432 men developed T2D . After adjustment for potential confounders , those in the highest compared with the lowest egg intake quartile had a 38 % ( 95 % CI : 18 % , 53 % ; P-trend across quartiles < 0.001 ) lower risk of incident T2D . Analyses with metabolic risk markers also suggested an inverse association with fasting plasma glucose and serum C-reactive protein but not with serum insulin . The associations between cholesterol intake and risk of T2D , plasma glucose , serum insulin , and C-reactive protein were mainly nonsignificant , especially after accounting for egg consumption . CONCLUSION Higher egg intake was associated with a lower risk of T2D in this cohort of middle-aged and older men Some previous studies have suggested that consuming dairy products , particularly the low-fat variety , lowers the incidence of type 2 diabetes . However , no study to our knowledge has focused on an ethnically diverse group of postmenopausal women , a population with a high risk of this disease . We conducted a prospect i ve cohort study of 82,076 postmenopausal women enrolled in the Women 's Health Initiative Observational Study who did not report diabetes at enrollment . Total , low-fat , and high-fat dairy product and yogurt intakes were estimated from FFQ at baseline and 3 y of follow-up . Treated diabetes incidence was ascertained from annual follow-up question naires . During 8 y of follow-up , 3946 cases of incident treated diabetes were reported ( annual incidence , 0.73 % ; cumulative incidence , 4.8 % ) . After multivariable adjustment , low-fat dairy product consumption was inversely associated with the risk of type 2 diabetes . RR was roughly 0.5 - 0.6 in the upper quintiles compared with the lowest quintile ( median servings/d , 2.8 in the 5th quintile and 1.5 in the 4th quintile vs. 0.05 in the first quintile ; P-trend < 0.001 ) . The inverse relationship was more pronounced in women with a higher BMI . High yogurt consumption was associated with a significant decrease in diabetes risk , whereas there was no relationship between high-fat dairy product consumption and diabetes risk . A diet high in low-fat dairy products is associated with lower diabetes risk in postmenopausal women , particularly those who are obese Abstract Purpose The possible effects of dairy consumption on diabetes prevention remain controversial . The aim of this study was to investigate the association between the dairy consumption and type 2 diabetes ( T2D ) risk in an elderly Mediterranean population at high cardiovascular risk . Methods We prospect ively followed 3,454 non-diabetic individuals from the PREDIMED study . Dairy consumption was assessed at baseline and yearly using food frequency question naires and categorized into total , low-fat , whole-fat , and subgroups : milk , yogurt , cheeses , fermented dairy , concentrated full fat , and processed dairy . Hazard ratios ( HRs ) were calculated using Cox proportional hazards regression models . Results During a median follow-up of 4.1 years , we documented 270 incident T2D cases . After multivariate adjustment , total dairy product consumption was inversely associated with T2D risk [ 0.68 ( 95 % CI 0.47–0.98 ) ; P-trend = .040 ] . This association appeared to be mainly attributed to low-fat dairy ; the multivariate HRs ( 95 % CIs ) comparing the highest versus the lowest tertile consumption were 0.65 ( 0.45–0.94 ) for low-fat dairy products and 0.67 ( 0.46–0.95 ) for low-fat milk ( both P-trend < .05 ) . Total yogurt consumption was associated with a lower T2D risk [ HR 0.60 ( 0.42–0.86 ) ; P-trend = .002 ] . An increased consumption of total low-fat dairy and total yogurt during the follow-up was inversely associated with T2D ; HRs were 0.50 ( 0.29–0.85 ) , 0.44 ( 0.26–0.75 ) , and 0.55 ( 0.33–0.93 ) , respectively . Substituting one serving/day of a combination of biscuits and chocolate and whole grain biscuits and homemade pastries for one serving/day of yogurt was associated with a 40 and 45 % lower risk of T2D , respectively . No significant associations were found for the other dairy subgroups ( cheese , concentrated full fat , and processed dairy products ) . Conclusions A healthy dietary pattern incorporating a high consumption of dairy products and particularly yogurt may be protective against T2D in older adults at high cardiovascular risk AIMS Diet and physical activity interventions can prevent diabetes in those at high risk due to impaired glucose tolerance . We determined whether simple measures of physical activity and diet predicted incident diabetes and enhanced prediction by known risk factors including age , body mass index and family history . METHODS This was a population -based prospect i ve cohort study ( EPIC-Norfolk ) . Participants aged 40 - 79 years ( n = 25,633 ) attended a health check between 1993 and 1998 and completed diet and activity question naires . We assessed the association between simple behavioural indices of physical activity and diet derived from the question naires as well as known risk score variables with incident diabetes at follow-up ( mean 4.6 years ) . We developed a new diabetes risk score incorporating simple behavioural indices in a r and omly selected half of the EPIC data set using forward step-wise multivariate logistic regression , and tested this score in the remaining half . We compared existing and new scores using receiver-operating characteristic ( ROC ) curves . RESULTS There were 417 incident cases of diabetes during 115,137 years of follow-up . A simple physical activity index independently predicted risk of diabetes . Eating one or more daily portion of vegetables , fresh fruit and wholemeal bread was associated with reduced risk ; whilst eating meat products was associated with increased risk . The area under the ROC curves for the new and original score was the same ( 76.3 % ) . CONCLUSIONS Simple indices of diet and activity are feasible to collect , predict future diabetes risk and might enhance routine data collection in primary care . However , they do not improve the prediction of risk scores based on known risk factors To examine the molecular mechanisms by which plasma amino acid elevation impairs insulin action , we studied seven healthy men twice in r and om order during infusion of an amino acid mixture or saline ( total plasma amino acid approximately 6 vs. approximately 2 mmol/l ) . Somatostatin-insulin-glucose clamps created conditions of low peripheral hyperinsulinemia ( approximately 100 pmol/l , 0 - 180 min ) and pr and ial-like peripheral hyperinsulinemia ( approximately 430 pmol/l , 180 - 360 min ) . At low peripheral hyperinsulinemia , endogenous glucose production ( EGP ) did not change during amino acid infusion but decreased by approximately 70 % during saline infusion ( EGP(150 - 180 min ) 11 + /- 1 vs. 3 + /- 1 mumol . kg(-1 ) . min(-1 ) , P = 0.001 ) . Pr and ial-like peripheral hyperinsulinemia completely suppressed EGP during both protocol s , whereas whole-body rate of glucose disappearance ( R(d ) ) was approximately 33 % lower during amino acid infusion ( R(d ) ( 330 - 360 min ) 50 + /- 4 vs. 75 + /- 6 mumol . kg(-1 ) . min(-1 ) , P = 0.002 ) indicating insulin resistance . In skeletal muscle biopsies taken before and after pr and ial-like peripheral hyperinsulinemia , plasma amino acid elevation markedly increased the ability of insulin to activate S6 kinase 1 compared with saline infusion ( approximately 3.7- vs. approximately 1.9-fold over baseline ) . Furthermore , amino acid infusion increased the inhibitory insulin receptor substrate-1 phosphorylation at Ser312 and Ser636/639 and decreased insulin-induced phosphoinositide 3-kinase activity . However , plasma amino acid elevation failed to reduce insulin-induced Akt/protein kinase B and glycogen synthase kinase 3alpha phosphorylation . In conclusion , amino acids impair 1 ) insulin-mediated suppression of glucose production and 2 ) insulin-stimulated glucose disposal in skeletal muscle . Our results suggest that overactivation of the mammalian target of rapamycin/S6 kinase 1 pathway and inhibitory serine phosphorylation of insulin receptor substrate-1 underlie the impairment of insulin action in amino acid-infused humans BACKGROUND Although fish intake can improve glucose metabolism , results of some prospect i ve studies in Western population s suggest potential adverse effects of environmental contaminants in fish on type 2 diabetes risk . However , data from population s with high fish consumption are scarce . OBJECTIVE We prospect ively investigated the association between fish intake and type 2 diabetes risk in Japanese adults . DESIGN The participants were 22,921 men and 29,759 women aged 45 - 75 y who completed a question naire of the second survey for the Japan Public Health Center-based Prospect i ve Study and who had no history of diabetes . Diet was ascertained by using a 147-item food-frequency question naire . ORs of self-reported , physician-diagnosed type 2 diabetes over 5 y were estimated by using logistic regression . RESULTS During the 5-y period , 971 new cases ( 572 men and 399 women ) of type 2 diabetes were self-reported . In men , fish intake was significantly associated with a decreased risk of type 2 diabetes ; multivariable-adjusted ORs of type 2 diabetes for the highest compared with the lowest quartile of intake were 0.73 ( 95 % CI : 0.54 , 1.00 ; P-trend = 0.04 ) for total fish and seafood and 0.68 ( 95 % CI : 0.50 , 0.92 ; P-trend = 0.016 ) for small and medium fish ( horse mackerel and sardine , saury and mackerel , and eel ) . Additional analysis by fat content of fish did not detect any significant association for each category . In women , fish intake was not appreciably associated with type 2 diabetes risk . CONCLUSION In a population with high fish and seafood intake , fish consumption was associated with a lower risk of type 2 diabetes in men but not in women It remains unclear what long-term effects of substituting carbohydrates at the expense of protein or fat may have with regard to diabetes risk . Our objective was to evaluate carbohydrate intake in predicting type 2 diabetes using substitution models for fat and protein . We conducted a prospect i ve cohort study of 9,702 men and 15,365 women aged 35 - 65 years and free of diabetes at baseline ( 1994 - 8 ) who were followed for incident type 2 diabetes until 2005 . Dietary intake of macronutrients was estimated with a vali date d FFQ . We estimated the relative risk ( RR ) using Cox proportional hazards analysis . During 176,117 person-years of follow-up we observed 844 incident cases of physician-confirmed type 2 diabetes . After adjustment for age , BMI , waist circumference , potential lifestyle and dietary confounders , substituting 5 % of energy intake from total , saturated , or monounsaturated fat with carbohydrates was not associated with diabetes risk . In contrast , substituting carbohydrates for protein or PUFA was inversely related to diabetes risk ( RR for 5 % energy substitution of protein 0.77 ( 95 % CI 0.64 , 0.91 ) ; RR for PUFA 0.83 ( 95 % CI 0.70 , 0.98 ) ) . These associations appeared to be similar for men and women , but gained statistical significance only among men for protein ( RR 0.78 ( 95 % CI 0.61 , 0.99 ) ) . Restricted cubic spline regression did not indicate non-linearity of these associations ( P for non-linearity in full cohort was 0.353 and 0.349 ) . In conclusion , a higher carbohydrate intake at the expense of protein and PUFA might be associated with decreased diabetes risk BACKGROUND Long-chain polyunsaturated n-3 ( omega-3 ) fatty acids , found mainly in fish , have been postulated to reduce type 2 diabetes ( T2D ) risk . However , the role of long-chain n-3 fatty acids and fish intake in the development of T2D remains unresolved . OBJECTIVE We examined associations between fish , shellfish , and long-chain n-3 fatty acids and the risk of T2D in a middle-aged Chinese population . DESIGN This was a prospect i ve population -based cohort study in 51,963 men and 64,193 women free of T2D , cardiovascular disease , and cancer at baseline with valid dietary information . Dietary intake , physical activity , and anthropometric measurements were collected . A Cox regression model was used to evaluate the association of fish , shellfish , and long-chain n-3 fatty acid ( in g/d ) with risk of T2D . RESULTS Fish , shellfish , and long-chain n-3 fatty acid intakes were inversely associated with T2D in women . The relative risks [ RRs ( 95 % CI ) ] for quintiles of fish intake were 1.00 , 0.96 ( 0.86 , 1.06 ) , 0.84 ( 0.75 , 0.94 ) , 0.80 ( 0.71 , 0.90 ) , and 0.89 ( 0.78 , 1.01 ) ( P for trend = 0.003 ) and for shellfish were 1.00 , 0.91 ( 0.82 , 1.01 ) , 0.79 ( 0.71 , 0.89 ) , 0.80 ( 0.71 , 0.91 ) , and 0.86 ( 0.76 , 0.99 ) ( P for trend = 0.006 ) . In men , only the association between shellfish intake and T2D was significant . The RRs ( 95 % CI ) for quintiles of fish intake were 1.00 , 0.92 ( 0.75 , 1.13 ) , 0.80 ( 0.65 , 1.00 ) , 0.89 ( 0.72 , 1.11 ) , and 0.94 ( 0.74 , 1.17 ) ( P for trend = 0.50 ) and for shellfish intake were 1.00 , 0.93 ( 0.76 , 1.12 ) , 0.70 ( 0.56 , 086 ) , 0.66 ( 0.53 , 0.82 ) , and 0.82 ( 0.65 , 1.02 ) ( P for trend = 0.003 ) . CONCLUSIONS An inverse association between fish and shellfish intake and T2D in women was found . No evidence of a detrimental effect of fish intake in this population was observed |
827 | 24,976,965 | The current evidence base suggests that online eLearning is equivalent , possibly superior to traditional learning . | BACKGROUND Health systems worldwide are facing shortages in health professional workforce .
Several studies have demonstrated the direct correlation between the availability of health workers , coverage of health services , and population health outcomes .
To address this shortage , online eLearning is increasingly being adopted in health professionals ' education .
To inform policy-making , in online eLearning , we need to determine its effectiveness . | AIMS AND OBJECTIVES To detect problems when classifying pressure ulcers and to examine whether an e-learning program is able to increase the classification skills of qualified nurses and nursing students . BACKGROUND Both the distinction between pressure ulcer grade s and the differentiation between moisture lesions is difficult . Misclassification and incorrect identification of the lesions results in inadequate preventive and therapeutic measures . Education and training are important for spreading evidence -based insights about this topic . DESIGN Repeated measure design , consisting of one pretest and three posttests . METHODS The experimental intervention consisted of a one-hour session during which the participants independently went over an e-learning program . The control intervention consisted of a one-hour lecture . Both interventions had the same learning contents . A convenience sample of 212 qualified nurses and 214 final-year nursing students was r and omly assigned to an experimental- and a control group . RESULTS In the pretest , the classification skills were low . After the intervention , these skills improved significantly in both groups . The nursing students achieved better results when using the e-learning program . Among the qualified nurses , there was no difference between the learning methods . Although the classification skills decreased in the posttests , they did not drop under the level of the pretest . CONCLUSION The actual classification system does not provide the necessary information about the severity of a pressure ulcer . The differential diagnosis between a moisture lesion was complicated . The classification skills of the qualified nurses and nursing students increased by both learning methods . Repetition remains , however , necessary . RELEVANCE TO CLINICAL PRACTICE Both instruction methods are adequate to acquire the knowledge about the differences between moisture lesions and pressure ulcers . E-learning allows study ing in one 's own time and place , and could therefore be very suitable for repetition of the training . How to organise this training could be a subject for further research OBJECTIVE Nurses need to be competent and confident in performing drug calculations to ensure patient safety . The purpose of this study is to compare an interactive e-drug calculations package , developed using Cognitive Load Theory as its theoretical framework , with traditional h and out learning support on nursing students ' drug calculation ability , self-efficacy and support material satisfaction . DESIGN A cluster r and omised controlled trial comparing the e-package with traditional h and out learning support was conducted with a September cohort ( n=137 ) and a February cohort ( n=92 ) of second year diploma nursing students . Students from each cohort were geographically dispersed over 3 or 4 independent sites . MEASUREMENTS Students from each cohort were invited to participate , halfway through their second year , before and after a 12 week clinical practice placement . During their placement the intervention group received the e-drug calculations package while the control group received traditional ' h and out ' support material . Drug calculation ability and self-efficacy tests were given to the participants pre- and post-intervention . Participants were given the support material satisfaction scale post-intervention . RESULTS Students in both cohorts r and omised to e-learning were more able to perform drug calculations than those receiving the h and out ( September : mean 48.4 % versus 34.7 % , p=0.027 ; February : mean 47.6 % versus 38.3 % , p=0.024 ) . February cohort students using the e-package were more confident in performing drug calculations than those students using h and outs ( self-efficacy mean 56.7 % versus 45.8 % , p=0.022 ) . There was no difference in improved self-efficacy between intervention and control for students in the September cohort . Students who used the package were more satisfied with its use than the students who used the h and out ( mean 29.6 versus 26.5 , p=0.001 ) , particularly with regard to the package enhancing their learning ( p=0.023 ) , being an effective way to learn ( p=0.005 ) , providing practice and feedback ( p<0.001 ) , being accessible ( p=0.027 ) , user friendly ( p=0.02 ) and providing learning enjoyment ( p=0.022 ) . CONCLUSION It is essential that nurses are educated and supported to become , and remain , confident and competent in performing drug calculations . This study found the e-drug calculations package , based on Cognitive Load Theory , to be significantly more effective than a h and out in improving students ' drug calculation ability and self-efficacy , with students who used the package being significantly more satisfied with its use than students who used the h and out . This package could particularly be useful for the continuing professional development of any healthcare professional involved in drug calculations Oral healthcare providers have a clinical opportunity for early detection of disordered eating behaviors because they are often the first health professionals to observe overt oral and physical signs . Curricula regarding early recognition of this oral/systemic medical condition are limited in oral health educational programs . Web-based learning can supplement and reinforce traditional learning and has the potential to develop skills . The study purpose was to determine the efficacy of a theory-driven Web-based training program to increase the capacity of oral health students to perform behaviors related to the secondary prevention of disordered eating behaviors . Using the Reach , Effectiveness , Adoption , Implementation and Maintenance evaluation framework , a longitudinal group-r and omized controlled trial involving 27 oral health classes from 12 oral health education programs in the United States was implemented to assess the efficacy of the Web-based training on attitudes , knowledge , self-efficacy and skills related to the secondary prevention of disordered eating behaviors . Mixed-model analysis of covariance indicated substantial improvements among students in the intervention group ( effect sizes : 0.51 - 0.83 ) on all six outcomes of interest . Results suggest that the Web-based training program may increase the capacity of oral healthcare providers to deliver secondary prevention of disordered eating behaviors . Implication s and value of using the Reach , Effectiveness , Adoption , Implementation and Maintenance framework are discussed The objective of this study was to evaluate the effectiveness of e-learning as a supplement to on-campus education for the acquisition of skills in palpation and ultrasound examination of the knee in a physiotherapy degree course . Forty-six students ( 28 females ) from the University of Granada , with a mean age of 21.5 yrs , received 4 h of theoretical and practical on-campus training on palpation and ultrasound examination of the knee joint . They were then r and omly distributed into two groups : experimental , with free access to the ECOFISIO website on musculoskeletal palpation and ultrasound assessment ; and control , with access to documents and books on the topic . Structured objective clinical evaluation ( SOCE ) and multiple-choice question naire ( MCQ ) were used to assess the educational intervention . We also measured the time taken by the students to generate a reliable ultrasound image and to localize a specific knee structure by palpation . There was no significant intergroup difference in the acquisition of theoretical knowledge as assessed by the MCQ ( p = 0.39 ) . Scores were significantly higher in the experimental group than in the control group for skills in palpation ability ( p = 0.041 ) and ultrasound assessment ( p < 0.001 ) of the knee . Students in the e-learning group needed less time to palpate the musculoskeletal structure ( p = 0.041 ) but more time ( p = 0.012 ) to obtain their superior ultrasound images . In conclusion , these results contribute evidence that e-learning is an effective educational strategy for physiotherapy students to acquire skills in palpation and ultrasound imaging of the knee as a supplement to on-campus education The purpose of the study was to assess the effectiveness of supplementing traditional classroom teaching with Web-based learning design when teaching intramuscular injection nursing skills . Four clusters of nursing students at a junior college in eastern Taiwan were r and omly assigned to experimental and control groups . A total of 147 students ( 80 in the experimental group , 67 in the control group ) completed the study . All participants received the same classroom lectures and skill demonstration . The experimental group interacted using a Web-based course and were able to view the content on dem and . The students and instructor interacted via a chatroom , the bulletin board , and e-mail . Participants in the experimental group had significantly higher scores on both intramuscular injection knowledge and skill learning . A Web-based design can be an effective supplementing learning tool for teaching nursing knowledge and skills Purpose Computer-based methods of instruction offer the possibility of helping medical students to learn clinical skills and professionalism . Without rigorous documentation of its pedagogic advantages , the utility of Internet-based teaching is not solidly grounded . The authors carried out a prospect i ve , r and omized study of educational outcomes , comparing a traditional classroom course in clinical ethics with the same course supplemented by Internet-based discussion . Methods Introduction to Clinical Ethics is a sophomore medical school course that teaches a specific method for analyzing clinical ethical problems . One sophomore class was r and omly assigned to either classroom teaching alone ( traditional group ; n = 65 ) or classroom teaching supplemented with Internet-based discussion s of cases illustrating ethical issues ( Internet component group ; n = 62 ) . A final case analysis comprehensively evaluated students ' underst and ing of the analytic method taught in the course . Grade s for both groups on the final case analyses , which were rated by two external review ers , were compared . Results The students ' underst and ing of ethical analysis , as measured by grade s of external review ers on the final paper , was significantly higher for those in the course with the Internet component than it was for those in the traditional course ( 3.0 ± 0.6 and 2.6 ± 0.7 , respectively ; p < .005 ) . Conclusion The study documents the incremental value of Internet-based teaching of clinical ethics to sophomore medical students Background Electronic Voting Systems have been used for education in a variety of disciplines . Outcomes from these studies have been mixed . Because results from these studies have been mixed , we examined whether an EVS system could enhance a lecture 's effect on educational outcomes . Methods A cohort of 127 Year 5 medical students at the University of Adelaide was stratified by gender , residency status and academic record then r and omised into 2 groups of 64 and 63 students . Each group received consecutive 40-minute lectures on two clinical topics . One group received the EVS for both topics . The other group received traditional teaching only . Evaluation was undertaken with two , 15- question multiple-choice question naires ( MCQ ) assessing knowledge and problem solving and undertaken as a written paper immediately before and after the lectures and repeated online 8–12 weeks later . St and ardised institutional student question naires were completed for each lecture and independent observers assessed student behaviour during the lectures . Lecturer 's opinions were assessed by a question naire developed for this study . Results Two-thirds of students r and omised to EVS and 59 % of students r and omised to traditional lectures attended . One-half of the students in the EVS group and 41 % in the traditional group completed all question naires . There was no difference in MCQ scores between EVS and traditional lectures ( p = 0.785 ) . The cervical cancer lectures showed higher student ranking in favour of EVS in all parameters . The breast cancer lectures showed higher ranking in favour of traditional lectures in 5 of 7 parameters ( p < 0.001 ) . The observed higher-order lecturer-students interactions were increased in the EVS lecture for one lecturer and reduced for the other . Both lecturers felt that the EVS lectures were difficult to prepare , that they were able to keep to time in the traditional lectures , that the educational value of both lecture styles was similar , and that they were neutral-to-slightly favourably disposed to continue with the EVS technology . The 2 lecturers disagreed regarding the ease of preparation of the traditional lecture , their ability to keep to time in the EVS lecture , and personal satisfaction with the EVS lecture . The lecturers felt that EVS encouraged student participation and helped identify where students were having difficulty . Conclusion In this setting , EVS technology used in large group lectures did not offer significant advantages over the more traditional lecture format OBJECTIVE The purpose of this study is to compare whether students ' learning outcomes would be better in a design ed learning environment ( WebCT ) than in a conventional web site ( WWW ) with similar course material but without special learning tools . CONTEXT Third-year medical students in an introductory course on medical informatics at the University of Helsinki , Finl and . METHODS Students were r and omly assigned to a WebCT group ( n=39 ) and a WWW group ( n=46 ) . The students in the WebCT group utilized the course material in general discussion groups , special discussion s about lectures , quizzes and students ' own notes . The WWW group had access only to the course material . The learning outcome was assessed by administering an on-line examination and the learning experience of the students was assessed by an on-line quiz . RESULTS The course grade was significantly higher in the WebCT group as compared to the WWW group . This finding was more prominent among females . The students of the WebCT group also experienced significantly more improvement in collaboration with the use of computers than the students in the WWW group . CONCLUSIONS Based on our results , web-based learning seems to be more effective when students are provided with specially design ed learning tools OBJECTIVES To compare the effectiveness of small-group training in correct inhaler technique with self-directed Internet-based training . DESIGN Pharmacy students were r and omly allocated to 1 of 2 groups : small-group training ( n = 123 ) or self-directed Internet-based training ( n = 113 ) . Prior to intervention delivery , all participants were given a placebo Turbuhaler and product information leaflet and received inhaler technique training based on their group . Technique was assessed following training and predictors of correct inhaler technique were examined . ASSESSMENT There was a significant improvement in the number of participants demonstrating correct technique in both groups ( small group training , 12 % to 63 % ; p < 0.05 ; and Internet-based training , 9 % to 59 % ; p < 0.05 ) post intervention , with no significant difference between the groups in the percent change ( n = 234 , p > 0.05 ) . Increased student confidence following the intervention was a predictor for correct inhaler technique . CONCLUSIONS Self-directed Internet-based training is as effective as small-group training in improving students ' inhaler technique This study examined the effectiveness of a series of Web-based , multimedia tutorials on methods of human body composition analysis . Tutorials were developed around four body composition topics : hydrodensitometry ( underwater weighing ) , dual-energy X-ray absorptiometry , bioelectrical impedance analysis , and total body electrical conductivity . Thirty-two students enrolled in the course were r and omly assigned to learn the material through either the Web-based tutorials only ( " Computer " ) , a traditional lecture format ( " Lecture " ) , or lectures supplemented with Web-based tutorials ( " Both " ) . All students were administered a vali date d pretest before r and omization and an identical posttest at the completion of the course . The reliability of the test was 0.84 . The mean score changes from pretest to posttest were not significantly different among the groups ( 65.4 plus minus 17.31 , 78.82 plus minus 21.50 , and 76 plus minus 21.22 for the Computer , Both , and Lecture groups , respectively ) . Additionally , a Likert-type assessment found equally positive attitudes toward all three formats . The results indicate that Web-based tutorials are as effective as the traditional lecture format for teaching these topics Background : Little evidence exists to guide the selection of methods for teaching clinical diagnosis . Purpose : To compare the efficacy , student preference , and cost of a Web-based ( WB ) program versus a st and ardized patient ( SP ) encounter for teaching clinical diagnosis skills to 2nd-year medical students . Methods : R and omized , controlled , crossover study comparing WB versus SP-based teaching for the clinical diagnosis of abdominal pain and headache . Outcome measures were performance on a 2-case SP examination ( scored on the basis of a checklist completed by a faculty observer and an objective score on a postencounter subjective- objective assessment plan [ SOAP ] note ) , format preferences as assessed by end-of-course evaluations , and cost . Results : Thirty students consented to participate . WB and SP training produced similar scores on both the Abdominal Pain checklist ( 66 % vs. 62 % ; p = . 17 ) and Headache checklist ( 56 % vs. 63 % ; p = . 07 ) . WB training produced a higher score on the Abdominal Pain SOAP note ( 69 % vs. 47 % ; p = . 006 ) , but not the Headache SOAP note ( 69 % vs. 67 % ; p = . 85 ) . Students rated the SP format higher than the WB format on all 7 preference measures . Start-up costs were estimated at $ 2,190 for the SP format and $ 2,250 for the WB format . Ongoing costs per case per student were estimated to be $ 45 for the SP format and $ 30 for the WB format . Conclusions : WB and SP learning outcomes were comparable , but students preferred the SP format . Start-up costs were comparable , but the ongoing costs of the WB format were less expensive , suggesting that WB teaching may be a viable strategy PURPOSE This study is an assessment of the acceptability and short-term educational efficacy of interactive spaced education compared to web based teaching cases within the compact time frame of a clinical clerkship . MATERIAL S AND METHODS All 237 third-year students completing their 3-month surgery clerkships at 2 medical schools were asked to complete a urology online-education program covering 4 core topics of benign prostatic hyperplasia , erectile dysfunction , prostate cancer and screening with prostate specific antigen . Students were stratified by clinical site and r and omized to 1 of 2 cohorts . Students in cohort A received interactive spaced education on prostate cancer/prostate specific antigen and web based teaching on benign prostatic hyperplasia/erectile dysfunction . Students in cohort B received interactive spaced education on benign prostatic hyperplasia/erectile dysfunction and web based teaching on prostate cancer/prostate specific antigen . A vali date d 28-item test on all 4 topics was administered at the end of the 10-week program . RESULTS No statistically significant differences in end-of-program test scores were observed between cohorts in the topics of prostate cancer/prostate specific antigen with 87.6 % ( SD 12.9 ) for cohort A ( interactive spaced education ) and 82.4 % ( SD 19.6 ) for cohort B ( web based teaching ) ( p = 0.25 ) . Similarly there was also no statistically significant difference in test scores in the topics of benign prostatic hyperplasia/erectile dysfunction with 79.5 % ( SD 15.9 ) for cohort A ( web based teaching ) and 82.1 % ( SD 14.7 ) for cohort B ( interactive spaced education , p = 0.28 ) . When students were asked which format they would prefer if they were to receive all their urology online education in a single format , 55 % of students ( 109 of 198 respondents ) preferred interactive spaced education while 45 % ( 89 of 109 ) preferred web based teaching ( p = 0.16 ) . CONCLUSIONS Within the compact time frame of a clinical clerkship interactive spaced education is equivalent to web based teaching in short-term learning gains and in acceptability by medical students The CONSORT ( Consoli date d St and ards of Reporting Trials ) statement is used worldwide to improve the reporting of r and omized , controlled trials . Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . BACKGROUND It is essential that medical students are adequately trained in smoking cessation . A web-based tobacco abstinence training program might supplement or replace traditional didactic methods . METHODS One-hundred and forty third-year medical students were all provided access to a self-directed web-based learning module on smoking cessation . Thereafter , they were r and omly allocated to attend 1 of 4 education approaches : ( a ) web-based training using the same tool , ( b ) lecture , ( c ) role playing , and ( d ) supervised interaction with real patients . RESULTS Success of the intervention was measured in an objective structured clinical examination . Scores were highest in Group 4 ( 35.9 ± 8.7 ) , followed by Groups 3 ( 35.7 ± 6.5 ) , 2 ( 33.5 ± 9.4 ) , and 1 ( 28.0 ± 9.6 ; p = .007 ) . Students in Groups 4 ( 60.7 % ) and 3 ( 57.7 % ) achieved adequate counseling skills more frequently than those in Groups 2 ( 34.8 % ) and 1 ( 30 % ; p = .043 ) . There was no difference in the scores reflecting theoretical knowledge ( p = .439 ) . Self- assessment of cessation skills and students ' satisfaction with training was significantly better in Groups 3 and 4 as compared with 1 and 2 ( p < .001 and p = .006 , respectively ) . CONCLUSIONS Role playing and interaction with real patients are equally efficient and both more powerful learning tools than web-based learning with or without a lecture BACKGROUND Despite calls for medical school curricula that address care for the underserved , published evaluations of such curricula are few and often do not assess clinical skills . This study assesses the changes in self-efficacy and clinical skills result ing from faculty-led or web-based curricula on care for the underserved . METHODS Third-year students on 6-week 2003 - 2004 pediatric clerkships were block-r and omized to a curriculum on caring for the underserved in one of three formats : established ( readings only ) , faculty-led , or web-based . Primary outcomes were pre- and post-curriculum changes in self-efficacy and clinical skills . ANCOVA was used to test differences among curriculum groups , adjusting for prior experiences with the underserved . Analyses were performed in 2007 . RESULTS A total of 138 students participated , with 121 ( 88 % ) completing both pre- and post-tests . Compared to the established-curriculum students , both faculty-led and web-based students improved their self-efficacy in establishing achievable goals with underserved families , while web-based students improved their self-efficacy around knowledge of community re sources . Significantly more new skills were performed by both faculty-led ( mean [SD]=3.3[1.8 ] ) and web-based curriculum students ( 2.9[1.5 ] ) , compared to established-curriculum students ( 1.5[1.4 ] ) . Compared to established-curriculum students , more faculty-led and web-based students also reported new skills in locating re sources to meet the needs of underserved patients and in following up on referrals to ensure that families accessed needed care . CONCLUSIONS Web-based and faculty-led curricula improve medical student self-efficacy and clinical skills . Results from specific self-efficacy and skill items facilitate targeted curricular improvement PURPOSE Spaced education is a novel form of online education that harnesses the 2 psychology research findings of spacing and testing effects . Spaced education is delivered by daily emails containing clinical ly relevant multiple choice questions . To take advantage of the spacing effect the questions are repeated at fixed intervals for a fixed number of repetitions . An adaptive spaced education system was developed to customize spacing intervals and the number of repetitions based on learner knowledge level . To determine whether this system improves learning efficiency I performed a r and omized trial to compare the learning efficiency of adaptive vs nonadaptive spaced education systems among surgery students at 2 medical schools . MATERIAL S AND METHODS A total of 62 year 3 students were r and omized to identical course content in adaptive or nonadaptive spaced education formats . The course consisted of 40 vali date d , spaced education items on the 4 urology topics benign prostatic hyperplasia , erectile dysfunction , prostate cancer and prostate specific antigen screening . The nonadaptive cohort received daily emails containing 2 questions with a linear review of the material 20 days after initial presentation . The adaptive cohort received daily emails via an adaptive algorithm that limited the repetition of mastered content . Each cohort completed a vali date d end of course test . RESULTS The adaptive cohort answered significantly fewer spaced education items than the nonadaptive cohort ( p = 0.001 ) but achieved comparable end of course test scores ( p = 0.37 ) . The adaptive algorithm increased learning efficiency by 38 % . CONCLUSIONS Adaptive spaced education boosts learning efficiency Purpose To evaluate a five-year experience ( 1995–2000 ) developing and integrating computer cases into a required clerkship . Method In Study 1 , 54 volunteer students were r and omly assigned to study articles , a paper case , or a computer case on low back pain/kidney stones . Students were given an exam immediately after the exercise and one week later . In Study 2 , 325 clerkship students were asked to select and complete two computer cases or to prepare assignments on unrelated topics . Among the cases offered were two test cases on low back pain/kidney stones and pneumonia . Questions specific to the computer test cases ( CC ) and other noncomputer cases ( NCC ) were in the final exam . Exam scores related to CC questions and NCC questions were compared between the groups of students who did and did not complete the computer cases . Students also rated the computer cases on a question naire . Results In Study 1 , reading articles required the most time and received the most negative comments . The students who completed the computer case scored the best on the exam one week later . In Study 2 , the students who completed the two computer cases scored significantly higher on the CC questions than did students who studied only one or none of the computer cases ( p < .001 ) . There was no difference among groups for the NCC scores ( p = .76 ) . Students rated the computer cases with a mean of 6 on a seven-point scale ( 7 = strongly agree ) . Conclusion Computer cases are effective learning tools , are well-received by students , and can be successfully integrated into existing clerkships Background Tanzania , like many developing countries , faces a crisis in human re sources for health . The government has looked for ways to increase the number and skills of health workers , including using distance learning in their training . In 2008 , the authors review ed and assessed the country 's current distance learning programmes for health care workers , as well as those in countries with similar human re source challenges , to determine the feasibility of distance learning to meet the need of an increased and more skilled health workforce . Methods Data were collected from 25 distance learning programmes at health training institutions , universities , and non-governmental organizations throughout the country from May to August 2008 . Methods included internet research ; desk review ; telephone , email and mail-in surveys ; on-site observations ; interviews with programme managers , instructors , students , information technology specialists , preceptors , health care workers and Ministry of Health and Social Welfare representatives ; and a focus group with national HIV/AIDS care and treatment organizations . Results Challenges include lack of guidelines for administrators , instructors and preceptors of distance learning programmes regarding roles and responsibilities ; absence of competencies for clinical components of curricula ; and technological constraints such as lack of access to computers and to the internet . Insufficient funding result ed in personnel shortages , lack of appropriate training for personnel , and lack of material s for students . Nonetheless , current and prospect i ve students expressed overwhelming enthusiasm for scale-up of distance learning because of the unique financial and social benefits offered by these programs . Participants were retained as employees in their health care facilities , and remained in their communities and supported their families while advancing their careers . Space in health training institutions was freed up for new students entering in-residence pre-service training . Conclusions A blended print-based distance learning model is most feasible at the national level due to current re source and infrastructure constraints . With an increase in staffing ; improvement of infrastructure , coordination and curricula ; and de central ization to the zonal or district level , distance learning can be an effective method to increase both the skills and the numbers of qualified health care workers capable of meeting the health care needs of the Tanzanian population Background Technology-enhanced learning ( TEL ) gives a view to improved education . However , there is a need to clarify how TEL can be used effectively . The study compared students ' attitudes and opinions towards a traditional face-to-face course on theoretical radiological science and a TEL course where students could combine face-to-face lectures and e-learning modules at their best convenience . Methods 42 third-year dental students were r and omly assigned to the traditional face-to-face group and the TEL group . Both groups completed question naires before the beginning and after completion of the course on attitudes and opinions towards a traditional face-to-face lectures and technology-enhanced learning . After completion of the course both groups also filled in the vali date d German- language TRIL ( Trierer Inventar zur Lehrevaluation ) question naire for the evaluation of courses given at universities . Results Both groups had a positive attitude towards e-learning that did not change over time . The TEL group attended significantly less face-to-face lectures than the traditional group . However , both groups stated that face-to-face lectures were the basis for education in a theoretical radiological science course . The members of the TEL group rated e-mail reminders significantly more important when they filled in the question naire on attitudes and opinions towards a traditional face-to-face lectures and technology-enhanced learning for the second time after completion of the course . The members of the technology-enhanced learning group were significantly less confident in passing the exam compared to the members of the traditional group . However , examination results did not differ significantly for traditional and the TEL group . Conclusions It seems that technology-enhanced learning in a theoretical radiological science course has the potential to reduce the need for face-to-face lectures . At the same time examination results are not impaired . However , technology-enhanced learning can not completely replace traditional face-to-face lectures , because students indicate that they consider traditional teaching as the basis of their education Background Writing plays a central role in the communication of scientific ideas and is therefore a key aspect in research er education , ultimately determining the success and long-term sustainability of their careers . Despite the growing popularity of e-learning , we are not aware of any existing study comparing on-line vs. traditional classroom-based methods for teaching scientific writing . Methods Forty eight participants from a medical , nursing and physiotherapy background from US and Brazil were r and omly assigned to two groups ( n = 24 per group ) : An on-line writing workshop group ( on-line group ) , in which participants used virtual communication , google docs and st and ard writing templates , and a st and ard writing guidance training ( st and ard group ) where participants received st and ard instruction without the aid of virtual communication and writing templates . Two outcomes , manuscript quality was assessed using the scores obtained in Six subgroup analysis scale as the primary outcome measure , and satisfaction scores with Likert scale were evaluated . To control for observer variability , inter-observer reliability was assessed using Fleiss 's kappa . A post-hoc analysis comparing rates of communication between mentors and participants was performed . Nonparametric tests were used to assess intervention efficacy . Results Excellent inter-observer reliability among three review ers was found , with an Intraclass Correlation Coefficient ( ICC ) agreement = 0.931882 and ICC consistency = 0.932485 . On-line group had better overall manuscript quality ( p = 0.0017 , SSQSavg score 75.3 ± 14.21 , ranging from 37 to 94 ) compared to the st and ard group ( 47.27 ± 14.64 , ranging from 20 to 72 ) . Participant satisfaction was higher in the on-line group ( 4.3 ± 0.73 ) compared to the st and ard group ( 3.09 ± 1.11 ) ( p = 0.001 ) . The st and ard group also had fewer communication events compared to the on-line group ( 0.91 ± 0.81 vs. 2.05 ± 1.23 ; p = 0.0219 ) . Conclusion Our protocol for on-line scientific writing instruction is better than st and ard face-to-face instruction in terms of writing quality and student satisfaction . Future studies should evaluate the protocol efficacy in larger longitudinal cohorts involving participants from different language In recent years , increasing attention has been paid to web-based learning although the advantages of computer-aided instruction over traditional teaching formats still need to be confirmed . This study examined whether participation in an online module on the differential diagnosis of dyspnoea impacts on student performance in a multiple choice examination of factual knowledge in cardiology and pneumology . A virtual problem-based learning environment for medical students supervised by postgraduate teachers was created . Seventy-four out of 183 fourth-year medical students volunteered to use the online module while attending a 6-week cardio-respiratory curriculum in summer 2007 . Of these , 40 were r and omly selected to be included ( intervention group ) ; the remaining 34 served as an internal control group . Analysis of all written exams taken during the preceding term showed that both groups were comparable ( 86.4 ± 1.1 vs. 85.9 ± 1.1 % ; p = 0.751 ) . Students in the intervention group scored significantly higher in the final course assessment than students allocated to the control group ( 84.8 ± 1.3 vs. 79.5 ± 1.4 % ; p = 0.006 ; effect size 0.67 ) . Thus , additional problem-based learning with an online module as part of an undergraduate cardio-respiratory curriculum lead to higher students ’ scores in an exam testing factual knowledge . Whether using this teaching format increases overall student motivation to engage in the learning process needs to be further investigated Background The present study aim ed at determining if the addition of spaced education to traditional face-to-face lectures increased the time students kept busy with the learning content of a theoretical radiological science course . Methods The study comprised two groups of 21 third-year dental students . The students were r and omly assigned to a “ traditional group ” and a “ spaced education group ” . Both groups followed a traditional face-to-face course . The intervention in the spaced education group was performed in way that these students received e-mails with a delay of 14 days to each face-to-face lecture . These e-mails contained multiple choice questions on the learning content of the lectures . The students returned their answers to the questions also by e-mail . On return they received an additional e-mail that included the correct answers and additional explanatory material .All students of both groups documented the time they worked on the learning content of the different lectures before a multiple choice exam was held after the completion of the course . All students of both groups completed the TRIL question naire ( Trierer Inventar zur Lehrevaluation ) for the evaluation of courses at university after the completion of the course . The results for the time invested in the learning content and the results of the question naire for the two groups were compared using the Mann – Whitney-U test . Results The spaced education group spent significantly more time ( 216.2 ± 123.9 min ) on keeping busy with the learning content compared to the traditional group ( 58.4 ± 94.8 min , p < .0005 ) . The spaced education group rated the didactics of the course significantly better than the traditional group ( p = .034 ) . The students of the spaced education group also felt that their needs were fulfilled significantly better compared to the traditional group as far as communication with the teacher was concerned ( p = .022 ) . Conclusions Adding spaced education to a face-to-face theoretical radiological science course activates students in a way that they spend significantly more time on keeping busy with the learning content Orthodontic records- study models , panoramic and cephalometric radiographs , and the patient 's facial and intraoral photographs-are used to collect data to establish a diagnosis and to develop problem-solution lists . These records , however , can be damaged or lost when dispensed to students and need to be stored and maintained every year . An orthodontic diagnosis web site , therefore , has been set up using digital records to provide students with an accessible source of complete , good- quality study material s. The web site is also used for clinical examination in orthodontic courses . The effectiveness of the web-based digital records in providing relevant information to students in comparison to the traditional records was evaluated by a r and omized controlled trial involving ninety-nine second-year dental students . One group ( fifty students ) studied two cases from the web site ; the other group ( forty-nine students ) studied the same two cases from traditional orthodontic records . Effectiveness was assessed by comparing test scores and the time spent on the tests by t-statistics . There were no significant differences between means for the two study groups in test performance or time . Attitudes of students toward the web site , assessed from post-test question naires , were positive . It was concluded that web-based digital orthodontic records were as effective in teaching clinical orthodontic diagnosis as were conventional records Background The world is short of 7.2 million health – care workers and this figure is growing . The shortage of teachers is even greater , which limits traditional education modes . eLearning may help overcome this training need . Offline eLearning is useful in remote and re source –limited setting s with poor internet access . To inform investments in offline eLearning , we need to establish its effectiveness in terms of gaining knowledge and skills , students ’ satisfaction and attitudes towards eLearning . Methods We conducted a systematic review of offline eLearning for students enrolled in undergraduate , health – related university degrees . We included r and omised controlled trials that compared offline eLearning to traditional learning or an alternative eLearning method . We search ed the major bibliographic data bases in August 2013 to identify articles that focused primarily on students ’ knowledge , skills , satisfaction and attitudes toward eLearning , and health economic information and adverse effects as secondary outcomes . We also search ed reference lists of relevant studies . Two review ers independently extracted data from the included studies . We synthesized the findings using a thematic summary approach . Findings Forty – nine studies , including 4955 students enrolled in undergraduate medical , dentistry , nursing , psychology , or physical therapy studies , met the inclusion criteria . Eleven of the 33 studies testing knowledge gains found significantly higher gains in the eLearning intervention groups compared to traditional learning , whereas 21 did not detect significant differences or found mixed results . One study did not test for differences . Eight studies detected significantly higher skill gains in the eLearning intervention groups , whilst the other 5 testing skill gains did not detect differences between groups . No study found offline eLearning as inferior . Generally no differences in attitudes or preference of eLearning over traditional learning were observed . No clear trends were found in the comparison of different modes of eLearning . Most of the studies were small and subject to several biases . Conclusions Our results suggest that offline eLearning is equivalent and possibly superior to traditional learning regarding knowledge , skills , attitudes and satisfaction . Although a robust conclusion can not be drawn due to variable quality of the evidence , these results justify further investment into offline eLearning to address the global health care workforce shortage summary A Web-based educational model , called JUTE , was developed for the early diagnosis of melanoma . It was compared with a control Website composed of information available on the Internet for teaching undergraduate medical students . The JUTE model was design ed to allow the student linear navigation of the main topics that were assumed to be important in learning to make a diagnosis . The rate of success in correctly deciding to refer pigmented lesions to a dermatologist was compared among 34 new medical students who were r and omly divided into two groups . There was no significant difference between the JUTE and control groups in the pre-test . When comparing the pre- and post-tests , the number of correct decisions increased significantly only in the JUTE group . In the JUTE group there was a slight but significant improvement when comparing decisions about thin melanoma before and after the training . The educational approach chosen for the JUTE Website appears to be useful for teaching the early recognition of melanoma and could be used for larger educational campaigns of skin cancer prevention OBJECTIVE Advancements in technology and personal computing afford the development of novel teaching modalities such as online Web-based modules . These modules are currently being incorporated into undergraduate medical curricula and , in some paradigms , have been shown to be superior to traditional methods of instruction . The purpose of this study was to evaluate the ability of a computer-assisted learning ( CAL ) module to demonstrate content and spatial information in the context of cranial nerve anatomy . STUDY POPULATION Undergraduate anatomy students . METHODS A prospect i ve , r and omized , controlled trial was conducted comparing a CAL module to traditional text-/image-based learning supplements . Indications of the participants ' ability to translate spatial relationships between the trigeminal nerve and the craniofacial skeleton were assessed via a postintervention knowledge quiz . RESULTS No significant difference was identified between the CAL module and the control group . Students in both groups performed poorly in questions testing spatial relationships . CONCLUSIONS The CAL module used in the present study did not objective ly contribute to the underst and ing of spatial anatomic relationships of the cranial nerves in novice students . Despite this , these modules may help pique student interest and motivation and , as such , may be used in the context of supplemental learning re sources in existing university curricula This study compared the effectiveness of different instructional communication methods in a Web-based course on students ' cognitive learning , satisfaction , and motivation to complete the course . A total of 174 undergraduate nursing students were selected r and omly and assigned to experimental or control groups . Instruments included a demographic data form , two examinations on course material , a course satisfaction scale , and calculation of completion rates . All students received identical didactic Web-based instructional material s. However , type of communication varied among groups . No significant group differences were found for cognitive learning or motivation to complete the course . A significant group difference was found for student satisfaction with the course , indicating carefully planned communication strategies can improve satisfaction . A need for technical support also was evident . More research is needed to determine the best strategies to enhance student learning outcomes and decrease student attrition in Web-based courses BACKGROUND AND OBJECTIVES Most medical students learn clinical reasoning skills informally during clinical rotations that have varying quality of supervision . We conducted a r and omized controlled trial to determine if a workshop that uses " illness scripts " could improve students ' clinical reasoning skills when making diagnoses of patients portrayed in written scenarios . METHODS In 2007 - -2008 , 53 fourth-year medical students were r and omly assigned to either a family medicine ( intervention ) or psychiatry ( control ) clerkship at The Chinese University of Hong Kong . Students in the intervention group participated in a 3-hour workshop on clinical reasoning that used illness scripts . The workshop was conducted with small-group teaching using a Web-based set of clinical reasoning problems , individualized feedback , and demonstration of tutors ' reasoning aloud . The effectiveness of the intervention was assessed using the Diagnostic Thinking Inventory ( DTI ) and the measurement of individual students ' performance in solving clinical reasoning problems ( CRP ) . RESULTS The post-intervention overall DTI scores between groups were similar ( mean difference 0 , 95 % confidence interval [CI]= -7.4 to 7.4 ) . However , the total scores on the CRP assessment were 14 % ( 95 % CI=8 % to 21 % ) higher in the intervention group than in controls . CONCLUSION A workshop on illness scripts may have some benefit for improving diagnostic performance in clinical reasoning problems BACKGROUND Mannequin and computer-based simulators are useful for the practice of patient management , physical procedures , and competency . However , they are ineffective in teaching clinical medicine . StepStone Interactive Medical Software ( SS ) is a web-based medical learning modality that provides the user with a highly focused set of evaluative and interventional tasks to treat memorable virtual patients in a visual case-based format . OBJECTIVE To determine whether the SS learning modality is superior to traditional lecture format in medical student learning and retention . METHODS After Institutional Review Board ( IRB ) approval was obtained and the consents were signed , 30 third-year medical students were assigned r and omly to 2 groups of 15 students each : The control group received two 30-minute PowerPoint lectures ( Microsoft Corporation , Redmond , Washington ) about torsades de pointes ( TdP ) and pulseless electrical activity ( PEA ) , and the SS group was given 1 hour to review 2 SS cases teaching TdP and PEA . A preintervention test was given to assess their baseline knowledge . An immediate postintervention test was given to both groups . Twenty-two days later , a long-term retention test was administered . The results were analyzed using a Student t test for continuous variables . RESULTS The mean scores for the preintervention test in the control and SS groups were 44.9 ± 3 % and 44.1 ± 2 % , respectively ( p = 0.41 ) . The mean scores for the postintervention test in the control and SS groups were 61.7 ± 2 % and 86.7 ± 2 % , respectively ( p < 0.001 ) . Improvement from baseline knowledge was calculated , and the mean improvement was 16.8 ± 3 % in the control group and 42.5 ± 2 % in the SS group ( p < 0.001 ) . The long-term retention test revealed the mean scores of 55.8 ± 3 % in the control group and 70.1 ± 3 % in the SS group ( p < 0.001 ) . Long-term improvement from baseline knowledge was calculated and the control group improved by 10.9 ± 4 % , whereas the SS group improved by 26 ± 3 % ( p = 0.002 ) . CONCLUSIONS The SS learning modality demonstrated a significant improvement in student learning retention compared to traditional didactic lecture format . SS is an effective web-based medical education tool AIM To compare the effectiveness of an online information literacy tutorial with a face-to-face session for teaching information literacy skills to nurses . DESIGN R and omised control trial . PARTICIPANTS Seventy-seven first year undergraduate pre- registration diploma nursing students . INTERVENTION Online in-house information literacy tutorial COMPARISON One hour face-to-face session , covering the same material as the intervention , delivered by the nursing subject librarian . METHODS Search histories were scored using a vali date d checklist covering keyword selection , boolean operators , truncation and synonyms . Skills retention was measured at 1 month using the same checklist . Inferential statistics were used to compare search skills within and between groups pre and post-session . RESULTS The search ing skills of first year pre- registration nursing students improve following information literacy sessions ( p<0.001 ) , and remain unchanged 1 month later , regardless of teaching method . The two methods produce a comparable improvement ( p=0.263 ) . There is no improvement or degradation of skills 1 month post-session for either method ( p=0.216 ) . CONCLUSION Nurses Information literacy skills improve after both face-to-face and online instruction . There is no skills degradation at 1 month post-intervention for either method Computerized technological re sources have become essential in education , particularly for teaching topics that require the performance of specific tasks . These re sources can effectively help the execution of such tasks and the teaching-learning process itself . After the development of a Web site on the topic of nursing staff scheduling , this study aim ed at comparing the development of students involved in the teaching-learning process of the previously mentioned topic , with and without the use of computer technology . Two r and om groups of undergraduate nursing students from a public university in São Paulo state , Brazil , were organized : a case group ( used the Web site ) and a control group ( did not use the Web site ) . Data were collected from 2003 to 2005 after approval by the Research Ethics Committee . Results showed no significant difference in motivation or knowledge acquisition . A similar performance for the two groups was also verified . Other aspects observed were difficulty in doing the nursing staff scheduling exercise and the students ' acknowledgment of the topic 's importance for their training and professional lives ; easy access was considered to be a positive aspect for maintaining the Web site BACKGROUND A challenge to the practice of third-year clerkship rotations at remote locations is the maintenance of equivalent didactic lectures , especially in subspecialty components . There has been little objective assessment of the results of videoconference lectures on medical student clerkship education . METHODS Third-year surgical clerkship students , r and omly assigned to a 4-week rotation 75 miles from the medical school , received subspecialty lectures by interactive teleconference via an ISDN line at 128 kb/s . Weekly quiz results ( % correct ) of students who received videoconference lectures were compared with students receiving conventional lectures , and were analyzed by 2-tailed t tests for e quality of means . RESULTS A mean of 12 students were tested per quiz ( range , 5 - 21 students ) after videoconference lectures , and 98 students were tested after conventional lectures ( range , 41 - 146 students ) . The mean quiz score of students receiving video lectures was 70.5 % ( range , 65.4 % to 73.6 % ) ; and after conventional lectures the mean quiz score was 71.4 % ( range , 69.5 % to 76.8 % ) . There were no significant differences in the mean scores of the individual quizzes ( P = .16-.92 ) or between the totals ( P = .65 ) . CONCLUSIONS Telemedicine , using interactive videoconferencing , is an effective method for didactic lectures in a surgical clerkship . This technology allows students to receive interactive lectures at distant clinical sites and limit their travel Objectives Undergraduate medical teaching in occupational health ( OH ) is a challenge in universities around the world . Case-based e-learning with an attractive clinical context could improve the attitude of medical students towards OH . The study question is whether case-based e-learning for medical students is more effective in improving knowledge , satisfaction and a positive attitude towards OH than non-case-based textbook learning . Methods Participants , 141 second year medical students , were r and omised to either case-based e-learning or text-based learning . Outcome measures were knowledge , satisfaction and attitude towards OH , measured at baseline , directly after the intervention , after 1 week and at 3-month follow-up . Results Of the 141 participants , 130 ( 92 % ) completed the question naires at short-term follow-up and 41 ( 29 % ) at 3-month follow-up . At short-term follow-up , intervention and control groups did not show a significant difference in knowledge nor satisfaction but attitude towards OH was significantly more negative in the intervention group ( F=4.041 , p=0.047 ) . At 3-month follow-up , there were no significant differences between intervention and control groups for knowledge , satisfaction and attitude . Conclusions We found a significant decrease in favourable attitude during the internship in the experimental group compared with the control group . There were no significant differences in knowledge or satisfaction between case-based e-learning and text-based learning . The attitude towards OH should be further investigated as an outcome of educational programmes Background : Although animations may intuitively seem more effective than static graphics for teaching , there is no clear-cut evidence for the superiority of simple computer-based animations in medical education . Aims : We investigated whether simple animations are better than static graphics as an aid to medical students in learning home safety assessment , an important part of geriatric curriculum . Methods : We used two versions of an interactive online module , one that depicted common home safety issues in static graphics and the other in animations . We r and omized first-year medical students who agreed to participate into two groups . After the module , students completed a cognitive burden scale and a st and ardized competency assessment test in which they had to identify the salient home safety issues and give recommendations based on the hazards . We also captured time spent on task . Results and conclusions : We found no significant differences between the groups in the cognitive burden level , competency assessment scores , and time spent on task . The much cheaper-to-produce static graphics were equally effective as simple animations in this medical education scenario BACKGROUND Video-based instructions for clinical procedures have been used frequently during the preceding decades . AIM To investigate in a r and omised controlled trial the learning effectiveness of fragmented videos vs. the complete sequential video and to analyse the attitudes of the user towards video as a learning aid . MATERIAL S AND METHODS An instructional video on surgical h and wash was produced . The video was available in two different forms in two separate web pages : one as a sequential video and one fragmented into eight short clips . Twenty-eight dental students in the second semester were r and omised into an experimental ( n = 15 ) and a control group ( n = 13 ) . The experimental group used the fragmented form of the video and the control group watched the complete one . The use of the videos was logged and the students were video taped whilst undertaking a test h and wash . The videos were analysed systematic ally and blindly by two independent clinicians . The students also performed a written test concerning learning outcome from the videos as well as they answered an attitude question naire . RESULTS The students in the experimental group watched the video significantly longer than the control group . There were no significant differences between the groups with regard to the ratings and scores when performing the h and wash . The experimental group had significantly better results in the written test compared with those of the control group . There was no significant difference between the groups with regard to attitudes towards the use of video for learning , as measured by the Visual Analogue Scales . Most students in both groups expressed satisfaction with the use of video for learning . CONCLUSION The students demonstrated positive attitudes and acceptable learning outcome from viewing CAL videos as a part of their pre- clinical training . Videos that are part of computer-based learning setting s would ideally be presented to the students both as a segmented and as a whole video to give the students the option to choose the form of video which suits the individual student 's learning style BACKGROUND All accredited US residency programs are expected to offer curricula and evaluate their residents in 6 general competencies . Medical schools are now adopting similar competency frameworks . We investigated whether a Web-based program could effectively teach and assess elements of systems-based practice . METHODS We enrolled 276 medical students and 417 residents in the fields of surgery , medicine , obstetrics-gynecology , and emergency medicine in a 9-week r and omized , controlled , crossover educational trial . Participants were asked to sequentially complete vali date d Web-based modules on patient safety and the US health care system . The primary outcome measure was performance on a 26-item vali date d online test administered before , between , and after the participants completed the modules . RESULTS Six hundred forty ( 92.4 % ) of the 693 enrollees participated in the study ; 512 ( 80.0 % ) of the participants completed all 3 tests . Participants ' test scores improved significantly after completion of the first module ( P<.001 ) . Overall learning from the 9-week Web-based program , as measured by the increase in scores ( posttest scores minus pretest scores ) , was 16 percentage points ( 95 % confidence interval , 14 - 17 percentage points ; P<.001 ) in public safety topics and 22 percentage points ( 95 % confidence interval , 20 - 23 percentage points ; P<.001 ) in US health care system topics . CONCLUSION A Web-based educational program on systems-based practice competencies generated significant and durable learning across a broad range of medical students and residents Objectives . To evaluate the effectiveness of Web-based multimedia vignettes on complex drug administration techniques to augment the training of pharmacy students in advanced community pharmacy practice experiences . Design . During the orientation for a community APPE , students were r and omly assigned to either a study group or control group After they began their APPE , students in the study group were given an Internet address to access multimedia vignettes which they were required to watch to augment their training and st and ardize their counseling of patients in the use of inhalers and ear and eye drops . Assessment . A 12-item question naire was administered to students in both groups at the orientation and again on the last day of the APPE to evaluate their knowledge of counseling patients in the use of inhalers and ear and eye drops . The control group did not experience any improvement in their counseling knowledge of the research topics during their month-long experience . Students in the intervention group scored higher on their postintervention test than students in the control group ( p < 0.001 ) . Conclusions . Student learning outcomes from experiential training can be improved through the use of Web-based multimedia instructional vignettes OBJECTIVE Over 40-million Americans are undiagnosed , misdiagnosed , or untreated for sleep disorders . Despite the growing need to integrate sleep medicine knowledge into the medical education curriculum , educational leaders have struggled to incorporate contemporary medical topics such as sleep medicine into the already packed curricula . We set out to examine the efficacy of an online , self-paced , sleep medicine learning module as an educational tool for medical students . METHODS We studied 87 Johns Hopkins medical students . Participants were r and omly assigned to the sham module ( SM , n=40 ) or learning module ( LM , n=47 ) . The efficacy of the tool was assessed based on changes in performance ( pre- and post-module completion ) on a vali date d sleep knowledge question naire ( the Dartmouth Sleep Knowledge and Attitude Survey ) . RESULTS Improvement in overall sleep knowledge , as measured by the Dartmouth Sleep Knowledge and Attitude Survey , was significantly higher in the LM group compared to the SM group ( F(1,84)=9.71 , p<.01 , η(2)=0.10 ) . Although the SM group 's improvement was significantly lower than the LM group , within-subject comparisons did show improvement from their pre- to post- assessment scores as well . CONCLUSION A self-paced learning module is an effective educational tool for delivering sleep medicine knowledge to medical students OBJECTIVE To determine the impact of adding audio-feed to an online lecture on screening given to medical students who were participating in an outpatient clerkship . DESIGN Prospect i ve , r and omised , controlled study . SETTING V and erbilt University School of Medicine , Nashville and Wake Forest Medical School , Winston-Salem . PARTICIPANTS A total of 59 Years 3 and 4 medical students . MAIN OUTCOME MEASURES Students ' use of time , satisfaction with the lecture experience , and knowledge . Educational intervention The online lecture was developed at V and erbilt University . At V and erbilt , 16 Year 4 medical students were r and omised to the lecture on screening with audio and 17 Year 4 medical students were r and omised to the same lecture without audio . At Wake Forest , 13 Year 3 medical students were r and omised to the lecture on screening with audio and 13 Year 3 students were r and omised to the same lecture without audio . RESULTS The audio lecture required 20 more minutes to complete than the non-audio lecture . Students in the audio group were more satisfied with their experience than students in the non-audio group . Students in the audio-feed group achieved a trend for higher post-intervention knowledge scores , with the difference attributed to the students at V and erbilt . CONCLUSION Audio narration is an important aspect of an online lecture . The distribution of online lectures to students at different sites and different training levels requires further study Objective : To develop a computer-assisted learning ( CAL ) model and evaluate its effectiveness in improving medical trainees ' knowledge of pediatric emergency procedures . Methods : Three common pediatric emergency procedures were selected : laceration repair , splinting of fractures , and lumbar puncture . Web-based computerized tutorials were developed using digital images , short video clips , and instructional text . The tutorials focused on indications/contraindications of procedure , steps of the procedure , and material s needed . A 20-item multiple-choice examination was developed to test content covered in the tutorials . Twenty-three , third- and fourth-year medical students were r and omly assigned to the CAL group or the nonintervention group . The 20-item multiple-choice examination was given to the trainee either before or after completion of the tutorials , based on group assignment . Both groups completed demographic information forms . Results : The 13 students in the intervention group had a significantly higher average examination score , 16.3 ( 81.5 % ) ( SD , 2.68 ) , compared with the average score of the nonintervention group , 10.9 ( 54.5 % ) ( SD , 1.37 ) ( Wilcoxon test P = 0.00001 ) . There was no significant difference between the 2 groups . Conclusion : The CAL model improves students ' knowledge of emergency procedures . This model can be used as an adjuvant to traditional teaching of emergency procedures . Strategies for their optimal use need to be explored and evaluated Background : Optimal methods of preparing students for high-stakes st and ardized patient ( SP ) examinations are unknown . Purpose s : The purpose is to compare the impact of two formats of a formative SP examination ( Web-based vs. in-person ) on scores on a subsequent high-stakes SP examination and to compare students ' satisfaction with each formative examination format . Methods : Clustered r and omized trial comparing a Web-based module versus in-person formative SP examination . We compared scores on a subsequent high-stakes SP examination and satisfaction . Results : Scores on the subsequent high-stakes SP examination did not differ between the two formative formats but were higher after the formative assessment than without ( p < .001 ) . Satisfaction was higher with the in-person than Web-based formative assessment format ( 4.00 vs. 3.62 on a 5-point scale , p = .01 ) . Conclusions : Two formats of a formative SP examination led to equivalent improvement in scores on a subsequent high-stakes examination . Students preferred an in-person formative examination to online but were satisfied with both OBJECTIVE : To compare pharmacy students ' acquired knowledge and ability to assess metered-dose inhaler ( MDI ) technique after a traditional lecture versus a Web-based MDI technique tutorial . METHODS : All 42 third-year PharmD students completed a baseline MDI technique knowledge test and were then r and omized into 1 of 3 groups . The Web group completed the tutorial on the college dispensing laboratory computers ; the lecture group participated in the MDI technique excerpt of the asthma therapeutics lecture ; and the control group participated in a 15-minute discussion of participants ' hobbies . Afterward , participants in each group completed an identical MDI technique knowledge posttest . Students then observed a st and ardized mock patient perform MDI technique , documenting steps that were conducted incorrectly . MDI technique knowledge test and MDI technique evaluation test scores were compared between groups using repeated measures ANOVA . RESULTS : There was no significant difference in the baseline MDI technique knowledge test scores between groups . The post-MDI technique knowledge test scores for the Web and lecture groups did not differ significantly ( p = 0.38 ) , and both were significantly different from the control group ( p < 0.001 ) . MDI technique knowledge scores increased significantly for the Web and lecture groups from pre- to post- assessment , but did not change for the control group . A 2-way repeated measures ANOVA analysis demonstrated no significant interaction of subject and group characteristics . The MDI technique evaluation scores for the Web and lecture groups were not significantly different ( p = 0.50 ) , and both were significantly different from the control group ( p ≤ 0.001 ) . CONCLUSIONS : The Web-based MDI technique tutorial was as effective as the st and ard lecture format in pharmacy students acquiring knowledge of MDI technique and in evaluating a mock-patient exhibiting incorrect MDI technique . Further testing is required to assess the longitudinal effect of the program PURPOSE The purpose of this study was to evaluate the relationship between individual learning styles , test performance , and attitudes toward the use of Web-based self-instruction and slide/audiotape self-instruction METHODS Participants consisted of 33 junior , first-year dental hygiene students enrolled in a university-based dental hygiene program . A stratified r and om allocation ( by gender , English as a second language , and prior dental experience ) and r and om number table were used to assign participants into one of two groups . Group one studied the m and ibular arch using the slide/audiotape format and the maxillary arch using the Web-based format , and group two studied the m and ibular arch using the Web-based format and the maxillary arch using the slide/audiotape format . A post-test was taken at the completion of each instructional format . The Kolb Learning Style Inventory was used to assess preferred learning styles , and a written survey was used for instructional format preference . Descriptive analyses , Pearson correlations , and unpaired t-tests were used to analyze the data . RESULTS Thirty-one subjects completed the study . By group , no difference in mean post-test performance was seen based on the sequence or order of instructional method ( P > 0.05 ) or by arch ( P > 0.05 ) . No difference in post-test performance based on Web-based and slide-tape instructional methods was seen . Predominate learning style did not predict preference of instructional format nor were they correlated with post-test scores . However , almost 70 % of all participants reported that they preferred using the Web-based format to the slide/audiotape . CONCLUSIONS A variety of learning styles and preferences may be accommo date d when substituting Web-based self-instruction for slide/audiotape self-instruction in normal radiographic anatomy Objectives : Since 2001 , an e-learning tool has been developed for dentistry . To compare online self study with traditional lectures , a module about instrumental occlusal analysis was offered by oral lecture and by a unit in the virtual library of the e-learning tool . Methods : 85 pre- clinical dental students were r and omly divided into two groups : the computer assisted learning ( CAL ) group ( n = 48 ) and the lecture group ( n = 37 ) . A pre-test was made to assess the students′ basic knowledge . The first post-test and the scoring of the teaching methods were performed immediately after the lecture or the self study ing by the online tool and a second post-test six weeks later . Results : The oral lecture got better educational and enjoyment values . The students prefer CAL in addition to traditional lectures . The results of the pre-tests were not different between the two groups ( p = 0.706 ) . The lecture group significantly improved their scores in the first post-test ( p = 0.011 ) , but the scores of the second post-test did not differ significantly ( p = 0.157 ) . Conclusions : In the short term , knowledge acquisition seems to be better in oral lectures but in the long term there is no difference in knowledge retention between the two learning scenarios Objective To evaluate the hypotheses that a blended learning approach would improve the newborn examination skills of medical students and yield a higher level of satisfaction with learning newborn examination . Method Undergraduate medical students at a tertiary teaching hospital were individually r and omised to receive either a st and ard neonatology teaching programme ( control group ) , or additional online access to the PENSKE Baby Check Learning Module ( blended learning group ) . The primary outcome was performance of newborn examination on st and ardised assessment by blinded investigators . The secondary outcomes were performance of all ‘ essential ’ items of the examination , and participant satisfaction . Results The recruitment rate was 88 % ( 71/81 ) . The blended learning group achieved a significantly higher mean score than the control group ( p=0.02 ) for newborn examination . There was no difference for performance of essential items , or satisfaction with learning newborn examination . The blended learning group rated the module highly for effective use of learning time and ability to meet specific learning needs . Conclusions A blended learning approach result ed in a higher level of performance of newborn examination on st and ardised assessment . This is consistent with published literature on blended learning and has implication s for all neonatal clinicians including junior doctors , midwifes and nurse practitioners The use of online learning tutorials to provide instruction in schools of nursing is growing in popularity ; however , the outcomes associated with this method of instruction are not well documented . The focus of this experimental study , conducted at 2 universities in northern California , was to determine the effectiveness of an online interactive multimedia-learning tool versus text only , text and images , and multimedia learning explanations on math achievement , math self-efficacy , and student satisfaction . Compared to students in the control groups , students in the interactive multimedia group demonstrated equal posttest and retest knowledge of math ; their math self-efficacy scores were also the same . Interactive multimedia group students were more satisfied with the method of learning , reported the technique to be enjoyable and more interesting , and provided sufficient feedback . An online interactive multimedia-learning tool is a realistic and creative method of teaching medication dosage calculations OBJECTIVE To evaluate the educational effectiveness of a novel , web-based neuroanatomical localization application . METHODS A prototype version of a neuroanatomical localization application was developed , limited to lesions involving Cranial Nerve ( CN ) VII . Second year medical students at the University of Ottawa were recruited to participate in the study . Participants were exposed to a didactic teaching session on CN VII anatomy . They were subsequently r and omized to two groups - one group was granted access to the localization application ( the " intervention group " ) , while the other group was given a booklet of st and ard textbook re sources ( the " control group " ) . Participants then completed a case-based multiple choice test on localization of neurologic lesions associated with CN VII , followed by a question naire regarding the experience . RESULTS Thirty-nine students volunteered to participate . Twenty were r and omized to the intervention group and 19 to the control group . There was a mean test score difference of 1.3 ( CI.95=0.2 , 2.3 ) that was significantly higher in the intervention group when compared to the control group . Significance was determined by a Wilcoxon rank test ( p=0.028 ) . Question naire results were similar for both groups , showing an overall favourable evaluation of the localization application . CONCLUSIONS The results support our hypotheses that students using the application would perform better on the multiple choice question ( MCQ ) test and there would be an overall preference for its use . The demonstrated educational benefit of the application , in addition to the dem and for such a re source expressed by the participants , warrant further investigation into the development of a neurological localization application Objectives : To determine the feasibility and effectiveness of virtual-patient computer-assisted instruction ( CAI ) in pre-clerkship undergraduate otolaryngology education . Study Design : Prospect i ve , r and omized , controlled trial . Subjects and Methods : Second-year medical students at the University of Western Ontario , Canada , were r and omized into two groups : group A was given a CAI module and group B was presented with two Internet review articles , both covered specific learning objectives for pediatric stridor . Students completed r and omized pre- and post-tests and a question naire one week later . Results : Fifty-five students completed the study with 28 in group A and 27 in group B. Mean pretest scores were 59.1 % in group A and 59.8 % in group B ( 95 % CI = −7.9 % to 10.4 % ) . Mean post-test scores were significantly elevated in group A ( 84.6 % , P < 0.001 ) and group B ( 74.3 % , P = 0.008 ) . Group A had a significantly higher ( P = 0.02 ) mean post-test score than group B ( mean difference of 10.2 % ) . Students spent significantly more time ( P < 0.001 ) reading text articles ( 25.5 minutes ) than completing the CAI ( 9.06 minutes ) . Forty-one ( 66 % ) students completed the survey . Thirty-six ( 88 % ) respondents indicated that they preferred CAI to online articles . Conclusion : CAI is a feasible , effective , and efficient means of enhancing self-directed learning as supplementation to the pre-clerkship undergraduate otolaryngology curriculum BACKGROUND In this study , we compared the educational value of a multimedia module about aortic valve replacement as a preparation for the operating room with a print medium of identical content . METHODS One hundred twenty-six students were r and omly assigned in a prospect i ve study to either use the multimedia course ( n = 69 ) or a print version ( n = 57 ) . A 20-item multiple-choice test was performed before and after learning with the respective medium . Both groups participated in an operation during which they were evaluated with 28 st and ardized tasks and questions . Individual motivation , computer literacy , and didactic quality of both media were assessed with psychometric tests . RESULTS There were no significant differences in the multiple-choice pretest ( multimedia , 30.6 % + /- 12.4 % versus print , 27.9 % + /- 11.4 % ) and posttest responses ( multimedia , 76.7 % + /- 13.3 % versus print , 76.9 % + /- 11.1 ) . Mean percentage of correct answers during the operation was 82.9 % + /- 10 % in the online group and 64.7 % + /- 12 % in the print group ( p < 0.0001 ) . The multimedia group needed significantly ( p < 0.001 ) less study time ( 105 + /- 24 minutes ) when compared with the text group ( 122 + /- 30 minutes ) . There were no statistically significant differences in motivation , computer literacy , and didactic quality of either medium . CONCLUSIONS Regarding factual knowledge , there is no difference between multimedia-driven learning and a print medium . During heart operations , when underst and ing of complex temporal and spatial events is essential , students ' performance is significantly improved by multimedia-enhanced teaching . The latter further proved to be more efficient in terms of study time With the rapid development of the Internet , online testing is becoming more widely-used in education . The purpose of this study is to explore the learning effectiveness of nursing students using online testing as an assistant tool . The participants were 146 junior college nursing students aged 19 to 20 taking the community health nursing course . With a class as the unit , three classes were r and omized and allocated to one experimental group and two control groups . Two structured question naires were used to obtain the basic data , and the groups ' examination results were also collected . The results of this study showed that before the intervention , there were no significant differences between the experimental and two control groups . After the intervention and adjusting for potential confounders , the score of midterm test in the experimental group was significantly better than those of the control groups . Over half of the students felt that answering 21 to 30 questions in 31 to 60 min for one unit of testing were appropriate . The results of this study showed that online testing is feasible for use as an assistant tool for learning . However , the positive effects of this approach appeared to be short- rather than long-term , and thus more studies are required in future OBJECTIVES To test the hypothesis that integration of the EMCyberSchool , a computer-assisted instruction ( CAI ) tool available on the Internet , into the curriculum of a senior medical student subinternship in emergency medicine ( EM ) would improve exam scores and course satisfaction . METHODS Students were prospect ively r and omized , by four-week blocks , into a CAI group and a no-CAI group . All students were surveyed on previous computer experience and their use and opinion of the EMCyberSchool . RESULTS Completed data were obtained from 100 of 120 students . Sixty-five percent of the students said they wanted CAI as an adjunct to their course curricula ; only 28 % actually used the educational tool . The students who used the site rated it useful ( 4.2/5 ) , easy to use ( 4.4/5 ) , and easy to access ( 4.1/5 ) . Of the students who had access , and chose not to use the EMCyberSchool , 77.8 % reported not having enough time as the reason for not using the site . The mean exam scores were 72.8 % for the students in the CAI group and 68.2 % for those in the no-CAI group ( p = 0.058 ) . In the CAI group , 77.5 % ( 31/40 ) of the students rated the course as outst and ing or excellent ; compared with 66 % ( 33/50 ) in the no-CAI group ( p = 0.23 ) . CONCLUSIONS Although desired , it remains unclear whether CAI on the Internet is a useful adjunct for teaching EM to medical students A r and omised controlled trial was design ed to test an Internet-based interactive application as a st and -alone support for the development of self- assessment skills among second-year dental students at the Faculty of Dentistry , University of Malmö , Sweden . Fifty-two students were r and omised into an experimental ( n = 26 ) and a control group ( n = 26 ) . Both groups went through four identical learning cases in elementary clinical Periodontology during a period of 1 month . The experimental group received the cases with the interactive software , while the control group received them through a static web page . After the end of the learning phase , both groups were assessed blindly by two assessors during the interactive examination methodology . There was a moderate agreement between the two assessors , but both failed to find any significant differences between the two groups with regard to self- assessment skills and overall performance of the students . Students positively received the Internet support , but several attitude differences were observed between the two groups during the study . Time on task and competence with computers were positively correlated to assessment results for both groups . On the basis of these findings , it remains unclear if computer-based applications with automated feedback can constitute an effective remedial support for the improvement of self- assessment skills of students . In addition , for such applications to be successfully accepted , two factors are critical : students must have a clear perception of the benefits deriving from the use of the software and the use of the software should be integrated in the curriculum , replacing some of the existing workload When considering implementing integrated curriculum models , such as problem-based learning ( PBL ) , concerns may be expressed about the need for increased staff re sources required to deliver tutor-led small group PBL . Less staff intensive ways of supporting PBL need to be explored . We compared the outcomes of a PBL module conducted in a large class format within a lecture theatre with a module having the same defined learning outcomes delivered in small group PBL format , both supported by e-learning re sources . The pre-existing 27 small groups within the whole class ( n = 246 ) of first year students undertaking a cardiovascular basic science module at Sheffield undergraduate medical school , UK , were r and omized to 22 groups undertaking the large class Integrated Learning Activity ( ILA ) and 5 groups to traditional small group facilitated PBL sessions . Outcome measures were : a pre – post knowledge based test , a student educational effectiveness question naire , and assessment of student group work and presentations . There seemed to be no significant differences in learning outcomes between the methods although it is recognized that students would prefer the small group teaching format . Within institutions where re sources to support small group PBL are limited , the large group ILA format supported with e-learning techniques may be a useful alternative approach Background : Clinical reasoning skills are essential for medical practice . Problem-based collaborative learning via the internet might prove useful in imparting these skills . Aim : This r and omized study assessed whether web-based learning ( WBL ) is superior to face-to-face problem-based learning ( PBL ) in the setting of a 6-week cardio-respiratory course . Methods : During winter term 2007/08 , all 148 fourth-year medical students enrolled in the 6-week course consented to be r and omized in small groups to diagnose a patient complaining of dyspnoea either using a virtual collaborative online module or a traditional PBL session . Clinical reasoning skills were assessed by means of a key feature examination at the end of the course . Results : No significant difference between the mean scores of both study groups was detected ( p = 0.843 ) . In virtual learning groups , costs for diagnostic tests were significantly correlated to the number of contributions to online group discussion s ( r = 0.881 ; p = 0.002 ) . Evaluation data favored traditional PBL sessions over virtual collaborative learning . Conclusion : While virtual collaborative learning was as effective as traditional PBL regarding the acquisition of clinical reasoning skills , it was less well accepted than traditional PBL . Future research needs to determine the ideal format and time-point for computer-assisted learning in medical education OBJECTIVE : To determine the impact of an online lecture versus a live lecture on screening given to medical students who are participating in an outpatient clerkship . DESIGN : Prospect i ve , r and omized , controlled study . PARTICIPANTS AND SETTING : Ninety-five senior medical students in a primary care medicine clerkship based at university and distant clinic sites . INTERVENTION AND MEASUREMENTS : Forty-eight medical students were r and omized to the live lecture on screening ( live lecture group ) , and forty-seven medical students were r and omized to the online lecture on screening ( online lecture group ) . Outcome measures included students ’ knowledge , use of time , and satisfaction with the lecture experience . RESULTS : Compared to students in the live lecture group , students in the online lecture group demonstrated equal post-intervention knowledge of screening ( P=.91 ) and expended 50 minutes less time to complete the lecture . Online lecture students who used the audio feed of the lecture were equally satisfied with the lecture as the live lecture students . Without the audio feed , online lecture students were less satisfied . CONCLUSIONS : An online lecture on screening is a feasible , efficient , and effective method to teach students on outpatient clerkships about principles of screening BACKGROUND The authors developed and evaluated an interactive , Web-based module to train medical students in screening and brief intervention ( SBI ) for unhealthy alcohol use . METHODS First-year students were r and omized to module versus lecture . Change in knowledge , attitudes , and confidence were compared . Performance was assessed by objective structured clinical examination ( OSCE ) and analyzed by intention to treat and treatment received . RESULTS Of 141 consenting students , 64 % ( n = 90 ) completed an intervention ( 54 % lecture vs. 70 % Web assigned ) . Knowledge , confidence , and attitudes improved in both groups , with more improvement in Advise-Assist knowledge for Web students ( 14 % vs. -3 % , p = .003 ) . Web students outperformed their lecture peers in both general communication ( 65 % vs. 51 % items well done , p = .004 ) and alcohol-specific tasks ( 54 % vs. 41 % , p = .021 ) on OSCE . Analysis by treatment received enhanced between-group differences . CONCLUSION Use of a Web-based module to teach SBI is associated with greater knowledge gain and skills performance compared with a lecture covering similar content . The module provides an efficient means for training in this area OBJECTIVE The purpose of this study was to determine whether the acquisition of competence in palpation and ultrasound imaging in the lumbopelvic region can be improved by the use of e-learning strategies . METHODS This study was a single-blind r and omized controlled study . Forty-four physical therapy undergraduate students ( 29 females ) from the University of Granada ( Spain ) received an educational module of on-campus training in palpation and ultrasound examination of the lumbopelvic area . The participants were r and omly distributed into 2 groups : the e-learning group , with free access to a Web site on musculoskeletal palpation and ultrasound assessment , and the control group , with access to documents and books on the topic . Objective structured clinical evaluation and reproducibility between professorial staff and students in multifidus cross-sectional area ultrasound imaging were used to assess the educational intervention . RESULTS Objective structured clinical evaluation scores were statistically significantly higher in the e-learning group than in the control group for skills in palpation ability and ultrasound assessment of the lumbopelvic area ( both P < .001 ) . CONCLUSION This study suggests that e-learning may be an adjunct educational strategy to acquire musculoskeletal manual skills and ultrasound imaging of the lumbopelvic area Purpose To investigate the impact of an adjuvant Web-based teaching program on medical students ’ learning during clinical rotations . Method From April 2003 to May 2004 , 351 students completing clinical rotations in surgery – urology at four U.S. medical schools were invited to volunteer for the study . Web-based teaching cases were developed covering four core urologic topics . Students were block r and omized to receive Web-based teaching on two of the four topics . Before and after a design ated duration at each institution ( ranging one to three weeks ) , students completed a vali date d 28-item Web-based test ( Cronbach ’s alpha = .76 ) covering all four topics . The test was also administered to a subset of students at one school at the conclusion of their third-year to measure long-term learning . Results Eighty-one percent of all eligible students ( 286/351 ) volunteered to participate in the study , 73 % of whom ( 210/286 ) completed the Web-based program . Compared to controls , Web-based teaching significantly increased test scores in the four topics at each medical school ( p < .001 , mixed analysis of variance ) , corresponding to a Cohen ’s d effect size of 1.52 ( 95 % confidence interval [ CI ] , 1.23–1.80 ) . Learning efficiency was increased three-fold by Web-based teaching ( Cohen ’s d effect size 1.16 ; 95 % CI 1.13–1.19 ) . Students who were tested a median of 4.8 months later demonstrated significantly higher scores for Web-based teaching compared to non-Web-based teaching ( p = .007 , paired t-test ) . Limited learning was noted in the absence of Web-based teaching . Conclusions This r and omized controlled trial provides Class I evidence that Web-based teaching as an adjunct to clinical experiences can significantly and durably improve medical students ’ learning BACKGROUND The effectiveness of computer-assisted instruction is unproven . OBJECTIVE To evaluate the effectiveness of an online computerized dermatology module compared to traditional lecture-based teaching to medical students . METHODS Medical students were r and omized to two groups . Group 1 of 37 students had access to a computer-based dermatology tutorial . Group 2 of 36 students attended a lecture on skin morphology , identical to the tutorial , given by a dermatology faculty member . The main outcome was the total number of correct answers on a multiple-choice morphologic terminology final examination . The mean number of questions answered correctly was 16.14 and 14.89 for group 1 and group 2 , respectively . RESULTS Unpaired statistical t tests showed the difference in mean scores between the two groups to be 1.25 ( 95 % confidence interval : -0.70 to 3.20 , p value = .20 ) . LIMITATIONS The study was small , with a small amount of material , and was brief in duration . CONCLUSIONS Within the limits of our study , computer-assisted instruction is at least as effective as traditional lecture teaching of dermatology morphology to medical students Background : Teaching seizure disorders requires use of multiple formats including pictures and videos . Web technology permits combination of formats and interactive features to deliver information . Purpose : The purpose of this study was to determine the benefits of incorporating Web-based interactive methodology into a neurology clerkship to enhance the teaching about seizure disorders to 3rd-year medical students . Methods : A Web-based interactive program was created and administered by the University of Florida blackboard . A multiple-choice question naire about epileptic disorders was utilized to assess the degree of learning . Participants were r and omized to a Web group or control . Twenty-two students in each group were enrolled . The control group was assigned to a traditional written material . In the Web study group 4 students failed to complete the test . Results : The Web group obtained better scores on Multiple Choice Question naire than the control group ( p = .03 ) . Conclusions : This small study suggests that an interactive format using Web technology enhances learning about seizure disorders , perhaps by stimulation of critical thinking and promoting greater student motivation |
828 | 12,172,463 | The authors determined that thrombolysis therapy results in greater lysis and complication rates than does anticoagulation alone .
The authors also found that PTS incidence is lower in patients treated with thrombolytics .
Therefore , the authors conclude that although the lysis rate is greater for thrombolytic agents , they can not be recommended routinely for DVT treatment | This article presents the rationale and evidence for the treatment of lower-extremity deep venous thrombosis ( DVT ) with thrombolytic agents .
DVT is a common condition that has both acute and chronic complications .
St and ard treatment including anticoagulation therapy and compression stockings may not be entirely adequate , because a significant proportion of patients eventually develop severe post-thrombotic syndrome ( PTS ) .
Thrombolytic agents offer a potential advantage because they may reduce residual vein stenosis and valve damage . | BACKGROUND Post-thrombotic syndrome varies from mild oedema to incapacitating swelling with pain and ulceration . We investigated the rate of post-thrombotic syndrome after a first episode of deep-vein thrombosis and assessed the preventive effect of direct application of a sized-to-fit grade d compression stocking . METHODS Patients with a first episode of venogram-proven proximal deep-vein thrombosis were r and omly assigned no stockings ( the control group ) or made-to-measure grade d compression elastic stockings for at least 2 years . Post-thrombotic syndrome was assessed with a st and ard scoring system that combined clinical characteristics and objective leg measurements . Patients were assessed every 3 months during the first 2 years , and every 6 months thereafter for at least 5 years . The cumulative incidence of mild-to-moderate post-thrombotic syndrome was the primary outcome measure . FINDINGS Of the 315 consecutive out patients considered for inclusion , 44 were excluded and 77 did not consent to take part . 194 patients were r and omly assigned compression stockings ( n = 96 ) or no stockings ( n = 98 ) . The median follow-up was 76 months ( range 60 - 96 ) in both groups . Mild-to-moderate post-thrombotic syndrome ( score > or = 3 plus one clinical sign ) occurred in 19 ( 20 % ) patients in the stocking group and in 46 ( 47 % ) control-group patients ( p < 0.001 ) . 11 ( 11 % ) patients in the stocking group developed severe post-thrombotic syndrome ( score > or = 4 ) , compared with 23 ( 23 % ) patients in the control group ( p < 0.001 ) . In both groups , most cases of post-thrombotic syndrome occurred within 24 months of the acute thrombotic event . INTERPRETATION About 60 % of patients with a first episode of proximal deep-vein thrombosis develop post-thrombotic syndrome within 2 years . A sized-to-fit compression stocking reduced this rate by about 50 % Fibrinolytic treatment of acute deep vein thrombosis ( DVT ) of the leg with high-dose streptokinase ( SK ) ( 100,000 U/h ) in 39 cases , or low-dose SK ( approx 10,000 U/h ) in combination with low-dose heparin in 41 cases , was studied in a prospect i ve r and omized trial . The degree of thrombolysis was similar in both groups and did not correlate with age or size of the thrombus or with fibrinogen level . The degree of late recanalization was also similar in both groups . There were however significantly more patients with postthrombotic changes in the low-dose group than in the high-dose group after a mean follow-up time of 31 and 38 months respectively . In the low-dose group 2 intracranial hemorrhages occurred ( one was fatal ) and one patient died of pulmonary embolism , but there were significantly less allergic side effects to SK . There were no cases of such serious side effects in the highdose group . Although low-dose SK has equal thrombolytic effect it seems inferior to high-dose SK , since it probably causes more severe hemorrhagic side-effects In a prospect i ve study , 174 patients ( 118 women and 56 men , average age 44 years , range 14 to 82 ) with proximal extensive thrombosis received streptokinase ( 100,000 U/hour ) for an average of 2.8 days ( range 0.5 to 7 ) through the catheter of a temporary caval filter . Twenty-seven of 45 ( 60 % ) patients with nonocclusive clots were completely free of clots at the second phlebography versus 17 of 116 ( 14 % ) with occlusive clots ( p less than 0.001 ) . Among nonocclusive clots , proximal ones ( caval , iliac and femoral ) were more easily lysed than popliteal clots ( 88 of 116 [ 76 % ] vs 26 of 58 [ 45 % ] ; p less than 0.001 ) . In 41 of 132 ( 31 % ) patients , a daily injection of contrast medium through the filter-carrying catheter enabled the observation of a clot in the filter , which was lysed by streptokinase . Seventy patients with follow-up greater than 2 years ( median 34 months ) were examined clinical ly . Nineteen of 22 ( 86 % ) patients with venograms free of clots at discharge were free of clinical sequelae versus 16 of 48 ( 33 % ) without normal venograms ( p less than 0.001 ) . It is concluded that : ( 1 ) in the case of occlusive clots , only a few patients were normalized after streptokinase ; ( 2 ) proximal nonocclusive clots were most effectively lysed ; ( 3 ) when venograms were free of clots at discharge , the majority of patients did not have venous sequelae at follow-up ; and ( 4 ) embolic migration seems to occur frequently with streptokinase Twenty patients with clinical signs of deep vein thrombosis of a duration not exceeding 72 hours , and with the condition confirmed phlebographically , were r and omly allocated to one of two groups in a double-blind study . In group 1 the patients received urokinase in a low-dose regimen of 200 000 Ploug units during the first 24 hours , followed by infusion of heparin , 40 000 units daily during the next 5 days . Patients in group 2 received heparin only , 40 000 units daily for 6 days . The clinical course was assessed daily . When the infusion period was completed , the phlebography was repeated , and the results of the two examinations were compared with respect to extent of filling defects and the degree of non-filling of the deep veins . We found no superiority in the regimen consisting of urokinase preceding heparin infusion , compared with that of heparin infusion alone . Most of the patients improved clinical ly during the 6-day infusion period , but the degree of thrombosis , evaluated phlebographically , was unaltered or even deteriorated during the period in all patients except two . Overt bleeding was noted in 6 patients Nineteen cases were reinvestigated 8 - 14 years after treatment with SK or heparin . Judging from personal interviews , foot volumometry and phlebography , treatment with SK appears to be more preferable since it was less often followed by late severe postthrombotic changes In a prospect i ve study all positive phlebographies within the well-defined population of the city of Malmö , Sweden , during 1987 were studied in order to determine the incidence of deep venous thrombosis ( DVT ) . Epidemiological data were analysed for the detection of patient groups at increased risk of DVT . The incidence was found to be equal for both sexes , i.e. 1.6 per 1000 inhabitants a year . Risk factors were found to be in accordance with earlier studies . The median age for men was 66 years , compared to 72 years for women . At diagnosis of DVT , 19 % of subjects had a known malignancy and within 1 year 5 % ( 19 cases ) developed a new malignancy . Of the men , 29 % had postoperative or post-traumatic ( fracture ) DVT , compared to 46 % of the women . Fewer patients with DVT than expected ( 39 % ) belonged to blood group 0 ( 31 % ) ( P less than 0.005 ) . Pulmonary embolism ( PE ) was clinical ly suspected in only 5 % of cases , and diagnosis was verified scintigraphically in 2 % of cases . None of these died of PE , but of 6 patients who were found to have PE at autopsy , four died about 4 weeks after the DVT was diagnosed In a prospect i ve and r and omized multicenter trial the efficacy of intermittent regional and systemic thrombolytic therapy for DVT was evaluated . 137 patients with phlebographically confirmed acute DVT above the calf region were treated with 20 mg of rt-PA for 4 h each day . Thrombolysis was applied either locally via a dorsal pedal vein of the firmly b and aged affected leg or systemically using a cubital vein . Treatment lasted for 4 - 7 days , and during this time unfractionated heparin was applied continuously with the dosage adjusted according to aPTT ( 1.5 - 2.0 times the normal value ) . A second phlebography was performed within 24 h after the end of treatment . Results were evaluated by an independent radiologist who was unaware of the treatment given . Significant thrombolytic results ( e.g. lysis of more than 50 % of the original thrombus and complete recanalization of all affected veins ) were reached in only 1/3 of all patients . Rates of recanalization did not differ in both groups and bleeding complications occurred in 26.5 % . We conclude that intermittent local or systemic application of 20 mg rt-PA seems to be ineffective in the treatment of DVT Bolus urokinase ( Abbokinase ) is effective for initial treatment of deep venous thrombosis but is associated with a high rate of rigors . This r and omized controlled trial was undertaken among patients with deep venous thrombosis to evaluate the efficacy and safety of a novel thrombolytic agent , recombinant urokinase ( rUK ) , administered as three bolus infusions of 1 million U over a 24-hour period versus heparin alone . Of 361 patients with DVT screened , 17 ( 5 % ) were enrolled . Recent surgery was the most common reason for exclusion ( n = 113 , 31 % ) . Images of the patients were obtained at baseline , 24 to 48 hours after r and omization , and before hospital discharge . Two patients in each treatment group had minor clot progression . One patient in the heparin group had no change ; all other patients showed mild ( < 50 % ; n = 5 in each group ) or moderate ( > 50 % ; n = 1 in each group ) improvement . No bleeding complications or rigors developed in patients r and omized to rUK . Mean bleeding times among patients given rUK were not significantly different from mean values of patients given heparin at any of the measured time points available for comparison ( 331 vs 387 seconds at baseline and 381 vs 416 seconds at 24 hours ) . However , mean fibrinogen levels declined with successive urokinase boluses and were significantly lower than levels in patients treated with heparin at 24 ( 233 mg/dl vs 466 mg/dl , p = 0.01 ) and 48 hours ( 270 mg/dl vs 474 mg/dl , p = 0.02 ) . Although bolus rUK had a favorable safety profile , rUK was no more effective than heparin in achieving clot lysis at the doses used in this trial A controlled , prospect i ve study comparing streptokinase and heparin treatment has been completed in 51 patients presenting with acute proximal venous thrombosis of less than 8 days ' clinical duration . Patients were studied by means of pre‐treatment , post‐treatment , 3‐ and 12‐monthly phlebography and pulmonary perfusion scanning and were followed up at 3‐monthly intervals PURPOSE To compare the efficacy and safety of recombinant human tissue-type plasminogen activator ( rt-PA , supplied as Activase ) with heparin alone or rt-PA plus heparin in the treatment of venographically documented proximal deep venous thrombosis ( DVT ) of the leg . PATIENTS AND METHODS Sixty-four patients underwent 65 r and omizations to rt-PA alone ( n = 36 ) , rt-PA plus heparin ( n = 17 ) , or heparin alone ( n = 12 ) in a prospect i ve , multicenter , r and omized , open-label trial , with efficacy assessed by a radiology panel unaware of treatment assignment . Patients r and omly assigned to rt-PA received 0.05 mg/kg/hour for 24 hours via a peripheral vein , with a maximum dose of 150 mg . All patients then received heparin and warfarin for the remainder of the hospitalization . Follow-up venography was performed 24 to 36 hours after initiation of therapy . RESULTS Complete or more than 50 % lysis occurred in 10 ( 28 % ) patients treated with rt-PA , five ( 29 % ) patients with rt-PA plus heparin , and no patient treated with heparin . No lysis occurred in 16 ( 44 % ) patients treated with rt-PA plus heparin , and 10 ( 83 % ) patients who received heparin alone ( p = 0.04 ) . There was one major complication , a nonfatal intracranial hemorrhage in a patient who received rt-PA alone . At 7 to 10 days after initiation of treatment , the level of serum glutamic oxaloacetic transaminase nearly doubled among all patients , including those assigned to receive heparin alone . CONCLUSION ( 1 ) rt-PA and rt-PA plus heparin cause more clot lysis than heparin alone ; ( 2 ) the addition of heparin to rt-PA does not improve the lysis rate ; ( 3 ) DVT treated with heparin is commonly associated with a rise in the transaminase level ; ( 4 ) heparin does not increase the risk of bleeding from rt-PA therapy ; and ( 5 ) alternative dosing regimens and modes of administration of rt-PA should be investigated to improve further its efficacy and safety in the treatment of acute DVT OBJECTIVES The goal of this study was to assess the short- and long-term efficacy of different thrombolytic therapy regimens in patients with leg or pelvic deep venous thrombosis ( DVT ) . BACKGROUND It is unclear whether locoregional or systemic thrombolysis is superior in treating acute leg DVT or even whether lysis is more effective than anticoagulation therapy in preventing postthrombotic syndrome . METHODS A total of 250 patients averaging 40 years of age with acute DVT were r and omized into five groups to receive full heparinization ( 1,000 IU/h ) and compression treatment , with four groups also administered locoregional tissue plasminogen activator ( 20 mg/day ) or urokinase ( 100,000 IU/day ) or systemic streptokinase ( 3,000,000 IU daily ) or urokinase ( 5,000,000 IU daily ) . All groups then received anticoagulation and compression treatment for one year . Primary efficacy criteria included the change after one year in the number of closed vein segments and the occurrence of postthrombotic syndrome . RESULTS Systemic thrombolytic therapy significantly reduced the number of closed vein segments after 12 months in patients with acute DVT compared with conventional treatment ( p < 0.05 ) . Postthrombotic syndrome also occurred with less frequency in systemically treated patients versus controls ( p < 0.001 ) . High-dose thrombolysis led to better rates of complete recanalization after seven days ( p < 0.01 ) than locoregional lysis . However , 12 patients receiving thrombolysis ( 9 systemic , 3 local ) suffered major bleeding complications ; 9 patients on systemic treatment developed pulmonary emboli . CONCLUSIONS Systemic thrombolytic treatment for acute DVT achieved a significantly better short- and long-term clinical outcome than conventional heparin/anticoagulation therapy but at the expense of a serious increase in major bleeding and pulmonary emboli . Given the inherent risks for such serious complications , systemic thrombolysis , although effective , should be used selectively in limb-threatening thrombotic situations PURPOSE To prospect ively assess the computed tomographic ( CT ) findings of iliofemoral deep venous thrombosis ( DVT ) and evaluate their relevance to the treatment of DVT with catheter-directed thrombolysis . MATERIAL S AND METHODS Twenty-four consecutive patients with symptomatic iliofemoral DVT were studied with both nonenhanced and contrast-enhanced CT before thrombolytic therapy . Mean duration of clinical symptom was 15.8 days + /- 20.8 ( range , 1 - 90 d ) . Selected CT findings were prospect ively evaluated and correlated with duration of symptoms and outcome of thrombolytic therapy , including attenuation number of the thrombus on nonenhanced CT ( in HU ) , presence of venous distention ( distention ratio : vein diameter divided by the diameter of corresponding normal contralateral vein ) , and poor venous wall demarcation . The following threshold variables were also evaluated : attenuation > or = 60 HU and distention ratio > or = 1.5 . RESULTS CT was suggestive of DVT in all patients , although different patterns were present . Higher attenuation on noncontrast CT was seen in patients who had favorable outcome of thrombolytic therapy compared to poor responders ( 66.1 + /- 8.7 vs 45.9 + /- 9.6 ; P < .0001 ) . Distention ratio was also significantly higher in the good response group ( 2.6 + /- 1.4 vs 1.4 + /- 0.7 ; P < .05 ) . Recent onset of clinical symptoms was associated with better outcome ( 9.4 d + /- 8.9 vs 28.6 d + /- 31.2 ; P < .03 ) . Multiple-stepwise regression analysis of these variable produce the results of " attenuation > 60 " as the most predictive variable of favorable outcome of thrombolysis , followed by " distention ratio > 1.5 " and poor demarcation . CONCLUSION Selected CT findings are better predictors of a favorable outcome of thrombolytic therapy than duration of clinical symptoms alone Deep venous thrombosis of the lower extremity is a serious disorder ; the estimated incidence is 1 per 1000 persons per year [ 1 - 3 ] . The disease can occur after surgical procedures and trauma and in the presence of cancer or inherited coagulation disorders ; it can also develop without any of these factors [ 3 ] . The clinical course of deep venous thrombosis might be complicated by pulmonary embolism , recurrent episodes of deep venous thrombosis , and the development of serious post-thrombotic sequelae , such as venous ulceration , debilitating pain , and intractable edema [ 3 ] . Patients with deep venous thrombosis are usually treated with an initial course of heparin ( 5 to 10 days ) followed by 3 to 6 months of oral anticoagulant therapy . This treatment regimen reduces the risk for short-term thromboembolic complications to approximately 5 % [ 4 , 5 ] . The long-term risk for recurrent venous thromboembolism and the incidence and severity of post-thrombotic sequelae in patients with symptomatic deep venous thrombosis have not been well documented . In a recent large r and omized , clinical trial comparing 6 weeks of oral anticoagulant therapy with 6 months of therapy [ 6 ] , patients with symptomatic deep venous thrombosis were followed for 2 years for recurrences and death . This trial showed a substantial reduction in the risk for recurrent venous thromboembolism among patients in the 6-month oral anticoagulant group , but the investigators did not report on the occurrence of the post-thrombotic syndrome . Another recent study [ 7 ] reported the 8-year incidence of recurrences and post-thrombotic manifestations in patients with confirmed symptomatic deep venous thrombosis . However , only a few patients were included in this study , and data were collected retrospectively . We assessed the clinical course of a first episode of symptomatic deep venous thrombosis in a large consecutive series of patients who had long-term follow-up . We assessed mortality and the long-term incidences of recurrent venous thromboembolism and the post-thrombotic syndrome . We also evaluated the potential risk factors for these three outcomes . Methods Identification of Inception Cohort The Department of Internal Medicine of the University of Padua , Padua , Italy , is a diagnostic facility for out patients with clinical ly suspected venous thromboembolism in a community of approximately 350 000 persons . All consecutive out patients with a first episode of clinical ly suspected deep venous thrombosis who were referred by their general practitioners between January 1986 and December 1991 had noninvasive testing [ 8 ] . Patients were potentially eligible for the study if confirmatory venography showed deep venous thrombosis . Patients were excluded from the study if they had been referred because of recurrent venous thrombosis , were geographically inaccessible for follow-up , or refused to give informed consent . The Institutional Review Board of the hospital of the University of Padua approved the study . Baseline Assessment At the time of referral , demographic characteristics were recorded and a medical history was taken ; information was elicited on the period between the onset of symptoms and presentation to the thrombosis service ( patientphysician delay ) , the presence of risk factors for thrombosis ( that is , cancer , surgery , trauma or fracture , immobilization for more than 7 days , pregnancy or childbirth , or estrogen use ) , and symptoms of pulmonary embolism . Information was also obtained on the history of venous thromboembolism in first-degree relatives . Antithrombin , protein C and S , and lupus-like anticoagulant levels were subsequently measured . Assays were done , and previously described criteria for abnormality and deficiency were used [ 9 ] . The venograms obtained at baseline were divided into those representing proximal venous thrombosis ( with or without concurrent venous thrombosis of the calf ) and those indicating isolated venous thrombosis of the calf . Proximal venous thrombosis was defined as thrombosis located above the trifurcation of the calf veins that involved at least the popliteal vein , superficial femoral vein , common femoral vein , or iliac vein . The location and occlusiveness of proximal thrombi were also determined . A patient was considered to have nonocclusive deep venous thrombosis if contrast material was seen between the thrombus and the vessel wall along the entire thrombus . Treatment Patients were admitted to the hospital and treated with an initial course of high-dose intravenous st and ard heparin ( a bolus of 5000 U followed by continuous infusion of 30 000 U/d , subsequently adjusted to maintain an activated partial thromboplastin time between 1.5 and 2.5 times the normal value ) or subcutaneous low-molecular-weight heparin ( 90 U of anti-factor Xa/kg of body weight twice daily ) . Therapy with oral anticoagulant agents ( warfarin ) was started on day 5 to 7 of treatment and was continued for 3 months . The oral anticoagulant dose was adjusted daily to maintain an international normalized ratio between 2.0 and 3.0 . Treatment with low-molecular-weight heparin was discontinued on day 10 or later if the international normalized ratio was less than 2.0 . This treatment strategy deviated in the following groups of patients : those with cancer , protein deficiencies , or lupus anticoagulant , in whom oral anticoagulation therapy was prolonged ; those with small isolated venous thrombosis of the calf , who received oral anticoagulation alone ; those with contraindications to anticoagulant treatment , who received no treatment or an inferior caval-vein filter ; those who refused to be hospitalized , who received low-dose heparin and oral anticoagulant agents ; and those with threatened viability of the leg , who received thrombolytic therapy . The actual type and duration of treatments were recorded . All patients were instructed to wear elastic graduated compression stockings ( providing 40 mm Hg of pressure at the ankle ) for at least 2 years . Follow-up All patients were seen 3 and 6 months after the initial referral and thereafter returned to the study center every 6 months for follow-up assessment s. Patients were asked to return to the thrombosis center immediately if symptoms suggestive of recurrent venous thromboembolism developed . Follow-up was continued for as long as 8 years or until July 1995 . To avoid diagnostic suspicion bias , the medical history on general health , symptoms of recurrent venous thromboembolism , and the post-thrombotic syndrome was obtained by using a st and ardized form . Patients who could not attend the follow-up sessions were visited at home . For all patients who died during follow-up , the date and cause of death were documented . Diagnosis of Recurrent Venous Thromboembolism and Hemorrhage Contrast venography of the symptomatic leg or legs was done as described previously [ 10 ] . The criteria for deep venous thrombosis were a constant intraluminal filling defect confirmed in at least two different projections or nonvisualization of a vein or a segment thereof , despite adequate technique and repeated injections with contrast material . The presence or absence of venous thrombosis was assessed by a panel of independent observers who were unaware of the patient 's other clinical features or previous test results . If a patient presented with clinical ly suspected recurrent venous thrombosis of the leg , venography was done . The criterion for recurrent venous thrombosis of the leg was a new intraluminal filling defect on the venogram . If the venogram was not diagnostic , recurrent venous thrombosis was diagnosed on the basis of an abnormal 125I-fibrinogen leg scan or results of noninvasive tests that had changed from normal to abnormal [ 11 , 12 ] . Patients with suspected pulmonary embolism had venography if they had concurrent leg symptoms or perfusion lung scanning in the absence of leg symptoms . Pulmonary embolism was excluded if the perfusion scan was normal . Because ventilation lung scanning was not available during the first years of the study and because pulmonary angiography could not routinely be done , we could not definitively diagnose pulmonary embolism in some patients . If a definitive diagnosis could not be made , patients were classified as not having recurrent venous thromboembolism . Perfusion lung scanning and pulmonary angiography were done and their results were interpreted according to st and ard procedures [ 13 ] . Hemorrhagic episodes were classified as major or minor , as reported previously [ 14 ] . The documentation of all patients suspected of having a recurrent venous thromboembolic or bleeding event was review ed by a three-member adjudication committee that was unaware of further clinical details of the patient . Criteria for the Post-Thrombotic Syndrome Presence of the post-thrombotic syndrome was assessed by investigators who were unaware of previous post-thrombotic manifestations and further clinical details of the patient . The presence of leg symptoms ( pain , cramps , heaviness , pruritus , and paresthesia ) and signs ( pretibial edema , in duration of the skin , hyperpigmentation , new venous ectasia , redness , and pain during calf compression ) was scored . For each item , the investigators assigned a score of 0 ( not present or minimal ) to 3 ( severe ) . The presence of a venous ulcer of the lower limb was recorded . In patients with bilateral thrombosis , the higher score was used . A total score of 15 or more on two consecutive visits or the presence of a venous ulcer indicated severe post-thrombotic syndrome , and a total score of 5 to 14 on two consecutive visits indicated mild post-thrombotic syndrome . This score has been shown to have good reproducibility , and it correlates well with the patient 's perception of the interference of leg symptoms with daily life [ 15 ] . Statistical Analysis We calculated Kaplan-Meier estimates and 95 % CIs for a visual assessment of survival and calculated the risk for recurrent venous thromboembolism and mild and severe A prospect i ve r and omized study was performed to investigate the long-term sequelae of calf vein thrombosis ( CVT ) and correlate them to the success of the initial treatment . Thirty-six patients with symptomatic CVT , verified by venography , were treated with heparin or low-dose streptokinase ( SK ) combined with low-dose heparin . Venography was repeated after 1 week , and long-term follow-up was performed clinical ly and with foot volumetry after an average of 5 years . Since the low-dose SK regimen led to serious hemorrhagic side-effects in a parallel study , the present investigation was discontinued prematurely . The thrombolysis achieved was greater with SK but , since the initial thrombi were somewhat larger in this group , no significant difference in the average size of the thrombi after therapy could be displayed between the groups . The long-term sequelae and results of foot volumetry were also equal . Signs or symptoms of venous insufficiency were found in 37 % , and foot volumetry showed deep venous insufficiency in 26 % of the cases . There was a correlation between the hemodynamic change , as assessed by foot volumetry , and the venographic severity . This relation was stronger for the size of the thrombus after treatment than for the initial size . Thus , it seems important to limit the extent of a CVT in order to minimize the long-term sequelae , but administration of SK is not justified due to side-effects In a previous study on 42 patients with acute deep vein thrombosis , r and omly allocated to treatment with streptokinase or heparin , we found that 71.4 % of the streptokinase-treated patients achieved phlebographically significant thrombolysis as compared to 23.8 % in the heparin group . These patients have been reevaluated after a mean observation period of 6 1/2 years . Seven patients had died and there were no other drop-outs . Thus , 35 patients were subjected to the follow-up study consisting of phlebography and clinical examination . The evaluations were performed without knowledge of the initial therapy . Seven patients had phlebographically normal veins , and all belonged to the streptokinase group . This difference between the treatment groups is statistically highly significant ( p less than 0.01 ) . At clinical examination , 13 of the 17 patients in the streptokinase group had normal legs and 4 exhibited moderate postthrombotic changes . In contrast , 3 of the heparin-treated patients showed serious postthrombotic changes with open leg ulcers , and only 6 of 18 patients in this group had normal legs . The present results strongly support the assumption that streptokinase therapy is the best treatment at present in patients with acute deep vein thrombosis . This has been shown for the initial thrombolysis , and now also for the avoidance of late postthrombotic changes Heparin or streptokinase was administered in a prospect i ve r and omized fashion to 50 patients with phlebographically confirmed venous thrombosis of the extremities of 14 days or less duration . A total of 49 patients completed the investigative protocol with 26 receiving heparin and 23 receiving streptokinase . All patients were evaluated with sequential phlebograms . Complete thrombolysis with restoration of venous valve function occurred in one of 26 patients receiving heparin and in six of 23 patients receiving streptokinase . Fifty per cent of the patients treated with streptokinase with a total duration of symptoms of three days or less achieved complete lysis . The total incidence of therapeutic complications was similar in the two groups , but was more severe in the streptokinase treated patients In a prospect i ve trial , 42 medical patients with a history of deep vein thrombosis of less than five days were allocated at r and om to treatment with streptokinase or heparin . Only patients with extensive thromboses were included . Streptokinase was given in a loading dose of 250 000 IU and a maintenance dose of 100 000 IU/hour for 4 days as a mean . Heparin was given in a loading dose of 15 000 IU and a maintenance dose of 20 000 - 50 000 IU/day . The therapeutic results were evaluated by phlebography . Significant thrombolysis occurred in 71.4 % of 21 patients treated with streptokinase and in 23.8 % of the 21 heparin-treated patients . Using the chi2-test for overall association , this difference was statistically highly significant ( p = 0.002 ) . Three patients in each treatment group experienced major bleeding , two in each group requiring blood transfusions . Minor bleeding and slight rise in temperature were encountered more often in the streptokinase than in the heparin group . It is concluded that patients with acute deep vein thrombosis with proximal extension of the thrombus beyond the calf veins should be offered a therapeutic trial with streptokinase Patients with symptoms of deep vein thrombosis for less than 10 days were treated with a st and ard dose of heparin . In the open label phase of the trial , 11 patients received 100 mg rt-PA on the first day and 50 mg on the subsequent day in an 8 hour infusion . In the double-blind phase , 8 patients were r and omized to the same rt-PA regimen , 6 patients to an infusion of 50 mg rt-PA over 8 hours on days 1 and 2 , and 7 patients to placebo infusions . The mean change in venographic score in all patients treated with rt-PA plus heparin is -3.8 units compared to -0.6 units in patients treated with heparin alone ( p = 0.06 ) . Bleeding complications classified as major were noted in 8/25 patients receiving the combined treatment Abstract : Since no previous r and omized comparison has been carried out between ultra-high and conventional dosage streptokinase therapy of fresh venous thromboses , the NBVL trial was carried out as a prospect i ve , r and omized , multicentre , phlebographically monitored comparison of the results and adverse effects of these two fibrinolytic treatment options . Using the normal exclusion criteria , 156 patients with a leg-pelvis venous thrombosis presumed to be a maximum of 14 days old were treated with 1.5 million U streptokinase/h for 6h daily ( n = 77 , group A ) or conventional dosage with 100 000 U streptokinase per hour ( n = 79 , group B ) . There were 15 patients ( eight in group A , seven in group B ) who had to stop therapy prematurely , and eight patients ( five in group A , three in group B ) could not be evaluated because of incorrect monitoring times . The phlebograms were evaluated using IFP-C scores . These showed a reduction in the IFP score from 4.55 to 2.2 in the 64 patients in group A after a mean of 2.7 ± 0.6 therapy cycles with administration of 24.4 ± 5.7 million U streptokinase , i.e. 47 % of the baseline value . The 69 patients in group B had a reduction in score from 4.2 to 2.93 after a mean of 3.7 ± 1.2 days of treatment with administration of 8.6 ± 3.3 million units , i.e. a fall of 30 % in the baseline values ( p = 0.007 ) . There were 132 out of 281 completely occluded venous segments in group A ( 47 % ) and 81 out of 279 segments in group B ( 29 % ) that showed complete patency . Eight out of 27 three-segment occlusions in group A and only one of 26 in group B showed complete patency . The IFP score improved by 55 % in the 45 men in group A , compared with only 30 % in the 47 men in group B ( p = 0.002 ) . When both dosages are combined , men showed a greater improvement in IFP score than women ( 42 versus 29 % ; p = 0.02 ) . The IFP score improved more in the 20 patients aged more than 60 years in group A than in the 19 patients aged over 60 years of age in group B ( 61 versus 20 % ; p = 0.003 ) . No other significant differences in effect were seen on analysis of sub-groups and individual factors ( sex , age , presumed age of thrombus and side of thrombosis ) . In the 77 patients in group A , haemorrhagic complications were less frequent than in the 79 patients in group B ( 22.1 versus 36.7 % ; p = 0.054 ) , especially concerning urogenital haemorrhage ( 6.5 versus 22.8 % ; p = 0.004 ) . Women were affected more frequently by haemorrhagic complications than men ( 35.2 versus 26.5 % ) , and the 19 patients aged more than 65 years old were affected more than the 137 younger patients ( 21.1 versus 13.9 % ) . There were no deaths , and clinical ly insignificant pulmonary emboli occurred three times . Ultra-high dosage streptokinase shows better and more rapid thrombolytic treatment for popliteal-femoral-iliac venous thromboses and causes fewer haemorrhagic complications than conventional dosage streptokinase . The better effect of ultra-high dosage can be observed particularly for three-segment occlusion as well as in male patients . In older patients , accurate diagnosis is required because of the higher rate of haemorrhagic complications Thirty patients with deep vein thrombosis of the legs of less than four days ' duration were allocated at r and om to treatment with heparin , streptokinase , or Arvin under laboratory control . When the fate of the thrombi was assessed by objective techniques — phlebography and the 125I-labelled fibrinogen test — the incidence of complete thrombolysis was greatest in the streptokinase group . Complications arose during treatment in each group but were least with Arvin . The natural history of the disease favours clinical but not always anatomical recovery Thirty-three patients with acute iliofemoral thrombosis were r and omly assigned to three treatment groups in a pilot dose-ranging study of thrombolytic therapy in deep vein thrombosis . One group received tissue culture urokinase in a dose of 2,200 I.U./kg/hr , and a second group in a dose of 1,100 I.U./kg/hr following a loading dose of 4,400 I.U./kg given in ten min . Urokinase was administered for 12 hr periods , alternating with 12 hr periods of heparin . A third group received an initial dose of 250,000 I.U. of streptokinase in 20 min , followed by 100,000 I.U./hr . Treatment of all patients continued for three days . At the end of this period little improvement , evaluated by " blinded " interpretation of pre- and post-treatment phlebograms , was found in five out of ten of the higher-dose urokinase patients , seven out of eleven of lower-dosage urokinase patients , and six out of ten of streptokinase patients . Optional treatment for another three days showed little further improvement of urokinase- patients and moderate further improvement in the streptokinase- patients . Neither of the 2 dosage schemes at intermittent application of urokinase appeared to be advantageous . Urokinase treated patients experienced fewer adverse reactions We performed a r and omized trial comparing two dosing regimens of recombinant tissue plasminogen activator ( rt-PA ) plus heparin vs heparin alone in the treatment of acute proximal deep vein thrombosis in 83 patients . Of 12 patients who received 0.5 mg/kg rt-PA plus heparin over 4 h , seven ( 58 percent ) had greater than 50 percent lysis of the thrombus , compared with none of 12 who received placebo plus heparin ( p = 0.002 ) . Of 28 patients who received 0.5 mg/kg rt-PA over 8 h , repeated in 24 h , six ( 21 percent ) had greater than 50 percent lysis , compared with two ( 7 percent ) of 30 patients who received placebo plus heparin ( p = 0.11 ) . The 4-h infusion of rt-PA produced a 40 percent reduction and the 8-h infusion an 11 percent reduction in plasma fibrinogen concentration . At long-term follow-up , three ( 25 percent ) of 12 patients in whom greater than 50 percent lysis was achieved had symptoms of the postphlebitic syndrome , compared with 19 ( 56 percent ) of 34 patients in whom lysis was less than 50 percent ( p = 0.07 ) |
829 | 20,464,742 | The involvement of IHW in asthma programs targeted for their own ethnic group in 2 small trials was beneficial in improving most , but not all asthma outcomes in children with asthma .
It is very likely that involvement of an IHW is beneficial . | BACKGROUND Asthma education is regarded as an important step in the management of asthma in national guidelines .
Racial , ethnicity and socio-economic factors are associated with markers of asthma severity , including recurrent acute presentations to emergency health facilities .
Worldwide , indigenous groups are disproportionately represented in the severe end of the asthma spectrum .
Appropriate models of care are important in the successful delivery of services , and are likely contributors to improved outcomes for people with asthma .
OBJECTIVES To determine whether involvement of an indigenous healthcare worker ( IHW ) in comparison to absence of an IHW in asthma education programs , improves asthma related outcomes in indigenous children and adults with asthma . | BACKGROUND Whether asthma morbidity in minority groups can be reduced by preventative health care measures delivered in the relevant ethnic dialects requires further evaluation . This study reports clinical outcomes and quality of life from a community based project investigating white European ( W/E ) and Indian subcontinent ( ISC ) ethnic groups with asthma living in deprived inner city areas of Birmingham , UK . METHODS Six hundred and eighty nine asthmatic subjects ( 345 W/E , 344 ISC ) of mean ( SD ) age 34.5 ( 15 ) years ( range 11–59 ) and mean forced expiratory volume in one second ( FEV1 ) of 80 % predicted were interviewed in English , Punjabi , Hindi , or Urdu . Subjects r and omised to the active limb of a prospect i ve , open , r and omised , controlled , parallel group , 12 month follow up study underwent individually based asthma education and optimisation of drug therapy with four monthly follow up ( active intervention ) . Control groups were seen only at the beginning and end of the study . Urgent or emergency interactions with primary and secondary health care ( clinical outcomes ) and both cross sectional and longitudinal data from an Asthma Quality of Life Question naire ( AQLQ ) were analysed . RESULTS Clinical outcomes were available for 593 subjects . Fewer of the active intervention group consulted their GP ( 41.8 % versus 57.8 % , odds ratio ( OR ) 0.52 ( 95 % CI 0.37 to 0.74 ) ) or were prescribed antibiotics ( 34.9 % versus 51.2 % , OR 0.51 ( 95 % CI 0.36 to 0.72 ) ) , but by ethnicity statistically significant changes occurred only in the W/E group with fewer also attending A&E departments and requiring urgent home visits . Active intervention reduced the number of hospital admissions ( 10 versus 30 ) , GP consultations ( 341 versus 476 ) , prescriptions of rescue oral steroids ( 92 versus 177 ) , and antibiotics ( 220 versus 340 ) , but again significant improvements by ethnicity only occurred in the active W/E group . AQLQ scores were negatively skewed to the higher values ; regression analysis showed that lower values were associated with ISC ethnicity . Longitudinal changes ( for 522 subjects ) in the mean AQLQ scores were small but statistically significant for both ethnic groups , with scores improving in the active and worsening in the control groups . CONCLUSIONS Active intervention only improved clinical outcomes in the W/E group . AQLQ scores , although lower in the ISC group , were improved by active intervention in both ethnic groups Background . Asthma , a leading chronic disease of children , currently affects about 6.2 million ( 8.5 % ) children in the United States . Despite advances in asthma research and availability of increasingly effective therapy , many children do not receive appropriate medications to control the disease , have overreliance on reliever medication , and lack systematic follow-up care . The situation is even worse for poor inner-city and minority children who have significantly worse asthma rates , severity , and outcomes . National Asthma Education and Prevention Program Guidelines recommend a multimodal , chronic care approach . Objective . The authors assessed the effectiveness of practice re design and computerized provider feedback in improving both practitioner adherence to National Asthma Education and Prevention Program Guidelines ( NAEPP ) , and patient outcomes in 295 poor minority children across four Federally Qualified Health Centers ( FQHC ) . Methods . In a nonr and omized , two-group ( intervention versus comparison ) , two-phase trial , all sites were provided re design support to provide quarterly well-asthma visits using structured visit forms , community health workers for outreach and follow-up , a Web-based disease registry for tracking and scheduling , and a provider education package . Intervention sites were given an additional Web-based , computerized patient-specific provider feedback system that produced a guideline -driven medication assessment prompt . Results . Logistic regression results showed that providers at intervention sites were more than twice as likely on average to prescribe guideline -appropriate medications after exposure to our feedback system during the Phase I enrollment period than providers at comparison sites ( exp(B ) = 2.351 , confidence interval [ CI ] = 1.315–4.204 ) . In Phase II ( the postenrollment visit period ) , hierarchical linear models ( HLMs ) and latent growth curves were used to show that asthma control improved significantly by .19 ( SE = .05 ) on average for each of the remaining four visits ( about 11 % of a st and ard deviation ) , and improved even more for patients at intervention sites . These results show that implementation of practice re design support guided by a pediatric chronic care model can improve provider adherence to treatment guidelines as well as patients ’ asthma control . Conclusions . The addition of patient-specific feedback for providers results in quicker adoption of guideline recommendations and potentially greater improvements in asthma control compared to the basic practice re design support alone OBJECTIVE To assess the outcomes of an education intervention for childhood asthma conducted by Australian Indigenous health care workers ( IHCWs ) . DESIGN AND SETTING R and omised controlled trial in a primary health care setting on Thursday Isl and and Horn Isl and , and in Bamaga , Torres Strait region of northern Australia , April 2005 to March 2007 . PARTICIPANTS 88 children , aged 1 - 17 years , with asthma diagnosed by a respiratory physician ( intervention group , 35 ; control group , 53 ; 98 % Indigenous children ) . INTERVENTIONS Children were r and omly allocated to : ( i ) three additional asthma education sessions with a trained IHCW , or ( ii ) no additional asthma education . Both groups were re-assessed at 12 months . MAIN OUTCOME MEASURES Primary endpoint : number of unscheduled visits to hospital or a doctor caused by asthma exacerbation . SECONDARY OUTCOMES measures of quality of life ( QoL ) and functional severity index ; asthma knowledge and underst and ing of asthma action plans ( AAPs ) ; and school days missed because of wheezing . RESULTS The groups were comparable at baseline ( except for asthma severity , which was adjusted for in the analysis ) . There were no significant differences in the primary outcome ( number of unscheduled medical visits for asthma ) . School children in the intervention group missed fewer school days because of wheezing ( 100 % < 7 days v 21 % of those in the control group missed 7 - 14 days ) . Significantly more carers in the intervention group could answer questions about asthma medication , knew where their AAP was kept ( 84 % v 56 % ) , and were able to describe the plan ( 67 % v 40 % ) . In both the intervention and control groups ( before- and -after comparison ) , there was a significantly reduced frequency of asthma exacerbations , as well as an improved QoL score and functional severity index , with no significant differences between the groups . CONCLUSIONS A community-based asthma education program conducted by trained IHCWs improves some important asthma outcomes in Indigenous children with asthma . TRIAL REGISTRATION Australian Clinical Trials Registry ACTRN012605000718640 OBJECTIVE To describe the management of asthma in children in a remote indigenous community and the delivery of subspecialist service through the indigenous health-care model . METHODOLOGY Children referred by indigenous health-care workers were evaluated prospect ively by paediatric respiratory physicians , based on a st and ardized protocol , at a primary health care setting at Thursday Isl and , Queensl and . RESULTS Forty of the 54 children referred with a provisional diagnosis of asthma did have asthma , with 30 % having persistent asthma . Only 59 % of parents knew the dose of the medication prescribed and 80 % had minimal knowledge of the medications . In 88 % of children , the management of asthma was improved by introduction of an appropriate spacer device and changing the dose and type of medications . CONCLUSIONS The management of children with asthma in the Torres region can be improved substantially by the use of age appropriate delivery devices and medications , and improving knowledge of asthma . Specialist delivery service to remote indigenous communities can be effectively delivered in partnership with the indigenous health service . The high proportion of persistent asthma in the Torres Straits community in comparison to urbanised Australia raises issues of inequity of appropriate medical service delivery to remote indigenous communities OBJECTIVE : Because asthma disproportionately affects minorities , we evaluated the effects of parent mentors ( PMs ) on asthma outcomes in minority children . METHODS : This r and omized , controlled trial allocated minority asthmatic children to the PM intervention or traditional asthma care . Intervention families were assigned PMs ( experienced parents of asthmatic children who received specialized training ) . PMs met monthly with children and families at community sites , phoned parents monthly , and made home visits . Ten asthma outcomes and costs were monitored for 1 year . Outcomes were examined by using both intention-to-treat analyses and stratified analyses for high participants ( attending ≥25 % of community meetings and completing ≥50 % of PM phone interactions ) . RESULTS : Patients were r and omly assigned to PMs ( n = 112 ) or the control group ( n = 108 ) . In intention-to-treat analyses , intervention but not control children experienced significantly reduced rapid-breathing episodes , asthma exacerbations , and emergency department ( ED ) visits . High participants ( but not controls or low participants ) experienced significantly reduced wheezing , asthma exacerbations , and ED visits and improved parental efficacy in knowing when breathing problems are controllable at home . Mean reductions in missed parental work days were greater for high participants than controls . The average monthly cost per patient for the PM program was $ 60.42 , and net savings of $ 46.16 for high participants . CONCLUSIONS : For asthmatic minority children , PMs can reduce wheezing , asthma exacerbations , ED visits , and missed parental work days while improving parental self-efficacy . These outcomes are achieved at a reasonable cost and with net cost savings for high participants . PMs may be a promising , cost-effective means for reducing childhood asthma disparities BACKGROUND Despite significant medical advances , many ethnic and racial minority children who live in inner cities continue to experience disproportionately high levels of asthma morbidity and mortality compared with white children . As a result , a growing number of psychosocial asthma management interventions are being developed to address their needs ; however , only a few of these interventions have incorporated cultural variables into their treatments and have had their efficacy evaluated . OBJECTIVE To examine the efficacy of the Multifamily Asthma Group Treatment ( MFAGT ) , design ed to enhance asthma management and reduce emergency department ( ED ) visits among African American and Hispanic families . METHODS Twenty-four African American and Hispanic families who have children with asthma were r and omly assigned to either the MFAGT or the St and ard Psychoeducational Asthma Intervention . Differences in the number of ED visits and the level of asthma management in both groups were compared 1 year before and 1 year after the intervention . In addition , these groups were contrasted to a control group that did not receive any psychoeducational intervention . RESULTS The MFAGT was significantly ( P = .04 ) more effective than the St and ard Psychoeducational Asthma Intervention and the control in decreasing ED visits and increasing parental asthma knowledge . CONCLUSIONS These preliminary results suggest that the MFAGT is efficacious in enhancing asthma management and in reducing ED visits in inner-city African American and Hispanic children from a lower socioeconomic background Although asthma self-management plans are widely recommended as essential in the long-term treatment of adult asthma , there have been few studies examining their use . Our objective was to assess the effect of a " credit card " adult asthma self-management plan in a community experiencing major health problems from asthma , by means of a before and after intervention trial of the efficacy of the " credit card " plan , when introduced through community-based asthma clinics . The participants were 69 Maori people with asthma . The " credit card " plan consisted of written guidelines for the self-management of asthma , based on self- assessment of asthma severity , printed on a plastic card . On one side , management guidelines were based on the interpretation of peak expiratory flow rate ( PEFR ) recordings , whilst the reverse side was based on symptoms . The outcome measures used were before and after comparison of markers of asthma morbidity and requirement for acute medical treatment ; and a structured question naire assessing the acceptability and use of the credit card plan . Following the introduction of the plan , the mean PEFR increased from 347 to 389 l.min-1 , the percentage of nights woken fell from 30.4 to 16.9 % , and the number of days " out of action " fell from 3.8 to 1.7 % . The requirements for acute medical treatment also fell during the intervention period . Most participants commented favourably on the content and usefulness of the plan . In the situation of worsening asthma , 28 % of subjects found the peak flow side of the card most helpful , 7 % the symptoms side , and 48 % found both sides equally helpful . ( ABSTRACT TRUNCATED AT 250 WORDS The aim of this study was to evaluate the effectiveness of an asthma education programme in moderate and severe asthma patients in a longitudinal , prospect i ve and r and omized study with a control group . Fifty-three asthmatic patients were studied , 26 of whom were assigned to the educational group and 27 to the control group . The educational group attended the programme regularly for a period of 6 months . The programme included information about asthma , instruction on the appropriate use of medication and training in the metered dose inhaler ( MDI ) technique , and information about the identification and control of asthma attacks and the recognition of early signs of exacerbation . The control group was su bmi tted to the routine care provided at the Asthma Clinic , with no formal instruction regarding asthma control . The groups were identical with regard to severity parameters , skills , lung function and quality of life at the beginning of the trial . At the end of the study , the education group showed significant differences when compared with the control group ( education/control ( mean values ) ) with respect to : visits to the asthma emergency room over the previous 6 months , 0.7/2 ( p=0.03 ) ; nocturnal symptoms , 0.3/0.7 ( p=0.04 ) ; score of symptoms , 1.3/2 ( p=0.04 ) . Improvements were also observed in skills and quality of life , knowledge of how to deal with attacks and how to control the environmental triggering factors , 73/35 ( < 0.05 ) ; correct use of the MDI , 8/4 ( 0.001 ) ; underst and ing of the difference between relief and anti-inflammatory medication , 86/20 ( < 0.05 ) ; and in the global limitation quality of life score , 28/50 ( 0.02 ) . It is concluded that the educational programme led to a significant improvement in asthma morbidity and that the implantation of educational programmes is possible for special population s when these programmes are adapted to the socioeconomic profile of the patients , with a significant gain in terms of the reduction of symptoms and improved pulmonary function and quality of life of asthmatics CONTEXT Increasing urban asthma prevalence and severity is found among minority , underserved population s. Improving asthma self-management includes home management of complex medical protocol s as well as environmental trigger removal . OBJECTIVE To study the effectiveness of a low-cost approach to improve control of asthma symptoms in an urban population through lay educators who promote a generalized approach to asthma trigger avoidance in the bedrooms of children with asthma . DESIGN AND PATIENTS Prospect i ve , r and omized controlled trial with two arms : historical controls and matched controls for each subject . SUBJECTS Two-hundred-eighty-one patients living in an urban environment , r and omized to receive home visits only ( n = 128 ) or home visits with environmental remediation ( n = 153 ) . One-hundred-fifteen controls matched according to age , gender and ethnicity did not receive any intervention . INTERVENTIONS In-home education visits covered asthma physiology , asthma trigger avoidance and asthma management . Environmental remediation was conducted together with the caregiver . OUTCOMES Primary outcomes include length of hospital stay , number of emergency visits and number of sick visits . Secondary outcomes are symptom frequency , medication management and trigger reduction . RESULTS Both intervention groups experienced reduction of hospitalizations , emergency room visits , sick visits and asthma symptoms . Both groups showed outcomes significantly superior to the matched control group . Intervention effectively reduced the presence of rodents and carpet in home and increased the use of mattress and pillow covers . CONCLUSIONS This study shows that low-cost in-home education and environmental remediation improve outcomes for children with asthma . Lay educators can deliver effective asthma-specific education that results in improved asthma control The objective of the study was to assess the feasibility of implementing and evaluating a culturally appropriate in-patient asthma education program specifically targeted for African-Americans . A consecutive sample of 28 African-American patients ages 18–50 who were hospitalized for asthma were r and omized to an intervention group , which received three one-on-one sessions on chronic asthma management , or a control group , which received the usual care . Data on symptom frequency , self-management behaviors , quality of life , depression , and health care re source use were collected at baseline and at 3 and 6 months . Although the time required to recruit our sample took longer than anticipated , 28 subjects agreed to be in the study ( 70 % acceptance rate ) and complete the baseline interview . We observed no statistically significant differences from baseline or changing trends in frequency of asthma symptoms , self-management behaviors , and health care re source use between the intervention and control groups at 3 and 6 months . However , patients in the intervention group demonstrated a greater average increase in asthma-related quality of life and a greater average decrease in depression than the control group . Feasibility issues included shortened length of stay , which necessitated conducting all three self-management sessions together , multiple interruptions during the sessions , and retention issues at 3- and 6-month follow-ups . The lessons learned from this pilot study are invaluable in that they will enable us to make changes in our existing protocol to ensure the success of a larger clinical trial OBJECTIVE To test whether community health workers are able to reach low-income parents of African American children hospitalized for asthma and to reduce rehospitalization among them . DESIGN A r and omized controlled evaluation of usual care vs 2-year asthma coach intervention . SETTING An urban children 's hospital and the surrounding community . PARTICIPANTS A population -based sample of 306 children hospitalized for asthma met the inclusion criteria of being 2 to 8 years of age , of African American ethnicity , and having Medicaid coverage . Of these , 200 were contacted and 191 recruited with commitment to evaluation activities but , in order to assess reach , no commitment to participating in intervention . INTERVENTIONS Coaches reinforced basic asthma education and encouraged key management behaviors through home visits and phone calls tailored to parent 's readiness to adopt management practice s and emphasizing a nondirective supportive style ( cooperative and accepting of feelings and choices ) . OUTCOME MEASURES The reach of intervention to parents , contacts with coaches , and rehospitalization over 2 years based on hospital records . RESULTS Within 3 months of r and omization to the asthma coach group , 89.6 % of parents had at least 1 substantive contact with the coach , with an average of 21.1 contacts per parent over the 24-month intervention . The proportion of children rehospitalized was 35 of 96 ( 36.5 % ) in the asthma coach group and 55 of 93 ( 59.1 % ) in the usual care group ( P < .01 ) , controlling for parental education and child age , sex , and hospitalization in the year prior to the index hospitalization . In surveys , parents indicated the importance of the nondirective approach to support . CONCLUSIONS An asthma coach can reach low-income parents of African American children hospitalized for asthma and reduce rehospitalization among the children OBJECTIVE To compare the marginal benefit of in-home asthma self-management support provided by community health workers ( CHWs ) with st and ard asthma education from clinic-based nurses . DESIGN R and omized controlled trial . SETTING Community and public health clinics and homes . PARTICIPANTS Three hundred nine children aged 3 to 13 years with asthma living in low-income households . INTERVENTIONS All participants received nurse-provided asthma education and referrals to community re sources . Some participants also received CHW-provided home environmental assessment s , asthma education , social support , and asthma-control re sources . OUTCOME MEASURES Asthma symptom-free days , Pediatric Asthma Caretaker Quality of Life Scale score , and use of urgent health services . RESULTS Both groups showed significant increases in caretaker quality of life ( nurse-only group : 0.4 points ; 95 % confidence interval [ CI ] , 0.3 - 0.6 ; nurse + CHW group : 0.6 points ; 95 % CI , 0.4 - 0.8 ) and number of symptom-free days ( nurse only : 1.3 days ; 95 % CI , 0.5 - 2.1 ; nurse + CHW : 1.9 days ; 95 % CI , 1.1 - 2.8 ) , and absolute decreases in the proportion of children who used urgent health services in the prior 3 months ( nurse only : 17.6 % ; 95 % CI , 8.1%-27.2 % ; nurse + CHW : 23.1 % ; 95 % CI , 13.6%-32.6 % ) . Quality of life improved by 0.22 more points in the nurse + CHW group ( 95 % CI , 0.00 - 0.44 ; P = .049 ) . The number of symptom-free days increased by 0.94 days per 2 weeks ( 95 % CI , 0.02 - 1.86 ; P = .046 ) , or 24.4 days per year , in the nurse + CHW group . While use of urgent health services decreased more in the nurse + CHW group , the difference between groups was not significant . CONCLUSION The addition of CHW home visits to clinic-based asthma education yielded a clinical ly important increase in symptom-free days and a modest improvement in caretaker quality of life BACKGROUND Reducing the impact of chronic disease in minority ethnic groups is an important public health challenge . Lay-led education may overcome cultural and language barriers that limit the effectiveness of professionally-led programmes . We report the first r and omised trial of a lay-led self-management programme - the Chronic Disease Self-Management Programme ( CDSMP ) ( Expert Patient Programme ) - in a south Asian group . AIM To determine the effectiveness of a culturally-adapted lay-led self-management programme for Bangladeshi adults with chronic disease . DESIGN OF STUDY R and omised controlled trial . SETTING Tower Hamlets , east London . METHOD We recruited Bangladeshi adults with diabetes , cardiovascular disease , respiratory disease or arthritis from general practice s and r and omised them to the CDSMP or waiting-list control . Self-efficacy ( primary outcome ) , self-management behaviour , communication with clinician , depression scores , and healthcare use were assessed by blinded interviewer-administered question naires in Sylheti before r and omisation and 4 months later . RESULTS Of the 1363 people invited , 476 ( 34 % ) agreed to take part and 92 % ( 439/476 ) of participants were followed up . The programme improved self-efficacy ( difference : 0.67 , 95 % confidence interval [ CI ] = 0.08 to 1.25 ) and self-management behaviour ( 0.53 ; 95 % CI = 0.01 to 1.06 ) . In the 51 % ( 121/238 ) of intervention participants attending three or more of the 6-weekly education sessions the programme led to greater improvements in self-efficacy ( 1.47 ; 95 % CI = 0.50 to 1.82 ) and self-management behaviour ( 1.16 ; 95 % CI = 0.50 to 1.82 ) , and reduced HADS depression scores ( 0.64 ; 95 % CI = 0.07 to 1.22 ) . Communication and healthcare use were not significantly different between groups . The programme cost pound123 ( 181 ) per participant . CONCLUSION A culturally-adapted CDSMP improves self-efficacy and self-care behaviour in Bangladeshi patients with chronic disease . Effects on health status were marginal . Benefits were limited by moderate uptake and attendance The purpose of this study was to test the feasibility and short-term outcomes of Asthma : It 's a Family Affair ! , a school-based intervention for adolescents with asthma and their caregivers . Twenty-four ethnic minority families with a middle school student with asthma were r and omized to immediate intervention or no-treatment control . Intervention students received six group sessions on prevention and management of asthma . Caregivers received five group sessions teaching child-rearing skills to support the youth 's autonomy and asthma self-management . All students attended all sessions ; caregivers attended an average of three . Two months post-intervention , relative to controls , intervention caregivers reported better problem-solving with children . Intervention students were more responsible for carrying medication , took more prevention steps , and woke fewer nights from asthma . The intervention result ed in positive short-term changes in family relations , asthma management by students , and health status OBJECTIVE Recent studies have shown that lack of continuing primary care for asthma is associated with increased levels of morbidity in low-income minority children . Although effective preventive therapy is available , many African-American and Latino children receive episodic treatment for asthma that does not follow current guidelines for care . To see if access , continuity , and quality of care could be improved in pediatric clinics serving low-income children in New York City , we trained staff in New York City Bureau of Child Health clinics to provide continuing , preventive care for asthma . METHODS We evaluated the impact of the intervention over a 2-year period in a controlled study of 22 clinics . Training for intervention clinic staff was based on National Asthma Education and Prevention Program guidelines for the diagnosis and management of asthma , and included screening to identify new cases and health education to improve family management . The intervention included strong administrative support by the Bureau of Child Health to promote staff behavior change . We hypothesized that after the intervention , clinics that received the intervention would , compared with control clinics , have increased numbers of children with asthma receiving continuing care in the clinics and increased staff use of new pharmacologic and educational treatment methods . RESULTS In both the first and second follow-up years , the intervention clinics had greater positive changes than control clinics on measures of access , continuity , and quality of care . For second year follow-up data these include : for access , greater rate of new asthma patients ( 40/1000 vs 16/1000 ; P < .01 ) ; for continuity , greater percentage of asthma patients returning for treatment 2 years in a row ( 42 % vs 12 % ; P < .001 ) and greater annual frequency of scheduled visits for asthma per patient ( 1.85 vs .88 ; P < .001 ) ; and for quality , greater percentage of patients receiving inhaled beta agonists ( 52 % vs 15 % ; P < .001 ) and inhaled antiinflammatory drugs ( 25 % vs 2 % ; P < .001 ) , and greater percentages of parents who reported receiving patient education on 12 topics from Bureau of Child Health physicians ( 71 % vs 58 % ; P < .01 ) and nurses ( 61 % vs 44 % ; P < .05 ) . CONCLUSION We conclude that the intervention substantially increased the Bureau of Child Health staff 's ability to identify children with asthma , involve them in continuing care , and provide them with state-of-the-art care for asthma |
830 | 30,081,902 | Conclusions Resistance generally increased soon after antibiotic use . | Background Antibiotic resistance is an urgent global problem , but reversibility is poorly understood .
We examined the development and decay of bacterial resistance in community patients after antibiotic use . | Jeremy Keenan and colleagues report that during a cluster-r and omized clinical trial in Ethiopia , nasopharyngeal pneumococcal resistance to macrolides was significantly higher in communities r and omized to receive azithromycin compared with untreated control communities ABSTRACT Mean fecal global yeast counts increased similarly during 7 days of treatment with telithromycin ( 800 mg once daily ) or amoxicillin-clavulanic acid ( amoxiclav ) ( 1 g of amoxicillin and 125 mg of clavulanic acid 3 times daily ) in human volunteers and decreased slowly thereafter . On skin , coagulase-negative staphylococci of decreased susceptibility ( DS ) to telithromycin increased in the telithromycin group , whereas those with DS to methicillin increased in the amoxiclav group . A similar antibiotic-related shift towards homologous DS was observed for oral nongroupable streptococci ( NGS ) , but in addition , the prevalence of NGS resistant to both classes of antibiotics was significantly greater in the amoxiclav group at days 8 ( P < 0.01 ) and 45 ( P < 0.015 ) Background Synthesis of multiple r and omized controlled trials ( RCTs ) in a systematic review can summarize the effects of individual outcomes and provide numerical answers about the effectiveness of interventions . Filtering of search es is time consuming , and no single method fulfills the principal requirements of speed with accuracy . Automation of systematic review s is driven by a necessity to expedite the availability of current best evidence for policy and clinical decision-making . We developed Rayyan ( http://rayyan.qcri.org ) , a free web and mobile app , that helps expedite the initial screening of abstract s and titles using a process of semi-automation while incorporating a high level of usability . For the beta testing phase , we used two published Cochrane review s in which included studies had been selected manually . Their search es , with 1030 records and 273 records , were uploaded to Rayyan . Different features of Rayyan were tested using these two review s. We also conducted a survey of Rayyan ’s users and collected feedback through a built-in feature . Results Pilot testing of Rayyan focused on usability , accuracy against manual methods , and the added value of the prediction feature . The “ taster ” review ( 273 records ) allowed a quick overview of Rayyan for early comments on usability . The second review ( 1030 records ) required several iterations to identify the previously identified 11 trials . The “ suggestions ” and “ hints , ” based on the “ prediction model , ” appeared as testing progressed beyond five included studies . Post rollout user experiences and a reflexive response by the developers enabled real-time modifications and improvements . The survey respondents reported 40 % average time savings when using Rayyan compared to others tools , with 34 % of the respondents reporting more than 50 % time savings . In addition , around 75 % of the respondents mentioned that screening and labeling studies as well as collaborating on review s to be the two most important features of Rayyan . As of November 2016 , Rayyan users exceed 2000 from over 60 countries conducting hundreds of review s totaling more than 1.6 M citations . Feedback from users , obtained mostly through the app web site and a recent survey , has highlighted the ease in exploration of search es , the time saved , and simplicity in sharing and comparing include-exclude decisions . The strongest features of the app , identified and reported in user feedback , were its ability to help in screening and collaboration as well as the time savings it affords to users . Conclusions Rayyan is responsive and intuitive in use with significant potential to lighten the load of review ers ABSTRACT To investigate the effect of slow-release ( SR ) clarithromycin on colonization and the development of resistance in oropharyngeal and nasal flora , a double-blind , r and omized , placebo-controlled trial was performed with 8 weeks of follow-up . A total of 296 patients with documented coronary artery disease were r and omized in the preoperative outpatient clinic to receive a daily dose of SR clarithromycin ( 500 mg ) ( CL group ) or placebo tablets ( PB group ) until the day of surgery . Nose and throat swabs were taken before the start of therapy , directly after the end of therapy , and 8 weeks later . The presence of potential pathogenic bacteria was determined , and if they were isolated , MIC testing was performed . Quantitative culture on media with and without macrolides was performed for the indigenous oropharyngeal flora . In addition , analysis of the mechanism of resistance was performed with the macrolide-resistant indigenous flora . Basic patient characteristics were comparable in the two treatment groups . The average number of tablets taken was 15 ( st and ard deviation = 6.4 ) . From the throat swabs , Haemophilus parainfluenzae was isolated and carriage was not affected in either of the treatment groups . Nasal carriage of Staphylococcus aureus , however , was significantly reduced in the CL group ( from 35.3 to 4.3 % ) compared to the PB group ( from 32.4 to 30.3 % ) ( P < 0.0001 ; relative risk [ RR ] , 7.0 ; 95 % confidence interval [ CI ] , 3.1 to 16.0 ) . Resistance to clarithromycin was present significantly more frequently in H. parainfluenzae in the CL group after treatment ( P = 0.007 ; RR , 1.6 ; 95 % CI , 1.1 to 2.3 ) ; also , the percentage of patients with resistance to macrolides in the indigenous flora after treatment was significantly higher in the CL group ( 31 to 69 % ) ( P < 0.0001 ; RR , 1.9 ; 95 % CI , 1.4 to 2.5 ) . This persisted for at least 8 weeks . This study shows that besides the effective elimination of nasal carriage of S. aureus , treatment with SR clarithromycin for approximately 2 weeks has a marked and sustained effect on the development of resistance in the oropharyngeal flora for at least 8 weeks BACKGROUND Acute otitis media is the leading reason for antibiotic prescriptions in childhood . The increase in antibiotic resistance of Streptococcus pneumoniae is generally attributed to the extensive use of antibiotics and the selective pressure on the bacterial strains of the nasopharyngeal flora . OBJECTIVE To evaluate the change in nasopharyngeal carriage of S. pneumoniae during antibiotic therapy prescribed for acute otitis media . METHODS Between October , 1993 , and March , 1994 , we conducted a clinical trial comparing cefpodoxime-proxetil and amoxicillin-clavulanate in acute otitis media . From 364 children , 4 months to 4.5 years old , a nasopharyngeal sample was obtained before and after treatment . Antibiotic susceptibility was established by determining minimal inhibitory concentrations by the agar dilution method . Serotype and r and omly amplified polymorphic DNA analysis were used to compare pre- and posttreatment S. pneumoniae strains . RESULTS The risk for a child to carry penicillin-resistant S. pneumoniae ( MIC > or = 0.125 mg/l ) did not increase after antibiotic treatment : 84 of 364 ( 23.1 % ) before , 70 of 364 ( 19.2 % ) after . There was a significant decrease of penicillin-susceptible S. pneumoniae carriage , 117 of 364 ( 32.1 % ) before treatment compared with 24 of 364 ( 6.6 % ) ( P = 0.0001 ) after treatment . However , among the children carrying S. pneumoniae at the end of the treatment there was an increase in the percentage of penicillin-resistant pneumococci : 84 of 201 ( 41.8 % ) before treatment and 70 of 94 ( 74.5 % ) after treatment . Among the 94 children carrying S. pneumoniae at the end of the treatment , 22 did not harbor pneumococcus before , 16 carried another genotypically different serotype and 56 harbored the same serotype . Among these 56 children 2 patients harbored strains that had increased MICs for the tested beta-lactam antibiotics . The r and omly amplified polymorphic DNA analysis showed that in one case , the strains were genetically different . CONCLUSIONS These data illustrate that antibiotic therapy did not increase the rate at which children carried penicillin-resistant S. pneumoniae , but there was an increase in the rate of resistance among the children carrying pneumococci at the end of the treatment , mainly as a result of reduction of susceptible strains Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more PURPOSE To assess the ecologic impact , in terms of selection of beta-lactamase-producing respiratory tract bacteria , of a single course of peroral beta-lactam antibiotics . PATIENTS AND METHODS One-hundred fifty consecutive children with clinical signs of bacterial respiratory tract infection were r and omly assigned to a seven-day course of treatment with either penicillin V , amoxicillin , or cefaclor . Bacteriologic specimens were collected before treatment , at its termination , and at follow-up four weeks later . RESULTS All three drugs investigated caused a similar increase in beta-lactamase-producing bacteria , both in absolute and relative terms , an increase that persisted over a period of at least one month after completion of treatment . CONCLUSION Penicillin V , amoxicillin , and cefaclor all act as selective agents for beta-lactamase-producing bacteria in the upper respiratory tract . Treatment with a peroral beta-lactam antibiotic puts patients at risk of becoming persistent carriers of beta-lactamase-producing bacteria CONTEXT Emerging drug resistance threatens the effectiveness of existing therapies for pneumococcal infections . Modifying the dose and duration of antibiotic therapy may limit the spread of resistant pneumococci . OBJECTIVE To determine whether short-course , high-dose amoxicillin therapy reduces risk of posttreatment resistant pneumococcal carriage among children with respiratory tract infections . DESIGN AND SETTING R and omized trial conducted in an outpatient clinic in Santo Domingo , Dominican Republic , October 1999 through July 2000 . PARTICIPANTS Children aged 6 to 59 months who were receiving antibiotic prescriptions for respiratory tract illness ( n = 795 ) . INTERVENTIONS Children were r and omly assigned to receive 1 of 2 twice-daily regimens of amoxicillin : 90 mg/kg per day for 5 days ( n = 398 ) or 40 mg/kg per day for 10 days ( n = 397 ) . MAIN OUTCOME MEASURES Penicillin-nonsusceptible Streptococcus pneumoniae carriage , assessed in nasopharyngeal specimens collected at days 0 , 5 , 10 , and 28 ; baseline risk factors for nonsusceptible pneumococcal carriage ; and adherence to regimen , compared between the 2 groups . RESULTS At the day 28 visit , risk of penicillin-nonsusceptible pneumococcal carriage was significantly lower in the short-course , high-dose group ( 24 % ) compared with the st and ard-course group ( 32 % ) ; relative risk ( RR ) , 0.77 ; 95 % confidence interval ( CI ) , 0.60 - 0.97 ; P = .03 ; risk of trimethoprim-sulfamethoxazole nonsusceptibility was also lower in the short-course , high-dose group ( RR , 0.77 ; 95 % CI , 0.58 - 1.03 ; P = .08 ) . The protective effect of short-course , high-dose therapy was stronger in households with 3 or more children ( RR , 0.72 ; 95 % CI , 0.52 - 0.98 ) . Adherence to treatment was higher in the short-course , high-dose group ( 82 % vs 74 % ; P = .02 ) . CONCLUSION Short-course , high-dose outpatient antibiotic therapy appears promising as an intervention to minimize the impact of antibiotic use on the spread of drug-resistant pneumococci Non-r and omised studies of the effects of interventions are critical to many areas of healthcare evaluation , but their results may be biased . It is therefore important to underst and and appraise their strengths and weaknesses . We developed ROBINS-I ( “ Risk Of Bias In Non-r and omised Studies - of Interventions ” ) , a new tool for evaluating risk of bias in estimates of the comparative effectiveness ( harm or benefit ) of interventions from studies that did not use r and omisation to allocate units ( individuals or clusters of individuals ) to comparison groups . The tool will be particularly useful to those undertaking systematic review s that include non-r and omised studies We conducted a multicenter prospect i ve study to document changes in nasopharyngeal carriage of Streptococcus pneumoniae , Haemophilus influenzae , and Branhamella catarrhalis during antibiotic therapy . A cohort of 629 children with respiratory tract infections underwent nasopharyngeal sampling before and after antibiotic treatment . Susceptibility testing , serotyping , arbitrarily primed polymerase chain reaction , and pulsed-field gel electrophoresis were used to compare pretreatment and posttreatment strains of S. pneumoniae . A significant decrease in carriage of all 3 species ( especially S. pneumoniae and B. catarrhalis ) was recorded . The increase in the proportion of penicillin-resistant pneumococci ( PRP ; 66 % vs. 44 % ) was due to the decreased carriage of penicillin-susceptible pneumococci ( 71 of 629 vs. 176 of 629 ) . The risk of PRP carriage in a given child did not increase . None of the children was found to harbor genetically related strains with increased minimum inhibitory concentrations . Given the multiple resistance of PRP , beta-lactam antibiotic therapy also increased the incidence of macrolide-resistant strains , whereas macrolides selected both macrolide- and penicillin-resistant strains The effect of daily administration of trimethoprim ( TMP ) , trimethoprim -- sulfamethoxazole ( TMP -- SMX ) , or placebo on aerobically grown fecal gram-negative bacteria was monitored in 136 students from the United States during a two-week diarrhea-prevention study in Mexico . Unlike patients in other studies with these agents , who had urinary-tract infection or granulocytopenia , most persons in this study had no change in total fecal Enterobacteriaceae and had high-level TMP and SMX resistance in virtually all these strains . Escherichia coli was the predominant TMP-resistant organism isolated ; 96 per cent of 165 TMP-resistant Esch . coli isolates were resistant to at least four antimicrobial agents , and 25 per cent were resistant to seven . TMP resistance was transferable in 40 ot 100 strains tested . Despite the lack of TMP resistance in other studies of prophylaxis , our results clearly demonstrate the remarkable capacity for emergence and dissemination of resistance to this agent OBJECTIVE To compare the efficacy and the safety of a single intramuscular dose of ceftriaxone , 50 mg/kg , vs. a 10-day course of amoxicillin/clavulanate ( amox/clav ) therapy , 80 mg/kg/day of amoxicillin : 10 mg/kg/day of clavulanate in three divided doses , in children with acute otitis media ( AOM ) and to evaluate the changes in nasopharyngeal flora after treatment . METHODS In a prospect i ve , comparative , open r and omized , multicenter trial , children were scheduled to return for visits on Days 12 to 14 ( main end point ) and Days 28 to 42 after the beginning of treatment for AOM . A nasopharyngeal swab for bacterial culture was obtained before the treatment and at Days 12 to 14 . RESULTS Between February , 1995 , and May , 1996 , 513 children with a mean age of 14.2 + /- 6.7 months were enrolled . All the patients were evaluable for the safety and intent-to-treat analyses and 463 for the per protocol efficacy . At Days 12 to 14 clinical success was obtained in 186 of the 235 children ( 79 % ) given ceftriaxone and in 188 of the 228 children ( 82.5 % ) treated with amox/clav . Among the patients with clinical success on Days 12 to 14 , the success was maintained at Days 28 to 42 for 108 of 183 ( 59 % ) patients in the ceftriaxone group and 103 of 187 ( 55 % ) patients in the amox/clav group . Before the antibiotic treatment the percentages of children carrying Streptococcus pneumoniae ( 59.1 % ) , Haemophilus influenzae ( 39.4 % ) , Moraxella catarrhalis ( 55.7 % ) and the rate of penicillin-resistant S. pneumoniae ( 52.2 % ) were comparable between the 2 groups . At Days 12 to 14 the carriage of S. pneumoniae and M. catarrhalis was significantly different between the patients treated with ceftriaxone , 43.9 and 42.2 , respectively , and the patients treated with amox/clav , 17.4 and 11.1 % , respectively . Among the children carrying S. pneumoniae at Days 12 to 14 , the percentage of penicillin-resistant strains reached 63.4 % in the ceftriaxone treatment group and 83.0 % in the amox/clav treatment group , ( P = 0.02 ) . Adverse events ( mainly diarrhea ) related to the study medication were reported more frequently ( P < 0.0001 ) in the amox/clav treatment group . CONCLUSIONS In an area with a high rate of penicillin-resistant S. pneumoniae , a single dose of ceftriaxone is as efficient as a 10-day course of amox/clav in the treatment of AOM in young children . There was for the two regimens an increased rate of penicillin-resistant strains among the pneumococci carried , whereas the chance for a child to carry a penicillin resistant S. pneumoniae did not increase after treatment A multicentre , open-label , r and omized study was performed in 501 out- patients with acute otitis media , aged 6 - 36 months , to study the impact of treatment with either cefixime suspension 8 mg/kg/day bd or co-amoxiclav suspension 80 mg/kg/day tds for 10 days on nasopharyngeal carriage of Streptococcus pneumoniae and Haemophilus influenzae . Of 426 patients with nasopharyngeal cultures at entry to the trial , end of treatment and at follow-up visit ( 35 days after inclusion ) , significant changes in carriage of S. pneumoniae were observed . The proportion of penicillin-resistant S. pneumoniae was higher in the sample s taken at the end of treatment and follow-up than in those taken at inclusion , while the total number of children with this microorganism was lower . The difference at the end of treatment was greater with co-amoxiclav than with cefixime . For H. influenzae the resistance rate remained steady while the number of children with this microorganism decreased . At follow-up there was no significant difference between the two groups in terms of nasopharyngeal positive culture for S. pneumoniae or H. influenzae . Despite these differences , successful clinical responses were similar at the end of treatment and at follow-up Background : This study compared the effects of 4 outpatient antibiotic regimens on colonization by penicillin-susceptible and -nonsusceptible pneumococci to assess their relative potential to promote colonization with Streptococcus pneumoniae with reduced susceptibility to penicillin . Methods : Children presenting with acute otitis media were r and omized to receive amoxicillin , cefprozil , ceftriaxone or azithromycin . Nasopharyngeal specimens were collected on days 0 , 3–5 , 10–14 and 28–30 and assessed for the presence of S. pneumoniae . At each visit , the proportions of penicillin-susceptible and -nonsusceptible pneumococci were compared among treatment groups . Results : Among 1009 enrollees , the prevalence of colonization by S. pneumoniae at baseline was 23.5 % , of which 41.1 % were penicillin-nonsusceptible . Colonization by nonsusceptible pneumococci was unaltered during the observation period in all treatment groups , with no detectable differences among groups at each visit . By contrast , there was a substantial reduction in the prevalence of colonization by penicillin-susceptible organisms , most notably in subjects treated with amoxicillin . This result ed in a proportional shift toward resistant organism colonization in all groups , with this shift being significantly more pronounced among amoxicillin recipients than in the other groups at 10–12 days ( P < 0.02 for each comparison with amoxicillin ) . Conclusions : Treatment with amoxicillin for acute otitis media result ed in a larger shift toward nonsusceptible organism colonization among those children still colonized postexposure than did treatment with 3 comparison agents . This phenomenon raises theoretical concerns that at the population level , amoxicillin produces conditions that promote the dissemination of the nonsusceptible phenotype more readily than other outpatient antibiotics . Confirmation of these results requires further study BACKGROUND Nasopharyngeal ( NP ) carriage of antibiotic-resistant Streptococcus pneumoniae was shown to be associated with recent antibiotic treatment . To date no studies have evaluated early dynamics of pneumococcal NP carriage during antibiotic treatment . OBJECTIVES To observe changes in NP pneumococcal carriage within 3 to 4 days after initiation of antibiotic treatment in acute otitis media ( AOM ) . METHODS Patients ages 3 to 36 months with AOM treated with various antibiotics were prospect ively followed . Nasopharyngeal culture for S. pneumoniae was obtained before ( Day 1 ) and 72 to 96 h after initiation of treatment ( Days 4 to 5 ) . Antibiogram and serotyping were performed in all isolates as was also the MIC of penicillin . The disappearance and persistence of the initial isolates as well as the appearance of isolates with new serotype or with new antibiotic susceptibility patterns were investigated . RESULTS A total of 120 patients were studied : 106 received beta-lactam antibiotics and 14 received azithromycin . Among the initial 76 pneumococcal isolates 63 , 37 and 13 % were resistant to > or = 1 , > or = 2 and > or =3 antibiotic drugs . After 3 to 4 days of treatment with various beta-lactam drugs , 45 , 63 and 100 % of isolates with MIC values of < 0.1 microg/ml , 0.125 to 0.25 microg/ml and 0.38 to 1.0 microg/ml , respectively , persisted in the NP ( P = 0.038 ) . There was a difference between the various beta-lactam drugs in their effect on NP colonization : a drug with lower MIC values ( cefuroxime-axetil ) had a better eradication rate of penicillin-susceptible organisms than a less active one ( cefaclor ) , but neither significantly reduced carriage of penicillin nonsusceptible isolates . Azithromycin eliminated carriage of macrolide-susceptible organisms but increased the carriage of macrolide-resistant ones . In 19 of 120 ( 16 % ) patients a new S. pneumoniae isolate was recovered 3 to 4 days after initiation of treatment . Of those 16 ( 84 % ) were resistant to the drug the patient was receiving . CONCLUSION A rapid selection of nonsusceptible NP pneumococcal isolates during antibiotic treatment for AOM is common . This phenomenon may contribute to the spread of resistant pneumococci BACKGROUND / AIMS The World Health Organisation has recommended repeated mass treatment of children in trachoma endemic areas with oral azithromycin . While chlamydia , the causative agent of trachoma , remains universally sensitive to azithromycin , there is concern that large scale programmes may alter the bacterial flora and induce resistance in streptococcal species . In this study the effect of a single dose of azithromcyin on the prevalence , species distribution , and resistance of conjunctival bacterial flora was determined . METHODS Baseline and 14 day follow up bacterial cultures were taken from the conjunctivae of 121 children who reside in a trachoma endemic area of Nepal . 91 children were treated with azithromycin at baseline and 31 children received deferred treatment at the 14 day follow up . RESULTS Although the prevalence of bacterial pathogens decreased significantly with azithromycin treatment , a significant change in the distribution of specific bacterial pathogens could not be demonstrated . Streptococcal resistance to azithromycin was found significantly more frequently after treatment . No change in the prevalence , distribution , or resistance pattern was found in the untreated control group . CONCLUSION Repeated mass treatment of trachoma endemic areas with oral azithromycin will have an effect on bacterial flora . However , further work needs to be done to determine if this will have any clinical relevance ABSTRACT Objective : To determine the proportion of subjects with oropharyngeal streptococci resistant to either levofloxacin or azithromycin prior to and during antibacterial exposure , and to follow temporal changes in the proportion of resistant and susceptible isolates through 6 weeks post-exposure . This r and omized , open-label , single-center study is registered with Clinical Trials.gov ( identifier : NCT00821 782 ) . Research design and methods : A total of 143 healthy volunteers ( levofloxacin , n = 71 ; azithromycin , n = 72 ) without antibacterial exposure in the previous 90 days received either levofloxacin 750 mg once daily for 5 days or azithromycin 500 mg once daily on day 1 and 250 mg once daily on days 2 through 5 . Oropharyngeal cultures were obtained pre-exposure , at day 5 , and at 2 , 4 , and 6 weeks post-dosing . Bacterial strains were identified and the minimum inhibitory concentrations for levofloxacin and azithromycin were determined . Results : At study entry 117 streptococci were isolated from 72 subjects r and omized to azithromycin and 53 ( 45.3 % ) were azithromycin-resistant . None of the 121 streptococci isolated from 71 subjects r and omized to.levofloxacin were colonized by a levofloxacin-resistant microorganism prior to dosing . At the end of dosing , the number of subjects with resistant streptococci ( S. mitis , S. salivarius , S. sanguis , or alpha streptococcus species [ spp . ] ) increased in azithromycin-exposed subjects and resistant isolates remained through 6 weeks post-dosing . In contrast , a small number of levofloxacin-resistant streptococci were observed at the end of dosing but decreased by week 2 post-dosing and continued to decrease through the 6-week evaluation period ( p < 0.001 azithromycin vs. levofloxacin for S. mitis , S. salivarius , S. sanguis and alpha streptococcus spp . at week 6 ) . Limitations of this study included the fact that , since previous antibiotic use was self-reported , genetic typing was not done . The results of this study may not be completely generalizable , because subjects in this study received study drug under directly-observed conditions , thus ensuring compliance . Conclusions : Both antibacterial agents were well tolerated . Levofloxacin 750 mg administered for 5 days was associated with less microbial resistance than that observed with azithromycin in healthy subjects . Trial registration : Clinical Trials.gov identifier : NCT00821782 BACKGROUND Invasive group A streptococcal ( GAS ) infections are a cause of serious morbidity and high mortality . There is a need for a simple , effective antimicrobial regimen that could be used to prevent invasive GAS disease in high risk situations . To assess azithromycin as a chemoprophylactic agent , we evaluated its efficacy for eradication of oropharyngeal ( OP ) GAS and its impact on the nasopharyngeal ( NP ) colonization rate of macrolide-resistant Streptococcus pneumoniae . METHODS We obtained OP and NP swabs for GAS and pneumococcus culture , respectively , from 300 schoolmates of a child with an invasive GAS infection . GAS culture-positive students were treated with daily azithromycin ( 12 mg/kg/day ) for 5 days . We obtained follow-up OP and NP swabs at 9 ( Day 17 ) and 24 ( Day 32 ) days post-treatment from those students identified as GAS carriers on Day 0 and determined macrolide susceptibility of GAS and pneumococcal isolates . RESULTS Of the 300 students swabbed 152 ( 50 % ) carried GAS in their oropharynx . On Day 17 , efficacy of azithromycin for GAS eradication was 95 % ( 140 of 147 ) for all students . NP colonization rates for pneumococci decreased from 46 % ( 67 of 146 ) to 12 % ( 17 of 144 ; P < 0.001 ) by Day 17 and to 20 % ( 27 of 137 ; P < 0.001 ) by Day 32 . The prevalence of erythromycin-resistant pneumococcal isolates increased from 2 % ( 3 of 146 ) to 4 % ( 6 of 144 ) by Day 17 and to 8 % ( 11 of 137 ; P = 0.04 ) by Day 32 . CONCLUSIONS Azithromycin is an effective short course regimen for eradication of oropharyngeal GAS . However , azithromycin selected for macrolide-resistant strains of pneumococci . These findings highlight the importance of determining the appropriate circumstances for antimicrobial prophylaxis to prevent invasive GAS infections OBJECTIVE We compared colonization and resistance rates of non-pneumococcal alpha-hemolytic streptococci ( AHS ) and Streptococcus pneumoniae in children receiving antibiotic therapy for acute otitis media . STUDY DESIGN Between December 1997 and September 1998 , children 6 months to 6 years of age , diagnosed with acute otitis media were r and omly assigned to receive amoxicillin/clavulanate ( Augmentin ) 45 mg/kg/d in 2 divided doses for 10 days or azithromycin ( Zithromax ) , 10 mg/kg , once on the first day , followed by 5 mg/kg daily for 4 days . Nasopharyngeal swabs for culture were obtained before and at 2 weeks and 2 months after the start of therapy . Streptococci were identified by species , and antibiotic susceptibility was determined by the epsilometric test . RESULTS One hundred six children completed the 2-week follow-up and 2-month follow-up , respectively . The nasopharyngeal carriage rate of non-pneumococcal AHS increased from 14 % before treatment to 32 % at the 2-week follow-up ( P = .02 ) and was similar in both treatment groups . In contrast , the carriage of S pneumoniae decreased from 51 % before therapy to 27 % at the 2-week follow-up ( P = .002 ) . The carriage of penicillin-resistant AHS strains ( minimum inhibitory concentration > 1 microg/mL ) increased from 9 % before treatment to 26 % at 2 weeks and 36 % at 2 months . CONCLUSIONS Amoxicillin/clavulanate and azithromycin therapy result ed in increased isolation of nasopharyngeal non-pneumococcal AHS , many of which were multidrug-resistant , in contrast to a decrease in pneumococcal carriage . This suggests that the competitive balance between these 2 groups of organisms was disturbed as a result of differential antibiotic susceptibility . The importance of drug-resistant AHS as a reservoir for resistance genes for S pneumoniae warrants further investigation OBJECTIVE To explore the experiences and opinions of family physicians and patients regarding the delay of antibiotic prescriptions , to be dispensed if symptoms persist or worsen over time , in treating upper respiratory tract infections . STUDY DESIGN Qualitative study using semistructured interviews conducted in family practice in Auckl and , New Zeal and . POPULATION Thirteen physicians recruited from a study of family physicians ' reported antibiotic prescribing and 13 patients recruited from the intervention arm of a r and omized controlled trial on delayed antibiotic prescribing . OUTCOMES MEASURED Patients ' and physicians ' experiences of delayed antibiotic prescriptions for upper respiratory tract infections . RESULTS The primary themes identified were value judgments of antibiotics , decreased antibiotic use , patient-centered factors , effects on the physician-patient relationship , patient convenience , adverse effects of delaying prescription , and selectivity for use of antibiotics . Many themes were common to both patients and physicians . Physicians valued empowering patients ' decision making about their health care management more highly than did patients . Decreasing antibiotic use was not a key factor for most patients . Both groups acknowledged the value in saving patients time and money . Physicians viewed the strategy as giving patients reassurance and meeting their expectations for antibiotics . Negative implication s included perception of physician incompetence and physician loss of management control . Opinions were mixed regarding which patients , under which conditions , were suitable for delayed antibiotic prescriptions . CONCLUSIONS Although delayed antibiotic prescriptions are effective in decreasing antibiotic use for conditions not clinical ly warranting antibiotics , neither patients nor physicians universally endorsed this strategy . Research to establish formalized recommendations for patient suitability and instructions for use would be of value Prior use of antibiotics is associated with carriage of resistant bacteria . Colonization by Streptococcus pneumoniae , Haemophilus influenzae , nonpneumococcal alpha-hemolytic streptococci ( NPAHS ) , and Staphylococcus aureus was evaluated in children receiving antibiotic therapy for acute otitis media and in untreated , healthy control subjects . Children were r and omly assigned to receive either amoxicillin/clavulanate ( 90 mg/kg per day ) or azithromycin . Swabs were obtained before initiating therapy and again 2 weeks and 2 months after initiating therapy . We also obtained swabs from control subjects at the time of enrollment and 2 weeks and 2 months after enrollment . The decrease in the rate of carriage of S. pneumoniae and H. influenzae at 2 weeks was significant only in the amoxicillin/clavulanate group ( P<.001 and P=.005 , respectively ) . The rate of nasopharyngeal colonization with NPAHS among treated patients increased from 23 % to 39 % at 2 months ( P=.01 ) . This increase was similar for both treatment groups . These results suggest that the competitive balance between organisms is altered by antibiotic therapy OBJECTIVES To determine the effect of amoxicillin treatment on resistance selection in patients with community-acquired lower respiratory tract infections in a r and omized , placebo-controlled trial . METHODS Patients were prescribed amoxicillin 1 g , three times daily ( n = 52 ) or placebo ( n = 50 ) for 7 days . Oropharyngeal swabs obtained before , within 48 h post-treatment and at 28 - 35 days were assessed for proportions of amoxicillin-resistant ( ARS ; amoxicillin MIC ≥2 mg/L ) and -non-susceptible ( ANS ; MIC ≥0.5 mg/L ) streptococci . Alterations in amoxicillin MICs and in penicillin-binding-proteins were also investigated . ITT and PP analyses were conducted . RESULTS ARS and ANS proportions increased 11- and 2.5-fold , respectively , within 48 h post-amoxicillin treatment compared with placebo [ ARS mean increase ( MI ) 9.46 , 95 % CI 5.57 - 13.35 ; ANS MI 39.87 , 95 % CI 30.96 - 48.78 ; P < 0.0001 for both ] . However , these differences were no longer significant at days 28 - 35 ( ARS MI -3.06 , 95 % CI -7.34 to 1.21 ; ANS MI 4.91 , 95 % CI -4.79 to 14.62 ; P > 0.1588 ) . ARS/ANS were grouped by pbp mutations . Group 1 strains exhibited significantly lower amoxicillin resistance ( mean MIC 2.8 mg/L , 95 % CI 2.6 - 3.1 ) than group 2 ( mean MIC 9.3 mg/L , 95 % CI 8.1 - 10.5 ; P < 0.0001 ) . Group 2 strains predominated immediately post-treatment ( 61.07 % ) and although decreased by days 28 - 35 ( 30.71 % ) , proportions remained higher than baseline ( 18.70 % ; P = 0.0004 ) . CONCLUSIONS By utilizing oropharyngeal streptococci as model organisms this study provides the first prospect i ve , experimental evidence that resistance selection in patients receiving amoxicillin is modest and short-lived , probably due to ' fitness costs ' engendered by high-level resistance-conferring mutations . This evidence further supports European guidelines that recommend amoxicillin when an antibiotic is indicated for community-acquired lower respiratory tract infections BACKGROUND Resistance to antibiotics is a major public-health problem , and studies that link antibiotic use and resistance have shown an association but not a causal effect . We used the macrolides azithromycin and clarithromycin to investigate the direct effect of antibiotic exposure on resistance in the oral streptococcal flora of healthy volunteers . METHODS Volunteers were treated with azithromycin ( n=74 ) , clarithromycin ( 74 ) , or placebo ( 76 ) in a r and omised , double-blind trial . Pharyngeal swabs were obtained before and after administration of study treatment through 180 days . The proportion of streptococci that were macrolide resistant was assessed and the molecular basis of any change in resistance investigated . Analyses were done on an intent-to-treat basis . This study is registered with Clinical Trials.gov , number NCT00354952 . FINDINGS The number of dropouts ( n=20 ) was much the same in all groups until day 42 ; dropouts increased substantially at day 180 ( 105 ) . Both macrolides significantly increased the proportion of macrolide-resistant streptococci compared with the placebo at all points studied , peaking at day 8 in the clarithromycin group ( mean increase 50.0 % , 95 % CI 41.7 - 58.2 ; p<0.0001 ) and at day 4 in the azithromycin group ( 53.4 % , 43.4 - 63.5 ; p<0.0001 ) . The proportion of macrolide-resistant streptococci was higher after azithromycin treatment than after clarithromycin use , with the largest difference between the two groups at day 28 ( 17.4 % difference , 9.2 - 25.6 ; p<0.0001 ) . Use of clarithromycin , but not of azithromycin , selected for the erm(B ) gene , which confers high-level macrolide resistance . INTERPRETATION This study shows that , notwithst and ing the different outcomes of resistance selection , macrolide use is the single most important driver of the emergence of macrolide resistance in vivo . Physicians prescribing antibiotics should take into account the striking ecological side-effects of such antibiotics |
831 | 30,357,268 | Even more compelling was the report that when these studies were stratified according to risk of bias , data from the higher- quality studies showed that hypothermia was effective when delivered immediately or soon after injury . | The report of the Prophylactic Hypothermia Trial to Lessen Traumatic Brain Injury — R and omized Clinical Trial ( POLAR RCT ) by Cooper and colleagues1 in this issue of JAMA describes an international , multicenter , r and omized clinical trial of early therapeutic hypothermia after traumatic brain injury ( TBI ) to increase favorable functional outcomes .
The hypothesis tested in this trial was that hypothermia could reduce intracranial pressure , inflammatory mediator release , free radical generation , and numerous other secondary injurious processes such that functional recovery would be improved.2 The 2 clinical conditions for which hypothermia has been most extensively studied are cardiac arrest and TBI .
Cardiac arrest results in temporary global cerebral ischemic injury and TBI involves a heterogeneous condition that includes focal and diffuse components .
The potential mechanisms of action may be different for these 2 conditions .
The reason for the many clinical studies involving TBI3 is that laboratory data evaluating early prophylactic hypothermia for neuroprotection are compelling.2 These data , derived from multiple models and species , have shown benefit at a wide range of the target temperatures delivered after TBI .
A previous study that did evaluate early hypothermia after TBI9 was criticized for method ological limitations , including the early rewarming strategy and intracranial pressure management in the hypothermia group.10 However , many of these concerns appeared to have been addressed by the POLAR RCT protocol , and the international , multicenter design of the trial increases the external validity of the results .
The ideal target temperature for therapeutic hypothermia after TBI is not known . | BACKGROUND The inconsistent effect of hypothermia treatment on severe brain injury in previous trials might be because hypothermia was induced too late after injury . We aim ed to assess whether very early induction of hypothermia improves outcome in patients with severe brain injury . METHODS The National Acute Brain Injury Study : Hypothermia II ( NABIS : H II ) was a r and omised , multicentre clinical trial of patients with severe brain injury who were enrolled within 2·5 h of injury at six sites in the USA and Canada . Patients with non-penetrating brain injury who were 16 - 45 years old and were not responsive to instructions were r and omly assigned ( 1:1 ) by a r and om number generator to hypothermia or normothermia . Patients r and omly assigned to hypothermia were cooled to 35 ° C until their trauma assessment was completed . Patients who had none of a second set of exclusion criteria were either cooled to 33 ° C for 48 h and then gradually rewarmed or treated at normothermia , depending upon their initial treatment assignment . Investigators who assessed the outcome measures were masked to treatment allocation . The primary outcome was the Glasgow outcome scale score at 6 months . Analysis was by modified intention to treat . This trial is registered with Clinical Trials.gov , NCT00178711 . FINDINGS Enrolment occurred from December , 2005 , to June , 2009 , when the trial was terminated for futility . Follow-up was from June , 2006 , to December , 2009 . 232 patients were initially r and omised a mean of 1·6 h ( SD 0·5 ) after injury : 119 to hypothermia and 113 to normothermia . 97 patients ( 52 in the hypothermia group and 45 in the normothermia group ) did not meet any of the second set of exclusion criteria . The mean time to 35 ° C for the 52 patients in the hypothermia group was 2·6 h ( SD 1·2 ) and to 33 ° C was 4·4 h ( 1·5 ) . Outcome was poor ( severe disability , vegetative state , or death ) in 31 of 52 patients in the hypothermia group and 25 of 56 in the normothermia group ( relative risk [ RR ] 1·08 , 95 % CI 0·76 - 1·53 ; p=0·67 ) . 12 patients in the hypothermia group died compared with eight in the normothermia group ( RR 1·30 , 95 % CI 0·58 - 2·52 ; p=0·52 ) . INTERPRETATION This trial did not confirm the utility of hypothermia as a primary neuroprotective strategy in patients with severe traumatic brain injury Objectives : Therapeutic hypothermia has been of topical interest for many years and with the publication of two international , multicenter r and omized controlled trials , the evidence base now needs updating . The aim of this systematic review of r and omized controlled trials is to assess the efficacy of therapeutic hypothermia in adult traumatic brain injury focusing on mortality , poor outcomes , and new pneumonia . Data Sources : The following data bases were search ed from January 1 , 2011 , to January 26 , 2018 : Cochrane Central Register of Controlled Trial , MEDLINE , PubMed , and EMBASE . Study Selection : Only foreign articles published in the English language were included . Only articles that were r and omized controlled trials investigating adult traumatic brain injury sustained following an acute , closed head injury were included . Two authors independently assessed at each stage . Data Extraction : Quality was assessed using the Cochrane Collaboration ’s tool for assessing the risk of bias . All extracted data were combined using the Mantel-Haenszel estimator for pooled risk ratio with 95 % CIs . p value of less than 0.05 was considered statistically significant . All statistical analyses were conducted using RevMan 5 ( Cochrane Collaboration , Version 5.3 , Copenhagen : The Nordic Cochrane Centre , The Cochrane Collaboration , 2014 ) . Data Synthesis : Twenty-two studies with 2,346 patients are included . R and omized controlled trials with a low risk of bias show significantly more mortality in the therapeutic hypothermia group ( risk ratio , 1.37 ; 95 % CI , 1.04–1.79 ; p = 0.02 ) , whereas r and omized controlled trials with a high risk of bias show the opposite with a higher mortality in the control group ( risk ratio , 0.70 ; 95 % CI , 0.60–0.82 ; p < 0.00001 ) . Conclusions : Overall , this review is in-keeping with the conclusions published by the most recent r and omized controlled trials . High- quality studies show no significant difference in mortality , poor outcomes , or new pneumonia . In addition , this review shows a place for fever control in the management of traumatic brain injury BACKGROUND Induction of hypothermia in patients with brain injury was shown to improve outcomes in small clinical studies , but the results were not definitive . To study this issue , we conducted a multicenter trial comparing the effects of hypothermia with those of normothermia in patients with acute brain injury . METHODS The study subjects were 392 patients 16 to 65 years of age with coma after sustaining closed head injuries who were r and omly assigned to be treated with hypothermia ( body temperature , 33 degrees C ) , which was initiated within 6 hours after injury and maintained for 48 hours by means of surface cooling , or normothermia . All patients otherwise received st and ard treatment . The primary outcome measure was functional status six months after the injury . RESULTS The mean age of the patients and the type and severity of injury in the two treatment groups were similar . The mean ( + /-SD ) time from injury to r and omization was 4.3+/-1.1 hours in the hypothermia group and 4.1+/-1.2 hours in the normothermia group , and the mean time from injury to the achievement of the target temperature of 33 degrees C in the hypothermia group was 8.4+/-3.0 hours . The outcome was poor ( defined as severe disability , a vegetative state , or death ) in 57 percent of the patients in both groups . Mortality was 28 percent in the hypothermia group and 27 percent in the normothermia group ( P=0.79 ) . The patients in the hypothermia group had more hospital days with complications than the patients in the normothermia group . Fewer patients in the hypothermia group had high intracranial pressure than in the normothermia group . CONCLUSIONS Treatment with hypothermia , with the body temperature reaching 33 degrees C within eight hours after injury , is not effective in improving outcomes in patients with severe brain injury Background Clinical trials in traumatic brain injury ( TBI ) are challenging . Previous trials of complex interventions were conducted in high-income countries , reported long lead times for site setup and low screened-to-recruitment rates . In this report we evaluate the internal pilot phase of an international , multicentre TBI trial of a complex intervention to assess : design and implementation of an online case report form ; feasibility of recruitment ( sites and patients ) ; feasibility and effectiveness of delivery of the protocol . Methods All aspects of the pilot phase of the trial were conducted as for the main trial . The pilot phase had oversight by independent Steering and Data Monitoring committees . Results Forty sites across 12 countries gained ethical approval . Thirty seven of 40 sites were initiated for recruitment . Of these , 29 had screened patients and 21 r and omized at least one patient . Lead times to ethics approval ( 6.8 weeks ) , hospital approval ( 18 weeks ) , interest to set up ( 61 weeks ) , set up to screening ( 11 weeks ) , and set up to r and omization ( 31.6 weeks ) are comparable with other international trials . Sixteen per cent of screened patients were eligible . We found 88 % compliance rate with trial protocol . Conclusion The pilot data demonstrated good feasibility for this large international multicentre r and omized controlled trial of hypothermia to control intracranial pressure . The sample size was reduced to 600 patients because of homogeneity of the patient group and we showed an optimized cooling intervention could be delivered . Trial registration Current Controlled Trials : IS RCT N34555414 BACKGROUND In patients with traumatic brain injury , hypothermia can reduce intracranial hypertension . The benefit of hypothermia on functional outcome is unclear . METHODS We r and omly assigned adults with an intracranial pressure of more than 20 mm Hg despite stage 1 treatments ( including mechanical ventilation and sedation management ) to st and ard care ( control group ) or hypothermia ( 32 to 35 ° C ) plus st and ard care . In the control group , stage 2 treatments ( e.g. , osmotherapy ) were added as needed to control intracranial pressure . In the hypothermia group , stage 2 treatments were added only if hypothermia failed to control intracranial pressure . In both groups , stage 3 treatments ( barbiturates and decompressive craniectomy ) were used if all stage 2 treatments failed to control intracranial pressure . The primary outcome was the score on the Extended Glasgow Outcome Scale ( GOS-E ; range , 1 to 8 , with lower scores indicating a worse functional outcome ) at 6 months . The treatment effect was estimated with ordinal logistic regression adjusted for prespecified prognostic factors and expressed as a common odds ratio ( with an odds ratio < 1.0 favoring hypothermia ) . RESULTS We enrolled 387 patients at 47 centers in 18 countries from November 2009 through October 2014 , at which time recruitment was suspended owing to safety concerns . Stage 3 treatments were required to control intracranial pressure in 54 % of the patients in the control group and in 44 % of the patients in the hypothermia group . The adjusted common odds ratio for the GOS-E score was 1.53 ( 95 % confidence interval , 1.02 to 2.30 ; P=0.04 ) , indicating a worse outcome in the hypothermia group than in the control group . A favorable outcome ( GOS-E score of 5 to 8 , indicating moderate disability or good recovery ) occurred in 26 % of the patients in the hypothermia group and in 37 % of the patients in the control group ( P=0.03 ) . CONCLUSIONS In patients with an intracranial pressure of more than 20 mm Hg after traumatic brain injury , therapeutic hypothermia plus st and ard care to reduce intracranial pressure did not result in outcomes better than those with st and ard care alone . ( Funded by the National Institute for Health Research Health Technology Assessment program ; Current Controlled Trials number , IS RCT N34555414 . ) Traumatic brain injury ( TBI ) is a significant cause of disability and death and a huge economic burden throughout the world . Much of the morbidity associated with TBI is attributed to secondary brain injuries result ing in hypoxia and ischemia after the initial trauma . Intracranial hypertension and decreased partial brain oxygen tension ( PbtO2 ) are targeted as potentially avoidable causes of morbidity . Therapeutic hypothermia ( TH ) may be an effective intervention to reduce intracranial pressure ( ICP ) , but could also affect cerebral blood flow ( CBF ) . This is a retrospective analysis of prospect ively collected data from 17 patients admitted to the Western General Hospital , Edinburgh . Patients with an ICP > 20 mmHg refractory to initial therapy were r and omized to st and ard care or st and ard care and TH ( intervention group ) titrated between 32 ° C and 35 ° C to reduce ICP . ICP and PbtO2 were measured using the Licox system and core temperature was recorded through rectal thermometer . Data were analyzed at the hour before cooling , the first hour at target temperature , 2 consecutive hours at target temperature , and after 6 hours of hypothermia . There was a mean decrease in ICP of 4.3±1.6 mmHg ( p<0.04 ) from 15.7 to 11.4 mmHg , from precooling to the first epoch of hypothermia in the intervention group ( n=9 ) that was not seen in the control group ( n=8 ) . A decrease in ICP was maintained throughout all time periods . There was a mean decrease in PbtO2 of 7.8±3.1 mmHg ( p<0.05 ) from 30.2 to 22.4 mmHg , from precooling to stable hypothermia , which was not seen in the control group . This research supports others in demonstrating a decrease in ICP with temperature , which could facilitate a reduction in the use of hyperosmolar agents or other stage II interventions . The decrease in PbtO2 is not below the suggested treatment threshold of 20 mmHg , but might indicate a decrease in CBF Although mild therapeutic hypothermia is an effective neuroprotective strategy for cardiac arrest/resuscitated patients , and asphyxic newborns , recent r and omized controlled trials ( RCTs ) have equally shown good neurological outcome between targeted temperature management at 33 ° C versus 36 ° C , and have not shown consistent benefits in patients with traumatic brain injury ( TBI ) . We aim ed to determine the effect of therapeutic hypothermia , while avoiding some limitations of earlier studies , which included patient selection based on Glasgow coma scale ( GCS ) , delayed initiation of cooling , short duration of cooling , inter-center variation in patient care , and relatively rapid rewarming . We conducted a multicenter RCT in patients with severe TBI ( GCS 4 - 8 ) . Patients were r and omly assigned ( 2:1 allocation ratio ) to either therapeutic hypothermia ( 32 - 34 ° C , n = 98 ) or fever control ( 35.5 - 37 ° C , n = 50 ) . Patients with therapeutic hypothermia were cooled as soon as possible for ≥ 72 h and rewarmed at a rate of < 1 ° C/day . All patients received tight hemodynamic monitoring under intensive neurological care . The Glasgow Outcome Scale was assessed at 6 months by physicians who were blinded to the treatment allocation . The overall rates of poor neurological outcomes were 53 % and 48 % in the therapeutic hypothermia and fever control groups , respectively . There were no significant differences in the likelihood of poor neurological outcome ( relative risk [ RR ] 1.24 , 95 % confidence interval [ CI ] 0.62 - 2.48 , p = 0.597 ) or mortality ( RR 1.82 , 95 % CI 0.82 - 4.03 , p = 0.180 ) between the two groups . We concluded that tight hemodynamic management and slow rewarming , together with prolonged therapeutic hypothermia ( 32 - 34 ° C ) for severe TBI , did not improve the neurological outcomes or risk of mortality compared with strict temperature control ( 35.5 - 37 ° C ) BACKGROUND Traumatic brain injury ( TBI ) is a major cause of disability and death in young adults worldwide . It results in around 1 million hospital admissions annually in the European Union ( EU ) , causes a majority of the 50,000 deaths from road traffic accidents and leaves a further ≈10,000 people severely disabled . OBJECTIVE The Eurotherm3235 Trial was a pragmatic trial examining the effectiveness of hypothermia ( 32 - 35 ° C ) to reduce raised intracranial pressure ( ICP ) following severe TBI and reduce morbidity and mortality 6 months after TBI . DESIGN An international , multicentre , r and omised controlled trial . SETTING Specialist neurological critical care units . PARTICIPANTS We included adult participants following TBI . Eligible patients had ICP monitoring in place with an ICP of > 20 mmHg despite first-line treatments . Participants were r and omised to receive st and ard care with the addition of hypothermia ( 32 - 35 ° C ) or st and ard care alone . Online r and omisation and the use of an electronic case report form ( CRF ) ensured concealment of r and om treatment allocation . It was not possible to blind local investigators to allocation as it was obvious which participants were receiving hypothermia . We collected information on how well the participant had recovered 6 months after injury . This information was provided either by the participant themself ( if they were able ) and /or a person close to them by completing the Glasgow Outcome Scale - Extended ( GOSE ) question naire . Telephone follow-up was carried out by a blinded independent clinician . INTERVENTIONS The primary intervention to reduce ICP in the hypothermia group after r and omisation was induction of hypothermia . Core temperature was initially reduced to 35 ° C and decreased incrementally to a lower limit of 32 ° C if necessary to maintain ICP at < 20 mmHg . Rewarming began after 48 hours if ICP remained controlled . Participants in the st and ard-care group received usual care at that centre , but without hypothermia . MAIN OUTCOME MEASURES The primary outcome measure was the GOSE [ range 1 ( dead ) to 8 ( upper good recovery ) ] at 6 months after the injury as assessed by an independent collaborator , blind to the intervention . A priori subgroup analysis tested the relationship between minimisation factors including being aged < 45 years , having a post-resuscitation Glasgow Coma Scale ( GCS ) motor score of < 2 on admission , having a time from injury of < 12 hours and patient outcome . RESULTS We enrolled 387 patients from 47 centres in 18 countries . The trial was closed to recruitment following concerns raised by the Data and Safety Monitoring Committee in October 2014 . On an intention-to-treat basis , 195 participants were r and omised to hypothermia treatment and 192 to st and ard care . Regarding participant outcome , there was a higher mortality rate and poorer functional recovery at 6 months in the hypothermia group . The adjusted common odds ratio ( OR ) for the primary statistical analysis of the GOSE was 1.54 [ 95 % confidence interval ( CI ) 1.03 to 2.31 ] ; when the GOSE was dichotomised the OR was 1.74 ( 95 % CI 1.09 to 2.77 ) . Both results favoured st and ard care alone . In this pragmatic study , we did not collect data on adverse events . Data on serious adverse events ( SAEs ) were collected but were subject to reporting bias , with most SAEs being reported in the hypothermia group . CONCLUSIONS In participants following TBI and with an ICP of > 20 mmHg , titrated therapeutic hypothermia successfully reduced ICP but led to a higher mortality rate and worse functional outcome . LIMITATIONS Inability to blind treatment allocation as it was obvious which participants were r and omised to the hypothermia group ; there was biased recording of SAEs in the hypothermia group . We now believe that more adequately powered clinical trials of common therapies used to reduce ICP , such as hypertonic therapy , barbiturates and hyperventilation , are required to assess their potential benefits and risks to patients . TRIAL REGISTRATION Current Controlled Trials IS RCT N34555414 . FUNDING This project was funded by the National Institute for Health Research ( NIHR ) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol . 22 , No. 45 . See the NIHR Journals Library website for further project information . The European Society of Intensive Care Medicine supported the pilot phase of this trial Importance After severe traumatic brain injury , induction of prophylactic hypothermia has been suggested to be neuroprotective and improve long-term neurologic outcomes . Objective To determine the effectiveness of early prophylactic hypothermia compared with normothermic management of patients after severe traumatic brain injury . Design , Setting , and Participants The Prophylactic Hypothermia Trial to Lessen Traumatic Brain Injury – R and omized Clinical Trial ( POLAR- RCT ) was a multicenter r and omized trial in 6 countries that recruited 511 patients both out-of-hospital and in emergency departments after severe traumatic brain injury . The first patient was enrolled on December 5 , 2010 , and the last on November 10 , 2017 . The final date of follow-up was May 15 , 2018 . Interventions There were 266 patients r and omized to the prophylactic hypothermia group and 245 to normothermic management . Prophylactic hypothermia targeted the early induction of hypothermia ( 33 ° C-35 ° C ) for at least 72 hours and up to 7 days if intracranial pressures were elevated , followed by gradual rewarming . Normothermia targeted 37 ° C , using surface-cooling wraps when required . Temperature was managed in both groups for 7 days . All other care was at the discretion of the treating physician . Main Outcomes and Measures The primary outcome was favorable neurologic outcomes or independent living ( Glasgow Outcome Scale – Extended score , 5 - 8 [ scale range , 1 - 8 ] ) obtained by blinded assessors 6 months after injury . Results Among 511 patients who were r and omized , 500 provided ongoing consent ( mean age , 34.5 years [ SD , 13.4 ] ; 402 men [ 80.2 % ] ) and 466 completed the primary outcome evaluation . Hypothermia was initiated rapidly after injury ( median , 1.8 hours [ IQR , 1.0 - 2.7 hours ] ) and rewarming occurred slowly ( median , 22.5 hours [ IQR , 16 - 27 hours ] ) . Favorable outcomes ( Glasgow Outcome Scale – Extended score , 5 - 8 ) at 6 months occurred in 117 patients ( 48.8 % ) in the hypothermia group and 111 ( 49.1 % ) in the normothermia group ( risk difference , 0.4 % [ 95 % CI , –9.4 % to 8.7 % ] ; relative risk with hypothermia , 0.99 [ 95 % CI , 0.82 - 1.19 ] ; P = .94 ) . In the hypothermia and normothermia groups , the rates of pneumonia were 55.0 % vs 51.3 % , respectively , and rates of increased intracranial bleeding were 18.1 % vs 15.4 % , respectively . Conclusions and Relevance Among patients with severe traumatic brain injury , early prophylactic hypothermia compared with normothermia did not improve neurologic outcomes at 6 months . These findings do not support the use of early prophylactic hypothermia for patients with severe traumatic brain injury . Trial Registration clinical trials.gov Identifier : NCT00987688 ; Anzctr.org.au Identifier : |
832 | 30,979,065 | The review highlights the potential of behavioural interventions to improve young adults ’ fruit and vegetable intake but was less convincing for other dietary outcomes . | Poor eating habits are common during young adulthood and influence chronic disease morbidity .
This systematic review evaluates the effectiveness of interventions aim ing to improve dietary intake among young adults and , identifies which behaviour change techniques ( BCTs ) are most effective . | BACKGROUND Healthy eating , such as the regular inclusion of fruits and vegetables in one 's diet , is essential for maintaining optimal weight , maximizing brain and immune system functioning , and reducing the risk for disease . Despite its importance , few students meet recommended guidelines for healthy dietary behavior . The current study was design ed to test the efficacy of two ehealth intervention approaches for increasing healthy eating behaviors among university students . METHODS Student volunteers from an introductory psychology class at a northeastern US university participated for class credit ( n=154 ) . Students were r and omized to either an assessment only ( AO ) , web-based nutrition intervention only ( WBO ) , or web-intervention with daily text-messaging condition ( WB+M ) . Participants completed measures of vegetable and fruit consumption and frequency of meals with design ated healthy food selection s at baseline and one-month follow-up . RESULTS Only the WB+M intervention significantly increased the likelihood of attaining vegetable consumption st and ards and increased the frequency of design ated healthy food choice options guidelines at follow-up compared to the AO condition . CONCLUSIONS Findings suggest that delivering a brief web-based intervention with daily text messages about personal nutrition and fitness goals may support healthier eating patterns among students The transition to college has been identified as a critical period for increases in overweight status . Overweight college students are at-risk of becoming obese adults , and , thus prevention efforts targeting college age individuals are key to reducing adult obesity rates . The current study evaluated an Internet intervention with first year college students ( N=170 ) r and omly assigned to one of four treatment conditions : 1 ) no treatment , 2 ) 6-week online intervention 3 ) 6-week weight and caloric feedback only ( via email ) , and 4 ) 6-week combined feedback and online intervention . The combined intervention group had lower BMI s at post-testing than the other three groups . This study demonstrated the effectiveness and feasibility of an online intervention to prevent weight gain among college students Background : Adequate calcium consumption during early adulthood can help prevent osteoporosis in women . Purpose : The effects of gain-framed , targeted messaging on calcium intake were examined over 12 months . Methods : Young women ( 18–19 years ) not consuming sufficient calcium were r and omly assigned to receive st and ard care material s ( control ) or gain-framed , targeted material s ( experimental ) . Health belief model ( HBM ) constructs , calcium intake and markers of bone formation , resorption and bone mineral density were assessed at various time points throughout the year . Results : Calcium intake increased significantly more in the experimental versus the control condition ( p < 0.01 ) . Self-efficacy was the only HBM construct to improve significantly more in the experimental condition versus control ( p = 0.05 ) . The HBM did not mediate changes in calcium intake . Measures of bone health did not differ between conditions by the end of this nonpharmacological intervention ( p 's > 0.05 ) . Conclusions : It is possible to increase young women 's calcium consumption through gain-framed , targeted messages Introduction Graphic warnings ( GWs ) on cigarette packs are widely used internationally and perhaps will be in the US but their impact is not well understood . This study tested support for competing hypotheses in different subgroups of young adults defined by their history of cigarette smoking and individual difference variables ( e.g. , psychological reactance ) . One hypothesis predicted adaptive responding ( GWs would lower smoking-related intentions ) and another predicted defensive responding ( GWs would raise smoking-related intentions ) . Methods Participants were an online sample of 1,169 Americans ages 18–24 , who were r and omly assigned either to view nine GWs design ed by the FDA or to a no-label control . Both the intention to smoke in the future and the intention to quit smoking ( among smokers ) were assessed before and after message exposure . Results GWs lowered intention to smoke in the future among those with a moderate lifetime smoking history ( between 1 and 100 cigarettes ) , and they increased intention to quit smoking among those with a heavy lifetime smoking history ( more than 100 cigarettes ) . Both effects were limited to individuals who had smoked in some but not all of the prior 30 days ( i.e. , occasional smokers ) . No evidence of defensive “ boomerang effects ” on intention was observed in any subgroup . Conclusion Graphic warnings can reduce interest in smoking among occasional smokers , a finding that supports the adaptive-change hypothesis . GWs that target occasional smokers might be more effective at reducing cigarette smoking in young adults OBJECTIVES To develop and test the effectiveness of a mobile-phone based ecological momentary intervention ( EMI ) to increase fruit and vegetable ( FV ) consumption in low-consuming young adults . METHODS A two-week r and omised controlled trial of low-FV consuming young adults ages 18 - 25 years ( n = 171 ) compared three conditions : ecological momentary intervention ( EMI ) , fruit and vegetable intervention ( FVI ) , and a diet-as-usual control ( ANZCTRN12615000183583 ) . Participants in the EMI condition were sent two targeted text messages a day for 13 days and were asked to increase daily FV consumption to at least five servings . These messages were design ed , using the Health Action Process Approach , to address salient beliefs identified as effective in a preliminary focus group investigation . Participants in the FVI condition were provided two servings of FV a day ( carrots , kiwifruit or oranges , and apples ) to eat in addition to their current diet . Control participants ate their normal diet . Participants reported their daily servings of FV each evening during the study using a smartphone-delivered survey . Blood sample s testing plasma vitamin C and total carotenoids were taken pre- and post-intervention as an objective biomarker of FV intake . RESULTS Participants in the EMI and FVI conditions reported higher daily servings of FV - approximately + 1 serving per day more compared to control ( EMI = 3.7 servings/day ; FVI = 3.7 servings/day ; Control = 2.8 servings/day ) and approximately + 1.2 servings compared to baseline . Increases in objective biomarkers for the experimental conditions supported the validity of self-reported FV consumption . CONCLUSIONS Our results provide initial proof of concept that EMI strategies ( with minor financial assistance ) are as effective as giving FV in increasing FV consumption in educated , low-consuming young adults Background The college experience is often the first time when young adults live independently and make their own lifestyle choices . These choices affect dietary behaviors , exercise habits , techniques to deal with stress , and decisions on sleep time , all of which direct the trajectory of future health . There is a need for effective strategies that will encourage healthy lifestyle choices in young adults attending college . Objective This preliminary r and omized controlled trial tested the effect of coaching and text messages ( short message service , SMS ) on self-selected health behaviors in the domains of diet , exercise , stress , and sleep . A second analysis measured the ripple effect of the intervention on health behaviors not specifically selected as a goal by participants . Methods Full-time students aged 18 - 30 years were recruited by word of mouth and campuswide advertisements ( flyers , posters , mailings , university website ) at a small university in western Pennsylvania from January to May 2015 . Exclusions included pregnancy , eating disorders , chronic medical diagnoses , and prescription medications other than birth control . Of 60 participants , 30 were r and omized to receive a single face-to-face meeting with a health coach to review results of behavioral question naires and to set a health behavior goal for the 8-week study period . The face-to-face meeting was followed by SMS text messages design ed to encourage achievement of the behavioral goal . A total of 30 control subjects underwent the same health and behavioral assessment s at intake and program end but did not receive coaching or SMS text messages . Results The texting app showed that 87.31 % ( 2187/2505 ) of messages were viewed by intervention participants . Furthermore , 28 of the 30 intervention participants and all 30 control participants provided outcome data . Among intervention participants , 22 of 30 ( 73 % ) showed improvement in health behavior goal attainment , with the whole group ( n=30 ) showing a mean improvement of 88 % ( 95 % CI 39 - 136 ) . Mean improvement in any behavioral domains was not seen in the control group . Intervention participants also increased their exercise significantly compared with controls , regardless of their self-selected goal category . The increased exercise was paralleled by significantly lower fasting glucose levels . Conclusions The health coaching session plus tailored SMS text messages improved self-selected health behaviors with a modest ripple effect to include unselected health behaviors . Trial Registration Clinical trials.gov NCT02476604 ; https:// clinical trials.gov/ct2/show/NCT02476604 ( Archived by WebCite at http://www.webcitation.org/6qAAryS5 t This study tests whether the effectiveness of implementation intention-based interventions to increase fruit and vegetable intake in a young adult population can be enhanced using additional pre-intervention instructions and alternative formats ; namely , an ‘ if-then ’ implementation intention versus a more general , ‘ global ’ plan that does not explicitly link a situational cue with a goal -directed response . Participants ( N = 557 ) completed pre-test measures of planning , motivation and behaviour with respect to increasing their fruit and vegetable intake before being r and omised to a 3 ( intervention format : control vs. ‘ if-then ’ vs. ‘ global ’ implementation intentions ) × 2 ( pre-intervention instruction vs. no pre-intervention instruction ) between- participants design . Results revealed a significant intervention format by time interaction , such that intake significantly increased by 0.50 portions in the if-then format condition compared with 0.31 in the global format and 0.01 in the control condition . These results suggest that ‘ if-then ’ manipulations are superior in promoting behaviour change in an applied setting . The use of pre-intervention instructions had no additional effect on behaviour , providing evidence for the efficacy of implementation intentions even when experimenter dem and is reduced . Evidence is also presented to suggest that reported increases in intake are not related to dem and characteristics Background Using various models of behavior change , a number of studies in the area of nutrition education have confirmed that nutrition habits and behaviors can be improved . Objectives This study sought to determine the effects of education on patterns of dietary consumption among medical students at the military university of Tehran , with a view to correcting those patterns . Methods In this quasi-experimental study , 242 medical students from the Military University of Tehran were chosen by convenience sampling and then divided into control ( n = 107 ) and intervention groups ( n = 135 ) by block r and omization . The self-administered question naire involving six categories of item ( knowledge , perceived benefits , perceived barriers , perceived threats , self-efficacy and behavior ) has been vali date d ( Cronbach alpha > 0.7 for each ) . Results Following the educational intervention , the mean score of knowledge , health belief model ( HBM ) structure , and behavior of students in relation to healthy patterns of food intake increased significantly ( P < 0.05 ) . The mean pre-intervention knowledge score was 6.76 ( 1.452 ) , referring to threats to HBM constructs including perceived threat 2.93 ( 1.147 ) , perceived benefits 7.28 ( 1.07 ) , perceived barriers 5.44 ( 1.831 ) , self- efficacy 4.28 ( 1.479 ) , and behavior 8.84 ( 2.527 ) . The post-intervention scores all improved as follows : knowledge 8.3 ( 1.503 ) , perceived threats 3.29 ( 1.196 ) , perceived benefits 7.71 ( 0.762 ) , perceived barriers 5.9 ( 1.719 ) , self- efficacy 4.6 ( 1.472 ) , and behavior 9.45 ( 2.324 ) . This difference in mean scores for knowledge , health belief structures and employee behavior before and after educational intervention was significant ( P ≤ 0.05 ) . Conclusions The significant improvement in the experimental group ’s mean knowledge , HBM structures , and behavior scores indicates the positive effect of the intervention This study evaluated the efficacy of a theory of planned behaviour ( TPB ) based intervention to increase fruit and vegetable consumption . The extent to which fruit and vegetable consumption and change in intake could be explained by the TPB was also examined . Participants were r and omly assigned to two levels of intervention frequency matched for intervention content ( low frequency n=92 , high frequency n=102 ) . Participants received TPB-based email messages design ed to increase fruit and vegetable consumption , messages targeted attitude , subjective norm and perceived behavioural control ( PBC ) . Baseline and post-intervention measures of TPB variables and behaviour were collected . Across the entire study cohort , fruit and vegetable consumption increased by 0.83 servings/day between baseline and follow-up . Intention , attitude , subjective norm and PBC also increased ( p<.05 ) . The TPB successfully modelled fruit and vegetable consumption at both time points but not behaviour change . The increase of fruit and vegetable consumption is a promising preliminary finding for those primarily interested in increasing fruit and vegetable consumption . However , those interested in theory development may have concerns about the use of this model to explain behaviour change in this context . More high quality experimental tests of the theory are needed to confirm this result Aim : The aim of the study was to develop and implement an obesity and weight gain prevention program targeted to a high-risk group . Method : Women , 18–28 years old , with at least one severely obese parent , were r and omized to the intervention or control group of the ‘ Health Hunters ’ program . During 1 year of follow-up , the intervention group received an individualized behavioral program focusing on food choice , physical activity and other lifestyle factors . Anthropometric measures , DXA-based body composition and fitness levels were measured at baseline and after 1 year . Self-reported changes in obesity-related behaviors were also assessed . Results : Baseline examinations were conducted in 40 women , of whom 30 completed follow-up examinations 1 year later . Pregnancy was the most common reason for failure to complete the study . Compared to the control group ( which gained weight ) , the intervention group displayed significant improvements in body weight , body mass index , waist circumference , waist-to-hip ratio and self-reported physical activity . Changes in body composition , although not significant , suggested that the intervention tended to be associated with improved body composition . Further analysis of changes in diet and fitness in relation to concurrent weight changes indicated that the strongest ‘ protective ’ associations were for energy percent protein , fiber density and fitness . Conclusion : Pilot data from the Health Hunters obesity prevention program indicates that it is effective in high-risk young women with familial predisposition for obesity The fight against excess weight and obesity is a health priority . The aim of this study was to analyze the anthropometric changes induced by two weight control programs based on approximating the diet to the theoretical ideal ( increasing the consumption of foods with the largest differences between the recommended and observed intakes : cereals and vegetables -- for which a minimum of 6 and 3 servings/day are recommended , respectively ) . The study subjects were 57 Spanish women with a body-mass index ( BMI ) of 24 - 35 kg/m2 , all of whom were r and omly assigned to one of two slightly hypocaloric diets for a six-week period : diet V , in which the consumption of greens and vegetables was increased , or diet C , in which the consumption of cereals was increased . Dietetic and anthropometric data were collected at the start of the study and again at two and six weeks . The dietary intervention approximated the subjects ' energy provision from proteins , fats , and carbohydrates to those recommended . The Healthy Eating Index ( HEI ) improved with both diets . Reductions in body weight , BMI , and the amount of body fat ( kg ) were also achieved with both diets . Weight loss was 1.56 + /- 0.93 kg and 1.02 + /- 0.55 kg at two weeks with diet C and V respectively , and 2.8 + /- 1.4 kg and 2.0 + /- 1.3 kg at six weeks ( p < 0.05 ) . Approximating the diet to the theoretical ideal by increasing the consumption of vegetables or cereals may therefore be of use in weight control . In terms of weight loss and the improvement of the diet quality ( energy profile and HEI ) , diet C was significantly more effective than diet Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more OBJECTIVE This paper describes the design and findings of a pilot Mothers In Motion ( P-MIM ) program . DESIGN A r and omized controlled trial that collected data via telephone interviews and finger stick at 3 time points : baseline and 2 and 8 months post-intervention . SETTING Three Special Supplemental Nutrition Program for Women , Infants , and Children ( WIC ) sites in southern Michigan . PARTICIPANTS One hundred and twenty nine overweight and obese African-American and white mothers , 18 - 34 years old . INTERVENTION The 10-week , theory-based , culturally sensitive intervention messages were delivered via a series of 5 chapters on a DVD and complemented by 5 peer support group teleconferences . MAIN OUTCOME MEASURES Dietary fat , fruit , and vegetable intake ; physical activity ; stress ; feelings ; body weight ; and blood glucose . ANALYSIS General linear mixed model was applied to assess treatment effects across 2 and 8 months post-intervention . RESULTS No significant effect sizes were found in primary and secondary outcome variables at 2 and 8 months post-intervention . However , changes in body weight and blood glucose showed apparent trends consistent with the study 's hypotheses . CONCLUSIONS AND IMPLICATION S The P-MIM showed promise for preventing weight gain in low-income overweight and obese women . However , a larger experimental trial is warranted to determine the effectiveness of this intervention Background The unprecedented rise in obesity among young adults , who have limited interaction with health services , has not been successfully abated . Objective The objective of this study was to assess the maintenance outcomes of a 12-week mHealth intervention on prevention of weight gain in young adults and lifestyle behaviors at 9 months from baseline . Methods A two-arm , parallel , r and omized controlled trial ( RCT ) with subjects allocated to intervention or control 1:1 was conducted in a community setting in Greater Sydney , Australia . From November 2012 to July 2014 , 18- to 35-year-old overweight individuals with a body mass index ( BMI ) of 25 - 31.99 kg/m2 and those with a BMI ≥ 23 kg/m2 and a self-reported weight gain of ≥ 2 kg in the past 12 months were recruited . A 12-week mHealth program “ TXT2BFiT ” was administered to the intervention arm . This included 5 coaching calls , 96 text messages , 12 emails , apps , and downloadable re sources from the study website . Lifestyle behaviors addressed were intake of fruits , vegetables , sugar-sweetened beverages ( SSBs ) , take-out meals , and physical activity . The control group received 1 phone call to introduce them to study procedures and 4 text messages over 12 weeks . After 12 weeks , the intervention arm received 2 further coaching calls , 6 text messages , and 6 emails with continued access to the study website during 6-month follow-up . Control arm received no further contact . The primary outcome was weight change ( kg ) with weight measured at baseline and at 12 weeks and self-report at baseline , 12 weeks , and 9 months . Secondary outcomes were change in physical activity ( metabolic equivalent of task , MET-mins ) and categories of intake for fruits , vegetables , SSBs , and take-out meals . These were assessed via Web-based surveys . Results Two hundred and fifty young adults enrolled in the RCT . Intervention participants weighed less at 12 weeks compared with controls ( model β=−3.7 , 95 % CI −6.1 to −1.3 ) and after 9 months ( model β=− 4.3 , 95 % CI − 6.9 to − 1.8 ) . No differences in physical activity were found but all diet behaviors showed that the intervention group , compared with controls at 9 months , had greater odds of meeting recommendations for fruits ( OR 3.83 , 95 % CI 2.10 - 6.99 ) ; for vegetables ( OR 2.42 , 95 % CI 1.32 - 4.44 ) ; for SSB ( OR 3.11 , 95 % CI 1.47 - 6.59 ) ; and for take-out meals ( OR 1.88 , 95 % CI 1.07 - 3.30 ) . Conclusions Delivery of an mHealth intervention for prevention of weight gain result ed in modest weight loss at 12 weeks with further loss at 9 months in 18- to 35-year-olds . Although there was no evidence of change in physical activity , improvements in dietary behaviors occurred , and were maintained at 9 months . Owing to its scalable potential for widespread adoption , replication trials should be conducted in diverse population s of overweight young adults . Trial Registration Australian and New Zeal and Clinical Trials Registry ( ANZCTR ) : ACTRN12612000924853 ; ( Archived by WebCite at http://www.webcitation.org/6i6iRag55 OBJECTIVE MyStudentBody.com-Nutrition ( MSB-N ) is an internet-based nutrition and physical activity education program for college students . METHOD Students from six universities ( N=476 ) in the U.S. were r and omly assigned in the fall of 2005 to one of three groups : MSB-N ( Experimental I ) , MSB-N plus Booster ( Experimental II ) , or an attention placebo control group . RESULTS Experimental I and II group participants increased their fruit and vegetable intake by .33 and .24 servings , respectively , relative to the control group at post-test . Both experimental groups improved their motivation to change eating behaviors ( p<.05 ) and were also more likely to increase their social support and self-efficacy for dietary change ( p's<.05 ) . Experimental groups also improved their attitude toward exercise ( p<.05 ) , but no behavioral changes in physical activity were noted . CONCLUSION MyStudentBody.com-Nutrition is an effective internet-based program that may have wide applicability on college campuses for nutrition education and promoting change in health behaviors OBJECTIVE To determine the accuracy of self-reported data regarding Fruit and Vegetable ( FV ) intake in college students at Utah State University after being presented with a descriptive normative message . INTERVENTION Participants ( N = 167 ) were recruited from general education courses and asked to complete a baseline survey containing a FV screener from the National Cancer Institute . They were then r and omized to receive one of four messages one week after the initial survey and asked to immediately complete the same FV screener . The Control group received no FV message . The Recommendation group received a message that the recommendation for FV is 4 - 5 cups per day . The two normative groups received a message that either 80 % of students ate more ( Low ) or less ( High ) FV than they did , regardless of actual intake , in addition to the recommended intake . ANALYSIS Repeated measures ANOVA was used to assess differences in reported FV intake and perceived FV intake of peers between the first and second assessment . RESULTS AND CONCLUSIONS Those receiving the message that they were in the lowest 20th percentile of intake reported a half-cup increase in self-reported FV intake and a one-cup increase in perception of peers ' intake ( p = 0.037 and p=<0.001 , respectively ) . No significant differences were observed in other groups . These results indicate that normative messaging may influence self-reported FV intake and perception of peer intake of college students when this message indicates that the participant is in the lowest percentile of their peers Background In young men , unhealthy lifestyle behaviours can be detrimental to their physical and /or mental health and set them on a negative health trajectory into adulthood . Despite this , there is a lack of evidence to guide development of effective health behaviour change interventions for young men . This study assessed the feasibility and preliminary efficacy of the ‘ HEYMAN ’ ( Harnessing Ehealth to enhance Young men ’s Mental health , Activity and Nutrition ) healthy lifestyle program for young men . Methods A pilot RCT with 50 young men aged 18–25 years r and omised to the HEYMAN intervention ( n = 26 ) or waitlist control ( n = 24 ) . HEYMAN was a 3-month intervention , targeted for young men to improve eating habits , activity levels and well-being . Intervention development was informed by a participatory research model ( PRECEDE-PROCEED ) . Intervention components included eHealth support ( website , wearable device , Facebook support group ) , face-to-face sessions ( group and individual ) , a personalised food and nutrient report , home-based resistance training equipment and a portion control tool . Outcomes included : feasibility of research procedures ( recruitment , r and omisation , data collection and retention ) and of intervention components . Generalized linear mixed models estimated the treatment effect at 3-months for the primary outcomes : pedometer steps/day , diet quality , well-being and several secondary outcomes . Results A 7-week recruitment period was required to enrol 50 young men . A retention rate of 94 % was achieved at 3-months post-intervention . Retained intervention participants ( n = 24 ) demonstrated reasonable usage levels for most program components and also reported reasonable levels of program component acceptability for attractiveness , comprehension , usability , support , satisfaction and ability to persuade , with scores ranging from 3.0 to 4.6 ( maximum 5 ) . No significant intervention effects were observed for the primary outcomes of steps/day ( 1012.7 , 95 % CI = −506.2 , 2531.6 , p = 0.191 , d = 0.36 ) , diet quality score ( 3.6 , 95 % CI = −0.4 , 7.6 , p = 0.081 , d = 0.48 ) or total well-being score ( 0.4 , 95 % CI = −1.6 , 2.5 , p = 0.683 , d = 0.11 ) . Significant intervention effects were found for daily vegetable servings , energy-dense , nutrient-poor foods , MVPA , weight , BMI , fat mass , waist circumference and cholesterol ( all p < 0.05 ) . Conclusions The HEYMAN program demonstrated feasibility in assisting young men to make some positive lifestyle changes . This provides support for the conduct of a larger , fully-powered RCT , but with minor amendments to research procedures and intervention components required . Trial registration Australian New Zeal and Clinical Trials Registry ACTRN12616000350426 Background Early adulthood represents the transition to independent living which is a period when changes in diet and body weight are likely to occur . This presents an ideal time for health interventions to reduce the effect of health problems and risk factors for chronic disease in later life . As young adults are high users of mobile devices , interventions that use this technology may improve engagement . The Connecting Health and Technology study aim ed to evaluate the effectiveness of tailored dietary feedback and weekly text messaging to improve dietary intake of fruit , vegetables and junk food over 6 months among a population -based sample of men and women ( aged 18–30 years ) . Methods A three-arm , parallel , r and omized control trial was conducted . After baseline assessment s , participants were r and omized to one of three groups : A ) dietary feedback and weekly text messages , B ) dietary feedback only or C ) control group . Dietary intake was assessed using a mobile food record App ( mFR ) where participants captured images of foods and beverages consumed over 4-days at baseline and post-intervention . The primary outcomes were changes in serves of fruits , vegetables , energy-dense nutrient-poor ( EDNP ) foods and sugar-sweetened beverages ( SSB ) . The intervention effects were assessed using linear mixed effect models for change in food group serves . Results Young adults ( n = 247 ) were r and omized to group A ( n = 82 ) , group B ( n = 83 ) , or group C ( n = 82 ) . Overall , no changes in food group serves for either intervention groups were observed . An unanticipated outcome was a mean weight reduction of 1.7 kg ( P = .02 ) among the dietary feedback only . Men who received dietary feedback only , significantly reduced their serves of EDNP foods by a mean of 1.4 serves/day ( P = .02 ) . Women who received dietary feedback only significantly reduced their intake of SSB ( P = .04 ) by an average of 0.2 serves/day compared with controls . Conclusions Tailored dietary feedback only result ed in a decrease in EDNP foods in men and SSB in women , together with a reduction in body weight . Using a mobile food record for dietary assessment and tailored feedback has great potential for future health promotion interventions targeting diet and weight in young adults . Trial Registration Australian Clinical Trials Registry Registration number : ACTRN12612000250831 Objectives To determine the effect on weight of two Mobile technology-based ( mHealth ) behavioral weight loss interventions in young adults . Methods R and omized , controlled comparative effectiveness trial in 18–35 year olds with BMI ≥ 25 kg/m2 ( overweight/obese ) , with participants r and omized to 24 months of mHealth intervention delivered by interactive smartphone application on a cell phone ( CP ) ; personal coaching enhanced by smartphone self-monitoring ( PC ) ; or Control . Results The 365 r and omized participants had mean baseline BMI of 35 kg/m2 . Final weight was measured in 86 % of participants . CP was not superior to Control at any measurement point . PC participants lost significantly more weight than Controls at 6 months ( net effect −1.92 kg [ CI −3.17 , −0.67 ] , p=0.003 ) , but not at 12 and 24 months . Conclusions Despite high intervention engagement and study retention , the inclusion of behavioral principles and tools in both interventions , and weight loss in all treatment groups , CP did not lead to weight loss and PC did not lead to sustained weight loss relative to control . Although mHealth solutions offer broad dissemination and scalability , the CITY results sound a caution ary note concerning intervention delivery by mobile applications . Effective intervention may require the efficiency of mobile technology , the social support and human interaction of personal coaching , and an adaptive approach to intervention design . Trial Registration Clinical Trials.gov Identifier NCT01092364 . https:// clinical Young women are gaining weight rapidly . Evidence for effective weight loss interventions targeting young women is lacking . This r and omized controlled trial assessed the efficacy and acceptability of a six-month targeted and tailored eHealth weight loss program for young women ( Be Positive Be Healthe ( BPBH ) ) . Women aged 18–35 years were r and omized to BPBH ( n = 29 ) or control ( n = 28 ) . BPBH supported participants to modify diet and physical activity behaviours using evidence d-based strategies ( e.g. , self-monitoring ) tailored for young women and delivered using e-health ( website , social media , smartphone application , email , text messages ) . The primary outcome was a change in weight ( kg ) at six months . Acceptability was assessed via a process evaluation survey and usage of intervention components . No significant between-group differences were observed for weight , with significant mean differences favouring the intervention group observed for body fat ( kg ) ( −3.10 ( −5.69 , 0.52 ) , p = 0.019 ) and intakes of alcohol ( g ) ( −0.69 ( −1.33 , 0.04 ) , p = 0.037 ) , vegetables ( % energy/day ) ( 4.71 ( −2.20 , 7.22 ) , p < 0.001 ) and energy-dense , nutrient-poor foods ( % energy/day ) ( −9.23 ( −16.94 , 1.52 ) , p = 0.018 ) . Retention , intervention usage and satisfaction were moderate . BPBH facilitated positive improvements in body fat and dietary intake , but not weight . Intervention acceptability findings support the use of some intervention components ( e.g. , Facebook , Smartphone app ) with young women Forming implementation intentions ( ‘ If I encounter situation X , then I will perform behaviour Y ! ’ ) increases the probability of carrying out goals . This study tested the hypothesis that mental imagery targeting key elements of implementation intentions further increases goal achievement . The residents of a student residence were assigned the goal of consuming extra portions of fruit every day for 7 days and r and omly assigned to one of four conditions : control ( active rehearsal ) , implementation intentions , goal intention mental imagery or mental imagery targeted to the implementation intentions . Among low fruit consumers , but not high fruit consumers , fruit consumption at follow-up was higher in the targeted mental imagery group than in the other group , with the lowest fruit consumption in the control group . The findings suggest that it may be beneficial to use targeted mental imagery when forming implementation intentions Background Vitamin D plays a key role in bone health . Consuming adequate vitamin D during young adulthood is important due to the development of peak bone mass ; however , many Canadian young adults do not meet vitamin D recommendations . This study aim ed to improve knowledge , perceptions , dietary intake and blood concentrations of vitamin D among a sample of young adults . Methods Using a pre-post design , 90 Ontario adults ( 38 men , 52 women ; 18–25 years ) , were r and omly assigned to intervention or control groups . Participants completed a socio-demographic survey , pre-post food frequency question naire , and a vitamin D knowledge question naire ( 3 time-points ) . The intervention group watched a video , received online information and tracked intake of vitamin D using a mobile application for 12 weeks . A sub- sample of participants completed pre-post blood 25(OH)D3 tests . Univariate ANOVA tested pre-post between-group differences in vitamin D intake and status . Repeated- measures ANOVA tested between-group differences in vitamin D knowledge and perceptions across 3 time-points . Results Mean vitamin D intake in the sample increased significantly from pre-test ( M = 407 , SD = 460 IU ) to post-test ( M = 619 , SD = 655 IU ) , t(88 ) = 5.37 , p < 0.001 . Mean intake increased significantly more in the intervention than control group after controlling for gender and education , F(1 , 85 ) = 4.09 , p = 0.046 . Mean blood vitamin D3 was significantly higher among non-Caucasian than Caucasian participants at baseline , t(56.7 ) = 3.49 , p = 0.001 . Mean blood vitamin D3 increased significantly from pre-test ( M = 28 , SD = 16 nmol/L ) to post-test ( M = 43 , SD = 29 nmol/L ) , t(53 ) = 11.36 , p < 0.001 , but did not differ significantly between groups . The increase in vitamin D knowledge from time 1–3 was significantly higher in the intervention than control group ( t(88 ) = 2.26 , p = 0.03 ) . The intervention group ( M = 3.52 , SE = 0.13 ) had higher overall perceived importance of vitamin D supplementation than the control ( M = 3.16 , SE = 0.12 ) , F(1 , 88 ) = 4.38 , p = 0.04 , ηp2 = 0.05 . Conclusions Although recommendations suggest blood 25(OH)D3 concentrations of ≥50 - 75 nmol/L , vitamin D status was below national recommendations . While participating in an intervention did not improve vitamin D status , it led to increased vitamin D intake , knowledge and perceived importance of supplementation . Trial registration Clinical Trails.gov registration # : NCT02118129 AIMS This study tested the impact of combining a motivational intervention based on protection motivation theory ( PMT , Rogers , 1983 [ 18 ] ) plus a volitional intervention based on action planning and coping planning , as a way to promote the prevention of type 2 diabetes among UK undergraduates . METHODS Eighty-four participants were r and omly assigned to either a control group or one of three experimental conditions : motivational intervention ( PMT ) , volitional intervention ( APCP ) , or combined motivational and volitional intervention ( PMT&APCP ) . PMT variables , dietary and exercise behaviours were measured at three time-points over a four-week period . RESULTS The motivational intervention significantly changed PMT variables . The combined motivational and volitional intervention significantly decreased fat intake and increased the frequency of exercise relative to all other groups , and significantly increased the amount of fruit and vegetables consumed relative to control and volitional intervention groups . CONCLUSIONS These results suggest that motivational intervention is effective at changing cognitions but changing behaviour requires an intervention based on both motivation and volition The objective of this study was to test the hypothesis that a nutrition course that stresses fundamental principles of human physiology , energy metabolism , and genetics helps prevent weight gain during the first 16 months of college life . A r and omized control trial was conducted from January 1997 to May 1998 using volunteers . Forty female college freshmen participated in the intervention ( college course , n = 21 ) and control ( no course , n = 19 ) groups . The intervention was a one-semester nutrition science college course . Body weight , nutrient intakes , and knowledge were measured at baseline , the end of the intervention ( 4 months from baseline ) , and 1 year later ( 16 months from baseline ) . Statistical analysis was conducted using a repeated-measure analysis of variance . Higher Body Mass Index ( BMI ) students ( BMI > 24 ) in the intervention group ( n = 11 ) reported lower fat ( p = .04 ) , protein ( p = .03 ) , and carbohydrate ( p = .008 ) intakes compared with the higher BMI students in the control group ( n = 6 ) . Dietary changes reported by the higher BMI intervention students were associated with the maintenance of baseline body weight for 1 year in contrast with the higher BMI control students who gained 9.2 6.8 kg ( p = .012 ) . The findings suggest that nutrition education emphasizing human physiology and energy metabolism is an effective strategy to prevent weight gain in at-risk college students Importance Effective long-term treatments are needed to address the obesity epidemic . Numerous wearable technologies specific to physical activity and diet are available , but it is unclear if these are effective at improving weight loss . Objective To test the hypothesis that , compared with a st and ard behavioral weight loss intervention ( st and ard intervention ) , a technology-enhanced weight loss intervention ( enhanced intervention ) would result in greater weight loss . Design , Setting , Participants R and omized clinical trial conducted at the University of Pittsburgh and enrolling 471 adult participants between October 2010 and October 2012 , with data collection completed by December 2014 . Interventions Participants were placed on a low-calorie diet , prescribed increases in physical activity , and had group counseling sessions . At 6 months , the interventions added telephone counseling sessions , text message prompts , and access to study material s on a website . At 6 months , participants r and omized to the st and ard intervention group initiated self-monitoring of diet and physical activity using a website , and those r and omized to the enhanced intervention group were provided with a wearable device and accompanying web interface to monitor diet and physical activity . Main Outcomes and Measures The primary outcome of weight was measured over 24 months at 6-month intervals , and the primary hypothesis tested the change in weight between 2 groups at 24 months . Secondary outcomes included body composition , fitness , physical activity , and dietary intake . Results Among the 471 participants r and omized ( body mass index [ BMI ] , 25 to < 40 ; age range , 18 - 35 years ; 28.9 % nonwhite , 77.2 % women ) , 470 ( 233 in the st and ard intervention group , 237 in the enhanced intervention group ) initiated the interventions as r and omized , and 74.5 % completed the study . For the enhanced intervention group , mean base line weight was 96.3 kg ( 95 % CI , 94.2 - 98.5 ) and 24-month weight 92.8 kg ( 95 % CI , 90.6- 95.0 ) [ corrected ] . For the st and ard intervention group , mean baseline weight was 95.2 kg ( 95%CI,93.0 - 97.3 ) and 24-month weight was 89.3 kg ( 95%CI , 87.1 - 91.5 ) [ corrected ] . Weight change at 24 months differed significantly by intervention group ( estimated mean weight loss , 3.5 kg [ 95 % CI , 2.6 - 4.5 } in the enhanced intervention group and 5.9 kg [ 95 % CI , 5.0 - 6.8 ] in the st and ard intervention group ; difference , 2.4 kg [ 95 % CI , 1.0 - 3.7 ] ; P = .002 ) . Both groups had significant improvements in body composition , fitness , physical activity , and diet , with no significant difference between groups . Conclusions and Relevance Among young adults with a BMI between 25 and less than 40 , the addition of a wearable technology device to a st and ard behavioral intervention result ed in less weight loss over 24 months . Devices that monitor and provide feedback on physical activity may not offer an advantage over st and ard behavioral weight loss approaches . Trial Registration clinical trials.gov Identifier : NCT01131871 OBJECTIVE Habit might be usefully characterized as a form of automaticity that involves the association of a cue and a response . Three studies examined habitual automaticity in regard to different aspects of the cue-response relationship characteristic of unhealthy and healthy habits . DESIGN , MAIN OUTCOME MEASURES , AND RESULTS In each study , habitual automaticity was assessed by the Self-Report Habit Index ( SRHI ) . In Study 1 SRHI scores correlated with attentional bias to smoking cues in a Stroop task . Study 2 examined the ability of a habit cue to elicit an unwanted habit response . In a prospect i ve field study , habitual automaticity in relation to smoking when drinking alcohol in a licensed public house ( pub ) predicted the likelihood of cigarette-related action slips 2 months later after smoking in pubs had become illegal . In Study 3 experimental group participants formed an implementation intention to floss in response to a specified situational cue . Habitual automaticity of dental flossing was rapidly enhanced compared to controls . CONCLUSION The studies provided three different demonstrations of the importance of cues in the automatic operation of habits . Habitual automaticity assessed by the SRHI captured aspects of a habit that go beyond mere frequency or consistency of the behavior OBJECTIVE This study assessed the effectiveness of a 4-month intervention using stage-based newsletters , computer-based communication , and motivational interviewing to increase fruit and vegetable consumption by college students aged 18 to 24 years . DESIGN Participants were stratified by stage of change for fruit and vegetable consumption and r and omized to an intervention or control group . Participants completed the staging algorithm for fruit and vegetable intake , which included a one-item food frequency question , a 26-item food frequency question naire ( FFQ ) , an 18-item decisional balance question naire , and a five-item self-efficacy question naire at baseline and completion of study . SUBJECTS A convenience sample of 437 college students enrolled in a rural , l and grant university was enrolled in the study . Only nondietetics majors between ages 18 to 24 years were included in the study . A total of 314 students finished the study for a completion rate of 72 % . INTERVENTION After baseline staging and r and omization , the intervention group participants received four stage-based newsletters , one motivational interview , and an individually tailored e-mail follow-up over a 4-month period . Control group participants only received assessment at baseline and at completion . MAIN OUTCOME MEASURES Two fruit and vegetable instruments , a one-item food frequency question , and a 26-item FFQ measured daily consumption of fruits and vegetables at baseline and postintervention . STATISTICAL ANALYSES PERFORMED The SAS system for Windows , version 8 ( 1999 , SAS Institute , Inc , Cary , NC ) , was used for analysis , including the following tests : PROC GLM , PROC FREQ , and PROC NPAR1WAY , Kruskal-Wallis , Fisher , Wilcoxon rank sum , and chi(2 ) . RESULTS Fruit and vegetable consumption increased significantly more for the intervention group than the control group . Consumption increased in the intervention group by one serving a day for both instruments compared with 0.4 servings a day in the control group for a one-item instrument and no change in the control group for a 26-item FFQ . CONCLUSIONS This intervention is an effective way to increase fruit and vegetable consumption by young adults Abstract Objective : Small-scale pilot testing of supplementing a required college health-related fitness course with a cognitive-behavioral exercise-support protocol ( The Coach Approach ) . Participants : Three classes were r and omly assigned to Usual processes ( n = 32 ) , Coach Approach – supplemented : Mid-size Groups ( n = 32 ) , and Coach Approach – supplemented : Small Groups ( n = 34 ) conditions . Methods : Repeated- measures analyses of variance ( ANOVAs ) assessed overall and between-class changes in the behavioral/physiological factors of exercise , fruit/vegetable intake , and body mass index ( BMI ) ; and the psychosocial factors of self-regulation , exercise self-efficacy , mood , and body satisfaction . Dependent t tests evaluated within-class changes . Multiple regression analyses tested prediction of exercise by changes in self-regulation , self-efficacy , and mood . Results : Significant improvements in self-regulation and fruit/vegetable intake were found in all classes . The Coach Approach – supplemented classes demonstrated significant increases in exercise . Significant improvements in BMI , self-efficacy , and body satisfaction were found in only The Coach Approach – supplemented : Small Groups class . Psychosocial changes predicted increased exercise . Self-regulation was the strongest contributor . Conclusions : Overall , results were positive and warrant more comprehensive testing Objective : Initial efficacy of a magazine-based discussion group for improving physical activity ( PA ) , self-worth , and eating behaviors in female college freshmen . Design : R and omized control trial . Setting : A large university in southwestern United States . Participants : Thirty-seven female college freshmen were r and omized to the intervention ( n = 17 ) and control groups ( n = 20 ) in September 2013 . Intervention : Participants completed an 8-week magazine-based discussion group program , Fit Minded College Edition , adapted from Fit Minded , a previously tested theory-based intervention . Education on PA , self-worth , and nutrition was provided using excerpts from women 's health magazines . Participants also had access to a Web site with supplementary health and wellness material . The control group did not attend meetings or have access to the Web site but received the magazines . Interventions focusing on concepts of self-worth with less focus on weight and appearance may promote long term PA participation and healthy eating behaviors in college women . Main Outcome Measures : Self-reported PA , global self-worth , knowledge self-worth , self-efficacy , social support , eating behaviors ( ie , fruit/veggie/junk food/sugar-sweetened beverage consumption ) , satisfaction , and Web site usage . Results : Mean age of participants was 18.11 ( SD = 0.32 ) years . Time × Intervention effects were observed for PA minutes per week ( Partial & eegr;2 = 0.34 ) , knowledge self-worth ( Partial & eegr;2 = 0.02 ) , and daily sugar-sweetened beverage consumption ( Partial & eegr;2 = 0.17 ) ( P < .05 ) , with the intervention group reporting greater increases in PA and knowledge self-worth and greater decreases in sugar-sweetened beverage consumption . Conclusions : A magazine-based discussion group may provide a promising platform to improve health behaviors in female college freshmen OBJECTIVE Evaluate the effects of a prevention program targeting both eating disorders and obesity at 1- and 2-year follow-ups . METHOD Female college students at risk for these outcomes because of body image concerns ( N = 398 ) were r and omized to the Healthy Weight 2 group-based 4-hr prevention program , which promotes lasting healthy improvements to dietary intake and physical activity and nutrition science health behavior change principles , or an educational brochure control condition . RESULTS Intervention participants showed significantly less body dissatisfaction and eating disorder symptoms and lower eating disorder onset through 2-year follow-up versus controls , but the former 2 effects were small . There were no main effects for body mass index ( BMI ) , depressive symptoms , dieting , caloric intake , physical activity , or obesity onset . Moderator analyses revealed stronger eating disorder symptom effects for youths with initially elevated symptoms and lower pressure to be thin , stronger BMI effects for youths with initially elevated symptoms and BMI scores , and weaker eating disorder symptom effects for youths with initially elevated pressure to be thin . CONCLUSIONS The 60 % reduction in eating disorder onset over the 2-year follow-up was clinical ly significant and a novel effect for a prevention program , but the main effects on continuous outcomes were small , suggesting that adding nutrition science principles weakened the intervention efficacy . Effects on both eating disorder symptoms and BMI were greater for those with elevated eating disorder symptoms and BMI at pretest , implying that it might be useful to target these individuals in future trials OBJECTIVE Evaluate a theory-based , Internet-delivered nutrition education module . DESIGN R and omized , treatment-control design with pre-post intervention assessment s. SETTING AND PARTICIPANTS Convenience sample of 160 young adults ( aged 18 - 24 ) recruited by community educators in 4 states . Study completers ( n = 96 ) included a mix of racial/ethnic groups and family demographics , but were predominately white females without children . INTERVENTION A Transtheoretical Model (TTM)-based , stage-tailored Internet program , F&V ( Fruit & Vegetable ) Express Bites , was delivered to treatment group participants ; controls received nontailored messages in a comparable format . MAIN OUTCOME MEASURES AND ANALYSIS : TTM constructs at baseline , immediately postviewing , and at 30-day follow-up were compared via chi-square , McNemar 's test , and logistic regression . Qualitative use and acceptability indicators were collected postviewing ( treatment only ) . RESULTS Of baseline respondents , 86.5 % completed the study . At follow-up , self-efficacy , decisional balance , and selected processes improved for both groups , with only marginal advantages for the theory-based version . Fruit and vegetable consumption changes were similar for both groups . Qualitative measures of knowledge , confidence , and motivation improved ( not measured for controls ) . Favorable ratings of treatment program acceptability and personal relevance were reported . CONCLUSIONS AND IMPLICATION S The Internet is a favorable option for reaching young adults with nutrition messages . This study did not identify strong advantages of theory-based tailoring , especially for fruit consumption , which had weaker barriers than vegetable consumption among this target audience Background : Using smartphone technology and text messaging for health is a growing field . This type of technology is well integrated into the lives of young adults . However , few studies have tested the effect of this type of technology to promote weight loss in young adults Objective : The purpose of this study is to test the effectiveness of a behaviorally based smartphone application for weight loss combined with text messaging from a health coach on weight , body mass index ( BMI ) , and waist circumference in young adults as compared with a control condition . Methods : Sixty-two young adults , aged 18 to 25 years , were r and omized to receive ( 1 ) a smartphone application + health coach intervention and counseling sessions or ( 2 ) control condition with a counseling session . All outcome measures were tested at baseline and 3 months . These included weight , BMI , waist circumference , dietary habits , physical activity habits , and self-efficacy for healthy eating and physical activity . Results : The sample was 71 % female and 39 % white , with an average age of 20 years and average BMI of 28.5 kg/m2 . Participants in the smartphone + health coach group lost significantly more weight ( P = .026 ) and had a significant reduction in both BMI ( P = .024 ) and waist circumference ( P < .01 ) compared with controls . Conclusions : The results of this weight loss trial support the use of smartphone technology and feedback from a health coach on improving weight in a group of diverse young adults Objective : Prevention would be the ideal public health strategy to face the current obesity epidemic . Adoption of healthy lifestyles during the first years of college or university could prevent the onset of weight gain associated with this period of acquired independence and eventually decrease the incidence of obesity . Design : R and omized-controlled trial over a period of 2 years . The subjects received an educational/behavioral intervention ( small group seminars ) design ed to help maintain a healthy lifestyle or no specific intervention ( control group).Subjects : One-hundred and fifteen non-obese freshmen in a Faculty of Medicine . Measurements : Anthropometric measurements , physical activity level , fitness level , food intake and lipid profile were recorded at predetermined intervals . Results : The control group gained weight , whereas the intervention group lost a slight amount of weight over 2 years . The difference between the two groups was 1.3 kg at the end of the follow-up , the trend of weight gain differing between the two groups during the 2-year intervention period ( P=0.04 ) . There was no detectable difference in fitness , physical activity level or total caloric intake between the two groups during follow-up . However , plasma triglyceride levels increased in the control group and decreased in the intervention group ( P=0.04 ) . Conclusion : In this r and omized-controlled trial , a small-group seminar educational/behavioral intervention successfully prevents weight gain in normal weight young healthy university students . Such small absolute changes in body composition and lipid profile , if maintained over a prolonged period , could result in significant long-term health benefits for the general population ( Clinical Trial.gov registration number : NCT00306449 ) Young adults are less likely than other adults to consume fruit and vegetables . Fresh Facts is a theory of planned behaviour based intervention design ed to promote fruit and vegetable consumption . The present study sought to evaluate Fresh Facts using a r and omised controlled trial . Australian young adults ( n = 162 ) were allocated to the Fresh Facts intervention or to the control group in 2011 . Intervention participants received automated email messages promoting fruit and vegetable consumption every 3 days over the course of the 1 month intervention . Messages targeted attitude , subjective norm , and perceived behavioural control . Theory of planned behaviour variables and fruit and vegetable intake were measured at baseline and post-intervention ( Day 30 ) . Significant increases in attitude and subjective norm relative to control were found among Fresh Facts participants . However , intention , perceived behavioural control and fruit and vegetable consumption did not change as a result of the intervention . Changes in intention reported by each participant between baseline and follow-up were not correlated with corresponding changes in fruit and vegetable consumption . Fresh Facts was not successful in increasing fruit and vegetable consumption . Current evidence does not support the use of the theory of planned behaviour in the design of interventions to increase fruit and vegetable intake in this population Purpose . To identify impact of an online nutrition and physical activity program for college students . Design . R and omized , controlled trial using online question naires and on-site physical and fitness assessment s with measurement intervals of 0 ( baseline ) , 3 ( postintervention ) , and 15 months ( follow-up ) . Setting . Online intervention delivered to college students ; a central ized Web site was used for recruitment , data collection , data management , and intervention delivery . Subjects . College students ( 18–24 years old , n = 1689 ) , from eight universities ( Michigan State University , South Dakota State University , Syracuse University , The Pennsylvania State University , Tuskegee University , University of Rhode Isl and , University of Maine , and University of Wisconsin ) . Intervention . A 10-lesson curriculum focusing on healthful eating and physical activity , stressing nondieting principles such as size acceptance and eating competence ( software developer : Rainstorm , Inc , Orono , Maine ) . Measures . Measurements included anthropometrics , cardiorespiratory fitness , fruit/vegetable ( FV ) intake , eating competence , physical activity , and psychosocial stress . Analysis . Repeated measures analysis of variance for outcome variables . Results . Most subjects were white , undergraduate females ( 63 % ) , with 25 % either overweight or obese . Treatment group completion rate for the curriculum was 84 % . Over 15 months , the treatment group had significantly higher FV intake ( + .5 cups/d ) and physical activity participation ( + 270 metabolic equivalent minutes per week ) than controls . For both groups , anthropometric values and stress increased , and fitness levels decreased . Gender differences were present for most variables . First-year males and females gained more weight than participants in other school years . Conclusion . A 10-week online nutrition and physical activity intervention to encourage competence in making healthful food and eating decisions had a positive , lasting effect on FV intake and maintained baseline levels of physical activity in a population that otherwise experiences significant declines in these healthful behaviors BACKGROUND Physical inactivity , low fruit and vegetable intake , hazardous drinking , and smoking are leading risk factors for disease and injury . The aim of this study was to obtain estimates of efficacy in reducing the first three of these behaviors . METHOD The design was a r and omized controlled trial : 218 patients ( 17 - 24 years ) attending a student health service at a New Zeal and university in 2003 were assigned to : ( A ) web-based assessment and personalized feedback ( n = 72 ) ; or ( B ) assessment only ( n = 74 ) ; or ( C ) minimal contact ( n = 72 ) . Outcome measures were the proportion meeting recommendations for fruit and vegetable consumption , physical activity , and alcohol consumption 6 weeks later . RESULTS Follow-up assessment s were attained for 86 % of participants , with no evidence of differential attrition . There were significant differences in the proportion meeting recommendations for fruit and vegetable consumption and physical activity in group A relative to C. Hazardous drinking prevalence did not vary significantly by group . CONCLUSIONS Differences appear attributable to the intervention . The intervention could be routinely provided in primary care , and its efficacy could be assessed in a large r and omized controlled trial ABSTRACT To evaluate the efficacy of a health-promotion intervention in increasing self-reported physical activity among university students in Sub-Saharan Africa . R and omly selected second-year students at a university in South Africa were r and omized to an intervention based on social cognitive theory : health-promotion , targeting physical activity and fruit , vegetable , and fat consumption ; or HIV risk-reduction , targeting sexual-risk behaviors . Participants completed assessment s via audio computer-assisted self-interviewing pre-intervention and 6 and 12 months post-intervention . A total of 176 were r and omized with 171 ( 97.2 % ) retained 12 months post-intervention . Generalized-estimating-equations analyses indicated that the health-promotion-intervention participants were more likely to meet physical-activity guidelines than were control participants , post-intervention , adjusting for pre-intervention physical activity ( odds ratio [ OR ] = 3.35 ; 95 % CI : 1.33–8.41 ) . Health-promotion participants reported a greater number of days they did vigorous-intensity ( risk ratio [ RR ] = 2.01 ; 95 % CI : 1.43–2.83 ) and moderate-intensity ( RR = 1.40 ; 95 % CI : 1.01–1.95 ) aerobic activity , but not strength-building activity ( RR = 1.37 ; 95 % CI : 0.091–2.07 ) . The intervention reduced self-reported servings of fried foods ( mean difference = −0.31 ; 95 % CI : −0.60 , −0.02 ) . The findings suggest that theory-based , context ually appropriate interventions may increase physical activity among university students in Sub-Saharan Africa Abstract Objective : To determine the impact of My Student Body (MSB)–Nutrition , an Internet-based obesity prevention program for college students . Participants : Three hundred and twenty ethnically diverse undergraduate students were r and omly assigned to 1 of 3 conditions : MSB-Nutrition program , an on-campus weight management course , and a comparison group . Methods : Students completed baseline and follow-up surveys regarding their nutrition and physical activity behaviors , self-efficacy , stress , attitudes , and body weight . Results : Compared with the on-campus course and a comparison group , the MSB-Nutrition program increased fruit and vegetable consumption , reduced stress , and increased fruit and vegetable self-efficacy but had no significant effect on students ’ exercise self-efficacy , exercise behavior , or weight loss . Conclusions : The MSB-Nutrition program was effective in changing students ’ nutrition behaviors but had no effect on physical activity behaviors or weight loss . Suggestions for improving Internet-based interventions aim ed at decreasing obesity rates among college students are offered Background / Aims : Young adults are at risk of weight gain , but little is known about design ing effective weight control trials for young adults or how to recruit and retain participants in these programs . The Choosing Healthy Options in College Environments and Setting s ( CHOICES ) study evaluated the effectiveness of a weight gain prevention intervention for 2-year college students . We describe the methods used to recruit and retain the colleges and their students , describe the sample and discuss recommendations for future studies . Methods : Students were recruited into a 24-month trial of a weight control intervention with assessment periods at baseline , 4- , 12- and 24-month follow-up . Results : We successfully recruited 441 students through partnerships with three 2-year colleges through a variety of campus-based methods . Ultimately , 83.4 % of the r and omized cohort participated in the 24-month assessment period . Those retained more often were White ( p = 0.03 ) compared to those who dropped out or were lost to follow-up ; no other socio-demographic factor ( e.g. gender , ethnicity and education ) , body mass index , body fat , waist circumference or weight status was observed to differ between r and omly assigned groups . Conclusion : Two-year colleges and their students are interested in participating in weight-related trials and partnering with universities for research . Research ers must work closely with administrators to identify benefits to their institutions and to resolve student-level barriers to recruitment and retention . Our experiences from the Choosing Healthy Options in College Environments and Setting s study should be useful in identifying effective recruitment and retention methods for weight gain prevention trials among young adults BACKGROUND Today 's generation of young adults are gaining weight faster than their parents ; however , there remains insufficient evidence to inform interventions to prevent this weight gain . Mobile phones are a popular means of communication that may provide a convenient , inexpensive means to deliver health intervention programmes . This pilot study aim ed to measure the effect of a 12-week mobile health ( mHealth ) intervention on body weight , body mass index and specific lifestyle behaviours addressed by the programme . METHODS University students and staff aged 18 - 35 years ( n = 51 ) were r and omised ( ratio 1 : 1 , intervention : control ) . Both groups received a printed diet booklet with instructions prepared by a dietitian . The intervention group also received Short Message Service ( SMS ) text messages ( four per week ) , e-mails ( four per week ) , and had access to smartphone applications and Internet forums . RESULTS Pre- to post-intervention , participants in the intervention group decreased their body weight [ mean ( SD ) ] [ -1.6 ( 2.6 ) kg ] , increased their light intensity activity [ 34 ( 35 ) min day(-1 ) ] and reported an increased vegetable ( 1.0 median serving day(-1 ) ) and decreased sugar-sweetened beverage intake [ -355 ( 836 ) mL week(-1 ) ] . Despite this , post-intervention changes in outcomes were not significantly different from controls . CONCLUSIONS The piloted mHealth programme provided some short-term positive changes in weight , nutrition and physical activity using a low cost , convenient delivery method for this population . However , changes were no different from those observed among controls . This might partly be explained by intervention participants ' low engagement with the programme , which is likely to require further modification to provide more regular , personalised , monitored support Fruit and vegetable consumption represents a nutritional goal to prevent obesity and chronic illness . To change dietary behaviors , people must be motivated to do so , and they must translate their motivation into actual behavior . The present experiment aims at the psychological mechanisms that support such changes , with a particular focus on dietary self-efficacy and planning skills . A r and omized controlled trial compared a theory-based psychological intervention with a health education session in 114 participants . Dependent variables were fruit and vegetable consumption , intention to consume more fruit and vegetables , planning to consume more , and dietary self-efficacy , assessed before the intervention , 1 week afterwards , and at 6-week follow up . Significant group by time interactions for all four dependent variables documented superior treatment effects for the psychological intervention group , with substantially higher scores at posttest and follow-up for the experimental group , although all students benefited from participation . To identify the contribution of the main intervention ingredients ( self-efficacy and planning ) , regression analyses yielded mediator effects for these two factors . A social-cognitive intervention to improve fruit and vegetable consumption was superior to a knowledge-based education session . Self-efficacy and planning seem to play a major role in the mechanisms that facilitate dietary changes OBJECTIVE To assess the effectiveness of a tailored theory-based , Web-delivered intervention ( Young Adults Eating and Active for Health ) developed using community-based participatory research process . DESIGN A 15-month ( 10-week intensive intervention with a 12-month follow-up ) r and omized , controlled trial delivered via Internet and e-mail . SETTING Thirteen college campuses . PARTICIPANTS A total of 1,639 college students . INTERVENTION Twenty-one mini-educational lessons and e-mail messages ( called nudges ) developed with the non-diet approach and focusing on eating behavior , physical activity , stress management , and healthy weight management . Nudges were short , frequent , entertaining , and stage-tailored to each behavior , and reinforced lesson content . MAIN OUTCOME MEASURE All participants were assessed at baseline , postintervention ( 3 months from baseline ) , and follow-up ( 15 months from baseline ) for primary outcomes of weight , body mass index ( BMI ) , fruit and vegetable intake ( FVI ) , physical activity ( PA ) , and perceived stress ; and secondary outcomes of waist circumference , percent dietary fat , energy from sugar-sweetened beverages , servings of whole grains , self-instruction and regulation for mealtime behavior , hours of sleep , and stage of readiness for change for consuming 5 cups of FVI , completing 150 minutes of PA/wk , and managing stress on most days of the week . Demographics were collected at baseline . ANALYSIS Chi-square analysis and mixed-models repeated measures analysis were performed to determine differences between experimental and control outcomes . RESULTS There were no differences between experimental and control participants in BMI , weight , and waist circumference . There were small improvements in FVI ( P = .001 ) , vigorous PA in females ( P = .05 ) , fat intake ( P = .002 ) , self-instruction ( P = .001 ) , and regulation ( P = .004 ) for mealtime behavior , and hours of sleep ( P = .05 ) at postintervention , but improvements were not maintained at follow-up . At postintervention , a greater proportion of experimental participants were in the action/maintenance stages for FVI ( P = .019 ) and PA ( P = .002 ) than control . CONCLUSIONS AND IMPLICATION S Young Adults Eating and Active for Health is one of the first studies to use the community-based participatory research process of PRECEDE-PROCEED to develop a non-diet approach intervention . Although there were no differences between experimental and control participants in weight change or BMI , the intervention supported positive change in behaviors that may mediate excessive weight gain , such as increasing FVI and more healthful self-regulation mealtime behaviors immediately postintervention . Additional strategies to maintain the behavior changes need to be explored Abstract Objective : The current study was a r and omized controlled trial investigating the effect of an innovative , short-term lifestyle intervention on weight gain in female freshman college students . Participants : Ninety-five freshmen were recruited from a large public university in the United States . Methods : Participants completed baseline assessment s and were r and omized to a 5-session , 4-week intervention or wait-list control , with assessment s at posttest and 3-month follow-up . Results : The hypothesized time by group interaction was not significant , p = .393 ; however , trends suggested that control participants maintained baseline weight , whereas intervention participants lost −2.07 kg by posttest but regained 1.05 kg at follow-up . Significantly more intervention participants ( 47.0 % ) decreased their daily caloric intake by ≥ 200 kcal compared with control ( 31.7 % ) , p = .050 . Conclusion : Brief intervention to prevent weight gain was not effective in this sample . Future studies should investigate lengthening the intervention to enhance effectiveness and increasing recruitment to improve statistical power OBJECTIVE This study examined whether 3-month outcomes of a brief image-based multiple behavior intervention on health habits and health-related quality of life of college students were sustained at 12-month follow-up without further intervention . METHODS A r and omized control trial was conducted with 303 undergraduates attending a public university in southeastern US . Participants were r and omized to receive either a brief intervention or usual care control , with baseline , 3-month , and 12-month data collected during fall of 2007 . RESULTS A significant omnibus MANOVA interaction effect was found for health-related quality of life , p=0.01 , with univariate interaction effects showing fewer days of poor spiritual health , social health , and restricted recent activity , p's<0.05 , for those receiving the brief intervention . Significant group by time interaction effects were found for driving after drinking , p=0.04 , and moderate exercise , p=0.04 , in favor of the brief intervention . Effect sizes typically increased over time and were small except for moderate size effects for social health-related quality of life . CONCLUSION This study found that 3-month outcomes from a brief image-based multiple behavior intervention for college students were partially sustained at 12-month follow-up Excess weight gain tends to occur in young adulthood . However , research examining effective weight-related interventions for this age group has been limited . As one of seven trials in the EARLY Trials consortium ( Early Adult Reduction of weight through LifestYle intervention ) , the CHOICES Study ( Choosing Healthy Options in College Environments and Setting s ) tested effects of a technology-integrated , young adult weight gain prevention intervention . It was a r and omized controlled trial with assessment s at baseline ( 2011 ) and 4- , 12- and 24-months post-intervention initiation and included 441 participants ( ages 18 - 35 ) who were students at three Minnesota community colleges . The 24-month intervention included a 1-credit academic course and social networking and support online intervention . This analysis examined effects on 12 secondary behavioral outcomes across three domains : diet ( fast food , sugary beverages , breakfast , at-home meal preparation ) , physical activity/screen time ( minutes and energy expenditure in leisure time physical activity , television viewing , leisure time computer use ) and sleep ( hours of sleep , time required to fall asleep , days not getting enough rest , difficulty staying awake ) . The intervention result ed in significant reductions in fast food ( p=0.007 ) but increases in difficulty staying awake ( p=0.015 ) . There was limited evidence of other behavior changes at 4months ( 0.05<p<0.1 ) in the expected direction but differences by treatment condition dissipated over time . Analyses examining summary treatment effects ( i.e. , modeling effects on all behavioral outcomes simultaneously ) indicated significant overall effects ( p=0.014 ) , largely driven by 4-month results ( p=0.005 ) . Additional research is needed to underst and effective obesity prevention among young adults , particularly when addressing multiple weight-related outcomes |
833 | 21,735,416 | Overall , SLIT is moderately effective in reducing total and individual ocular symptom scores in participants with ARC and AC . | BACKGROUND Allergic ocular symptoms , although frequently trivialised , are common and represent an important comorbidity of allergic rhinitis .
Sublingual Immunotherapy ( SLIT ) is an effective and well-tolerated treatment for allergic rhinitis , but its effects on symptoms of ocular allergy have not been well established .
OBJECTIVES To evaluate the efficacy of SLIT compared with placebo for reductions in ocular symptoms , topical ocular medication requirements and conjunctival immediate allergen sensitivity . | BACKGROUND The efficacy and safety of the 300-index of reactivity ( IR ) dose of 5-grass-pollen sublingual immunotherapy ( SLIT ) tablets ( Stallergènes , Antony , France ) have been demonstrated for the treatment of hay fever in adults . OBJECTIVE We sought to assess the efficacy and safety of this tablet in children and adolescents with grass pollen-related allergic rhinitis . METHODS In this multinational , r and omized , double-blind , placebo-controlled study , 278 children ( 5 - 17 years of age ) with grass pollen-related rhinoconjunctivitis ( confirmed by means of a positive grass pollen skin prick test response and serum-specific IgE measurement ) received once-daily SLIT tablets or placebo . Treatment was initiated 4 months before the estimated pollen season and continued throughout the season . The primary outcome was the rhinoconjunctivitis total symptom score ( RTSS ) , a sum of 6 individual symptom scores : sneezing , runny nose , itchy nose , nasal congestion , watery eyes , and itchy eyes . Secondary end points included rescue medication intake , individual scores , and safety . RESULTS The intent-to-treat population included 266 children ( mean age , 10.9 + /- 3.22 years ) . The RTSS for the 300-IR group was highly significantly different from that of the placebo group ( P = .001 ) . The 300-IR group showed a mean improvement for the RTSS of 28.0 % over that seen with placebo and a median improvement of 39.3 % . Significant differences between the 300-IR and placebo groups were also observed regarding rescue medication score and proportion of days using rescue medication during the pollen season ( P = .0064 and P = .0146 , respectively ) . Adverse events were generally mild or moderate in intensity and expected . No serious side effects were reported . CONCLUSION Five-grass-pollen SLIT tablets ( 300 IR ) reduce both symptom scores and rescue medication use in children and adolescents with grass pollen-related rhinoconjunctivitis BACKGROUND This is an interim analysis of a r and omized , double-blind , placebo-controlled phase III trial with 3 years of daily treatment with grass tablet immunotherapy ( GRAZAX ; ALK-Abelló A/S , Hørsholm , Denmark ) or placebo , followed by 2 years of follow-up to assess the persistent efficacy . OBJECTIVE We sought to evaluate the efficacy and safety of specific immunotherapy with grass allergen tablets compared with placebo after treatment covering 2 consecutive grass pollen seasons . METHODS The interim analyses included 351 adult participants with moderate-to-severe allergic rhinoconjunctivitis caused by grass pollen . Participants were treated with active ( n = 189 ) or placebo ( n = 162 ) tablets for an average of 22 months . All participants were allowed to use symptomatic rescue medication . RESULTS The primary efficacy analysis showed highly significant mean reductions of 36 % in rhinoconjunctivitis symptom score ( P < .0001 ; median reduction , 44 % ) and 46 % in rhinoconjunctivitis medication score ( P < .0001 ; median reduction , 73 % ) in the active group relative to the placebo group . Mean rhinoconjunctivitis quality of life was 33 % better ( P < .0001 ; median , 40 % ) . Clinical improvements were paralleled by significant changes in allergen-specific immunoglobulins . The treatment was well tolerated , and adverse events led to withdrawal in less than 1 % of participants . There were no serious adverse events related to treatment . CONCLUSION Grass allergen tablet immunotherapy showed progressive immunologic changes and highly significant efficacy over 2 years of continued treatment Background : Local application of allergen extracts in specific immunotherapy is accompanied by increased compliance and significantly reduced side effects . However , efficacy of local immunotherapy in children has yet not been sufficiently demonstrated . This study was performed to determine clinical efficacy of high dose sublingual swallow immunotherapy ( SLIT ) by a double‐blind placebo‐controlled study in children with grass pollen allergy using high dose allergen extracts UNLABELLED SAFETY and efficacy of sublingual ( sublingual-swallow ) immunotherapy ( IT ) with house dust mite extract were evaluated in 30 children ( 6 - 15 2/3 years of age ) over the first 12 months of an ongoing study . The cumulative dose was 570 micrograms Der p I ( five times that administered with subcutaneous therapy ) . SAFETY One patient on active treatment dropped out after 8 weeks because of a subjective feeling of severe weakness , question ably induced by the therapy . Five patients on active therapy and one patient on placebo reported minor local side effects . EFFICACY Pulmonary symptoms were reduced after 12 months in actively treated asthmatics , but this was not consistent with the lack of improvement in bronchial reactivity , skin sensitivity and specific IgG and IgG4 against D.pt . in this group . In patients with rhinitis nasal sensitivity was reduced in the placebo group without concomitant improvement in the nasal symptom score . Specific IgE ( D.pt . and D.f . ) increased significantly more in the active treatment group after 3 and 12 months . We conclude that sublingual IT over 12 months with the fivefold Der p 1 dose of subcutaneous IT was well tolerated , but there was no consistent clinical or immunological benefit compared to placebo BACKGROUND Cross-reactivity between the major birch pollen allergen , Bet v 1 , and the apple protein , Mal d 1 , frequently causes food allergy . OBJECTIVE To investigate the effects of successful sublingual immunotherapy ( SLIT ) with birch pollen extract on apple allergy and the immune response to Bet v 1 and Mal d 1 . METHODS Before and after 1 year of SLIT , Bet v 1-sensitized patients with oral allergy syndrome to apple underwent nasal challenges with birch pollen and double-blind placebo-controlled food challenges with apple . Bet v 1-specific and Mal d 1-specific serum antibody levels and proliferation in P BMC s and allergen-specific T-cell lines ( TCLs ) were determined . Bet v 1-specific TCLs were mapped for T-cell epitopes . RESULTS In 9 patients with improved nasal provocation scores to birch pollen , apple-induced oral allergy syndrome was not significantly reduced . Bet v 1-specific IgE and IgG(4 ) levels significantly increased . Bet v 1-specific T-cell responses to all epitopes and those cross-reactive with Mal d 1 significantly decreased . However , neither Mal d 1-specific IgE and IgG(4 ) levels nor Mal d 1-induced T-cell proliferation changed significantly . In contrast , Mal d 1-specific TCLs showed increased responses to Mal d 1 after 1 year of SLIT . CONCLUSION This longitudinal study indicates that pollen SLIT does not efficiently alter the immune response to pollen-related food allergens , which may explain why pollen-associated food allergy is frequently not ameliorated by pollen immunotherapy even if respiratory symptoms significantly improve . CLINICAL IMPLICATION S SLIT with birch pollen may have no clinical effect on associated apple allergy A double-blind , placebo-controlled study of immunotherapy was conducted in 31 patients with allergic rhinitis due to Parietaria pollen to evaluate the efficacy and safety of high doses of allergen via the sublingual route . The patients were assessed before and after a 10-month period of treatment by clinical ( symptom-medication scores and specific nasal reactivity ) and immunological ( total IgE , specific IgE , IgG and IgG4 antibodies ) parameters . High doses of Parietaria extract corresponding to a cumulative dose of 105 BU for each patient were administered with negligible side effects . The actively treated patients had significantly lower medication scores than those on placebo ( p < 0.05 ) when the maximum pollen count was recorded , and at the end of the trial they showed a significant decrease in nasal reactivity ( p < 0.02 ) and a significant increase in serum specific IgG4 ( p = 0.02 ) . No differences were detected in any of these parameters in the placebo group . Possible explanations for the mechanisms of sublingual immunotherapy are proposed OBJECTIVE To evaluate the safety and efficacy of sublingual immunotherapy with ' Dermatophagoides Farinae Drops ' in D. farinae allergic asthma and /or rhinitis patients . METHODS A 25-week double-blind , placebo-controlled , multi-centered trail was conducted in 278 children ( aged 4 - 18 yr ) with mite-induced asthma and /or rhinitis . Patients were r and omly assigned to receive sublingual immunotherapy ( SLIT ) with ' Dermatophagoides Farinae Drops ' ( n = 139 ) or placebo ( n = 139 ) for 25 weeks and the dosage and administration strictly followed the manufacturer 's instructions . At the beginning of the 2nd , 3rd , 4th , 6th , 10th , 14th , 18th , 22nd week of the treatment , the patients were asked to accept follow-up visit , during the clinical trial all patients and parents were asked to keep a daily record of their asthma symptom scores , rescue medicine use , rhinitis symptom scores , morning and evening peak expiratory flow . Asthma symptom scores , reduction in use of rescue medicine , rhinitis symptom scores , lung function tests , skin sensitivity to mite , mite-specific immunoglobulin ( Ig ) E and IgG4 , and quality of life and adverse effect were assessed during the study . RESULT ( 1 ) Of the 278 children , 27 dropped out before the study completion . ( 2 ) After 25 weeks of treatment , the median variability of PEFR was -1.38 for SLIT group and -0.90 for the placebo ( P < 0.05 ) . ( 3 ) Besides , the mean variability of medicine score of asthma was -0.08 for SLIT group and 0.52 for the plcebo ( P < 0.05 ) . ( 4 ) The median variability of rhinitis symptom score was -1.96 for SLIT group and -1.03 for the placebo ( P < 0.01 ) . ( 5 ) The rescue medicine usage of SLIT reduced but did not show significant differences between SLIT and placebo . ( 6 ) After 25 weeks treatment , the increase of D. farinae specific IgE antibody of two groups were similar , while specific IgG4 increased significantly in SLIT compared to the patients in control one ( P < 0.01 ) ; ( 7 ) No severe adverse events happened in the trial and the most-likely adverse events were mild asthma and local rash . CONCLUSION Dermatophagoides Farinae Drops is safe and effective in treating allergic asthma and atopic rhinitis BACKGROUND Allergen immunotherapy ( desensitization ) by injection is effective for seasonal allergic rhinitis and has been shown to induce long-term disease remission . The sublingual route also has potential , although definitive evidence from large r and omized controlled trials has been lacking . OBJECTIVE The aim was to confirm the efficacy of a rapidly dissolving grass allergen tablet ( GRAZAX , ALK-Abelló , Hørsholm , Denmark ) compared with placebo in patients with seasonal rhinoconjunctivitis . METHODS A longitudinal , double-blind , placebo-controlled , parallel-group study that included 51 centers from 8 countries . Subjects were r and omized ( 1:1 ) to receive a grass allergen tablet or placebo once daily . A total of 634 subjects with a history of grass pollen-induced rhinoconjunctivitis for at least 2 years and confirmation of IgE sensitivity ( positive skin prick test and serum-specific IgE ) were included in the study . Subjects commenced treatment at least 16 weeks before the grass pollen season , and treatment was continued throughout the entire season . RESULTS The primary efficacy analysis showed a reduction of 30 % in rhinoconjunctivitis symptom score ( P < .0001 ) and a reduction of 38 % in rhinoconjunctivitis medication score ( P < .0001 ) compared with placebo . Side effects mainly comprised mild itching and swelling in the mouth that was in general well tolerated and led to treatment withdrawal in less than 4 % of participants . There were no serious local side effects and no severe systemic adverse events . CONCLUSION Sublingual immunotherapy with grass allergen tablets was effective in grass pollen-induced rhinoconjunctivitis . The tablet was well tolerated with minor local side effects . CLINICAL IMPLICATION S The grass allergen tablet represents a safe alternative to injection immunotherapy suitable for home use BACKGROUND Sublingual immunotherapy ( SLIT ) is accepted as a safe and effective route for the treatment of grass pollen allergy , but clarification of its clinical and biological efficacy requires more study . OBJECTIVE To evaluate the efficacy , safety , and compliance of SLIT with a st and ardized 3-grass pollen extract in patients with grass pollen seasonal allergic rhinoconjunctivitis , with or without mild asthma . METHODS This multicenter , r and omized , double-blind study included 127 patients ( aged 12 - 41 years ; mean age , 24.9 years ) with grass pollen seasonal allergic rhinoconjunctivitis , with or without mild asthma . They received either SLIT with a high-dose , st and ardized , 3-grass pollen extract or placebo for 10 months before and during the grass pollen season . The efficacy evaluation compared weekly clinical scores ( defined as the sum of the symptom score and rescue medication score ) to measure rhinoconjunctivitis and asthma for the first 8 weeks of the pollen season . We also evaluated safety and compliance and measured changes in anti-Dactylis specific IgG4 antibody levels . RESULTS There was a trend in favor of the study group in the mean adjusted clinical score . The groups were not comparable on inclusion ( P = .02 ) : the SLIT group included more subjects with asthma and had a higher mean IgG4 serum level . Additional exploration according to subgroups with and without asthma found that among the patients without asthma , the SLIT group had a significantly better clinical score ( P = .045 ) . Anti-Dactylis specific IgG4 levels increased significantly in the SLIT group . CONCLUSION SLIT with a st and ardized , high-dose , 3-grass pollen extract is safe and significantly improves the clinical score in patients with hay fever and without asthma during the pollen season Thirty-four patients suffering from rhinoconjunctivitis with or without asthma due to grass pollen , were su bmi tted to sublingual immunotherapy according to a double blind placebo controlled experimental plan ; eighteen patients received the active therapy , sixteen the placebo . A rush preseasonal treatment schedule was followed in order to reach the maintenance dose in 15 days with two administrations per day ; the top dose reached was then administered three times a week until the end of the pollen season . The symptoms and drugs related to rhinoconjunctivitis and asthma were recorded by means of diary cards and grass pollen counts were performed during the season . The actively treated group showed a reduction of symptoms of rhinoconjunctivitis and asthma and a lower intake of drugs for the same symptoms ; all these differences result ed to be statistically significant . No patient showed local or systemic side effects of any relevance . According to these results of our study , sublingual rush immunotherapy is clinical ly effective and because of the ease of h and ling , the shortness of the treatment , the absence of relevant side effects and the high compliance of the patient can be considered as an alternative to classic injective immunotherapy in grass pollen allergic patients BACKGROUND Sublingual swallow immunotherapy has been increasingly recognized as a safe and efficacious alternative to parenteral specific immunotherapy . OBJECTIVE To determine the safety and efficacy of sublingual swallow immunotherapy ragweed allergen extract for rhinoconjunctivitis treatment starting just before and continuing through the ragweed pollen season . METHODS This r and omized , double-blind , placebo-controlled study was performed in children and adults with a documented history of allergic rhinoconjunctivitis during ragweed season at 9 Canadian allergy centers . Active treatment was st and ardized extract of ragweed allergen administered as sublingual swallow drops at increasing doses starting shortly before the pollen season and maintenance doses continued daily during the season . Primary efficacy variables were symptom and medication scores , and secondary variables included global evaluation of efficacy and immunologic measurements . RESULTS Eighty-three patients were included in the safety analysis ; 76 patients were included in the intent-to-treat analysis . Nine placebo recipients and 1 treatment recipient withdrew for lack of efficacy ( P = .004 ) . Nine patients in the treatment group withdrew because of adverse events , none serious ( P = .003 ) . Investigator evaluation of efficacy showed that significantly more patients improved and fewer deteriorated in the treatment group vs the placebo group ( P = .047 ) . Ragweed IgE and IgG4 levels increased significantly in treatment recipients vs placebo users ( P < .001 ) . Sneezing and nasal pruritus approached significant improvement in the treatment group vs the placebo group ( P = .09 and .06 , respectively ) . Quebec City experienced low pollen counts . Excluding Quebec City , significant improvement was seen for these 2 symptoms ( P = .04 ) . CONCLUSION Sublingual swallow immunotherapy seems to be safe and efficacious for ragweed rhinoconjunctivitis even when started immediately before the ragweed pollen season Background : Data supporting a carry‐over effect with sublingual immunotherapy ( SLIT ) are scarce . This r and omized , double‐blind , placebo‐controlled study evaluated the efficacy , carry‐over effect and safety of grass pollen SLIT using co‐seasonal treatment Background : Especially in childhood , sublingual immunotherapy ( SLIT ) could offer advantages over subcutaneous therapy . However , limited data on its efficacy is available Sublingual immunotherapy has been suggested for the treatment of respiratory allergies . Many controversial studies have been reported on the efficacy of sublingual immunotherapy . The aim of this prospect i ve study was to evaluate whether sublingual immunotherapy was effective according to clinical and laboratory results in pediatric allergies . Thirty-nine allergic , grass pollen sensitive children were admitted into the study . Sublingual immunotherapy was given over a 12-month period to 21 children ( mean age 10.5 + /- 3.3 years ) , 10 of whom had seasonal allergic rhinitis and 11 seasonal allergic asthma . During the same period , 18 children ( mean age 11.1 + /- 2.5 years ) , 10 with seasonal allergic rhinitis and eight with seasonal allergic asthma , received placebo . Symptom scores and drug requirements were recorded and urine sample s were collected to detect urinary levels of leukotrienes ( Uc-LTB4 and Uc-LTE4 ) . In patients who received sublingual immunotherapy , the symptom scores of seasonal allergic rhinitis significantly decreased , but no statistically significant changes were observed in terms of symptoms of seasonal allergic asthma . Uc-LTE4 and Uc-LTB4 levels of seasonal allergic rhinitis , with a geometric mean and 95 % confidence interval ( CI ) , were significantly decreased from 216 ( 103 - 464 ) and 61 ( 22 - 198 ) pmol/mmol creatinine to 78 ( 29 - 159 ) and 35 ( 12 - 118 ) pmol/mmol creatinine , respectively ( p < 0.05 and p < 0.05 ) . On the other h and , Uc-LTE4 and Uc-LTB4 levels for seasonal allergic asthma were 180 ( 92 - 355 ) and 78 ( 44 - 258 ) pmol/mmol creatinine and decreased to 156 ( 72 - 402 ) and 69 ( 32 - 254 ) pmol/mmol creatinine , respectively . These changes were not statistically significant ( p > 0.05 ) . According to our clinical results and urinary levels of leukotrienes , which are mediators showing the severity of allergic inflammation , it can be suggested that sublingual immunotherapy may be useful in the treatment of seasonal allergic rhinitis but not of seasonal allergic asthma BACKGROUND sublingual immunotherapy has been recognised as safe and effective but it is still poorly documented in tree pollen allergy . Allergy to alder , birch and hazel is important in Northern European countries but its clinical relevance is increasing in Southern Europe . METHODS thirty patients , selected and observed for one pollen season , were r and omised to receive placebo ( 15 patients ) or active treatment ( 15 patients ) . Twenty-seven patients completed the first year and 24 of them were treated with active therapy during the second year of the study in comparison to a parallel group of ten patients treated only with drugs . Symptom and drug scores during each pollen season , birch-specific IgE , changes in skin test reactivity , changes in specific Nasal Provocation Test and the daily average pollen count for the relevant trees were considered for the assessment of the efficacy of the treatment . RESULTS both active and placebo group showed a statistically significant improvement in scores in comparison to the previous year , under a lower allergenic pressure . The improvement was higher in the active group ( 76.04 % reduction of drugs ) but not significantly different from that registered in the placebo group ( 37.05 % reduction ) . In the open phase of the study , treated patients showed significantly better scores in comparison to the control group . No significant changes in skin reactivity , specific IgE and Nasal Provocation Test were registered . SLIT tolerance was very good . CONCLUSIONS our data show a better but not statistically significant clinical outcome for patients actively treated with SLIT , but the placebo effect and the year-by-year variability of the environmental allergenic load in our small-size pilot study do not allow for a conclusive statement about the efficacy of this form of therapy BACKGROUND Allergic rhinoconjunctivitis patients are often treated with nasal or systemic allergy therapy , forgoing therapy for ocular symptoms . This treatment regimen leaves important aspects of the allergic reaction untreated and affects quality of life ( QoL ) . The Rhinoconjunctivitis Quality of Life Question naire and the Allergic Conjunctivitis Quality of Life Question naire quantify separate aspects of QoL. OBJECTIVE To determine the benefit gained in QoL , measured by these question naires , when antiallergy eyedrops ( olopatadine ) were added to patients ' preexisting regimens of nasal or systemic allergic rhinitis treatment . METHODS This was a 4-week prospect i ve , multicenter , open-label , crossover , environmental QoL study . Visit 1 r and omized patients to treatment group A or B and included baseline examinations and question naires . Group A instilled olopatadine twice daily and concomitantly with previously prescribed nasal or systemic antiallergy medication for 2 weeks . Group B received no ocular therapy and used only previously prescribed antiallergy medication for 2 weeks . Treatment group crossover occurred at visit 2 . Patients again completed the question naires at visits 2 and 3 . RESULTS Two hundred patients completed the study , 97 in group A and 103 in group B. Groups A and B experienced ocular allergic symptoms for 3.88 and 3.96 days , respectively , during the week before baseline . At visits 2 and 3 , question naire scores were significantly improved for each group when olopatadine was added compared with the nontreatment periods . By visit 2 , olopatadine improved QoL by 49 % compared with 5 % in the nontreated group ( P < .001 ) . CONCLUSIONS In this study , 90.5 % of patients with allergic rhinitis treated nasally or systemically also had ocular allergic symptoms . Adding olopatadine to these patients ' medication regimens significantly improved ocular allergic symptoms and overall Sublingual‐swallow immunotherapy ( SLIT ) using high doses of st and ardized allergen extracts has been found to be effective in reducing allergic symptoms and medication needs . A double‐blind , placebo‐controlled study was carried out in a large number of patients to determine whether medication needs can be reduced by SLIT . Some 136 patients with grass‐pollen rhinitis with or without mild asthma were studied . Patients received either placebo or SLIT with a st and ardized grass‐pollen extract administered daily with increasing doses up to 300 IR ( index of reactivity ) from January to the end of July 1994 . During the grass‐pollen season , patients were instructed to use medications as required and to visit their doctors in case of asthma . Symptom‐medications scores were assessed during the pollen season , and serum‐specific IgG4 was measured before and at the end of SLIT . In the SLIT group , drug consumption dropped significantly throughout the pollen season ( P<0.02 ) . Moreover , at the peak of the pollen season , betamethasone consumption was significantly reduced in the SLIT group ( P<0.02 ) . Only one patient in the SLIT group had an asthma attack compared to eight patients in the placebo group ( P<0.02 ) . IgG4 levels increased significantly in the SLIT group ( P<0.001 ) but without correlation with symptoms . Side‐effects were comparable in both groups . This study indicates that SLIT in grass‐pollen rhinitis is well tolerated , improves overall clinical symptoms , and reduces drug consumption and the need for oral corticosteroids In a double-blind , placebo-controlled , pilot clinical trial we evaluated the clinical efficacy and safety of immunotherapy ( IT ) with an extract of the pollen of the tree Olea europaea administered sublingually . The parameters tested were symptom score , dose-response bioassay of skin prick test and specific IgE and IgG , and the absolute value at a single serum dilution of each IgG subclass . Fifteen patients allergic to this pollen with symptomatology of rhinitis and /or rhinoconjunctivitis were r and omly allocated to the placebo group ( 6 patients ) or to the extract group ( 9 patients ) . Immunotherapy was administered in a short preseasonal period of time , practically no side effects being recorded . The group of patients treated with extract presented a slightly lower incidence ( 0.05 < p < 0.1 ) of nasal symptoms of sneezing and obstruction , and , more importantly , developed less dyspnea ( p < 0.05 ) than the group treated with placebo , suggesting that IT can act as prophylaxis for the development of bronchial symptoms . No differences were observed in the immunological determinations . Differences in skin tests between the two groups displayed a slight significance ( 0.05 < p < 0.1 ) at the end of the trial ; hence , a higher concentration of the allergen was needed in the group treated with extract to induce the same wheal as in the placebo group . In both groups the size of the wheal showed a time-dependent variation , which was dependent on the time of the year and independent of the type of treatment received , indicating a significant modification in the in vivo skin response to allergen challenge , demonstrated by a shift in the kinetics of allergen-lig and binding ( slope ) and in the magnitude of the measured response ( intercept ) BACKGROUND The aim of this study was to confirm the clinical efficacy and safety of a preseasonal sublingual immunotherapy ( SLIT ) in a group of allergic patients with seasonal rhinoconjunctivitis with or without mild intermittent or mild persistent asthma . The immunotherapy was administered through the oral mucosa with a monomeric carbamylated allergoid ( allergoid SLIT ) for grass pollens . A secondary endpoint was to evaluate the effect of the allergoid SLIT on nasal reactivity . METHODS AND RESULTS A single-center , r and omized , double-blind , placebo-controlled study was performed . Patients were selected and r and omly allocated to two groups : one group received active treatment ( allergoid SLIT ) for 2 years and the other received placebo . Both groups received the necessary drug treatment throughout the trial . Thirty-three out patients ( 20 men and 13 women , mean age : 30 years ; range : 19 - 43 ) attending our center were enrolled in the study . Symptoms and medications were scored on diary cards during the pollen season . An allergen nasal challenge was performed at baseline and after 2 years of SLIT to evaluate nasal reactivity . Because the clinical scores were non-normally distributed , the Mann-Whitney and the Chi-square tests for intergroup comparisons and the Wilcoxon test for intragroup comparisons were used . The results were evaluated after 1 and 2 years of treatment . Between the first and second years of treatment , no changes in the scores for the placebo group were found , while for the active vaccine group significant decreases were found in rhinorrhea ( p < 0.03 ) , sneezing ( p < 0.03 ) , and conjunctivitis ( p < 0.02 ) . Symptom scores after nasal challenge decreased ( p < 0.03 ) after 2 years ' treatment . Nasal steroid use significantly decreased in the active treatment group during May and June in both the years of treatment ( p < 0.02 ) . Only two mild local adverse events were reported in the active group and none was reported in the placebo group . CONCLUSIONS The results of this study show that the allergoid SLIT is safe and effective in decreasing symptom scores and drug use in rhinitic patients allergic to grass pollen OBJECTIVE The purpose of this r and omized , double-blind , placebo-controlled study was to evaluate the clinical efficacy and tolerance of once-daily sublingual immunotherapy without updosing . Reduction in symptoms and medication use was the primary endpoint . METHODS One hundred five patients with rhinitis and /or asthma due to grass and olive sensitization were r and omized to be treated with placebo or active sublingual immunotherapy with the SLITone grass mix plus olive pollen extract for 6 months before the 2005 pollen season . Patients recorded symptoms and medication intake for 8 weeks during the pollen seasons in 2004 ( n=37 ) and 2005 ( n=85 ) . RESULTS Allergic symptoms were significantly decreased in the active immunotherapy group ( P = .004 ) but not in the placebo group . There were no differences in scores between groups during the 2005 pollen season . Subjective assessment s on a visual analog scale and a quality -of-life question naire indicated an improvement in actively treated patients with significant differences in both symptoms and medication use ( P = .006 ) . The rate of systemic adverse reactions was comparable in the 2 groups . No anaphylactic or severe adverse reactions were reported . Local adverse reactions , which were more common in the active immunotherapy group , were mostly immediate , were limited to the lips and mouth , and did not require treatment . CONCLUSION Once-daily sublingual immunotherapy without updosing was well tolerated . The actively treated patients showed a significant reduction in symptom and medication scores and an improvement in their quality of life although there were no significant differences between the groups probably due to the low allergen season in which the study was evaluated Background The safety and the efficacy of sublingual‐swallow immunotherapy ( SLIT ) in perennial conjunctivitis caused by house dust mite were evaluated in a double‐blind , placebo‐controlled study including 60 patients for 24 months BACKGROUND The efficacy and safety of a 5-grass-pollen sublingual immunotherapy ( SLIT ) tablet ( Stallergènes SA , Antony , France ) have been evaluated in clinical studies during the pollen season . The allergen challenge chamber ( ACC ) has been developed as a pharmacodynamic assessment tool to control the environmental allergens and to avoid all problems associated with unpredictable pollen seasons . OBJECTIVE We sought to evaluate the onset of action and efficacy of 300-IR ( index of reactivity ) SLIT tablets by using an ACC . METHODS Patients with grass pollen-induced rhinoconjunctivitis were r and omized into the active or placebo groups . A st and ardized allergen challenge with grass pollen and symptom evaluation every 15 minutes was performed at baseline , 1 week , and 1 , 2 , and 4 months of treatment . The primary end point was the average rhinoconjunctivitis total symptom score ( ARTSS ) . Allergen-specific basophil activation , T-cell proliferation , and plasmatic IgE and IgG responses were assessed before and after treatment . RESULTS In the intention-to-treat population ( n = 89 ) a significant treatment effect was achieved after the first month ( P = .0042 ) and second month ( P = .0203 ) and was maintained through to the fourth month ( P = .0007 ) . In the active group the ARTSS ( means + /- SDs ) decreased at each challenge : week 1 , 7.40 + /- 2.682 ; month 1 , 5.89 + /- 2.431 ; month 2 , 5.09 + /- 2.088 ; and month 4 , 4.85 + /- 1.999 . An improvement ( vs placebo ) of 29.3 % for the mean ARTSS ( median , 33.3 % ) was observed at end point . Furthermore , the induction of grass pollen allergen-specific IgGs was associated with clinical response . The most frequent adverse reactions were local : oral pruritus , ear pruritus , and throat irritation . CONCLUSIONS In this ACC study the 300-IR 5-grass-pollen SLIT tablets had a significant effect on rhinoconjunctivitis symptoms ( vs placebo ) from the first month of treatment onward BACKGROUND Specific immunotherapy is the only treatment modality that has the potential to alter the natural course of allergic diseases . Sublingual immunotherapy has been developed to facilitate access to this form of treatment and to minimize serious adverse events . OBJECTIVE To investigate the efficacy and safety of sublingual grass allergen tablets in seasonal allergic rhinoconjunctivitis . METHODS A multinational , multicenter , r and omized , placebo-controlled trial conducted during 2002 and 2003 . Fifty-five centers in 8 countries included 855 participants age 18 to 65 years who gave a history of grass pollen-induced allergic rhinoconjunctivitis and had a positive skin prick test and elevated serum allergen-specific IgE to Phleum pratense . Participants were r and omized to 2500 , 25,000 , or 75,000 SQ-T grass allergen tablets ( GRAZAX ; ALK-Abelló , Hørsholm , Denmark ) or placebo for sublingual administration once daily . Mean duration of treatment was 18 weeks . RESULTS Average rhinoconjunctivitis scores during the season showed moderate reductions of symptoms ( 16 % ) and medication use ( 28 % ) for the grass allergen tablet 75,000 SQ-T ( P = .0710 ; P = .0470 ) compared with placebo . Significantly better rhinoconjunctivitis quality of life scores ( P = .006 ) and an increased number of well days ( P = .041 ) were also observed . Efficacy was increased in the subgroup of patients who completed the recommended preseasonal treatment of at least 8 weeks before the grass pollen season ( symptoms , 21 % , P = .0020 ; and medication use , 29 % , P = .0120 ) . No safety concerns were observed . CONCLUSION This study confirms dose-dependent efficacy of the grass allergen tablet . Although further studies are required , the greater tolerability of the tablet may permit immunotherapy to be available to a much broader group of patients with impaired quality of life caused by grass pollen allergy . CLINICAL IMPLICATION S For patients with grass pollen allergy , sublingual immunotherapy is well tolerated and can reduce symptoms and improve quality of life Background The optimal dose of grass pollen tablets for sublingual immunotherapy ( SLIT ) in allergic rhinoconjunctivitis patients was previously established in a multinational , r and omized , double‐blind , placebo‐controlled study in 628 adults . Patients were r and omized to receive once‐daily 5‐grass pollen sublingual tablets of 100 IR ( index of reactivity ) , 300 IR or 500 IR , or placebo starting 4 months before the pollen season BACKGROUND Although several studies support the efficacy of specific immunotherapy in allergic asthma , its benefit compared with that of st and ardized pharmacologic intervention remains unknown . OBJECTIVE A double-blind , placebo-controlled trial in 72 patients with mild-to-moderate asthma and allergy to house dust mite ( HDM ; Dermatophagoides species ) was conducted to assess the effects of specific immunotherapy added to guideline -adjusted pharmacologic treatment and allergen avoidance . METHODS After 1 observational year of pharmacologic treatment and st and ard measures of HDM avoidance , 2 groups of asthmatic subjects were r and omly assigned to receive specific immunotherapy consisting of subcutaneous injections of either a mixture of Dermatophagoides pteronyssinus and Dermatophagoides farinae vaccine ( n=41 ) or placebo ( n=31 ) for 3 years . Medications were adjusted every 3 months according to the Global Initiative for Asthma guidelines . RESULTS The adjustment of treatment was associated with a reduction in asthma symptom scores in all subjects . The addition of specific immunotherapy was associated with a decrease in the number of subjects requiring rescue bronchodilators , an increase in morning and evening peak expiratory flow , and a reduced skin sensitivity to HDM extracts . The addition of specific immunotherapy had no significant effects on the cumulative dose of inhaled corticosteroids , asthma symptoms , lung volumes , or bronchial responsiveness to methacholine . CONCLUSION These results suggest that specific immunotherapy added to pharmacologic treatment and HDM avoidance provides marginal but statistically significant clinical benefits , possibly by reducing the allergic response of asthmatic patients sensitized to HDM Forty-one patients suffering from grass pollen allergy underwent specific immunotherapy with st and ardized allergen extract consisting of six grass pollens ( H-Al per os ) administered either sublingually or supralingually for one year . In order to investigate clinical and immunological changes induced by the administration of allergens via the oral mucosa , the double-blind , placebo-controlled , r and omized design of the trial with 30 other patients enrolled in placebo groups was applied . Specific immunotherapy with oral drops administered sublingually or supralingually was performed in the same way , keeping the drops under or on the tongue , respectively , for 1 - 2 min before swallowing them ; at the end of the trial the cumulative dose of the allergen was almost 20 times higher than that of the subcutaneous therapy with corresponding allergen preparation . Data about symptoms scores and drugs intake during grass pollen season , as well as skin reactivity , levels of specific IgG and IgE antibodies , before the study and after the study 's completion , were obtained . It was found that both routes of administration are effective according to subjective clinical parameters and drug consumption , with a highly significant reduction of symptoms and drug intake favoring sublingual administration where a reduction of more than 60 % was achieved . Only sublingual active group showed a significant increase in Dactylis glomerata-specific IgG serum levels . Adverse effects were limited to a small number of generally mild local and /or systemic reactions . The results suggest that the administration of allergens via the oral mucosa is safe and clinical ly effective , favoring the sublingual rather than supralingual route Sublingual immunotherapy ( SLIT ) has been recommended as a viable alternative to subcutaneous injection therapy in the treatment of airway allergies , though more data is needed from well-controlled studies for documenting its efficacy in different ethnic population s. Ninety-seven children ( age range 6 - 12 years ) , mild-to-moderate asthma with a single sensitization to mite allergen , were enrolled from 5 medical centers in Taiwan to evaluate the efficacy and safety of SLIT with st and ardized mite extracts , which contain Dermatophagoides pteronyssinus ( D.p . ) and Dermatophagoides farinae ( D.f . ) . Patients were double blinded and r and omly assigned to either a SLIT or placebo group . Following 24 weeks of study period , symptom and medication scores , lung function tests , skin prick tests , total serum IgE , and specific IgE to D.p . and D.f . were recorded . The results showed that there was statistically significant difference between these two groups in the analysis of daily ( P=0.011 ) , nighttime ( P=0.028 ) , and daytime ( P=0.009 ) asthmatic scores after 24 weeks of treatment . Patients receiving SLIT improved their forced vital capacity ( FVC ) , forced expiratory volume in 1s ( FEV1 ) , and peak expiratory flow ( PEF ) as compared to baseline ( P=0.042 , P=0.048 , and P=0.001 , respectively ) . No differences were found in skin prick test , total serum IgE and specific IgE to D.p . and D.f . Tolerance with high-dose SLIT was good with few minor adverse events reported . Our results indicated that a 24-week SLIT is of clinical benefit to mite-sensitive asthmatic children in Taiwan BACKGROUND Non-injective routes of immunotherapy are thought to be valuable therapeutic options for respiratory allergy . We investigated the clinical efficacy and the effects of sublingual/oral immunotherapy on conjunctival allergic inflammation in patients with mite-induced respiratory allergy . METHODS We used a double-blind placebo-controlled design . 20 patients with mite-induced rhinoconjunctivitis ( six of whom also had mild asthma ) were r and omly assigned sublingual/oral immunotherapy ( n=10 ) or placebo ( n=10 ) for 2 years . We assessed symptom score by diary cards and inflammatory-cell infiltrate , and expression of intercellular adhesion molecule 1 ( ICAM-1 ) in the conjunctiva after specific allergen challenge at enrollment and after 12 and 24 months of treatment . FINDINGS We found significantly lower symptom scores in the immunotherapy group than in the placebo group in most of the winter months ( p=0.05 ) . Compared with the placebo group , inflammatory-cell infiltration after conjunctival challenge , and ICAM-1 expression on conjunctival epithelium decreased significantly in the first year of treatment in the immunotherapy group ( p=0.04 and p=0.02 , respectively ) . These effects were also seen for the minimum persistent inflammation , in symptom-free patients exposed constantly to allergens ( p=0.02 ) . Serum concentrations of eosinophil cationic protein decreased significantly ( p=0.04 ) . Immunotherapy was well tolerated and compliance was good . INTERPRETATION Our results suggest that this immunotherapy is clinical ly effective in rhinoconjunctivitis and that it decreases the immune-mediated inflammatory responses to the allergen UNLABELLED Sublingual immunotherapy ( SLIT ) has been recognized as a viable alternative to subcutaneous immunotherapy for respiratory allergies both in adults and children , but clinical documentation about safety and efficacy in children is still poor . The purpose of this study was to assess the efficacy and tolerance of SLIT in children who are sensitized to grass pollen . METHODS Children with a clinical history of intermittent rhinoconjunctivitis , with or without mild asthma and positive skin prick tests to grass pollen , were selected to participate in a 2-year double-blind , placebo-controlled study with SLIT , using a grass extract ( ALK-Abellò ) . RESULTS 22 children were analyzed at the end of the study . No relevant side effects occurred in the active group . A statistically significant difference ( p = 0.05 ; Mann-Whitney test ) in favor of the active group ( n = 10 ) could be shown for drug consumption during the second year , as well as a significant improvement as compared to the first year of SLIT ( p = 0.05 ; Wilcoxon test ) . CONCLUSIONS Despite the small number of patients , our data suggest that SLIT with a grass pollen extract is well tolerated in children and is able to significantly reduce drug consumption during the second year of treatment . Studies in larger groups of children sensitized to both grass and tree pollens are needed to definitively assess the role of SLIT in intermittent , seasonal rhinitis and pollen asthma Background Immunotherapy is a recognized treatment for allergic respiratory diseases Parallel follow-up of clinical and inflammatory markers during sub-lingual immunotherapy ( SLIT ) is highly beneficial . Twenty-four children ( age 4 - 16 ) monosensitized to house dust mite were r and omized to receive either active or placebo SLIT for 1 yr in a double-blind placebo controlled design ( Marcucci et al. , Allergy 2003 : 58 : 657 - 62 ) . Thereafter , for 2 yr they all received active treatment . Symptom scores for rhinitis , asthma , and drug usage were daily recorded . Eosinophil cationic protein ( ECP ) and tryptase in sputum and nasal secretions , serum and nasal mite-specific immunoglobulin E ( IgE ) were recorded before treatment and at 10 - 12 months intervals . Nasal ECP and nasal tryptase after specific nasal provocation tests were significantly reduced as compared to baseline values ( p = 0.0043 and 0.0195 , respectively ) in the third year of active treatment . None of the other inflammatory parameters was increased . In placebo treated patients all these parameters tended to decrease only after switching to active treatment . Clinical scores did not improve in treated vs. placebo patients in the double-blind placebo-controlled phase of the study . In both cohorts a clinical benefit was observed as intra-group score reduction as compared to baseline . A significant difference was reached in patients treated for 2 yr for rhinitis and asthma ( p = 0.0009 and 0.0019 , respectively ) but not for drug usage and in patients treated for 3 yr for rhinitis , asthma , and drug usage ( p = 0.0105 , 0.0048 , and 0.02 , respectively ) . SLIT in children monosensitized to mites reverted the spontaneous increase in nasal IgE and in local parameters of allergic inflammation . These outcomes were followed by a consoli date d clinical improvement in the second and third year of treatment BACKGROUND Sublingual immunotherapy ( SLIT ) is considered safer and more convenient than subcutaneous therapy and therefore has been proposed as especially suitable for children and in primary care . Most efficacy studies in children lack power to be conclusive , and all have been performed in referral centers . OBJECTIVE To investigate the efficacy of SLIT with grass pollen allergen in children and adolescents with rhinoconjunctivitis in a primary care setting . METHODS Youngsters aged 6 - 18 years with hay fever were enrolled from general practice s and r and omly assigned to receive placebo or grass pollen mix for 2 years . The primary outcome was the mean daily total symptom score ( scale 0 - 15 ) comprising sneezing , itching nose , watery running nose , nasal blockage , and itching eyes during the months May-August of the second treatment year . RESULTS Out of 204 youngsters r and omized , 168 entered the intention-to-treat analysis ( 91 verum , 77 placebo ) . The mean daily total symptom score did not differ between participants allocated to verum and those allocated to placebo ( difference for verum minus placebo : -0.08 , 95%CI , -0.66 - 0.50 ; P = .78 ) . No differences were found for rescue medication-free days , disease-specific quality of life , and overall evaluation of the treatment effect . Local side effects were more frequent in the verum group ( 39 % vs 17 % of participants ; P = .001 ) . CONCLUSION Sublingual immunotherapy with grass pollen in a primary care setting is not effective in children and adolescents . CLINICAL IMPLICATION S Currently , SLIT can not be recommended for general practitioners as a therapeutic modality in youngsters with grass pollen allergy BACKGROUND Sublingual immunotherapy is well tolerated and data suggest its effectiveness for the treatment of allergic rhinitis in adults , but it lacks optimum dose definition . OBJECTIVE To assess the efficacy , safety , and optimal dose of grass pollen tablets for immunotherapy of patients with allergic rhinoconjunctivitis . METHODS In this multinational , r and omized , double-blind , placebo-controlled study , 628 adults with grass pollen rhinoconjunctivitis ( confirmed by positive skin prick test and serum-specific IgE ) received 1 of 3 doses of a st and ardized 5-grass pollen extract , or placebo , administered sublingually using a once-daily tablet formulation . The treatment was initiated 4 months before the estimated pollen season and continued throughout the season . The primary outcome was Rhinoconjunctivitis Total Symptom Score ; secondary outcomes included 6 individual symptom scores , rescue medication use , quality of life , and safety assessment s. RESULTS Both the 300-index of reactivity ( IR ) and 500-IR doses significantly reduced mean Rhinoconjunctivitis Total Symptom Score ( 3.58 + /- 3.0 , P = .0001 ; and 3.74 + /- 3.1 , P = .0006 , respectively ) compared with placebo ( 4.93 + /- 3.2 ) in the intent-to-treat and per- protocol analyses . The 100-IR group ( 4.70 + /- 3.1 ) score was not significantly different from placebo . Analysis of all secondary efficacy variables ( sneezing , runny nose , itchy nose , nasal congestion , watery eyes , itchy eyes , rescue medication usage , and quality of life ) confirmed the efficacy of the 300-IR and 500-IR doses . No serious side effects were reported . CONCLUSION In the first pollen season , the efficacy and safety of sublingual immunotherapy with grass tablets was confirmed . The 300-IR and 500-IR doses both demonstrated significant efficacy compared with placebo . CLINICAL IMPLICATION S The risk-benefit ratio favors the use of 300-IR tablets for clinical practice Background Previous studies suggest that sublingual immunotherapy ( SLIT ) represents a safer alternative to injection immunotherapy but equivalent efficacy is yet to be confirmed BACKGROUND Sublingual immunotherapy ( SLIT ) is a recognized and safe treatment for allergic rhinitis and conjunctivitis . The aim was to evaluate the efficacy and safety of tablets for grass and rye pollen- induced rhinitis and conjunctivitis . METHODS A double-blind , r and omized , placebo-controlled trial was carried out over 9 months . 105 patients received a st and ardized grass/rye mix extract or a placebo using sublingual drops during the build-up phase . Drops were replaced by sublingual tablets during the maintenance phase ( 300 IR/daily ) . RESULTS In patients that received active treatment , a significantly lower total symptom score ( rhinitis and conjunctivitis ) compared to the placebo group was observed ( p = 0.038 ) . The investigators ' assessment revealed a significant improvement in favor of the active treatment group ( p = 0.018 ) . Skin reactivity to grass and rye pollen was significantly reduced in the active treatment group ( p < 0.05 ) . No statistical difference was observed between the two groups for serum-specific IgG4 levels . Side effects were local and mild , and no severe systemic reactions were reported . CONCLUSION This study indicates that tablet-based sublingual immunotherapy was safe and significantly improved grass/rye pollen-induced rhinoconjunctivitis symptoms . It was also associated with a significant inhibition of the immediate skin response Few studies have evaluated the occurrence of immediate adverse reactions in allergic patients after an ultra-rush regimen of different commercial allergen extracts for sublingual immunotherapy ( SLIT ) Methods : 679 patients took part in trials of specific ultra-rush SLIT for the treatment of IgE – mediated rhinitis and /or IgE – mediated asthma . 14 patients received two different sublingual allergen vaccines during two distinct SLIT sessions . On the whole , 699 SLIT sessions were performed . The build up ultra-rush phase involved the administration every five minutes of increasing doses of either different allergen extracts . The cumulative allergen extract solution after half an hour was several times the dose administered at the start of subcutaneous immunotherapy ( range 4.7–525μg of major allergens ) . All patients tolerated the treatment very well . 122 ( 17.96 % ) had mild local symptoms ( pruritus of the buccal cavity ) that spontaneously disappeared with increasing dose . Two patients allergic to Parietaria had urticaria about three hours after the last sublingual Parietaria -extract intake . A subject allergic to Artemisia vulgaris pollen had urticaria and rhinitis two hours later than the last dose of vaccine . As reported in our previous study , no immediate severe adverse reactions were observed after that rapidly increasing doses of allergen extract were administered in a very short period to a large number of patients , showing the excellent safety profile of ultra-rush SLIT To evaluate the efficacy of specific sublingual immunotherapy ( SLIT ) , we enrolled 15 children with asthma and rhinitis ( 7 girls , 8 boys , mean + /- SD age of 11.7 + /- 3.3 ) allergic to house dust mite ( HDM ) into a double-blind , placebo-controlled study . After a run-in period , patients were r and omized to receive either placebo ( n = 7 ) or SLIT ( n = 8) with a st and ardized Dermatophagoides pteronyssinus ( D. pteronyssinus ) + Dermatophagoides farinea ( D. farinea ) 50/50 extract . They received increasing doses up to 100 index units of reactivity ( IR ) every day for 4 weeks , then 100 IR/day for another 4 weeks , followed by maintenance therapy consisting of 20 drops 2 times a week for 4 months . Efficacy was assessed at the end of 6 months of therapy according to symptom and medication scores , serum total IgE levels , results of lung function tests , methacholine provocation tests , and skin prick tests . Daily means for the asthma score and use of inhaled beta-2-mimetics decreased significantly in the SLIT group ( P = 0.05 , P = 0.028 , respectively ) , whereas no such difference was observed in the placebo group . At the end of follow-up , mean daily doses of intranasal steroids needed for control of rhinitis symptoms decreased significantly in the SLIT group ( P = 0.04 ) . Baseline skin sensitivity to D. pteronyssinus and D. farinea was not significantly different between in the two groups , whereas end-point wheal diameter obtained with D. pteronyssinus extract was significantly less in the SLIT vs. the placebo group ( P = 0.026 ) . At the end of 6 months , peak expiratory flow ( PEF ) values in the placebo group was significantly lower than in the SLIT group ( P = 0.049 ) . Throughout the treatment period , the SLIT group was found to have less asthma exacerbations than the placebo group ( P = 0.007 ) . The provocation concentration causing a 20 % drop in forced expired volume in 1 sec did not change throughout the treatment period in either groups . None of the patients reported local or systemic side effects from SLIT . Results of this study suggests that SLIT may be a useful alternative or additional therapy in the treatment of children with asthma/rhinitis due to HDM BACKGROUND Sublingual-swallow immunotherapy was recently recognized in the World Health Organization Position Paper ( Allergen immunotherapy : therapeutic vaccines for allergic diseases ) " as a viable alternative to parenteral injection therapy to treat allergic diseases " in adults . More controlled studies were required to assess the efficacy and safety of this treatment in children . OBJECTIVE This study was carried out to assess the clinical efficacy and safety profile of sublingual-swallow immunotherapy with high-dose allergen in children with allergies . METHODS We used a double-blind placebo-controlled design . Forty-one children with Parietaria -induced rhinoconjunctivitis were r and omized to receive sublingual st and ardized Parietaria judaica extract ( n = 20 ) or placebo ( n = 21 ) for 2 years . The cumulative dose of allergen was 375 times higher than that used in parenteral immunotherapy and the cumulative dose of Par j 1 major allergen was 52.5 mg over 2 years . The main efficacy assessment criteria were symptoms and rescue medication scores recorded on the patients ' diary cards . Secondary criteria were changes in skin and conjunctival specific reactivity as well as blood parameters , analyzed after 1 and 2 years of immunotherapy . The safety of the treatment was assessed by evaluating the frequency and severity of adverse effects . RESULTS A significant reduction in rhinitis symptoms was observed in the active treatment group during the second season ( P = .02 ) , with no difference in medication scores . A significant decrease in skin reactivity ( P = .002 after 2 years of treatment ) and an increase in the threshold dose for conjunctival allergen provocation test ( P = .02 ) were observed in the active treatment group compared with the group receiving placebo . A significant increase in specific IgG(4 ) levels ( P = .02 ) was also observed in the active group . Immunotherapy was well tolerated . CONCLUSION Sublingual-swallow immunotherapy in Parietaria -allergic children provided a clinical benefit and a decreased specific reactivity to the allergen . The safety profile of this treatment , which constitutes an important issue , indicated good tolerance and compliance BACKGROUND In light of the controversial status of sublingual immunotherapy in patients with allergic rhinitis , we undertook a double-blind study of this form of treatment . METHODS Forty-one subjects with cat allergy presenting as rhinoconjunctivitis underwent 105 days of sublingual immunotherapy , with 20 subjects receiving a st and ardized cat extract ( total dose approximately 4,500,000 allergy units ) and 21 a matching placebo . Effectiveness of treatment was assessed by changes in symptoms and nasal-blockage index during 90 minutes of exposure in an apartment containing cat d and er , which was performed before and after the course of treatment . Changes in cat-specific IgG and IgE levels and skin-test reactions were also monitored . RESULTS Although there were fewer symptoms and less nasal obstruction on cat d and er exposure at the end of the study the changes were not significantly different in those receiving active or placebo treatment . Specific IgG and IgE levels and prick skin test results did not change significantly during the course of the study . CONCLUSIONS We conclude that sublingual immunotherapy with high-dose st and ardized cat extract was no more effective than placebo in reducing symptoms or affecting immunologic measures of cat sensitivity The aim of this double-blind placebo-controlled study was to evaluate the efficacy and tolerability of short-term birch pollen sublingual immunotherapy . Forty-one patients suffering from allergic rhinoconjunctivitis caused by Betula alba were included . Exclusion criteria were the following : undergoing immunotherapy within the last 2 years , contraindications to immunotherapy , pregnancy and nursing . The treatment schedule comprised a 28-day basic course , followed by a 3-month maintenance treatment . The evaluation of the parameters was performed before treatment and 4 months after the last maintenance dose . Skin prick test and conjunctival provocation test ( CPT ) in a dilution series were carried out to determine the threshold of the reaction . The objective parameters used were the diameter of the skin wheals and the lowest concentration , of the allergen extract to induce the symptoms of itching and reddening of the eyes . The allergic reaction in general was evaluated with the help of a 2-h birch pollen challenge in the Vienna Challenge Chamber ( VCC ) ; nasal flow and resistance was measured by rhinomanometry ; and nasal secretion was quantified by weighing used h and kerchiefs . Bronchial reactions were objectified by spirometry ; subjective symptoms of the eyes , the nose and the bronchial tract were documented by the patients via a visual analog scale . Birch pollen specific IgE and IgG were evaluated by monoclonal antibody enzyme immunoassay before ( T0 ) and after ( T1 ) treatment . For statistics p < 0.05 was applied . At T0 there was no decisive difference in the in vitro and in vivo results between the two groups . After the treatment period ( T1 ) , actively treated patients showed a significantly higher tolerance to the birch pollen CPT ( p < 0.01 ) . The skin reaction was significantly lower than in the placebo group . Furthermore , actively treated patients produced less than half of the nasal secretion of placebo-treated patients during the challenge session . The rhinomanometry analysis during the challenge showed significant differences for verum and placebo in favor of the actively treated patients ( p = 0.033 ) . There was no significant difference in the specific IgE and IgG concentrations . The side effects and compliance during the treatment were comparable in both groups . In conclusion , sublingual immunotherapy is a well tolerated and clinical ly effective method of treatment BACKGROUND Sublingual immunotherapy ( SLIT ) is increasingly being used for the treatment of allergic rhinitis , but there are conflicting study results demonstrating clinical ly relevant efficacy . OBJECTIVE To show clinical efficacy and safety of a new high-dose grass pollen preparation for SLIT . METHODS In a 2-year , double-blind , placebo-controlled trial , 185 subjects with rhinitis or rhinoconjunctivitis , with or without asthma , were treated with a recently developed , high-dose , 6-grass pollen mixture for SLIT once daily . RESULTS The primary end point , a combined symptom-medication score , showed almost no change in the placebo group during a 42-day evaluation period in the grass pollen season from 2003 to 2005 , whereas active treatment was associated with a significant and clinical ly relevant improvement ( full analysis set , P = .01 ; main data set , P = .002 ) . The effect was irrespective of asthma diagnosis . Allergen-specific IgE showed no difference in both groups , and specific IgG4 and IgG1 increased with active treatment in the first and second study years compared with placebo , clearly indicating the immunogenic effect of the active treatment . The SLIT was well tolerated . No serious adverse drug reactions occurred . CONCLUSIONS High-dose , sublingual , specific immunotherapy with an extract of a 6-grass pollen mixture showed a significant and clinical ly relevant improvement in subjects with grass pollen-associated rhinitis or rhinoconjunctivitis , with or without asthma . The treatment with the sublingual solution was well tolerated Fifty eight patients under 12 years of age , positive to mites ( Dermatophagoides pteronyssinus and D. farinae ) according to prick , " in vitro " specific IgE and challenge tests , suffering from asthma and rhinitis , were r and omly assigned on a double blind basis to receive per os either a biologically st and ardized extract of mites ( active therapy TA = 30 patients ) or a saline buffered solution ( placebo = 28 patients ) . Patients took sublingually increasing doses of the solution , followed by maintenance therapy consisting of 15 drops 3 times a week . The results of the trial were assessed after 12 an 18 months , according to the following parameters : symptom scores recorded in diary cards , total and specific IgE levels , total IgG level , IgG1 and IgG4 levels , lymphocytes under population s , nasal challenge test , side effects . During the first 18 months , the patients on active therapy had significantly lower scores ( p less than 0.001 ) and clear variations of rhinomanometric parameters ( p less than 0.01 ) ; IgG also significantly increased . After 12 months , bronchial specific and specific challenge tests showed significantly higher threshold values in comparison to initial values ( p less than 0.05 ) . No statistically significative variation was registered in the placebo group Background : Clinical documentation about effects on local markers of inflammation of sublingual immunotherapy ( SLIT ) in children is still poor BACKGROUND Specific immunotherapy is widely used to treat allergic rhinitis , but few large-scale clinical trials have been performed . OBJECTIVE We sought to assess the efficacy and safety of specific immunotherapy with 2 doses of Alutard grass pollen in patients with moderately severe seasonal allergic rhinitis inadequately controlled with st and ard drug therapy . METHODS We performed a double-blind , r and omized , placebo-controlled study of 410 subjects ( 203 r and omized to 100,000 st and ardized quality units [ SQ-U ] maintenance , 104 to 10,000 SQ-U , and 103 to placebo ) . Three hundred forty-seven ( 85 % ) completed treatment . Groups were well matched for demographics and symptoms . RESULTS Across the whole pollen season , mean symptom and medication scores were 29 % and 32 % lower , respectively , in the 100,000-SQ-U group compared with those in the placebo group ( both P < .001 ) . Over the peak pollen season , mean symptom and medication scores were 32 % and 41 % lower , respectively , than those in the placebo group . The 10,000-SQ-U group had 22 % less symptoms than the placebo group over the whole season ( P < .01 ) , but medication scores reduced by only 16 % ( P = .16 ) . Quality -of-life measures confirmed the superiority of both doses to placebo . Local and delayed side effects were common but generally mild . Clinical ly significant early and delayed systemic side effects were confined to the 100,000-SQ-U group , but no life-threatening reactions occurred . CONCLUSIONS One season of immunotherapy with Alutard grass pollen reduced symptoms and medication use and improved the quality of life of subjects with moderately severe hay fever . The 100,000-SQ-U regimen was more effective , but the 10,000-SQ-U regimen caused fewer side effects Background Injective immunotherapy is a well‐known and recognized treatment for allergic diseases , but its safety has been question ed during recent years . Alternative administration routes have been proposed and there is a growing interest and experience in sublingual therapy . The safety of alternative routes is nonetheless a real advantage , so long as it is not counterbalanced by a loss of clinical benefit Sublingual immunotherapy is safe and efficacious in the treatment of patients with allergic rhinitis . The clinical and biological efficacy of modified allergens ( allergoids ) has not been fully clarified . We investigated in birch allergic patients the effect of a pre-co-seasonal sublingual immunotherapy regimen with a modified allergen extract on clinical parameters and on T cell proliferation and regulatory cytokine production ( IL-10 , TGF-beta ) . We found that during the birch pollen season symptoms and drug usage scores were 30 and 40 % improved , respectively , in treated versus control subjects ( p<0.0001 for both comparisons ) whereas well days were 23.5 ( 33 % ) versus 16.9 ( 23 % ) ( p=0.0024 ) , respectively . Bet v 1 allergen specific proliferation decreased ( p = 0.0010 ) , whereas IL-10 transcription increased ( p = 0.0010 ) in treated , but not in control patients . Moreover , TGF-beta transcription was increased , although not significantly ( p=0.066 ) , following immunotherapy . Thus , sublingual immunotherapy with modified allergen in birch-allergic subjects was safe , clinical ly efficacious and associated with the reduction of allergen-specific proliferation and with the increased production of the IL-10 regulatory cytokine OBJECTIVE The research ers sought to assess whether the widely used 1994 Cochrane Highly Sensitive Search Strategy ( HSSS ) for r and omized controlled trials ( RCTs ) in MEDLINE could be improved in terms of sensitivity , precision , or parsimony . METHODS A gold st and ard of 1,347 RCT records and a comparison group of 2,400 non-trials were r and omly selected from MEDLINE . Terms occurring in at least 1 % of RCT records were identified . Fifty percent of the RCT and comparison group records were r and omly selected , and the ability of the terms to discriminate RCTs from non-trial records was determined using logistic regression . The best performing combinations of terms were tested on the remaining records and in MEDLINE . RESULTS The best discriminating term was " Clinical Trial " ( Publication Type ) . In years where the Cochrane assessment of MEDLINE records had taken place , the strategies identified few additional unindexed records of trials . In years where Cochrane assessment has yet to take place , " R and omized Controlled Trial " ( Publication Type ) proved highly sensitive and precise . Adding six more search terms identified further , unindexed trials at reasonable levels of precision and with sensitivity almost equal to the Cochrane HSSS . CONCLUSIONS Most reports of RCTs in MEDLINE can now be identified easily using " R and omized Controlled Trial " ( Publication Type ) . More sensitive search es can be achieved by a brief strategy , the Centre for Review s and Dissemination/Cochrane Highly Sensitive Search Strategy ( 2005 revision ) Background : New routes of administering immunotherapy in respiratory allergy are being studied as an alternative to conventional injective immunotherapy . We carried out a study to evaluate the clinical efficacy and effects of sublingual immunotherapy in patients with Parietaria judaica‐induced respiratory allergy For evaluation of the efficacy and the safety of specific sublingual immunotherapy with high allergen dose , 66 children with seasonal asthma , rhinitis , and conjunctivitis due to sensitization to olive pollen were enrolled in a double‐blind , r and omized , placebo‐controlled study between October 1994 and October 1996 in Greece . Thirty‐four patients were r and omly allocated to the active group , and 32 received placebo . Immunotherapy consisted of olive‐allergen extracts ( Stallergenes SA ) administered sublingually pre‐ and coseasonally from January to July for 2 consecutive years . Serial concentrations from 1 to 300 IR were used up to the maintenance dose of 20 drops of 300 IR daily . The cumulative dose for each patient was 300 times higher than in parenteral immunotherapy , and the cumulative dose of the major allergen Ole e 1 was 8.1 mg/2 years . The patients were assessed by clinical parameters ( symptom and medication scores from patients ' daily diaries ) and immunologic measurements ( specific IgE. lgG4 . eosinophil cationic protein [ ECP ] ) were performed . The actively treated patients had a significantly lower score for dyspnea ( P<0.04 during the first season ; P<0.03 during the second season ) . At the poUinic peak during the second year , a lower score of conjunctivitis was recorded ( P<0.05 ) in the actively treated patients . The analysis of intragroup evolution showed that the total score of rhinitis increased significantly during the pollinic peak in the group under placebo , whereas there was no symptomatic peak for the same period in the group under active treatment . However , the difference between the groups was not significant . The medication score did not differ significantly between the groups . Oral steroids were the only variables with a P value near the significance level ( P=0.06 ) in favor of the actively treated group . A significant decrease in skin reactivity was recorded in the active group after 2 years of treatment . No significant variation in specific IgE and IgG4 was detected . A significantly lower level of serum ECP was observed at the pollinic peak in the actively treated patients during the first pollen season ( P=0.01 ) , but this was not confirmed the second year when the ECP levels doubled in both groups without correlation to the clinical findings . Tolerance was excellent with only a few minor side‐effects reported . In conclusion , high‐dose specific sublingual immunotherapy appears to be safe and effective in improving mild seasonal asthma and conjunctivitis linked to olive‐pollen sensitization The clinical efficacy of sublingual immunotherapy ( SLIT ) has been demonstrated , but its mechanism of action is still controversial . The most recent experimental observations suggest that a critical role in the modulation of immune response is sustained by Th2 cytokines , such as interleukin-4 ( IL-4 ) , IL-5 and IL-13 , by co-stimulatory molecules , such as CD40 on B cells , and by hormones and neuropeptides . To better underst and whether SLIT affects immune responses we used a double-blind placebo-controlled design . Eighty-six children with mild asthma due to allergy to Dermatophagoides pteronyssinus ( 33 of whom also had rhinoconjunctivitis ) were r and omly assigned SLIT ( n = 47 ) or placebo ( n = 39 ) . We assessed symptom scores using diary cards of each patient and determined the expression of CD40 on B cells and the serum concentration of ECP , IL-13 , prolactin ( PRL ) and ACTH at enrolment and after 6 months of therapy . We observed a significant reduction in asthma and rhinitis scores in the immunotherapy group compared with the placebo group , no variation in CD40 and ACTH , but a significant decrease in ECP , IL-13 and PRL after 6 months of therapy ( p < 0.01 ) . Our results confirm the efficacy and safety of SLIT , and lead us to believe that it could modulate the synthesis of Th2 cytokines , as revealed from the decrease of IL-13 . In addition , the reduction of PRL might be a signal of reduced activation of T lymphocytes BACKGROUND Seasonal allergic rhinitis ( SAR ) induced by Japanese cedar pollen is a substantial problem in Japan . Sublingual immuno-therapy ( SLIT ) is safer than conventional antigen-specific immunotherapy , the only treatment modality by which complete cure of the disease can be expected . We investigated the safety and efficacy of SLIT in the treatment of cedar pollinosis patients compared to placebo . METHODS A r and omized , placebo-controlled , double-blind study was conducted in 61 cedar pollinosis patients . Increasing doses of st and ardized Japanese cedar extract or placebo were administered sublingually in intervals ranging from daily to once a week after six weeks . The primary efficacy variable was the mean of the daily total symptom scores ( TSS ) during the pollen dispersing period . Secondary efficacy variables included the QOL scores and related variables . RESULTS Primary efficacy variable scores were significantly lower for some days in the SLIT group than in the placebo group ( P < .01 or P < .05 ) . Secondary efficacy for the QOL score in SLIT group was almost of half of placebo group . There was no significant difference in the overall incidence of side effects between the SLIT group and the placebo group . CONCLUSIONS SLIT was effective and safe in the treatment of cedar pollinosis Background : The efficacy and safety of sublingual immunotherapy ( SLIT ) in patients with chronic rhinitis related to sensitization to house dust mites are still controversial BACKGROUND Sustained and disease-modifying effects of sublingual immunotherapy have never before been confirmed in a large-scale r and omized , double-blind , placebo-controlled trial . OBJECTIVE We sought to investigate sustained efficacy 1 year after a 3-year period of daily treatment with the SQ-st and ardized grass allergy immunotherapy tablet Grazax ( Phleum pratense 75,000 SQ-T/2,800 BAU ; ALK-Abelló , Hørsholm , Denmark ) . METHODS A r and omized , double-blind , placebo-controlled , phase III trial including adults with a history of moderate-to-severe grass pollen induced rhinoconjunctivitis inadequately controlled by symptomatic medications . The analysis set comprised 257 subjects at the follow-up . Efficacy end points were rhinoconjunctivitis symptom and medication scores , quality of life , and percentages of symptom and medication free days . Immunologic end points included grass pollen-specific serum IgG4 and IgE-blocking factor . Safety was assessed based on adverse events . RESULTS Significant improvements in efficacy were consistently shown during 3 years ' treatment . One year after treatment , the active group showed sustained reductions in mean rhinoconjunctivitis symptom scores ( 26 % , P < .001 ) and medication scores ( 29 % , P = .022 ) when compared with placebo . This level was similar to the efficacy observed during the 3-year treatment period . The differences in percentages of symptom- and medication-free days were significant during and 1 year after treatment . The active group also reported sustained and significant improvements in quality of life . Sustained clinical benefit was accompanied by immunologic changes . No safety issues were identified . CONCLUSION Three years of treatment with the SQ-st and ardized grass allergy immunotherapy tablet result ed in consistent clinical improvement and accompanying immunologic changes that were sustained 1 year after treatment , which is indicative of disease modification and associated long-term benefits BACKGROUND Seasonal allergic rhinitis is common and troublesome . Sublingual immunotherapy ( SLIT ) has been proposed as an alternative to injection immunotherapy and might offer some advantages if it were effective and practical in a community setting . OBJECTIVES To assess the efficacy and side-effect profile of SLIT in patients with summer hay fever uncontrolled on current st and ard medication . To assess the feasibility of delivering SLIT in a United Kingdom general practice setting . METHODS Double-blind , placebo-controlled study in 186 patients with severe summer hay fever identified from 16 United Kingdom general practice s. After a baseline year to ensure balanced groups , subjects were r and omized , and SLIT was given for 1 or 2 years and compared with placebo . The principal outcome measure was symptoms as recorded on diary cards . Secondary criteria were skin and conjunctival reactivity , allergen-specific IgE and IgG 4 , and the frequency and severity of adverse effects . RESULTS One hundred thirty-six subjects completed the study . After 1 year , no significant differences were found between actively treated subjects and the placebo group . After the second year of therapy , subjects who had received 2 years treatment were 6.8 times more likely to show a reduction in nose running ( P < .001 ) and 2.4 times more likely to have reduced sneezing ( P < .05 ) compared with subjects in the placebo group . Benefits for nasal blockage were found at the peak pollen season and were similar in both actively treated groups . CONCLUSION Sublingual immunotherapy can be given successfully and safely in the community . High-dose SLIT has beneficial effects on nasal symptoms during the peak pollen season in patients with severe seasonal allergic rhinitis . At least 2 years of treatment with SLIT is required to show a benefit Background : Sublingual‐swallow immunotherapy ( SLIT ) is an accepted treatment for allergic rhinitis but its optimal dosage is scantly investigated . We studied the dose dependence of clinical efficacy and immunological response to SLIT by administering two different dosages of the same allergen in rhinitic children monosensitized to grass pollen Background : Sublingual immunotherapy ( SLIT ) has been demonstrated to be a viable alternative to injection immunotherapy . Administration of high doses of allergens to ensure efficacy has been shown to be well tolerated . The aim of the present study was the first step to address the issue of fast-induction regimens using various induction SLIT regimens in paediatric and adult patients . Methods : Sixty-four patients ( age range 5–46 years ) with grass pollen rhinoconjunctivitis were enrolled in an 8-month double-blind , placebo-controlled trial of SLIT . Sixty-three patients were r and omized to four groups and evaluated at the end of the study . One group received placebo ( n = 16 ) and the other three groups ( n = 47 ) received five grass pollen extracts according to three different induction regimens : regimen 1 starting with 3 IR tablets ( n = 15 ) , regimen 2 starting with 10 IR ( n = 16 ) and regimen 3 starting with 30 IR ( n = 16 ) . The maintenance phase was made with sublingual-swallow drops at the same concentration of 300 IR/ml for all the patients . Adverse events were recorded on diary cards . Results : During induction phase , 25/47 patients in the SLIT groups had adverse reactions in comparison to 2/16 patients in the placebo group ( p < 0.05 ) . The rate of adverse reactions was 33.3 % ( 11.8–61.6 ) ( 95 % CI ) for regimen 1 , 31.3 % ( 11.0–58.7 ) for regimen 2 , 43.8 % ( 19.8–70.1 ) for regimen 3 and 12.5 % ( 1.6–38.3 ) for placebo . Fifty-seven reactions were local reactions involving the oral region ( 54 SLIT , 3 placebo ) and 13 were systemic reactions ( all in the SLIT groups ) . 11/13 reactions were mild ( gastrointestinal disorders , rhinoconjunctivitis ) , 1/13 consisted of moderate asthma and 1/13 consisted of severe abdominal pain . No urticaria , angioedema or life-threatening events were observed . Conclusions : These preliminary data showed that various induction regimens for SLIT are generally well tolerated and could allow a fast build-up phase of SLIT BACKGROUND non-injective routes of immunotherapy in respiratory allergy have being proposed as an alternative to conventional immunotherapy . We carried out a study to evaluate the clinical efficacy and effects sublingual immunotherapy ( SLIT ) in patient with Cupressaceae pollen respiratory allergy . METHODS twenty patients with Cupressaceae pollen ( C. sempervirens ) rhinoconjunctivitis , mild asthma or both were r and omly chosen for sublingual immunotherapy ( 10 patients ) or placebo treatment ( 10 patients ) using a double blind placebo controlled technique . We have used an extract of Cupressus arizonica because of its better stability in solution and its crossreactivity with Cupressus sempervirens . The patients underwent treatment for 12 months ( from april 1999 to april 2000 ) . Symptoms and drug scores as well as nasal provocation tests were recorded . The pollen counts were carried out , during all the same period . RESULTS we found significantly lower symptom scores ( p < 0.05 ) and drug consumption scores ( p < 0.05 ) in the immunotherapy group than in the placebo group , during the pollen season , after the first year of therapy . Besides threshold of allergen reactivity in nasal provocation tests was increased in the active group ( p < 0.01 ) . No untoward reactions have been observed . CONCLUSIONS SLIT with Cupressus arizonica ( pollen extracts ) produced , after one year treatment , a significant improvement of allergic symptoms and a decrease of drug consumption scores and allergen-specific nasal reactivity . SLIT with Cupressus arizonica appeared to be effective and safe in the treatment of Cupressaceae pollen respiratory allergy In a multi-centre , r and omized , double-blind , placebo-controlled clinical trial over 3 years high dose sublingual specific immunotherapy with an extract of a 6-grass-pollen mixture showed a highly significant and clinical ly relevant improvement in patients with grass pollen rhinitis/-conjunctivitis with or without asthma and an increase in allergen specific antibodies ( IgG1 , IgG4 ) indicating immunological efficacy . A difference of 46 % in mean symptom medication score between active and placebo group was seen . The treatment with the sublingual solution was well tolerated . High dose sublingual immunotherapy can therefore be considered as an efficient therapeutic option in the management of IgE-mediated allergic airway diseases BACKGROUND To date , there have been no r and omized , double-blind studies showing the effectiveness of sublingual immunotherapy with multiple allergens . OBJECTIVE The purpose of this study was to examine whether the efficacy of sublingual immunotherapy ( SLIT ) with st and ardized timothy extract was reduced by combination with other allergen extracts . METHODS A single-center , r and omized , double-blind , placebo-controlled trial with SLIT was conducted . After an observational grass season , SLIT was administered for 10 months to 54 patients r and omized to 1 of 3 treatment arms : placebo , timothy extract ( 19 microg Phl p 5 daily ) as monotherapy , or the same dose of timothy extract plus 9 additional pollen extracts . Symptom and medication scores were collected and titrated nasal challenges , titrated skin prick tests , specific IgE , IgG4 and cytokines release by timothy-stimulated lymphocyte proliferation were performed . RESULTS Perhaps because of a very low grass pollen season in 2008 , there were no significant differences in medication or symptom scores in either treatment group compared with placebo . Compared with placebo , in the timothy monotherapy group , thresholds for titrated nasal challenge and skin prick tests ( P = .03 and P = .001 , respectively ) , and serum-specific IgG4 levels ( P = .005 ) significantly increased , and IFN- gamma levels decreased ( P = .02 ) , whereas in the multiallergen group , there was significant improvement only in the titrated skin prick tests ( P = .04 ) which was less than in the monotherapy group . There were no significant differences between the 2 active groups in any outcome measure , and both active groups experienced more adverse events than placebo . There were no systemic reactions . CONCLUSION Improvement in multiple relevant outcomes strongly suggests that SLIT with timothy extract alone was effective ; however , the results for symptom and medication scores were not significant . The differences between multiple allergen SLIT and placebo only in skin sensitivity to timothy suggest a reduction in SLIT efficacy in this group . However , further studies are required to confirm these observations Background : Immunotherapy through local routes is thought to be a valuable therapeutic option for respiratory allergy . We investigated the clinical efficacy and immunologic effects of sublingual immunotherapy ( SLIT ) in asthmatic children with mite‐induced respiratory allergy In a double‐blind placebo‐controlled cross‐over trial , low dose sublingual therapy with house dust mite was effective in relieving symptoms in 72 % of the group of patients with perennial rhinitis due to house dust mite ( P < 0·03 ) . Following active treatment , there was a significant increase in morning peak nasal inspiratory flow rate ( P < 0·01 ) in those who improved ( thirteen out of eighteen ) and resistance to nasal provocation with house dust mite also increased , in some cases up to 1000‐fold ( P < 0·05 ) . Oral therapy is safe and avoids the side effects of desensitizing injections which can be serious . The potential for oral desensitization is great and further studies on this form of treatment are needed Background : The safety and efficacy of sublingual‐swallow immunotherapy ( SLIT ) in rhinitis caused by house‐dust mite were evaluated in a double‐blind , placebo‐controlled study including 75 patients for 24 months Background : Both sublingual allergen‐specific immunotherapy ( SLIT ) and subcutaneous immunotherapy ( SCIT ) have a documented clinical efficacy , but only few comparative studies have been performed Thirty patients with asthma and /or monosensitized allergic rhinitis caused by grass pollen whose ages ranged from 15 to 35 years were selected . Two groups were established at r and om : an active group and a placebo group , and a double‐blind study was done on treatment with immunotherapy for a period of 3 continuous years , with initiation doses administered according to the rush immunotherapy technique . Grass‐pollen allergen extract Alutard SQ and histamine as a placebo were used . The objective parameters of efficacy evaluated were end‐point cutaneous tests , conjunctival provocation , bronchial provocation , and symptom/medication scores , as well as specific immunoglobulin determinations . The statistical evaluation of the results was significant for the differences existing between the initial and final time of the active group , and there were significant differences between the two groups for all of the parameters considered . We found no relationship between clinical improvement and the range of specific immunoglobulin E values . Regarding the safety of the treatment , systemic adverse effects were manifested only in the initial phase ( rush immunotherapy ) . and were easily controlled by treatment . We conclude that the efficacy and safety of immunotherapy with grass pollen make it possible to consider this treatment fundamental in these patients Background : Japanese cedar pollen represents an important and unique allergen . Sublingual immunotherapy ( SLIT ) has been suggested to be a highly effective route of desensitization against a variety of allergens . However , little information is available about its use in cedar pollen allergy . Methods : A blinded r and omized , placebo-controlled trial employing SLIT for cedar pollinosis was conducted over a period of 6 months . Sixty-seven subjects were enrolled and the symptom scores during the pollen season were evaluated by a symptom diary , measurement of cedar-specific IgE and IgG4 , and determination of Cry j-specific Th2 clones before SLIT and before and after the pollen season . Results : No major adverse effects were observed in either group . The serum-specific IgG4 activity increased significantly after SLIT in the active group . The active group also exhibited significantly lower symptom scores compared to the placebo . The specific Th2 clone sizes were not significantly different between the groups before the pollen season . However , an increase in the clone size was observed after the pollen season in the placebo group , but not in the active group . Conclusion : Use of SLIT for Japanese cedar pollinosis was found to be safe and associated with an increase in cedar-specific IgG4 levels . Such therapy inhibited the increase in Cry j-specific Th2 clone size induced by pollen exposure . Finally , use of SLIT result ed in significant improvement of the clinical symptoms of cedar pollinosis in this patient population . These observations suggest that SLIT may offer another safe approach to the management of cedar pollinosis Background : Recent studies have demonstrated the efficacy of sublingual‐swallow immunotherapy ( SLIT ) in seasonal and perennial rhinitis . Sublingual administration of solutions is not convenient for all patients . The aim of the study was to evaluate the efficacy and safety of immunotherapy administered sublingually , initially as drops , and then as tablets during maintenance therapy BACKGROUND The efficacy of therapy with sublingual allergen extracts is unproven . OBJECTIVE To evaluate the clinical and immunologic outcome of sublingual immunotherapy and to compare the results with subcutaneous immunotherapy and placebo in 36 patients with rhinitis and asthma due to mite allergy . METHOD Thirty-six patients with rhinitis and asthma due to mite allergy were r and omly divided into three groups in order to receive subcutaneous injections with allergenic extracts , sublingual drops with solutions of purified st and ardized allergen preparations , or sublingual placebo for a period of 1 year . Assessment of clinical and immunologic efficacy included symptom and medication scores , methacholine provocation tests , skin prick tests , and specific IgE and IgG4 antibody concentrations . RESULTS Subcutaneous immunotherapy for both rhinitis and asthma was clinical ly effective . Patients treated with sublingual immunotherapy had decreased rhinitis symptoms ( P < .01 ) but no change in asthma scores . Medication scores significantly decreased in both actively treated groups ( P < .01 ) at the first year compared with baseline . When skin prick tests were evaluated , the subcutaneously treated group had a significant decrease in the wheal diameter of D. pteronyssinus ( P < .01 ) , D. farinae ( P < .05 ) , and histamine ( P < .05 ) while other two groups showed no difference . There was no significant change in methacholine PC20 values in all groups at the end of the first year when compared with baseline . No change in D. pteronyssinus and D. farinae specific IgE levels were observed ; however , specific IgG4 concentrations were significantly higher than baseline both in sublingual and subcutaneous immunotherapy groups ( P < .05 ) after 1 year immunotherapy . No significant difference was obtained in any of these parameters in the placebo group . CONCLUSION Sublingual immunotherapy may be effective in patients with allergic rhinitis . Further , we believe it is a potential therapy for allergic asthmatic patients . The clinical usefulness of this form of immunotherapy ( when administered to larger study groups for a longer time ) and the mechanisms underlying its immunologic effect deserve additional studies Background : We assessed the efficacy of preseasonal local allergoid immunotherapy in a group of children with asthma and /or rhinitis and /or rhinoconjunctivitis due to grass pollen BACKGROUND The local ( noninjection ) routes of immunotherapy are presently regarded as viable therapeutic options for respiratory allergy , and their mechanisms of action are currently undergoing investigation . OBJECTIVE We evaluated the clinical efficacy of a preseasonal rush sublingual-swallow immunotherapy and its effects on allergic inflammation in patients with seasonal rhinoconjunctivitis caused by Parietaria species . METHODS Thirty patients with Parietaria species-induced rhinoconjunctivitis ( 13 with mild intermittent asthma ) were r and omly assigned sublingual-swallow immunotherapy or placebo in a rush preseasonal course . We assessed the seasonal symptom-drug intake score by diary card and the inflammatory infiltration and the intercellular adhesion molecule 1 expression on nasal epithelium after specific allergenic challenge before and after treatment . RESULTS The investigated immunotherapy was well tolerated , and no side effects were recorded . A significant reduction of the symptom score ( P = .016 ) and drug intake score ( P = . 008 ) after immunotherapy was observed only in the active group . A decrease of the cumulative score was observed also in the placebo group ( P = .046 ) , but the significance was clearly higher ( P = .006 ) in the active group . In the active group a reduction of neutrophils ( P = .001 ) , eosinophils ( P = .01 ) , and intercellular adhesion molecule 1 expression ( P = .04 ) after specific nasal challenge was also detected . CONCLUSION The present results suggest that this sublingual-swallow immunotherapy administered through a rush schedule is clinical ly effective and safe and that it decreases the immune-mediated inflammatory responses to the allergen Fifty‐eight patients with well‐documented history of seasonal rhinoconjunctivitis caused by grass pollens were allocated r and omly on a double‐blind basis to receive either sublingual therapy with a solution of purified , st and ardized allergen preparation ( Stallergenes ) or a matched placebo for 17 weeks . The assessment of the effect of oral immunotherapy , done with drops of five‐grass allergen extract , was on the clinical symptoms and on the medication score of the authorized rescue treatments . The actively treated patients had significantly ( P<0.05 to P<0.01 ) fewer symptoms of rhinitis ( sneezing and rhinorrhea ) and of conjunctivitis ( redness and tears ) during the pollen season than the placebo group . Consumption of nasal solution of sodium cromoglycate and of betamethasone and dexchlorpheniramine was significantly less in the desensitized group ( P<0.01 ) . Side‐effects were negligible . This study concludes that perlingual immunotherapy with grass pollen extract in grass‐pollen‐sensitive seasonal hay fever and conjunctivitis patients is effective , easy to perform , inexpensive , and safe Background Allergic conjunctivitis ( AC ) is frequently associated with allergic rhinitis ( AR ) and affects up to 91 % of patients with AR . Desloratadine , an orally administered , non‐sedating second‐generation antihistamine , has proven efficacy and safety in the control of nasal and non‐nasal – including ocular – symptoms of AR . This r and omized‐controlled trial is the first to evaluate the effects of continuous oral desloratadine treatment on ocular symptoms after conjunctival allergen challenge |
834 | 32,168,461 | FP/SAL is recommended for the initiation therapy just in a small percentage of symptomatic patients that are at high risk of exacerbation with blood eosinophil counts ≥300 cells per μl . | Introduction : Recently , the generic formulation of FP/SAL FDC has been approved in COPD .
Although FP/SAL FDC has been the first long acting FDC approved in COPD , no systematic review assessed the effect of this combination for the treatment of COPD by considering specifically Phase IV studies .
The aim of this review was to systematic ally assess the effect of FP/SAL FDC in COPD patients enrolled in Phase IV studies .
Areas covered : The question of this systematic review was to examine the evidence regarding the impact of FP/SAL FDC for the treatment of COPD by search ing for Phase IV studies in the Clinical Trials.gov data base . | Purpose Triple therapy using salmeterol/fluticasone propionate ( FP ) and tiotropium bromide is commonly used to treat chronic obstructive pulmonary disease ( COPD ) , but sparse efficacy data exist in COPD patients with fewer symptoms and with a lower dose of inhaled corticosteroid in Japanese patients . The effects of of salmeterol/fluticasone propionate 50/250 μg ( SFC250 ) twice daily plus tiotropium 18 μg ( TIO ) once daily and individual treatments on lung function were compared . Patients and methods Fifty three Japanese COPD patients participated in this r and omized , double-blind , double-dummy , Williams square design crossover study . Lung function was assessed by plethysmography and spirometry . Results The primary endpoint of postdose specific airway conductance area under the curve ( AUC0–4h ) on day 28 was significantly higher following SFC250 + TIO ( 0.854 ) compared with TIO ( 0.737 , 15.8 % ) and SFC250 ( 0.663 , 28.8 % ) alone . SFC250 + TIO significantly improved trough forced expiratory volume in 1 second from baseline versus TIO ( 0.161 L , P<0.001 ) and SFC250 ( 0.103 L , P=0.008 ) . SFC250 + TIO significantly improved residual volume compared with TIO ( P<0.001 ) and SFC250 ( P=0.003 ) on day 28 . Nonsignificant improvements were seen in trough inspiratory capacity , total lung capacity , and thoracic gas volume . There was no mean change seen in rescue medication . Conclusion Triple therapy using SFC250 + TIO was well tolerated and gave a greater improvement in bronchodilation compared with TIO and SFC250 alone in Japanese patients with COPD . There was improvement in few symptoms , but no mean change was seen in patient-reported outcomes measured by rescue medication use Purpose : To provide information on the efficacy and safety of Fluticasone Propionate/Salmeterol Hydrofluoroalkane 134a Metered-Dose-Inhaler 230/42mcg ( FSC MDI ) and its comparable dose of Fluticasone Propionate/Salmeterol DISKUS 250/50mcg ( FSC DISKUS ) in patients with COPD . Methods : This multicenter , r and omized , double-blind , 12 week study was design ed to evaluate FSC MDI treatment responses as compared with FSC DISKUS . The primary comparison of interest was non-inferiority between the FSC MDI treatment group and the FSC DISKUS treatment group assessed in terms of 2-hour post-dose FEV1 change from baseline at endpoint . The non-inferiority criterion bound was 75mL ( lower confidence limit of -75mL ) . Inclusion criteria : Male or female aged ≥ 40 , post-bronchodilator FEV1 ≤ 70 % predicted normal , FEV1/FVC ≤ 70 % and ≥ 10 pack years smoking history . Adverse events were recorded by patients throughout the study on daily diary cards . Adverse events were collected in eCRFs at all clinic visits and during a final follow-up phone call . Results : Patients ( N=247 ) were r and omized to FSC MDI ( FEV1 % 49.3 ± 12.3 , FEV1/FVC 50.5 ± 10.0 ) and FSC DISKUS ( FEV1 % 48.4 ± 11.0 , FEV1/FVC 50.3 ± 10.3 ) . From an ANCOVA model the least squares ( LS ) mean difference ( FSC MDI– FSC DISKUS ) for the 2-hour post dose FEV1 at endpoint was -2.0mL ( 95 % CI -64mL , 59mL ) . Pre-dose FEV1 , FVC , PEF , and albuterol use were also similar between the two formulations . The most common adverse events ( AE ) during treatment were headache ( 8 % and 6 % of patients ) , nasopharyngitis ( 4 % and 6 % ) , cough ( 3 % and 4 % ) , and sinusitis ( 2 % and 5 % ) for FSC MDI and FSC DISKUS , respectively . Pneumonia was recorded as an AE for 2 ( 2 % ) patients in the FSC DISKUS arm . Conclusion : This is the first study to demonstrate that FSC MDI has a similar efficacy and safety profile to FSC DISKUS in COPD patients Background Supporting 21st century health care and the practice of evidence -based medicine ( EBM ) requires ubiquitous access to clinical information and to knowledge-based re sources to answer clinical questions . Many questions go unanswered , however , due to lack of skills in formulating questions , crafting effective search strategies , and accessing data bases to identify best levels of evidence . Methods This r and omized trial was design ed as a pilot study to measure the relevancy of search results using three different interfaces for the PubMed search system . Two of the search interfaces utilized a specific framework called PICO , which was design ed to focus clinical questions and to prompt for publication type or type of question asked . The third interface was the st and ard PubMed interface readily available on the Web . Study subjects were recruited from interns and residents on an inpatient general medicine rotation at an academic medical center in the US . Thirty-one subjects were r and omized to one of the three interfaces , given 3 clinical questions , and asked to search PubMed for a set of relevant articles that would provide an answer for each question . The success of the search results was determined by a precision score , which compared the number of relevant or gold st and ard articles retrieved in a result set to the total number of articles retrieved in that set . Results Participants using the PICO templates ( Protocol A or Protocol B ) had higher precision scores for each question than the participants who used Protocol C , the st and ard PubMed Web interface . ( Question 1 : A = 35 % , B = 28 % , C = 20 % ; Question 2 : A = 5 % , B = 6 % , C = 4 % ; Question 3 : A = 1 % , B = 0 % , C = 0 % ) 95 % confidence intervals were calculated for the precision for each question using a lower boundary of zero . However , the 95 % confidence limits were overlapping , suggesting no statistical difference between the groups . Conclusion Due to the small number of search es for each arm , this pilot study could not demonstrate a statistically significant difference between the search protocol s. However there was a trend towards higher precision that needs to be investigated in a larger study to determine if PICO can improve the relevancy of search results Long-acting muscarinic antagonist ( LAMA ) or long-acting β2-agonist ( LABA ) bronchodilators and their combination are recommended for the maintenance treatment of chronic obstructive pulmonary disease ( COPD ) . Although the efficacy of LAMAs and LABAs has been well established through r and omized controlled trials ( RCTs ) , questions remain regarding their cardiovascular ( CV ) safety . Furthermore , while the safety of LAMA and LABA monotherapy has been extensively studied , data are lacking for LAMA/LABA combination therapy , and the majority of the studies that have reported on the CV safety of LAMA/LABA combination therapy were not specifically design ed to assess this . Evaluation of CV safety for COPD treatments is important because many patients with COPD have underlying CV comorbidities . However , severe CV and other comorbidities are often exclusion criteria for RCTs , contributing to a lack in external validity and generalizability . Real-world observational studies are another important tool to evaluate the effectiveness and safety of COPD therapies in a broader population of patients and can improve upon the external validity limitations of RCTs . We examine what is already known regarding the CV and cerebrovascular safety of LAMA/LABA combination therapy from RCTs and real-world observational studies , and explore the advantages and limitations of data derived from each study type . We also describe an ongoing prospect i ve , observational , comparative post-authorization safety study of a LAMA/LABA combination therapy ( umeclidinium/vilanterol ) and LAMA monotherapy ( umeclidinium ) versus tiotropium , with a focus on the relative merits of the study design Background : Patients with chronic obstructive pulmonary disease ( COPD ) often experience symptoms and problems with activities early in the morning . This is the first study to compare the effect of budesonide/formoterol and salmeterol/fluticasone on lung function , symptoms and activities early in the morning . Methods : Lung function ( peak expiratory flow [ PEF ] and forced expiratory volume in 1 second [ FEV 1 ] ) and symptoms were measured at bedside and activities were measured during the morning using a six-item question naire concerning basic morning routines . In a r and omised , double-blind , multicentre , cross-over study , 442 patients with COPD aged ≥40 years ( pre-bronchodilator FEV1 ≤50 % ; FEV1/vital capacity < 70 % ) received budesonide/formoterol ( 320/9 µg , one inhalation twice daily ) dry powder inhaler ( DPI ) or salmeterol/fluticasone ( 50/500 µg , one inhalation twice daily ) DPI daily , for 1 week each , separated by a 1- to 2-week washout . Lung function ( PEF and FEV1 ) shortly after rising from bed in the morning , symptoms and basic morning activities were assessed by electronic diary ( e-Diary ) recordings . Results : Budesonide/formoterol and salmeterol/fluticasone treatment increased morning PEF 5 minutes post-dose , measured as a mean improvement from baseline over the full study period ( primary endpoint ; adjusted mean change : 15.1 l/min and 14.2 l/min , respectively [ difference 1.0 l/min ; p = 0.603 ] ) . Mean morning FEV1 improved more following budesonide/ formoterol treatment versus salmeterol/fluticasone at 5 minutes ( 0.12 l versus 0.09 l ; p = 0.090 ) and 15 minutes ( 0.14 l versus 0.10 l ; p < 0.05 ) post-dose . Budesonide/formoterol demonstrated a more rapid onset of effect as reflected by increases in e-Diary-recorded PEF and FEV 1 from pre-dose to 5 and 15 minutes post-dose ( all p < 0.001 ) and spirometry at the clinic measured after the first dose ( FEV1 p < 0.001 ; 5 minutes post-dose ) . Improvements in symptom scores within 15 minutes after drug administration were similar for both drugs , but budesonide/formoterol treatment result ed in significantly greater improvements in total morning activities score ( getting washed , dried , dressed , eating breakfast and walking around the home ; 0.22 versus 0.12 respectively , p < 0.05 ) . Both treatments were well tolerated . Conclusions : Short-term treatment with budesonide/formoterol DPI or salmeterol/fluticasone DPI was effective in patients with COPD . Budesonide/formoterol had a more rapid onset of effect compared with salmeterol/fluticasone and result ed in greater improvements in ability to perform morning activities despite the lower inhaled corticosteroid dose The Indacaterol : Switching Non-exacerbating Patients with Moderate COPD From Salmeterol/Fluticasone to Indacaterol ( INSTEAD ) study investigated the effect of switching patients at low risk of chronic obstructive pulmonary disease ( COPD ) exacerbations from salmeterol/fluticasone ( SFC ; inhaled corticosteroid ( ICS ) regimen ) to indacaterol monotherapy ( non-ICS regimen ) . This 26-week , double-blind , double-dummy , parallel-group , phase IV study , r and omised 581 patients with moderate COPD to indacaterol 150 μg once daily or SFC 50/500 μg twice daily . Patients had been receiving SFC 50/500 μg for ≥3 months , with no COPD exacerbations for more than a year before the study ( patients for whom ICS is not recommended ) . The primary objective was to demonstrate non-inferiority of indacaterol to SFC , measured by trough forced expiratory volume in 1 second ( FEV1 ) after 12 weeks ( non-inferiority margin of 0.06 L ) . The primary objective was met , with a mean treatment difference of 9 mL ( 95 % CI -45–26 mL ) . There were no significant differences between treatments in terms of breathlessness ( transition dyspnoea index ) or health status ( Saint George ’s Respiratory Question naire ) at weeks 12 or 26 , or rescue medication use or COPD exacerbation rates over 26 weeks . Safety profiles of both treatments were as expected . This study demonstrated that patients with moderate COPD and no exacerbations in the previous year can be switched from SFC to indacaterol 150 μg with no efficacy loss . Moderate COPD patients can switch from salmeterol/fluticasone to indacaterol with no efficacy loss Objectives To test the reliability , validity and responsiveness of the 13-item Shortness of Breath with Daily Activities ( SOBDA ) question naire , and determine the threshold for response and minimal important difference ( MID ) . Design 6 week , r and omised , double-blind , placebo-controlled study . Setting 40 centres in the USA between 29 October 2009 and 1 July 2010 . Primary and secondary outcome measures 547 patients with chronic obstructive pulmonary disease ( COPD ) were enrolled and 418 entered the 2-week run-in period . Data from the run-in period were collected to test internal consistency , test – retest reliability , convergent validity and known-groups validity of the SOBDA . Three hundred and sixty six patients were r and omised 2:2:1 to fluticasone propionate/salmeterol 250/50 µg , salmeterol 50 µg or placebo , twice daily . Results from the SOBDA question naire , Patient Global Assessment of Change Question , modified Medical Research Council Dyspnoea Scale ( mMRC ) , Clinician Global Impression of Dysponea Severity ( CGI-S ) , Clinician Global Impression of Change Question and Chronic Respiratory Disease Question naire self-administered st and ardised version ( CRQ-SAS ) were evaluated ; spirometry and safety parameters were measured . Study endpoints were selected to investigate the cross-sectional and longitudinal validity of the SOBDA question naire in relation to the clinical criteria . Results Internal consistency of the SOBDA question naire ( Cronbach α ) was 0.89 . Test – retest reliability ( intraclass correlation ) was 0.94 . The SOBDA weekly scores correlated with the patient-reported and clinician-reported mMRC , CGI-S and CRQ-SAS dyspnoea domain scores ( 0.29 , 0.24 , 0.24 and –0.68 , respectively ) . The SOBDA weekly scores differentiated between the responders and the non-responders as rated by the patients and the clinicians . Anchor-based and supportive distribution-based analyses produced a range of the potential values for the threshold for the responders and MID . Conclusions The 13-item SOBDA question naire is reliable , valid and responsive to change in patients with COPD . On using anchor-based methods , the proposed responder threshold shows a −0.1 to −0.2 score change . A specific threshold value will be identified as more data are generated from future clinical trials . Trial registration NCT00984659 ; GlaxoSmithKline study number : ASQ112989 Background and objective The Global initiative for chronic Obstructive Lung Disease ( GOLD ) Committee has proposed a chronic obstructive pulmonary disease ( COPD ) assessment framework focused on symptoms and on exacerbation risk . This study will evaluate a symptom and exacerbation risk-based treatment strategy based on GOLD in a real-world setting in Japan . Optimal management of COPD will be determined by assessing symptoms using the COPD Assessment Test ( CAT ) and by assessing the frequency of exacerbations . Methods This study ( Clinical Trials.gov identifier : NCT01762800 ) is a 24-week , multicenter , r and omized , double-blind , double-dummy , parallel-group study . It aims to recruit 400 patients with moderate-to-severe COPD . Patients will be r and omized to receive treatment with either salmeterol/fluticasone propionate ( SFC ) 50/250 μg twice daily or with tiotropium bromide 18 μg once daily . Optimal management of patients will be assessed at four-weekly intervals and , if patients remain symptomatic , as measured using the CAT , or experience an exacerbation , they have the option to step up to treatment with both drugs , ie , SFC twice daily and tiotropium once daily ( TRIPLE therapy ) . The primary endpoint of the study will be the proportion of patients who are able to remain on the r and omized therapy . Results No data are available . This paper summarizes the methodology of the study in advance of the study starting . Conclusion The results of this study will help physicians to underst and whether TRIPLE therapy is more effective than either treatment strategy alone in controlling symptoms and exacerbations in patients with moderate-to-severe COPD . It will also help physicians to underst and the GOLD recommendation work in Japan Background Inhaled long-acting beta2agonists used alone and in combination with an inhaled corticosteroid reduce the risk of exacerbations in patients with stable COPD . However , the relative efficacy of these agents in preventing recurrent exacerbations in those recovering from an initial episode is not known . This study compared the rate of COPD exacerbations over the 26 weeks after an initial exacerbation in patients receiving the combination of fluticasone propionate and salmeterol ( FP/SAL ) or SAL alone . Methods Patients ( n = 639 ) aged ≥40 years were r and omized to either twice-daily inhaled FP/SAL 250/50 μg or SAL 50 μg . Primary , and secondary , endpoints were rates of recurrent severe , and moderate/severe , exacerbations of COPD . Lung function , health outcomes and levels of biomarkers of systemic inflammation were also assessed . Results There was no statistically significant treatment difference in rates of recurrent severe exacerbations ( treatment ratio 0.92 [ 95 % CI : 0.58 , 1.45 ] ) and moderate/severe exacerbations ( 0.82 [ 0.64 , 1.06 ] ) between FP/SAL and SAL in the intent-to-treat population . Pre-dose morning FEV1change from baseline was greater ( 0.10 L [ 0.04 , 0.16 ] ) with FP/SAL than SAL . No treatment difference was seen for other endpoints including patient-reported health outcomes and biomarker levels for the full cohort . Conclusions No significant treatment difference between FP/SAL and SAL was seen in COPD exacerbation recurrence for the complete cohort . Treatment benefit with FP/SAL over SAL ( treatment ratio 0.68 [ 0.47 , 0.97 ] ) was seen in patients having FEV1≥ 30 % and prior exposure to ICS . No unexpected safety issues were identified with either treatment . Patients with the most severe COPD may be more refractory to treatment . Trial registration Clinical Trials.gov ( identifier http:// clinical trials.gov/show/NCT01110200 ) . This study was funded by GlaxoSmithKline ( study number ADC113874 ) BACKGROUND Data comparing two bronchodilators vs. one bronchodilator plus inhaled corticosteroid ( ICS ) on hyperinflation and exercise endurance in chronic obstructive pulmonary disease ( COPD ) are scarce , though these therapeutic strategies are widely used in clinical practice . METHODS We performed a r and omized , crossover clinical trial of two × 8 weeks comparing tiotropium ( 18 μg once daily ) + salmeterol ( 50 μg twice daily ) ( T + S ) to salmeterol + fluticasone ( 50/500 μg twice daily ) ( S + F ) in COPD ( forced expiratory volume in 1 s ( FEV(1 ) ) ≤65 % predicted , and thoracic gas volume ( TGV ) ≥120 % predicted ) . Co primary endpoints were postbronchodilator TGV and exercise endurance time ( EET ) . RESULTS In 309 patients , at baseline , prebronchodilator FEV(1 ) was 1.36 L ( 46 % predicted ) , TGV was 5.42 L ( 165 % predicted ) , and EET = 458 s. Relative to S + F , T + S lowered postdose TGV by 182 ± 44 ml after 4 weeks ( p < 0.0001 ) and 87 ± 44 ml after 8 weeks ( p < 0.05 ) . EET was nonsignificantly increased following T + S treatment ( 20 ± 15 s at 4 weeks , 15 ± 13 s at 8 weeks ) vs. S + F. BORG dyspnea score at exercise isotime was reduced in favor of T + S. CONCLUSION The two bronchodilators decreased hyperinflation significantly more than one bronchodilator and ICS . This difference was not reflected in EET . ( Clinical Trials.gov number , NCT00530842 ) BACKGROUND COPD is associated with increased arterial stiffness which may in part explain the cardiovascular morbidity observed in the disease . A causal relationship between arterial stiffness and cardiovascular events has not been established , though their strong association raises the possibility that therapies that reduce arterial stiffness may improve cardiovascular outcomes . Prior studies suggest that fluticasone propionate/salmeterol ( FSC ) may improve cardiovascular outcomes in COPD and we hypothesized that FSC would reduce arterial stiffness in these patients . METHODS This multicenter , r and omized , double-blind , placebo-controlled study compared the effects of FSC 250/50 μg twice-daily and placebo on aortic pulse wave velocity ( aPWV ) as determined by ECG-gated carotid and femoral artery waveforms . The primary endpoint was aPWV change from baseline at 12-weeks ( last measure for each patient ) . RESULTS 249 patients were r and omized ; the mean FEV(1 ) in each group was similar ( 55 % predicted ) and 60 % of patients reported a cardiovascular disorder . At 12-weeks , aPWV between FSC and placebo was -0.42 m/s ( 95%CI -0.88 , 0.03 ; p = 0.065 ) . A statistically significant reduction in aPWV between FSC and placebo was observed in those who remained on study drug throughout the treatment period [ -0.49 m/s ( 95%CI -0.98 , -0.01 ; p = 0.045 ) ] . A post hoc analysis suggested the effect of FSC was greater in patients with higher baseline aPWV . CONCLUSION FSC does not reduce aPWV in all patients with moderate to severe COPD , but may have effects in those with elevated arterial stiffness . Additional studies are required to determine if aPWV could serve as a surrogate for cardiovascular events in COPD & NA ; Rationale : There are no studies on withdrawal of inhaled corticosteroids in patients on long‐term triple therapy in the absence of frequent exacerbations . Objectives : To evaluate the efficacy and safety of direct de‐escalation from long‐term triple therapy to indacaterol/glycopyrronium in nonfrequently exacerbating patients with chronic obstructive pulmonary disease ( COPD ) . Methods : This 26‐week , r and omized , double‐blind , triple‐dummy study assessed the direct change from long‐term triple therapy to indacaterol/glycopyrronium ( 110/50 & mgr;g once daily ) or continuation of triple therapy ( tiotropium [ 18 & mgr;g ] once daily plus combination of salmeterol/fluticasone propionate [ 50/500 & mgr;g ] twice daily ) in nonfrequently exacerbating patients with moderate‐to‐severe COPD . Primary endpoint was noninferiority on change from baseline in trough FEV1 . Moderate or severe exacerbations were predefined secondary endpoints . Measurements and Main Results : A total of 527 patients were r and omized to indacaterol/glycopyrronium and 526 to triple therapy . Inhaled corticosteroids withdrawal led to a reduction in trough FEV1 of −26 ml ( 95 % confidence interval , −53 to 1 ml ) with confidence limits exceeding the noninferiority margin of −50 ml . The annualized rate of moderate or severe COPD exacerbations did not differ between treatments ( rate ratio , 1.08 ; 95 % confidence interval , 0.83 to 1.40 ) . Patients with ≥300 blood eosinophils/&mgr;l at baseline presented greater lung function loss and higher exacerbation risk . Adverse events were similar in the two groups . Conclusions : In patients with COPD without frequent exacerbations on long‐term triple therapy , the direct de‐escalation to indacaterol/glycopyrronium led to a small decrease in lung function , with no difference in exacerbations . The higher exacerbation risk in patients with ≥300 blood eosinophils/&mgr;l suggests that these patients are likely to benefit from triple therapy . Clinical trial registered with www . clinical trials.gov ( NCT 02603393 ) BACKGROUND Patients with severe or very severe chronic obstructive pulmonary disease ( COPD ) frequently suffer repeated exacerbations generating high health care utilization costs . Combined corticosteroid and bronchodilator treatment using a single inhaler might - via improved compliance - reduce exacerbation rates . OBJECTIVES Our aim was to obtain descriptive data on exacerbation rates in patients with severe or very severe COPD ( GOLD Stages III and IV as per GOLD 2009 classification ) receiving salmeterol xinafoate/fluticasone propionate via a single inhaler ( SFC ) or via separate inhalers ( Sal/FP ) in addition to individual existing therapy in order to investigate the potential benefit of a fixed combination device as compared with two separate devices due to potentially improved patients ' compliance . METHODS This prospect i ve , r and omized , open-label , parallel-group , multi-center , exploratory study was conducted in Germany in 2007 - 2009 . Patients were required to have suffered ≥ 2 moderate/severe exacerbations in the preceding year . RESULTS 213 patients ( SFC : 108 patients , Sal/FP : 105 patients ) from 23 centers were evaluated . Approximately 25 % of patients showed COPD Stage IV . On average patients had suffered 2.3 ± 0.6 moderate/severe exacerbations in the preceding year . The annual rate of moderate/severe exacerbations observed in the study was similar in both treatment groups ( SFC : 0.86 ± 0.13 ; Sal/FP : 0.86 ± 0.14 ; exacerbation rate ratio SFC/Sal/FP : 1.00 ; p = 0.73 ; negative binomial model ) . Compliance was high and comparable in both groups . Besides COPD exacerbations , pneumonia ( 5.6 % ) and nasopharyngitis ( 5.2 % ) were the most common adverse events . CONCLUSION Observed exacerbation rates were lower than those reported at baseline . No substantial difference was observed between administration of salmeterol xinafoate/fluticasone propionate via a single inhaler and separate inhalers . Treatment was safe and well tolerated . Clinical Trials.gov Identifier : NCT00527826 BACKGROUND AND OBJECTIVE Combination long-acting β2 -agonist/long-acting muscarinic antagonist ( LABA/LAMA ) has demonstrated superior clinical outcomes over LABA/inhaled corticosteroid ( ICS ) in chronic obstructive pulmonary disease ( COPD ) patients ; however , data from blinded r and omized controlled trials on direct switching from LABA/ICS to LABA/LAMA are lacking . FLASH ( Assessment of switching salmeterol/Fluticasone to indacateroL/glycopyrronium in A Symptomatic COPD patient coHort ) investigated if direct switch , without a washout period , from salmeterol/fluticasone ( SFC ) to indacaterol/glycopyrronium ( IND/GLY ) in COPD patients improves lung function and is well tolerated . METHODS In this 12-week , multicentre , double-blind study , patients with moderate-to-severe COPD and up to one exacerbation in previous year , receiving SFC for ≥3 months , were r and omized to continue SFC 50/500 μg twice daily ( bd ) or switch to IND/GLY 110/50 μg once daily ( od ) . Primary endpoint was pre-dose trough forced expiratory volume in 1 s ( FEV1 ) at Week 12 . RESULTS In total , 502 patients were r and omized ( 1:1 ) to IND/GLY or SFC . Patients switched to IND/GLY demonstrated superior lung function ( pre-dose trough FEV1 ) versus SFC at Week 12 ( treatment difference ( Δ ) = 45 mL ; P = 0.028 ) . IND/GLY provided significant improvements in pre-dose trough forced vital capacity ( FVC ; Δ = 102 mL ; P = 0.002 ) and numerical improvements in transition dyspnoea index ( TDI ; Δ = 0.46 ; P = 0.063 ) . Rescue medication use and COPD assessment test ( CAT ) scores were comparable between groups . Both treatments had similar safety profiles . CONCLUSION FLASH demonstrated that a direct switch to IND/GLY from SFC improved pre-dose FEV1 and FVC in COPD patients with up to one exacerbation in the previous year . No new safety signals were identified Background The Global initiative for chronic Obstructive Lung Disease strategy document for COPD recommends treatment changes according to the persistence of symptoms or exacerbations . This study assessed the feasibility and outcomes of a structured step-up/step-down treatment approach in a r and omized controlled clinical trial setting . Methods Japanese patients with moderate-to-severe COPD were r and omized to blinded , double-dummy treatment with twice-daily fluticasone propionate/salmeterol ( FP/SAL ) 250/50 µg or once-daily tiotropium bromide ( TIO ) 18 µg for 24 weeks ( dual bronchodilator was not available ) . At 4-weekly intervals , patients remaining symptomatic ( COPD Assessment Test score > 10 ) or experiencing an exacerbation were offered the option to use triple therapy . Primary endpoint was the proportion of patients remaining on r and omized therapy . Results In total , 406 patients participated ( mean FEV1 59%±13 % predicted ; COPD Assessment Test 12±6 ) . Of these , 204 and 201 patients were included in the FP/SAL and TIO groups , respectively , of whom 67 % and 63 % continued treatment throughout the study ; this difference was not statistically significant . Time to first therapy switch was longer with FP/SAL , but not significantly ( P=0.21 ) . More patients in Global initiative for chronic Obstructive Lung Disease ( 2011 criteria ) groups C/D switched ( FP/SAL 55 % , TIO 63 % ) than in groups A/B ( FP/SAL 27 % , TIO 27 % ) . Conclusion Given the choice , patients with more symptoms or those experiencing an exacerbation will agree to step-up therapy . Effectiveness of disease management pathways can be tested using double-blind studies Background In patients with chronic obstructive pulmonary disease , all efforts should be made to prevent exacerbations because each event modifies the trajectory of the disease . Treatment recommendations are mostly built on results from r and omized controlled trials ( RCTs ) whose methodology ensure internal validity . However , their relevance may be compromised by the lack of generalizability , due to poor representability of study population s compared to real-life patients .In order to delimit to whom the results of studies on current and future treatments apply , we sought to identify and characterize the fraction of COPD population that would be eligible for inclusion into RCTs aim ing at decreasing exacerbation risk . Methods We used the Initiatives-BPCO data base , a French cohort of 1309 real-life COPD patients monitored in academic centers . We identified industry-sponsored phase III and IV trials that enrolled more than 500 patients , lasted at least one year and used exacerbations related endpoints . Eligibility criteria were extracted from each trial and applied to the patients . Results The eligibility criteria of 16 RCTs were applied to the 1309 patients . The most discriminating eligibility criteria were FEV1 , minimum exacerbation rate in the previous year and smoking history , responsible for the exclusion of 39.9 , 36.7 and 16.8 % of patients , respectively . Altogether , 2.3 to 46.7 % of our patients would have satisfied all eligibility criteria . Conclusion These analyses confirm that an important gap exists between real-life patients and clinical trials population s in COPD , which limits the relevance of results and therefore should be considered when grading levels of evidence and design ing future studies Background : Wixela ® Inhub ® was developed to deliver inhaled fluticasone propionate/salmeterol ( FP/S ) combination as a substitutable generic equivalent to Advair ® Diskus ® . These studies aim ed to confirm the pharmacokinetic bioequivalence ( BE ) of FP/S after single doses of Wixela Inhub ( test [ T ] ) and Advair Diskus ( reference [ R ] ) . Methods : Three open-label , r and omized , two-way crossover , single-dose studies in healthy subjects ( N = 66 each ) compared the systemic exposure of FP and salmeterol after inhalation from three dose strengths of FP/S ( 100/50 , 250/50 , or 500/50 μg ) delivered from T and R. Primary BE endpoints were the area under the plasma concentration-time curve from time = 0 to the last measurable concentration ( AUC(0-t ) ) and the maximum observed plasma concentration ( Cmax ) for both FP and S. The BE acceptance criteria specified that the 90 % confidence intervals ( CIs ) of the geometric mean T/R ratios for AUC(0-t ) and Cmax can be contained within 0.80–1.25 for both FP and salmeterol . Results : Wixela Inhub met the acceptance criteria for BE for FP and salmeterol at each dose strength . Estimated AUC(0-t ) and Cmax geometric mean ratios ( T/R [ 90 % CI ] ) for FP were , respectively , 1.04 ( 1.00–1.08 ) and 0.92 ( 0.87–0.96 ) for 100/50 μg FP/S , 1.07 ( 1.02–1.13 ) and 1.01 ( 0.95–1.07 ) for 250/50 μg , and 0.97 ( 0.92 , 1.00 ) and 0.90 ( 0.86–0.93 ) for 500/50 μg . Estimated AUC(0-t ) and Cmax ratios for salmeterol were , respectively , 1.08 ( 1.04–1.11 ) and 1.00 ( 0.94–1.04 ) for 100/50 μg FP/S , 1.03 ( 0.99–1.07 ) and 0.93 ( 0.87–1.00 ) for 250/50 μg , and 1.00 ( 0.96–1.04 ) and 0.86 ( 0.81–0.91 ) for 500/50 μg . FP/S at all doses via both T and R was comparably well tolerated . Conclusions : Wixela Inhub was bioequivalent to Advair Diskus at all three dose strengths for both FP and S , providing direct evidence of equivalent systemic safety and indirect evidence for equivalent pulmonary deposition BACKGROUND Treatment with inhaled glucocorticoids in combination with long-acting bronchodilators is recommended in patients with frequent exacerbations of severe chronic obstructive pulmonary disease ( COPD ) . However , the benefit of inhaled glucocorticoids in addition to two long-acting bronchodilators has not been fully explored . METHODS In this 12-month , double-blind , parallel-group study , 2485 patients with a history of exacerbation of COPD received triple therapy consisting of tiotropium ( at a dose of 18 μg once daily ) , salmeterol ( 50 μg twice daily ) , and the inhaled glucocorticoid fluticasone propionate ( 500 μg twice daily ) during a 6-week run-in period . Patients were then r and omly assigned to continued triple therapy or withdrawal of fluticasone in three steps over a 12-week period . The primary end point was the time to the first moderate or severe COPD exacerbation . Spirometric findings , health status , and dyspnea were also monitored . RESULTS As compared with continued glucocorticoid use , glucocorticoid withdrawal met the prespecified noninferiority criterion of 1.20 for the upper limit of the 95 % confidence interval ( CI ) with respect to the first moderate or severe COPD exacerbation ( hazard ratio , 1.06 ; 95 % CI , 0.94 to 1.19 ) . At week 18 , when glucocorticoid withdrawal was complete , the adjusted mean reduction from baseline in the trough forced expiratory volume in 1 second was 38 ml greater in the glucocorticoid-withdrawal group than in the glucocorticoid-continuation group ( P<0.001 ) ; a similar between-group difference ( 43 ml ) was seen at week 52 ( P=0.001 ) . No change in dyspnea and minor changes in health status occurred in the glucocorticoid-withdrawal group . CONCLUSIONS In patients with severe COPD receiving tiotropium plus salmeterol , the risk of moderate or severe exacerbations was similar among those who discontinued inhaled glucocorticoids and those who continued glucocorticoid therapy . However , there was a greater decrease in lung function during the final step of glucocorticoid withdrawal . ( Funded by Boehringer Ingelheim Pharma ; WISDOM Clinical Trials.gov number , NCT00975195 . ) |
835 | 12,137,682 | REVIEW ER 'S CONCLUSIONS There is no evidence from r and omised controlled trials to support or refute the efficacy of feed thickeners in newborn infants with GOR .
Given the absence of evidence , we can not recommend using thickening agents for management of GOR in newborn infants | BACKGROUND Gastro-oesophageal reflux ( GOR ) is common in newborn infants .
A common first line management is the use of feed thickeners .
OBJECTIVES In newborn infants with GOR , to evaluate the use of feed thickeners in reducing signs and symptoms of GOR , acid episodes on pH monitoring and histological evidence of oesophagitis . | OBJECTIVE Thickening of formula feedings is part of the therapeutic approach for gastroesophageal reflux ( GER ) in infants . However , its mechanism of action , especially regarding the occurrence of nonacid ( pH > 4 ) GER , has not yet been clearly described . The aim of this r and omized , placebo-controlled crossover study was to examine the influence of formula thickened with carob ( St. John 's bread ) bean gum on acid and nonacid GER . METHODS Infants with recurrent regurgitation and without other symptoms were fed alternately ( A-B-A-B-A-B ) with thickened ( A ) and nonthickened ( B ) but otherwise identical formula . Documentation of GER episodes during the study was performed by simultaneous intraesophageal impedance measurement ( intraluminal electrical impedance ; IMP ) and pH monitoring . The IMP technique is able to detect bolus movements inside a luminal organ . The use of multiple measuring segments on a single catheter allowed the analysis of direction , height , and duration of the bolus transport . Continuous videorecording and visual surveillance of regurgitation frequency and amount result ed in a severity score . RESULTS Fourteen infants ( 42 + /- 32 days old ) were examined during 6 feeding intervals each for a total measuring time of 342 hours . A total of 1183 GER episodes and 83 episodes of regurgitation were registered . Regurgitation frequency ( 15 vs 68 episodes ) and amount ( severity score 0.6 vs 1.8 ) were significantly lower after feedings with thickened formula . The difference regarding the occurrence of GER documented by IMP was also pronounced ( 536 vs 647 episodes ) . Although not statistically significant , maximal height reached by the refluxate in the esophagus was decreased after thickened feedings . Mean GER duration and the frequency of acid ( pH < 4 ) GER were not altered . CONCLUSIONS Thickened feeding has a significant effect on the reduction of regurgitation frequency and amount in otherwise healthy infants . This effect is caused by a reduction in the number of nonacid ( pH > 4 ) GER episodes , but also because of a decrease of mean reflux height reached in the esophagus . However , the occurrence of acid GER is not reduced . The combination of IMP and pH monitoring allows the complete registration and description of these GER episodes . Thickening of formula feedings with carob bean gum is an efficient therapy for uncomplicated GER in infants Gastro-oesophageal reflux ( GOR ) occurs mainly during postcibal ( PC ) periods . The duration of PC gastric acidity and the incidence of GOR were analysed in 11 asymptomatic premature infants . GOR was studied during PC periods of 120 min and also during the following 120 min defined as fasting ( FT ) periods . These infants were subjected to simultaneous continuous gastric and oesophageal pH monitoring using a double-blind crossover technique . Two formulae with different fat contents ( 2.6 vs 3.6 g/100 ml ) and different carbohydrate concentrations ( 8.1 vs 7.3 g/100 ml ; malto-dextrin 2.8 vs 1.9 g/100 ml ) were given . Gastric acidity ( pH<4 ) in the PC periods lasted significantly ( P<0.001 ) longer ( 68 min±10 ) with the low fat/high malto-dextrin formula versus 43 min±11 with the high fat/low malto-dextrin formula . Oesophageal pH monitoring data were within normal limits for the total investigation time in all infants . During PC periods acid GOR was detected more frequently in the group with a low fat formula . More PC GOR was recorded when the gastric acidity time was longer An open multicenter study was performed to assess the efficacy and safety of alginic acid in two different dosages in 76 pediatric patients with gastroesophageal reflux confirmed by pH monitoring . Among the 69 patients in whom endoscopy was carried out before treatment , 18 had erythematous esophagitis and 5 had erosive esophagitis . Irrespective of the dosage used , the frequency of regurgitation and vomiting decreased significantly ( p < 0.00001 and p = 0.01 , respectively ) . Clinical and biochemical tolerance were outst and ing and no adverse effects were recorded . On the basis of these data , the recommended dosage is 1 to 2 ml/kg/day in divided doses after meals To evaluate a pre-thickened formula ( Enfamil AR1/2 ) for regurgitant gastroesophageal reflux , 104 infants were enrolled in a 5-week , multi center , double-blind , r and omized , place bo controlled parallel group trial . The Enfamil AR group showed greater symptom reduction by the end of the first week : percent feedings with any regurgitation ( p=0.045 ) , total regurgitation volume score ( p=0.035 ) , and percent feedings with choke-gag-cough ( p=0.004 ) . The most symptomatic infants at baseline had a reduction in trouble sleeping significantly with Enfamil AR by the end of the study ( p=0.030 ) . This formula flows through a st and ard nipple , reduces regurgitation and choking-gagging-coughing within a week , and improves sleep in the most symptomatic babies by 5 weeks , without causing constipation Summary The role of delayed gastric emptying ( GE ) in the pathogenesis of gastroesophageal reflux ( GER ) in infants is controversial at present . GE has been shown to be altered by the composition and osmolality of the feedings . This prospect i ve study was undertaken to assess the changes in the GE and the percentage of time GER was detected by scintigraphy using three different formulas on consecutive days in infants with GER . Twenty-eight infants under 1 year of age diagnosed to have GER by extended intraesophageal pH monitoring ( pH being < 4.0 for > 5 % of the duration of the test ) , underwent scintigraphy on three consecutive days using the same volume per single feeding of a casein-predominant , soy , or a wheyhydrolysate formula in a r and omized order . The formulas were isocaloric . Gastric emptying and percentage of GER into the esophagus were estimated for 60 min following these feedings . Mean GER percent during the study was 20.39 , 17.68 , and 16.34 on casein-predominant , soy , and whey-hydrolysate formulas , respectively , and was not significantly different . Mean values of GE were 39.7 % , 44.6 % , and 48.5 % on casein , soy , and whey formula , respectively . No significant difference in GE was also observed between casein-predominant and soy formula . However , a significant difference was observed ( p < 0.05 ) on GE between casein-predominant and whey-hydrolysate feedings . Our data suggest that formula selection may be important in the treatment of conditions associated with delayed gastric emptying To determine whether thickening of infant formula feedings with rice cereal increases coughing , we studied 25 infants from birth to 6 months of age , referred for evaluation of gastroesophageal reflux . Coughing was blindly quantified after each of a pair of isocaloric meals ( one thickened and one unthickened ) . Coughing was more frequent after thickened feedings than after unthickened feedings We compared the efficacy of the prokinetic agent cisapride with that of Gaviscon ( an alginate/alkaline compound ) plus Carobel ( carob seed flour ) in the treatment of gastrooesophageal reflux ( GOR ) . Fifty infants with confirmed GOR received either oral cisapride ( 0.8 mg/kg/day ) or Gaviscon plus Carobel for one month in a r and omised , parallel group study . Parental evaluations , diary scores , and 24 hour lower oesophageal pH recordings before and at the end of each treatment were compared . In the cisapride group 14/26 ( 53 % ) were considered better by their parents compared with 19/24 ( 79 % ) of those who received Gaviscon plus Carobel . Diary scores , range ( 0.00 - 1.00 ) , improved in both groups with the median change being greater in the Gaviscon plus Carobel group ( -0.21 ) than the cisapride group ( -0.15 ) . Five of 17 pH variables had significantly improved from baseline in infants who had received cisapride compared with 11/17 in those receiving Gaviscon plus Carobel . However , unpaired analysis of diary and pH data showed no significant differences between the two groups . We conclude that first line treatment of GOR with cisapride is no more effective than conventional treatment with Gaviscon plus Carobel We assessed the efficacy of a natural clay ( smectite ) on the frequency and the duration of acid ( pH less than 4 ) and very acid ( pH less than 3 ) gastroesophageal reflux ( GER ) measured by 24-hour continuous pH recording ( CPR ) . Twenty newborn infants were enrolled in this double-blind controlled study owing to pathological CPR in supine position . After inclusion , all the patients were maintained in the 30-degree elevated prone position and received either smectite ( 3 g/day ; n = 10 ) or placebo ( n = 10 ) for 7 days . On the 8th day , a second 24-hour CPR was performed in supine position . The postural therapy alone ( placebo group ) was followed by a significant decrease in the numbers of acid GER ( p less than 0.05 ) during the second CPR . The combination of postural therapy and smectite treatment was followed by a decrease in the number of acid ( p less than 0.05 ) and very acid GER ( p = 0.01 ) , the percentages of time spent at pH below 4 ( p less than 0.05 ) and 3 ( p less than 0.01 ) and the maximal duration of acid GER ( p less than 0.05 ) The aim of the present study was to compare the efficacy and safety of a new aluminium-free formulation of alginate with placebo in infants with recurrent gastro-oesophageal reflux . This was a double-blind , r and omised , parallel-group study conducted at 25 centres in the UK . Of the 90 paediatric patients recruited in a general practice setting , 42 were r and omised to receive alginate and 48 to receive placebo . Infants were assessed before treatment and again after seven and 14 days of treatment . Analyses were based on the last , valid , non-missing observation for each variable for the intent-to-treat ( ITT ) population of 42 alginate and 46 placebo patients . For the primary efficacy measure ( number of vomitting/regurgitation episodes ) , alginate was significantly superior to placebo ( p = 0.009 ) . For the secondary efficacy measure ( severity of vomiting ) , a trend in favour of alginate was observed ( p = 0.061 ) . Patients receiving alginate achieved superior assessment s of treatment outcome by both investigators ( p = 0.008 ) and parent/guardians ( p = 0.002 ) alike . In addition , alginate achieved a significantly greater reduction in the mean severity of vomiting episodes recorded in a daily diary compared with placebo ( p = 0.027 ) and result ed in more patients having at least 10 % symptom-free days ( p = 0.027 ) . For none of the variables measured did placebo have a superior effect . More than one-half of all patients experienced some adverse event , although no statistically significant differences were observed between the two treatment groups ( p > 0.1 ) , and adverse events accounted for withdrawal in only 12.5 % of the patients ( alginate , n = 4 ; placebo , n = 7 ) . Aluminium-free alginate demonstrated superior efficacy over placebo in treating recurrent gastro-oesophageal reflux in paediatric patients . The safety profile of alginate was similar to that of placebo |
836 | 26,558,273 | Implementation of systematic approaches to pain assessment appears to associate with more frequent documented reports of pain and more efficient decisions for pain management .
There was evidence of favorable effects on pain intensity , duration of mechanical ventilation , length of ICU stay , mortality , adverse events , and complications .
This systematic review demonstrates a link between systematic pain assessment and outcome in critical illness . | In critically ill patients , pain is a major problem .
Efficient pain management depends on a systematic , comprehensive assessment of pain .
We aim ed to review and synthesize current evidence on the impact of a systematic approach to pain assessment on critically ill patients ' outcomes . | Purpose Systematic monitoring of sedation , pain and delirium in the ICU is of paramount importance in delivering adequate patient care . While the use of systematic monitoring instruments is widely agreed upon , these tools are infrequently implemented into daily ICU care . The aim of this study is to compare the effectiveness of two different training strategies ( training according to the local st and ard vs. modified extended method ) on the implementation rate of scoring instruments on the ICU . Methods In this experimental cohort study we analyzed the frequency of scoring on three surgical ICUs before and after training , and in a 1 year follow-up . A modified extended training included establishing a local support team helping to resolve immediate problems . In addition we evaluated the impact on patients ’ outcome . Results ICUs trained by the modified extended method showed increased documentation rates of all scores per patient and day . In a 1 year follow-up , increased scoring rates for all scores were maintained . Scoring rates with training according to the local st and ard training protocol did not increase significantly . Implementation of delirium and pain monitoring were associated with a decrease in mortality [ odds ratio ( OR ) 0.451 ; 95 % confidence interval ( CI ) : 0.22–0.924 , and , respectively , OR 0.348 ; 95 % CI : 0.140–0.863 ] . Monitoring had no significant influence on ventilation time or ICU length of stay . Conclusions A modified extended training strategy for ICU monitoring tools ( sedation , pain , delirium ) leads to higher intermediate and long-term implementation rates and is associated with improved patient outcome . However , these findings may have been biased by unmeasured confounders There has been growing interest in determining the possible immune consequences of opioid administration for the management of postoperative pain . We studied the effects of morphine and tramadol on pain and immune function during the postoperative period in 30 patients undergoing abdominal surgery for uterine carcinoma . Phytohemoagglutinin-induced T lymphocyte proliferation and natural killer cell activity were evaluated immediately before and after surgery , and 2 h after the acute administration of either 10 mg of morphine IM or 100 mg tramadol IM for pain . In all patients , phytohemagglutinin-induced lymphoproliferation was significantly depressed by surgical stress . However , in the morphine-treated group , proliferative values remained lower than basal levels for 2 h after treatment , whereas in tramadol-administered patients proliferative values returned to basal levels . Natural killer cell activity was not significantly affected by surgery nor by morphine administration , whereas tramadol significantly enhanced the activity of natural killer cells . Both drugs produced a comparable reduction in postoperative pain . We conclude that , as previously observed in the experimental animal , tramadol and morphine , when administered in analgesic doses , induce different immune effects . Implication s Recent studies suggest that opioids can have an adverse impact on the immune system . Because surgical stress also induces immune dysfunction , the search for analgesic drugs devoid of immunosuppressive effects is of import . This study compared the effects on immune responses of morphine and of the atypical opioid analgesic , tramadol , given for postoperative pain to gynecological cancer patients . Tramadol and morphine showed comparable analgesic activity ; however , tramadol , in contrast to morphine , induced an improvement of postoperative immunosuppression and , therefore , may be preferred to morphine for the treatment of postoperative pain Objective To establish the validity and reliability of a new behavioral pain scale ( BPS ) for critically ill se date d adult patients . Design Prospect i ve evaluation . Setting Ten-bed trauma and surgical intensive care unit in a university teaching hospital . Patients Thirty mechanically ventilated patients who were receiving analgesia and sedation . Intervention Assessment s with the BPS were completed consecutively at st and ardized times ( morning , afternoon , night ) by pairs of evaluators ( nurse and nurse ’s aide ) . They collected physiologic parameters and BPS results before and during care procedures : nonnociceptive ( group 1 , compression stockings application and central venous catheter dressing change ) , nociceptive ( group 2 , endotracheal suctioning and mobilization ) , and retested nociceptive ( group 3 ) . The BPS score was the sum of three items that had a range score of 1–4 : facial expression , movements of upper limbs , and compliance with mechanical ventilation . Measurements and Main Results Two hundred and sixty nine assessment s were completed , including 104 , 134 , and 31 measurements in groups 1 , 2 and 3 , respectively . There was no difference in Ramsay scale scores between the three groups ( Ramsay 4–6 ) . Nociceptive stimulations ( group 2 ) result ed in significantly higher BPS values than nonnociceptive ones ( group 1 , 4.9 vs. 3.5 , p < .01 ) , whereas the two groups had comparable BPS values before stimulation ( 3.1 vs. 3.0 ) . A trend was found in group 2 between the dosage of sedation/analgesia and BPS : the higher the dosage , the lower BPS values and BPS changes to nociceptive stimulation . Group 3 had BPS values similar to group 2 at rest ( 3.2 vs. 3.2 ) and during the procedure ( 4.4 vs. 4.5 ) , with good interrater correlations ( r2 = .71 and .50 , respectively ) . Conclusions These results indicate that the expression of pain can be scored validly and reliably by using the BPS in se date d , mechanically ventilated patients . Further studies are warranted regarding the utility of the BPS in making clinical decisions about the use of analgesic drugs in the intensive care unit Objective : To measure the impact of implementation of the systematic evaluation of pain and agitation by nurses using the Behavioral Pain Scale ( BPS ) , the Numerical Rating Scale ( NRS ) for pain , and the Richmond Agitation Sedation Scale ( RASS ) associated with medical staff education in analgesia and sedation management in intensive care unit ( ICU ) patients . Design : Two-phase , prospect i ve , controlled study . Setting : Twelve-bed medical-surgical ICU in a university hospital . Patients : Consecutive patients staying > 24 hrs in ICU . Interventions : BPS , NRS , and RASS were measured twice daily , at rest , by independent observers during 21 wks ( control group ) and after 4 wks of training , by nurses during 29 wks ( intervention group ) . In the intervention group , the treating physician was alerted in case of pain defined by BPS > 5 or NRS > 3 or in case of agitation defined by RASS > 1 . Measurements and Main Results : A total of 230 patients were included ( control group , n = 100 ; intervention group , n = 130 ) . Baseline characteristics were not significantly different . The incidence of pain and agitation decreased significantly in the intervention group : 63 % vs. 42 % ( p = .002 ) and 29 % vs. 12 % ( p = .002 ) , respectively . Rate of severe pain and agitation events defined by NRS > 6 and RASS > 2 , respectively , also decreased significantly . There were significantly more therapeutic changes in the intervention group in the way of an escalation but also in the way of a de-escalation for analgesic and psychoactive drugs . Compared with the control group , there was a marked decrease in the duration of mechanical ventilation ( 120 [ interquartile range 48–312 ] vs. 65 ( 24–192 ) hrs , p = .01 ) and nosocomial infections rate ( 17 % vs. 8 % , p < .05 ) in the intervention group . There was no significant difference in median length of stay ( 9 [ 4 , 15 ] vs. 7 [ 4 , 13 ] days ) and mortality in ICU ( 12 vs. 15 % ) . Conclusions : Systematic evaluation of pain and agitation , and analgesics and sedatives need was associated with a decrease in incidence of pain and agitation , duration of mechanical ventilation and nosocomial infections Background : Critically ill patients frequently experience pain , but assessment rates remain below 40 % in mechanically ventilated patients . Whether pain assessment affects patient outcomes is largely unknown . Methods : As part of a prospect i ve cohort study of mechanically ventilated patients who received analgesia on day 2 of their stay in the intensive care unit ( ICU ) , the investigators performed propensity-adjusted score analysis to compare the duration of ventilator support and duration of ICU stay between 513 patients who were assessed for pain and 631 patients who were not assessed for pain . Results : Patients assessed for pain on day 2 were more likely to receive sedation level assessment , nonopioids , and dedicated analgesia during painful procedures than patients whose pain was not assessed . They also received fewer hypnotics and lower daily doses of midazolam . Patients with pain assessment had a shorter duration of mechanical ventilation ( 8 vs. 11 days ; P < 0.01 ) and a reduced duration of stay in the ICU ( 13 vs. 18 days ; P < 0.01 ) . In propensity-adjusted score analysis , pain assessment was associated with increased odds of weaning from the ventilator ( odds ratio , 1.40 ; 95 % confidence interval , 1.00–1.98 ) and of discharge from the ICU ( odds ratio , 1.43 ; 95 % confidence interval , 1.02–2.00 ) . Conclusions : Pain assessment in mechanically ventilated patients is independently associated with a reduction in the duration of ventilator support and of duration of ICU stay . This might be related to higher concomitant rates of sedation assessment s and a restricted use of hypnotic drugs when pain is assessed BACKGROUND Pain can adversely affect a patient 's physiological and psychological recovery , yet little is known about the pain experience of cardiac surgical patients . OBJECTIVES To examine nursing practice regarding analgesic administration and measure pain intensity and patient satisfaction with pain management practice s. METHODS To establish baseline nursing practice regarding analgesic administration , charts were review ed retrospectively in 50 adult cardiac surgical patients , and the same information was collected concurrently for a prospect i ve sample of 51 patients . The subjects completed visual analogue scales as a measure of pain intensity twice daily while in the cardiothoracic intensive care unit and Pain Relief Satisfaction Question naires on the day after transfer from the unit . RESULTS Patients in the prospect i ve group received significantly more analgesia . Pain intensity was moderate ( 4 or greater on the Visual Analogue Scale ) . Women had higher overall visual analogue scale scores than did men , 4.57 versus 3.70 . Patients in whom an internal mammary artery had been used as a bypass graft had significantly higher scores compared with patients with vein grafts . The Pain Relief Satisfaction Question naire responses indicated that 96 % of the patients experienced effective pain management in the cardiothoracic intensive care unit . CONCLUSIONS Despite receiving analgesic doses twice those reported elsewhere for similar population s , the patients in this study reported moderate pain intensity . This finding was confounded by the fact that 96 % expressed satisfaction with their pain management in the cardiothoracic intensive care unit . Frequent assessment and documentation of both pain and pain relief from interventions are necessary if the healthcare team is to implement an individualized analgesic regimen Background : The authors conducted a patient-based survey of practice s to fully describe the assessment and the management of pain and sedation of a large cohort of mechanically ventilated patients during their first week of intensive care unit ( ICU ) stay . Methods : A total of 1,381 adult patients were included in a prospect i ve , observational study in 44 ICUs in France . Pain and sedation assessment , analgesic and sedative use , and analgesic management during procedural pain were collected on days 2 , 4 , and 6 of the ICU stay . Results : The observed rates of assessment on day 2 for sedation ( 43 % ) and analgesia ( 42 % ) were significantly smaller than that of use of sedatives ( 72 % ) and opioids ( 90 % ) , also noted on days 4 and 6 . The use of protocol s/ guidelines for sedation/analgesia in the ICU reduced the proportion of patients who were treated , although not evaluated . A large proportion of assessed patients were in a deep state of sedation ( 40–50 % ) . Minor changes in the dosages of the main prescribed agents for sedation ( midazolam , propofol ) and analgesia ( sufentanil , fentanyl , morphine , remifentanil ) were found across 6 days of the patient ’s ICU stay . Procedural pain was specifically managed for less than 25 % of patients ; during those procedures , the proportion of patients with pain significantly increased from the baseline pain evaluation . Conclusions : Excessively deep states of sedation and a lack of analgesia during painful procedures must be prevented . To facilitate systematic pain and sedation assessment and to adjust daily drug dosages accordingly , it seems crucial to promote educational programs and elaboration of protocol s/ guidelines in the ICU BACKGROUND Administration of analgesics per patient request or r and om pain assessment s may provide inadequate pain management . OBJECTIVE To examine the impact of nurses ' use of a st and ardized pain flowsheet to document pain assessment and pharmacologic management on patient-reported pain intensity . METHODS A pre-post intervention design was used to compare 61 patients . In the preimplementation group , traditional charting of pain presence or absence was documented in the narrative notes and pharmacologic management was recorded on the medication profile . In the postimplementation group , the intensity of pain and pharmacologic management were documented on a pain flowsheet . Within 24 hours after transfer to the step-down unit , patients were interviewed regarding pain intensity experienced in the surgical heart unit and at the time of question ing . The distribution of these pain intensity scores was compared . RESULTS The postimplementation group reported significantly lower pain intensity ratings for the average amount of pain experienced while in the surgical heart unit , the least amount of pain experienced while in the surgical heart unit , and the pain experienced at the moment of question ing . CONCLUSIONS Use of a st and ardized pain flowsheet to assess pain intensity and document pharmacologic intervention may improve pain management in postsurgical cardiovascular patients Objective : To determine physician and nurse adherence with sedative , analgesic , and neuromuscular blocking agent guidelines in the management of mechanically ventilated patients in a medical intensive care unit . Design : Prospect i ve cohort study . Subjects : One hundred consecutively admitted patients to a medical intensive care unit who required mechanical ventilatory support . A sample of 29 nurses , residents , and attending physicians were interviewed regarding their attitudes and perceptions of the guidelines . Measurement : Data were collected from concurrent medical records and included the following : demographic characteristics ; clinical variables ; physician prescriptions of sedative , analgesic , and /or neuromuscular blocking agents ; nurse administration of these medications ; documentation of monitoring ; and assessment of patient hemodynamic status and behaviors . A semistructured interview was elicited from both nurses and physicians about their rationale for the use or nonuse of the guidelines . Results : Patients ranged in age from 24 to 87 yrs , mean 60.7 ( ±15.3 ) yrs . Admission Acute Physiology and Chronic Health Evaluation III scores ranged from 36 to 192 , mean 93.8 ( ±30.5 ) and median 88 . Length of mechanical ventilatory support ranged from 1 to 112 days , mean 14.8 ( ±20.0 ) days , and median 8 days ; medical intensive care unit length of stay ranged from 1 to 46 days , with a mean of 9.8 ( ±8.1 ) days and a median of 8 days . Of the 100 patients , 47 % died , 28 % returned home , and 25 % were discharged to a nursing facility . Eighty‐five patients were administered one or more sedative , analgesic , and /or neuromuscular blocking agent , range 1‐9 drugs , mean 2.5 ( ±1.5 ) drugs . Physicians prescribed 14 different medications ; the most commonly administered drug was lorazepam ( n = 71 ) , followed by morphine ( n = 39 ) . Physicians and nurses had partial or total adherence to the guidelines in 58 % of patients . The initial choice of the drug followed the guidelines in 60 % of patients ; the overall guideline was followed in 23 % of patients . The most common rationale s for nonadherence to the guidelines stated by both physicians and nurses were patient‐specific factors , resident guideline learning curve , and physician medication preferences . Conclusion : Most patients required treatment for agitated behaviors . The majority of treatment regimens partially or totally adhered to the guidelines . Factors such as patient‐specific disease states , resident guideline learning curve , and physician preferences of medications may have decreased adherence . Improving adherence to the guidelines is essential to assess their effectiveness in improving clinical outcomes OBJECTIVE To establish the validity and reliability of a new sedation scale , the Motor Activity Assessment Scale ( MAAS ) . DESIGN Prospect i ve , psychometric evaluation . SETTING Sixteen-bed surgical intensive care unit ( SICU ) of a 937-bed tertiary care , university-affiliated teaching hospital . PATIENTS Twenty-five r and omly selected , adult , mechanically ventilated , nonneurosurgical patients who were admitted to the SICU > or = 12 hrs after surgery and were not receiving neuromuscular blockers . INTERVENTION Four hundred assessment s ( eight per patient ) were completed consecutively but independently , in pairs , at st and ardized times ( both day and night ) by two nurses who were preselected for each assessment from a pool of 32 pretrained SICU nurses . MEASUREMENTS AND MAIN RESULTS To estimate validity , paired assessment s ( four/patient ) compared the MAAS result with the subjective assessment using a 10-cm visual analog sedation scale , the percent change in blood pressure and heart rate from the previous 4-hr baselines , and the number of recent agitation-related sequelae . To estimate reliability , paired assessment s ( four/patient ) measured correlation between assessment s of the same type ( e.g. , MAAS-MAAS ) . Generalized estimating equations , which accounted for the four repeated measures in each patient , supported MAAS validity by finding a linear trend between MAAS and the visual analog scale ( p < .001 ) , blood pressure ( p < .001 ) , heart rate ( p < .001 ) , and agitation-related sequelae ( p < .001 ) end points . The MAAS ( kappa = 0.83 [ 95 % confidence interval , 0.72 to 0.94 ] ) was found to be more reliable than subjective assessment using the visual analog scale ( intraclass correlation coefficient = 0.32 [ 95 % confidence interval , 0.05 to 0.55 ] ) . CONCLUSIONS The MAAS is a valid and reliable sedation scale for use with mechanically ventilated patients in the SICU . Further studies are warranted regarding the effect of MAAS implementation in our SICU on patient outcomes , such as quality of sedation and length of mechanical ventilation , as well as the use of the MAAS in other patient population s ( e.g. , medical ) BACKGROUND Critically ill adults often can not self-report pain . OBJECTIVE To determine the effect of the Critical-Care Pain Observation Tool on frequency of documentation of pain assessment and administration of analgesics and sedatives in critically ill patients unable to self-report pain . METHODS Data on patients in 2 intensive care units of a university-affiliated hospital were collected before and after implementation of the tool . Patients were prospect ively screened for eligibility ; data were extracted retrospectively . RESULTS Data were recorded for a maximum of 72 hours before and after implementation of the tool in the cardiovascular intensive care unit ( 130 patients before and 132 after ) and in the medical/surgical/trauma unit ( 59 patients before and 52 after ) . Proportion of pain assessment intervals with pain assessment documented increased from 15 % to 64 % ( P < .001 ) in the cardiovascular unit and from 22 % to 80 % ( P < .001 ) in the other unit . Median total dose of opioid analgesics decreased from 5 mg to 4 mg in the cardiovascular unit ( P = .02 ) and increased from 27 mg to 75 mg ( P = .002 ) in the other unit . Median total dose of benzodiazepines decreased from 12 mg to 2 mg ( P < .001 ) in the cardiovascular unit and remained unchanged in the other unit . Increased documentation of pain assessment was associated with increased age in the cardiovascular unit and with decreased maximum scores on the Sequential Organ Failure Assessment in the other unit . CONCLUSION Implementation of the tool increased frequency of pain assessment and appeared to influence administration of analgesics in both units BACKGROUND The Cochrane Collaboration is strongly encouraging the use of a newly developed tool , the Cochrane Collaboration Risk of Bias Tool ( CCRBT ) , for all review groups . However , the psychometric properties of this tool to date have yet to be described . Thus , the objective of this study was to add information about psychometric properties of the CCRBT including inter-rater reliability and concurrent validity , in comparison with the Effective Public Health Practice Project Quality Assessment Tool ( EPHPP ) . METHODS Both tools were used to assess the method ological quality of 20 r and omized controlled trials included in our systematic review of the effectiveness of knowledge translation interventions to improve the management of cancer pain . Each study assessment was completed independently by two review ers using each tool . We analysed the inter-rater reliability of each tool 's individual domains , as well as final grade assigned to each study . RESULTS The EPHPP had fair inter-rater agreement for individual domains and excellent agreement for the final grade . In contrast , the CCRBT had slight inter-rater agreement for individual domains and fair inter-rater agreement for final grade . Of interest , no agreement between the two tools was evident in their final grade assigned to each study . Although both tools were developed to assess ' quality of the evidence ' , they appear to measure different constructs . CONCLUSIONS Both tools performed quite differently when evaluating the risk of bias or method ological quality of studies in knowledge translation interventions for cancer pain . The newly introduced CCRBT assigned these studies a higher risk of bias . Its psychometric properties need to be more thoroughly vali date d , in a range of research fields , to underst and fully how to interpret results from its application Purpose Our aim was to describe analgo-sedation and antipsychotic and neuromuscular blocking drug ( NMBD ) use in critically ill patients , management strategies , and variables associated with these practice patterns . Methods This prospect i ve observational study in 51 intensive care units ( ICUs ) included all patients who underwent invasive mechanical ventilation ( MV ) over a two-week period during 2008 - 2009 . Results We included 712 patients representing 3,620 patient-days . Median MV duration was 3.0 days ( interquartile range 2 - 6 ) . During MV , 92 % of patients received analgo-sedation , 32 % an adjunct agent ( e.g. , acetaminophen ) , 18 % NMBDs , and 10 % antipsychotics . Opioids were used more frequently than benzodiazepines or propofol ( 84.8 % vs 62.2 % vs 10.1 % patients , respectively , P < 0.0001 ) . Independent predictors of opioid and benzodiazepine use were a longer MV duration , assessment scales , physical restraints , and university-affiliated hospital . Although more than 50 % of ICUs reported that assessment tools , protocol s , and daily sedation interruption ( DSI ) were available for use , application was modest : sedation scale 53.0 % , pain scale 19.1 % , delirium scale 5.2 % , protocol 25.0 % , DSI 42.1 % . Accidental device removal occurred in 4.6 % of patients , with 75.8 % of events during DSI . Daily sedation interruption was associated with protocol use , physical restraints , university-affiliated hospital , and short- duration MV . Variables associated with protocol use included assessment scales , longer MV duration , lack of physical restraints , and admission to a community hospital . Conclusion Nearly all MV patients received analgo-sedation . Opioids were used more often than sedatives despite infrequent use of pain scales . Few patients received antipsychotic therapy , but physical restraint was common . Protocol use was poor compared to DSI . Duration of MV predicted the use of either . RésuméObjectifNotre objectif était de décrire l’utilisation des médicaments antalgiques-sédatifs et bloqueurs neuromusculaires ( NMBD ) chez des patients dans un état critique , les stratégies de prise en charge et les variables associées aux pratiques habituelles . MéthodesCette étude observationnelle prospect i ve menée dans 51 unités de soins intensifs ( USI ) a inclus tous les patients ayant bénéficié d’une ventilation mécanique ( VM ) invasive sur une période de deux semaines au cours des années 2008 - 2009.RésultatsNous avons inclus 712 patients représentant 3 620 jours- patients . La durée médiane de VM a été de 3,0 jours ( intervalle interquartile : 2 - 6 ) . Au cours de la VM , 92 % des patients ont reçu une analgésie-sédation , 32 % ont reçu un médicament d’appoint ( par exemple : acétaminophène ) , 18 % des NMBD , et 10 % des antipsychotiques . Les morphiniques ont été utilisés plus souvent que les benzodiazépines ou le propofol ( respectivement , 84,8 % contre 62,2 % et 10,1 % des patients , P < 0,0001 ) . Les facteurs prédictifs indépendants de l’utilisation des morphiniques et des benzodiazépines étaient une plus longue durée de VM , les échelles d’évaluation , la contention physique et l’affiliation universitaire de l’hôpital . Bien que plus de 50 % des USI aient indiqué la disponibilité d’outils d’évaluation , de protocol es et d’interruptions quotidiennes de la sédation ( DSI ) , leur utilisation pratique a été modeste : échelle de sédation 53,0 % , échelle de douleur 19,1 % , échelle d’évaluation du délire 5,2 % , protocol e 25,0 % , DSI 42,1 % . Un retrait accidentel du dispositif est survenu chez 4,6 % des patients , 75,8 % de ces événements survenant au cours d’une DSI . L’interruption quotidienne de la sédation était associée à l’utilisation d’un protocol e , une contention physique , l’affiliation universitaire de l’hôpital et la courte durée de la VM . Les variables associées à l’utilisation d’un protocol e incluaient les échelles d’évaluation , une plus longue durée de VM , l’absence de contrainte physique et l’hospitalisation dans un hôpital général . Conclusion Presque tous les patients sous VM ont reçu une analgésie-sédation . Les morphiniques ont été utilisés plus souvent que les sédatifs en dépit de l’utilisation rare des échelles de douleur . Peu de patients ont reçu un traitement antipsychotique , mais les dispositifs de contention étaient courants . L’utilisation d’un protocol e a été faible par rapport à la DSI . La durée de la VM a prédit l’utilisation des deux |
837 | 18,159,405 | RESULTS The results of the comparative and single meta-analyses revealed no major differences between the new fluoroquinolones .
Results indicate that , in general , fluoroquinolones had similar efficacy , overall safety and dropout rates | BACKGROUND Despite a relatively large number of clinical studies comparing oral fluoroquinolones to one antibiotic class comparator , there is limited information on the relative efficacy of different fluoroquinolones .
OBJECTIVE To examine the efficacy and tolerability of oral fluoroquinolones in the treatment of mild to moderate community-acquired pneumonia , acute exacerbations of chronic bronchitis and sinusitis . | In this prospect i ve , multicenter , double-blind study , the efficacy of ciprofloxacin was compared with that of clarithromycin as therapy for patients with acute bacterial exacerbations of chronic bronchitis ( ABECB ) from whom a pretherapy pathogen was isolated ; the efficacy was measured by the infection-free interval . Clinical and microbiological responses at the end of therapy were secondary efficacy variables . Patients r and omly received either ciprofloxacin or clarithromycin ( 500 mg twice a day for 14 days ) . Three hundred seventy-six patients with acute exacerbations of chronic bronchitis were enrolled in the study of whom 234 had an ABECB . Clinical resolution was observed in 90 % ( 89 of 99 ) of ciprofloxacin recipients and 82 % ( 75 of 91 ) of clarithromycin recipients for whom efficacy could be evaluated . The median infection-free interval was 142 days for ciprofloxacin recipients and 51 days for clarithromycin recipients ( P = .15 ) . Bacteriologic eradication rates were 91 % ( 86 of 95 ) for ciprofloxacin recipients and 77 % ( 67 of 87 ) for clarithromycin recipients ( P = .01 ) . In summary , compared with clarithromycin , treatment of ABECB with ciprofloxacin was associated with a trend toward a longer infection-free interval and a statistically significantly higher bacteriologic eradication rate In an open r and omized study 218 out patients ( 159 males and 59 females ) ranging between 18 and 85 years of age ( mean 61.9 ) suffering from bacterial exacerbation of chronic bronchitis have been r and omly treated : 79 with co-amoxiclav ( amoxicillin 875 mg+clavulanic acid 125 mg ) twice daily , 69 with cefixime ( 400 mg ) once daily , and 70 with ciprofloxacin ( 500 mg ) twice daily for an average period of 10 days . Before treatment start , 234 bacterial strains ( 105 Gram-positive and 129 Gram-negative ) were isolated as the cause of exacerbation ; the leading pathogens were Streptococcus pneumoniae and Haemophilus spp . Eradication rates at the end of treatment were 82.2 % for the co-amoxiclav group , 77.6 % for the cefixime group , and 81.2 % for ciprofloxacin group . Clinical success ( cure+improvement ) was obtained in 90.8 % of the cases treated with co-amoxiclav , in 80.9 % for the cefixime group and in 85.7 % of patients treated with ciprofloxacin . Seven adverse events ( 8.9 % ) of which 4 cases of diarrhea and 3 of itching , were recorded in the co-amoxiclav group . Eleven adverse events ( 14.7 % ) were recorded in the cefixime group including gastrointestinal disturbances in 6 patients and mild to moderate increase of liver function in 2 . Nine adverse events ( 12.9 % ) occurred in the ciprofloxacin group , including insomnia in 3 patients , gastrointestinal disturbances in 2 , and serious increase of liver function tests in one patient . It can be concluded that there were no statistically significant differences among the three treatment groups . However , co-amoxiclav demonstrated a higher efficacy rate than cefixime and ciprofloxacin and was better tolerated . Therefore , it can be used as a first-choice drug in the treatment of exacerbation of chronic bronchitis Chronic bronchitis is common among adults and infectious exacerbations contribute considerably to morbidity and mortality . We aim ed to compare the safety and efficacy of moxifloxacin to azithromycin for the treatment of patients with acute exacerbations of chronic bronchitis ( AECB ) of suspected bacterial origin . Between October 1998 and April 1999 , 567 patients with AECB were enrolled at 37 centers across the United States and Canada of which 280 ( 49 % ) had acute bacterial exacerbation of chronic bronchitis ( i.e. pretherapy pathogen ) . Patients were r and omized to either oral moxifloxacin 400 mg administered once daily for 5 days or azithromycin for 5 days ( 500 mg qd x 1 , then 250 mg qd x 4 ) . For the purpose of study blinding , all patients received encapsulated tablets . The main outcome measure was clinical response at the test-of-cure visit ( 14 - 21 days post-therapy ) . Secondary measures included bacteriologic response and a time-course of bacteriological eradication ( one center only ) . Three patient population s were analysed for efficacy : clinical ly-valid , microbiologically-valid ( i.e. those with a pretherapy pathogen ) , and intent-to-treat ( i.e. received at least one dose of study drug ) . For the efficacy-valid group , clinical response at the test-of-cure visit was 88 % for patients in each treatment group . In 237 microbiologically-valid patients , corresponding clinical resolution rates were 88 % for 5-day moxifloxacin vs. 86 % for 5-day azithromycin . Bacteriological eradication rates at the end of therapy were 95 % for 5-day moxifloxacin and 94 % for the azithromycin group . Corresponding eradication rates at the test-of-cure visit were 89 % and 86 % , respectively . Of note , eradication rates at test-of-cure for Haem . philos influenzae and H. parainfluenzae for moxifloxacin were 97 % and 88 % compared to 83 % and 62 % respectively for azithromycin . Among 567 intent-to-treat patients ( 283 moxifloxacin and 284 azithromycin ) , drug-related events were reported for 22 % and 17 % , respectively . Diarrhea and nausea were the most common drug-related events reported in each treatment group . Moxifloxacin 400 mg once daily for 5 days was found to be clinical ly and bacteriologically equivalent to 5-day azithromycin for the treatment of AECB of proven bacterial etiology . Given its excellent in-vitro activity , especially against antibiotic-resistant respiratory pathogens , and its acceptable safety profile , moxifloxacin should be considered an effective alternative therapy for patients with AECB of suspected bacterial origin The objective of this r and omized , double-blind study was to compare the clinical efficacy of levofloxacin at two different dosages with that of cefuroxime axetil in patients with acute purulent exacerbations of chronic bronchitis and , in particular , to assess the impact of the susceptibility to levofloxacin on the clinical findings . In total , 124 evaluable patients were treated for 7 days with oral levofloxacin 250 mg or 500 mg od , or cefuroxime axetil 250 mg bd . Sputum cultures were monitored pre-treatment , and at 1 and 7 days after the end of treatment . The susceptibility of Streptococcus pneumoniae isolates was tested by agar dilution in Columbia blood agar and by disc diffusion , but all other isolates were tested solely by the disc diffusion method . A greater number of infections were eradicated by levofloxacin than by cefuroxime axetil : infections were eradicated in 68 % of patients receiving the 500 mg dosage and in 63 % of those taking 250 mg levofloxacin , whereas the eradication rate with the comparator drug was much lower ( 48 % ) . Against all pre-treatment S. pneumoniae isolates ( n = 39 ) , the MICs of levofloxacin were between 0.25 and 2 mg/L ( geometric mean 0.95 mg/L ) , similar to those of the post-treatment strains ( n = 32 ; mean 1.11 mg/L ) . All except one of the S. pneumoniae isolates were susceptible to penicillin G ( MIC < or = 0.06 mg/L ) , and the remaining isolate was inhibited by 0.5 mg/L of penicillin G , but was fully susceptible to levofloxacin . Some pretreatment strains of Pseudomonas aeruginosa were resistant to levofloxacin , but many more resistant strains were encountered afterwards . All strains of Moraxella catarrhalis and Haemophilus influenzae were highly susceptible to levofloxacin in the disc diffusion tests . All the antimicrobial agents used in the study were well tolerated : only two patients discontinued treatment because of adverse drug effects . The results of this study indicated that , although there were some failures in patients with S. pneumoniae and P. aeruginosa infections , resistance to levofloxacin did not emerge rapidly among strains of S. pneumoniae during therapy with levofloxacin , and that natural resistance among pneumococci , H. influenzae and M. catarrhalis was rare This investigation compared the efficacy of oral formulations of amoxycillin/clavulanate and ciprofloxacin in acute exacerbations of chronic bronchitis . Forty patients were r and omized to receive either Augmentin ( 1,000 mg amoxycillin + 250 mg clavulanate ) tds or ciprofloxacin ( 500 mg ) bd . During and before therapy sputum sample s were taken for bacteriology , sputum volume measurement and histamine determination . Lung function was also monitored . From sputum , 143 bacterial isolates and 15 yeast strains were obtained before therapy . During therapy with amoxycillin/clavulanate the incidence of Gram-positive isolates decreased significantly whereas ciprofloxacin left their frequency unchanged . On the other h and , ciprofloxacin more effectively diminished the incidence of Gram-negative isolates . Yeasts were grown from the sputum of several patients before and during therapy . Their number did not increase during amoxycillin/clavulanate therapy while it increased under ciprofloxacin . The groups showed no significant differences with regard to sputum production , histamine concentration or lung function . The majority of patients ( 28/40 ) acknowledged improvement of their symptoms . There was no significant difference between the groups . On the basis of these results both amoxycillin/clavulanate and ciprofloxacin appear of similar value for treatment of patients with exacerbations of chronic bronchitis In this multinational , r and omized , double-blind study , the efficacy and safety of a 5 day course of moxifloxacin 400 mg orally od was compared with that of a 7 day course of clarithromycin 500 mg orally bd . in 750 patients with acute exacerbations of chronic bronchitis , characterized by at least two of the symptoms : sputum purulence , increased sputum volume or increased dyspnoea . Seven days after the end of therapy , clinical cure was achieved for 89 % ( 287 of 322 ) of efficacy-evaluable patients in the moxifloxacin group and 88 % ( 289 of 327 ) of patients in the clarithromycin group ( 95 % CI , -3.9 % , 5.8 % ) . At follow-up ( 21 - 28 days post-treatment ) , the continued clinical cure rates were 89 % ( 256 of 287 ) for moxifloxacin and 89 % ( 257 of 289 ) for clarithromycin . A total of 342 pathogenic bacteria were isolated from the sputum of 287 patients . The most common pathogens were Haemophilus influenzae ( 37 % ) , Streptococcus pneumoniae ( 31 % ) and Moraxella catarrhalis ( 18 % ) . Seven days post-treatment , a successful bacteriological response was obtained for 77 % ( 89 of 115 ) of patients in the moxifloxacin group and 62 % ( 71 of 114 ) of patients in the clarithromycin group , indicating superiority of moxifloxacin ( 95 % CI , 3.6 % , 26.9 % ) . Both treatments were well tolerated with few adverse events . This study demonstrated that for the treatment of acute exacerbations of chronic bronchitis a 5 day course of moxifloxacin 400 mg od was clinical ly equivalent and bacteriologically superior to a 7 day course of clarithromycin 500 mg bd OBJECTIVE This study compared the use and efficacy of ciprofloxacin to cefuroxime axetil for adult patients with acute bacterial sinusitis . METHOD We conducted a prospect i ve , r and omized , double-blind pilot study of oral ciprofloxacin ( 500 mg twice daily ) versus cefuroxime axetil ( 250 mg twice daily ) for 2 to 3 weeks in the treatment of adult patients with a clinical diagnosis of acute bacterial maxillary sinus infections or acute exacerbation of chronic bacterial sinusitis . Patients with microbiologically and radiologically confirmed sinusitis infection composed the efficacy population . RESULTS Of the 83 patients enrolled , 13 of 42 ( 31 % ) ciprofloxacin- and 19 of 41 ( 46 % ) cefuroxime axetil-treated patients had a respiratory pathogen isolated from a sinus aspiration . The most frequent pretherapy isolated included Haemophilus influenzae ( 11 ) , streptococcus species ( 20 ) , staphylococcus species ( 7 ) , Proteus mirabilis ( 3 ) , and Neisseria sicca ( 3 ) . At the end of therapy , clinical resolution or improvement in efficacy-valid patients was achieved in 12 ( 100 % ) ciprofloxacin-treated patients and in 14 ( 74 % ) cefuroxime axetil recipients . The five ( 26 % ) cefuroxime axetil clinical failures were due to development of superinfection . Bacteriologic eradication occurred in 12 ( 100 % ) and 14 ( 100 % ) ciprofloxacin and cefuroxime axetil patients , respectively . Similar clinical and bacteriologic response rates were observed at the 2- to 4-week follow-up . Among 83 intent-to-treat patients , 19 ( 45 % ) ciprofloxacin and 14 ( 34 % ) cefuroxime axetil patients had drug-related adverse events . The most common adverse event in both treatment groups was gastrointestinal . CONCLUSION This pilot study suggests that ciprofloxacin is efficacious in the management of acute bacterial sinusitis This multicenter , r and omized , double-blind trial compared the efficacy and safety of ciprofloxacin ( CIP ; 500 mg twice daily for 10 days , placebo for 4 days ) to those of clarithromycin ( CLARI ; 500 mg twice daily for 14 days ) in 560 adults with clinical ly documented and radiologically confirmed acute sinusitis . Of 457 efficacy-valid adults ( 236 CIP , 221 CLARI ) , clinical resolution plus improvement at the end of therapy was 84 % for CIP-treated patients compared to 91 % of CLARI recipients ( CI95 = -0.131 , -0.013 ) . At the 1-month follow-up , more than twice as many CLARI-treated patients , 18 ( 10 % ) , experienced a relapse , compared to 7 ( 4 % ) CIP-treated patients . The combined clinical response analyses ( end of therapy and 1 -month follow-up ) demonstrated that CIP and CLARI were statistically equivalent ( CI95 = -0.106 , 0.044 ) . Diarrhea , nausea , headache , and dizziness were the most frequently reported drug-related adverse events in both treatment groups ; diarrhea and taste perversion were reported more frequently among CLARI recipients . In summary , the combined end of therapy and follow-up clinical evaluation analyses revealed that CIP and CLARI were equally effective in the management of acute sinusitis , although twice as many relapses were reported among CLARI recipients In this comparative trial , out patients with acute sinusitis were r and omly assigned to receive levofloxacin ( 500 mg orally once daily ) or amoxicillin-clavulanate ( 500/125 mg orally 3 times daily ) for 10 to 14 days . The success rates ( cured and improved ) 2 to 5 days after the end of treatment were 88.4 % for the 267 clinical ly evaluable patients who received levofloxacin and 87.3 % for the 268 clinical ly evaluable patients who received amoxicillin-clavulanate . Drug-related adverse events occurred in a smaller percentage of patients in the levofloxacin treatment group ( 7.4 % ) than in the amoxicillin-clavulanate treatment group ( 21.2 % ) . The most common of these were nausea , diarrhea , vaginitis , and abdominal pain for levofloxacin-treated patients and diarrhea , vaginitis , nausea , genital moniliasis , abdominal pain , vomiting , and flatulence for amoxicillin-clavulanate-treated patients . The results of this study show that once-daily administration of levofloxacin is as effective and better tolerated than amoxicillin-clavulanate administered 3 times daily for treating acute sinusitis in adult out patients A r and omized , prospect i ve , double-blind , double-dummy , multicenter study investigated the efficacy and safety of 10 days of oral therapy with grepafloxacin at 400 mg once daily , grepafloxacin at 600 mg once daily , or ciprofloxacin at 500 mg twice daily in 624 patients with acute bacterial exacerbations of chronic bronchitis . At the end of treatment , clinical success ( cure or improvement ) was achieved for 93 % ( 140 of 151 ) , 88 % ( 137 of 156 ) , and 91 % ( 145 of 160 ) of patients in the groups receiving grepafloxacin at 400 mg , grepafloxacin at 600 mg , and ciprofloxacin , respectively ( clinical ly evaluable population ) . At follow-up ( 14 to 28 days posttreatment ) , the clinical success rates were 87 % ( 124 of 143 ) , 81 % ( 122 of 151 ) , and 80 % ( 123 of 154 ) in the groups receiving grepafloxacin at 400 mg and 600 mg and ciprofloxacin , respectively . A total of 379 pathogens were isolated from 290 patients , with the most common isolates being Moraxella catarrhalis ( 21 % ) , Staphylococcus aureus ( 20 % ) , Haemophilus influenzae ( 18 % ) , and Streptococcus pneumoniae ( 7 % ) . For the evaluable population , successful bacteriologic response was obtained at the end of treatment for 96 % ( 92 of 96 ) , 98 % ( 87 of 89 ) , and 92 % ( 82 of 90 ) of patients receiving grepafloxacin at 400 mg , grepafloxacin at 600 mg , and ciprofloxacin , respectively , and was maintained in 86 % ( 82 of 95 ) , 88 % ( 78 of 89 ) , and 82 % ( 69 of 84 ) of patients , respectively , at follow-up . All pretreatment S. pneumoniae isolates were susceptible to grepafloxacin , but two strains were resistant to ciprofloxacin . All treatments were well tolerated , with the most frequently reported drug-related adverse events being nausea , taste perversion , and headache . All drug-related adverse events in the grepafloxacin groups were mild or moderate in severity . This study demonstrates that 10-day courses of grepafloxacin given at 400 or 600 mg once daily were as effective , clinical ly and bacteriologically , as ciprofloxacin given at 500 mg twice daily for the treatment of acute bacterial exacerbations of chronic bronchitis 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 STUDY OBJECTIVES Comparison of the efficacy and safety of moxifloxacin vs amoxicillin for treatment of mild-to-moderate , suspected pneumococcal community-acquired pneumonia ( CAP ) in adult patients . DESIGN Multinational , multicenter , double-blind , r and omized study . SETTING Eighty-two centers in 20 countries ( Argentina , Brazil , Chile , Croatia , Czech Republic , Estonia , France , Hong Kong , Hungary , Lithuania , Mexico , Portugal , Russia , Slovenia , South Africa , Spain , Turkey , Ukraine , United Kingdom , and Uruguay ) . PATIENTS Four hundred eleven adults ( in patients or out patients ) with suspected pneumococcal CAP . INTERVENTIONS R and omization 1:1 to moxifloxacin , 400 mg/d , or amoxicillin , 1,000 g tid , for 10 days . RESULTS Primary efficacy parameter was clinical response , 3 to 5 days after therapy ( end of therapy [ EOT ] ) in the per protocol ( PP ) population ( 362 patients ) . The clinical success rate in the PP population was 91.5 % ( moxifloxacin ) and 89.7 % ( amoxicillin ; two-sided 95 % confidence interval , -4.2 to 7.8 % ) . The clinical cure rate in patients with proven pneumococcal pneumonia was similar in both treatment groups ( 87.8 % ) . The bacteriologic success rate in 136 bacteriologically evaluable patients at the EOT was 89.7 % ( moxifloxacin ) and 82.4 % ( amoxicillin ) . The bacteriologic success rate against Streptococcus pneumoniae was 89.6 % ( moxifloxacin ) and 84.8 % ( amoxicillin ) . The frequency of adverse events was comparable in both treatment groups . Digestive symptoms were the most common drug-related adverse events in both treatment groups . CONCLUSIONS Moxifloxacin was statistically at least as effective as high-dose amoxicillin for treatment of mild-to-moderate , suspected pneumococcal CAP . Moxifloxacin may be an alternative for empiric CAP treatment , especially in areas where multidrug resistance in S pneumoniae is sufficiently prevalent to preclude routine penicillin BACKGROUND The ideal duration of antibiotic therapy for acute exacerbation of chronic bronchitis ( AECB ) remains controversial . OBJECTIVE This study compared short-course , 5-day gatifloxacin treatment with st and ard 10-day clarithromycin treatment in patients with AECB ; 7-day gatifloxacin therapy was a secondary comparator . METHODS This was a multicenter , prospect i ve , r and omized , double-blind study in which adult out patients with AECB were r and omized to 1 of 3 treatment groups : 5 days of gatifloxacin , 7 days of gatifloxacin , or 10 days of clarithromycin . Clinical cure and microbiologic eradication rates were determined 7 to 14 days after the completion of antibiotic treatment . RESULTS A total of 527 patients with AECB were enrolled and treated with study drug ( 174 , gatifloxacin 5-day ; 175 , gatifloxacin 7-day ; 178 , clarithromycin 10-day ) . Most patients ( 82 % ) had type 1 ( severe ) exacerbations , and a bacterial pathogen was isolated from pretreatmer , sputum sample s in 59 % of patients . The overall clinical cure rates among clinical ly evaluable patients were comparable between groups : 89 % ( 135/151 patients ) in the gatifloxacin 5-day group ; 88 % ( 136/154 ) in the gatifloxacin 7-day group ; and 89 % ( 145/163 ) in the clarithromycin 10-day group . The 95 % CIs for the differences in response rates were -6.1 to 7.0 for gatifloxacin 5-day versus clarithromycin , -8.9 to 5.0 for gatifloxacin 7-day versus clarithromycin , and -5.5 to 8.0 for gatifloxacin 5-day versus 7-day . These observations did not appear to be affected by use of corticosteroids or smoking status , type of exacerbation , or duration of current episode . The microbiologic eradication rate among microbiologically evaluable pathogens was > 90 % in all treatment groups . No clinical ly meaningful differences were noted in the incidence of drug-related adverse events . CONCLUSION Short-course , 5-day gatifloxacin therapy in patients with AECB result ed in clinical cure and microbiologic eradication rates comparable to those of st and ard 7- and 10-day therapies A multicenter , investigator-blinded , r and omized , parallel-group study was conducted to compare oral levofloxacin 500 mg once/day for 14 days with clarithromycin 500 mg twice/day for 14 days in the treatment of acute bacterial sinusitis . Of 216 adult out patients r and omized to treatment , 190 were evaluable for efficacy . The primary efficacy measure was clinical response , based on resolution of signs and symptoms 2 - 5 days after therapy . A secondary efficacy measure was relapse rate 1 month after therapy . Among evaluable patients , clinical success rates ( cured or improved ) were 96.0 % and 93.3 % for levofloxacin ( L ) and clarithromycin ( C ) , respectively ( 95 % CI -9.2 % , 3.7 % ) . The confidence interval ( CI ) for treatment difference ( C-L ) included zero and its upper limit was less than 15 % , indicating that levofloxacin was as effective as clarithromycin . In all , 4.1 % of patients receiving levofloxacin and 7.2 % receiving clarithromycin had a relapse of symptoms 1 month after therapy ( 95 % CI-12.2 % , 3.2 % ) . Long-term success ( initial success , absence of relapse at 1 month , no further antibacterial therapy 2 - 5 days after therapy ) was 79.2 % in the levofloxacin group and 76.4 % in the clarithromycin group ( 95 % CI -14.7 % , 9.0 % ) . Based on investigator-assessed treatment-emergent adverse events , overall tolerability of the drugs was similar , except for a higher frequency of taste perversion and diarrhea in the clarithromycin group . Levofloxacin had an advantage over clarithromycin based on two quality -of-life ( QOL ) parameters : number of times taking other drugs for targeted medical conditions and mean total cost of these drugs . No statistical significance was found in other QOL variables . These findings suggest that the efficacy and tolerability of levofloxacin 500 mg once/day are comparable with those of clarithromycin 500 mg twice/day in the treatment of acute bacterial sinusitis A r and omized , double-blind , double-dummy , three-arm parallel design , multicentre study was conducted among adult patients with acute exacerbation of chronic bronchitis ( AECB ) in order to compare the efficacy and safety of two different doses of levofloxacin with cefuroxime axetil . A total of 832 patients were r and omized to receive oral levofloxacin ( 250 mg od or 500 mg od ) or oral cefuroxime axetil ( 250 mg bd ) for 7 - 10 days . The primary efficacy analysis was based on the clinical response in patients with bacteriologically confirmed AECB , determined 5 - 14 days after the end of therapy ( per- protocol population ) . Of 839 patients enrolled ( at 71 centres in 14 countries ) , seven were not treated , giving an intention-to-treat ( ITT ) population of 832 . In total , 281 patients received levofloxacin 250 mg , 280 received levofloxacin 500 mg and 271 received cefuroxime axetil . The cure rates in the ITT population were : levofloxacin 250 mg , 70 % ( 196/281 ) ; levofloxacin 500 mg , 70 % ( 195/280 ) ; cefuroxime axetil , 61 % ( 166/271 ) ; those in the per- protocol population were : 78 % ( 121/156 ) , 79 % ( 108/137 ) and 66 % ( 88/134 ) , respectively . Both doses of levofloxacin were at least as effective as cefuroxime axetil and were active against the main pathogens of clinical relevance ( Haemophilus influenzae , Streptococcus pneumoniae and Moraxella catarrhalis ) . All three treatment regimens were equally well tolerated . In conclusion , the results show that levofloxacin ( 250 mg and 500 mg ) od is effective and well tolerated in the treatment of AECB in adult patients 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 Chronic bronchitis is common among adults and infectious exacerbations contribute considerably to morbidity and mortality . We aim ed to compare the safety and efficacy of moxifloxacin to clarithromycin for the treatment of patients with acute bacterial exacerbations of chronic bronchitis ( ABECB ) using a prospect i ve , r and omized , double-blind , parallel group trial . Between November 21 , 1996 and April 7 , 1998 , 936 patients with acute exacerbations of chronic bronchitis ( AECB ) were enrolled at 56 centers across the United States of which 491 ( 52 % ) had ABECB ( i.e. pretherapy pathogen ) . Patients were r and omized to either oral moxifloxacin 400 mg administer once daily , for either 5 or 10 days , or clarithromycin 500 mg bid for 10 days . For the purpose of study blinding , the patients taking moxifloxacin received placebo to maintain uniform dosing . The main outcome measures were bacteriological response at the end of therapy ( post-therapy days 0 - 6 ) and follow-up ( 7 - 17 days post-therapy ) visits , as well as overall clinical response , clinical response at the end of therapy and clinical response at follow-up . Two patient population s were analyzed : efficacy-valid ( i.e. , those with a pretherapy pathogen ) and intent-to-treat ( i.e. , all subjects that took drug ) . In 420 efficacy valid patients with a pretherapy organism , overall clinical resolution was 89 % for 5 days moxifloxacin vs. 91 % for 10 day moxifloxacin vs. 91 % for 10 day clarithromycin . Bacteriological eradication rates at the end of therapy were 94 % and 95 % for 5-day moxifloxacin and 10-day moxifloxacin , respectively , and 91 % for the clarithromycin group . Eradication rates at follow-up were 89 % and 91 % for 5-day moxifloxacin and 10-day moxifloxacin respectively , and 85 % for the clarithromycin group . Among 926 intent-to-treat patients ( 312 5-day moxifloxacin , 302 10-day moxifloxacin and 312 clarithromycin ) , drug-related events were reported for 26 % , 30 % and 35 % , respectively . Moxifloxacin 400 mg once daily , as a 5 or 10 day regimen , was found to be clinical ly and bacteriologically equivalent to 10 day clarithromycin for the treatment of ABECB . Given its favorable safety and tolerability profile , moxifloxacin administered once daily for 5 days may be as effective and a more convenient treatment than a st and ard course of clarithromycin for patients with ABECB |
838 | 25,772,272 | Conclusions This systemic review found moderate support for the effectiveness of electrical stimulation therapy in slow transit constipation in children . | Purpose Slow transit constipation is a common disorder in children , which often does not respond well to ordinary treatments .
We have conducted a systematic review of reported studies in order to better define the current state of knowledge about electrical stimulation treatment of slow transit constipation in children . | Purpose Transcutaneous electrical stimulation ( TES ) speeds up colonic transit in children with slow-transit constipation ( STC ) . This study examined if concurrent upper gastrointestinal dysmotility ( UGD ) affected response to TES . Methods Radio-nuclear transit studies ( NTS ) were performed before and after TES treatment of STC as part of a larger r and omised controlled trial . UGD was defined as delayed gastric emptying and /or slow small bowel transit . Improvement was defined as increase of ≥1 Geometric Centre ( median radiotracer position at each time [ small bowel = 1 , toilet = 6 ] ) . Results Forty-six subjects completed the trial , 34 had NTS after stimulation ( 21 M , 8–17 years , mean 11.3 years ; symptoms > 9 years ) . Active stimulation increased transit in > 50 % versus only 25 % with sham ( p = 0.04 ) . Seventeen children also had UGD . In children with STC and either normal upper GI motility ( NUGM ) and UGD , NTS improved slightly after 1 month ( 57 vs. 60 % ; p = 0.9 ) and more after 2 months ( 88 vs. 40 % ; p = 0.07 ) . However , mean transit rate significantly increased with NUGM , but not UGD ( 5.0 ± 0.2 : 3.6 ± 0.6 , p < 0.01 ) . Conclusion Transcutaneous electrical stimulation was beneficial for STC , with response weakly associated with UGD . As measured by NTS , STC children with NUGM responded slightly more , but with significantly greater increased transit compared to those with UGD . Higher numbers are needed to determine if the difference is important PURPOSE Idiopathic slow transit constipation ( STC ) describes a clinical syndrome characterised by intractable constipation . It is diagnosed by demonstrating delayed colonic transit on nuclear transit studies ( NTS ) . A possible new treatment is interferential therapy ( IFT ) , which is a form of electrical stimulation that involves the transcutaneous application of electrical current . This study aim ed to ascertain the effect of IFT on colonic transit time . METHODS Children with STC diagnosed by NTS were r and omised to receive either 12 real or placebo IFT sessions for a 4-week period . After a 2-month break , they all received 12 real IFT sessions-again for a 4-week period . A NTS was repeated 6 to 8 weeks after cessation of each treatment period where able . Geometric centres ( GCs ) of activity were calculated for all studies at 6 , 24 , 30 , and 48 hours . Pretreatment and posttreatment GCs were compared by statistical parametric analysis ( paired t test ) . RESULTS Thirty-one pretreatment , 22 postreal IFT , and 8 postplacebo IFT studies were identified in 26 children ( mean age , 12.7 years ; 16 male ) . Colonic transit was significantly faster in children given real treatment when compared to their pretreatment NTS at 24 ( mean CG , 2.39 vs 3.04 ; P < or = .0001 ) , 30 ( mean GC , 2.79 vs 3.47 ; P = .0039 ) , and 48 ( mean GC , 3.34 vs 4.32 ; P = .0001 ) hours . By contrast , those children who received placebo IFT had no significant change in colonic transit . CONCLUSIONS Transcutaneous electrical stimulation with interferential therapy can significantly speed up colonic transit in children with slow transit constipation AIMS Transcutaneous electrical stimulation ( TES ) was used to treat children with slow-transit constipation ( STC ) for 1 to 2 months in a r and omized controlled trial during 2006 to 2008 . We aim ed to determine long-term outcomes , hypothesizing that TES produced sustained improvement . METHODS Physiotherapists administered 1 to 2 months of TES to 39 children ( 20 minutes , 3 times a week ) . Fifteen continued to self-administer TES ( 30 minutes daily for more than 2 months ) . Mean long-term follow-up of 30 of 39 patients was conducted using question naire review 3.5 years ( range 1.9 - 4.7 years ) later . Outcomes were evaluated by confidence intervals or paired t test . RESULTS Seventy-three percent of patients perceived improvement , lasting more than 2 years in 33 % and less than 6 months in 25 % to 33 % . Defecation frequency improved in 30 % . Stools got wetter in 62 % after stimulation and then drier again . Soiling improved in 75 % and abdominal pain in 59 % . Laxative use stopped in 52 % , and 43 % with appendicostomies stopped washouts . Soiling/Holschneider continence score improved in 81 % ( P = .0002 ) . Timed sits switched to urge-initiated defecations in 80 % patients . Eighty percent of relapsed patients elected to have home stimulation . CONCLUSION TES holds promise for STC children . Improvement occurred in two thirds of children , lasting more than 2 years in one third , whereas symptoms recurred after 6 months in one third of children PURPOSE Transcutaneous electrical stimulation ( TES ) ( 3 sessions/wk ) over the abdomen stimulated bowel functions in a r and omized controlled trial . This pilot study assessed whether daily TES at home with a safe , portable machine would be possible and more efficacious than trial results . METHODS Eleven patients ( 6 male/5 female ; mean age , 14 years ; range , 12 - 18 years ) with slow-transit constipation who relapsed or responded poorly in the trial were recruited ( 11 + /- 5 months later ) . An EPM-IF-4160 ( Fuji Dynamics , Hong Kong ) portable machine ( sine waveform , 4 kHz carrier frequency , 80 - 160 Hz beat frequency , intensity <33 mA ) delivering interferential current ( 2 electrodes over epigastrium + 2 over kidneys ) was applied 1 hour daily at home . Continence diaries were kept for 1 month before and 2 months during treatment . RESULTS All children completed more than 1 month of treatment after baseline recording . Defecation increased in 9 of 11 children , and soiling decreased in 4 of 11 children . There was a significant increase in total episodes of defecation per week ( mean + /- SD , 2.5 + /- 2.1 vs 6.7 + /- 4.4 ; P = .008 ) and a nonsignificant decrease in soiling ( 3.8 + /- 1.6 vs 1.1 + /- 0.5 episodes/wk , P = .1 ) . Daily stimulation does not affect abdominal pain . No adverse events occurred . CONCLUSIONS Daily TES at home is safe and significantly improved bowel function in children who did not respond to 3 times per week of TES . Home TES may be a novel treatment of intractable slow transit constipation , avoiding hospital visits BACKGROUND Slow transit constipation ( STC ) causes intractable symptoms not responsive to medical treatment . Children have irregular bowel motions , colicky abdominal pain , and frequent soiling . Transcutaneous electrical stimulation using interferential current ( interferential therapy [ IFT ] ) is a novel treatment of STC . This study assessed quality of life ( QOL ) in STC children before and after IFT treatment . METHODS Eligible STC children were r and omized to receive either real or placebo IFT ( 12 sessions for 4 weeks ) . Question naires ( Pediatric Quality of Life Inventory ) were administered before and 6 weeks after treatment , with parallel parent and child self-report scales . Higher scores indicate better QOL . Holschneider and Templeton scores were also obtained . The QOL scores were compared using paired t tests . RESULTS Thirty-three children ( 21 male ) , with a mean age of 11.8 years ( range , 7.4 - 16.5 years ) , were recruited ; 16 received real IFT . Child-perceived QOL was improved after real IFT compared with baseline ( 81.1 vs 72.9 , P = .005 ) but not after placebo IFT ( 78.1 vs 74.9 , P = .120 ) . The Holschneider score improved after real IFT ( 10 vs 8 , P = .015 ) but not after placebo IFT ( 9 vs 8 , P = .112 ) . Parentally perceived QOL was similar after real IFT ( 70.1 vs 70.3 , P = .927 ) and placebo IFT ( 70.2 vs 69.8 , P = .899 ) . There were no differences in Templeton scores . CONCLUSION Interferential therapy is a novel therapy for children with STC that improves their self-perceived QOL PURPOSE This study aim ed to test the effectiveness of home transcutaneous electrical stimulation ( TES ) when patients with slow-transit constipation ( STC ) were trained by a naive clinician . METHODS A surgeon was trained to teach the TES method to STC children who then self-administered at home ( 1 hour a day , 3 - 6 months ) using a battery-powered interferential stimulator . Bowel diaries , PedsQL4.0 question naires , and radio-nuclear colonic transit studies were completed before and after treatment . RESULTS Thirty-two children ( 16 female ; mean age , 8.3 years ; range , 3 - 17 years ) self-administered 3 to 6 months of TES . Three did not return diaries . Group 1 ( n = 13 ) started with less than 3 bowel actions per week , and group 2 ( n = 16 ) , with more than 3 bowel actions per week . Defecation frequency increased in 69 % of group 1 ( mean , 1.4 - 3.0 per week ; P = .02 ) . Soiling frequency decreased in 50 % of group 2 ( 5.4 - 1.9 per week , P = .04 ) . Of 13 patients , 7 improved with development of urge-initiated defecation . Abdominal pain decreased in 48 % ( 1.6 episodes per week to 0.9 per week , P = .06 ) . Stool consistency improved in 56 % . There was significant improvement in child-reported and parent-reported PedsQL Scores . Colonic transit improved in 13 of 25 patients . CONCLUSION Home TES provides a new treatment for STC children , with 50 % of treatment-resistant patients benefited . Success requires clinician training and close patient contact . Transcutaneous electrical stimulation increased defecation and reduced soiling The second part of the Consensus Statement of the Italian Association of Hospital Gastroenterologists and Italian Society of Colo-Rectal Surgery reports on the treatment of chronic constipation and obstructed defecation . There is no evidence that increasing fluid intake and physical activity can relieve the symptoms of chronic constipation . Patients with normal-transit constipation should increase their fibre intake through their diet or with commercial fibre . Osmotic laxatives may be effective in patients who do not respond to fibre supplements . Stimulant laxatives should be reserved for patients who do not respond to osmotic laxatives . Controlled trials have shown that serotoninergic enterokinetic agents , such as prucalopride , and prosecretory agents , such as lubiprostone , are effective in the treatment of patients with chronic constipation . Surgery is sometimes necessary . Total colectomy with ileorectostomy may be considered in patients with slow-transit constipation and inertia coli who are resistant to medical therapy and who do not have defecatory disorders , generalised motility disorders or psychological disorders . R and omised controlled trials have established the efficacy of rehabilitative treatment in dys-synergic defecation . Many surgical procedures may be used to treat obstructed defecation in patients with acquired anatomical defects , but none is considered to be the gold st and ard . Surgery should be reserved for selected patients with an impaired quality of life . Obstructed defecation is often associated with pelvic organ prolapse . Surgery with the placement of prostheses is replacing fascial surgery in the treatment of pelvic organ prolapse , but the efficacy and safety of such procedures have not yet been established |
839 | 27,343,750 | The remaining studies generally found low or no incidence of PID among IUD users .
No direct evidence addresses potential differences in HIV disease progression or transmission by HIV disease severity .
CONCLUSION Limited evidence of fair to poor quality found no differences in infectious complications when comparing IUD complication rates among women with varying levels of HIV disease severity .
One study found that IUD use was not associated with HIV transmission , and studies generally found no differences in genital viral shedding or disease progression ; however , there was little direct evidence to address potential differences related to HIV severity | BACKGROUND Use of highly effective contraception among women living with HIV is critical to prevent unintended pregnancy and subsequent risk of maternal complications and perinatal HIV transmission .
However , it is not known whether use of intrauterine devices ( IUDs ) among women with advanced HIV disease poses an increased risk of pelvic infection or HIV progression and transmission .
OBJECTIVES To identify evidence regarding the risk of pelvic infection , HIV disease progression or HIV transmission among women with HIV using IUDs and whether this risk differs by severity of HIV disease . | OBJECTIVE : To compare discontinuation rates of the levonorgestrel and copper intrauterine devices ( IUDs ) among women with human immunodeficiency virus . METHODS : A double-masked r and omized trial was conducted at Mulago Hospital , Ug and a. Women received either a copper or levonorgestrel IUD . The primary outcome was discontinuation of intrauterine contraception within 1 year of placement . The secondary outcomes were incidence of side effects and severe adverse events . To discern a difference of 10 % from a copper IUD discontinuation rate of 18 % , power of 80 % , and 95 % confidence interval ( CI ) , a sample size of 351 per arm was estimated . Analysis of the primary outcome was by intension-to-treat principle . RESULTS : From September 2013 to December 2014 , 979 were screened and 703 r and omized as follows : 349 to the copper group and 354 to the levonorgestrel group . In total , 8.6 % ( 29/338 ) women in the copper group compared with 8.1 % ( 27/334 ) in the levonorgestrel group discontinued intrauterine conception within 1 year of placement ( incidence rate ratio 1.1 [ 95 % CI 0.64–1.96 ] ) . Overall , the incidence of heavy bleeding was higher in the copper group ( 37 % [ 125/338 ] ) than in the levonorgestrel group ( 19.5 % [ 65/334 ] ) . However , the incidence of amenorrhea , which occurred in 3.3 % ( 11/338 ) of women , was lower in the copper group than the 19.8 % ( 66/334 ) of women who reported amenorrhea in the levonorgestrel group . CONCLUSION : There was no difference in discontinuation rates between the copper and levonorgestrel devices . Women in the levonorgestrel group had reduced incidence of heavy bleeding and a higher incidence of amenorrhea compared with those in the copper group . CLINICAL TRIAL REGISTRATION : Pan African Clinical Trial Registry , www.pactr.org , PACTR 201308000561212 . LEVEL OF EVIDENCE : Objective : To determine the effect of cryotherapy on HIV-1 cervical shedding . Design : Prospect i ve cohort study . Methods : Five hundred HIV-positive women enrolled at an HIV treatment clinic in Nairobi , Kenya were screened for cervical cancer . Women diagnosed with cervical intraepithelial neoplasia stage 2 or 3 ( CIN 2/3 ) by histology were offered cryotherapy treatment . The first 50 women had cervical swabs taken at baseline and at 2 and 4 weeks following treatment . Swabs were analyzed for HIV-1 RNA and compared using General Estimating Equation ( GEE ) with binomial or Gaussian links . Results : Of the 50 women enrolled , 40 were receiving antiretroviral therapy ( ART ) and 10 were not receiving ART at the time of cryotherapy and during study follow-up . Among all women , the odds of detectable cervical HIV-1 RNA did not increase at 2 weeks [ odds ratio ( OR ) 1.18 ; 95 % confidence interval ( CI ) 0.65–2.13 ] or 4 weeks ( OR 1.29 ; 95 % CI 0.71–2.33 ) following cryotherapy . Among 10 women not receiving ART , the OR of detectable shedding at 2 weeks was higher , but not statistically significant ( OR 4.02 ; 95 % CI 0.53–30.79 ; P = 0.2 ) , and at 4 weeks remained unchanged ( OR 1.00 ; 95 % CI 0.27–3.74 ) . Conclusion : There was no increase in detectable cervical HIV-1 RNA among HIV-positive women after cryotherapy . The risk of HIV-1 transmission after cryotherapy may not be significant , particularly among women already on ART at the time of cervical treatment . However , further investigation is needed among women not receiving ART OBJECTIVE To assess outcome in HIV-positive women undergoing the loop electrosurgical excision procedure ( LEEP ) . METHOD A prospect i ve study was conducted with 789 out patients undergoing LEEP at Chiang Mai University Hospital between October 2004 and June 2008 . RESULTS The 70 HIV-positive women ( 8.9 % ) were younger ( P<0.001 ) and had a lower parity ( P<0.001 ) than the remaining women . The proportion of women undergoing LEEP for persistent low- grade lesions was higher ( 8.6 % vs 1.9 % ) and the prevalence of margin involvement was higher ( 60.0 % vs 49.4 % ) among the HIV-positive women . After adjusting for age , parity , menopausal status , size of excised lesion , and histopathologic result , HIV infection was not significantly associated with LEEP complications ( adjusted odds ratio , 0.41 ; 95 % confidence interval , 0.15 - 1.15 ) . CONCLUSION The higher risk of resection margin involvement in HIV-infected women was not associated with LEEP complications STUDY QUESTION Does laboratory testing after syndromic screening for sexually transmitted infections ( STIs ) reduce the rate of intrauterine contraception ( IUC ) removal among women living with HIV/AIDS ( WLHA ) ? SUMMARY ANSWER Additional laboratory testing after syndromic screening for STIs did not affect the likelihood that a woman would remove an IUC immediately or within 1 year of IUC use or the frequency of post-insertion unscheduled clinic visits . In low-risk WLHA , the incidence rate of IUC removal is low with or without laboratory testing . WHAT IS KNOWN ALREADY Fear of infectious morbidity remains an obstacle to uptake of IUC by WLHA . The value of laboratory testing after syndromic screening for STI before the insertion of IUC remains uncertain . STUDY DESIGN , SIZE , DURATION We enrolled WLHA from 2 September to 6 December 2013 and followed them up to 31 December 2014 . After syndromic screening , 703 women free of STIs were r and omized to either additional laboratory screening or no additional screening for STI before IUC insertion . The r and omization sequence was generated by an independent statistician and r and omization numbers placed in opaque sequentially numbered sealed envelopes . All women r and omized had an IUC inserted and in all 672 participants completed the 1-year follow-up . The study staff who followed up the participants were blinded to the study allocation groups . Incidence rate ratios ( IRRs ) were used to compare the incidence rates of IUC removal , unscheduled clinic attendance and IUC continuation between the two groups . PARTICIPANTS / MATERIAL S , SETTING , METHODS Women eligible to participate were 18 - 49 years old at study entry , in a relationship with a male partner , wanted to avoid pregnancy for at least 1 year and were undergoing HIV/AIDS care at Mulago Hospital , Ug and a. Participants completed a baseline question naire and up to four follow-up question naires until discontinuation of IUC , loss to follow-up or end of study observation after 12 months . MAIN RESULTS AND THE ROLE OF CHANCE The rate of IUC removal was 8.8 % ( 29/331 ) in the no additional screening group and 8.0 % ( 27/341 ) in the additional laboratory screening group [ IRR 1.1 ( 95 % CI 0.63 - 1.93 ) ] . Unscheduled clinic attendances were similar in the two groups at 1 year of IUC insertion : 13.6 % ( 45/331 ) in the no additional screening group and 12.3 % ( 42/241 ) in the additional laboratory screening group . During the 1-year follow-up , only five women , three from the no additional screening group and two from the additional laboratory screening group , developed pelvic inflammatory disease ( PID ) , as defined by established diagnostic criteria . LIMITATIONS , REASONS FOR CAUTION We were not able to carry out STI risk assessment directly from the men thus women with high-risk partners could have been included in the study and this may be responsible for the lack of a demonstrable effect of additional laboratory screening on incidence rates of IUC removals and unscheduled clinic attendance . The diagnosis of PID was based on clinical signs and symptoms ; therefore , sub clinical PID could have been missed . WIDER IMPLICATION S OF THE FINDINGS Among WLHA , the incidence rate of IUC removal is low and IUC continuation high . Syndromic screening for STIs could be sufficient in indentifying WLHA who are suitable for IUC use . However , our findings are only generalizable to women in HIV/AIDS care who have access to good follow-up . STUDY FUNDING /COMPETING INTERESTS The study was supported by Medical Education for Equitable Services to all Ug and ans , a Medical Education Partnership Initiative grant number 5R24TW008886 from the office of Global AIDS Coordinator and the US Department of Health and Human Services , Health Re sources and Services Administration and National Institutes of Health . Additional funding was from the Swedish International Development Agency , Swedish Research Council ( SIDA/VR ) . The authors have no competing interests to declare . TRIAL REGISTRATION NUMBER This trial was registered at Pan African Clinical Trial , Registry . PACTR 201308000561212 BACKGROUND Plasma HIV-1 RNA concentration has been the best predictor for risk of heterosexual and perinatal transmission . However , direct contact with HIV-1 present locally in the genital tract might be necessary for transmission . We aim ed to assess the relation between HIV-1 shedding ( RNA or culturable virus ) in female genital secretions and other factors that might affect HIV-1 shedding . METHODS This was a cross-sectional study within the Women 's Interagency HIV Study ( WIHS ) , a prospect i ve longitudinal cohort study of HIV-infected women . We enrolled 311 HIV positive women from Jan 30 , 1997 to July 1 , 1998 . We did clinical assessment s , cultured HIV-1 , and measured RNA in peripheral blood mononuclear cells ( P BMC ) and genital secretions . We compared the results with univariate and multivariate analyses . Presence of HIV-1 RNA or culturable virus in genital secretions was defined as HIV-1 shedding . FINDINGS HIV-1 RNA was present in genital secretions of 57 % ( 152/268 ) of women whereas infectious virus was detected only in 6 % ( 17/271 ) . Genital tract HIV-1 shedding was found in 80 % ( 130/163 ) of women with detectable plasma RNA and 78 % ( 116/148 ) of women with positive P BMC cultures . 33 % ( 27/83 ) of women with less than 500 copies/mL plasma RNA and 39 % ( 35/90 ) of those with negative P BMC cultures also had genital tract shedding . INTERPRETATION Plasma RNA concentration , both qualitatively and quantitatively , was the most important factor in predicting genital HIV-1 shedding , even among women receiving potent antiretroviral therapy . However , HIV-1 shedding did occur in women with less than 500 copies/mL plasma HIV-1 RNA . This finding suggests that a separate reservoir of HIV-1 replication may exist in some women BACKGROUND The effects of estrogen-containing contraceptives on disease activity in women with systemic lupus erythematosus have not been determined . METHODS We conducted a single-blind clinical trial involving 162 women with systemic lupus erythematosus who were r and omly assigned to combined oral contraceptives , a progestin-only pill , or a copper intrauterine device ( IUD ) . Disease activity was assessed at 0 , 1 , 2 , 3 , 6 , 9 , and 12 months according to the Systemic Lupus Erythematosus Disease Activity Index ( SLEDAI ) . The primary outcome was global disease activity , which we estimated by measuring the area under the SLEDAI curve . Secondary outcomes included the maximum SLEDAI score , change in SLEDAI score , incidence of lupus flares , median time to first flare , systemic lupus erythematosus treatment , and adverse events . The results were analyzed by the intention-to-treat method . RESULTS At baseline , all demographic features and disease characteristics were similar in the three groups . The mean ( + /-SD ) SLEDAI score was 6.1+/-5.6 in the group assigned to combined oral contraceptives , 6.4+/-4.6 in the group assigned to the progestin-only pill , and 5.0+/-5.3 in the group assigned to the IUD ( 54 patients in each group ) ( P=0.36 ) . Disease activity remained mild and stable in all groups throughout the trial . There were no significant differences among the groups during the trial in global or maximum disease activity , incidence or probability of flares , or medication use . The median time to the first flare was three months in all groups . Thromboses occurred in four patients ( two in each of the two groups receiving hormones ) , and severe infections were more frequent in the IUD group . One patient receiving combined oral contraceptives died from amoxicillin-related severe neutropenia . CONCLUSIONS Global disease activity , maximum SLEDAI score , incidence of flares , time to first flare , and incidence of adverse events were similar among women with systemic lupus erythematosus , irrespective of the type of contraceptive they were using OBJECTIVE Hormonal contraception has been associated with an increased prevalence of cervical shedding of HIV-1 DNA among infected women . We conducted this study to evaluate the effect of the use of an intrauterine device ( IUD ) on the detection of HIV-1 DNA in cervical secretions . DESIGN A prospect i ve study of HIV-1-seropositive women undergoing IUD insertion at two public family planning clinics in Nairobi , Kenya . METHODS Cervical swab sample s were collected before IUD insertion and approximately 4 months thereafter for the detection of HIV-1-infected cells using polymerase chain reaction ( PCR ) amplification of HIV-1 gag DNA sequences . RESULTS Ninety-eight women were enrolled and followed after IUD insertion . The prevalence of HIV-1 DNA cervical shedding was 50 % at baseline and 43 % at follow-up [ odds ratio ( OR ) 0.8 , 95 % confidence interval ( CI ) 0.5 - 1.2 ] . There was no statistically significant difference between the baseline and follow-up shedding rates in a multivariate model that controlled for previous hormonal contraceptive use , condom use , cervical ectopy , friable cervix , cervical infections at an interim visit , and CD4 lymphocyte levels ( OR 0.6 , 95 % CI 0.3 - 1.1 ) . CONCLUSION The insertion of an IUD did not significantly alter the prevalence of cervical shedding of HIV-1-infected cells . The use of IUDs , in conjunction with condoms , may be an appropriate method of contraception for HIV-1-infected women from the st and point of potential infectivity to the male partner through exposure to genital HIV-1 OBJECTIVE To evaluate contraceptive adherence to the copper intrauterine device ( Cu-IUD ) and the injectable depot medroxyprogesterone acetate ( DMPA ) among women with HIV in Lilongwe , Malawi . METHODS We r and omized 200 HIV-infected women on highly active antiretroviral therapy ( HAART ) to either the Cu-IUD or DMPA and followed these women prospect ively , evaluating adherence and factors associated with nonadherence . RESULTS There was no difference in contraceptive adherence : 68 % of Cu-IUD and 65 % of DMPA users were adherent at 48 weeks . Receiving first-choice contraceptive was not associated with adherence . Women commonly cited partner 's disapproval as an indication for discontinuation . Women who experienced heavy menstruation and first-time contraceptive users were more likely to be nonadherent . Among ongoing users at study conclusion , 95 % were happy with their method , and 98 % would recommend their method to a friend . CONCLUSION Contraceptive adherence between the Cu-IUD and DMPA was similar at 1 year . With similar adherence and similar high rates of satisfaction among users of both methods at 1 year , the Cu-IUD offers a hormone-free alternative to DMPA . IMPLICATION S Adherence to the Cu-IUD and DMPA is similar at 1 year among HIV-infected women on HAART in a r and omized controlled trial . Despite high method satisfaction , partner disapproval and heavy bleeding contribute to reduced adherence . Receiving a method that differs from participant 's first-choice method did not influence adherence OBJECTIVE To assess whether the risk of complications is higher in HIV-1-infected women compared with non-infected women in the two years following insertion of the intrauterine contraceptive device . DESIGN Prospect i ve cohort study . POPULATION Six hundred and forty-nine women ( 156 HIV-1-infected , 493 non-infected ) in Nairobi , Kenya who requested an intrauterine contraceptive device and met local eligibility criteria . METHODS We gathered information on complications related to the use of the intrauterine contraceptive device , including pelvic inflammatory disease , removals due to infection , pain or bleeding , expulsions , and pregnancies at one , four , and 24 months after insertion by study physicians masked to participants ' HIV-1 status . Cox regression was used to estimate hazard ratios . RESULTS Complications were identified in 94 of 636 women returning for follow up ( 14.7 % of HIV-1-infected , 14.8 % of non-infected ) . The incidence of pelvic inflammatory disease was rare in both infected ( 2.0 % ) and non-infected ( 0.4 % ) groups . Multivariate analyses suggested no association between HIV-1 infection and increased risk of overall complications ( hazard ratio = 1.0 ; 95 % CI 0.6 - 1.6 ) . Infection-related complications ( e.g. any pelvic tenderness , removal for infection or pain ) were also similar between groups ( 10.7 % of HIV-1-infected , 8.8 % of non-infected ; P = 0.50 ) , although there was a non-significant increase in infection-related complications among HIV-1-infected women with use of the intrauterine contraceptive device longer than five months ( hazard ratio = 1.8 ; 95 % CI 0.8 - 4.4 ) . Neither overall nor infection-related complications differed by CD4 ( immune ) status . CONCLUSIONS HIV-1-infected women often have a critical need for safe and effective contraception . The intrauterine contraceptive device may be an appropriate contraceptive method for HIV-1-infected women with ongoing access to medical services The objective of this study was to evaluate the treatment outcomes and complications in human immunodeficiency virus (HIV)–infected women undergoing loop electrosurgical excision procedure ( LEEP ) for cervical neoplasia . The medical record of 60 evaluable HIV-infected women who had abnormal Papanicolaou ( Pap ) smear and underwent LEEP following colposcopy at Chiang Mai University Hospital between May 1998 and June 2004 was review ed . Thirty-one ( 51.7 % ) had associated genital infection at screening . Twenty-five ( 41.7 % ) had opportunistic infection , but only 18 ( 30.0 % ) were treated with antiretroviral therapy . The most common abnormal Pap smear was high- grade squamous intraepithelial lesion ( 46.7 % ) , followed by low- grade squamous intraepithelial lesion ( 40.0 % ) . Forty ( 66.7 % ) women had clear surgical margins after LEEP . Only one ( 1.7 % ) woman had severe intraoperative hemorrhage . Early and late postoperative hemorrhage were noted in three ( 5 % ) women of each period . Localized infection of the cervix was detected in seven ( 11.7 % ) women . Two ( 3.3 % ) women developed cervical stenosis at 6 months after LEEP . There was no significant difference in overall complications between HIV-infected women and the control group ( P = 0.24 ) . Among 60 HIV-infected women , no statistical difference in the rate of margins involvement ( P = 1.00 ) and complications ( P = 0.85 ) could be demonstrated between HIV-infected women who received antiretroviral therapy and those who did not . Disease-free rate at 6 and 12 months were 97.1 % and 88 % , respectively . These data demonstrated that LEEP appears to be safe and effective in HIV-infected women BACKGROUND Safe and effective contraceptives are needed for human immunodeficiency virus (HIV)-infected women . The levonorgestrel-releasing intrauterine system ( LNG-IUS ) is a highly effective contraceptive with additional health benefits . The objective of this study was to evaluate the effects of the LNG-IUS among HIV-infected women . METHODS Twelve systematic ally managed HIV-infected women were studied prospect ively . Following a 2-month run-in period , the subjects had an LNG-IUS inserted and were followed up for 1 year . Patterns of bleeding , blood haemoglobin and CD4-lymphocyte content , plasma HIV RNA , serum levels of LNG , of estradiol ( E(2 ) ) and of ferritin and genital shedding of HIV RNA were monitored . RESULTS Menstrual bleeding was reduced significantly during the use of the LNG-IUS ; this was associated with slight increases in serum haemoglobin and ferritin levels . Serum E(2 ) concentrations remained in the follicular range in all subjects . Among subjects using antiretroviral medication , the proportion of cervicovaginal lavage specimens with detectable HIV RNA was 10 % before and after the insertion of the LNG-IUS . CONCLUSIONS The effects of the LNG-IUS on bleeding patterns , body iron stores and ovarian function were similar to those seen in healthy women . Genital shedding of HIV RNA was not affected by the LNG-IUS . These data encourage further studies on the effects of the LNG-IUS on reproductive health among HIV-infected women OBJECTIVE The purpose of this study was to determine whether the intrauterine contraceptive device ( IUD ) is effective and safe among women who are infected with the human immunodeficiency virus ( HIV ) . STUDY DESIGN We r and omly assigned 599 postpartum , HIV-infected women in Zambia to receive either a copper IUD or hormonal contraception and followed them for at least 2 years . RESULTS Women who were assigned r and omly to hormonal contraception were more likely to become pregnant than those who were assigned r and omly to receive an IUD ( rate , 4.6/100 vs 2.0/100 woman-years ; hazards ratio , 2.4 ; 95 % CI , 1.3 - 4.7 ) . One woman who was assigned to the IUD experienced pelvic inflammatory disease ( crude rate , 0.16/100 woman-years ; 95 % CI , 0.004 - 868 ) ; there was no pelvic inflammatory disease among those women who were assigned to hormonal contraception . Clinical disease progression ( death or CD4 + lymphocyte count dropping below 200 cells/microL ) was more common in women who were allocated to hormonal contraception ( 13.2/100 woman-years ) than in women who were allocated to the IUD ( 8.6/100 woman-years ; hazard ratio , 1.5 ; 95 % CI , 1.04 - 2.1 ) . CONCLUSION The IUD is effective and safe in HIV-infected women . The unexpected observation that hormonal contraception was associated with more rapid HIV disease progression requires urgent further study OBJECTIVE The primary target cells for the human immunodeficiency virus ( HIV ) infection in the genital tract are CD4 T cells that express CCR5 on the surface . Alterations in genital tract T cells that express CCR5 could impact HIV acquisition risk . We hypothesized that , when compared with baseline , the use of a hormonal intrauterine device ( IUD ) would alter HIV target cells ( primarily CCR5 + CD4 cells ) in the female genital tract more than a nonhormonal IUD . STUDY DESIGN Thirty-four healthy HIV-negative women aged 18 - 40 years who were seeking an IUD for contraception were assigned r and omly to receive a levonorgestrel IUD or a copper T380A IUD . A parallel group of 8 control women who did not need contraception was also enrolled . Genital tract mucosal immune cell population s that were collected by cervical cytobrush and endometrial biopsy before and 2 months after IUD placement were analyzed by flow cytometry . Mean differences in cell number and percent that expressed receptors from baseline to follow-up examination were evaluated with the use of paired Student t tests . RESULTS Neither IUD altered the number of T cells within the upper and lower genital tracts . Levonorgestrel IUD users had a decrease in T cells that expressed the HIV coreceptor CCR5 in the endometrium and cervix after 2 months of use compared with baseline . There was a decrease in activated endometrial T cells in levonorgestrel IUD users and a decrease in activated cervical T cells in copper IUD users after 2 months of IUD use , compared with baseline . CONCLUSION Women who use IUDs have reduced expression of the CCR5 HIV coreceptor on T cells in the endometrium and cervix compared with expression before IUD placement . These findings suggest that susceptibility to HIV infection would not be increased by IUD use Background : HIV-infected women need access to safe contraception . We hypothesized that women using depomedroxyprogesterone acetate ( DMPA ) contraception would have faster HIV disease progression than women using oral contraceptive pills ( OCPs ) and nonhormonal methods . Methods : In a previously reported trial , we r and omized 599 HIV-infected women to the intrauterine device ( IUD ) or hormonal contraception . Women r and omized to hormonal contraception chose between OCPs and DMPA . This analysis investigates the relationship between exposure to hormonal contraception and HIV disease progression [ defined as death , becoming eligible for antiretroviral therapy ( ART ) , or both ] . Results : Of the 595 women not on ART at the time of r and omization , 302 were allocated to hormonal contraception , of whom 190 ( 63 % ) initiated DMPA and 112 ( 37 % ) initiated OCPs . Women starting IUD , OCPs , or DMPA were similar at baseline . Compared with women using the IUD , the adjusted hazard of death was not significantly increased among women using OCPs [ 1.24 ; 95 % confidence interval ( CI ) 0.42–3.63 ] or DMPA ( 1.83 ; 95 % CI 0.82–4.08 ) . However , women using OCPs ( adjusted hazard ratio ( AHR ) 1.69 ; 95 % CI 1.09–2.64 ) or DMPA ( AHR 1.56 ; 95 % CI 1.08–2.26 ) trended toward an increased likelihood of becoming eligible for ART . Women exposed to OCPs ( AHR 1.67 ; 95 % CI 1.10–2.51 ) and DMPA ( AHR 1.62 ; 95 % CI 1.16–2.28 ) also had an increased hazard of meeting our composite disease progression outcome ( death or becoming ART eligible ) than women using the IUD . Conclusion : In this secondary analysis , exposure to OCPs or DMPA was associated with HIV disease progression among women not yet on ART . This finding , if confirmed elsewhere , would have global implication s and requires urgent further investigation |
840 | 27,878,357 | Results Pooled data revealed that the occurrence of ST and ETS ≥20 % ( v < 20 % ) during anti-EGFR MoAb treatment were both associated with better OS , PFS and ORR .
This association could not be disturbed by KRAS status .
Mean changes in safety follow-up life health state from baseline appeared unaffected by ST .
Only mCRC patients with wild-type KRAS tumor who suffered grade 2 + ST could benefit from additional anti-EGFR treatment to chemotherapy or best supportive care ( BSC ) alone .
ETS was also a predictor for absolute survival benefit acquired from additional anti-EGFR treatment for patients with wild-type KRAS tumors , and the more early shrinkage the tumor was , the much benefit was observed .
ConclusionS T and ETS are predictive of absolute benefit acquired from anti-EGFR treatment in mCRC patients with wild-type KRAS tumors . | Purpose Skin toxicity ( ST ) and early tumor shrinkage ( ETS ) are early phenomenon during the anti-epidermal growth factor receptor ( EGFR ) monoclonal antibody ( MoAb ) treatment . | Importance RAS wild-type ( wt ) status is necessary but not sufficient for response to anti-epidermal growth factor receptor ( EGFR ) agents in advanced colorectal cancer ( aCRC ) . RNA expression of EGFR lig and s epiregulin ( EREG ) and amphiregulin ( AREG ) may correlate with EGFR-targeted therapy efficacy in aCRC , so may represent a much-needed additional predictive marker for these drugs . Objective To examine a novel lig and model in a r and omized clinical trial of panitumumab , irinotecan , and ciclosporin in colorectal cancer ( PICCOLO ) with with the a priori hypothesis that high tumor expression of either AREG or EREG would predict panitumumab therapy benefit in RAS-wt patients ; and low expression , lack of efficacy . Design , Setting , and Participants Prospect ively planned retrospective biomarker study from the PICCOLO trial , which tested the addition of panitumumab to irinotecan therapy in patients with KRAS wt aCRC who experienced failure with prior fluoropyrimidine treatment . The analysis was conducted between 2012 and 2014 . A predefined dichotomous model classified tumors as " high expressor " ( either EREG or AREG in top tertile for messenger RNA level ) or " low expressor " ( neither EREG nor AREG in top tertile ) . Lig and expression was assessed as a prognostic and predictive biomarker . Expression of AREG/EREG and RAS and BRAF mutations were assessed in archival tumor tissue . Main Outcomes and Measures Primary end point was progression-free survival ( PFS ) ; secondary end points were response rate and overall survival ( OS ) . Results Of the 696 PICCOLO trial patients in the irinotecan-vs-irinotecan with panitumumab r and omization , 331 had sufficient tumor tissue available and measurement of lig and expression was successful in 323 . High lig and expression was not prognostic for OS ( hazard ratio [ HR ] , 0.79 [ 95 % CI , 0.58 - 1.09 ] ; P = .15 ) or PFS ( HR , 0.93 [ 95 % CI , 0.68 - 1.27 ] ; P = .64 ) . The primary population had RAS wt aCRC ( n = 220 ) ; for RAS wt patients with high lig and expression , median ( interquartile range [ IQR ] ) PFS was 8.3 [ 4.0 - 11.0 ] months ( irinotecan with panitumumab ) vs 4.4 [ 2.8 - 6.7 ] months ( irinotecan alone ) ; HR , 0.38 [ 95 % CI , 0.24 - 0.61 ] ; P < .001 ) . In RAS wt patients with low lig and expression , median ( IQR ) PFS was 3.2 [ 2.7 - 8.1 ] months ( irinotecan with panitumumab ) vs 4.0 [ 2.7 - 7.5 ] months ( irinotecan ) ; HR , 0.93 [ 95 % CI , 0.64 - 1.37 ] ; P = .73 ; interaction test results were significant [ P = .01 ] ) . Less marked effects were seen for response rate ( interaction P = .17 ) and OS ( interaction P = .11 ) . Conclusions and Relevance High lig and expression is a predictive marker for panitumumab therapy benefit on PFS in RAS wt patients ; conversely , patients with low lig and expression gained no benefit . The current " opt-in " strategy for anti-EGFR therapy in all patients with RAS wt aCRC should be question ed . Expression of EREG/AREG is a useful biomarker for anti-EGFR therapy ; optimization for clinical use is indicated . Trial Registration is rct n Identifier : IS RCT N93248876 The epidermal growth factor receptor ( EGFR ) , which participates in signalling pathways that are deregulated in cancer cells , is frequently mutated in colorectal-cancer cells . Cetuximab is a monoclonal antibody that specifically blocks the EGFR . We evaluated the efficacy of cetuximab in weekly combination with irinotecan in metastatic colorectal cancer patients refractory to previous treatments based on oxaliplatin or irinotecan . We included 55 heavily pretreated patients ( colon/rectum : 34/11 , M/F : 16/29 , median age 63 years , range : 27–79 ) whose disease had progressed during or within an oxaliplatin-based first-line chemotherapy and a irinotecan-based second-line regimen . Patients were followed for tumour response and were also evaluated for the time to tumour progression , and safety of treatment . Cetuximab was given at an initial dose of 400 mg m−2 , followed by weekly infusions of 250 mg m−2 . Irinotecan was administered weekly at the dose of 90 mg m−2 . All patients were assessable for treatment efficacy and safety response rate was 25.4 % ( 95 % CI : 21.7–39.6 % ) ; 38.2 % ( 95 CI : 18.6–39.8 % ) of patients showed a disease stability as the best response . As a consequence , the overall tumour control rate was 63.6 % ( 95 % CI : 46.4–70.6 % ) . The median time to progression was 4.7 months ( 95 % CI : 2.5–7.1 months ) and the median survival time was 9.8 months ( 95 % CI : 3.9–10.1 months ) . The most common G3 - 4 noncutaneous side toxicities were : diarrhoea ( 16.4 % ) , fatigue ( 12.7 % ) and stomatitis ( 7.3 % ) . 89.1 % of patients developed skin toxicity and 32.6 % of cases was of grade 3–4 . No allergic reactions were identified at any courses in any patients . Fever was documented in 27.3 % of patients and was most commonly recorded after the first administration . Cetuximab has clinical ly significant activity even in heavily pretreated colorectal cancer patients progressed after both oxaliplatin and irinotecan-based chemotherapy regimens BACKGROUND Cetuximab , an IgG1 chimeric monoclonal antibody against epidermal growth factor receptor ( EGFR ) , has activity against colorectal cancers that express EGFR . METHODS From December 2003 to August 2005 , 572 patients who had colorectal cancer expressing immunohistochemically detectable EGFR and who had been previously treated with a fluoropyrimidine , irinotecan , and oxaliplatin or had contraindications to treatment with these drugs underwent r and omization to an initial dose of 400 mg of cetuximab per square meter of body-surface area followed by a weekly infusion of 250 mg per square meter plus best supportive care ( 287 patients ) or best supportive care alone ( 285 patients ) . The primary end point was overall survival . RESULTS In comparison with best supportive care alone , cetuximab treatment was associated with a significant improvement in overall survival ( hazard ratio for death , 0.77 ; 95 % confidence interval [ CI ] , 0.64 to 0.92 ; P=0.005 ) and in progression-free survival ( hazard ratio for disease progression or death , 0.68 ; 95 % CI , 0.57 to 0.80 ; P<0.001 ) . These benefits were robust after adjustment in a multivariable Cox proportional-hazards model . The median overall survival was 6.1 months in the cetuximab group and 4.6 months in the group assigned to supportive care alone . Partial responses occurred in 23 patients ( 8.0 % ) in the cetuximab group but in none in the group assigned to supportive care alone ( P<0.001 ) ; the disease was stable in an additional 31.4 % of patients assigned to cetuximab and in 10.9 % of patients assigned to supportive care alone ( P<0.001 ) . Quality of life was better preserved in the cetuximab group , with less deterioration in physical function and global health status scores ( both P<0.05 ) . Cetuximab treatment was associated with a characteristic rash ; a rash of grade 2 or higher was strongly associated with improved survival ( hazard ratio for death , 0.33 ; 95 % CI , 0.22 to 0.50 ; P<0.001 ) . The incidence of any adverse event of grade 3 or higher was 78.5 % in the cetuximab group and 59.1 % in the group assigned to supportive care alone ( P<0.001 ) . CONCLUSIONS Cetuximab improves overall survival and progression-free survival and preserves quality -of-life measures in patients with colorectal cancer in whom other treatments have failed . ( Clinical Trials.gov number , NCT00079066 [ Clinical Trials.gov ] . ) The authors explored the association of skin toxicity ( ST ) severity as measured by patient‐reported ST and Common Terminology Criteria for Adverse Events ( CTCAE ) grading with efficacy of panitumumab , a fully human antiepidermal growth factor receptor antibody , from a phase 3 metastatic colorectal cancer ( CRC ) trial |
841 | 15,495,019 | 2 .
Antihistamines were no more effective than placebo in relieving cough symptoms .
REVIEW ERS ' CONCLUSIONS There is no good evidence for or against the effectiveness of OTC medicines in acute cough .
More evidence about the effectiveness of OTC cough preparations would be helpful , as identification of effective self-care treatments may help reduce the burden of days lost at work due to acute cough as well as the number of consultations in primary care .
Identification of ineffective preparations could avoid costs for consumers and health care providers | BACKGROUND Acute cough due to upper respiratory tract infection ( URTI ) is a common symptom .
Many health practitioners recommend non-prescription over-the-counter ( OTC ) medicines as a first-line treatment for cough , but there is little evidence as to whether these drugs are effective .
OBJECTIVES To assess the effects of oral over-the-counter cough preparations for acute cough . | Codeine is generally accepted as the st and ard antitussive against which new antitussive medications are compared . This presents a problem because the support for codeine 's antitussive activity comes from studies on cough in animals , and chronic and induced cough models in man , whereas antitussives are almost exclusively used for the treatment of cough associated with acute upper respiratory tract infection ( URTI ) . The aims of this study were twofold . Firstly , to study the antitussive efficacy of codeine in cough associated with URTI and , secondly , to vali date a sound meter as tool for quantifying cough . The efficacy of codeine was assessed in a double-blind , stratified , placebo-controlled , parallel-group , clinical trial using three different measures of cough : cough sound-pressure levels ( CSPLs ) measured on a sound meter ; subjective scores of cough severity ; and cough frequency recorded by means of a microphone connected to an ink-pen recorder . A group of 82 subjects ( 51 females and 31 males ; mean age 23.5 years , range 18 - 46 years ) with cough owing to acute URTI were included in the study . The study took place on two separate study days . On study day 1 cough measurements were made before and 90 min after treatment with a single dose of either 50 mg codeine or matched placebo in capsule form . The same three measures of cough were repeated 2 - 5 days later ( study day 2 ) . On study day 1 a highly significant ( P < 0.0001 ) decrease in all three measures of cough was found after treatment with both placebo and codeine yet there was no significant difference between the treatment groups . A highly significant ( P < 0.0001 ) decrease in the three measures of cough was also found between days 1 and 2 . The results demonstrate that codeine is no more effective than placebo in reducing cough associated with acute URTI , as measured by CSPLs , cough frequency or subjective symptom scores . This result might be explained on the basis of two central pathways for cough ; a reflex pathway via the brain-stem which is sensitive to codeine and a voluntary pathway via the cortex which is unaffected by codeine . The results also demonstrate that the sound-level meter appears to be a potentially useful investigative tool for the assessment of cough and antitussive efficacy To determine whether the cough of the common cold arises from upper respiratory stimuli and whether antihistamine-decongestant therapy is an effective treatment for this cough , we prospect ively evaluated volunteers with uncomplicated common colds in a r and omized , double-blind , placebo-controlled study . After completing a st and ardized question naire and undergoing a physical examination , throat-culturing , and pulmonary function testing , subjects took the active drug or identical-appearing placebo for 7 days while they kept a diary in which they ranked the severity of 17 symptoms for 14 days . Pulmonary function testing was repeated , on average , on Days 4 , 8 , and 14 . Forty-six percent of the variation in cough severity could be explained by throat-clearing and 47 % of the variation in throat-clearing severity by postnasal drip . FIF50 % , the only physiologic parameter that significantly correlated with cough , rose as cough severity fell . Antihistamine-decongestant therapy reduced postnasal drip and significantly decreased the severity of cough , nasal obstruction , nasal discharge , and throat-clearing during the first few days of the common cold . In addition , cough was 20 to 30 % less prevalent in the active drug group within 3 days of starting therapy . We conclude that the cough of the common cold arose from upper respiratory tract stimuli and that cough and other cardinal symptoms of the common cold were reduced with antihistamine-decongestant therapy when these symptoms were at their worst The efficacy of guaifenesin in reducing cough frequency in young adults with acute respiratory disease was evaluated by both an objective cough counting system and a question naire . A guaifenesin cough preparation and the syrup vehicle were administered in a double-blind manner . Coughs were recorded on tape over a 24-hour baseline evaluation period and a 36-hour treatment period for 42 patients . A pronounced diurnal variation in cough frequency was observed . The evaluation of efficacy was based upon comparisons between equivalent six-hour time periods of successive days . No antitussive effect of guaifenesin was demonstrated . The question naire was administered to 65 patients , including the 42 whose coughs were recorded . Of 26 patients with productive cough receiving guaifenesin , 25 ( 96 percent ) reported a decrease in sputum thickness compared to 13 ( 54 percent ) of 24 patients receiving the vehicle ( p = 0.01 , Fisher exact test ) . Twenty-three of 26 ( 88 percent ) patients receiving guaifenesin also reported reduction in sputum quantity compared to 15 of 24 ( 62.5 percent ) receiving the vehicle ( p = 0.07 , Fisher exact test ) . The diurnal variation in cough frequency measured by the tape recording was not apparent from the subjective cough frequency estimates obtained by the question naire A double blind vs placebo study was carried out to study the effect of letosteine on the symptoms and clinical course of paediatric patients suffering from acute febrile bronchitis . Forty children were recruited for the research : 20 were treated with letosteine in a dose of 25 mg x 3 g/die and 20 with placebo ; treatment lasted 10 days . The following parameters were assessed during the trial : body temperature , cough , thoracic objectivity , respiratory function indices . The results of the study show that in the letosteine treated group there is a statistically significant decrease in fever , a favourable evolution of thoracic objectivity and an improvement in certain respiratory function parameters ( MEF 75 , PEF ) . It is concluded that treatment with letosteine leads to a significant increase in the rate of regression of thoracic symptomatology and a faster , more substantial reduction in fever in children suffering from acute bronchitis . This is probably the result of drug action on mucus viscosity , restoring optimal mucociliary clearance , and through action fostering the penetration of antibacterial substances into the mucus Codeine is often used as a st and ard antitussive against which new antitussives are compared . However there is little information available about the effects of codeine on cough associated with upper respiratory tract infection . The present study investigated the effects of codeine syrup B.P. ( 30 mg/10 ml , q.d.s . ) or syrup vehicle on cough frequency and the subjective severity of cough during a 3-h laboratory phase and a 4-day home phase of treatment . Cough frequency and subjective scores of cough severity were significantly decreased during the 3-h laboratory phase but at no time point was there a significant difference between the codeine- and placebo-treated groups . The results of the 4-day home phase diary were similar to those of the laboratory phase as at no time point was there a significant difference between the mean scores for the codeine- and placebo-treated groups . The results indicate that codeine , either as a single 30-mg dose or in a total daily dose of 120 mg , is no more effective than the syrup vehicle in controlling cough associated with acute upper respiratory tract infection We tested the hypothesis that antihistamine-decongestant combinations cause no clinical ly significant relief of the symptoms of upper respiratory tract infections in young children by r and omly assigning 96 children to one of three treatment groups : antihistamine-decongestant , placebo , and no treatment . There were no differences among the three study groups in the proportion of children considered " better " overall by the parent 48 hours after the initial assessment ( drug , 67 % ; placebo , 71 % ; no treatment , 57 % ; p = 0.53 ) . There were no differences among groups in individual or composite symptom score changes . Two thirds of parents whose children were eligible for the drug trial believed that their child needed medicine for cold symptoms . In the proportion of parents believing that their child needed medicine , there was no difference between those who consented to participate and those who refused . Parents who wanted medicine at the initial visit reported more improvement at follow-up , regardless of whether the child received drug , placebo , or no treatment . We conclude that there is no clinical ly significant improvement in symptoms of upper respiratory tract infection , including no significant placebo effect , in young children for whom an antihistamine-decongestant is prescribed The efficacy of an antitussive-beta 2-sympathomimetic combination ( dextromethorphan-salbutamol ) was compared with that of a plain antitussive ( dextromethorphan ) and a placebo in a double-blind trial in 108 out- patients with cough associated with acute respiratory infection . The dextromethorphan-salbutamol combination was superior to dextromethorphan or placebo in the suppression of cough at night , although a spontaneous improvement occurred in all treatment groups during the 4-day treatment period . No statistically significant differences between the treatments were shown in the symptom scores for the cough frequency and severity during the day , sputum quantity or ease of expectoration . A significant improvement in cough during the day was observed in all treatment groups . The results suggest that the use of antitussives is usually unnecessary ; the only indication might be symptomatic relief , especially at night . An antitussive combined with a beta 2-sympathomimetic might be the most effective treatment in this type of cough The antitussive efficacy and tolerability of dropropizine and of its enantiomer levodropropizine were evaluated in children with non-productive cough ; 258 were evaluable for tolerability and 254 for efficacy . Patients r and omly received either 1 mg/kg dropropizine or 2 mg/kg levodropropizine orally , three times daily for 3 days . There were statistically significant decreases in the frequency of coughing spells and nocturnal awakenings after both levodropropizine and dropropizine treatments ( P < 0.001 ) . Gastrointestinal symptoms were mild in the two groups ; somnolence was twice as frequent in the dropropizine group ( 10.3 % vs 5.3 % ) and the difference is clinical ly relevant , though not statistically significant . Levodropropizine is as effective as an antitussive as dropropizine , but appears to carry a lower risk of daytime somnolence To test the hypothesis that codeine and dextromethorphan are effective in alleviating the symptoms of acute cough , we conducted a r and omized , controlled trial . Eligible patients were children 18 months to 12 years of age , seen in private pediatric practice s , with significant night cough of less than 14 days ' duration . Study patients were r and omly selected to receive codeine , dextromethorphan , or placebo at bedtime for 3 consecutive nights . Outcomes were assessed by the use of a parent question naire rating the severity of symptoms at the initiation of therapy , and after each night of the study . Every patient had a cough score ( range 0 to 4 ) and composite symptom score ( range 0 to 9 ) computed for each day of the study . One hundred forty-one doses of study medication were evaluated in 49 patients , including 13 children receiving placebo , 19 dextromethorphan , and 17 codeine . Mean cough and composite symptom scores decreased in each of the three treatment groups on each day of the study ; there were no significant differences . Regression analysis , with reduction in cough score as the outcome of interest , showed that neither dextromethorphan nor codeine was significantly more effective than placebo ( p = 0.41 and 0.70 , respectively ) . Reduction in cough score was positively correlated with the severity of cough at the start of treatment ( p = 0.007 ) . Our data suggest that , in the doses used , neither codeine nor dextromethorphan is superior to placebo in treating night cough in children OTHER investigators,1 - 6utilizing various techniques , have attempted to determine objective ly the response of cough to antitussive medication . Volunteer adult patients were used almost exclusively in those studies . The techniques employed have consisted of induction of cough by artificial means , such as successive inhalations of an irritant aerosol , and of assay of antitussive activity of cough medications based on reduction in number of coughs provoked by the irritant . The irritant usually was citric acid or acetylcholine . While the data obtained gave a valid indication of a cough-suppressing effect , experimental production of cough by chemical or mechanical irritants is subject to certain limitations and criticisms . First , the healthy volunteer after repeated exposure develops a tolerance to the irritant , especially when the latter is citric acid . Second , the frequency and intensity of artificially induced cough vary with the concentration of the irritant and the interval between challenges . Third , the artificially induced One hundred and thirty out- patients , affected by acute and chronic cough caused by upper respiratory tract inflammation , took part in two clinical studies aim ed at evaluating the efficacy and tolerability of glaucine , a new antitussive agent . The first study involved 90 patients in a double-blind comparative trial of glaucine and codeine : both treatments were administered as a syrup at a dosage of 30 mg 3-times daily for 7 days . The cough suppressant effect of the two treatments was checked by the physician and the patient using a 4-point scale ( from absent to severe ) , and by the patient using a visual analogue scale . Mean scores of the physician 's evaluation decreased from 3.0 to 1.10 after codeine and from 3.0 to 0.47 after glaucine ( p less than 0.001 between treatments ) . Mean values of the patients ' visual analogue scales decreased from 83 mm to 17 mm after codeine , and from 85 mm to 7 mm after glaucine ( p less than 0.001 between treatments ) . Constipation and nausea were reported by 9 patients on codeine and by no patient on glaucine ( p less than 0.01 ) . One patient on codeine was withdrawn from the study after 3 days because of vomiting , constipation and nausea . The second study was an open trial in 40 patients who received glaucine capsules at a dosage of 30 mg 3-times daily for 28 days . The antitussive effect of the treatment was evaluated on the basis of the same criteria as in the first study . The mean score of the physician 's evaluation decreased from 3.0 to 0.15 ( p less than 0.001 ) ; the mean value of the patients ' visual analogue scales decreased from 93 mm to 1 mm ( p less than 0.001 ) . ( ABSTRACT TRUNCATED AT 250 WORDS Methodology to evaluate the efficacy of antitussive drugs rely largely on subjective methods and cough counts . There are few studies in cough due to natural disease especially using objective techniques . This paper presents data from a series of r and omized , double blind , placebo controlled clinical trials in cough due to both chronic bronchopulmonary disease and acute upper respiratory tract infections . In these studies , cough was quantified using a st and ardized and vali date d computerized system for the acquisition and multidimensional analysis of the cough sound . Key objective parameters like cough counts , intensity , latency and total effort expended were studied . Guaiphenesin and bromhexine showed significant expectorant effects in patients with productive cough due to chronic bronchopulmonary disease . Differences were observed in speed of action , and objective and subjective measures , that probably indicate differences in drug action . More recently , three studies evaluated the antitussive drug dextromethorphan in non-productive cough due to uncomplicated upper respiratory tract infections . Reproducible cough suppressant effects were demonstrated after a single 30 mg dose using objective measures of cough counts , latency and total effort . These results establish the sensitivity and robustness of the cough quantitation methodology in the objective evaluation of cough treatments Dextromethorphan is one of the most widely used antitussives for the treatment of cough associated with acute upper respiratory tract infection . However , there is very little data to support the efficacy of dextromethorphan in this disease state . This aim of this study was to obtain more information about the efficacy of a single dose of 30 mg dextromethorphan in the treatment of cough associated with acute upper respiratory tract infection . The study was a double-blind , stratified , r and omized and parallel group design . Both objective and subjective measurements of cough were recorded over 10-min recording periods in a quiet room before ( baseline ) and at 90 , 135 and 180 min after treatment . Forty-three patients ( 30 females and 13 males ) , mean age 22.9 years ( range 18 - 46 years ) , with acute dry or slightly productive cough and otherwise healthy were included in the study . Patients were r and omized to placebo treatment ( n = 22 ) and dextromethorphan treatment ( n=21 ) . The results showed similar trends in both treatment groups with statistically significant reductions ( P < 0.05 ) in cough sound pressure level ( CSPL ) , cough frequency ( CF ) and subjective scores for cough severity within treatment groups but little difference between the treatment groups during the study period . The only statistically significant difference between treatment groups was for the mean CSPL changes from baseline to 90 min ( P=0.019 ) . There was a significant positive correlation between CSPL and CF ( r = 0.752 , P= 0.000 ) for changes in cough measurements from baseline to 90 min after treatment and this indicates that CSPL may be a useful measure of cough severity . This study provides very little if any support for clinical ly significant antitussive activity of a single 30 mg dose of dextromethorphan in patients with cough associated with acute upper respiratory tract infection The role of histamine in the pathogenesis of infectious rhinitis is unclear , as is the efficacy of antihistaminic drugs in the treatment of the common cold . This study evaluated the short-term efficacy of oral terfenadine ( Seldane ) in the treatment of the common cold . Over a 5-week period , the authors recruited 250 adults who had developed cold symptoms within 6 to 48 hours prior to enrollment . Volunteers had a primary complaint of runny or stuffy nose ; at least one other respiratory symptom ; no fever or exudative pharyngitis ; and no history of atopy , sinusitis , or use of cold preparations within 1 week of enrollment . Out of the eligible subjects , 126 were r and omly assigned terfenadine ( 60 mg ) , and 124 received placebo . Volunteers self-administered either terfenadine or placebo twice a day on Days 1 , 2 and 3 , and a final dose on the morning of Day 4 . They also recorded the severity of their clinical symptoms ( runny nose , sniffles , sneezing , postnasal drip , cough and sore throat ) on symptom cards . Both groups reported similar severity scores throughout the treatment period . Average symptom burdens declined at almost identical rates for both groups . Terfenadine was well tolerated and had a low incidence of side effects . According to subject evaluation , terfenadine was no more effective than placebo . The mean + /- SD score of global efficacy was 2.2 + /- 1.1 in the terfenadine group and 2.1 + /- 1.3 in the placebo group ( P = NS ) . Slightly fewer terfenadine recipients ( 41 % ) than placebo recipients ( 48 % ) said they would use the study medication again for treating cold symptoms . ( ABSTRACT TRUNCATED AT 250 WORDS Seventy subjects suffering from the common cold were recruited at general practitioner surgeries and were treated with an evening dose of a syrup† containing 600 mg paracetamol , 15 mg dextromethorphan hydrobromide , 8 mg ephedrine sulphate , 7.5 mg doxylamine succinate per 30 ml or an identical-appearing and flavoured control syrup without the active ingredients , in a double-blind crossover design study , lasting two days . Subjects were r and omly allotted to two equal groups . One group took active formulation the first evening followed by the control formulation the second evening . The second group took the two formulations in the reverse order . Evaluation of symptomatic relief on a 6-point rating scale against eight major cold symptoms was carried out by each subject at 10 a.m. following the administration of active or control formulation the previous evening . Following combination of data for the two groups , results showed a significant degree of relief provided by the active formulation compared to control for the following symptoms , cough , nasal congestion , nasal discharge , sneezing , generally feeling unwell , headache , sore throat , disturbed sleep , the difference between the two preparations in relief of cough being highly significantly in favour of the “ active ” preparation . Additionally , a highly significant number of the subjects expressed a preference for the global symptomatic relief provided by the active formulation as compared to control . These results have demonstrated that the “ active ” formulation provides effective therapy for night-time symptomatic relief of the eight major symptoms of the common cold OBJECTIVE To determine whether an antihistamine-decongestant combination ( ADC ) is superior to placebo in temporarily relieving symptoms of upper respiratory tract infection ( URI ) in preschool children . DESIGN R and omized , double-blind , placebo-controlled trial . SETTING Four pediatric offices in the Seattle , Wash , area . PARTICIPANTS Children 6 months through 5 years of age with a URI of less than 7 days ' duration . METHODS Children were r and omly assigned to receive an ADC ( brompheniramine maleate-phenylpropanolamine hydrochloride ) or placebo as needed for URI symptoms . Two hours after each dose of study medication , changes in the child 's runny nose , nasal congestion , cough , and sleep status were assessed by means of a st and ardized question naire . RESULTS A total of 175 responses were recorded for 59 patients . There were no statistically significant differences in symptom improvement between the ADC and the placebo group ( runny nose , p = 0.48 ; nasal congestion , p = 0.94 ; cough , p = 0.66 ) . However , the proportion of children asleep 2 hours after receiving the ADC was significantly higher than the proportion receiving placebo ( 46.6 % vs 26.5 % ; p = 0.01 ) . Results were unchanged after control for the correlated nature of repeated responses , age , symptom duration , use of acetaminophen , time that the medication was given , and parental desire for medication . CONCLUSIONS The ADC was equivalent to placebo in providing temporary relief of URI symptoms in preschool children . However , the ADC did have significantly greater sedative effects than did placebo |
842 | 14,973,997 | The use of sclerosants ( mitozantrone , talc and tetracycline combined)compared with control ( instillation of isotonic saline or equivalent pH isotonic saline or tube drainage alone ) was associated with an increased efficacy of pleurodesis .
REVIEW ER 'S CONCLUSIONS The available evidence supports the need for chemical sclerosants for successful pleurodesis , the use of talc as the sclerosant of choice , and thoracoscopic pleurodesis as the preferred technique for pleurodesis based on efficacy .
There was no evidence for an increase in mortality following talc pleurodesis | BACKGROUND Approximately half of all patients with metastatic cancer develop a malignant pleural effusion which is likely to lead to a significant reduction in quality of life secondary to symptoms such as dyspnoea and cough .
The aim of pleurodesis in these patients is to prevent re-accumulation of the effusion and thereby of symptoms , and avoid the need for repeated hospitalization for thoracocentesis .
Numerous clinical studies have been performed to try to determine the optimal pleurodesis strategy , and synthesis of the available evidence should facilitate this .
OBJECTIVES The aims of this review were to ascertain the optimal technique of pleurodesis in cases of malignant pleural effusion ; to confirm the need for a sclerosant ; and to clarify which , if any , of the sclerosants is the most effective . | Treatment of patients with malignant pleural effusions is mostly palliative . Tetracycline and bleomycin are the two most commonly used agents for the treatment of pleurodesis . In this study , the authors used a combination of the two drugs for this particular purpose Summary The current prospect i ve r and omized study was design ed to compare the effects of intracavitary ( i.c . ) chemotherapy vs immunotherapy vs immunochemotherapy for malignant effusion . Between 1992 and 1995 , a total of 42 patients with malignant effusion were registered , and 41 patients were eligible for statistical analysis . The primary diseases of the eligible patients included 27 gastric , four colorectal , four pancreatic , three lung , two liver and one oesophageal cancers . The patients with malignant effusion were r and omly assigned into one of three i.c . therapeutic regimens : chemotherapy alone with weekly injection of anticancer agents ( ACAs : cisplatin , mitomycin-C , adriamycin , etc . ) ( Group A , n = 13 ) ; immunotherapy alone with weekly injection of streptococcal preparation OK-432 ( Group B , n = 14 ) ; or immunochemotherapy with ACAs and OK-432 ( Group C , n = 14 ) . The response of the effusion , patient survival and the kinetics of cytokines in the effusion were compared . There were no differences in the patients ’ background s. The side-effects of the regimens included pain , anorexia , fever , leucopenia and anaemia and there were no differences in their incidence among the three groups . One patient died after cisplatin ( CDDP ) administration in Group A. Cytologic examination revealed that tumour cells in the effusion disappeared in 23 % of Group A cases , 36 % of Group B cases and 36 % of Group C cases . The malignant effusion did not disappear in any of the Group A cases ; however , the effusion disappeared in 29 % of Group B cases and 43 % of Group C cases ( P = 0.03 , Group A vs Group C ) . Furthermore , the 50 % survival period was 1.6 months for Group A , 2.4 months for Group B and 3.5 months for Group C. The 6-month survival rate was 7 % for Group A , 6 % for Group B and 34 % for Group C , and the 1-year survival rate was 0 % , 0 % and 17 % respectively ( P = 0.048 , Group A vs Group C by the log-rank test ) . The analysis of the cytokine kinetics revealed a prominent increase in the level of interleukin-6 in the effusion in Group C. These results suggest that i.c . immunochemotherapy with OK-432 and ACAs may be more beneficial than i.c . chemotherapy alone or immunotherapy alone STUDY OBJECTIVE To determine the feasibility of rapid pleurodesis in patients with malignant pleural effusions in order to reduce hospital length of stay in patients with a limited life expectancy . DESIGN Prospect i ve case series . SETTING Two university hospital programs . PATIENTS Thirty-eight patients with symptomatic pleural effusions associated with malignancy . INTERVENTIONS A 14F catheter was inserted percutaneously into the pleural space after radiographic confirmation of free fluid by lateral decubitus views . Following radiographic confirmation of complete fluid evacuation , a sclerosing agent ( ie , talc slurry or bleomycin ) was instilled into the pleural space . This was accomplished within 2 h of chest tube insertion , unless the tube was inserted in the evening or if the lung was trapped . After clamping the tube for 90 min , the pleural space was drained for 2 h , after which the chest tube was removed . The intervention was scored as " successful " if no radiographic evidence of fluid reaccumulation was noted at 4 weeks . A " partial successful " score indicated reaccumulation of fluid that did not produce symptoms and did not require repeat pleural drainage of any sort . All other outcomes were scored as " unsuccessful . " MEASUREMENTS AND RESULTS Forty chest tubes were inserted into 38 patients . Four procedures revealed the presence of a trapped lung and did not result in any attempt at pleurodesis . Five patients who received pleurodesis died in less than 1 month and therefore were not evaluable . Two patients had technical problems with the chest tube and were not evaluable . Of the remaining 29 procedures , drainage procedures with pleurodesis were performed in 27 patients , a complete response was seen in 14 patients ( 48 % ) , a partial response was seen in 9 patients ( 31 % ) , and 6 patients ( 21 % ) did not respond to pleurodesis . Chemical pleurodesis was completed as an outpatient procedure in only two patients . In one of these , the outcome was unsuccessful . In the remainder , insertion of the chest tube in the evening or additional medical problems necessitated hospital admission , but the entire procedure was completed within 24 h. CONCLUSIONS Chemical pleurodesis can be accomplished with good results in < 24 h in the majority of patients with malignant pleural effusions In a controlled r and omized trial , 46 patients with pleural effusions secondary to breast cancer were treated at first diagnosis with either intracavitary mustine or talc , to determine which agent produced the more effective pleurodesis . Of the 37 evaluable patients , control of the effusion was achieved in 9/17 ( 56 % ) of those treated with mustine and 18/20 ( 90 % ) of the talc group ( P > 0.025 ) . This suggests that early treatment with intracavitary talc can effectively palliate this complication of breast cancer Thirty two patients with malignant pleural effusion were r and omly allocated to treatment with intrapleural Corynebacterium parvum or tetracycline hydrochloride in an attempt to prevent symptomatic recurrence of pleural fluid . Success in preventing recurrence of fluid at one month , using up to 2 doses of each drug , was 14 of 16 cases for Corynebacterium parvum , 5 of 9 for tetracycline given via an intercostal needle , and 6 of 7 for tetracycline given through an intercostal tube . These difference were not statistically significant . Corynebacterium parvum was significantly more likely to produce pyrexia equal or greater than 38 degrees C ( P less than 0.001 ) and pain requiring analgesia ( P less than 0.05 ) than tetracycline hydrochloride . Corynebacterium parvum is a useful agent for the management of malignant pleural effusion , but is associated with more side effects than tetracycline Malignant pleural effusions are commonly managed with tube thoracostomy drainage followed by chemical pleurodesis . Both tetracycline and bleomycin have been shown to be effective for intrapleural instillation , although neither agent has definitively proved advantages over the other . The aim of the present study was to compare these two agents in terms of response rate and toxicity profile . A prospect i ve , r and omized trial was carried out in a single centre . Between May 1993 and January 1996 , 62 evaluable patients with proved malignant pleural effusion were allocated to receive either intrapleural tetracycline ( 1.5 g ) or bleomycin ( 60 mg ) after the same drainage procedure . Demographic , clinical and fluid parameter data were comparable in both groups . Response was evaluated at 1 , 3 and 6 months after pleurodesis . Mean survival and time to relapse did not differ between the two groups . No statistically significant differences were found in terms of efficacy at each evaluation time . Overall , 16 ( 52 % ) and 20 ( 64 % ) patients had a recurrence of pleural effusion during follow-up in the tetracycline and bleomycin arms , respectively . Fever was most common in bleomycin-treated patients ( p=0.024 ) while pain was most frequent in the tetracycline arm ( nonsignificant ) . Since no study agent was superior to the other in this trial , we suggest that economic costs , drug availability and medical skill should be considered in the choice of a sclerosing agent Fifty-eight patients with malignant pleural effusions were entered into a prospect ively r and omized clinical trial comparing the efficacy of a local instillation of bleomycin or corynebacterium parvum ( C. parvum ) in controlling fluid reaccumulation after simple needle aspiration ( thoracentesis ) . The response was assessed at 30 days by chest X-ray and clinical examination . There were 44 evaluable patients ; 18 of 25 ( 72 % ) of those receiving bleomycin and 9/19 ( 47 % ) of those who had C. parvum gained a complete or partial response . This difference in response rate was not statistically significant ( p = 0.13 ) . The majority of patients had an effusion from a primary breast carcinoma and the response in this group was almost statistically significant ( p = 0.06 ) with 74 % of bleomycin patients and 43 % of C. parvum patients responding . Fever following instillation was more common with C. parvum ( 53 % of patients compared with 24 % after bleomycin , p = 0.02 ) , whereas nausea was more common after bleomycin ( 28 % vs. 10.5 % , p = 0.16 ) . Local chest pain after aspiration occurred in 52 % of the bleomycin group and 47 % of the C. parvum subjects . There was no significant difference between the groups in age , sex , tumour type , presenting symptoms , volume of aspirate , systemic therapy or number of previous aspirations . Both of these agents appeared to be active in the control of malignant pleural effusions although the response rate was higher with bleomycin and overall , both have acceptable levels of toxicity BACKGROUND --A study was undertaken to compare the efficacy of short term tube thoracostomy drainage with st and ard tube thoracostomy drainage before instillation of tetracycline for sclerotherapy of malignant pleural effusions . METHODS --The study consisted of a r and omised clinical trial in a sequential sample of 25 patients with malignant pleural effusions documented cytopathologically . Fifteen patients were r and omly assigned to group 1 ( st and ard protocol ) and 10 to group 2 ( short term protocol ) . Patients in group 1 had tube thoracostomy suction drainage until radiological evidence of lung re-expansion was obtained and the amount of fluid drained was < 150 ml/day , before tetracycline ( 1.5 g ) was instilled . The chest tube was removed when the amount of fluid drained after instillation was < 150 ml/day . Patients in group 2 also had suction drainage , but the tetracycline ( 1.5 g ) was instilled when the chest radiograph showed the lung to be re-exp and ed and the effusion drained , which was usually within 24 hours . The chest tube was removed the next day . RESULTS --The response to tetracycline sclerotherapy in the two groups was the same ( 80 % ) but the duration of chest tube drainage was significantly shorter for patients in group 2 ( median two days ) than for those in group 1 ( median seven days ) . CONCLUSIONS --The duration of chest tube drainage before sclerotherapy for malignant pleural effusions need not be influenced by the amount of fluid drained daily but by radiographic evidence of fluid evacuation and lung re-expansion . Shorter duration of drainage will reduce the length of hospital stay without sacrificing the efficacy of pleurodesis BACKGROUND Talc has been generally accepted to be the most effective sclerosant for chemical pleurodesis , although the optimal route of administration remains unclear . METHODS We design ed a prospect i ve , r and omized study to compare video-assisted thoracoscopic talc insufflation with bedside talc slurry in the treatment of malignant pleural effusion . From September 1993 to November 1995 , 57 patients were recruited and r and omized to either video-assisted thoracoscopic talc insufflation under general anesthesia ( n = 28 ) or talc slurry by the bedside ( n = 29 ) . Patients with poor general condition ( Karnofsky score less than 30 % ) , poor pulmonary function ( forced expiratory volume in 1 second less than 0.5 L ) , or trapped lungs were excluded from this study . Five grams of purified talc was used for either video-assisted thoracoscopic talc insufflation or talc slurry . RESULTS There was no statistically significant difference between the two groups of patients with respect to age , sex ratio , chest drainage duration , postprocedural hospital stay , parenteral narcotics requirement , complications , or procedure failure ( ie , recurrence ) . CONCLUSIONS Video-assisted thoracoscopic talc insufflation has not been shown to be a superior approach compared with talc slurry in our study . Because the former dem and s more re sources , we advocate that talc slurry should be considered as the procedure of choice in the treatment of symptomatic malignant pleural effusion in patients who do not have trapped lungs The efficacy and safety of intrapleural LC9018 ( Yakult Co. Ltd. , Tokyo , Japan ) with or without doxorubicin ( Adriamycin ; Adria Laboratories , Columbus , OH ) were evaluated in a r and omized , controlled trial performed in 95 patients with malignant pleural effusions secondary to lung cancer . Seventy‐six patients were eligible for the assessment of efficacy . The response rate for treatment with intrapleural doxorubicin plus LC9018 ( 38 patients ) was 73.7 % , which was significantly higher than the response rate of 39.5 % for the control group treated with doxorubicin alone ( 38 patients ) ( P < 0.01 ) . The LC9018 group also showed a significantly greater improvement in performance status ( PS ) and symptoms ( chest pain , chest discomfort , and anorexia ) than the control group ( P < 0.05 ) . A significant prolongation of survival was noticed in the LC9018 group ( P < 0.05 ) . The main side effects of LC9018 were fever and transient hepatic dysfunction , but there were no serious adverse reactions . These results suggest that the intrapleural instillation of LC9018 can be recommended for the treatment of malignant pleural effusions BACKGROUND --The treatment of recurrent pleural effusion in advanced malignant disease should be efficient and with tolerable side effects . Since 1983 intrathoracic instillation of the anti-malaria drug mepacrine has been used to achieve pleurodesis . The cytotoxic drug bleomycin has been cl aim ed to be equally effective and with fewer side effects . The present study was design ed to compare these two agents . METHODS --Forty patients with carcinoma and pleural effusions refractory to repeated pleural aspirations over the previous 12 weeks were r and omised to receive treatment with intrathoracic instillation of mepacrine or bleomycin . Fluid volumes before and after pleurodesis , drainage time , and side effects were registered and analysed , and the response to treatment was evaluated by clinical examination and chest radiography . RESULTS --The amount of fluid produced after treatment in the patients receiving mepacrine was lower than in those receiving bleomycin , and the duration of chest drainage was shorter . After 30 days 16 of 20 in the mepacrine group responded to treatment and 10 of 20 in the bleomycin group . Most patients died during the three months observation period . Moderate side effects occurred equally in both groups . CONCLUSIONS --Chemical pleurodesis can reduce or stop pleural effusion in many patients , and in this study mepacrine appeared to be more efficient than bleomycin . A prospect i ve study with a larger number of patients is now warranted The aim of this prospect i ve , r and omized study was to investigate the possibility of performing pleurodesis using a small percutaneous catheter ( Cystofix catheter , CH10 , 65 cm ) inserted at bedside in patients with recurrent malignant pleural effusion and to compare this catheter with a conventional large bore chest tube ( CH24 ) placed in connection with diagnostic thoracoscopy . After drainage pleurodesis was performed with tetracycline as sclerosing agent . Of 18 evaluable consecutive patients ( mean age 67.8 years ) nine were r and omized for pleurodesis with the small and nine for the large catheter . In the former group , the majority ( seven of nine ) did not find insertion of the catheter more unpleasant than thoracentesis . In the latter group only a few ( two of nine ) found insertion comparable with thoracentesis ( P < 0.05 ) . All patients found the presence of the large catheter very or somewhat unpleasant ( two and seven patients ) , whereas this was only the case for a few ( no and two patients ) treated with the small catheter ( P < 0.05 ) . In the former group three patients required new thoracentesis , whereas this was only the case for two patients in the latter group ( P > 0.05 ) . No complications were seen . We conclude that pleurodesis in patients with recurrent malignant pleural effusion can be performed with a small percutaneous catheter ( Cystofix ) with an effect similar to that obtained with a large-bore chest tube and with less discomfort for the patient The purpose of this study was to compare the effectiveness and safety of a chronic indwelling pleural catheter with doxycycline pleurodesis via tube thoracostomy in the treatment of patients with recurrent symptomatic malignant pleural effusions ( MPE ) In a prospect i ve r and omized study , patients with pleural effusions secondary to breast carcinoma were r and omly allocated to be treated by pleurodesis using either intracavitary talc or bleomycin . For 25 assessable treatments in 22 patients , recurrence of effusion was observed in 5 of 15 ( 33 per cent ) of the bleomycin group compared with none in the talc group . It is concluded that talc is superior to bleomycin in controlling pleural effusions secondary to breast carcinoma , but bleomycin may have a role in patients unfit for general anaesthesia or with extensive disease elsewhere 30 patients with malignant pleuritis were r and omised to be treated , either with intrapleural instillation of mepacrine chloride or with mitoxantrone . The patients were evaluated with chest X-ray and a symptom question naire during a follow-up period of 12 weeks . Mitoxantrone levels in the pleural space and plasma were measured at different time points in some of the patients . High concentrations of mitoxantrone were found in the pleural fluid while the plasma concentrations were low , giving a plasma/intracavity ratio generally of less than 1:60 . The chest X-rays showed excellent results for both treatment modalities . However , the patients treated with mepacrine chloride experienced greater discomfort with fever and pain , and those treated with mitoxantrone reported significantly less dyspnoea and less asthenia after 4 weeks . We conclude that both treatments are equally effective in preventing the recurrence of malignant effusion . However , mitoxantrone seems to have further advantages when it comes to improving the quality of life As professionals , we want to use the best treatments ; as patients , we want to be given them . Knowing whether an intervention works ( or does not work ) is fundamental to clinical decision making . However , clinical decision making involves more than simply taking published results of research directly to the bedside . Physicians need to consider how similar their patients are to those in the published studies , to take the values and preferences of their patients into account , and to consider their own experience with a given test or treatment . Evidence from clinical research is becoming increasingly important in medical- practice decisions as more and better evidence is published . But when is the evidence strong enough to justify changing a practice ? Individual studies that involve only small numbers of patients may have results that are distorted by the r and om play of chance and thus lead to less than optimal decisions . As is clear from other papers in this series , systematic review s identify , critically appraise , and review all the relevant studies on a clinical question and are more likely to give a valid answer . They use explicit methods and quality st and ards to reduce bias . Their results are the closest we can come to reaching the truth given our current state of knowledge . The questions about an intervention that a systematic review should answer are the following : 1 . Does it work ? 2 . If it works , how well does it work in general and compared with placebo , no treatment , or other interventions that are currently in use ? 3 . Is it safe ? 4 . Will it be safe and effective for my patients ? Whereas the critical appraisal and qualitative synthesis provided by review articles can be interpreted directly , the numerical products of quantitative review s can be more difficult to underst and and apply in daily clinical practice . This paper provides guidance on how to interpret the numerical and statistical results of systematic review s , translate these results into more underst and able terms , and apply them directly to individual patients . Many of these principles can also be used to interpret the numerical results of individual clinical studies . They are particularly relevant to systematic review s , however , because such review s contain more information than do primary studies and often exert greater influence than do individual studies . Making Sense of the Numerical Results of Clinical Studies Although the results of clinical studies can be expressed in intuitively meaningful ways , such results do not always easily translate into clinical decision making . For example , results are frequently expressed in terms of risk , which is an expression of the frequency of a given outcome . ( Risks are probabilities , which can vary between 0.0 and 1.0 . A probability of 0.0 means that the event will never happen , and a probability of 1.0 means that it always happens . ) Consider a hypothetical study of the recurrence of migraine headaches in a control group receiving placebo and a treatment group receiving a new antimigraine preparation , drug M ( a secondary prevention trial ) . Suppose that at the end of the trial , migraines recurred in 30 % of the control group ( the risk for recurrence was 0.30 ) but in only 5 % of the drug M group ( risk of 0.05 ) ( Table 1 ) . Table 1 . Numerical Expression of Hypothetical Clinical Trial Results The outcomes of the study are clear enough for the two groups when they are examined separately . But clinicians and patients are more interested in the comparative results , that is , the outcome in one group relative to the outcome in the other group . This overall ( comparative ) result can be expressed in various ways . For example , the relative risk , which is the risk in the treatment group relative to that in the control group , is simply the ratio of the risks in the two groups . In other words , relative risk is the risk in the treatment group divided by that in the control group , 0.05 0.30 , or 0.17 . The comparison can also be expressed as the reduction in relative risk , which is the ratio between the decrease in risk ( in the treatment group ) and the risk in the control group , 0.25 0.30 , or 0.83 ( Table 1 ) . ( The relative risk reduction can also be calculated as 1 relative risk ) . Although the clinical meaning of relative risk ( and relative risk reduction ) is reasonably clear , relative risk has the distinct disadvantage that a given value ( for example , 0.17 ) is the same whether the risk with treatment decreases from 0.80 to 0.14 , from 0.30 to 0.05 , from 0.001 to 0.00017 , and so forth . The clinical implication s of these changes clearly differ from one another enormously and depend on the specific disease and intervention . An important alternate expression of comparative results , therefore , is the absolute risk reduction . Absolute risk reduction is determined by subtracting the risk in one group from the risk in the other ( for example , the risk in the treatment group is subtracted from the risk in the placebo group ) . In the case of our migraine study , the absolute risk reduction would be 0.30 0.05 , which equals 0.25 , or 25 percentage points . In contrast , for a study in which the risk decreased from 0.001 to 0.00017 , the absolute risk reduction would be only 0.00083 , or 0.083 percentage points , which is a trivial change in comparison ( Table 1 ) . This arithmetic emphasizes the difficulty of expressing the results of clinical studies in meaningful ways . Relative risk and relative risk reduction clearly give a quantitative sense of the effects of an intervention in proportional terms but provide no clue about the size of an effect on an absolute scale . In contrast , although it tells less about proportional effects , absolute risk says a great deal about whether an effect is likely to be clinical ly meaningful . Despite this benefit , even absolute risk is problematic because it is a dimensionless , abstract number ; that is , it lacks a direct connection with the clinical situation in which the patient and physician exist . However , another way of expressing clinical research results can provide that clinical link : the number needed to treat ( NNT ) . Number Needed To Treat The NNT for a given therapy is simply the reciprocal of the absolute risk reduction for that treatment [ 1 , 2 ] . In the case of our hypothetical migraine study ( in which risk decreased from 0.30 without treatment with drug M to 0.05 with treatment with drug M , for a relative risk of 0.17 , a relative risk reduction of 0.83 , and an absolute risk reduction of 0.25 ) , the NNT would be 1 0.25 , or 4 . In concrete clinical terms , an NNT of 4 means that you would need to treat four patients with drug M to prevent migraine from recurring in one patient . To emphasize the difference between the concepts embodied in NNT and relative risk , recall the various situations mentioned above , in all of which the relative risk was 0.17 but in which the absolute risk decreased from 0.80 to 0.14 in one case and from 0.001 to 0.00017 in another . Note that the corresponding NNTs in these two other cases are 1.5 and 1204 , respectively : that is , you would need to treat 1.5 and 1204 patients to obtain a therapeutic result in these two situations compared with 4 patients with drug M ( Table 1 ) . The NNT can be calculated easily and kept as a single numerical reminder of the effectiveness ( or , as we will see , the potential for harm ) of a particular therapy . As we suggested , the NNT has the crucial advantage of direct applicability to clinical practice because it shows the effort that is required to achieve a particular therapeutic target . The NNT has the additional advantage that it can be applied to any beneficial outcome or any adverse event ( when it becomes the number needed to harm [ NNH ] ) . The concept of NNT always refers to a comparison group ( in which patients receive placebo , no treatment , or some other treatment ) , a particular treatment outcome , and a defined period of treatment . In other words , the NNT is the number of patients that you will need to treat with drug or treatment A to achieve an improvement in outcome compared with drug or treatment B for a treatment period of C weeks ( or other unit of time ) . To be fully specified , NNT and NNH must always specify the comparator , the therapeutic outcome , and the duration of treatment that is necessary to achieve the outcome . Important Qualities of the Number Needed To Treat The NNT is treatment specific . It describes the difference between treatment and control in achieving a particular clinical outcome . Table 2 shows NNTs from a selection of systematic review s and large r and omized , controlled trials . Table 2 . Numbers Needed To Treat from Systematic Review s and R and omized , Controlled Trials A very small NNT ( that is , one that approaches 1 ) means that a favorable outcome occurs in nearly every patient who receives the treatment and in few patients in a comparison group . Although NNTs close to 1 are theoretically possible , they are almost never found in practice . However , small NNTs do occur in some therapeutic trials , such as those comparing antibiotics with placebo in the eradication of Helicobacter pylori infection or those examining the use of insecticide for head lice ( Table 2 ) . An NNT of 2 or 3 indicates that a treatment is quite effective . In contrast , such prophylactic interventions as adding aspirin to streptokinase to reduce 5-week vascular mortality rates after myocardial infa rct ion may have NNTs as high as 20 to 40 and still be considered clinical ly effective . Limitations of the Number Needed To Treat Although NNTs are powerful instruments for interpreting clinical effects , they also have important limitations . First , an NNT is generally expressed as a single number , which is known as its point estimate . As with all experimental measurements , however , the true value of the NNT can be higher or lower than the point estimate determined through clinical studies . The 95 % CIs of the NNT are useful in this regard because they provide an indication that Malignancy is the most common cause of exudative pleural effusion in patients over the age of 60 years . Control of the effusion significantly reduces morbidity and improves quality of life . Tube thoracostomy with subsequent chemical pleurodesis is the treatment of choice for patients with tumors that are relatively insensitive to systemic chemotherapy . The agents most commonly used for chemical pleurodesis are tetracycline and bleomycin . A 13-center r and omized trial compared tetracycline 1 g and bleomycin 60 U. Median time to recurrence or progression of the malignant effusion was 32 days for tetracycline and more than 46 days for bleomycin ( P = .037 ) . The recurrence rate within 30 days of instillation was 36 % for bleomycin ( 10 of 28 patients ) and 67 % ( 18 of 27 patients ) for tetracycline ( P = .023 ) . At 90 days , the recurrence rate was 30 % ( 11 of 37 ) for bleomycin , and 53 % ( 19 of 36 ) for tetracycline ( P = .047 ) . From this study , the authors concluded that intrapleural bleomycin appears superior to tetracycline for controlling malignant pleural effusions . Selected patients who fail tube thoracostomy and chemical pleurodesis should be considered for pleuroperitoneal shunting or pleurectomy Fifty patients with malignant pleural effusion were r and omized to receive one or two doses of tetracycline sclerotherapy . We found that a single sclerotherapy treatment with tetracycline at a dose of 20 mg/kg was as effective as two sclerotherapy treatments and provided symptomatic relief in 46 of the 50 patients BACKGROUND Malignant pleural effusions are a common problem for patients with metastatic disease . Most patients are treated with tube thoracostomy and sclerotherapy , although there remains no st and ard approach . The purpose of this study was to compare the efficacy of bleomycin with doxycycline sclerotherapy for the treatment of malignant pleural effusions using small-bore catheters . METHODS All patients with a symptomatic malignant pleural effusion referred for chest tube drainage and sclerotherapy over a 2-year period were considered eligible . Using image guidance , a 14F self-retaining catheter was inserted into the pleural space and connected to continuous wall suction . When drainage fell below 200 mL/d , patients were r and omized to 60 U of bleomycin or 500 mg of doxycycline sclerotherapy . Response at 30 days was determined . RESULTS One hundred six patients were enrolled in the study . Fifteen men ( 29 % ) and 37 women ( 71 % ) with a mean age of 57 years received bleomycin sclerotherapy . Twenty-one of the 29 patients ( 72 % ) alive and evaluable at 30 days had successful sclerotherapy . Twenty-three men ( 43 % ) and 31 women ( 57 % ) with a mean age of 61 years received doxycycline sclerotherapy . Twenty-three of the 29 patients ( 79 % ) alive and evaluable at 30 days had successful sclerotherapy . There was no significant difference in response rates between doxycycline and bleomycin ( p=0.760 ) . CONCLUSIONS These data continue to support a role for small-bore chest drainage and sclerotherapy , although there was no significant difference in 30-day response rates between doxycycline and bleomycin OBJECTIVE To evaluate the efficacy of treating malignant pleural effusion with cisplatine and vindesine by injection through thoracic tube intubation . METHODS 60 cases with malignant pleural effusion , after drainage , vindesine 4 mg , cisplatine 40 mg/m(2 ) were injectred into pleural cavity in therapy group ( T ) , and only cisplatine 40 mg/m(2 ) in control group ( C ) . the tretment was repeated after a week , then evaluate the efficacy , survival rate , toxicities and quality of life . RESULTS The response rate was 81 % in T group and 50 % in C group . There was statistical difference in two groups ( P < 0.05 ) . The Karnofsky score is higher in T group than in C group . The half-year , one-year , one and half-year , two-year survival rates were 97 % , 59 % , 44 % , 6 % in T group and 71 % , 50 % , 14 % , 4 % in C group . Grade I leukopenia is higher in T group than in C group . CONCLUSION The treatment to use Vindesine and cisplatine through thoracic tube is regarded as effective , slight side-effect and well tolerated method for malignant pleural effusion Both bleomycin and tetracycline have been suggested as the sclerosing agent of choice in the management of malignant pleural effusions . To determine if one drug is superior to the other in this role , patients with malignant pleural effusions were r and omly assigned to receive either bleomycin or tetracycline in the previously evacuated pleural space through a thoracostomy tube . Following instillation of the assigned agent , the tube was clamped for 8 hours and then reattached to suction . When the chest tube drainage had slowed to less than 40 ml in a 24-hour period or if 7 days had passed , the tube was removed . Pleural sclerosis was attempted 42 times in 34 patients . No statistically significant differences were found between the two treatment groups when prevention of effusion reaccumulation and time to removal of the chest tube ( efficiency ) were compared . Side effects including pleural pain and fever , occurred with both agents , but were manageable . Since one drug was not clearly superior to the other , and bleomycin is more costly , we suggest that tetracycline rather than bleomycin be used when pleural sclerosis is needed to manage malignant pleural effusions Pleurodesis with doxycycline ( 100 mg and 600 mg ) and Corynebacterium parvum ( 1 mg and 7 mg ) were compared in 41 patients with malignant effusion . To evaluate the mechanisms , pleural fluid pH , leukocytes , granulocytes , interleukin-6 ( IL-6 ) and serum IL-6 , as well as C-reactive protein ( CRP ) were measured before and on 2 consecutive days after treatment . Corynebacterium parvum produced a greater acute-phase response measured with fever , serum CRP and IL-6 than doxycycline . However , no change in pleural fluid IL-6 was demonstrated . Among the 35 assessed patients , 26 had objective response , similar in all four treatment groups . Side-effects were more common with Corynebacterium parvum . Based on this preliminary study we conclude that doxycycline , even in low doses , is a highly effective and well tolerated agent for palliative treatment of malignant pleural effusion . As the responses were similar despite different inflammatory reactions , the two agents probably induce pleural obliteration through different mechanisms In a controlled clinical trial we investigated 102 patients with malignant pleural effusion due to breast cancer , lung cancer , ovarian cancer and other tumors to compare the therapeutic effect and adverse events of pleurodesis with bleomycin ( BMC ) or mitoxantrone ( MIT ) via chest tube . Finally 96 patients had been treated according to the protocol . Age , gender , Broca index , performance score or distribution of primary tumors were not statistically different between the BMC ( n = 49 ) or MIT group ( n = 47 ) . We found no differences between intention-to-treat and according-to- protocol groups as well . 30 days after BMC pleurodesis we found remissions of the effusion in 91 % of patients ( complete remission [ CR ] 51 % , partial remission [ PR ] 40 % ) , after 90 days in 83 % ( 40 % CR , 43 % PR ) . 30 days after MIT instillation we found remission in 73 % of patients ( 35 % CR , 38 % PR ) , after 90 days in 61 % ( 29 % CR , 32 % PR ) ( 30 and 90 days : p < 0.05 ) . Adverse events were not different between BMC and MIT group . BMC is a safe and effective sclerosing agent for pleurodesis via chest tube OBJECTIVE Symptomatic malignant pleural effusions are common sequelae in patients with certain malignancies . Pleurodesis via bedside thoracostomy is the current treatment option most commonly used . To our knowledge , this is the first prospect i ve r and omized trial to examine which agent , bleomycin or talc slurry , is superior in terms of effectiveness , safety , and cost . PATIENTS AND METHODS Between July 1992 and March 1995 , 35 patients presenting to our medical center with symptomatic malignant pleural effusions were prospect ively r and omized to undergo chemical pleurodesis with either bleomycin or talc slurry via bedside thoracostomy . The conditions of patients were assessed and grade d before and after treatment concerning pain , dyspnea , and chest radiographs . RESULTS Twenty-nine patients who underwent 33 treatments ( 14 with bleomycin and 19 with talc ) were available for follow-up . Follow-up ranged from 2 weeks to 8 months ( mean , 1.7 months ) . Both groups demonstrated notable improvement in both pain and dyspnea following treatment , but there were no statistically significant differences between groups in the amount of improvement ( two-tailed Student 's t test ) . Permanent control of effusions , defined objective ly on chest radiograph , was achieved with 11 bleomycin treatments ( 79 % ) and 17 talc treatments ( 90 % ) ( p=0.388 ) . The procedures were well tolerated and no significant adverse effects were observed . Talc is a much less costly agent than bleomycin ( $ 12.36 cost to our medical center per treatment for talc vs $ 955.83 for bleomycin ) . CONCLUSION Given the similar efficacy and significant cost advantage , we conclude that talc is the agent of choice when utilizing pleurodesis for control of symptomatic malignant pleural effusions The st and ard palliation of malignant pleural effusions involves tube thoracostomy drainage with chemical pleurodesis . The insufflation of intrapleural talc under thoracoscopic guidance ( n = 39 ) was evaluated against documented controls that consisted of patients ( n = 85 ) who participated in a r and omized study with tube thoracostomy drainage followed by either bleomycin or tetracycline sclerosis . Under local anesthesia , which was supplemented by intravenous sedation , patients in the talc group underwent complete pleural fluid evacuation . The talc was then insufflated evenly on the entire pleural surface under thoracoscopic guidance . Of the patients in the talc group who survived their disease process , 97 % had a successful pleurodesis at 30 days and 95 % at 90 days . In comparison , the bleomycin group demonstrated a success rate of 64 % at 30 days and 70 % at 90 days ( p = 0.003 and p = 0.047 versus the talc group ) . The tetracycline group had successful pleurodesis in only 33 % at 30 days and 47 % at 90 days ( p < 0.001 and p < 0.001 versus the talc group ) . There were only two patients in the talc group in whom pleurodesis was not successful , and both were subsequently found to have extraluminal compression of the right lower lobe bronchus , which prevented lung reexpansion . These data demonstrate that the insufflation of talc into the pleural cavity under thoracoscopic guidance is a safe and efficacious procedure in the control of malignant pleural effusions In order to determine whether pleural drainage with talc instillation was better than pleural drainage alone , in the treatment of malignant effusion , the present trial was initiated . Thirty-one patients with malignant pleural effusion and progressive disease , resistant to conventional therapy , were included . All patients had pleural drainage applied . After re-expansion of the lung , half of the patients had talc instilled through the chest tube . Twenty-one of the 31 treated patients were evaluable . After pleural drainage with talc instillation , all of 9 treated patients obtained complete resolution of the effusion and subjective improvement . After pleural drainage alone , 7 of 12 patients obtained complete resolution of the malignant effusion . If it is possible to re-exp and the lung during pleural drainage in patients with a malignant pleural effusion , pleurodesis can be obtained in 60 % of the treated patients with pleural drainage alone . This study showed a statistically significant improvement in the treatment associated with instillation of talc into the pleural cavity and this was achieved without causing increased discomfort to the patient Pleural sclerosis after tube thoracostomy was performed in 40 patients with malignant pleural effusions . The patients were r and omly allocated to intrapleural therapy with tetracycline or mechlorethamine . Follow up was obtained on each patient to determine if a symptomatic effusion recurred . The response was classified as a complete or partial response and failure . ( Complete response : complete lack of reaccumulation of pleural fluid for at least 60 days . Partial response : small pleural effusion asymptomatic not requiring further treatment for at least 60 days . Failure : all other cases ) . Tetracycline produced complete or partial control of the effusion in 16 of 20 trials for a duration of 6.1 + /- 4.1 months ( range 2 - 14 months ) . Mechlorethamine produced control of the effusion in 12 of 20 trials for a duration of 4.4 + /- 1 months ( range 2 - 8 months ) . These findings indicate that intracavitary tetracycline is a more effective treatment than intracavitary mechlorethamine for the control of neoplastic pleural effusion A r and omized phase III trial of bleomycin , tetracycline and talc following chest tube drainage and a meta- analysis of relative benefit of bleomycin and tetracycline as sclerosing agents were performed to determine the optimal approach to malignant pleural effusion ( MPE ) . Fifty patients were r and omized to receive bleomycin ( n=16 ) , tetracycline ( n=19 ) or talc ( n=16 ) following chest tube drainage . Treatment groups were balanced for pretreatment characteristics . The study was ended prematurely because of the removal of parenteral tetracycline from the market . Overall , 52 % of r and omized patients had successful control of effusion 30 days after sclerosis . There were no differences between any of the three treatment groups in terms of 30 day control of effusion , overall survival ( 6 months ) , resclerosis rate , pain with sclerosis , fever , or duration of hospitalization ( 6 days ) . A meta- analysis was performed using the four previously reported trials of tetracycline vs. bleomycin and revealed a 20.6 % advantage to the use of bleomycin ( 95 % C.I. 7.9%-33.3 % ) ( p=0.002 ) . This phase III failed to demonstrate a significant difference between the three agents in terms of control of MPE at 30 days , side effects or survival . However , because of small sample size , this study lacks sufficient power to observe potentially clinical ly important differences between treatment groups . Inclusion of data from four previous trials in a meta- analysis showed that bleomycin may be superior . The median duration of hospitalization and the overall success rate of all three sclerosing agents in this study argue convincingly that new approaches to palliate MPE are needed Between December 1985 and August 1988 , there were 115 patients at 13 centers who were entered on a r and omized comparison of tetracycline and bleomycin for treatment of malignant pleural effusions . Fifteen patients were not treated , primarily due to rapid progression of systemic cancer . Fifteen patients entered on a high-dose regimen of bleomycin ( 120 units ) were excluded from this analysis ( following early closure of that arm ) , leaving 85 patients r and omized to low-dose bleomycin ( 60 units ; 44 patients ) or tetracycline ( 1 g ; 41 patients ) . Patients were required to have a cytologically positive pleural effusion , good performance status ( 0 , 1 , or 2 ) , lung reexpansion following tube thoracostomy with drainage rates of 100 ml/24 or less , no prior intrapleural therapy , no prior systemic bleomycin therapy , no chest irradiation , and no recent ( four weeks ) change in systemic therapy . A total of 11 patients ( five with bleomycin and six with tetracycline ) were not evaluable due to technical problems with tube drainage ( one ) , loss to follow-up ( two ) , sudden death due to pulmonary embolus ( one ) , and rapid progression of systemic disease ( seven ) . There were no clinical ly significant differences in demographic factors , primary site , performance status , or presence of metastases other than pleural effusion . Overall survival did not differ between the two groups . Median time to recurrence or progression of the effusion was 32 days for tetracycline-treated patients and at least 46 days for bleomycin-treated patients ( p = 0.037 ) . The recurrence rate within 30 days of instillation was 36 percent ( 10/28 ) with bleomycin and 67 percent ( 18/27 ) with tetracycline ( p = 0.023 ) ( not all patients were restudied in the first 30 days ) . By 90 days the corresponding recurrence rates were 30 percent ( 11/37 ) for bleomycin and 53 percent ( 19/36 ) for tetracycline ( p = 0.047 ) . Toxicity was similar between groups OBJECTIVE Differing success rates of various pleurodesis agents have been reported in the management of malignant pleural effusions . A r and omized clinical trial was conducted to compare the efficacy of two commonly used agents , talc and bleomycin , for the pleurodesis of malignant pleural effusions . METHODOLOGY Inclusion in the study required proof of a malignant pleural effusion by fluid cytology or pleural biopsy . Exclusion criteria included trapped lung , loculated effusions , recurrent effusions and life expectancy < 1 month . Five grams of talc or 1 unit per kilogram bodyweight of bleomycin mixed in 150 mL of normal saline was administered via tube thoracostomy after complete drainage of the pleural effusion in each patient . Treatment success was defined as the absence of recurrent pleural effusion on the chest radiograph 1 month after pleurodesis . RESULTS Treatment success was achieved in 16 out of 18 patients ( 89 % ) in the talc slurry group versus 14 out of 20 patients ( 70 % ) in the bleomycin group ( P=0.168 ) . Fever and pain were the only side-effects of pleurodesis in both groups . CONCLUSION These results indicate that talc slurry is as effective as bleomycin in preventing early recurrence of malignant pleural effusions . Pleurodesis with talc instead of bleomycin can result in significant cost savings Forty-one patients with malignant pleural effusions secondary to breast cancer were r and omly allocated to treatment with either intracavitary talc or intracavitary tetracycline . Of 33 evaluable patients , radiological control was achieved in 11/12 ( 92 % ) of the talc group compared with 10/21 ( 48 % ) of the tetracycline group ( P = 0.022 ) . Intracavitary talc provides effective palliation of metastatic pleural effusions secondary to breast cancer Talc pleurodesis is an effective technique for the management of symptomatic malignant pleural effusions . It is assumed that a good dispersion of talc suspension contributes to the final success of this treatment . For this purpose , guidelines often advise to rotate the patient after intra-pleural instillation of the sclerosant . This prospect i ve , r and omized study analyses the dispersion of talc suspension and the overall success rate in patients with malignant effusions . After instillation of 99mTc-sestamibi-labeled talc suspension ten subjects were rotated for 1 h , while the ten other patients remained in a stable supine body position . Scintigraphic imaging was done in two directions immediately after instillation and after 1 h with a clamped drain . The overall success of the treatment was assessed 1 month after the pleurodesis . The dispersion of talc was limited and unequal in 75 % of the subjects . In two patients with apparently good distribution on anterior views , the lateral views of the scintigraphy showed only limited distribution . Rotation of the patients did not influence the dispersion of sludge after 1 min or 1 h. Pleurodesis was successful in 85 % of the patients after 1-month follow-up . St and ard rotation protocol s for patients with malignant pleural effusion do not affect the overall dispersion of talc suspension and should be abolished because of the discomfort caused to the patients Induction of pleurodesis offers benefit for patients with metastatic tumors and symptomatic malignant pleural effusions , but the best method for achieving this is still unknown . In this prospect i ve , r and omized comparison of two well-established pleurodesis procedures , 36 patients with malignant pleural effusions , exp and ed lungs after drainage , and expected survival of > 1 mo received either bleomycin instillation ( 60E ) via a small-bore thoracostomy tube or thoracoscopic talc poudrage ( 5 g ) under local anesthesia . Efficacy , safety , and cost could be evaluated for 32 treatments ( 17 bleomycin , 15 talc ) in 31 patients . Recurrence rates of effusion with bleomycin and talc poudrage after 30 d were 41 % and 13 % ( p = 0.12 ) , respectively , those after 90 d were 59 % and 13 % , respectively ( p = 0.01 ) , and those after 180 d were 65 % and 13 % ( p = 0.005 ) , respectively . Neither procedure showed any major adverse effect , and both were equally well tolerated . Cost estimation favored thoracoscopic talc poudrage , both for the initial hospitalization and with regard to recurrences . In conclusion , thoracoscopic talc pleurodesis under local anesthesia is superior to bleomycin instillation for pleurodesis in cases of malignant pleural effusion The search for the ideal agent to achieve pleurodesis for malignant pleural effusions is still on . Twenty-two patients with dyspnea-producing , recurrent pleural effusions secondary to epithelial neoplasms were subjected to instillation into the pleural cavity of either iodopovidone ( 14 patients ) or bleomycin ( 8 patients ) through a large bore chest tube . The results showed that in 9 of the 14 patients receiving iodopovidone ( 64.2 % ) and in 7 of the 8 patients in the bleomycin group ( 87.5 % ) there was no further need for drainage of the pleural space . Local or systematic complications occurred in 8 patients ; no complication was severe . In conclusion in this preliminary study , iodopovidone has shown promise as an effective , readily available and inexpensive alternative to achieve chemical pleurodesis in cases of recurrent , incapacitating effusions secondary to malignant epithelial neoplasms ; further studies are needed to confirm these initial results In a r and omized trial , pleurodesis was attempted with Corynebacterium parvum in one group and bleomycin in another . Patients with malignant pleural effusion which required repeated drainage were treated with instillation of one of these agents after complete drainage of the pleural effusion . There were 32 patients who could be evaluated . Sixty-five per cent of the patients treated with C. parvum had no recurrence after one treatment and another 29 % after two treatments . In the bleomycin group , two patients needed only one treatment while the remainder - 13 out of 15 patients - needed further drainage treatments even after two instillations of the drug . The difference was highly significant ( p less than 0.001 ) In comparative studies with other agents , insufflated talc has been shown to be the most effective agent in achieving chemical pleurodesis in patients with malignant pleural effusions . The objective of this study is to compare the efficacy of talc administered as slurry ( 5 g in 50 mL saline ) via tube thoracostomy with that of bleomycin ( 1 mg/kg in 50 mL saline ) ( which is the most effective agent other than talc ) . In a r and omised , prospect i ve comparative study , twenty-six consecutive patients with proven malignant pleural effusions ( recurrent after at least two pleuroscenteses ) in whom no pleurodesis attempt had yet been made , and who were symptomatic , had a Karnovski index < or = 50 , and an expected survival of one year or less , were included . Therapeutic failure was defined as recurrent pleural fluid > or = 50 % of initial volume or requiring pleurocentesis . Recurrence rates ( 25 % vs 21.4 % , NS ) , fever ( 25 % vs 35.7 % , NS ) , pain ( 0 % both groups ) and survival ( 3.75 + /- 3 vs 5.82 + /- 7.15 months , NS ) did not differ between bleomycin or talc treated patients . There were no major complications ( e.g. , empyema ) or side-effects . In conclusion , talc slurry and bleomycin are equally effective in achieving chemical pleurodesis via thoracostomy in patients with malignant pleural effusions , and the safety profile of both agents is similar . Since talc is substantially less expensive than bleomycin , talc slurry probably represents the agent of choice for chemical tube thoracostomy pleurodesis Effusions are common in advanced cancer . Intracavitary instillation of various agents such as bleomycin has achieved control rates varying between 20 % and 60 % . However , serious side effects have also been observed , and cases of death due , for instance , to bleomycin have been reported . Mitoxantrone has been tested recently in the treatment of effusions , and preliminary results suggest high efficacy of this drug in the treatment of peritoneal , pericardial , and pleural effusions . Nevertheless , certain results have been conflicting . In the present study , 29 patients with pleural effusions were treated either with intracavitary bleomycin or intracavitary mitoxantrone . Effusions were controlled almost equally by both agents ; 67 % with mitoxantrone and 64 % with bleomycin . We conclude that both agents can be used successfully in the treatment of pleural effusions From 11/87 until 7/90 103 patients entered a prospect i ve r and omized trial on the treatment of malignant pleural effusions ( MPE ) with intrapleural mitoxantrone versus placebo ( pleural tube alone with instillation of isotonic NaCl ) . Our data suggest no statistically significant difference between the two arms with respect to response and response duration . There is no influence on survival time . The toxicity is moderate , with only fever occurring more often in the mitoxantrone arm . We recommend performance of pleurodesis in patients with MPE first by sufficient drainage with a tube of 16 - 20 char . Only in instances of failure it is necessary to add sclerosing agents such as tetracycline , etc STUDY OBJECTIVE To evaluate the efficacy of small-bore ( 12 French vanSonnenberg ) catheters compared with st and ard large-bore chest tubes in the drainage and sclerotherapy of malignant pleural effusions . DESIGN Retrospective review . SETTING An academic tertiary care hospital . PATIENTS Adult patients with documented neoplasms and malignant pleural effusions , treated between 1986 and 1995 . INTERVENTION All patients included in the study underwent drainage of malignant pleural effusions either by large-bore chest tube or by ultrasound-guided small-bore catheter . After drainage , pleurodesis was performed . RESULTS Outcome as defined by recurrence of effusion was determined by blinded examination of all postpleurodesis chest radiographs . We identified 58 cases of malignant pleural effusion in which small-bore catheters were used and 44 in which large-bore chest tubes were used . The majority of patients had breast ( n = 56 , 55 % ) or lung cancer ( n = 29 , 28 % ) . The median age was 65 years . Fifty-nine patients were actively being treated with chemotherapy at the time of pleurodesis . The following sclerosing agents were used : talc , 27 ( 26 % ) ; tetracycline , 72 ( 70 % ) ; bleomycin , 2 ( 2 % ) ; and interferon , 1 ( 1 % ) . Actuarial probabilities of recurrence at 6 weeks and 4 months were 45 % and 53 % for the small tubes vs 45 % and 51 % for the large tubes . Univariate and multivariate analyses failed to demonstrate that tube size had any influence on the rate of recurrence . CONCLUSIONS We were unable to detect any major differences in outcomes with the use of either size of chest tube . Our study suggests that small-bore catheters may be effective in the treatment of malignant pleural effusions and deserve further evaluation in prospect ively design ed trials A prospect i ve r and omized study to compare the effectiveness of pleurodesis by two new sclerosing agents : OK‐432 and mitomycin C were conducted in S3 patients with malignant pleural effusion caused by lung cancer . None of the patients received concomitant systemic chemotherapy or radiation therapy during the study . After complete drainage of pleural fluid , the patients were allocated r and omly to receive 10 Klinische Einheit units of OK‐432 or 8 mg of mitomycin C by intrapleural injection at weekly intervals . The treatment was terminated if the pleural effusion disappeared or the patients had received four consecutive procedures . There were 26 patients who received pleurodesis with OK‐432 and 27 , with mitomycin C. Patient characteristics in the two treatment groups ( age , sex , histologic type , performance status , and prior treatment before pleurodesis ) were compatible . These results showed that pleurodesis with OK‐432 achieved a higher complete response rate ( 73 % ) than that of mitomycin C ( 41 % ) . The rates of objective treatment response ( complete response plus partial response ) were comparable in both groups ( 88 % for OK‐432 and 67 % for mitomycin C ) . The average number of intrapleural injections needed to achieve complete response was fewer in the OK‐432 group ( 1.9 + M 0.9 ) than in mitomycin C group ( 2.8 + M 0.9 ) . There was no significant difference in the median survival of the patients who received pleurodesis with OK‐432 ( 5.8 months ) or mitomycin C ( 5.1 months ) . However , the effusion‐free period in the OK‐432 group was significantly longer than that in the mitomycin C group ( 7.0 months versus 1.5 months ) . Patients who underwent OK‐432 pleurodesis had a higher complication rate ( 80 % ) than did those in the mitomycin C group ( 30 % ) . Transient febrile reaction was the most common reaction encountered . The immunologic study in OK‐432 group showed an increase in peripheral leukocyte count and decrease in the OKT4/OKT8 ratio . The mitomycin C group had a mild reduction in peripheral blood leukocyte count and no significant change in the OKT4/OKT8 ratio . It was concluded that pleurodesis with OK‐432 is an effective alternative treatment for malignant effusion in patients with lung cancer Intrapleural instillation of tetracycline ( TCN ) has been shown to be effective in preventing the recurrence of malignant pleural effusions . Although the precise mechanism of action is unknown , it has been postulated that the pH of the TCN solution may be an important factor . Thirty patients with malignant pleural effusions were r and omized in a double‐blind trial to receive intrapleural administration of either 500 mg of tetracycline in solution ( pH = 2.8 ) or a solution of similar pH and appearance . All patients had chest tube drainage of their effusion . There were 24/30 patients evaluable . There were 9/13 patients in the TCN group and 1/9 patients in the control group who had no reaccumulation of fluid ( P < 0.05 ) . These results would suggest that the efficacy of TCN as a sclerosing agent is not related to its acidic pH and that intrapleural TCN is more effective than chest tube drainage alone for control of malignant effusions Malignant pleural effusion is a frequent complication of metastatic breast cancer leading to a significant degree of morbidity . Drainage of the effusion by thoracocentesis and pleurodesis with tetracycline as the sclerosing agent is an established means of symptomatic relief in these patients . To determine whether the efficacy of tetracycline pleurodesis is improved by surgical rather than medical drainage and instillation of sclerosant , 34 patients were prospect ively r and omised to a trial comparing the two treatment modalities , of whom 29 were evaluable for response . The total failure rate of primary pleurodesis was 13.4 % , the rate of recurrence of effusion within the first month was 24 % , and only 1 patient ( 3.4 % ) required repeat aspiration in that time period . There was no significant difference in the rate of recurrence or reaspiration of effusion between the two treatment groups . Although the overall survival time from treatment of effusion is significantly longer in the surgical treatment group than in the medical treatment group ( P = 0.03 ) , this is likely to be due to factors other than the method of treating the effusion . We conclude that surgical tetracycline pleurodesis has no advantage over medical tetracycline pleurodesis |
843 | 21,491,383 | Naltrexone was not superior to benzodiazepines and to buprenorphine for retention and abstinence and side effects .
The findings of this review suggest that oral naltrexone did not perform better than treatment with placebo or no pharmacological agent with respect to the number of participants re-incarcerated during the study period .
If oral naltrexone is compared with other pharmacological treatments such as benzodiazepine and buprenorphine , no statistically significant difference was found .
The conclusion of this review is that the studies conducted have not allowed an adequate evaluation of oral naltrexone treatment in the field of opioid dependence .
Consequently , maintenance therapy with naltrexone can not yet be considered a treatment which has been scientifically proved to be superior to other kinds of treatment | BACKGROUND Research on clinical application of oral naltrexone agrees on several things .
From a pharmacological perspective , naltrexone works .
From an applied perspective , the medication compliance and the retention rates are poor .
OBJECTIVES To evaluate the effects of naltrexone maintenance treatment versus placebo or other treatments in preventing relapse in opioid addicts after detoxification . | BACKGROUND Expansion of access to effective treatments for heroin dependence is a worldwide health priority that will also reduce HIV transmission . We compared the efficacy of naltrexone , buprenorphine , and no additional treatment , in patients receiving detoxification and subsequent drug counselling , for maintenance of heroin abstinence , prevention of relapse , and reduction of HIV risk behaviours . METHODS 126 detoxified heroin-dependent patients , from an outpatient research clinic and detoxification programme in Malaysia , were r and omly assigned by a computer-generated r and omisation sequence to 24 weeks of manual-guided drug counselling and maintenance with naltrexone ( n=43 ) , buprenorphine ( n=44 ) , or placebo ( n=39 ) . Medications were administered on a double-blind and double-dummy basis . Primary outcomes , assessed by urine testing three times per week , were days to first heroin use , days to heroin relapse ( three consecutive opioid-positive urine tests ) , maximum consecutive days of heroin abstinence , and reductions in HIV risk behaviours over 6 months . The study was terminated after 22 months of enrolment because buprenorphine was shown to have greater efficacy in an interim safety analysis . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT00383045 . FINDINGS We observed consistent , linear contrasts in days to first heroin use ( p=0.0009 ) , days to heroin relapse ( p=0.009 ) , and maximum consecutive days abstinent ( p=0.0007 ) , with all results best for buprenorphine and worst for placebo . Buprenorphine was associated with greater time to first heroin use than were naltrexone ( hazard ratio 1.87 [ 95 % CI 1.21 - 2.88 ] ) or placebo ( 2.02 [ 1.29 - 3.16 ] ) . With buprenorphine , we also recorded significantly greater time to heroin relapse ( 2.17 [ 1.38 - 3.42 ] ) , and maximum consecutive days abstinent than with placebo ( mean days 59 [ 95 % CI 43 - 76 ] vs 24 [ 13 - 35 ] ; p=0.003 ) ; however , for these outcomes , differences between buprenorphine and naltrexone were not significant . Differences between naltrexone and placebo were not significant for any outcomes . HIV risk behaviours were significantly reduced from baseline across all three treatments ( p=0.003 ) , but the reductions did not differ significantly between the three groups . INTERPRETATION Our findings lend support to the widespread dissemination of maintenance treatment with buprenorphine as an effective public-health approach to reduce problems associated with heroin dependence Federal probationers or parolees with a history of opioid addiction were referred by themselves or their probation/parole officer for a naltrexone treatment study . Participation was voluntary and subjects could drop out of the study at any time without adverse consequences . Following orientation and informed consent , 51 volunteers were r and omly assigned in a 2:1 ratio to a 6-month program of probation plus naltrexone and brief drug counseling , or probation plus counseling alone . Naltrexone subjects received medication and counseling twice a week ; controls received counseling at similar intervals . All therapy and medication were administered in an office located adjacent to the federal probation department . Fifty-two percent of subjects in the naltrexone group continued for 6 months and 33 % remained in the control group . Opioid use was significantly lower in the naltrexone group . The overall mean percent of opioid positive urine tests among the naltrexone subjects was 8 % , versus 30 % for control subjects ( p < .05 ) . Fifty-six percent of the controls and 26 % of the naltrexone group ( p < .05 ) had their probation status revoked within the 6-month study period and returned to prison . Treatment with naltrexone and brief drug counseling can be integrated into the Federal Probation/Parole system with favorable results on both opioid use and re-arrest rates The goals of this study were two-fold : ( 1 ) to test the hypothesis that retention of patients in naltrexone treatment could be improved by educating and preparing them for it while enrolled in a LAAM ( l-alpha-acetylmethadol ) detoxification program ; and ( 2 ) to compare the safety and efficacy of 60 mg vs. 120 mg administered thrice weekly in a double-blind , sequential trial design . Patients were allowed a maximum of 365 days on naltrexone , and a maximum of four admissions ; 119 patients received at least one dose of naltrexone . We found no clinical ly important differences between the two dosages , and retention in treatment was similar to that reported in earlier clinical trials . Slightly more than half the patients ever used heroin while receiving naltrexone , and only 9 % of all urine tests were positive for opiates . Craving for heroin decreased dramatically by the end of the first week . We found no side-effect or toxicity due to naltrexone AIM To investigate the efficacy of low doses of naltrexone in relapse prevention for heroin dependence . DESIGN Double blind , r and omised comparison of three groups-Group 1 taking 50 mg per day , Group 2 : 0.5 mg per day , and Group 3 : 0.05 mg per day . PARTICIPANTS Sixty-six dependent heroin users . INTERVENTIONS After detoxification followed by 1 week on 50 mg per day naltrexone , participants were r and omised to trial medication . All were offered counselling and monitored with weekly clinical review s. Research interviews were conducted at three and 6 months . OUTCOME MEASURES Retention in treatment and heroin use at 3 and 6 months . Secondary outcome measures were side effects and craving . FINDINGS Mean days retained in r and omised treatment were-Group 1 : 58.9 days ; Group 2 : 46.6 days ; and Group 3 : 47.8 days . Differences in retention were not significant using survival analysis . However , nine of the first 60 participants , transferred to the 50 mg dose , and one transferred to a lower dose ( chi-square = 0.142 ; P = 0.018 ) . At follow-up , there was no relationship between abstinence from heroin and naltrexone dose , nor between level of heroin use and dose . There were no differences between groups in craving or depression . CONCLUSION Low doses of naltrexone had no discernible advantage , and participants preferred 50 mg per day . Despite preference for blocking doses of naltrexone , outcomes appeared to be independent of naltrexone dose The effectiveness of antagonist maintenance with oral naltrexone for opioid dependence has been limited by high dropout rates . Behavioral Naltrexone Therapy ( BNT ) was developed to improve retention on oral naltrexone by integrating voucher incentives , Motivational and Cognitive Behavioral therapies , and a significant other for monitoring medication adherence . In a 6-month , r and omized , controlled trial in heroin dependent patients , BNT ( N = 36 ) improved retention in treatment compared to a st and ard treatment control ( Compliance Enhancement ( CE ) ; N = 33 ) ( log rank = 4.28 ; p = .04 ) . Most patients retained beyond 3 months achieved abstinence from opioids , but retention at 6 months was only 22 % on BNT and 9 % on CE . A systematic review of related controlled trials revealed similar effect sizes in the small to medium range , and substantial dropout . There may be a limit on the extent to which behavioral therapy can overcome poor adherence to oral naltrexone . Future research should consider combinations of behavioral methods with new long-acting injectable or implantable naltrexone formulations In a double blind study , out of 31 newly abstinent patients who underwent opioid free detoxification , 15 were started on the opiate antagonist Naltrexone for 2 months , and 16 were put on placebo for the same period . Given Naltrexone 's known efficacy in blocking euphorigenic effects of opioid intake , and in decreasing cravings for the drug , the authors have tried to assess eventual drug taking , specifically in the context of suburban housing projects , and evaluate the rate of retention in a rehabilitative program for both the Naltrexone and placebo groups . An Opioid free condition was followed up for a year , also respecting double blind conditions . Naltrexone did not appear to be superior to the placebo with regards to retention rate . In the Naltrexone group ( n = 15 ) , 9 finished the two-month treatment , and 8 remained opioid-free for a year . In the placebo group ( n = 16 ) , 8 finished the 2 month trial and 6 remained opioid-free for a year . Naltrexone blocked opioid-induced euphoria and decreased the craving for opium , but it did not inhibit drug usage . The retention rate registered during the course of the study , as well as an opioid-free condition in the follow-up year , correlated with a patient profile defined by good social functioning and stable relationships . The inherent method ological limitations of this study did not allow for the discrimination of the role of non-pharmacological factors , such as psychotherapy , supportive family framework , community assistance , and staff motivation , concerning the clinical results . Further investigation of Naltrexone in larger sample s is needed Naltrexone and placebo as adjuvant treatment of opioid dependence were compared in a double-blind , controlled clinical trial in 50 heroin addicts . The overall efficacy was assessed by the degree of treatment acceptance , percentage of relapse in heroin consumption , presence of side effects , and overall retention on naltrexone . A total of 50 patients of both sexes , aged from 18 to 30 years , who fulfilled DSM-III-R criteria for opioid dependence were included in the study . All patients completed detoxification with clonidine on an inpatient basis for 2 weeks and subsequently , on an out-patient basis , received oral naltrexone ( 350 mg per week ) for a month . At the beginning of the second month patients were r and omly allocated to treatment with naltrexone ( 28 patients ) or placebo ( 22 patients ) until a 6-month treatment period in a double-blind fashion had been completed . During the study period ( 1 year ) all patients followed the same therapeutic schedule . Patients in both groups were comparable in terms of socio-demographic data and toxicological history . The efficacy of naltrexone was not superior to that of placebo as there were no significant differences in acceptance of treatment , retention rates , opioid and other drug consumption , drug compliance or side effects This r and omized placebo-controlled trial tested the efficacy of oral naltrexone with or without fluoxetine for preventing relapse to heroin addiction and for reducing HIV risk , psychiatric symptoms , and outcome . All patients received drug counseling with parental or significant-other involvement to encourage adherence . Patients totaling 414 were approached , 343 gave informed consent , and 280 were r and omized ( mean age , 23.6 + /- 0.4 years ) . At 6 months , two to three times as many naltrexone patients as naltrexone placebo patients remained in treatment and had not relapsed , odds ratio ( OR ) = 3.5 ( 1.96 - 6.12 ) , p < .0001 . Overall , adding fluoxetine did not improve outcomes , OR = 1.35 ( 0.68 - 2.66 ) , p = .49 ; however , women receiving naltrexone and fluoxetine showed a trend toward a statistically significant advantage when compared to women receiving naltrexone and fluoxetine placebo , OR = 2.4 ( 0.88 - 6.59 ) , p = .08 . HIV risk , psychiatric symptoms , and overall adjustment were markedly improved among all patients who remained on treatment and did not relapse , regardless of group assignment . More widespread use of naltrexone could be an important addition to addiction treatment and HIV prevention in Russia The efficacy of Naltrexone in preventing reabuse of heroin among heroin addicts in Israel was studied in a double-blind , controlled design . Naltrexone ( or placebo ) treatment was given as part of a general treatment plan that continued for 12 weeks . Thirty-two addicts who successfully completed a detoxification program and met research criteria , were included in the study . Fifty milligrams of Naltrexone were taken orally three times a week ( 25 mg twice a week for the first 2 weeks ) . The follow-up procedure included an interview , urine tests , and screening for possible adverse effects . In addition , social and psychological parameters were evaluated . Fewer heroin-positive urine tests were found the Naltrexone group than in the placebo group . Throughout the entire study , the number of drug-free patients in the Naltrexone group was higher than in the placebo group . The Naltrexone group showed a significant improvement in most psychological parameters as compared with the placebo group . No differences were found in compliance or ratio of adverse effects between the Naltrexone and placebo groups . The concept " heroin abuse load " based on daily heroin consumption and duration of addiction enabled us to predict which addicts would complete the treatment program . The results suggest that heroin addicts in Israel may benefit from treatment with Naltrexone Good results in detoxification methods have been reached using both together clonidine and opiate receptors antagonists . One hundred fifty-two heroin-abusing patients were studied evaluating withdrawal symptoms after therapy with ( a ) clonidine only , ( b ) clonidine and naltrexone , ( c ) clonidine and naloxone , and ( d ) placebos . Treatment results , emotional and behavioral changes , and involvement in psychosocial programs were evaluated after a 6-month follow-up . Although opiate antagonists were able to induce slight and transient withdrawal signs and symptoms , there was , in the group of patients treated with clonidine and naltrexone together , a low percentage of catabolites in urine and an improvement in mood and family relationships . Furthermore , the patients that underwent longer naltrexone treatment showed a stronger involvement in psychosocial programs , and even their relatives demonstrated more interest in the recovery program . A decrease in the difficulties of accepting an opiate antagonists treatment and a different evaluation of withdrawal syndrome were the results of an early use of naltrexone Naltrexone treatment , used to prevent relapse among former opioid addicts , is reported to have an extraordinary rate of noncompliance . Since activation of opioid receptors produces a sense of well-being , naltrexone 's blockade of these receptors might produce dysphoria , which could contribute to noncompliance among addicts under treatment . To test this hypothesis , the authors administered naltrexone to four men who had been free of opioids for 9 to 44 months using a 6-week , placebo-controlled crossover design . One subject dropped out with abstinence-like symptoms , and two others reported mild but significantly greater dysphoria during naltrexone administration . The results suggest that naltrexone may induce mild dysphoria long after addicts stop using opioids In a controlled double-blind clinical study , 42 patients reported side effects and severity of side effects to naltrexone on three different first-day doses and maintenance dosage regimens . Initiating doses of 25 , 100 , and 150 mg were administered . The maintenance regimens involved 350 mg of naltrexone per week for 4 weeks with drug administration in Group A , five times weekly ; in Group B , three times weekly ; and in Group C , twice weekly . All three groups received identical doses for the last dosage administered each week . The first-day doses produced no significant quantitative difference in side effects . Overall , the three groups reported little difference in side effects . Nonetheless , the regimen with the least number of patients reporting side effects daily was that of Group B. In no case , regardless of dose or dosage regimen , did any patient have side effects of such a nature as to require termination of their participation in the study One hundred nineteen patients were admitted to a six-month ( 26-week ) prenaltrexone detoxification program comparing abrupt and gradual withdrawal from methadyl acetate ( LAAM ) therapy . All patients were brought to a maintenance level of 50 , 50 , and 65 mg ( Monday , Wednesday , and Friday ) . Patients r and omly assigned to the gradual group ( group G ) began 4-mg/wk reduction the Monday of week 9 and reached zero dosage ( placebo ) the Monday of week 23 ; patients in the abrupt group ( group A ) continued to receive 50 , 50 , and 65 mg until the Monday of week 23 , when their dosage was dropped to zero ( placebo ) . All patients were given placebo for four weeks . This study showed the superiority of abrupt withdrawal over this gradual-withdrawal schedule . Forty-six percent of group P compared with 28 % of group G made the transition to naltrexone treatment . Severity of withdrawal problems was in no case significantly greater in group The induction side effects of cyclazocine and naltrexone were compared in double-blind placebo-controlled studies involving 40 patients ( 20 for each drug ) . These studies were carried out with a twice-a-day dosage regimen . Naltrexone produced fewer side effects than cyclazocine . Naltrexone side effects fell to levels indistinguishable from those of placebo in the " induction after placebo " phase . In contrast , cyclazocine " induction after placebo " produced an even higher level of side effects than found in its induction . In no case was naltrexone discontinued because of side effects . On the other h and , three of 20 cyclazocine-treated patients discontinued the drug because of distressing side effects . No toxicity was noted with either agent . The controlled data reported supports the clinical impression that naltrexone produces fewer induction side effects than cyclazocine Naltrexone may be more effective for treating opioid ( heroin ) dependence in Russia than in the U.S. because patients are mostly young and living with their parents , who can control medication compliance . In this pilot study we r and omized 52 consenting patients who completed detoxification in St. Petersburg to a double blind , 6-month course of biweekly drug counseling and naltrexone , or counseling and placebo naltrexone . Significant differences in retention and relapse favoring naltrexone were seen beginning at 1 month and continuing throughout the study . At the end of 6 months , 12 of the 27 naltrexone patients ( 44.4 % ) remained in treatment and had not relapsed as compared to 4 of 25 placebo patients ( 16 % ; p<0.05 ) . Since heroin dependence is the main way HIV is being spread in Russia , naltrexone is likely to improve treatment outcome and help reduce the spread of HIV if it can be made more widely available A review of the data from a double-blind , placebo-controlled human study places the validity of the classic double-blind crossover design for psychoactive drugs in question . Two comparable groups of 20 adult , male inmates , all with a history of opiate addiction , were studied . In each group , half the subjects were placed on placebo while the other half were placed on a narcotic antagonist ( cyclazocine for one group , naltrexone for the other ) . The initial placebo recipients were subsequently placed on the drug . It was expected that placebo pretreatment would “ wash out ” placebo responses , and that the drug administered after placebo would show a lessened response . With naltrexone , the agent producing fewer side effects , the level of effects after placebo was much lower than on initial exposure , as expected . In contrast , cyclazocine produced more effects after placebo than on initial exposure . It is hypothesized as a result of this study that a threshold level of effects exists below which psychoactive effect Naltrexone ( NTX ) is widely used to prevent relapse of opioid-dependent patients but its association with insomnia and " hyperexcitability " can result in treatment withdrawal . We evaluated whether NTX combined with the benzodiazepine prazepam was more effective than NTX in keeping patients opioid-free . We determined the relapse rate over 6 months in 56 opioid-dependent subjects , divided into 4 equal groups . All groups received psychological support and underwent urine tests for drug metabolites twice weekly . Group 1 did not receive pharmacological treatment ( controls ) . Group 2 received NTX alone ( one 50-mg tablet daily ) ; group 3 received NTX ( one 50-mg tablet daily ) plus placebo ( one tablet twice daily ) ; and group 4 received NTX ( one 50-mg tablet daily ) plus prazepam ( one 10-mg tablet twice daily ) . Ten patients of group 1 relapsed within 3 months , one after 6 months and three remained opioid-free . Six patients of group 2 relapsed within three months , two after 6 months , and six remained opioid-free . Seven patients of group 3 relapsed three months , one after 6 months and six patients remained opioid-free . In group 4 , one patient relapsed within 3 months and one patient after 6 months ; 12 patients of this group remained opioid-free . At urine tests , a significantly higher percent patients of group 4 remained free of Delta(9)-tetrahydrocannabinol versus patients of groups 2 and 3 . In conclusion , many patients remained opioid-free on NTX alone or combined with prazepam , with a significant advantage for the NTX plus prazepam group Naltrexone ( EN-1639A ) is approximately 17 times more potent than nalorphine as an antagonist in man . It is virtually devoid of agonistic activity , including the ability to induce nalorphine-like dysphoric effects . Its duration of action is longer than that of naloxone , but shorter than that of cyclazocine . It is effective orally . When administered in a dose level of 50 mg/day , it produces a degree of blockade of the effects of morphine and heroin that is comparable to that obtained with 4 mg of cyclazocine per day orally . Naltrexone , thus , appears to be a relatively pure potent narcotic antagonist which is effective orally and which may have utility in the treatment of heroin and narcotic dependence Thirty-eight , adult , male , detoxified , Malaysian opiate addicts participated in this double-blind clinical evaluation of naltrexone . Addicts from three ethnic groups : Chinese , Malays , and Indians received a weekly regimen of naltrexone ( 100 mg on Days 1 and 3 , and 150 mg on Day 5 ) . Subjects were r and omly assigned to receive intravenous challenge with either 25 mg heroin or placebo 12 , 24 , 48 , and 72 h after the third naltrexone dose . Physiological and subjective parameters were measured at each challenge interval . Results indicated that naltrexone was effective in blocking the physiological and psychological effects of heroin for at least 48 and 72 h , respectively , in detoxified Malaysian opiate addicts . The efficacy of naltrexone did not differ among the three ethnic groups evaluated in this study |
844 | 30,255,989 | Results from our systematic review suggest that MSC therapy for ischemic heart disease appears to be safe . | Pre clinical and clinical evidence suggests that mesenchymal stem cells ( MSCs ) may be beneficial in treating both acute myocardial infa rct ion ( AMI ) and ischemic heart failure ( IHF ) .
However , the safety profile and efficacy of MSC therapy is not well-known . | Introduction In large-animal acute myocardial infa rct ion ( AMI ) models , Wharton 's jelly ( umbilical cord matrix ) mesenchymal stem cells ( WJMSCs ) effectively promote angiogenesis and drive functional myocardial regeneration . Human data are lacking . Aim To evaluate the feasibility and safety of a novel myocardial regeneration strategy using human WJMSCs as a unique , allogenic but immuno-privileged , off-the-shelf cellular therapeutic agent . Material and methods The inclusion criterion was first , large ( LVEF ≤ 45 % , CK-MB > 100 U/l ) AMI with successful infa rct -related artery primary percutaneous coronary intervention reperfusion ( TIMI ≥ 2 ) . Ten consecutive patients ( age 32–65 years , peak hs-troponin T 17.3 ±9.1 ng/ml and peak CK-MB 533 ±89 U/l , sustained echo LVEF reduction to 37.6 ±2.6 % , cMRI LVEF 40.3 ±2.7 % and infa rct size 20.1 ±2.8 % ) were enrolled . Results 30 × 106 WJMSCs were administered ( LAD/Cx/RCA in 6/3/1 ) per protocol at ≈ 5–7 days using a cell delivery-dedicated , coronary-non-occlusive method . No clinical symptoms or ECG signs of myocardial ischemia occurred . There was no epicardial flow or myocardial perfusion impairment ( TIMI-3 in all ; cTFC 45 ±8 vs. 44 ±9 , p = 0.51 ) , and no patient showed hs-troponin T elevation ( 0.92 ±0.29 ≤ 24 h before vs. 0.89 ±0.28 ≤ 24 h after ; decrease , p = 0.04 ) . One subject experienced , 2 days after cell transfer , a transient temperature rise ( 38.9 ° C ) ; this was reactive to paracetamol with no sequel . No other adverse events and no significant arrhythmias ( ECG Holter ) occurred . Up to 12 months there was one new , non-index territory lethal AMI but no adverse events that might be attributable to WJMSC treatment . Conclusions This study demonstrated the feasibility and procedural safety of WJMSC use as off-the-shelf cellular therapy in human AMI and suggested further clinical safety of WJMSC cardiac transfer , providing a basis for r and omized placebo-controlled endpoint-powered evaluation Background The use of adult stem cells is limited by the quality and quantity of host stem cells . It has been demonstrated that Wharton ’s jelly – derived mesenchymal stem cells ( WJMSCs ) , a primitive stromal population , could integrate into ischemic cardiac tissues and significantly improve heart function . In this r and omized , controlled trial , our aim was to assess the safety and efficacy of intracoronary WJMSCs in patients with ST-elevation acute myocardial infa rct ion ( AMI ) . Methods In a multicenter trial , 116 patients with acute ST-elevation MI were r and omly assigned to receive an intracoronary infusion of WJMSCs or placebo into the infa rct artery at five to seven days after successful reperfusion therapy . The primary endpoint of safety : the incidence of adverse events ( AEs ) within 18 months , was monitored and quantified . The endpoint of efficacy : the absolute changes in myocardial viability and perfusion of the infa rct ed region from baseline to four months , global left ventricular ejection fraction ( LVEF ) from baseline to 18 months were measured using F-18-fluorodeoxyglucose positron emission computed tomography ( F-18-FDG-PET ) and 99mTc-sestamibi single-photon emission computed tomography ( 99mTc-SPECT ) , and two-dimensional echocardiography , respectively . Results During 18 months follow-up , AEs rates and laboratory tests including tumor , immune , and hematologic indexes were not different between the two groups . The absolute increase in the myocardial viability ( PET ) and perfusion within the infa rct ed territory ( SPECT ) was significantly greater in the WJMSC group [ 6.9 ± 0.6 % ( 95 % CI , 5.7 to 8.2 ) ] and [ 7.1 ± 0.8 % ( 95 % CI , 5.4 to 8.8 ) than in the placebo group [ 3.3 ± 0.7 % ( 95 % CI , 1.8 to 4.7 ) , P < 0.0001 ] and 3.9 ± 0.6(95 % CI , 2.8 to 5.0 ) , P = 0.002 ] at four months . The absolute increase in the LVEF at 18 months in the WJMSC group was significantly greater than that in the placebo group [ 7.8 ± 0.9 ( 6.0 to approximately 9.7 ) vs. 2.8 ± 1.2 ( 0.4 to approximately 5.1 ) , P = 0.001 ] . Concomitantly , the absolute decreases in LV end-systolic volumes and end-diastolic volumes at 18 months in the WJMSC group were significantly greater than those in the placebo group ( P = 0.0004 , P = 0.004 , respectively ) . Conclusions Intracoronary infusion of WJMSCs is safe and effective in patients with AMI , providing clinical ly relevant therapy within a favorable time window . This study encourages additional clinical trials to determine whether WJMSCs may serve as a novel alternative to BMSCs for cardiac stem cell-based therapy . Trial registration Clinical Trials NCT01291329 ( 02/05/2011 ) In experimental studies , mesenchymal stem cell ( MSC ) transplantation in acute myocardial infa rct ion ( AMI ) models has been associated with enhanced neovascularization and myogenesis . Clinical data however , are scarce . Therefore , the present study evaluates the safety and feasibility of intramyocardial MSC injection in nine patients , shortly after AMI during short-term and 5-year follow-up . Periprocedural safety analysis demonstrated one transient ischemic attack . No other adverse events related to MSC treatment were observed during 5-year follow-up . Clinical events were compared to a nonr and omized control group comprising 45 matched controls . A 5-year event-free survival after MSC-treatment was comparable to controls ( 89 vs. 91 % , P = 0.87 ) . Echocardiographic imaging for evaluation of left ventricular function demonstrated improvements up to 5 years after MSC treatment . These findings were not significantly different when compared to controls . The present safety and feasibility study suggest that intramyocardial injection of MSC in patients shortly after AMI is feasible and safe up to 5-year follow-up Recent studies suggest that the intracoronary administration of bone marrow (BM)-derived mesenchymal stem cells ( MSCs ) may improve left ventricular function in patients with acute myocardial infa rct ion ( AMI ) . However , there is still argumentative for the safety and efficacy of MSCs in the AMI setting . We thus performed a r and omized pilot study to investigate the safety and efficacy of MSCs in patients with AMI . Eighty patients with AMI after successful reperfusion therapy were r and omly assigned and received an intracoronary administration of autologous BM-derived MSCs into the infa rct related artery at 1 month . During follow-up period , 58 patients completed the trial . The primary endpoint was changes in left ventricular ejection fraction ( LVEF ) by single-photon emission computed tomography ( SPECT ) at 6 month . We also evaluated treatment-related adverse events . The absolute improvement in the LVEF by SPECT at 6 month was greater in the BM-derived MSCs group than in the control group ( 5.9%±8.5 % vs 1.6%±7.0 % ; P=0.037 ) . There was no treatment-related toxicity during intracoronary administration of MSCs . No significant adverse cardiovascular events occurred during follow-up . In conclusion , the intracoronary infusion of human BM-derived MSCs at 1 month is tolerable and safe with modest improvement in LVEF at 6-month follow-up by SPECT . ( Clinical Trials.gov registration number : NCT01392105 BACKGROUND The study assessed long-term safety and efficacy of intramyocardial injection of autologous bone-marrow derived mesenchymal stromal cells ( BMMSCs ) in patients with severe stable coronary artery disease ( CAD ) and refractory angina . METHODS Thirty-one patients with severe stable CAD and refractory angina were included . Patients had reversible myocardial ischemia and no further revascularization options . Autologous BMMSCs were isolated , culture exp and ed and stimulated with vascular endothelial growth-factor to facilitate endothelial differentiation . BMMSCs were injected into an ischemic , viable region of the myocardium . Patients were followed for 3 years . RESULTS We found significant clinical improvements in exercise time ( p=0.0016 ) , angina class ( CCS ) ( p<0.0001 ) , weekly number of angina attacks ( p<0.0001 ) and use of nitroglycerine from ( p=0.0017 ) . In the Seattle Angina Question naire there were significant improvements in physical limitation score , angina stability score , angina frequency score and quality of life score ( all p<0.0001 ) . When comparing all hospital admissions from 3 years before to 3 years after treatment , we observed highly reduced admission rates for stable angina ( p<0.0001 ) , revascularization ( p=0.003 ) and overall cardiovascular disease ( p<0.0001 ) . No early or late side-effects of the treatment were observed . CONCLUSIONS The final 3-year follow-up data after intramyocardial injection of autologous BMMSCs , in patients with severe CAD and refractory angina , demonstrated sustained clinical effects , reduced hospital admissions for cardiovascular disease and excellent long-term safety . The results indicate that autotransplantation of BMMSCs to the heart does not only improve symptoms but also slows down disease progression Bone marrow stem cells are able to repair infa rct ed human myocardium following intracoronary transplantation via the infa rct -relative artery . However , traditional reperfusion strategies fail to open the artery in some patients , making effective delivery impossible . Our previous study demonstrated a safe and efficient approach to delivering bone marrow stem cells via a noninfa rct ed artery in an animal myocardial infa rct ion model . The objective of the present study was to evaluate the safety and feasibility of autologous bone marrow mesenchymal stem cell transplantation via such an approach in patients with acute myocardial infa rct ion ( AMI ) . Sixteen patients with anterior AMI who had successfully undergone percutaneous coronary intervention ( PCI ) were enrolled in this pilot , r and omized study . Three weeks after PCI , cultured bone marrow mesenchymal stem cells were injected into the myocardium via either the infa rct -relative artery ( left anterior descending branch artery , LAD ) or a noninfa rct -relative artery ( right coronary artery , RCA ) . The safety and feasibility of the cell infusion were evaluated during the procedure and during 6 months of follow-up . In addition , 2D echocardiography , technetium-99 m methoxyisobutylisonitrile ( 99mTc-MIBI ) and 18F-deoxyglucose single photon emission computed tomography were employed to examine cardiac function , myocardial perfusion , and viable cardiomyocytes , respectively , at day 4 after PCI and 6 months after the cell infusion . There were no arrhythmia and any other side-effects , including infections , allergic reactions or adverse clinical events , during , immediately after , or 6 months after cell transplantation . Cardiac function and myocardial perfusion had improved 6 months after PCI/bone marrow stem cells transplantation . Viable cardiomyocytes metabolism was detected in the infa rct ed areas in both groups after the cell infusion , as demonstrated by 18F-deoxyglucose . Intracoronary infusion of autologous bone marrow mesenchymal stem cells via a noninfa rct -relative artery appears safe and feasible in the treatment of patients with AMI BACKGROUND The infa rct size determines the long-term prognosis of patients with acute myocardial infa rct ion ( AMI ) . There is a growing interest in repairing scar area by transplanting bone marrow stem cells . However , effectiveness of intracoronary injection of bone marrow mesenchymal stem cells ( BMSCs ) in patients with AMI still remains unclear . METHODS Sixty-nine patients with AMI after percutaneous coronary intervention ( PCI ) were r and omly divided into intracoronary injection of BMSCs ( n = 34 ) and saline ( control group , n = 35 ) groups . Serial single positron emission computer tomography ( SPECT ) , cardiac echo and cardiac electromechanical mapping were done at the design ed time intervals until six months after transplantation of BMSCs or injection of saline . RESULTS The proportion with functional defect decreased significantly in the BMSCs patients after three months [ ( 13 + /- 5)% ] compared with that pre-transplantation [ ( 32 + /- 11)% ] and the control group [ ( 28 + /- 10)% ] at three month follow-up ( P < 0.05 , respectively ) . Wall movement velocity over the infracted region increased significantly in the BMSCs group [ ( 4.2 + /- 2.5 ) cm/s vs ( 2.2 + /- 1.3 ) cm/s , P < 0.05 ] , but not in the control group [ ( 2.2 + /- 1.5 ) cm/s vs ( 2.7 + /- 1.7 ) cm/s , P > 0.05 ] . Left ventricular ejection fraction ( LVEF ) three months after transplantation in BMSCs group increased significantly compared with that pre-implantation and with that of the control group at three months post-injection [ ( 67 + /- 11)% vs ( 49 + /- 9)% and ( 53 + /- 8)% , P < 0.05 respectively ] . SPECT scan results showed that perfusion defect was improved significantly in BMSCs group at three-month follow-up compared with that in the control group [ ( 134 + /- 66 ) cm(2 ) vs ( 185 + /- 87 ) cm(2 ) , P < 0.01 ] . At the same time , left ventricular end-diastolic volume [ ( 136 + /- 31 ) ml vs ( 162 + /- 27 ) ml , P < 0.05 ] and end-systolic volume [ ( 63 + /- 20 ) ml vs ( 88 + /- 19 ) ml , P < 0.05 ] decreased synchronously . The ratio of end-systolic pressure to end-systolic volume [ Psyst/ESV , ( 2.84 + /- 1.30 ) mmHg/ml vs ( 1.72 + /- 1.23 ) mmHg/ml , P < 0.05 ] increased significantly . Cardiac electromechanical mapping demonstrated significant improvement at three months after implantation of BMSCs compared with that pre-injection in both cardiac mechanical capability as left line local shorting [ LLS , ( 11.29 + /- 1.64)% vs ( 7.32 + /- 1.86)% , P < 0.05 ] and electrical property as left ventricular endocardial unipolar voltage [ UV , ( 10.38 + /- 1.12 ) mV vs ( 7.61 + /- 1.09 ) mV , P < 0.01 ] ; perfusion defect decreased from ( 36.2 + /- 6.2)% to ( 20.3 + /- 5.31)% ( P < 0.01 ) . Twenty-four-hour electrocardiographic monitoring demonstrated no arrhythmias occurred at three-months follow-up . CONCLUSIONS The transplantation of BMSCs might improve the cardiac function and it is safe and feasible with no deaths or malignant arrhythmias IMPORTANCE Whether culture-exp and ed mesenchymal stem cells or whole bone marrow mononuclear cells are safe and effective in chronic ischemic cardiomyopathy is controversial . OBJECTIVE To demonstrate the safety of transendocardial stem cell injection with autologous mesenchymal stem cells ( MSCs ) and bone marrow mononuclear cells ( BMC s ) in patients with ischemic cardiomyopathy . DESIGN , SETTING , AND PATIENTS A phase 1 and 2 r and omized , blinded , placebo-controlled study involving 65 patients with ischemic cardiomyopathy and left ventricular ( LV ) ejection fraction less than 50 % ( September 1 , 2009-July 12 , 2013 ) . The study compared injection of MSCs ( n=19 ) with placebo ( n = 11 ) and BMC s ( n = 19 ) with placebo ( n = 10 ) , with 1 year of follow-up . INTERVENTIONS Injections in 10 LV sites with an infusion catheter . MAIN OUTCOMES AND MEASURES Treatment-emergent 30-day serious adverse event rate defined as a composite of death , myocardial infa rct ion , stroke , hospitalization for worsening heart failure , perforation , tamponade , or sustained ventricular arrhythmias . RESULTS No patient had a treatment-emergent serious adverse events at day 30 . The 1-year incidence of serious adverse events was 31.6 % ( 95 % CI , 12.6 % to 56.6 % ) for MSCs , 31.6 % ( 95 % CI , 12.6%-56.6 % ) for BMC s , and 38.1 % ( 95 % CI , 18.1%-61.6 % ) for placebo . Over 1 year , the Minnesota Living With Heart Failure score improved with MSCs ( -6.3 ; 95 % CI , -15.0 to 2.4 ; repeated measures of variance , P=.02 ) and with BMC s ( -8.2 ; 95 % CI , -17.4 to 0.97 ; P=.005 ) but not with placebo ( 0.4 ; 95 % CI , -9.45 to 10.25 ; P=.38 ) . The 6-minute walk distance increased with MSCs only ( repeated measures model , P = .03 ) . Infa rct size as a percentage of LV mass was reduced by MSCs ( -18.9 % ; 95 % CI , -30.4 to -7.4 ; within-group , P = .004 ) but not by BMC s ( -7.0 % ; 95 % CI , -15.7 % to 1.7 % ; within-group , P = .11 ) or placebo ( -5.2 % ; 95 % CI , -16.8 % to 6.5 % ; within-group , P = .36 ) . Regional myocardial function as peak Eulerian circumferential strain at the site of injection improved with MSCs ( -4.9 ; 95 % CI , -13.3 to 3.5 ; within-group repeated measures , P = .03 ) but not BMC s ( -2.1 ; 95 % CI , -5.5 to 1.3 ; P = .21 ) or placebo ( -0.03 ; 95 % CI , -1.9 to 1.9 ; P = .14 ) . Left ventricular chamber volume and ejection fraction did not change . CONCLUSIONS AND RELEVANCE Transendocardial stem cell injection with MSCs or BMC s appeared to be safe for patients with chronic ischemic cardiomyopathy and LV dysfunction . Although the sample size and multiple comparisons preclude a definitive statement about safety and clinical effect , these results provide the basis for larger studies to provide definitive evidence about safety and to assess efficacy of this new therapeutic approach . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00768066 OBJECTIVES Our aim was to investigate the safety and efficacy of intravenous allogeneic human mesenchymal stem cells ( hMSCs ) in patients with myocardial infa rct ion ( MI ) . BACKGROUND Bone marrow-derived hMSCs may ameliorate consequences of MI , and have the advantages of preparation ease , allogeneic use due to immunoprivilege , capacity to home to injured tissue , and extensive pre- clinical support . METHODS We performed a double-blind , placebo-controlled , dose-ranging ( 0.5 , 1.6 , and 5 million cells/kg ) safety trial of intravenous allogeneic hMSCs ( Prochymal , Osiris Therapeutics , Inc. , Baltimore , Maryl and ) in reperfused MI patients ( n=53 ) . The primary end point was incidence of treatment-emergent adverse events within 6 months . Ejection fraction and left ventricular volumes determined by echocardiography and magnetic resonance imaging were exploratory efficacy end points . RESULTS Adverse event rates were similar between the hMSC-treated ( 5.3 per patient ) and placebo-treated ( 7.0 per patient ) groups , and renal , hepatic , and hematologic laboratory indexes were not different . Ambulatory electrocardiogram monitoring demonstrated reduced ventricular tachycardia episodes ( p=0.025 ) , and pulmonary function testing demonstrated improved forced expiratory volume in 1 s ( p=0.003 ) in the hMSC-treated patients . Global symptom score in all patients ( p=0.027 ) and ejection fraction in the important subset of anterior MI patients were both significantly better in hMSCs versus placebo subjects . In the cardiac magnetic resonance imaging sub study , hMSC treatment , but not placebo , increased left ventricular ejection fraction and led to reverse remodeling . CONCLUSIONS Intravenous allogeneic hMSCs are safe in patients after acute MI . This trial provides pivotal safety and provisional efficacy data for an allogeneic bone marrow-derived stem cell in post-infa rct ion patients . ( Safety Study of Adult Mesenchymal Stem Cells [ MSC ] to Treat Acute Myocardial Infa rct ion ; NCT00114452 ) CONTEXT Mesenchymal stem cells ( MSCs ) are under evaluation as a therapy for ischemic cardiomyopathy ( ICM ) . Both autologous and allogeneic MSC therapies are possible ; however , their safety and efficacy have not been compared . OBJECTIVE To test whether allogeneic MSCs are as safe and effective as autologous MSCs in patients with left ventricular ( LV ) dysfunction due to ICM . DESIGN , SETTING , AND PATIENTS A phase 1/2 r and omized comparison ( POSEIDON study ) in a US tertiary-care referral hospital of allogeneic and autologous MSCs in 30 patients with LV dysfunction due to ICM between April 2 , 2010 , and September 14 , 2011 , with 13-month follow-up . INTERVENTION Twenty million , 100 million , or 200 million cells ( 5 patients in each cell type per dose level ) were delivered by transendocardial stem cell injection into 10 LV sites . MAIN OUTCOME MEASURES Thirty-day postcatheterization incidence of predefined treatment-emergent serious adverse events ( SAEs ) . Efficacy assessment s included 6-minute walk test , exercise peak VO2 , Minnesota Living with Heart Failure Question naire ( MLHFQ ) , New York Heart Association class , LV volumes , ejection fraction ( EF ) , early enhancement defect ( EED ; infa rct size ) , and sphericity index . RESULTS Within 30 days , 1 patient in each group ( treatment-emergent SAE rate , 6.7 % ) was hospitalized for heart failure , less than the prespecified stopping event rate of 25 % . The 1-year incidence of SAEs was 33.3 % ( n = 5 ) in the allogeneic group and 53.3 % ( n = 8) in the autologous group ( P = .46 ) . At 1 year , there were no ventricular arrhythmia SAEs observed among allogeneic recipients compared with 4 patients ( 26.7 % ) in the autologous group ( P = .10 ) . Relative to baseline , autologous but not allogeneic MSC therapy was associated with an improvement in the 6-minute walk test and the MLHFQ score , but neither improved exercise VO2 max . Allogeneic and autologous MSCs reduced mean EED by −33.21 % ( 95 % CI , −43.61 % to −22.81 % ; P < .001 ) and sphericity index but did not increase EF . Allogeneic MSCs reduced LV end-diastolic volumes . Low-dose concentration MSCs ( 20 million cells ) produced greatest reductions in LV volumes and increased EF . Allogeneic MSCs did not stimulate significant donor-specific alloimmune reactions . CONCLUSIONS In this early-stage study of patients with ICM , transendocardial injection of allogeneic and autologous MSCs without a placebo control were both associated with low rates of treatment-emergent SAEs , including immunologic reactions . In aggregate , MSC injection favorably affected patient functional capacity , quality of life , and ventricular remodeling . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01087996 AIMS Regenerative treatment with mesenchymal stromal cells ( MSCs ) has been promising in patients with ischaemic heart failure but needs confirmation in larger r and omized trials . We aim ed to study effects of intra-myocardial autologous bone marrow-derived MSC treatment in patients with severe ischaemic heart failure . METHODS AND RESULTS The MSC-HF trial is a r and omized , double-blind , placebo-controlled trial . Patients were r and omized 2 : 1 to intra-myocardial injections of MSC or placebo , respectively . The primary endpoint was change in left ventricular end-systolic volume ( LVESV ) , measured by magnetic resonance imaging or computed tomography at 6 months follow-up . Sixty patients aged 30 - 80 years with severe ischaemic heart failure , New York Heart Association ( NYHA ) classes II-III , left ventricular ejection fraction ( LVEF ) < 45 % and no further treatment options were r and omized . Fifty-five patients completed the 6-month follow-up ( 37 MSCs vs. 18 placebo ) . At 6 months , LVESV was reduced in the MSC group : -7.6 ( 95 % CI -11.8 to -3.4 ) mL ( P = 0.001 ) , and increased in the placebo group : 5.4 ( 95 % CI -0.4 to 11.2 ) mL ( P = 0.07 ) . The difference between groups was 13.0 ( 95 % CI 5.9 - 20.1 ) mL ( P = 0.001 ) . Compared with placebo , there were also significant improvements in LVEF of 6.2 % ( P<0.0001 ) , stroke volume of 18.4 mL ( P < 0.0001 ) , and myocardial mass of 5.7 g ( P = 0.001 ) . No differences were found in NYHA class , 6-min walking test and Kansas City cardiomyopathy question naire . No side effects were identified . CONCLUSION Intra-myocardial injections of autologous culture exp and ed MSCs were safe and improved myocardial function in patients with severe ischaemic heart failure . STUDY REGISTRATION NUMBER NCT00644410 ( Clinical Trials.gov ) BACKGROUND The MESAMI 1 trial was a bicentric pilot study design ed to test the feasibility and safety of intramyocardially injected autologous bone marrow-derived mesenchymal stromal cells ( MSCs ) for the treatment of ischemic cardiomyopathy . METHODS AND RESULTS The study included 10 patients with chronic myocardial ischemia , left ventricular ( LV ) ejection fractions ( EFs ) of ≤35 % , and reversible perfusion defects who were on stable optimal medical therapy and were not c and i date s for revascularization . MSCs ( mean : 61.5 × 10(6 ) cells per patient ) were injected into 10 - 16 viable sites at the border of the LV scar via a NOGA-guided catheter . Both primary endpoints , feasibility ( successful harvest , expansion , and injection of autologous MSCs ) and safety ( absence of severe adverse events [ SAEs ] ) were met in all 10 patients at the 1-month follow-up time point , and none of the SAEs reported during the full 2-year follow-up period were attributable to the study intervention . The results of secondary efficacy endpoint analyses identified significant improvements from baseline to Month 12 in LVEF ( 29.4±2.0 % versus 35.7±2.5 % ; p=0.003 ) , LV end-systolic volume ( 167.8±18.8mL versus 156.1±28.6mL ; p=0.04 ) , 6-min walk test and NYHA functional class . CONCLUSIONS Our results suggest that autologous MSCs can be safely administered to the hearts of patients with severe , chronic , reversible myocardial ischemia and impaired cardiac function and may be associated with improvements in cardiac performance , LV remodeling , and patient functional status . A r and omized , double blind , multicenter , placebo-controlled clinical trial ( MESAMI 2 ) will evaluate the efficacy of this treatment approach in a larger patient population . CLINICAL TRIAL REGISTRATION Unique identifier : NCT01076920 BACKGROUND AIMS Cell therapy is promising as an exploratory cardiovascular therapy . We have recently developed an investigational new drug named Stempeucel ( bone marrow-derived allogeneic mesenchymal stromal cells ) for patients with acute myocardial infa rct ion ( AMI ) with ST-segment elevation . A phase I/II r and omized , double-blind , single-dose study was conducted to assess the safety and efficacy of intravenous administration of Stempeucel versus placebo ( multiple electrolytes injection ) . METHODS Twenty patients who had undergone percutaneous coronary intervention for AMI were r and omly assigned ( 1:1 ) to receive intravenous Stempeucel or placebo and were followed for 2 years . RESULTS The number of treatment-emergent adverse events observed were 18 and 21 in the Stempeucel and placebo groups , respectively . None of the adverse events were related to Stempeucel according to the investigators and independent data safety monitoring board . There was no serious adverse event in the Stempeucel group and there were three serious adverse events in the placebo group , of which one had a fatal outcome . Ejection fraction determined by use of echocardiography showed improvement in both Stempeucel ( 43.06 % to 47.80 % ) and placebo ( 43.44 % to 45.33 % ) groups at 6 months ( P = 0.26 ) . Perfusion scores measured by use of single-photon emission tomography and infa rct volume measured by use of magnetic resonance imaging showed no significant differences between the two groups at 6 months . CONCLUSIONS This study showed that Stempeucel was safe and well tolerated when administered intravenously in AMI patients 2 days after percutaneous coronary intervention . The optimal dose and route of administration needs further evaluation in larger clinical trials ( http:// clinical trials.gov/show/NCT00883727 ) |
845 | 30,646,283 | Meaning Early childhood is a crucial period for children ’s social , emotional , and cognitive development , and these findings highlight what appears to be benefit of social and emotional learning interventions for young children across developmental domains | Key Points Question How effective are universal curriculum-based social and emotional learning programs delivered in early childhood education and care centers at improving children ’s social and emotional development ? | BACKGROUND 13 - 18 % of all preschool children have severe behavioral problems at least transiently , sometimes with long-term adverse consequences . In this study , the social training program " Lubo aus dem All ! - Vorschulalter " ( Lubo from Outer Space , Preschool Version ) was evaluated in a kindergarten setting . METHODS 15 kindergartens were r and omly assigned to either an intervention group or a control group , in a 2:1 ratio . The intervention was design ed to strengthen emotional knowledge and regulation , the ability to take another person 's point of view , communication skills , and social problem solving . The control group continued with conventional kindergarten activities . The primary endpoint was improvement in social-cognitive problem solving strategies , as assessed with the Wally Social Skills and Problem Solving Game ( Wally ) . Secondary endpoints were improvement in prosocial behavior and reduction in problematic behavior , as assessed with the Preschool Social Behavior Question naire ( PSBQ ) and the Caregiver-Teacher Report Form ( C-TRF ) . Data were collected before and after the intervention and also 5 months later . Mixed models were calculated with r and om effects to take account of the cluster design and for adjustment for confounding variables . RESULTS 221 children in kindergarten , aged 5 - 6 years , were included in the study . R and omization was unsuccessful : the children in the intervention group performed markedly worse on the tests carried out before the intervention . Five months after the end of the intervention , the social-cognitive problem solving strategies of the children in the intervention group had improved more than those of the children in the control group : the intergroup difference in improvement was 0.79 st and ard deviations of the Wally test ( 95 % confidence interval [ CI ] 0.13 - 1.46 ) . This effect was just as marked 5 months later ( 0.63 , 95 % CI 0.03 - 1.23 ) . Prosocial behavior , as measured by the PSBQ , also improved more in the intervention group , with an intergroup difference of 0.37 st and ard deviations ( 95 % CI 0.05 - 0.71 ) . CONCLUSION An age-appropriate program to prevent behavioral disorders among kindergarten children improved both the children 's knowledge of prosocial problem solving strategies and their prosocial behavior Self-regulatory abilities are robust predictors of important outcomes across the life span , yet they are rarely taught explicitly in school . Using a r and omized controlled design , the present study investigated the effects of a 12-week mindfulness-based Kindness Curriculum ( KC ) delivered in a public school setting on executive function , self-regulation , and prosocial behavior in a sample of 68 preschool children . The KC intervention group showed greater improvements in social competence and earned higher report card grade s in domains of learning , health , and social-emotional development , whereas the control group exhibited more selfish behavior over time . Interpretation of effect sizes overall indicate small to medium effects favoring the KC group on measures of cognitive flexibility and delay of gratification . Baseline functioning was found to moderate treatment effects with KC children initially lower in social competence and executive functioning demonstrating larger gains in social competence relative to the control group . These findings , observed over a relatively short intervention period , support the promise of this program for promoting self-regulation and prosocial behavior in young children . They also support the need for future investigation of program implementation across diverse setting Deficits in behavioral and cognitive regulation are prevalent in children reared in poverty relative to more affluent children due to the effects of adverse conditions on the developmental underpinnings of these skills . Despite evidence to suggest that these emergent processes are susceptible to environmental inputs , research documenting short-term intervention program influences on these regulatory domains in young impoverished children is limited . We sought to determine the proximal effects of a universal school-based intervention ( the PATHS Curriculum ) on social , emotional , relational , and cognitive outcomes in urban poor kindergarten children . Four schools in high-poverty neighborhoods with similar demographic characteristics were r and omly assigned to either PATHS or an attentional control . Teacher-reported measures of behavior ( e.g. , attention , concentration , aggression ) , peer nominations ( e.g. , likability , aggression , acceptance ) , and tasks gauging inhibitory control were administered in the fall of kindergarten and again in the spring after one academic year ( about 6 months ) of PATHS . Children who received PATHS exhibited significantly greater improvements than control students across all teacher-rated behavioral measures of social competence ( i.e. , emotion regulation , prosocial behavior , peer relations ) and behavioral problems ( i.e. , aggression , internalizing behaviors , impulsivity and hyperactivity ) at post-test as well as improvements in motor inhibition . This line of research constitutes an important frontier for prevention research given the implication s for improving ultimate outcomes for otherwise disadvantaged children This study evaluated the post-treatment outcome effects of a classroom-based social skills program for pre-kindergarten children , using a teacher-consultation model . The pre-K RECAP ( Reaching Educators , Children , and Parents ) program is a semi-structured , cognitive-behavioral skills training program that provides teachers with in-classroom consultation on program implementation and classroom-wide behavior management . Data on children 's social skills and behavior problems were collected from parents and teachers at pre- and post-treatment , for 149 children aged 4–5 years ( of whom 56 % were girls ) . Significant treatment effects were found for teacher but not parent reports , with treatment group children improving significantly more than comparison group children in their teacher-rated social skills and internalizing and externalizing problems . These results provide some preliminary support for the efficacy of the program on children 's social skills and behavior problems , and for a teacher-consultation model for training teachers to implement school-based mental health programs Annual screenings of preschool children at kindergarten registration identified 158 children having high levels of aggressive , hyperactive , impulsive , and inattentive behavior . These " disruptive " children were r and omly assigned to four treatment conditions lasting the kindergarten school year : no treatment , parent training only , full-day treatment classroom only , and the combination of parent training with the classroom treatment . Results showed that parent training produced no significant treatment effects , probably owing largely to poor attendance . The classroom treatment produced improvement in multiple domains : parent ratings of adaptive behavior , teacher ratings of attention , aggression , self-control , and social skills , as well as direct observations of externalizing behavior in the classroom . Neither treatment improved academic achievement skills or parent ratings of home behavior problems , nor were effects evident on any lab measures of attention , impulse control , or mother-child interactions . It is concluded that when parent training is offered at school registration to parents of disruptive children identified through a brief school registration screening , it may not be a useful approach to treating the home and community behavioral problems of such children . The kindergarten classroom intervention was far more effective in reducing the perceived behavioral problems and impaired social skills of these children . Even so , most treatment effects were specific to the school environment and did not affect achievement skills . These findings must be viewed as tentative until follow-up evaluations can be done to determine the long-term outcomes of these interventions Separate studies of rural and urban Head Start systems tested the hypothesis that an emotion-based prevention program ( EBP ) would accelerate the development of emotion and social competence and decrease agonistic behavior and potential precursors of psychopathology . In both studies , Head Start centers were r and omly assigned to treatment and control/comparison group conditions . In Study 1 ( rural community ) , results of hierarchical linear modeling analyses showed that compared to the control condition ( Head Start as usual ) , EBP produced greater increases in emotion knowledge and emotion regulation and greater decreases in children 's negative emotion expressions , aggression , anxious/depressed behavior , and negative peer and adult interactions . In Study 2 ( inner city ) , compared to the established prevention program I Can Problem Solve , EBP led to greater increases in emotion knowledge , emotion regulation , positive emotion expression , and social competence . In Study 2 , emotion knowledge mediated the effects of EBP on emotion regulation , and emotion competence ( an aggregate of emotion knowledge and emotion regulation ) mediated the effects of EBP on social competence This article reports findings from a cluster-r and omized study of an integrated literacy- and math-focused preschool curriculum , comparing versions with and without an explicit socioemotional lesson component to a business-as-usual condition . Participants included 110 classroom teachers from r and omized classrooms and approximately eight students from each classroom ( N = 760 ) who averaged 4.48 ( SD = 0.44 ) years of age at the start of the school year . There were positive impacts of the two versions of the curriculum on language , phonological awareness , math , and socioemotional outcomes , but there were no added benefits to academic or socioemotional outcomes for the children receiving explicit socioemotional instruction . Results are discussed with relevance to early childhood theory , policy , and goals of closing the school readiness gap ABSTRACT The present study investigates whether training preschool children in the active use of emotional state talk plays a significant role in bringing about greater underst and ing of emotion terms and improved emotion comprehension . Participants were 100 preschool children ( M=52 months ; SD=9·9 ; range : 35 - 70 months ) , r and omly assigned to experimental or control conditions . They were pre- and post-tested to assess their language comprehension , metacognitive language comprehension and emotion underst and ing . Analyses of pre-test data did not show any significant differences between experimental and control groups . During the intervention phase , the children were read stories enriched with emotional lexicon . After listening to the stories , children in the experimental group took part in conversational language games design ed to stimulate use of the selected emotional terms . In contrast , the control group children did not take part in any special linguistic activities after the story readings . Analyses revealed that the experimental group outperformed the control group in the underst and ing of inner state language and in the comprehension of emotion This paper reports the results from a r and omized clinical trial evaluating an adaptation of the Promoting Alternative Thinking Strategies curriculum ( PATHS ) for preschool-age children in Head Start . PATHS is a universal , teacher-taught social-emotional curriculum that is design ed to improve children ’s social competence and reduce problem behavior . Twenty classrooms in two Pennsylvania communities participated in the study . Teachers in the 10 intervention classrooms implemented weekly lessons and extension activities across a 9-month period . Child assessment s and teacher and parent reports of child behavior assessment s were collected at the beginning and end of the school year . Analysis of covariance was used to control for baseline differences between the groups and pretest scores on each of the outcome measures . The results suggest that after exposure to PATHS , intervention children had higher emotion knowledge skills and were rated by parents and teachers as more socially competent compared to peers . Further , teachers rated intervention children as less socially withdrawn at the end of the school year compared to controls . Editors ’ Strategic Implication s : n Findings from this and other r and omized clinical trials confirm that the Preschool PATHS program is clearly a promising practice for improving children ’s social and emotional competence . Head Start and school programs will find these multi-informant data to be of interest as they consider a curriculum to help prepare children for school entry Behavior problems among preschool children are common . They are important targets for intervention because early externalizing problems and self-regulation issues tend to persist without appropriate attention , and can affect later mental health and school achievement outcomes . However , few preschool curricula addressing social and emotional development exist , and evidence for effects are mixed . In this study , the Second Step Pre/Kindergarten Social and Emotional Learning curriculum was adapted and tested in a small cluster r and omized pilot study of community preschool classrooms to determine if it could improve outcomes in : ( 1 ) individual children ’s teacher-rated behavior problems and prosocial skills ; ( 2 ) classroom climate ( classroom interactions and two measures of disruptive behavior ) ; and ( 3 ) teacher interaction skills . Year 1 outcomes were modest and were accounted for by baseline differences . In Year 2 , classroom climate , measured by independent observers , differed significantly in intervention classrooms , largely because of declines in control classrooms , and there was some evidence for better teacher interaction skills in intervention classrooms . The pattern of effects suggests important impacts on classroom quality worth investigating in a larger study . Both fidelity and implementation rates , as well as positive teacher responses to the curriculum , indicate potential for widespread adoption Using information from research on the neuroplasticity of selective attention and on the central role of successful parenting in child development , we developed and rigorously assessed a family-based training program design ed to improve brain systems for selective attention in preschool children . One hundred forty-one lower socioeconomic status preschoolers enrolled in a Head Start program were r and omly assigned to the training program , Head Start alone , or an active control group . Electrophysiological measures of children ’s brain functions supporting selective attention , st and ardized measures of cognition , and parent-reported child behaviors all favored children in the treatment program relative to both control groups . Positive changes were also observed in the parents themselves . Effect sizes ranged from one-quarter to half of a st and ard deviation . These results lend impetus to the further development and broader implementation of evidence -based education programs that target at-risk families Despite reports of positive effects of high- quality child care , few experimental studies have examined the process of improving low- quality center-based care for toddler-age children . In this article , we report intervention effects on child care teachers ' behaviors and children 's social , emotional , behavioral , early literacy , language , and math outcomes as well as the teacher-child relationship . The intervention targeted the use of a set of responsive teacher practice s , derived from attachment and sociocultural theories , and a comprehensive curriculum . Sixty-five childcare classrooms serving low-income 2- and 3-year-old children were r and omized into 3 conditions : business-as-usual control , Responsive Early Childhood Curriculum ( RECC ) , and RECC plus explicit social-emotional classroom activities ( RECC+ ) . Classroom observations showed greater gains for RECC and RECC+ teachers ' responsive practice s including helping children manage their behavior , establishing a predictable schedule , and use of cognitively stimulating activities ( e.g. , shared book reading ) compared with controls ; however , teacher behaviors did not differ for focal areas such as sensitivity and positive discipline supports . Child assessment s demonstrated that children in the interventions outperformed controls in areas of social and emotional development , although children 's performance in control and intervention groups was similar for cognitive skills ( language , literacy , and math ) . Results support the positive impact of responsive teachers and environments providing appropriate support for toddlers ' social and emotional development . Possible explanations for the absence of systematic differences in children 's cognitive skills are considered , including implication s for practice and future research targeting low-income toddlers The Incredible Years parent and classroom interventions were evaluated for the first time in elementary schools . Culturally diverse , socioeconomically disadvantaged schools were r and omly assigned to intervention or control ( CON ) . In intervention schools , all children received a 2-year classroom intervention beginning in kindergarten . In addition , indicated children were r and omly assigned to also receive parent training ( PT + CR ) or only the classroom intervention ( CR ) . PT + CR mothers reported that , following intervention , children showed fewer externalizing problems and more emotion regulation than CR or CON children . Observations showed that child – mother bonding was stronger in the PT + CR condition than in the CON condition , and PT + CR mothers were significantly more supportive and less critical than CR or CON mothers . Teachers reported that PT + CR mothers were significantly more involved in school and that children in the PT + CR and the CR conditions had significantly fewer externalizing problems than in the CON condition BACKGROUND School readiness , conceptualized as three components including emotional self-regulation , social competence , and family/school involvement , as well as absence of conduct problems play a key role in young children 's future interpersonal adjustment and academic success . Unfortunately , exposure to multiple poverty-related risks increases the odds that children will demonstrate increased emotional dysregulation , fewer social skills , less teacher/parent involvement and more conduct problems . Consequently intervention offered to socio-economically disadvantaged population s that includes a social and emotional school curriculum and trains teachers in effective classroom management skills and in promotion of parent-school involvement would seem to be a strategic strategy for improving young children 's school readiness , leading to later academic success and prevention of the development of conduct disorders . METHODS This r and omized trial evaluated the Incredible Years ( IY ) Teacher Classroom Management and Child Social and Emotion curriculum ( Dinosaur School ) as a universal prevention program for children enrolled in Head Start , kindergarten , or first grade classrooms in schools selected because of high rates of poverty . Trained teachers offered the Dinosaur School curriculum to all their students in bi-weekly lessons throughout the year . They sent home weekly dinosaur homework to encourage parents ' involvement . Part of the curriculum involved promotion of lesson objectives through the teachers ' continual use of positive classroom management skills focused on building social competence and emotional self-regulation skills as well as decreasing conduct problems . Matched pairs of schools were r and omly assigned to intervention or control conditions . RESULTS Results from multi-level models on a total of 153 teachers and 1,768 students are presented . Children and teachers were observed in the classrooms by blinded observers at the beginning and the end of the school year . Results indicated that intervention teachers used more positive classroom management strategies and their students showed more social competence and emotional self-regulation and fewer conduct problems than control teachers and students . Intervention teachers reported more involvement with parents than control teachers . Satisfaction with the program was very high regardless of grade levels . CONCLUSIONS These findings provide support for the efficacy of this universal preventive curriculum for enhancing school protective factors and reducing child and classroom risk factors faced by socio-economically disadvantaged children Forty-four Head Start classrooms were r and omly assigned to enriched intervention ( Head Start REDI- Research -based , Developmentally Informed ) or " usual practice " conditions . The intervention involved brief lessons , " h and s-on " extension activities , and specific teaching strategies linked empirically with the promotion of : ( a ) social-emotional competencies and ( b ) language development and emergent literacy skills . Take-home material s were provided to parents to enhance skill development at home . Multi method assessment s of three hundred and fifty-six 4-year-old children tracked their progress over the course of the 1-year program . Results revealed significant differences favoring children in the enriched intervention classrooms on measures of vocabulary , emergent literacy , emotional underst and ing , social problem solving , social behavior , and learning engagement . Implication s are discussed for developmental models of school readiness and for early educational programs and policies |
846 | 31,434,526 | Conclusion : An increasing number of studies in palliative care are using observational measures of level of consciousness .
However , only a few of these tools have been tested for their psychometric performance in that context . | Background : The use of observational measures to assess palliative care patients ’ level of consciousness may improve patient care and comfort .
However , there is limited knowledge regarding the validity and reliability of these measures in palliative care setting s. Aim : To identify and evaluate the psychometric performance of observational level of consciousness measures used in palliative care . | OBJECTIVE Knowledge of symptom prevalence and adequate assessment of such symptoms at the end of life is important in clinical practice . We determined the frequency and severity of symptom distress and delirium using the Edmonton Assessment Scale ( ESAS ) and the Memorial Delirium Assessment Scale ( MDAS ) and evaluated the clinical utility of the Nursing Delirium Screening Scale ( Nu-DESC ) as scored by a caregiver as a screening tool for delirium . METHOD We conducted a secondary analysis of the data from a previous r and omized controlled trial on parenteral hydration at the end of life of patients admitted to home hospice . Only patients that had assessment s within the last week of life were included . We collected the ESAS , MDAS , Nu-DESC , and Richmond Agitation Sedation Scale ( RASS ) results . The sensitivity and specificity of the Nu-DESC were then calculated . RESULTS Some 78 of 261 patients were included in our study , 62 ( 80 % ) of which had moderate-to-severe symptoms corresponding to an ESAS score > 4 . These symptoms include : 73 ( 94 % ) anorexia , 63 ( 81 % ) fatigue , 56 ( 73 % ) drowsiness , 58 ( 75 % ) decreased well-being , and 39 ( 51 % ) pain . Delirium was diagnosed in 34 ( 44 % ) of patients using the MDAS . The Nu-DESC was found to have a sensitivity of 35 % , a specificity of 80 % , a positive predictive value ( PPV ) of 58 % , and an negative predictive value ( NPV ) of 61 % when used by caregivers . SIGNIFICANCE OF RESULTS Hospice patients at the end of life have a high rate of symptom distress and delirium . The Nu-DESC is not a reliable tool for screening delirium when scoring is conducted by a caregiver . Our study illustrates the need for routine use of assessment tools to improve care Introduction : Patients with end-stage interstitial lung disease ( ILD ) do not appear to receive adequate palliative care despite apparent suffering before death . The aim of this study was to evaluate their signs , symptoms , and treatment received before death . Methods : Patients with ILD and lung cancer ( LC ) who were hospitalized and died in our hospital were enrolled retrospectively . Signs and symptoms and treatments at 7 days , 3 days , and 1 day before death were evaluated and compared between the two groups of patients . Results : A total of 23 patients with ILD and 59 patients with LC group were eligible for participation . Significantly more LC patients had loss of consciousness than ILD patients on 7 days ( ILD : LC = 1 [5.6%]:24 [ 41 % ] , P = 0.013 ) , 3 days ( 1 [5.6%]:33 [ 56 % ] , P < 0.001 ) . Significantly more ILD patients had dyspnea than LC patients on 3 days ( 16 [89%]:38 [ 64 % ] , P = 0.047 ) 1 day before death ( 21 [91%]:33 [ 56 % ] , P = 0.001 ) . On 1 day before death , significantly more LC patients received morphine than ILD patients ( 2 [ 8.7 % ] : 14 [ 24 % ] , P = 0.015 ) . More ILD patients received sedation ( 11 [ 48 % ] : 11 [ 19 % ] , P = 0.007 ) . Conclusions : End-stage ILD patients may experience dyspnea more frequently than terminal LC patients , and they need sedation . Morphine should be administered to ILD patients who have dyspnea . Additional prospect i ve studies are needed Importance The use of benzodiazepines to control agitation in delirium in the last days of life is controversial . Objective To compare the effect of lorazepam vs placebo as an adjuvant to haloperidol for persistent agitation in patients with delirium in the setting of advanced cancer . Design , Setting , and Participants Single-center , double-blind , parallel-group , r and omized clinical trial conducted at an acute palliative care unit at MD And erson Cancer Center , Texas , enrolling 93 patients with advanced cancer and agitated delirium despite scheduled haloperidol from February 11 , 2014 , to June 30 , 2016 , with data collection completed in October 2016 . Interventions Lorazepam ( 3 mg ) intravenously ( n = 47 ) or placebo ( n = 43 ) in addition to haloperidol ( 2 mg ) intravenously upon the onset of an agitation episode . Main Outcomes and Measures The primary outcome was change in Richmond Agitation-Sedation Scale ( RASS ) score ( range , −5 [ unarousable ] to 4 [ very agitated or combative ] ) from baseline to 8 hours after treatment administration . Secondary end points were rescue neuroleptic use , delirium recall , comfort ( perceived by caregivers and nurses ) , communication capacity , delirium severity , adverse effects , discharge outcomes , and overall survival . Results Among 90 r and omized patients ( mean age , 62 years ; women , 42 [ 47 % ] ) , 58 ( 64 % ) received the study medication and 52 ( 90 % ) completed the trial . Lorazepam + haloperidol result ed in a significantly greater reduction of RASS score at 8 hours ( −4.1 points ) than placebo + haloperidol ( −2.3 points ) ( mean difference , −1.9 points [ 95 % CI , −2.8 to −0.9 ] ; P < .001 ) . The lorazepam + haloperidol group required less median rescue neuroleptics ( 2.0 mg ) than the placebo + haloperidol group ( 4.0 mg ) ( median difference , −1.0 mg [ 95 % CI , −2.0 to 0 ] ; P = .009 ) and was perceived to be more comfortable by both blinded caregivers and nurses ( caregivers : 84 % for the lorazepam + haloperidol group vs 37 % for the placebo + haloperidol group ; mean difference , 47 % [ 95 % CI , 14 % to 73 % ] , P = .007 ; nurses : 77 % for the lorazepam + haloperidol group vs 30 % for the placebo + haloperidol group ; mean difference , 47 % [ 95 % CI , 17 % to 71 % ] , P = .005 ) . No significant between-group differences were found in delirium-related distress and survival . The most common adverse effect was hypokinesia ( 3 patients in the lorazepam + haloperidol group [ 19 % ] and 4 patients in the placebo + haloperidol group [ 27 % ] ) . Conclusions and Relevance In this preliminary trial of hospitalized patients with agitated delirium in the setting of advanced cancer , the addition of lorazepam to haloperidol compared with haloperidol alone result ed in a significantly greater reduction in agitation at 8 hours . Further research is needed to assess generalizability and adverse effects . Trial Registration clinical trials.gov Identifier : Introduction Continuous palliative sedation ( PS ) is currently titrated based on clinical observation ; however , it is often unclear if patients are still aware of their suffering . The aim of this prospect i ve study is to characterize the level of consciousness in patients undergoing PS using Bispectral Index ( BIS ) monitoring . Patients and methods We enrolled consecutive patients with refractory symptoms requiring PS . We documented the level of sedation using Ramsay Sedation Scale ( RSS ) and BIS at 0 , 2 , 4 , 6 , 12 , and 24 h during the first day of PS and examined their degree of association . Intravenous midazolam or propofol was titrated according to the sedation level . Results Twenty patients on PS were recruited and had BIS continuous monitoring . Delirium was the most frequent reason for PS ( n = 15 , 75 % ) . The median time of sedation was 24.5 h ( interquartile range 6–46 ) . The average time to achieve the desired sedation level was 6 h , and dose titration was required in 80 % of the cases . At baseline , 14 ( 70 % ) patients were considered to be awake according to RSS ( i.e. , 1–3 ) and 19 ( 95 % ) were awake according to BIS ( i.e. , > 60 % ) . This proportion decreased to 31 and 56 % at 4 h , 27 % and 53 at 6 h , and 22 and 33 % at 24 h. RS and BIS had moderate correlation ( rho = −0.58 to −0.65 ) ; however , a small proportion of patients were found to be awake by BIS ( i.e. , ≥60 % ) despite clinical observation ( i.e. , RSS 4–6 ) indicating otherwise . Conclusions The BIS is a noninvasive , bedside , real-time continuous monitoring method that may facilitate the objective assessment of level of consciousness and dose titration in patients undergoing PS CONTEXT Knowledge of determinants that are associated with the administration of continuous palliative sedation ( CPS ) helps physicians identify patients who are at risk of developing refractory symptoms , thereby enabling proactive care planning . OBJECTIVES This study aims to explore which patient-related factors at admission are associated with receiving CPS later in the terminal phase of life . METHODS A prospect i ve multicenter observational study was performed in six Dutch hospices and three nursing home-based palliative care units . The association between patient-related variables at admission ( age , gender , diagnosis , use of opioids or psycholeptics , number of medications , Karnofsky Performance Status scale score , Edmonton Symptom Assessment System distress score , and Glasgow Coma Scale score ) and the administration of CPS at the end of life was analyzed . RESULTS A total of 467 patients died during the study period , of whom 130 received CPS . In univariate analysis , statistically significant differences were noted between the se date d and nonse date d patients with respect to younger age ( P = 0.009 ) , malignancy as a diagnosis ( P = 0.05 ) , higher Karnofsky Performance Status score ( P = 0.03 ) , the use of opioids ( P < 0.001 ) , the use of psycholeptics ( P = 0.003 ) , and higher Edmonton Symptom Assessment System distress score ( P = 0.05 ) . Multivariate logistic regression analysis showed that only the use of opioids at admission ( odds ratio 1.90 ; 95 % confidence interval 1.18 - 3.05 ) was significantly associated with the administration of CPS . CONCLUSION Physicians should be aware that patients who use opioids at admission have an increased risk for the administration of CPS at the end of life . In this group of patients , a comprehensive personalized care plan starting at admission is m and atory to try to prevent the development of refractory symptoms . Further research is recommended , to identify other determinants of the administration of CPS and to investigate which early interventions will be effective to prevent the need for CPS in patients at high risk CONTEXT If regular therapies can not relieve symptoms sufficiently in the last days of life , continuous palliative sedation may serve to reduce consciousness . Sedation level can be measured with EEG monitoring with the bispectral index ( BIS ) monitor . OBJECTIVES To determine the feasibility and validity of BIS monitoring in terminally ill patients . METHODS In this prospect i ve study , BIS registration s were performed in unconscious end-of-life patients admitted to a palliative care center . Vali date d scores were used to measure level of sedation ( Ramsay score ) , pain ( Numeric Rating Scale or Rotterdam Elderly Pain Observations Scale ) , delirium ( Delirium Observation Screening score ) , and overall comfort ( Numeric Rating Scale ) . Validity and sensitivity to change of BIS values were considered , and the effects of medication and the time till death on BIS values were evaluated in a linear mixed model analysis . RESULTS Fifty-eight patients were included for analysis . BIS monitoring was acceptable to patients , relatives , and medical staff . BIS values were moderately correlated with Ramsay scores ( 0.46 ) but were highly variable for deeply se date d patients . BIS values changed significantly before and after a midazolam dose ( P < 0.001 ) . Midazolam treatment result ed on average in a statistically significant reduction of the BIS values ( -4.5 , 95 % CI -7.0 to -2.0 ) , whereas morphine and haloperidol did not . CONCLUSION This is one of the first validation studies in which BIS monitoring in end-of-life patients is described . BIS monitoring is feasible in unconscious terminally ill patients . However , based on our results , the wide range of BIS values in deeply se date d and comfortable patients seems to hamper its use in daily clinical practice Purpose To describe the practice of palliative sedation ( PS ) in patients with advanced cancer in a specialized palliative care ( PC ) unit in Colombia . Methods Descriptive prospect i ve study including all adults with cancer hospitalized under PS in a cancer institute between January and July 2015 in Colombia . Variables examined were diagnosis , physical functioning , symptoms at the start of sedation , medications and dosages used , and type , level , and time of sedation . Descriptive and correlational statistics were obtained . Results Sixty-six patients were included , 70 % of which were women . The patients had an average age of 61 years ( range 24–87 ) , and 74 % had a Karnofsky Index ( KI ) of 50 % or less . The most frequent diagnosis was breast cancer ( 22 % ) , and 82 % had metastatic cancer . The prevalence of palliative sedation was 2 % and the most common symptoms indicating it were dyspnea ( 59 % ) , delirium ( 45 % ) , and pain ( 32 % ) . All patients received midazolam as a sedative . The average time between the interval start and culmination of sedation was 44 h. There was a significant and inverse relationship between functionality and time under sedation . Conclusions Palliative sedation is a valid therapeutic option for refractory symptoms causing suffering . The results correspond to international reports and guidelines , which suggests that PS is tailored to the needs of the individual patient while maintaining a high scientific st and ard , even in a context where PC is under development . However , further development of strategies and clear indications towards the use of PS in Colombia are needed , given its still scarce use CONTEXT Observer-based sedation scales have been used to provide a measurable estimate of the comfort of nonalert patients in palliative sedation . However , their usefulness and appropriateness in this setting has not been demonstrated . OBJECTIVES To study the reliability and validity of observer-based sedation scales in palliative sedation . METHODS A prospect i ve evaluation of 54 patients under intermittent or continuous sedation with four sedation scales was performed by 52 nurses . Included scales were the Minnesota Sedation Assessment Tool ( MSAT ) , Richmond Agitation-Sedation Scale ( RASS ) , Vancouver Interaction and Calmness Scale ( VICS ) , and a sedation score proposed in the Guideline for Palliative Sedation of the Royal Dutch Medical Association ( KNMG ) . Inter-rater reliability was tested with the intraclass correlation coefficient ( ICC ) and Cohen 's kappa coefficient . Correlations between the scales using Spearman 's rho tested concurrent validity . We also examined construct , discriminative , and evaluative validity . In addition , nurses completed a user-friendliness survey . RESULTS Overall moderate to high inter-rater reliability was found for the VICS interaction subscale ( ICC = 0.85 ) , RASS ( ICC = 0.73 ) , and KNMG ( ICC = 0.71 ) . The largest correlation between scales was found for the RASS and KNMG ( rho = 0.836 ) . All scales showed discriminative and evaluative validity , except for the MSAT motor subscale and VICS calmness subscale . Finally , the RASS was less time consuming , clearer , and easier to use than the MSAT and VICS . CONCLUSION The RASS and KNMG scales st and as the most reliable and valid among the evaluated scales . In addition , the RASS was less time consuming , clearer , and easier to use than the MSAT and VICS . Further research is needed to evaluate the impact of the scales on better symptom control and patient comfort Background In 2005 , a national palliative guideline was launched in The Netherl and s. The authors describe the practice of continuous palliative sedation until death ( CPS ) after the introduction of this guideline . Methods In 2008 , a r and om sample of physicians ( n=1580 ) were asked to fill out a question naire regarding the last patient in whom they had provided CPS until death . Results The response was 38 % . In all , 82 % of the respondents were aware of the existence of the national guideline . Dyspnoea , pain and physical exhaustion were most often mentioned as decisive indications for continuous sedation . The decision to use sedation was discussed with all competent patients , but in 18 % this merely involved informing the patient . Life expectancy at the start of continuous sedation was estimated to be less than 2 weeks in 97 % of the cases . In 14 % , the physicians had felt pressure to start the sedation , predominantly from patients and relatives . Physicians were present at the start of the sedation in 81 % of the cases . Midazolam was used to induce the sedation in 92 % . Overall , 41 % of the physicians estimated that continuous sedation had hastened death to some extent . Most physicians thought that patients ' complaints were adequately relieved by continuous sedation , that relatives were satisfied and that a good quality of dying was achieved . Interpretation Continuous palliative sedation practice in The Netherl and s largely reflects the recommendations from the national guideline . Issues needing further attention are the pressure felt by physicians to start continuous sedation and the potential life-shortening effect as mentioned by the physicians Background There is scant research concerning the prediction of imminent death , and current studies simply list events “ that have already occurred ” around 48 h of the death . We sought to determine what events herald the onset of dying process using the length of time from “ any change ” to death . Methods This is a prospect i ve observational study with chart audit . Inclusion criteria were terminal cancer patients who passed away in a palliative care unit . The analysis was limited to 181 patients who had medical records for their final week . Commonly observed events in the terminally ill were determined and their significant changes were defined beforeh and . We selected the statistically significant changes by multiple logistic regression analysis and evaluated their predictive values for “ death within 48 h. ” Results The median age was 67 years and there were 103 male patients . After adjusting for age , sex , primary cancer site , metastatic site , and cancer treatment , multiple logistic regression analyses for association between the events and “ death within 48 h ” revealed some significant changes : confused mental state , decreased blood pressure , increased pulse pressure , low oxygen saturation , death rattle , and decreased conscious level . The events that had higher predictability for death within 48 h were decreased blood pressure and low oxygen saturation , and the positive and negative predictive values of their combination were 95.0 and 81.4 % , respectively . Conclusion The most reliable events to predict impending death were decreased blood pressure and low oxygen saturation Goals The goal of this study is to evaluate the feasibility and efficacy of palliative sedation at home ( PSH ) to approach refractory symptoms in dying cancer patients . Material s and methods Charts of 121 patients , observed by “ L'Aquila per la Vita ” Home Care Unit , from August 2006 to May 2008 , were review ed . Sixteen patients out of 44 who died at home ( 36.4 % ) were se date d. Indication for sedation was agitated delirium in 13 patients and dyspnea in three patients . A multistep midazolam-based protocol was administered . Results In all patients , a deep , prolonged , continuous sedation was obtained . No treatment-related complications were registered . Conclusion A midazolam-based protocol for PSH is feasible and effective . Our results need to be confirmed by prospect i ve , multicentric , controlled studies OBJECTIVES To study the practice of continuous palliative sedation ( CPS ) by Dutch nursing home physicians in 2007 . DESIGN A structured retrospective question naire . SETTING Nationwide nursing home physician study in the Netherl and s. PARTICIPANTS One thous and two hundred fifty-four nursing home physicians received a question naire concerning their last case of CPS in 2007 ; 54 % ( n=675 ) responded . MEASUREMENTS Characteristics of CPS and requests for euthanasia were measured . RESULTS Three hundred sixteen patients were described . The majority had cancer or dementia . The most-reported refractory symptoms were pain ( 52 % ) , anxiety ( 44 % ) , exhaustion ( 44 % ) , dyspnea ( 40 % ) , delirium ( 24 % ) , loss of dignity ( 18 % ) , and existential distress ( 16 % ) . In 98 % of cases , CPS was aim ed at symptom relief . Of patients with cancer , 17 % had previously requested euthanasia . The mean starting dose of midazolam was 31 mg every 24 hours ( range 0 - 240 mg/24 h ) , and the mean end dose was 48 mg every 24 hours ( range 0 - 480 mg/24 h ) . CONCLUSION In addition to physical symptoms , anxiety , exhaustion , loss of dignity , and existential distress are often mentioned as refractory symptoms in the decision to start CPS by nursing home physicians . Furthermore , close to one in five patients with cancer had made a previous request for euthanasia . The dosage range of midazolam in this study fits the recommendations of the Dutch national guideline on palliative sedation , although international studies show smaller dosage ranges . Finally , prospect i ve research about the acceptability and assessment of nonphysical symptoms as indications for CPS is recommended Background The Richmond Agitation-Sedation Scale ( RASS ) , which assesses level of sedation and agitation , is a simple observational instrument which was developed and vali date d for the intensive care setting . Although used and recommended in palliative care setting s , further validation is required in this patient population . The aim of this study was to explore the validity and feasibility of a version of the RASS modified for palliative care population s ( RASS-PAL ) . Methods A prospect i ve study , using a mixed methods approach , was conducted . Thirteen health care professionals ( physicians and nurses ) working in an acute palliative care unit assessed ten consecutive patients with an agitated delirium or receiving palliative sedation . Patients were assessed at five design ated time points using the RASS-PAL . Health care professionals completed a short survey and data from semi-structured interviews was analyzed using thematic analysis . Results The inter-rater intraclass correlation coefficient range of the RASS-PAL was 0.84 to 0.98 for the five time points . Professionals agreed that the tool was useful for assessing sedation and was easy to use . Its role in monitoring delirium however was deemed problematic . Professionals felt that it may assist interprofessional communication . The need for formal education on why and how to use the instrument was highlighted . Conclusion This study provides preliminary validity evidence for the use of the RASS-PAL by physicians and nurses working in a palliative care unit , specifically for assessing sedation and agitation levels in the management of palliative sedation . Further validity evidence should be sought , particularly in the context of assessing delirium Introduction Our case series prospect ively evaluate the concept of Patient/Family-Controlled Sedation with midazolam , as an alternative to sedation by continuous infusion in terminal cancer patients .Cases presentationOur method was applied in 8 pts . Midazolam was administered in a Patient Control Analgesia mode . The infusion pump was activated " as-needed " by the pt or a caretaker . Sedation was rated as : 1 ) awake 2 ) arousable to voice 3 ) arousable to light pain or 4 ) unarousable . Family satisfaction was rated as : 1 ) good , 2 ) fair , 3 ) poor , or 4 ) unacceptable . Mean midazolam consumption was 12 – 40 mg/24 hours . We did not observe respiratory depression . Death occurred 1–6 days after sedation started . Family satisfaction was mainly good and median sedation was in the range 2 – 3 . Conclusion Patient/Family-Controlled Sedation with midazolam was effective in providing comfort , by allowing titration of sedation to each patient 's needs Purpose This study investigated the effect of two types of palliative sedation defined using intervention protocol s : proportional and deep sedation . Methods We retrospectively analyzed prospect ively recorded data of consecutive cancer patients who received the continuous infusion of midazolam in a palliative care unit . Attending physicians chose the sedation protocol based on each patient ’s wish , symptom severity , prognosis , and refractoriness of suffering . The primary endpoint was a treatment goal achievement at 4 h : in proportional sedation , the achievement of symptom relief ( Support Team Assessment Schedule ( STAS ) ≤ 1 ) and absence of agitation ( modified Richmond Agitation-Sedation Scale ( RASS ) ≤ 0 ) and in deep sedation , the achievement of deep sedation ( RASS ≤ − 4 ) . Secondary endpoints included mean scores of STAS and RASS , deep sedation as a result , and adverse events . Results Among 398 patients who died during the period , 32 received proportional and 18 received deep sedation . The treatment goal achievement rate was 68.8 % ( 22/32 , 95 % confidence interval 52.7–84.9 ) in the proportional sedation group vs. 83.3 % ( 15/18 , 66.1–100 ) in the deep sedation group . STAS decreased from 3.8 to 0.8 with proportional sedation at 4 h vs. 3.7 to 0.3 with deep sedation ; RASS decreased from + 1.2 to − 1.7 vs. + 1.4 to − 3.7 , respectively . Deep sedation was needed as a result in 31.3 % ( 10/32 ) of the proportional sedation group . No fatal events that were considered as probably or definitely related to the intervention occurred . Conclusion The two types of intervention protocol well reflected the treatment intention and expected outcomes . Further , large-scale cohort studies are promising Abstract Objective To determine the efficacy of oral morphine in relieving the sensation of breathlessness in patients in whom the underlying aetiology is maximally treated . Design R and omised , double blind , placebo controlled crossover study . Setting Four outpatient clinics at a hospital in South Australia . Participants 48 participants who had not previously been treated with opioids ( mean age 76 , SD 5 ) with predominantly chronic obstructive pulmonary disease ( 42 , 88 % ) were r and omised to four days of 20 mg oral morphine with sustained release followed by four days of identically formulated placebo , or vice versa . Laxatives were provided as needed . Main outcome measures Dyspnoea in the morning and evening as shown on a 100 mm visual analogue scale , quality of sleep , wellbeing , performance on physical exertion , and side effects as measured at the end of the four day treatment period . Results 38 participants completed the study ; three withdrew because of definite and two because of possible side effects of morphine ( nausea , vomiting , and sedation ) . Participants reported significantly different dyspnoea scores when treated with morphine : an improvement of 6.6 mm ( 95 % confidence interval 1.6 mm to 11.6 mm ) in the morning and of 9.5 mm ( 3.0 mm to 16.1 mm ) in the evening ( P = 0.011 and P = 0.006 , respectively ) . During the period in which they were taking morphine participants also reported better sleep ( P = 0.039 ) . More participants reported distressing constipation while taking morphine ( 9 v 1 , P = 0.021 ) in spite of using laxatives . All other side effects were not significantly worse with morphine , although the study was not powered to address side effects . Conclusions Sustained release , oral morphine at low dosage provides significant symptomatic improvement in refractory dyspnoea in the community setting Concern that opioids hasten death may be among the reasons that pain is treated inadequately in population s with advanced illness . Studies that assess the true risks are needed . To determine whether survival after last opioid dose change is associated with opioid dosing characteristics and other factors , data from the National Hospice Outcomes Project , a large prospect i ve cohort study involving 13 U.S. hospice programs , were analyzed . Of 1,306 patients , 725 received opioids and underwent at least one dose change before death . Sub sample s based on maximum opioid dose compared patients receiving usual doses with those receiving high-dose therapy . Spearman rank correlations examined bivariate associations between survival after final dose change and other variables , including dose in morphine equivalent mg and percentage dose increase . Multivariate least squares regression analyses determined associations between survival and other variables , including those significant in bivariate analyses . The mean+/-SD number of days between final dose change and death was 12.46+/-23.11 . Multivariate models demonstrated a significant association between shorter survival and higher opioid dose , a cancer diagnosis , unresponsiveness , and pain of < 5 on a 0 - 10 scale , but none of these models explained > 10 % of the variance in time till death . Analyses of sub sample s did not reveal additional effects of dose . This analysis revealed that opioid dosing was associated with time till death , but this factor would explain very little of the variation in survival . In a hospice population , survival is influenced by complex factors , many of which may not be measurable . Based on these findings , concern about hastening death does not justify withholding opioid therapy BACKGROUND The trajectory of dyspnea has been reported among patients approaching the end of life . However , patients near death have been dropped from longitudinal studies or excluded altogether because of an inability to self-report ; proxy estimates have been reported . It is not known whether dyspnea or respiratory distress remains stable , escalates , or abates as patients reach last days . OBJECTIVE Determine trajectory of dyspnea ( self-reported ) and respiratory distress ( observed ) among patients who were approaching death . DESIGN A prospect i ve , repeated- measures study of dyspnea/respiratory distress among a sample of hospice patients was done . Measures were collected at each patient encounter from hospice enrollment until patient death . MEASUREMENTS Dyspnea was measured in response to " Are you short of breath ? " and using the numeric rating scale anchored at 0 and 10 . Nurses measured respiratory distress with the Respiratory Distress Observation Scale ( RDOS ) . Patient consciousness ( Reaction Level Scale ) , nearness to death ( Palliative Performance Scale ) , diagnoses , and demographics were recorded . Data for the 30-day interval before death were analyzed . RESULTS The sample was 91 patients who were female ( 58 % ) and Caucasian ( 83 % ) with dementia ( 32 % ) , heart failure ( 26 % ) , and cancer ( 13 % ) . RDOS increased significantly from mild distress 30 days before death to moderate/severe distress on the day of death ( F = 10.8 , p < 0.0001 ) . Distress was strongly correlated with nearness to death ( r = -0.97 , p < 0.0001 ) and consciousness ( r = 0.97 , p < 0.0001 ) . CONCLUSIONS Respiratory distress escalated in the last days . Inability to self-report raises care concerns about under-recognition and under-treatment of respiratory distress Abstract Objectives : Palliative sedation is a therapeutic option to control refractory symptoms in terminal palliative patients . This study aims at describing the occurrence and characteristics of suboptimal palliative sedations in primary care and at exploring the way general practitioners ( GPs ) experience suboptimal palliative sedation in their practice . Methods : We conducted a mixed methods study with a quantitative prospect i ve survey in primary care and qualitative semi-structured interviews with GPs . The research team defined suboptimal palliative sedation as a time interval until deep sleep > 1.5 h and / or > 2 awakenings after the start of the unconsciousness . Descriptive statistics were calculated on the quantitative data . Thematic analysis was used to analyse interview transcripts . Results : We registered 63 palliative sedations in 1181 home deaths , 27 forms were completed . Eleven palliative sedations were suboptimal : eight due to the long time span until deep sleep ; three due the number of unintended awakenings . GPs ’ interview analysis revealed two major themes : the shifting perception of failure and the burden of responsibility . Conclusions : Suboptimal palliative sedation occurs frequently in primary palliative care . Efficient communication towards family members is needed to prevent them from having unrealistic expectations and to prevent putting pressure on the GP to hasten the procedure . Sharing the burden of decision-making during the procedure with other health care professionals might diminish the heavy responsibility as perceived by GPs Background : Patients suffering from a terminal illness often are confronted with severe symptoms during the last phase of their lives . Palliative sedation , although one of the options of last resort , remains a much debated and controversial issue and is often referred to as a form of slow euthanasia or euthanasia in disguise . Methods : A prospect i ve longitudinal and descriptive design was used . Each patient admitted in one of the 8 participating units was included if they met the inclusion criteria and gave written informed consent . Results : 266 patients were included . The incidence of palliative sedation was 7;5 % . For the group of se date d patients results show that 90 % entered the palliative care unit being fully conscious . Two patients were comatose upon arrival . 90 % of the patients remained fully conscious up to the day palliative sedation was started . When looking at the effect of palliative sedation on the level of consciousness the analysis strongly suggest that the palliative sedation - as expected- has an impact on the GCS score . Irrespective of the dichotomization of the score the probability of having a lower GCS increases substantially once sedation is initiated . Additionally , results show that once palliative sedation is administered , the level of consciousness gradually goes down up until the day of death . Conclusion : Palliative sedation is nor slow euthanasia nor an ambivalent practice . It is an intentional medical treatment which is administered in a proportional way when refractory suffering occurs . It occurs in extraordinary situations and at the very end of the dying process Dementia patients frequently die after a pneumonia or prolonged intake problems . Maintaining comfort is a goal of palliative care in end-stage dementia . To compare discomfort in dementia patients dying after a pneumonia with patients dying after intake problems , and to assess associations with treatment , we combined 2 Dutch prospect i ve studies . We selected 559 pneumonia patients and 166 patients with intake problems who had no pneumonia . Discomfort was observed with the Discomfort Scale – Dementia of Alzheimer Type ( DS-DAT ) . Linear regression was performed with the dependent DS-DAT levels shortly before death in 314 patients who died within 2 weeks . Compared with discomfort in patients with intake problems , unadjusted and adjusted discomfort in patients with pneumonia was higher both at t 0 and before death . In adjusted analyses , antibiotic treatment ( mostly oral ) was associated with less discomfort before death ( beta −1.1 , CI −2.2 – −0.03 ) , while invasive rehydration ( received by only 8 patients ) was associated with more discomfort ( beta 3.5 , CI 0.6 − 6.3 ) . Death from pneumonia may cause great suffering in dementia patients . If confirmed in a study with different case mix and treatments , antibiotics may be used to decrease discomfort even when death is imminent STUDY OBJECTIVE We determine how the alert/verbal/painful/unresponsive ( AVPU ) responsiveness scale ( alert , responsive to verbal stimulation , responsive to painful stimulation , and unresponsive ) corresponds to the Glasgow Coma Scale ( GCS ) when assessing consciousness level in the poisoned patient . METHODS Consciousness level was assessed using the AVPU responsiveness scale and the GCS in all patients admitted to the hospital during a 6-month period with deliberate or accidental poisoning . An AVPU responsiveness scale algorithm and details of the individual components of the GCS were provided . Data were recorded prospect ively on admission to the toxicology ward by nursing staff in the majority of cases and from case records for the small number of patients admitted directly to the ICU . Nursing staff also recorded any difficulty assessing consciousness level using either scoring system . RESULTS Of the 1,384 patients studied , 1,138 patients were alert , 114 patients responded to a verbal stimulus , 87 patients responded to a painful stimulus , and 15 patients were unresponsive . The median GCS scores with interquartile ranges ( IQR ) for each AVPU responsiveness category were 15 ( IQR 15 ) , 13 ( IQR 12 to 14 ) , 8 ( IQR 7 to 9 ) , and 3 ( IQR 3 ) , respectively . There was a degree of overlap between the range of GCS scores for each category . Nursing staff recorded more difficulty using the GCS than the AVPU responsiveness scale . Alcohol-intoxicated patients proved to be the most difficult to assess . All patients who were unresponsive required intubation . No patient with a GCS score greater than 6 was intubated . CONCLUSION Each AVPU category can be shown to correspond to a range of GCS scores . The AVPU responsiveness scale appears to provide a rapid simple method of assessing consciousness level in most poisoned patients , but difficulty was still observed in assessing alcohol-intoxicated patients CONTEXT A tool to quantify agitation severity and sedation level in patients with advanced cancer is needed . OBJECTIVES To test the appropriateness and reliability of the Richmond Agitation-Sedation Scale ( RASS ) in Spanish patients with advanced cancer . METHODS The original RASS was translated into Spanish according to the st and ard guidelines . Face validity was assessed by members of the palliative care team , and interrater reliability was assessed , using a weighted kappa , from observations of patients admitted to the palliative care unit . The association between scores of the RASS , Ramsay Sedation Scale , and Glasgow Coma Scale was evaluated using Spearman 's ρ . RESULTS Three hundred twenty-two observations were performed in 156 patients : 116 observations were performed for delirious patients , 76 observations for se date d patients , and 130 observations for patients admitted for other symptom control . The weighted kappa values were practically equal to or greater than 0.90 between nurses and nurses and physicians . The agreement level between observers for each RASS score was roughly 90 % . The correlation between the RASS and the Ramsay and Glasgow Scale values was analyzed for 196 observations recorded in 80 patients . The sedation scale of the RASS had a strong correlation with both the Ramsay ( Spearman 's ρ , -0.89 ; P < 0.001 ) and the Glasgow Coma Scales ( Spearman 's ρ , 0.85 ; P < 0.001 ) . CONCLUSION These data support the use of the RASS in Spanish patients with advanced cancer To determine the physical and medical change in the dying process , a prospect i ve study was performed on 100 terminally ill cancer patients . The mean ( median ) time from the onset of death rattle , respiration with m and ibular movement ( RMM ) , cyanosis on extremities , and pulselessness on the radial artery to death was 57 ( 23 ) hours , 7.6 ( 2.5 ) hours , 5.1 ( 1.0 ) hours , and 2.6 ( 1.0 ) hours , respectively . Death rattle preceded the other three conditions in 74 percent of the subjects , while RMM preceded cyanosis and pulselessness in 63 percent . The ratio of awake-drowsy-comatose patients was 56 - 44 - 0 percent one week before death , 26 - 62 - 12 percent in the last 24 hours , and 8 - 42 - 50 percent in the final six hours . The number of opioid users and average dose increased significantly as death approached , from 42 percent and 49 mg/day ( parental morphine equivalent ) four weeks before death to 87 percent and 139 mg/day in the final 48 hours . The frequency of extra dosage also increased significantly , from 32 percent ( opioid ) and 40 percent ( non-opioid ) one week before death to 68 percent and 66 percent in the last 48 hours , respectively . The change of physical signs and medical intervention when death is impending has a common pathway in spite of large individual variations ; thus , underst and ing this nature can help clinicians to offer better palliative care to terminal cancer patients We report an open , uncontrolled study to evaluate the effectiveness of regular oral morphine as symptomatic treatment of dyspnoea in patients with advanced cancer receiving st and ard clinical care . Fifteen patients were assessed initially , and then 48 h and 7 - 10 days after starting treatment with oral morphine or having their dose increased . Dyspnoea , measured on a visual analogue scale ( 0 - 100 ) , fell by a median of 14 ( 95 % confidence interval -1.5 , 25.5 ; Wilcoxon statistic 32.0 ; P = 0.06 ) in the nine who completed all three assessment s. The three patients who died during the study did not show symptomatic benefit and , like the three who withdrew , experienced increased sedation and /or dizziness . Sedation was significantly increased at 48 h ; median rise 10.5 ( 95 % confidence interval 7 , 25 ; Wilcoxon statistic 74 ; P = 0.007 ) . Baseline respiratory function ( FEV 1 , FVC , peak flow ) was poor and the patients ' respiratory rate was unaffected . Regular , titrated oral morphine may improve dyspnoea in some patients with advanced cancer but can cause significant short-term adverse effects . Oral morphine should be given to these patients as a therapeutic trial . Patients should be advised about side-effects and carefully monitored . Larger studies are needed to establish which patients are most likely to benefit and optimal dosage regimens BACKGROUND While there is debate about whether it may be better to forgo than to initiate artificial nutrition and hydration ( ANH ) in nursing home patients with severe dementia , the consequences of forgoing ANH in these patients , in particular their discomfort , have not yet been investigated . METHODS In this prospect i ve , longitudinal , observational study of 178 patients in Dutch nursing homes , discomfort was measured at all measurement times according to the observational Discomfort Scale-Dementia of Alzheimer Type . Furthermore , at all measurement times , plausible determinants of discomfort were registered . Data were analyzed with the statistical technique of generalized estimated equations . RESULTS Decisions to forgo ANH were made most often in severely demented , female patients with an acute illness as the most important diagnosis at that time . The mean level of discomfort was highest at the time of the decision and decreased in the days thereafter . There were substantial differences in level of discomfort between patients . Dyspnea , restlessness , and physicians ' observations of pain and dehydration were associated with higher levels of discomfort . Furthermore , patients who were awake had higher levels of observed discomfort than patients who were asleep . CONCLUSIONS Forgoing ANH in patients with severe dementia who scarcely or no longer eat or drink seems , in general , not to be associated with high levels of discomfort . The individual differences emphasize the need for constant attention for possible discomfort CONTEXT Palliative sedation remains a much debated and controversial issue . The limited literature on the topic often fails to answer ethical questions concerning this practice . OBJECTIVES The aim of this study was to describe the characteristics of patients who are being se date d for refractory symptoms in palliative care units ( PCUs ) from the time of admission until the day of death . METHODS A prospect i ve , longitudinal , descriptive design was used to assess data in eight PCUs . The total sample consisted of 266 patients . Information on demographics , medication , food and fluid intake , decision making , level of consciousness , and symptom experience were gathered by nurses and research ers three times a week . If patients received palliative sedation , extra information was gathered . RESULTS Of all included patients ( n=266 ) , 7.5 % received palliative sedation . Sedation started , on average , 2.5 days before death and for half of these patients , the form of sedation changed over time . At the start of sedation , patients were in the end stage of their illness and needed total care . Patients were fully conscious and had very limited oral food or fluid intake . Only three patients received artificial fluids at the start of sedation . Patients reported , on average , two refractory symptoms , the most important ones being pain , fatigue , depression , drowsiness , and loss of feeling of well-being . In all cases , the patient gave consent to start palliative sedation because of increased suffering . CONCLUSION This study revealed that palliative sedation is only administered in exceptional cases where refractory suffering is evident and for those patients who are close to the ends of their lives . Moreover , this study supports the argument that palliative sedation has no life-shortening effect The Observer 's Assessment of Alertness/Sedation ( OAA/S ) Scale was developed to measure the level of alertness in subjects who are se date d. This scale was tested in 18 subjects in a three-period crossover study to assess its reliability and its criterion , behavioral , and construct validity . After receiving either placebo or a titrated dose of midazolam to produce light or heavy sedation , each subject was administered two sedation scales ( OAA/S Scale and a Visual Analogue Scale ) and two performances tests ( Digit Symbol Substitution Test and Serial Sevens Subtraction ) . Two raters individually evaluated the subject 's level of alertness on each of the two sedation scales . The results obtained on the OAA/S Scale were reliable and valid as measured by high correlations between the two raters and high correlations between the OAA/S Scale and two of the three st and ard tests used in this study . The OAA/S Scale was sensitive to the level of midazolam administered ; all pairwise comparisons were significant ( p < 0.05 ) for all three treatment levels at both test periods Death rattle is frequently observed in cancer patients whose death is impending and may contribute to the severe distress of patients and their family members . To identify risk factors for development and persistency of death rattle , a prospect i ve study was performed on 245 hospice in patients . One-hundred- and -seven patients ( 44 % ) developed death rattle , 71 % of whom achieved satisfactory symptom palliation until death . A multiple regression analysis identified neoplasms of brain and lung as independent risk factors for development of death rattle , while refractory symptoms were significantly associated with pulmonary neoplasms and infection/oedema . In conclusion , development of death rattle was influenced by both brain and lung malignancies , while its persistency was mainly determined by pulmonary pathology . A clinical classification of death rattle based on these factors would be established by a further confirmatory study CONTEXT Clinicians prescribe and administer oxygen in response to reports of dyspnea , in the face of dropping oxygen saturation , as a " routine " comfort intervention , or to support anxious family members . Oxygen may produce nasal irritation and increase the cost of care . OBJECTIVES To determine the benefit of administering oxygen to patients who are near death . METHODS A double-blind , repeated-measure observation with the patient as his/her own control was conducted . The Respiratory Distress Observation Scale ( © ) measured presence and intensity of distress at baseline and at every gas or flow change . Medical air , oxygen , and no flow were r and omly alternated every 10 minutes via nasal cannula with patients who were near death , at risk for respiratory distress , with no distress at the baseline of testing . Each patient had two encounters under each condition , yielding six encounters per patient . RESULTS Patients were 66 % female , 34 % white , and 66 % African American , and ages 56 - 97 years . Patients had heart failure ( 25 % ) , chronic obstructive pulmonary disease ( 34 % ) , pneumonia ( 41 % ) , or lung cancer ( 9 % ) . Most ( 91 % ) patients tolerated the protocol with no change in respiratory comfort . Three patients ( 9 % ) displayed distress and were restored to baseline oxygen ; one patient died during the protocol while displaying no distress . Repeated-measure analysis of variance revealed no differences in the Respiratory Distress Observation Scale under changing gas and flow conditions . CONCLUSION The routine application of oxygen to patients who are near death is not supported . The n-of-1 trial of oxygen in clinical practice is appropriate in the face of hypoxemic respiratory distress Terminally ill cancer patients near the end of life may experience intolerable suffering refractory to palliative treatment . Although sedation is considered to be an effective treatment when aggressive efforts fail to provide relief in terminally ill patients , it remains controversial . The aim of this study was to assess the need and effectiveness of sedation in dying patients with intractable symptoms , and the thoughts of relatives regarding sedation . A prospect i ve cohort study was performed on a consecutive sample of dying patients admitted to an acute pain relief and palliative care unit within a cancer center . Indications for sedation , opioid and midazolam doses , level of delirium and sedation , nutrition , hydration , rattle , inability to cough and swallow , pharyngeal aspiration , duration of sedation and survival , and use of anticholinergics or other drugs were recorded . Family members were interviewed . Forty-two of 77 dying patients were se date d , and had a longer survival than those who were not se date d ( P=0.003 ) . Prevalent indications for sedation were dyspnea and /or delirium . Twelve patients began with an intermediate sedation , and 38 patients started with definitive sedation . The median sedation duration was 22 hours . Opioid doses did not change during sedation . Agitated delirium significantly decreased with increasing doses of midazolam , whereas the capacity to communicate concomitantly decreased . Interviewed relatives were actively involved in the process of end-of-life care , and the decision to se date , and the efficacy of sedation , were considered appropriate by almost all relatives . Controlled sedation is successful in dying patients with untreatable symptoms , did not hasten death , and yielded satisfactory results for relatives . This study also points to the importance of palliative care and the experience of professionals skilled in both symptom control and end-of-life care CONTEXT Death rattle ( DR ) is a dramatic sign in the dying patient . Existing studies with anticholinergic agents are controversial , as this class of drugs has been commonly administered without considering the rationale of the mechanism of action . A meaningful use of these drugs may provide a better outcome . OBJECTIVES The aim of this study was to assess the efficacy of hyoscine butylbromide ( HB ) , given prophylactically in comparison with HB administered once DR occurs . METHODS Dying patients having a score of ≥3 in the Richmond Agitation-Sedation Scale-palliative version were included in the study . HB ( 60 mg/day ) was given when DR occurred ( Group 1 ) or as pre-emptive treatment ( Group 2 ) . The onset of DR ( death rattle free time ) and intensity of DR were recorded at intervals until death . RESULTS Eighty-one and 51 patients were r and omized to Group 1 and 2 , respectively . Patients in Group 2 survived longer than those in Group 1 ( P < 0.05 ) . DR occurred in 49 ( 60.5 % ) and three patients ( 5.9 % ) in Group 1 and 2 , respectively ( P = 0.001 ) . A significant difference in the number of patients reporting DR was found at intervals examined ( 30 minutes , one hour , and then every six hours until death [ P = 0.001 ] ) . In Group 1 and 2 , DR free time was 20.4 ( 20.5 ) and 27.3 hours ( 25.2 ) , respectively ( P = 0.001 ) . In Group 1 , the treatment was considered effective in 10 patients ( 20.4 % ) only , after a mean of 14.4 hours ( SD 8.57 ) . CONCLUSION The prophylactic use of HB is an efficient method to prevent DR , whereas the late administration produces a limited response , confirming data from traditional studies performed with anticholinergics . This could be considered a new paradigm to manage a difficult and dramatic sign , such as DR CONTEXT An unresponsive patient 's need and their response to breakthrough medication is determined by clinical assessment and /or observational measures . How closely these methods match the patient 's experience is unknown . OBJECTIVES Determine the efficacy and effectiveness of breakthrough medication in unresponsive patients and the perception of patient comfort made by nurses and family . METHODS A prospect i ve study of breakthrough medication in unresponsive patients . The Richmond Agitation-Sedation Scale ( RASS ) and Patient Comfort Score ( PCS ) were compared with time-matched Bispectral Index ( BIS ) Scores . The effects of opioid vs. opioid + benzodiazepine breakthroughs and the relation between synchronous nurse and family measurements of the PCS were evaluated . Analysis of variance and paired t-tests were used for BIS analyses and nonparametric Mann-Whitney tests for RASS and PCS . RESULTS Significant reductions at 30 and 60 minutes after breakthrough medication were noted for BIS ( P < 0.0004 ) , RASS ( P = 0.043 and 0.004 , respectively ) , and PCS ( P < 0.0004 ) . A direct comparison of the effect of opioid breakthrough medication vs. opioid plus benzodiazepine revealed no significant difference ( BIS , P = 0.512 ; RASS , P = 0.195 ; PCS , P = 0.119 ) . Of the 157 synchronous nurse and family measures of patient comfort , families rated patient discomfort significantly higher than nurses ( P < 0.0004 ) . CONCLUSION This study provides additional evidence for the efficacy and effectiveness of breakthrough medication and the merit of observational measures in determining a patient 's response . The onset of action is evident at 30 minutes after injection . Family assessment of patient comfort may be more nuanced than that of nurses , and they not uncommonly rate patient discomfort higher than nurses Importance Antipsychotics are widely used for distressing symptoms of delirium , but efficacy has not been established in placebo-controlled trials in palliative care . Objective To determine efficacy of risperidone or haloperidol relative to placebo in relieving target symptoms of delirium associated with distress among patients receiving palliative care . Design , Setting , and Participants A double-blind , parallel-arm , dose-titrated r and omized clinical trial was conducted at 11 Australian inpatient hospice or hospital palliative care services between August 13 , 2008 , and April 2 , 2014 , among participants with life-limiting illness , delirium , and a delirium symptoms score ( sum of Nursing Delirium Screening Scale behavioral , communication , and perceptual items ) of 1 or more . Interventions Age-adjusted titrated doses of oral risperidone , haloperidol , or placebo solution were administered every 12 hours for 72 hours , based on symptoms of delirium . Patients also received supportive care , individualized treatment of delirium precipitants , and subcutaneous midazolam hydrochloride as required for severe distress or safety . Main Outcome and Measures Improvement in mean group difference of delirium symptom score ( severity range , 0 - 6 ) between baseline and day 3 . Five a priori secondary outcomes : delirium severity , midazolam use , extrapyramidal effects , sedation , and survival . Results Two hundred forty-seven participants ( mean [ SD ] age , 74.9 [ 9.8 ] years ; 85 women [ 34.4 % ] ; 218 with cancer [ 88.3 % ] ) were included in intention-to-treat analysis ( 82 receiving risperidone , 81 receiving haloperidol , and 84 receiving placebo ) . In the primary intention-to-treat analysis , participants in the risperidone arm had delirium symptom scores that were significantly higher than those among participants in the placebo arm ( on average 0.48 Units higher ; 95 % CI , 0.09 - 0.86 ; P = .02 ) at study end . Similarly , for those in the haloperidol arm , delirium symptom scores were on average 0.24 Units higher ( 95 % CI , 0.06 - 0.42 ; P = .009 ) than in the placebo arm . Compared with placebo , patients in both active arms had more extrapyramidal effects ( risperidone , 0.73 ; 95 % CI , 0.09 - 1.37 ; P = .03 ; and haloperidol , 0.79 ; 95 % CI , 0.17 - 1.41 ; P = .01 ) . Participants in the placebo group had better overall survival than those receiving haloperidol ( hazard ratio , 1.73 ; 95 % CI , 1.20 - 2.50 ; P = .003 ) , but this was not significant for placebo vs risperidone ( hazard ratio , 1.29 ; 95 % CI , 0.91 - 1.84 ; P = .14 ) . Conclusions and Relevance In patients receiving palliative care , individualized management of delirium precipitants and supportive strategies result in lower scores and shorter duration of target distressing delirium symptoms than when risperidone or haloperidol are added . Trial Registration anzctr.org.au Identifier : ACTRN12607000562471 |
847 | 26,976,529 | There was little or no difference in clinical outcomes ( based on moderate certainty evidence ) .
It is possible that the findings may change with the inclusion of large ongoing well-organised trials in future up date s. The results suggest an improvement in health outcomes if interventions can be targeted at risk factors such as depression , or specific functional difficulties in people with multimorbidity | BACKGROUND Many people with chronic disease have more than one chronic condition , which is referred to as multimorbidity .
The term comorbidity is also used but this is now taken to mean that there is a defined index condition with other linked conditions , for example diabetes and cardiovascular disease .
It is also used when there are combinations of defined conditions that commonly co-exist , for example diabetes and depression .
While this is not a new phenomenon , there is greater recognition of its impact and the importance of improving outcomes for individuals affected .
Research in the area to date has focused mainly on descriptive epidemiology and impact assessment .
There has been limited exploration of the effectiveness of interventions to improve outcomes for people with multimorbidity .
OBJECTIVES To determine the effectiveness of health-service or patient-oriented interventions design ed to improve outcomes in people with multimorbidity in primary care and community setting s. Multimorbidity was defined as two or more chronic conditions in the same individual . | Background Chronic diseases represent a major challenge for health care and social services . A number of people with chronic diseases require more services due to characteristics that increase their vulnerability . Given the burden of increasingly vulnerable patients on primary care , a pragmatic intervention in four Family Medicine Groups ( primary care practice s in Quebec , Canada ) has been proposed for individuals with chronic diseases ( diabetes , cardiovascular diseases , respiratory diseases , musculoskeletal diseases and /or chronic pain ) who are frequent users of hospital services . The intervention combines case management by a nurse with group support meetings encouraging self-management based on the Stanford Chronic Disease Self-Management Program . The goals of this study are to : ( 1 ) analyze the implementation of the intervention in the participating practice s in order to determine how the various context s have influenced the implementation and the observed effects ; ( 2 ) evaluate the proximal ( self-efficacy , self-management , health habits , activation and psychological distress ) and intermediate ( empowerment , quality of life and health care use ) effects of the intervention on patients ; ( 3 ) conduct an economic analysis of the efficiency and cost-effectiveness of the intervention . Methods / Design The analysis of the implementation will be conducted using realistic evaluation and participatory approaches within four categories of stakeholders ( Family Medicine Group and health centre management , Family Medicine Group practitioners , patients and their families , health centre or community partners ) . The data will be obtained through individual and group interviews , project documentation review s and by documenting the intervention . Evaluation of the effects on patients will be based on a pragmatic r and omized before-after experimental design with a delayed intervention control group ( six months ) . Economic analysis will include cost-effectiveness and cost-benefit analysis . Discussion The integration of a case management intervention delivered by nurses and self-management group support into primary care practice s has the potential to positively impact patient empowerment and quality of life and hopefully reduce the burden on health care . Decision-makers , managers and health care professionals will be aware of the factors to consider in promoting the implementation of this intervention into other primary care practice s in the region and elsewhere . Trial Registration Background Care management programmes are an effective approach to care for high risk patients with complex care needs result ing from multiple co-occurring medical and non-medical conditions . These patients are likely to be hospitalized for a potentially " avoidable " cause . Nurse-led care management programmes for high risk elderly patients showed promising results . Care management programmes based on health care assistants ( HCAs ) targeting adult patients with a high risk of hospitalisation may be an innovative approach to deliver cost-efficient intensified care to patients most in need . Methods / Design PraCMan is a cluster r and omized controlled trial with primary care practice s as unit of r and omisation . The study evaluates a complex primary care practice -based care management of patients at high risk for future hospitalizations . Eligible patients either suffer from type 2 diabetes mellitus , chronic obstructive pulmonary disease , chronic heart failure or any combination . Patients with a high likelihood of hospitalization within the following 12 months ( based on insurance data ) will be included in the trial . During 12 months of intervention patients of the care management group receive comprehensive assessment of medical and non-medical needs and re sources as well as regular structured monitoring of symptoms . Assessment and monitoring will be performed by trained HCAs from the participating practice s. Additionally , patients will receive written information , symptom diaries , action plans and a medication plan to improve self-management capabilities . This intervention is addition to usual care . Patients from the control group receive usual care . Primary outcome is the number of all-cause hospitalizations at 12 months follow-up , assessed by insurance cl aims data . Secondary outcomes are health-related quality of life ( SF12 , EQ5D ) , quality of chronic illness care ( PACIC ) , health care utilisation and costs , medication adherence ( MARS ) , depression status and severity ( PHQ-9 ) , self-management capabilities and clinical parameters . Data collection will be performed at baseline , 12 and 24 months ( 12 months post-intervention ) . Discussion Practice -based care management for high risk individuals involving trained HCAs appears to be a promising approach to face the needs of an aging population with increasing care dem and s . Trial registration Current Controlled Trials IS RCT OBJECTIVE To examine to what extent general practitioners in consultations after a geriatric assessment set shared health priorities with older patients experiencing multimorbidity and to what extent this was facilitated through patient-centered behavior . METHODS Observation of consultations embedded in a cluster r and omized controlled trial,(1 ) in which 317 patients from 41 general practice s received the STEP assessment followed by a care planning consultation with their GPs . GPs in the intervention group used a structured procedure for setting health ( care ) priorities in contrast to control GPs . A sample of 43 consultations ( 24 intervention ; 19 control ) were recorded , transcribed and analyzed with regard to priority setting and patient-centeredness . RESULTS Patient-centeredness was only moderately apparent in consultations dealing with complex care plans for older patients with multimorbidity . The shared determination of health priorities seemed unusual for both doctors and patients and was rarely practice d , albeit more frequently in intervention consultations . CONCLUSION Setting health care priorities with patients experiencing multimorbidity is ethically desirable and medically appropriate . Yet a short structured guide for doctors can not easily achieve this . PRACTICE IMPLICATION S More research is needed in regard to h and ling complex health needs of older patients . It requires a professional approach and training in patient-centered holistic care planning Background Care management interventions in the German health-care system have been evaluated with promising results , but further research is necessary to explore their full potential in the context of multi-morbidity . Our aim in this trial is to assess the efficacy of a primary care practice network – based care management intervention in improving self-care behaviour among patients with type 2 diabetes mellitus and multiple co-occurring chronic conditions . Methods / Design The study is design ed as a prospect i ve , 18-month , multicentre , investigator-blinded , two-arm , open-label , individual-level , r and omized parallel-group superiority trial . We will enrol 582 patients with type 2 diabetes mellitus and at least two severe chronic conditions and one informal caregiver per patient . Data will be collected at baseline ( T0 ) , at the primary endpoint after 9 months ( T1 ) and at follow-up after 18 months ( T2 ) . The primary outcome will be the differences between the intervention and control groups in changes of diabetes-related self-care behaviours from baseline to T1 using a German version of the revised Summary of Diabetes Self-Care Activities ( SDSCA-G ) . The secondary outcomes will be the differences between the intervention and control groups in : changes in scores on the SDSCA-G subscales , glycosylated haemoglobin A level , health-related quality of life , self-efficacy , differences in ( severe ) symptomatic hypoglycaemia , cost-effectiveness and financial family burden . The intervention will be delivered by trained health-care assistants as an add-on to usual care and will consist of three main elements : ( 1 ) three home visits , including structured assessment of medical and social needs ; ( 2 ) 24 structured telephone monitoring contacts ; and ( 3 ) self-monitoring of blood glucose levels after T1 in 3-month intervals . The control group will receive usual care . The confirmatory primary analysis will be performed following the intention-to-treat ( ITT ) principle . The efficacy of the intervention will be quantified using two-level linear regression stratified by type of medical treatment adjusted for baseline values on the SDSCA-G. Secondary analyses will be performed according to the ITT principle . In health economic evaluations , we will estimate the incremental cost-effectiveness ratios . Discussion We hope that the results of this study will provide insights into the efficacy of practice network – based care management among patients with complex health-care needs . Trial registration Current Controlled Trials IS RCT N83908315 ( IS RCT N assigned 25 February 2014 ) Background Frail elderly people need an integrated and coordinated care . The two-armed study " Continuum of care for frail elderly people " is a multi-professional and multidimensional intervention for frail community-dwelling elderly people . It was design ed to evaluate whether the intervention programme for frail elderly people can reduce the number of visits to hospital , increase satisfaction with health and social care and maintain functional abilities . The implementation process is explored and analysed along with the intervention . In this paper we present the study design , the intervention and the outcome measures as well as the baseline characteristics of the study participants . Methods / design The study is a r and omised two-armed controlled trial with follow ups at 3 , 6 and 12 months . The study group includes elderly people who sought care at the emergency ward and discharged to their own homes in the community . Inclusion criteria were 80 years and older or 65 to 79 years with at least one chronic disease and dependent in at least one activity of daily living . Exclusion criteria were acute severely illness with an immediate need of the assessment and treatment by a physician , severe cognitive impairment and palliative care . The intention was that the study group should comprise a representative sample of frail elderly people at a high risk of future health care consumption . The intervention includes an early geriatric assessment , early family support , a case manager in the community with a multi-professional team and the involvement of the elderly people and their relatives in the planning process . Discussion The design of the study , the r and omisation procedure and the protocol meetings were intended to ensure the quality of the study . The implementation of the intervention programme is followed and analysed throughout the whole study , which enables us to generate knowledge on the process of implementing complex interventions . The intervention contributes to early recognition of both the elderly peoples ' needs of information , care and rehabilitation and of informal caregivers ' need of support and information . This study is expected to show positive effects on frail elderly peoples ' health care consumption , functional abilities and satisfaction with health and social care . Trial registration Clinical Trials.gov : OBJECTIVE Sub clinical depression is one of the most frequent mental comorbidities in patients with diabetes and is associated with a poorer long-term prognosis . Since there is a lack of specific intervention concepts for this patient group , a self-management – oriented group program ( DIAMOS [ Diabetes Motivation Strengthening ] ) was newly developed and evaluated in a r and omized trial . RESEARCH DESIGN AND METHODS DIAMOS is composed of cognitive behavioral interventions aim ing at the reduction of diabetes distress . The active control group ( CG ) received diabetes education . The primary outcome was depressive symptoms . Secondary outcomes were diabetes distress , well-being , self-care behavior , diabetes acceptance , diabetes treatment satisfaction , HbA1c , and sub clinical inflammation . RESULTS Two hundred fourteen participants ( mean age 43.3 ± 13.3 years , female sex 56.5 % , type 2 diabetes 34.1 % , mean diabetes duration 14.2 ± 10.5 years , HbA1c 8.9 ± 1.8 % , BMI 28.7 ± 71 kg/m2 ) were r and omized . The 12-month follow-up revealed a significantly stronger reduction of depressive symptoms ( Center for Epidemiologic Studies Depression Scale score ) in the DIAMOS group compared with the CG ( Δ3.9 [ 95 % CI 0.6–7.3 ] , P = 0.021 ) . Of the secondary variables , the Patient Health Question naire-9 ( Δ1.7 [ 95 % CI 0.2–3.2 ] , P = 0.023 ) , Problem Areas in Diabetes scale ( Δ8.2 [ 95 % CI 3.1–13.3 ] , P = 0.002 ) , and Diabetes Distress Scale scores ( Δ0.3 [ 95 % CI 0.1–0.5 ] , P = 0.012 ) displayed significant treatment effects . Moreover , the risk of incident major depression in the DIAMOS group was significantly reduced ( odds ratio 0.63 [ 95 % CI 0.42–0.96 ] , P = 0.028 ) . Inflammatory variables were not substantially affected . CONCLUSIONS DIAMOS is more effective in lowering depressive symptoms and diabetes-related distress in diabetic patients with sub clinical depression . DIAMOS also has a preventive effect with respect to the incidence of major depression BACKGROUND In the Medicare Modernization Act of 2003 , Congress required the Centers for Medicare and Medicaid Services to test the commercial disease-management model in the Medicare fee-for-service program . METHODS The Medicare Health Support Pilot Program was a large , r and omized study of eight commercial programs for disease management that used nurse-based call centers . We r and omly assigned patients with heart failure , diabetes , or both to the intervention or to usual care ( control ) and compared them with the use of a difference-in-differences method to evaluate the effects of the commercial programs on the quality of clinical care , acute care utilization , and Medicare expenditures for Medicare fee-for-service beneficiaries . RESULTS The study included 242,417 patients ( 163,107 in the intervention group and 79,310 in the control group ) . The eight commercial disease-management programs did not reduce hospital admissions or emergency room visits , as compared with usual care . We observed only 14 significant improvements in process-of-care measures out of 40 comparisons . These modest improvements came at substantial cost to the Medicare program in fees paid to the disease-management companies ( $ 400 million ) , with no demonstrable savings in Medicare expenditures . CONCLUSIONS In this large study , commercial disease-management programs using nurse-based call centers achieved only modest improvements in quality -of-care measures , with no demonstrable reduction in the utilization of acute care or the costs of care Background With increasing age and longevity , the rising number of frail elders with complex and numerous health-related needs dem and s a coordinated health care delivery system integrating cure , care and welfare . Studies on the effectiveness of such comprehensive chronic care models targeting frail elders show inconclusive results . The CareWell- primary care program is a complex intervention targeting community-dwelling frail elderly people , that aims to prevent functional decline , improve quality of life , and reduce or postpone hospital and nursing home admissions of community dwelling frail elderly . Methods / design The CareWell- primary care study includes a ( cost- ) effectiveness study and a comprehensive process evaluation . In a one-year pragmatic , cluster controlled trial , six general practice s are non-r and omly recruited to adopt the CareWell- primary care program and six control practice s will deliver ‘ care as usual ’ . Each practice includes a r and om sample of fifty frail elders aged 70 years or above in the cost-effectiveness study . A sample of patients and informal caregivers and all health care professionals participating in the CareWell- primary care program are included in the process evaluation . In the cost-effectiveness study , the primary outcome is the level of functional abilities as measured with the Katz-15 index . Hierarchical mixed-effects regression models / multilevel modeling approach will be used , since the study participants are nested within the general practice s. Furthermore , incremental cost-effectiveness ratios will be calculated as costs per QALY gained and as costs weighed against functional abilities . In the process evaluation , mixed methods will be used to provide insight in the implementation degree of the program , patients ’ and professionals ’ approval of the program , and the barriers and facilitators to implementation . Discussion The CareWell- primary care study will provide new insights into the ( cost- ) effectiveness , feasibility , and barriers and facilitators for implementation of this complex intervention in primary care . Trial registration The CareWell- primary care study is registered in the Clinical Trials.gov Protocol Registration System : Background Depression is common in people with coronary heart disease ( CHD ) and associated with worse outcome . This study explored the acceptability and feasibility of procedures for a trial and for an intervention , including its potential costs , to inform a definitive r and omized controlled trial ( RCT ) of a nurse-led personalised care intervention for primary care CHD patients with current chest pain and probable depression . Methods Multi-centre , outcome assessor-blinded , r and omized parallel group study . CHD patients reporting chest pain and scoring 8 or more on the HADS were r and omized to personalized care ( PC ) or treatment as usual ( TAU ) for 6 months and followed for 1 year . Primary outcome was acceptability and feasibility of procedures ; secondary outcomes included mood , chest pain , functional status , well being and psychological process variables . Result 1001 people from 17 General Practice CHD registers in South London consented to be contacted ; out of 126 who were potentially eligible , 81 ( 35 % female , mean age = 65 SD11 years ) were r and omized . PC participants ( n = 41 ) identified wide ranging problems to work on with nurse-case managers . Good acceptability and feasibility was indicated by low attrition ( 9 % ) , high engagement and minimal nurse time used ( mean/SD = 78/19 mins assessment , 125/91 mins telephone follow up ) . Both groups improved on all outcomes . The largest between group difference was in the proportion no longer reporting chest pain ( PC 37 % vs TAU 18 % ; mixed effects model OR 2.21 95 % CI 0.69 , 7.03 ) . Some evidence was seen that self efficacy ( mean scale increase of 2.5 vs 0.9 ) and illness perceptions ( mean scale increase of 7.8 vs 2.5 ) had improved in PC vs TAU participants at 1 year . PC appeared to be more cost effective up to a QALY threshold of approximately £ 3,000 . Conclusions Trial and intervention procedures appeared to be feasible and acceptable . PC allowed patients to work on unaddressed problems and appears cheaper than TAU . Trial Registration Controlled-Trials.com IS RCT Background : Anxiety and depression are common features of coeliac disease . Depression is cause of non‐compliance to treatment in chronic illness Background and aims Although a growing number of older people are suffering from multimorbidity , most of the health problems related to multimorbidity can be improved by self-management . The aim of this study was to examine the effectiveness of a health coaching self-management program for older adults with multimorbidity in nursing homes . Methods Older adults with multimorbidity from one nursing home in Korea were r and omly allocated to either an intervention group ( n=22 ) or conventional group ( n=21 ) . Participants in the intervention group met face to face with the research ers twice a week for 8 weeks , during which time the research ers engaged them in goal setting and goal performance using the strategies in the health coaching self-management program . Regular care was provided to the other participants in the conventional group . Results Participants in the intervention group had significantly better outcomes in exercise behaviors ( P=0.015 ) , cognitive symptom management ( P=0.004 ) , mental stress management/relaxation ( P=0.023 ) , self-rated health ( P=0.002 ) , reduced illness intrusiveness ( P<0.001 ) , depression ( P<0.001 ) , and social/role activities limitations ( P<0.001 ) . In addition , there was a significant time-by-group interaction in self-efficacy ( P=0.036 ) . According to the goal attainment scales , their individual goals of oral health and stress reduction were achieved . Conclusion The health coaching self-management program was successfully implemented in older adults with multimorbidity in a nursing home . Further research is needed to develop and evaluate the long-term effects of an intervention to enhance adherence to self-management and quality of life for older adults with multimorbidity Introduction The objective of this pilot 6-month r and omized controlled trial was to determine the effectiveness of an intensive , community-based , group intervention that focused on diet , physical activity , and peer support for reducing weight among urban-dwelling African Americans with comorbid type 2 diabetes and hypertension . Methods Sixty-one participants were r and omized into an intervention or control group . The 6-month intervention consisted of 18 group sessions led by a dietitian in a community setting and weekly telephone calls from a peer supporter . The intervention featured culturally tailored nutrition education , behavioral skills training , and social support focused on changes to diet and physical activity . The control group consisted of two 3-hour group sessions of diabetes self-management education taught by a community health worker . Outcome measures were assessed at baseline and 6 months . The primary outcome was achievement of a 5 % weight reduction at 6 months . A secondary outcome was achievement of a 0.5 percentage-point reduction in hemoglobin A1c ( HbA1c ) . Results Groups did not differ in achievement of the weight-loss goal . Intervention participants lost a mean of 2.8 kg ( P = .01 ) ; control participants did not lose a significant amount of weight . A greater proportion of intervention ( 50.0 % ) than control ( 21.4 % ) participants reduced HbA1c by 0.5 percentage points or more at 6 months ( P = .03 ) . Conclusion The intervention was more effective than usual care ( short-term diabetes education ) at improving glycemic control , but not weight , in low-income African Americans with comorbid diabetes and hypertension . A community-based 6-month group class with culturally tailored education , behavioral skills training , and peer support can lead to a clinical ly significant reduction in HbA1c BACKGROUND Home telehealth programs often focus on a single disease , yet many patients who need monitoring have multiple conditions . This study evaluated secondary outcomes from a clinical trial evaluating the efficacy of home telehealth to improve outcomes of patients with co-morbid diabetes and hypertension . SUBJECTS AND METHODS A single-center r and omized controlled clinical trial compared two remote monitoring intensity levels ( low and high ) and usual care in patients with type 2 diabetes and hypertension being treated in primary care . Secondary outcomes assessed were knowledge ( diabetes , hypertension , medications ) , self-efficacy , adherence ( diabetes , medications ) , and patient perceptions of the intervention mode . RESULTS Knowledge scores improved in the high-intensity intervention group participants , but upon further analysis , we found the intervention effect was not mediated by gain in knowledge . No significant differences were found across the groups in self-efficacy , adherence , or patient perceptions of the intervention mode . CONCLUSIONS Home telehealth can enhance detection of key clinical symptoms that occur between regular physician visits . While our intervention improved glycemic and blood pressure control , the mechanism of the effect for this improvement was not clear Background Chronic illness is a significant driver of the global burden of disease and associated health care costs . People living with severe chronic illness are heavy users of acute hospital services ; better coordination of their care could potentially improve health outcomes while reducing hospital use . The Care Navigation trial will evaluate an in-hospital coordinated care intervention on health service use and quality of life in chronically ill patients . Methods / Design A r and omised controlled trial in 500 chronically ill patients presenting to the emergency department of a hospital in Western Sydney , Australia . Participants have three or more hospital admissions within a previous 12 month period and either aged ≥70 years ; or aged ≥45 years and of Aboriginal or Torres Strait Isl and er descent ; or aged ≥ 16 with a diagnosis of a respiratory or cardiology related illness . Patients are r and omised to either the coordinated care program ( Care Navigation ) , or to usual care . The Care Navigation program consists of dedicated nurses who conduct patient risk assessment s , oversee patient nursing while in hospital , and guide development of a care plan for the management of chronic illness after being discharged from hospital . These nurses also book community appointments and liaise with general practitioners . The main outcome variables are the number of emergency department re-presentations and hospital readmissions , and quality of life during a 24 month follow-up . Secondary outcomes are length of hospital stay , mortality , time to first hospital re-admission , time to first emergency department re-presentation , patient satisfaction , adherence to prescribed medications , amount and type of in-hospital referrals made for consultations and diagnostic testing , and the number and type of community health referrals . A process evaluation and economic analysis will be conducted alongside the r and omised trial . Discussion A trial of in-hospital care coordination may support recent evidence that engaging primary health services in care plans linked to multidisciplinary team support improves patient outcomes and reduces costs to the health system . This will inform local , national and international health policy . Trial registration Australia New Zeal and Clinical Trials Registry Integrated mental health and substance abuse treatment within an assertive community treatment ( ACT ) approach was compared to that within a st and ard case management approach for 223 patients with dual disorders over three years . ACT patients showed greater improvements on some measures of substance abuse and quality of life , but the groups were equivalent on most measures , including stable community days , hospital days , psychiatric symptoms , and remission of substance use disorder OBJECTIVES This study evaluated the effectiveness ( changes in health behaviors , health status , and health service utilization ) of a self-management program for chronic disease design ed for use with a heterogeneous group of chronic disease patients . It also explored the differential effectiveness of the intervention for subjects with specific diseases and comorbidities . METHODS The study was a six-month r and omized , controlled trial at community-based sites comparing treatment subjects with wait-list control subjects . Participants were 952 patients 40 years of age or older with a physician-confirmed diagnosis of heart disease , lung disease , stroke , or arthritis . Health behaviors , health status , and health service utilization , as determined by mailed , self-administered question naires , were measured . RESULTS Treatment subjects , when compared with control subjects , demonstrated improvements at 6 months in weekly minutes of exercise , frequency of cognitive symptom management , communication with physicians , self-reported health , health distress , fatigue , disability , and social/role activities limitations . They also had fewer hospitalizations and days in the hospital . No differences were found in pain/physical discomfort , shortness of breath , or psychological well-being . CONCLUSIONS An intervention design ed specifically to meet the needs of a heterogeneous group of chronic disease patients , including those with comorbid conditions , was feasible and beneficial beyond usual care in terms of improved health behaviors and health status . It also result ed in fewer hospitalizations and days of hospitalization Background The advantages of patient-held portable health files ( PHF ) and personal health records ( PHR ) , paper or electronic , are said to include improved health-care provider continuity-of-care and patient empowerment in maintaining health . Top-down approaches are favored by public sector government and health managers . Bottom-up approaches include systems developed directly by health-care providers , consumers and industry , implemented locally on devices carried by patient-consumers or shared via web-based portals . These allow individuals to access , manage and share their health information , and that of others for whom they are authorized , in a private , secure and confidential environment . Few medical record technologies have been evaluated in r and omized trials to determine whether there are important clinical benefits of these interventions . The COMMUNICATE trial will assess the acceptability and long-term clinical outcomes of an electronic and paper patient-held PHF . Methods / Design This is a 48-month , open-label pragmatic , superiority , parallel-group design r and omized controlled trial . Subjects ( n=792 ) will be r and omized in a 1:1:1 ratio to each of the trial arms : the electronic PHF added to usual care , the paper PHF added to usual care and usual care alone ( no PHF ) . Inclusion criteria include those 60 years or older living independently in the community , but who have two or more chronic medical conditions that require prescription medication and regular care by at least three medical practitioners ( general and specialist care ) . The primary objective is whether use of a PHF compared to usual care reduces a combined endpoint of deaths , overnight hospitalizations and blindly adjudicated serious out-of-hospital events . All primary analyses will be undertaken masked to r and omized arm allocation using intention-to-treat principles . Secondary outcomes include quality of life and health literacy improvements . Discussion Lack of blinding creates potential for bias in trial conduct and ascertainment of clinical outcomes . Mechanisms are provided to reduce bias , including balanced study contact with all participants , a blinded adjudication committee determining which out-of-hospital events are serious and endpoints that are objective ( overnight hospitalizations and mortality ) . The PRECIS tool provides a summary of the trial ’s design on the Pragmatic-Explanatory Continuum . Trial registration Registered with Clinical trials.gov ( identifier : NCT01082978 ) on 8 March 2010 Background Exercise reduced tolerance and breathlessness are common in the elderly and can result in substantial loss in functionality and health related quality of life . Heart failure ( HF ) and chronic obstructive pulmonary disease ( COPD ) are common underlying causes , but can be difficult to disentangle due to overlap in symptomatology . In addition , other potential causes such as obesity , anaemia , renal dysfunction and thyroid disorders may be involved . We aim to assess whether screening of frail elderly with reduced exercise tolerance leads to high detection rates of HF , COPD , or alternative diagnoses , and whether detection of these diseases would result in changes in patient management and increase in both functionality and quality of life . Methods / Design A cluster r and omized diagnostic trial . Primary care practice s are r and omized to the diagnostic-treatment strategy ( screening ) or care as usual . Patient population : Frail ( defined as having three or more chronic or vitality threatening diseases and /or receiving five or more drugs chronically during the last year ) community-dwelling persons aged 65 years and older selected from the electronic medical files of the participating general practitioners . Those with reduced exercise tolerance or moderate to severe dyspnoea ( ≥2 score on the Medical Research Counsel dyspnoea scale ) are included in the study .The diagnostic screening in the intervention group includes history taking , physical examination , electrocardiography , spirometry , blood tests , and echocardiography . Subsequently , participants with new diagnoses will be managed according to clinical guidelines . Participants in the control arm receive care as usual . All participants fill out health status and other relevant question naires at baseline and after 6 months of follow-up . Discussion This study will generate information on the yield of screening for previously unrecognized HF , COPD and other chronic diseases in frail elderly with reduced exercise tolerance and /or exercise induced dyspnoea . The cluster r and omized comparison will reveal whether this yield will result in subsequent improvements in functional health and /or health related quality of life . Trial registration Clinical Trials.gov BACKGROUND Patients with depression and poorly controlled diabetes , coronary heart disease , or both have an increased risk of adverse outcomes and high health care costs . We conducted a study to determine whether coordinated care management of multiple conditions improves disease control in these patients . METHODS We conducted a single-blind , r and omized , controlled trial in 14 primary care clinics in an integrated health care system in Washington State , involving 214 participants with poorly controlled diabetes , coronary heart disease , or both and coexisting depression . Patients were r and omly assigned to the usual-care group or to the intervention group , in which a medically supervised nurse , working with each patient 's primary care physician , provided guideline -based , collaborative care management , with the goal of controlling risk factors associated with multiple diseases . The primary outcome was based on simultaneous modeling of glycated hemoglobin , low-density lipoprotein ( LDL ) cholesterol , and systolic blood-pressure levels and Symptom Checklist-20 ( SCL-20 ) depression outcomes at 12 months ; this modeling allowed estimation of a single overall treatment effect . RESULTS As compared with controls , patients in the intervention group had greater overall 12-month improvement across glycated hemoglobin levels ( difference , 0.58 % ) , LDL cholesterol levels ( difference , 6.9 mg per deciliter [ 0.2 mmol per liter ] ) , systolic blood pressure ( difference , 5.1 mm Hg ) , and SCL-20 depression scores ( difference , 0.40 points ) ( P<0.001 ) . Patients in the intervention group also were more likely to have one or more adjustments of insulin ( P=0.006 ) , antihypertensive medications ( P<0.001 ) , and antidepressant medications ( P<0.001 ) , and they had better quality of life ( P<0.001 ) and greater satisfaction with care for diabetes , coronary heart disease , or both ( P<0.001 ) and with care for depression ( P<0.001 ) . CONCLUSIONS As compared with usual care , an intervention involving nurses who provided guideline -based , patient-centered management of depression and chronic disease significantly improved control of medical disease and depression . ( Funded by the National Institute of Mental Health ; Clinical Trials.gov number , NCT00468676 . ) Objectives To determine the effectiveness of collaborative care in reducing depression in primary care patients with diabetes or heart disease using practice nurses as case managers . Design A two-arm open r and omised cluster trial with wait-list control for 6 months . The intervention was followed over 12 months . Setting Eleven Australian general practice s , five r and omly allocated to the intervention and six to the control . Participants 400 primary care patients ( 206 intervention , 194 control ) with depression and type 2 diabetes , coronary heart disease or both . Intervention The practice nurse acted as a case manager identifying depression , review ing pathology results , lifestyle risk factors and patient goals and priorities . Usual care continued in the controls . Main outcome measure A five-point reduction in depression scores for patients with moderate-to-severe depression . Secondary outcome was improvements in physiological measures . Results Mean depression scores after 6 months of intervention for patients with moderate-to-severe depression decreased by 5.7±1.3 compared with 4.3±1.2 in control , a significant ( p=0.012 ) difference . ( The plus – minus is the 95 % confidence range . ) Intervention practice s demonstrated adherence to treatment guidelines and intensification of treatment for depression , where exercise increased by 19 % , referrals to exercise programmes by 16 % , referrals to mental health workers ( MHWs ) by 7 % and visits to MHWs by 17 % . Control- practice exercise did not change , whereas referrals to exercise programmes dropped by 5 % and visits to MHWs by 3 % . Only referrals to MHW increased by 12 % . Intervention improvements were sustained over 12 months , with a significant ( p=0.015 ) decrease in 10-year cardiovascular disease risk from 27.4±3.4 % to 24.8±3.8 % . A review of patients indicated that the study 's safety protocol s were followed . Conclusions TrueBlue participants showed significantly improved depression and treatment intensification , sustained over 12 months of intervention and reduced 10-year cardiovascular disease risk . Collaborative care using practice nurses appears to be an effective primary care intervention . Trial registration ACTRN12609000333213 ( Australia and New Zeal and Clinical Trials Registry ) Background Drug dosing errors are common in renal-impaired patients . Appropriate dosing adjustment and drug selection is important to ensure patients ’ safety and to avoid adverse drug effects and poor outcomes . There are few studies on this issue in community pharmacies . The aims of this study were , firstly , to determine the prevalence of dosing inadequacy as a consequence of renal impairment in patients over 65 taking 3 or more drug products who were being attended in community pharmacies and , secondly , to evaluate the effectiveness of the community pharmacist ’s intervention in improving dosing inadequacy in these patients when compared with usual care . Methods The study was carried out in 40 Spanish community pharmacies . The study had two phases : the first , with an observational , multicentre , cross sectional design , served to determine the dosing inadequacy , the drug-related problems per patient and to obtain the control group . The second phase , with a controlled study with historical control group , was the intervention phase . When dosing adjustments were needed , the pharmacists made recommendations to the physicians . A comparison was made between the control and the intervention group regarding the prevalence of drug dosing inadequacy and the mean number of drug-related problems per patient . Results The mean of the prevalence of drug dosing inadequacy was 17.5 % [ 95 % CI 14.6 - 21.5 ] in phase 1 and 15.5 % [ 95 % CI 14.5 - 16.6 ] in phase 2 . The mean number of drug-related problems per patient was 0.7 [ 95 % CI 0.5 - 0.8 ] in phase 1 and 0.50 [ 95 % CI 0.4 - 0.6 ] in phase 2 . The difference in the prevalence of dosing inadequacy between the control and intervention group before the pharmacists ’ intervention was 0.73 % [ 95 % CI ( −6.0 ) - 7.5 ] and after the pharmacists ’ intervention it was 13.5 % [ 95 % CI 8.0 - 19.5 ] ( p < 0.001 ) while the difference in the mean of drug-related problems per patient before the pharmacists ’ intervention was 0.05 [ 95 % CI ( -0.2 ) - 0.3 ] and following the intervention it was 0.5 [ 95 % CI 0.3 - 0.7 ] ( p < 0.001 ) . Conclusion A drug dosing adjustment service for elderly patients with renal impairment in community pharmacies can increase the proportion of adequate drug dosing , and improve the drug-related problems per patient . Collaborative practice with physicians can improve these results Objectives Rheumatoid arthritis ( RA ) patients are at an increased risk of developing comorbid conditions . A close monitoring of the disease targeting a status of low disease activity is associated with a better outcome . The aim of this trial was to evaluate the impact of a nurse-led programme on comorbidities and the impact of patient self- assessment of disease activity on the management of RA . Methods We enrolled 970 patients ( mean age 58 years , 79 % women ) in a prospect i ve , r and omised , controlled , open-label , 6-month trial . In the comorbidity group ( n=482 ) , the nurse checked comorbidities and sent the programme results to the attending physicians . In the self- assessment group ( n=488 ) , the nurse taught the patient how to calculate his/her Disease Activity Score which had to be reported on a booklet to be shared with the treating rheumatologist . The number of measures taken for comorbidities and the percentage of patients recording a change ( initiation , switch or increased dose ) in disease-modifying antirheumatic drugs ( DMARDs ) in the 6 months follow-up period of the study defined the outcomes of the trial . Results The number of measures taken per patient was statistically higher in the comorbidity group : 4.54±2.08 versus 2.65±1.57 ( p<0.001 ) ; incidence rate ratio : 1.78 ( 1.61–1.96 ) and DMARD therapy was changed more frequently in the self- assessment group : 17.2 % versus 10.9 % ( OR=1.70 ( 1.17 ; 2.49 ) , p=0.006 ) . Conclusions This study demonstrates the short-term benefit of a nurse-led programme on RA comorbidity management and the impact of patient self- assessment of disease activity on RA treatment intensification . Trial registration number NCT # 01315652 Background Depression is common among people with diabetes , negatively affecting quality of life , treatment adherence and diabetes outcomes . In routine clinical care , diabetes patients have limited access to mental health services and depression therefore often remains untreated . Web-based therapy could potentially be an effective way to improve the reach of psychological care for diabetes patients , at relatively low costs . This study seeks to test the effectiveness of a web-based self-help depression programme for people with diabetes and co-morbid depression . Methods / Design The effectiveness of a web-based self-help course for adults with diabetes with co-morbid depression will be tested in a r and omised trial , using a wait-list controlled design . The intervention consists of an 8-week , moderated self-help course that is tailored to the needs of persons living with diabetes and is offered on an individual basis . Participants receive feedback on their homework assignments by e-mail from their coach . We aim to include 286 patients ( 143/143 ) , as power analyses showed that this number is needed to detect an effect size of 0.35 , with measurements at baseline , directly after completing the web-based intervention and at 1 , 3 , 4 and 6 months follow-up . Patients in the control condition are placed on a waiting list , and follow the course 12 weeks after r and omisation . Primary outcomes are depressive symptoms and diabetes-specific emotional distress . Secondary outcomes are satisfaction with the course , perceived health status , self-care behaviours , glycaemic control , and days in bed/absence from work . Question naires are administered via the Internet . Discussion The intervention being trialled is expected to help improve mood and reduce diabetes-specific emotional distress in diabetes patients with depression , with subsequent beneficial effects on diabetes self-care and glycaemic outcomes . When proven efficacious , the intervention could be disseminated to reach large groups of patients with diabetes and concurrent depressive symptoms . Trial registration Current Controlled Trials IS RCT Background The percentage of older and chronically ill workers is increasing rapidly in the US and in many other countries , but few interventions are available to help employees overcome the workplace challenges of chronic pain and other physical health conditions . While most workers are eligible for job accommodation and disability compensation benefits , other workplace strategies might improve individual-level coping and problem solving to prevent work disability . In this study , we hypothesize that an employer-sponsored group intervention program employing self-management principles may improve worker engagement and reduce functional limitation associated with chronic disorders . Methods In a r and omized controlled trial ( RCT ) , workers participating in an employer-sponsored self-management group intervention will be compared with a no-treatment ( wait list ) control condition . Volunteer employees ( n = 300 ) will be recruited from five participating employers and r and omly assigned to intervention or control . Participants in the intervention arm will attend facilitated group workshop sessions at work ( 10 hours total ) to explore methods for improving comfort , adjusting work habits , communicating needs effectively , applying systematic problem solving , and dealing with negative thoughts and emotions about work . Work engagement and work limitation are the principal outcomes . Secondary outcomes include fatigue , job satisfaction , self-efficacy , turnover intention , sickness absence , and health care utilization . Measurements will be taken at baseline , 6- , and 12-month follow-up . A process evaluation will be performed alongside the r and omized trial . Discussion This study will be most relevant for organizations and occupational setting s where some degree of job flexibility , leeway , and decision-making autonomy can be afforded to affected workers . The study design will provide initial assessment of a novel workplace approach and to underst and factors affecting its feasibility and effectiveness . Trial registration Clinical trials.gov : NCT01978392 ( Issued November 6 , 2013 OBJECTIVE The authors ' goal was to compare the efficacy of a manualized cognitive behavior therapy that addresses both posttraumatic stress disorder ( PTSD ) and substance abuse ( seeking safety ) with a manualized cognitive behavior therapy that addresses only substance abuse ( relapse prevention ) and with st and ard community care for the treatment of comorbid posttraumatic stress disorder ( PTSD ) and substance use disorder . METHOD One hundred seven women from an urban , low-income population who had comorbid PTSD and substance use disorder were r and omly assigned to receive the two kinds of cognitive behavior therapy or received st and ard community treatment . Participants were recruited from both community and clinical population s and evaluated with structured clinical instruments . Forty-one women received seeking safety therapy , 34 received relapse prevention therapy , and 32 received st and ard community care . RESULTS At the end of 3 months of treatment , participants in both cognitive behavior therapy conditions had significant reductions in substance use , PTSD , and psychiatric symptoms , but community care participants worsened over time . Both groups receiving cognitive behavior therapy sustained greater improvement in substance use and PTSD symptoms at 6-month and 9-month follow-ups than subjects in the community care group . CONCLUSIONS Seeking safety and relapse prevention are efficacious short-term treatments for low-income urban women with PTSD , substance use disorder , and other psychiatric symptoms Background Many patients with chronic disease do not reach goals for management of their conditions . Self-management support provided by medical assistant health coaches within the clinical setting may help to improve clinical outcomes , but most studies to date lack statistical power or method ological rigor . Barriers to large scale implementation of the medical assistant coach model include lack of clinician buy-in and the absence of a business model that will make medical assistant health coaching sustainable . This study will add to the evidence base by determining the effectiveness of health coaching by medical assistants on clinical outcomes and patient self-management , by assessing the impact of health coaching on the clinician experience , and by examining the costs and potential savings of health coaching . Methods / Design This r and omized controlled trial will evaluate the effectiveness of clinic-based medical assistant health coaches to improve clinical outcomes and self-management skills among low-income patients with uncontrolled type 2 diabetes , hypertension , or hyperlipidemia . A total of 441 patients from two San Francisco primary care clinics have been enrolled and r and omized to receive a health coach ( n = 224 ) or usual care ( n = 217 ) . Patients participating in the health coaching group will receive coaching for 12 months from medical assistants trained as health coaches . The primary outcome is a change in hemoglobin A1c , systolic blood pressure , or LDL cholesterol among patients with uncontrolled diabetes , hypertension and hyperlipidemia , respectively . Self-management behaviors , perceptions of the health care team and clinician , BMI , and chronic disease self-efficacy will be measured at baseline and after 12 months . Clinician experience is being assessed through surveys and qualitative interviews . Cost and utilization data will be analyzed through cost-predictive models . Discussion Medical assistants are an untapped re source to provide self-management support for patients with uncontrolled chronic disease . Having successfully completed recruitment , this study is uniquely poised to assess the effectiveness of the medical assistant health coaching model , to describe barriers and facilitators to implementation , and to develop a business case for sustainability . Trial registration Clinical Trials.gov identifier Aim To examine the effects of a nurse-led case management programme for hospital-discharged older adults with co-morbidities . Background The most significant chronic conditions today involve diseases of the cardiovascular , respiratory , endocrine and renal systems . Previous studies have suggested that a nurse-led case management approach using either telephone follow-ups or home visits was able to improve clinical and patient outcomes for patients having a single , chronic disease , while the effects for older patients having at least two long-term conditions are unknown . A self-help programme using motivation and empowerment approaches is the framework of care in the study . Design R and omized controlled trial . Method The study was conducted from 2010–2012 . Older patients having at least two chronic diseases were included for analysis . The participants were r and omized into three arms : two study groups and one control group . Data were collected at baseline and at 4 and 12 weeks later . Results Two hundred and eighty-one patients completed the study . The interventions demonstrated significant differences in hospital readmission rates within 84 days post discharge . The two intervention groups had lower readmission rates than the control group . Patients in the two study arms had significantly better self-rated health and self-efficacy . There was significant difference between the groups in the physical composite score , but no significant difference in mental component score in SF-36 scale . Conclusion The postdischarge interventions led by the nurse case managers on self-management of disease using the empowerment approach were able to provide effective clinical and patient outcomes for older patients having co-morbidities BACKGROUND Optimal utilization of health care re sources for patients with chronic conditions is an increasing focus of health care policy research ers and clinicians . Kidney disease , diabetes ( DM ) and cardiovascular disease ( CVD ) often coexist within one individual , but current systems are design ed to manage individual conditions . We sought to examine if streamlining medical care of complex patients ( two or more conditions ) is associated with similar , worse or improved outcomes using a r and omized controlled study design . METHODS Patients attending a kidney care clinic ( KCC ) and at least one other specialty clinic of interest ( DM , CVD ) were r and omly assigned to either the ' combined clinic ( CC ) ' arm , where re sources from all three were integrated into one clinic , or to the ' st and ard care ' arm with continued attendance at multiple specialty clinics ( MC ) , including the KCC . The primary outcome was hospitalization rate and sample size was calculated based on non-inferiority . RESULTS Of 150 subjects enrolled , 11 subjects exited before study commencement : 139 remained for final analysis . Other than older age in the MC group ( P = 0.009 ) , the demographics were comparable . Hospitalization rates were not different ( 95 % CI for the difference : 0.013 - 0.207 ; P = 0.03 ) . Similar proportions in each group achieved clinical and laboratory targets . Mortality ( 13 % ) and dialysis ( 32 % ) rates were the same between groups . Differences in the cost of clinic visits alone were $ 86,400 per year in favor of the CC . CONCLUSIONS Medical care of complex patients may be delivered in a single combined specialty clinic as compared to multiple disease specific clinics without compromising patient care or important health outcomes , with demonstrable outpatient costs savings BACKGROUND regular medication review has been recommended for those over 75 and those on multiple drug therapy . Pharmacists are a potential source of assistance in review ing medication . Evidence of the benefits of this process is needed . OBJECTIVE to study the effect of medication review led by a pharmacist on resolution of pharmaceutical care issues , medicine costs , use of health and social services and health-related quality of life . DESIGN r and omized , controlled trial . SETTING general medical practice s in the Grampian region of Scotl and . SUBJECTS patients aged at least 65 years , with at least two chronic disease states who were taking at least four prescribed medicines regularly . METHODS pharmacists review ed the drug therapy of 332 patients , using information obtained from the practice computer , medical records and patient interviews . In 168 patients , a pharmaceutical care plan was then drawn up and implemented . The 164 control patients continued to receive normal care . All outcome measures were assessed at baseline and after 3 months . RESULTS all patients had at least two pharmaceutical care issues at baseline . Half of these were identified from the prescription record , the rest from notes and patient interview . Of all the issues , 21 % were resolved by information found in notes and 8.5 % by patient interview . General practitioners agreed with 96 % of all care issues documented on the care plans in the intervention group . At the time of follow-up , 70 % of the remaining care issues had been resolved in the intervention group , while only 14 % had been resolved in the control group . There were no changes in medicine costs or health-related quality of life in either group . There were small increases in contacts with health-care professionals and slightly fewer hospital admissions among the intervention group than the control group . CONCLUSIONS pharmacist-led medication review has the capacity to identify and resolve pharmaceutical care issues and may have some impact on the use of other health services OBJECTIVES To test the efficacy of a multicomponent intervention to reduce functional difficulties , fear of falling , and home hazards and enhance self-efficacy and adaptive coping in older adults with chronic conditions . DESIGN A prospect i ve , two-group , r and omized trial . Participants were r and omized to a treatment group or no-treatment group . SETTING Urban community-living older people . PARTICIPANTS Three hundred nineteen community-living adults aged 70 and older who reported difficulty with one or more activities of daily living . INTERVENTION Occupational and physical therapy sessions involving home modifications and training in their use ; instruction in strategies of problem-solving , energy conservation , safe performance , and fall recovery techniques ; and balance and muscle strength training . MEASUREMENTS Outcome measures included self-rated functional difficulties with ambulation , instrumental activities of daily living , activities of daily living , fear of falling , confidence performing daily tasks , and use of adaptive strategies . Observations of home hazards were also conducted . RESULTS At 6 months , intervention participants had less difficulty than controls with instrumental activities of daily living ( P=.04 , 95 % confidence interval (CI)=-0.28 - 0.00 ) and activities of daily living ( P=.03 , 95 % CI=-0.24 to -0.01 ) , with largest reductions in bathing ( P=.02 , 95 % CI=-0.52 to -0.06 ) and toileting ( P=.049 , 95 % CI=-0.35 - 0.00 ) . They also had greater self-efficacy ( P=.03 , 95 % CI=0.02 - 0.27 ) , less fear of falling ( P=.001 , 95 % CI=0.26 - 0.96 ) , fewer home hazards ( P=.05 , 95 % CI=-3.06 - 0.00 ) , and greater use of adaptive strategies ( P=.009 , 95 % CI=0.03 - 0.22 ) . Benefits were sustained at 12 months for most outcomes . CONCLUSION A multicomponent intervention targeting modifiable environmental and behavioral factors results in life quality improvements in community-dwelling older people who had functional difficulties , with most benefits retained over a year Background We investigated the effectiveness of an occupational therapy led self-management support programme , OPTIMAL , design ed to address the challenges of living with multiple chronic conditions or multimorbidity in a primary care setting . Methods Pragmatic feasibility r and omised controlled trial including fifty participants with multimorbidity recruited from family practice and primary care setting s. OPTIMAL is a six-week community-based programme , led by occupational therapy facilitators and focuses on problems associated with managing multimorbidity . The primary outcome was frequency of activity participation . Secondary outcomes included self-perception of , satisfaction with and ability to perform daily activities , independence in activities of daily living , anxiety and depression , self-efficacy , health-related quality of life , self-management support , healthcare utilisation and individualised goal attainment . Outcomes were collected within two weeks of intervention completion . Results There was a significant improvement in frequency of activity participation , measured using the Frenchay Activities Index , for the intervention group compared to the control group ( Adjusted Mean Difference at follow up 4.22 . 95 % Confidence Interval 1.59 - 6.85 ) . There were also significant improvements in perceptions of activity performance and satisfaction , self-efficacy , independence in daily activities and quality of life . Additionally , the intervention group demonstrated significantly higher levels of goal achievement , following the intervention . No significant differences were found between the two groups in anxiety , depression , self-management scores or healthcare utilisation . Conclusions OPTIMAL significantly improved frequency of activity participation , self-efficacy and quality of life for patients with multimorbidity . Further work is required to test the sustainability of these effects over time but this study indicates that it is a promising intervention that can be delivered in primary care and community setting s . Trial registration Trial Number : IS RCT Background The intervention ; “ Continuum of Care for Frail Older People ” , was design ed to create an integrated continuum of care from the hospital emergency department through the hospital and back to the older person ’s own home . The aim of this study is to evaluate the effects of the intervention on functional ability in terms of activities of daily living ( ADL ) . Methods The study is a non-blinded controlled trial with participants r and omised to either the intervention group or a control group with follow-ups at three- , six- and 12 months . The intervention involved collaboration between a nurse with geriatric competence at the emergency department , the hospital wards and a multi-professional team for care and rehabilitation of the older people in the municipality with a case manager as the hub . Older people who sought care at the emergency department at Sahlgrenska University Hospital/Mölndal and who were discharged to their own homes in the municipality of Mölndal , Sweden were asked to participate . Inclusion criteria were age 80 and older or 65 to 79 with at least one chronic disease and dependent in at least one ADL . Analyses were made on the basis of the intention-to-treat principle . Outcome measures were ADL independence and eight frailty indicators . These were analysed , using Chi-square and odds ratio ( OR ) . Results A total of 161 participated in the study , 76 persons allocated to the control group and 85 to the intervention group were analysed throughout the study . There were no significant differences between the groups with regards to change in frailty compared to baseline at any follow-up . At both the three- and twelve-month follow-ups the intervention group had doubled their odds for improved ADL independence compared to the control ( OR 2.37 , 95 % CI ; 1.20 – 4.68 ) and ( 2.04 , 95 % CI ; 1.03 – 4.06 ) respectively . At six months the intervention group had halved their odds for decreased ADL independence ( OR 0.52 , 95 % CI ; 0.27 – 0.98 ) compared to the control group . Conclusions The intervention has the potential to reduce dependency in ADLs , a valuable benefit both for the individual and for society . Trial registration Clinical Trials.gov : PURPOSE We wanted to examine whether integrating depression treatment into care for hypertension improved adherence to antidepressant and antihypertensive medications , depression outcomes , and blood pressure control among older primary care patients . METHODS Older adults prescribed pharmacotherapy for depression and hypertension from physicians at a large primary care practice in West Philadelphia were r and omly assigned to an integrated care intervention or usual care . Outcomes were assessed at baseline , 2 , 4 , and 6 weeks using the Center for Epidemiologic Studies Depression Scale ( CES-D ) to assess depression , an electronic monitor to measure blood pressure , and the Medication Event Monitoring System to assess adherence . RESULTS In all , 64 participants aged 50 to 80 years participated . Participants in the integrated care intervention had fewer depressive symptoms ( CES-D mean scores , intervention 9.9 vs usual care 19.3 ; P < .01 ) , lower systolic blood pressure ( intervention 127.3 mm Hg vs usual care 141.3 mm Hg ; P < .01 ) , and lower diastolic blood pressure ( intervention 75.8 mm Hg vs usual care 85.0 mm Hg ; P < .01 ) compared with participants in the usual care group at 6 weeks . Compared with the usual care group , the proportion of participants in the intervention group who had 80 % or greater adherence to an antidepressant medication ( intervention 71.9 % vs usual care 31.3 % ; P < .01 ) and to an antihypertensive medication ( intervention 78.1 % vs usual care 31.3 % ; P < .001 ) was greater at 6 weeks . CONCLUSION A pilot , r and omized controlled trial integrating depression and hypertension treatment was successful in improving patient outcomes . Integrated interventions may be more feasible and effective in real-world practice s , where there are competing dem and s for limited re sources Both congestive heart failure and chronic obstructive pulmonary disease are more common among Māori than non-Māori people , and the cultural acceptability of home-based remote monitoring technology has not been tested . We conducted a 12-month pilot trial of home telemonitoring . Patients were r and omly assigned to the control and intervention groups . Patients in the control group showed no clear differences in quality of life at the end of the trial . The telehealth group showed a consistent trend towards improved quality of life on several instruments , including the SF-36 , the St George Respiratory Question naire and the K10 question naire ; the improvement in the latter was significant . Hospitalizations were reduced in both the control ( −19 % ) and telehealth group ( −25 % ) . Patient interviews indicated that the technology was acceptable to most patients and their families , including the Māori . The results from the pilot trial suggest that wider implementation with a cost benefit evaluation could be worthwhile Introduction Chronic diseases and falls substantially contribute to morbidity/mortality among seniors , causing this population to frequently seek emergency medical care . Research suggests the paramedic role can be successfully exp and ed to include community-based health promotion and prevention . This study implements a community paramedicine programme targeting seniors in subsidised housing , a high-risk population and frequent users of emergency medical services ( EMS ) . The aims are to reduce EMS calls , improve health outcomes and healthcare utilisation . Methods / analysis This is a pragmatic clustered r and omised control trial in four communities across Ontario , Canada . Within each , four to eight seniors ’ apartment buildings will be paired and within each pair one building will be r and omly assigned to receive the Community Health Assessment Programme through EMS ( CHAP-EMS ) intervention , while the other building receives no intervention . During the 1-year intervention , paramedics will run weekly sessions in a common area of the building , assessing risk factors for cardiovascular disease , diabetes and falls ; providing health education and referrals to community programmes ; and communicating results to the participant 's primary physician . The primary outcomes are rate of emergency calls per 100 residents , change in blood pressure and change in Canadian Diabetes Risk ( CANRISK ) score , as collected by the local EMS and study data bases . The secondary outcomes are change in health behaviours , measured using a preintervention and postintervention survey and healthcare utilisation , available through administrative data bases . Analysis will mainly consist of descriptive statistics and generalised estimating equations , including subgroup cluster analysis . Ethics/dissemination This study is approved by the Hamilton Integrated Research Ethics Board and will follow the Tri-Council Policy Statement . Findings will be disseminated through reports to local stakeholders , publication in peer- review ed journals and conference presentations . Trial registration number NCT02152891 Background With an ageing population in most Western countries , people are living longer but often with one or more chronic physical health problems . Older people in physically poor health are at greater risk of developing clinical depression . Cognitive Behavioural Therapy ( CBT ) and Problem Solving Therapy ( PST ) have both been found to be efficacious in treating late-life depression , however patients with “ multi-morbidity ” ( i.e. more than one chronic condition ) are often excluded from these trials . The aim of this study is to compare the efficacy of CBT and PST in treating older adults who have one or more chronic physical health conditions and a diagnosable depressive disorder . This study will be the first to explicitly target the treatment of depression in older people in primary care setting s presenting with a range of health problems using behavioural interventions . Methods / design The PROMISE-D study is a r and omised controlled trial of two evidence -based treatments for late-life major or minor depression for patients who also have at least one co-morbid chronic health problem . Participants will be r and omised to two active interventions ( PST or CBT ) or enhanced treatment-as-usual ( E-TAU ) . Primary outcomes will be depression diagnostic status and severity of depression ( according to the Hamilton Depression Rating Scale and the Geriatric Depression Scale ) . Secondary outcomes will be anxiety severity , quality of life and health care utilisation . Assessment s will be conducted by a research er who remains blind to the patient ’s treatment allocation and will be conducted pre and post-treatment and at six and 12 months follow-up . Health care utilisation will be assessed throughout a two year period following entry to the trial . Executive function , rumination and emotion regulation will also be measured to determine the impact of these factors on treatment response in two treatment groups . Discussion Multi-morbidity , the experience of two or more chronic health problems , is becoming an increasing problem internationally , particularly amongst the elderly . Evidence -based psychological treatments exist for late-life depression and these have been shown to be effective for participants with individual health problems and depression . However , there are no studies that have compared the two leading psychotherapies shown to be effective in the treatment of late-life depression . In addition , many trials of psychotherapy with older adults exclude those with multi-morbidity . Hence , this trial will confirm whether CBT and PST are efficacious in the treatment of depression in the context of complex medical needs and determine which of these two interventions is most efficacious . Trial registration Background This paper presents the evaluation of “ Moving On ” , a generic self-management program for people with a chronic illness developed by Arthritis NSW . The program aims to help participants identify their need for behaviour change and acquire the knowledge and skills to implement changes that promote their health and quality of life . Method A prospect i ve pragmatic r and omised controlled trial involving two group programs in community setting s : the intervention program ( Moving On ) and a control program ( light physical activity ) . Participants were recruited by primary health care providers across the north-west region of metropolitan Sydney , Australia between June 2009 and October 2010 . Patient outcomes were self-reported via pre- and post-program surveys completed at the time of enrolment and sixteen weeks after program commencement . Primary outcomes were change in self-efficacy ( Self-efficacy for Managing Chronic Disease 6-Item Scale ) , self-management knowledge and behaviour and perceived health status ( Self-Rated Health Scale and the Health Distress Scale ) . Results A total of 388 patient referrals were received , of whom 250 ( 64.4 % ) enrolled in the study . Three patients withdrew prior to allocation . 25 block r and omisations were performed by a statistician external to the research team : 123 patients were allocated to the intervention program and 124 were allocated to the control program.97 ( 78.9 % ) of the intervention participants commenced their program . The overall attrition rate of 40.5 % included withdrawals from the study and both programs . 24.4 % of participants withdrew from the intervention program but not the study and 22.6 % withdrew from the control program but not the study . A total of 62 patients completed the intervention program and follow-up evaluation survey and 77 patients completed the control program and follow-up evaluation survey . At 16 weeks follow-up there was no significant difference between intervention and control groups in self-efficacy ; however , there was an increase in self-efficacy from baseline to follow-up for the intervention participants ( t=−1.948 , p=0.028 ) . There were no significant differences in self-rated health or health distress scores between groups at follow-up , with both groups reporting a significant decrease in health distress scores . There was no significant difference between or within groups in self-management knowledge and stage of change of behaviours at follow-up . Intervention group attenders had significantly higher physical activity ( t=−4.053 , p=0.000 ) and nutrition scores ( t=2.315 , p= 0.01 ) at follow-up ; however , these did not remain significant after adjustment for covariates . At follow-up , significantly more participants in the control group ( 20.8 % ) indicated that they did not have a self-management plan compared to those in the intervention group ( 8.8 % ) ( X2=4.671 , p=0.031 ) . There were no significant changes in other self-management knowledge areas and behaviours after adjusting for covariates at follow-up . Conclusions The study produced mixed findings . Differences between groups as allocated were diluted by the high proportion of patients not completing the program . Further monitoring and evaluation are needed of the impact and cost effectiveness of the program . Trial registration Australian New Zeal and Clinical Trials Registry : Background Depression and diabetes cause significant burden for patients and the healthcare system and , when co-occurring , result in poorer self-care behaviors and worse glycemic control than for either condition alone . However , the clinical management of these comorbid conditions is complicated by a host of patient , provider , and system-level barriers that are especially problematic for patients in rural locations . Patient-centered medical homes provide an opportunity to integrate mental and physical health care to address the multifaceted needs of complex comorbid conditions . Presently , there is a need to not only develop robust clinical interventions for complex medically ill patients but also to find feasible ways to embed these interventions into the frontlines of existing primary care practice s. Methods / design This r and omized controlled trial uses a hybrid effectiveness-implementation design to evaluate the Healthy Outcomes through Patient Empowerment ( HOPE ) intervention , which seeks to simultaneously address diabetes and depression for rural veterans in Southeast Texas . A total of 242 Veterans with uncontrolled diabetes and comorbid symptoms of depression will be recruited and r and omized to either the HOPE intervention or to a usual-care arm . Participants will be evaluated on a host of diabetes and depression-related measures at baseline and 6- and 12-month follow-up . The trial has two primary goals : 1 ) to examine the effectiveness of the intervention on both physical ( diabetes ) and emotional health ( depression ) outcomes and 2 ) to simultaneously pilot test a multifaceted implementation strategy design ed to increase fidelity and utilization of the intervention by coaches interfacing within the primary care setting . Discussion This ongoing blended effectiveness-implementation design holds the potential to advance the science and practice of caring for complex medically ill patients within the constraints of a busy patient-centered medical home . Trial registration Behavioral Activation Therapy for Rural Veterans with Diabetes and Depression : NCT01572389 Background Co-morbid major depression is a significant problem among patients with type 2 diabetes mellitus and /or coronary heart disease and this negatively impacts quality of life . Subthreshold depression is the most important risk factor for the development of major depression . Given the highly significant association between depression and adverse health outcomes and the limited capacity for depression treatment in primary care , there is an urgent need for interventions that successfully prevent the transition from subthreshold depression into a major depressive disorder . Nurse led stepped-care is a promising way to accomplish this . The aim of this study is to evaluate the cost-effectiveness of a nurse-led indicated stepped-care program to prevent major depression among patients with type 2 diabetes mellitus and /or coronary heart disease in primary care who also have subthreshold depressive symptoms . Methods / design An economic evaluation will be conducted alongside a cluster-r and omized controlled trial in approximately thirty general practice s in the Netherl and s. R and omization takes place at the level of participating practice nurses . We aim to include 236 participants who will either receive a nurse-led indicated stepped-care program for depressive symptoms or care as usual . The stepped-care program consists of four sequential but flexible treatment steps : 1 ) watchful waiting , 2 ) guided self-help treatment , 3 ) problem solving treatment and 4 ) referral to the general practitioner . The primary clinical outcome measure is the cumulative incidence of major depressive disorder as measured with the Mini International Neuropsychiatric Interview . Secondary outcomes include severity of depressive symptoms , quality of life , anxiety and physical outcomes . Costs will be measured from a societal perspective and include health care utilization , medication and lost productivity costs . Measurements will be performed at baseline and 3 , 6 , 9 and 12 months . Discussion The intervention being investigated is expected to prevent new cases of depression among people with type 2 diabetes mellitus and /or coronary heart disease and subthreshold depression , with subsequent beneficial effects on quality of life , clinical outcomes and health care costs . When proven cost-effective , the program provides a viable treatment option in the Dutch primary care system . Trial registration Dutch Trial Register BACKGROUND Efficiently caring for frail older adults will become an increasingly important part of health care reform;telemonitoring within homes may be an answer to improve outcomes . This study sought to assess differences in hospitalizations and emergency department ( ED ) visits among older adults using telemonitoring vs usual care . METHODS A r and omized controlled trial was performed among adults older than 60 years at high risk for rehospitalization . Participants were r and omized to telemonitoring ( with daily input ) or to patient-driven usual care . Telemonitoring was accomplished by daily biometrics , symptom reporting , and videoconference . The primary outcome was a composite end point of hospitalizations and ED visits in the 12 months following enrollment . Secondary end points included hospitalizations , ED visits , and total hospital days . Intent-to-treat analysis was performed . RESULTS Two hundred five participants were enrolled , with a mean age of 80.3 years . The primary outcome of hospitalizations and ED visits did not differ between the telemonitoring group ( 63.7 % ) and the usual care group(57.3 % ) ( P=.35 ) . No differences were observed in secondary end points , including hospitalizations , ED visits , and total hospital days . No significant group differences in hospitalizations and ED visits were found between the pre-enrollment period vs the post-enrollment period . Mortality was higher in the telemonitoring group (14.7%)than in the usual care group ( 3.9 % ) ( P=.008 ) . CONCLUSIONS Among older patients , telemonitoring did not result in fewer hospitalizations or ED visits . Secondary outcomes demonstrated no significant differences between the telemonitoring group and the usual care group . The cause of greater mortality in the telemonitoring group is unknown Background When depression accompanies diabetes , it complicates treatment , portends worse outcomes and increases health care costs . A collaborative care case-management model , previously tested in an urban managed care organization in the US , achieved significant reduction of depressive symptoms , improved diabetes disease control and patient-reported outcomes , and saved money . While impressive , these findings need to be replicated and extended to other healthcare setting s. Our objective is to comprehensively evaluate a collaborative care model for comorbid depression and type 2 diabetes within a Canadian primary care setting . Methods / design We initiated the TeamCare model in four Primary Care Networks in Northern Alberta . The intervention involves a nurse care manager guiding patient-centered care with family physicians and consultant physician specialists to monitor progress and develop tailored care plans . Patients eligible for the intervention will be identified using the Patient Health Question naire-9 as a screen for depressive symptoms . Care managers will then guide patients through three phases : 1 ) improving depressive symptoms , 2 ) improving blood glucose , blood pressure and cholesterol , and 3 ) improving lifestyle behaviors . We will employ the RE- AIM framework for a comprehensive and mixed- methods approach to our evaluation . Effectiveness will be assessed using a controlled “ on-off ” trial design , whereby eligible patients would be alternately enrolled in the TeamCare intervention or usual care on a monthly basis . All patients will be assessed at baseline , 6 and 12 months . Our primary analyses will be based on changes in two outcomes : depressive symptoms , and a multivariable , scaled marginal model for the combined outcome of global disease control ( i.e. , A1c , systolic blood pressure , LDL cholesterol ) . Our planned enrolment of 168 patients will provide greater than 80 % power to observe clinical ly important improvements in all measured outcomes . Direct costing of all intervention components and measurement of all health care utilization using linked administrative data bases will be used to determine the cost-effectiveness of the intervention relative to usual care . Discussion Our comprehensive evaluation will generate evidence to reliability , effectiveness and sustainability of this collaborative care model for patients with chronic diseases and depression . Trials registration Clintrials.gov Identifier : Objective To test the effectiveness of an integrated collaborative care model for people with depression and long term physical conditions . Design Cluster r and omised controlled trial . Setting 36 general practice s in the north west of Engl and . Participants 387 patients with a record of diabetes or heart disease , or both , who had depressive symptoms ( ≥10 on patient health question aire-9 ( PHQ-9 ) ) for at least two weeks . Mean age was 58.5 ( SD 11.7 ) . Participants reported a mean of 6.2 ( SD 3.0 ) long term conditions other than diabetes or heart disease ; 240 ( 62 % ) were men ; 360 ( 90 % ) completed the trial . Interventions Collaborative care included patient preference for behavioural activation , cognitive restructuring , grade d exposure , and /or lifestyle advice , management of drug treatment , and prevention of relapse . Up to eight sessions of psychological treatment were delivered by specially trained psychological wellbeing practitioners employed by Improving Access to Psychological Therapy services in the English National Health Service ; integration of care was enhanced by two treatment sessions delivered jointly with the practice nurse . Usual care was st and ard clinical practice provided by general practitioners and practice nurses . Main outcome measures The primary outcome was reduction in symptoms of depression on the self reported symptom checklist-13 depression scale ( SCL-D13 ) at four months after baseline assessment . Secondary outcomes included anxiety symptoms ( generalised anxiety disorder 7 ) , self management ( health education impact question naire ) , disability ( Sheehan disability scale ) , and global quality of life ( WHOQOL-BREF ) . Results 19 general practice s were r and omised to collaborative care and 20 to usual care ; three practice s withdrew from the trial before patients were recruited . 191 patients were recruited from practice s allocated to collaborative care , and 196 from practice s allocated to usual care . After adjustment for baseline depression score , mean depressive scores were 0.23 SCL-D13 points lower ( 95 % confidence interval −0.41 to −0.05 ) in the collaborative care arm , equal to an adjusted st and ardised effect size of 0.30 . Patients in the intervention arm also reported being better self managers , rated their care as more patient centred , and were more satisfied with their care . There were no significant differences between groups in quality of life , disease specific quality of life , self efficacy , disability , and social support . Conclusions Collaborative care that incorporates brief low intensity psychological therapy delivered in partnership with practice nurses in primary care can reduce depression and improve self management of chronic disease in people with mental and physical multimorbidity . The size of the treatment effects were modest and were less than the prespecified effect but were achieved in a trial run in routine setting s with a deprived population with high levels of mental and physical multimorbidity . Trial registration IS RCT N80309252 BACKGROUND Adverse events related to drugs occur frequently among in patients , and many of these events are preventable . However , few data are available on adverse drug events among out patients . We conducted a study to determine the rates , types , severity , and preventability of such events among out patients and to identify preventive strategies . METHODS We performed a prospect i ve cohort study , including a survey of patients and a chart review , at four adult primary care practice s in Boston ( two hospital-based and two community-based ) , involving a total of 1202 out patients who received at least one prescription during a four-week period . Prescriptions were computerized at two of the practice s and h and written at the other two . RESULTS Of the 661 patients who responded to the survey ( response rate , 55 percent ) , 162 had adverse drug events ( 25 percent ; 95 percent confidence interval , 20 to 29 percent ) , with a total of 181 events ( 27 per 100 patients ) . Twenty-four of the events ( 13 percent ) were serious , 51 ( 28 percent ) were ameliorable , and 20 ( 11 percent ) were preventable . Of the 51 ameliorable events , 32 ( 63 percent ) were attributed to the physician 's failure to respond to medication-related symptoms and 19 ( 37 percent ) to the patient 's failure to inform the physician of the symptoms . The medication classes most frequently involved in adverse drug events were selective serotonin-reuptake inhibitors ( 10 percent ) , beta-blockers ( 9 percent ) , angiotensin-converting-enzyme inhibitors ( 8 percent ) , and nonsteroidal antiinflammatory agents ( 8 percent ) . On multivariate analysis , only the number of medications taken was significantly associated with adverse events . CONCLUSIONS Adverse events related to drugs are common in primary care , and many are preventable or ameliorable . Monitoring for and acting on symptoms are important . Improving communication between out patients and providers may help prevent adverse events related to drugs Background Chronic Obstructive Pulmonary Disease ( COPD ) and asthma are common chronic diseases that are frequently accompanied by depression and /or anxiety . However , symptoms of depression and anxiety are often not recognized and therefore not treated . Currently , only a few studies have tested new clinical approaches that could improve the treatment of co-morbid depression and anxiety in these groups of patients . Methods / design The present r and omized controlled study will be conducted within the framework of PoZoB ( Praktijk Ondersteuning Zuid-Oost Brabant ) , a large primary care organization in the Netherl and s. Patients with asthma/ COPD and co-morbid anxiety/depression will be included in order to test the effectiveness of a disease management approach to treat these co-morbid disorders . Important elements of this approach are : 1 ) systematic screening to improve detection of anxiety and depression 2 ) treatment in case of positive screening 3 ) monitoring of anxiety and depression 4 ) intensified treatment in case of non-remission ( stepped care ) . Discussion The present study is a large primary care study on the treatment of co-morbid depression and anxiety in patients with asthma and COPD . Strengths of this study are its r and omized design , the focus on implementation in primary care and the fact that it applies the latest findings on the treatment of depression and anxiety . First results are expected in 2012/2013.Trial registration Netherl and s Trial Register ( NTR ) : Background Multimorbidity has a negative impact on health-related quality of life ( HRQL ) . Previous studies included only a limited number of conditions . In this study , we analyse the impact of a large number of conditions on HRQL in multimorbid patients without pre selecting particular diseases . We also explore the effects of these conditions on the specific dimensions of HRQL . Material s and Methods This analysis is based on a multicenter , prospect i ve cohort study of 3189 multimorbid primary care patients aged 65 to 85 . The impact of 45 conditions on HRQL was analysed . The severity of the conditions was rated . The EQ-5D , consisting of 5 dimensions and a visual-analogue-scale ( EQ VAS ) , was employed . Data were analysed using multiple ordinary least squares and multiple logistic regressions . Multimorbidity measured by a weighted count score was significantly associated with lower overall HRQL ( EQ VAS ) , b = −1.02 ( SE : 0.06 ) . Parkinson ’s disease had the most pronounced negative effect on overall HRQL ( EQ VAS ) , b = −12.29 ( SE : 2.18 ) , followed by rheumatism , depression , and obesity . With regard to the individual EQ-5D dimensions , depression ( OR = 1.39 to 3.3 ) and obesity ( OR = 1.44 to 1.95 ) affected all five dimensions of the EQ-5D negatively except for the dimension anxiety/depression . Obesity had a positive effect on this dimension , OR = 0.78 ( SE : 0.07 ) . The dimensions “ self-care ” , OR = 4.52 ( SE : 1.37 ) and “ usual activities ” , OR = 3.59 ( SE : 1.0 ) , were most strongly affected by Parkinson ’s disease . As a limitation our sample may only represent patients with at most moderate disease severity . Conclusions The overall HRQL of multimorbid patients decreases with an increasing count and severity of conditions . Parkinson ’s disease , depression and obesity have the strongest impact on HRQL . Further studies should address the impact of disease combinations which require very large sample sizes as well as advanced statistical methods OBJECTIVE The Re sources for Health trial evaluates a social-ecologically based lifestyle ( physical activity and diet ) intervention targeting low-income , largely Spanish-speaking patients with multiple chronic conditions . DESIGN A r and omized controlled trial was conducted with 200 patients recruited from an urban community health center and assigned to intervention and usual care conditions . Intervention involved 2 face-to-face , self-management support and community linkage sessions with a health educator , 3 follow-up phone calls , and 3 tailored newsletters . MAIN OUTCOME MEASURES Primary outcomes measured at 6-months were changes in dietary behavior and physical activity . Changes in multilevel support for healthy living were evaluated as a secondary outcome . RESULTS After adjustment for age , sex , language , and number of chronic conditions , significant intervention effects were observed for dietary behavior and multilevel support for healthy lifestyles but not for physical activity . CONCLUSION The Re sources for Health intervention provides an effective and practical model for improving health behavior among low-income , Spanish-speaking patients with multiple chronic conditions Background Physical activity is an important aspect in the treatment of patients with chronic obstructive pulmonary disease or type-2 diabetes . A monitoring and feedback tool combined with guidance by a primary care provider might be a successful method to enhance the level of physical activity in these patients . As a prerequisite for useful technology , it is important to involve the end-users in the design process from an early stage . Objective The aim of this study was to investigate the user requirements for a tool to stimulate physical activity , embedded in primary care practice . The leading principle of this tool is to change behavior by self-monitoring , goal - setting , and feedback . Methods The research team collected qualitative data among 15 patients , 16 care professionals , and several experts . A prototype was developed in three stages . In stage 1 , the literature was search ed to identify end-users and context . In stage 2 , the literature , experts and patient representatives were consulted to set up a use case with the general idea of the innovation . In stage 3 , individual interviews and focus groups were held to identify the end-user requirements . Based on these requirements a prototype was built by the engineering team . Results The development process has led to a tool that generally meets the requirements of the end-users . A tri-axial activity sensor , worn on the hip , is connected by Bluetooth to a smartphone . In an app , quantitative feedback is given about the amount of activity and goals reached by means of graphical visualization , and an image shows a sun when the goal is reached . Overviews about activity per half an hour , per day , week , and month are provided . In the menu of the app and on a secured website , patients can enter information in individual sessions or read feedback messages generated by the system . The practice nurse can see the results of all patients on a secure webpage and can then discuss the results and set personalized goals in consultation with the patient . Conclusions This study demonstrates that a user-centered approach brings in valuable details ( such as the requirements for feedback in activity minutes per day ) to improve the fit between the user , technology , and the organization of care , which is important for the usability and acceptability of the tool . The tool embedded in primary care will be evaluated in a r and omized controlled trial Introduction In its final stages , chronic obstructive pulmonary disease is a severely disabling condition that is characterised by dyspnoea , which causes substantial anxiety . Anxiety is associated with an impaired quality of life and increased hospital admissions . Untreated comorbid anxiety can have devastating consequences for both patients and their relatives . Non-pharmacological interventions , including cognitive – behavioural therapy , have been effective in managing anxiety and dyspnoea in patients with chronic obstructive pulmonary disease . However , the majority of existing interventions have tested the efficacy of relatively intensive comprehensive programmes and primarily targeted patients who have moderate pulmonary disease . We present the rationale and design for a trial that focused on addressing the challenges experienced by severe pulmonary disease population s. The trial investigates the efficacy of a minimal home-based psychoeducative intervention versus usual care for patients with severe chronic obstructive pulmonary disease . Methods and analysis The trial is a r and omised controlled trial with a 4-week and 3-month follow-up . 66 patients with severe chronic obstructive pulmonary disease and associated anxiety will be r and omised 1:1 to either an intervention or control group . The intervention consists of a single psychoeducative session in the patient 's home in combination with a telephone booster session . The intervention is based on a manual , with a theoretical foundation in cognitive – behavioural therapy and psychoeducation . The primary outcome is patient-reported anxiety as assessed by the Hospital and Anxiety and Depression Scale ( HADS ) . Ethics and dissemination This trial complies with the latest Declaration of Helsinki , and The Ethics Committee of the Capital Region of Denmark ( number H-1 - 2013 - 092 ) was queried for ethical approval . Trial results will be disseminated in peer- review ed publications and presented at scientific conferences . Trial registration number NCT02366390 Objectives Prevalence estimates of multimorbidity vary widely due to inconsistent definitions and measurement methods . This study examines the independent effects on prevalence estimates of how ‘ disease entity ’ is defined — as a single chronic condition or chapters/domains in the International Classification of Primary Care ( V.2 ; ICPC-2 ) , International Classification of Disease ( 10th revision ; ICD-10 ) or the Cumulative Illness Rating Scale ( CIRS ) , the number of disease entities required for multimorbidity , and the number of chronic conditions studied . Design National prospect i ve cross-sectional study . Setting Australian general practice . Participants 8707 r and om consenting deidentified patient encounters with 290 r and omly selected general practitioners . Main outcome measures Prevalence estimates of multimorbidity using different definitions . Results Data classified to ICPC-2 chapters , ICD-10 chapters or CIRS domains produce similar multimorbidity prevalence estimates . When multimorbidity was defined as two or more ( 2 + ) disease entities : counting individual chronic conditions and groups of chronic conditions produced similar estimates ; the 12 most prevalent chronic conditions identified about 80 % of those identified using all chronic conditions . When multimorbidity was defined as 3 + disease entities : counting individual chronic conditions produced significantly higher estimates than counting groups of chronic conditions ; the 12 most prevalent chronic conditions identified only two-thirds of patients identified using all chronic conditions . Conclusions Multimorbidity defined as 2 + disease entities can be measured using different definitions of disease entity with as few as 12 prevalent chronic conditions , but lacks specificity to be useful , especially in older people . Multimorbidity , defined as 3 + , requires more measurement conformity and inclusion of all chronic conditions , but provides greater specificity than the 2 + definition . The proposed concept of “ complex multimorbidity ” , the co-occurrence of three or more chronic conditions affecting three or more different body systems within one person without defining an index chronic condition , may be useful in identifying high-need individuals Background An ageing population increases dem and on health and social care . New approaches are needed to shift care from hospital to community and general practice . A predictive risk stratification tool ( Prism ) has been developed for general practice that estimates risk of an emergency hospital admission in the following year . We present a protocol for the evaluation of Prism . Methods / Design We will undertake a mixed methods progressive cluster-r and omised trial . Practice s begin as controls , delivering usual care without Prism . Practice s will receive Prism and training r and omly , and thereafter be able to use Prism with clinical and technical support . We will compare costs , processes of care , satisfaction and patient outcomes at baseline , 6 and 18 months , using routine data and postal question naires . We will assess technical performance by comparing predicted against actual emergency admissions . Focus groups and interviews will be undertaken to underst and how Prism is perceived and adopted by practitioners and policy makers . We will model data using generalised linear models and survival analysis techniques to determine whether any differences exist between intervention and control groups . We will take account of covariates and explanatory factors . In the economic evaluation we will carry out a cost-effectiveness analysis to examine incremental cost per emergency admission to hospital avoided and will examine costs versus changes in primary and secondary outcomes in a cost-consequence analysis . We will also examine changes in quality of life of patients across the risk spectrum . We will record and transcribe focus groups and interviews and analyse them thematically . We have received full ethical and R&D approvals for the study and Information Governance Review Panel ( IGRP ) permission for the use of routine data . We will comply with the CONSORT guidelines and will disseminate the findings at national and international conferences and in peer- review ed journals . Discussion The proposed study will provide information on costs and effects of Prism ; how it is used in practice , barriers and facilitators to its implementation ; and its perceived value in supporting the management of patients with and at risk of developing chronic conditions . Trial registration Controlled Clinical Trials IS RCT N no. IS RCT N55538212 Background More than half of the patients with type 2 diabetes ( T2DM ) patients are diagnosed with one or more comorbid disorders . They can participate in several single-disease oriented disease management programs , which may lead to fragmented care because these programs are not well prepared for coordinating care between programs . Comorbid patients are therefore at risk for suboptimal treatment , unsafe care , inefficient use of health care services and unnecessary costs . Case management is a possible model to counteract fragmented care for comorbid patients . It includes evidence -based optimal care , but is tailored to the individual patients ' preferences . The objective of this study is to examine the effectiveness of a case management program , in addition to a diabetes management program , on the quality of care for comorbid T2DM patients . Methods / Design The study is a r and omized controlled trial among patients with T2DM and at least one comorbid chronic disease ( N = 230 ) , who already participate in a diabetes management program . R and omization will take place at the level of the patients in general practice s. Trained practice nurses ( case managers ) will apply a case management program in addition to the diabetes management program . The case management intervention is based on the Guided Care model and includes six elements ; assessing health care needs , planning care , create access to other care providers and community re sources , monitoring , coordinating care and recording of all relevant information . Patients in the control group will continue their participation in the diabetes management program and receive care-as-usual from their general practitioner and other care providers . Discussion We expect that the case management program , which includes better structured care based on scientific evidence and adjusted to the patients ' needs and priorities , will improve the quality of care coordination from both the patients ' and caregivers ' perspective and will result in less consumption of health care services . Trial registration Netherl and s Trial Register ( NTR ) : Background The prevalence of type 2 diabetes is rising internationally . Patients with diabetes have a higher risk of cardiovascular events accounting for substantial premature morbidity and mortality , and health care expenditure . Given healthcare workforce limitations , there is a need to improve interventions that promote positive self-management behaviours that enable patients to manage their chronic conditions effectively , across different cultural context s. Previous studies have evaluated the feasibility of including telephone and Short Message Service ( SMS ) follow up in chronic disease self-management programs , but only for single diseases or in one specific population . Therefore , the aim of this study is to evaluate the feasibility and short-term efficacy of incorporating telephone and text messaging to support the care of patients with diabetes and cardiac disease , in Australia and in Taiwan . Methods / design A r and omised controlled trial design will be used to evaluate a self-management program for people with diabetes and cardiac disease that incorporates the use of simple remote-access communication technologies . A sample size of 180 participants from Australia and Taiwan will be recruited and r and omised in a one-to-one ratio to receive either the intervention in addition to usual care ( intervention ) or usual care alone ( control ) . The intervention will consist of in-hospital education as well as follow up utilising personal telephone calls and SMS reminders . Primary short term outcomes of interest include self-care behaviours and self-efficacy assessed at baseline and four weeks . Discussion If the results of this investigation substantiate the feasibility and efficacy of the telephone and SMS intervention for promoting self management among patients with diabetes and cardiac disease in Australia and Taiwan , it will support the external validity of the intervention . It is anticipated that empirical data from this investigation will provide valuable information to inform future international collaborations , while providing a platform for further enhancements of the program , which has potential to benefit patients internationally . Trial registration ACTRN 12611001196932 OBJECTIVE This study tested the efficacy of a patient engagement intervention for older adults with multiple chronic illnesses . METHODS Seventy-nine participants were r and omly assigned to receive the intervention ( Intervention Group ) , contacts on a different topic ( Safety Group ) , or Usual Care . The Intervention and Safety Groups attended a 2-h workshop and participated in phone calls ; one before and one after a naturally-occurring medical encounter . The Intervention Group discussed patient engagement concepts from publicly distributed content . The Safety Group discussed general safety ( e.g. , fire safety , identity theft ) . Self-report measures were gathered by telephone interview at Baseline and 6-months following Baseline . RESULTS We did not find expected improvements in patient activation and health-related quality of life . However , the Intervention Group was the only group to show a statistically significant improvement in self-efficacy for self-management . CONCLUSION The intervention shows promise for improving quality of life and /or health , but requires refinement to reach persons not already engaged in their healthcare and to strengthen its effects . PRACTICE IMPLICATION S Patient-directed skills training interventions may be a successful way to support clinicians ' and others ' efforts to encourage older patients to be actively involved in their care PURPOSE The impact of comorbidity on use of primary care and specialty services is poorly understood . The purpose of this study was to determine the relationship between morbidity burden , comorbid conditions , and use of primary care and specialist services METHODS The study population was a 5 % r and om sample of Medicare beneficiaries , taken from 1999 Medicare files . We analyzed the number of ambulatory face-to-face patient visits to primary care physicians and specialists for each diagnosis , with each one first considered as the “ main ” one and then as a comorbid diagnosis to another . Each patient was categorized by extent of total morbidity burden using the Johns Hopkins Adjusted Clinical Group case-mix system . RESULTS Higher morbidity burden was associated with more visits to specialists , but not to primary care physicians . Patients with most diagnoses had more visits , both to primary care and specialist physicians for comorbid diagnoses than for the main diagnosis itself . Although patients , especially those with high morbidity burdens , generally made more visits to specialists than to primary care physicians , this finding was not always the case . For patients with 66 diagnoses , primary care visits for those diagnoses exceeded specialist visits in all morbidity burden groups ; for patients with 87 diagnoses , specialty visits exceeded primary care visits in all morbidity burden groups . CONCLUSION In the elderly , a high morbidity burden leads to higher use of specialist physicians , but not primary care physicians , even for patients with common diagnoses not generally considered to require specialist care . This finding calls for a better underst and ing of the relative roles of generalists and specialists in the US health services system Background Evidence -based interventions to reduce hospital readmissions may not generalize to re source -constrained safety-net hospitals . Objective To determine if an intervention by patient navigators ( PNs ) , hospital-based Community Health Workers , reduces readmissions among high risk , low socioeconomic status patients . Design R and omized controlled trial . Participants General medicine in patients having at least one of the following readmission risk factors : ( 1 ) age ≥60 years , ( 2 ) any in-network inpatient admission within the past 6 months , ( 3 ) length of stay ≥3 days , ( 4 ) admission diagnosis of heart failure , or ( 5 ) chronic obstructive pulmonary disease . The analytic sample included 585 intervention patients and 925 controls . Interventions PNs provided coaching and assistance in navigating the transition from hospital to home through hospital visits and weekly telephone outreach , supporting patients for 30 days post-discharge with discharge preparation , medication management , scheduling of follow-up appointments , communication with primary care , and symptom management . Main Measures The primary outcome was in-network 30-day hospital readmissions . Secondary outcomes included rates of outpatient follow-up . We evaluated outcomes for the entire cohort and stratified by patient age > 60 years ( 425 intervention/584 controls ) and ≤60 years ( 160 intervention/341 controls).Key Results Overall , 30-day readmission rates did not differ between intervention and control patients . However , the two age groups demonstrated marked differences . Intervention patients > 60 years showed a statistically significant adjusted absolute 4.1 % decrease [ 95 % CI : −8.0 % , -0.2 % ] in readmission with an increase in 30-day outpatient follow-up . Intervention patients ≤60 years showed a statistically significant adjusted absolute 11.8 % increase [ 95 % CI : 4.4 % , 19.0 % ] in readmission with no change in 30-day outpatient follow-up . Conclusions A patient navigator intervention among high risk , safety-net patients decreased readmission among older patients while increasing readmissions among younger patients . Care transition strategies should be evaluated among diverse population s , and younger high risk patients may require novel strategies OBJECTIVE Clients with co-occurring severe mental and substance use disorders are at high risk of institutionalization and other adverse outcomes . Although integrated mental health and substance abuse treatment is becoming a st and ard clinical approach for such clients , the optimal method for delivering integrated treatment remains unclear . METHOD This study compared integrated treatment delivered within two different models of community-based case management ( assertive community treatment and st and ard clinical case management ) . A total of 198 clients in two urban sites who had co-occurring disorders and were homeless or unstably housed were r and omly assigned to one of two treatment conditions and were followed for three years . RESULTS Participants in both treatment conditions improved over time in multiple outcome domains , and few differences were found between the two models . Decreases in substance use were greater than would be expected given time alone . At the site that had higher rates of institutionalization , clients who received st and ard case management were more likely to be institutionalized . However , in the site that had lower rates of institutionalization , no differences in the rate of institutionalization were found between the two treatment conditions . CONCLUSIONS Integrated treatment can be successfully delivered either by assertive community treatment or by st and ard clinical case management Six weekly sessions of group cognitive-behavioral therapy for insomnia and osteoarthritis pain ( CBT-PI ) , and for osteoarthritis pain alone ( CBT-P ) were compared to an education only control ( EOC ) . Basic education about pain and sleep was comparable , so EOC controlled for information and group participation . Active interventions differed from EOC in training pain coping skills ( CBT-P and CBT-PI ) and sleep enhancement techniques ( CBT-PI ) . Persons with osteoarthritis age 60 or older were screened for osteoarthritis pain and insomnia severity via mailed survey . Primary outcomes were pain severity ( pain intensity and interference ratings from the Grade d Chronic Pain Scale ) and insomnia severity ( Insomnia Severity Index ) . Secondary outcomes were arthritis pain ( AIMS -2 symptom scale ) and sleep efficiency assessed by wrist actigraphy . Ancillary outcomes included : cognitive function , depression , and health care use . A clustered r and omized design provided adequate power to identify moderate effects on primary outcomes ( effect size>0.35 ) . Modified intent to treat analyses , including all participants who attended the first session , assessed effects across CBT-PI , CBT-P , and EOC groups . Treatment effects were assessed post-intervention ( 2 months ) and at 9 months , with durability of intervention effects evaluated at 18 months . The trial was executed in 6 primary clinics , r and omizing 367 participants , with 93.2 % of r and omized patients attending at least 4 group sessions . Response rates for post-intervention and 9 month assessment s were 96.7 % and 92.9 % respectively . This hybrid efficacy-effectiveness trial design evaluates whether interventions yield specific benefits for clinical and behavioral outcomes relative to an education only control when implemented in a primary care setting PURPOSE We studied the effect of 3 antidepressant treatments on outcomes ( depressive severity , medication tolerability , and psychosocial functioning ) in depressed patients having comorbid general medical conditions in the Combining Medications to Enhance Depression Outcomes ( CO-MED ) trial . METHODS Adult out patients who had chronic and /or recurrent major depressive disorder ( MDD ) with and without general medical conditions were r and omly assigned in 1:1:1 ratio to 28 weeks of single-blind , placebo-controlled antidepressant treatment with ( 1 ) escitalopram plus placebo , ( 2 ) bupropion-SR plus escitalopram , or ( 3 ) venlafaxine-XR plus mirtazapine . At weeks 12 and 28 , we compared response and tolerability between participants with 0 , 1 , 2 , and 3 or more general medical conditions . RESULTS Of the 665 evaluable patients , 49.5 % reported having no treated general medical conditions , 23.8 % reported having 1 , 14.8 % reported having 2 , and 11.9 % reported having at least 3 . We found only minimal differences in antidepressant treatment response between these groups having different numbers of conditions ; patients with 3 or more conditions reported higher rates of impairment in social and occupational functioning at week 12 but not at week 28 . Additionally , we found no significant differences between the 3 antidepressant treatments across these groups . CONCLUSIONS Patients with general medical conditions can be safely and effectively treated for MDD with antidepressants with no additional adverse effect or tolerability burden relative to their counterparts without such conditions . Combination therapy is not associated with an increased treatment response beyond that found with traditional monotherapy in patients with MDD , regardless of the presence and number of general medical conditions OBJECTIVE Guided Care ( GC ) is a model of proactive , evidence -based comprehensive healthcare provided by physician-nurse teams for people with several chronic health conditions . Our objective was to evaluate the preliminary effects of GC on health service utilization and costs . STUDY DESIGN Cluster-r and omized controlled trial of GC involving 14 primary care teams ( 49 physicians ) and 904 of their chronically ill patients age 65 years or older . METHODS Using insurance cl aims , we compared the health services used by patients who received GC with the health services used by patients who received usual care during the first 8 months of the study . RESULTS After adjustment for baseline characteristics , GC patients experienced , on average , 24 % fewer hospital days ( 95 % confidence interval [ CI ] : 49 % fewer , 13 % more ) , 37 % fewer skilled nursing facility days ( 95 % CI : 65 % fewer , 5 % more ) , 15 % fewer emergency department visits ( 95 % CI : 38 % fewer , 18 % more ) , and 29 % fewer home healthcare episodes ( 95 % CI : 53 % fewer , 8 % more ) , as well as 9 % more specialist visits ( 95 % CI : 8 % fewer , 29 % more ) . Based on current Medicare payment rates and GC costs , these differences in utilization represent an annual net savings of $ 75,000 ( 95 % CI : -$244,000 , $ 150,900 ) per nurse , or $ 1364 per patient . CONCLUSIONS Initial introduction of GC into primary care practice s may be associated with less use of expensive health services and a net savings in healthcare costs among older patients with several chronic health conditions . Final results from the remaining 2 years of this ongoing study will be published in 2011 The prevalence of older Australians with multiple chronic diseases is increasing and now accounts for a large proportion of total health care utilisation . Chronic disease self-management support ( CDSMS ) has become a core service component of many community based health programs because it is considered a useful tool in improving population health outcomes and reducing the financial burden of chronic disease care . However , the evidence base to justify these support programs is limited , particularly for older people with multiple chronic diseases . We describe an ongoing trial examining the effectiveness of a particular CDSMS approach called the Flinders Program . The Flinders Program is a clinician-led generic self-management intervention that provides a set of tools and a structured process that enables health workers and patients to collaboratively assess self-management behaviours , identify problems , set goals , and develop individual care plans covering key self-care , medical , psychosocial and carer issues . A sample of 252 older Australians that have two or more chronic conditions will be r and omly assigned to receive either CDSMS or an attention control intervention ( health information only ) for 6 months . Outcomes will be assessed using self-reported health measures taken at baseline and post-intervention . This project will be the first comprehensive evaluation of CDSMS in this population . Findings are expected to guide consumers , clinicians and policymakers in the use of CDSMS , as well as facilitate prioritisation of public monies towards evidence -based services The Indiana Chronic Disease Management Program ( ICDMP ) is intended to improve the quality and cost-effectiveness of care for Medicaid members with congestive heart failure ( chronic heart failure ) , diabetes , asthma , and other conditions . The ICDMP is being assembled by Indiana Medicaid primarily from state and local re sources and has seven components : ( 1 ) identification of eligible participants to create regional registries , ( 2 ) risk stratification of eligible participants , ( 3 ) nurse care management for high-risk participants , ( 4 ) telephonic intervention for all participants , ( 5 ) an Internet-based information system , ( 6 ) quality improvement collaboratives for primary care practice s , and ( 7 ) program evaluation . The evaluation involves a r and omized controlled trial in two inner-city group practice s , as well as a statewide observational design . This article describes the ICDMP , highlights challenges , and discusses approaches to its evaluation OBJECTIVES To evaluate the long-term mortality effect of a home-based intervention previously shown to reduce functional difficulties and whether survivorship benefits differ according to initial mortality risk level . DESIGN Two-group r and omized trial with survivorship followed up to 4 years from study entry . SETTING Homes of urban community-living elderly people . PARTICIPANTS Three hundred nineteen adults aged 70 and older with difficulties performing daily activities . INTERVENTION Occupational and physical therapy sessions to instruct participants in compensatory strategies , home modifications , home safety , fall recovery techniques , and balance and muscle strength exercises . MEASUREMENTS Survival time was number of days between baseline interview and date of death , as determined using data from the National Death Index or December 31 , 2005 . Participants were stratified according to baseline mortality risk ( low , moderate , high ) using a prognostic indicator . RESULTS At 2 years , intervention participants ( n=160 ) had a 5.6 % mortality rate ( n=9 deaths ) and controls ( n=159 ) a 13.2 % rate ( n=21 deaths ; P=.02 ) . Mortality rates remained lower for intervention participants up to 3.5 years from study entry . At 2 years , intervention participants with moderate mortality risk had a 16.7 % mortality rate ( n=16 deaths/96 ) , compared with 28.2 % for equivalent control group participants ( n=24 deaths/85 ; P=.02 ) . By 3 years , mortality rates were not statistically significantly different between the experimental and control groups . CONCLUSIONS The intervention extended survivorship up to 3.5 years and maintained statistically significant differences for 2 years . Subjects at moderate mortality risk derived the most intervention benefit . Findings suggest that the intervention could be a low-cost clinical tool to delay functional decline and mortality BACKGROUND Depression is common in older adults and often coexists with multiple chronic diseases , which may complicate its diagnosis and treatment . OBJECTIVE To determine whether or not the presence of multiple comorbid medical illnesses affects patient response to a multidisciplinary depression treatment program . DESIGN , SETTING AND PARTICIPANTS Preplanned analyses of Improving Mood-Promoting Access to Collaborative Treatment ( IMPACT ) , a r and omized controlled trial of 1801 depressed older adults ( > or = 60 years ) , which was performed at 18 primary care clinics from eight health care organizations in five states across the United States from July 1999 to August 2001 . INTERVENTION Intervention patients had access for up to 12 months to a depression care manager , supervised by a psychiatrist and a primary care expert , who offered education , care management and support of antidepressant management by the patient 's primary care physician , or provided brief psychotherapy ( Problem-Solving Treatment in Primary Care ) . MEASUREMENTS Depression , quality of life ( QOL ; scale of 0 - 10 ) and mental health component score ( MCS ) of the Short-Form 12 assessed at baseline , 3 , 6 and 12 months . RESULTS Patients suffered from an average of 3.8 chronic medical conditions . Although patients with more chronic medical conditions had higher depression severity at baseline , the number of chronic diseases did not affect the likelihood of response to the IMPACT intervention when compared to care as usual . Intervention patients experienced significantly lower depression during all follow-up time points as compared with patients in usual care independent of other comorbid illnesses ( P<.001 ) . Intervention patients were also more likely to experience substantial response ( at least a 50 % reduction in depressive symptoms ) regardless of the number of comorbidities , to experience improved MCS-12 scores at 3 and 12 months , and to experience improved QOL . CONCLUSIONS The presence of multiple comorbid medical illnesses did not affect patient response to a multidisciplinary depression treatment program . The IMPACT collaborative care model was equally effective for depressed older adults with or without comorbid medical illnesses Objective To determine the effectiveness of an intervention to enhance self management support for patients with chronic conditions in UK primary care . Design Pragmatic , two arm , cluster r and omised controlled trial . Setting General practice s , serving a population in northwest Engl and with high levels of deprivation . Participants 5599 patients with a diagnosis of diabetes ( n=2546 ) , chronic obstructive pulmonary disease ( n=1634 ) , and irritable bowel syndrome ( n=1419 ) from 43 practice s ( 19 intervention and 22 control practice s ) . Intervention Practice level training in a whole systems approach to self management support . Practice s were trained to use a range of re sources : a tool to assess the support needs of patients , guidebooks on self management , and a web based directory of local self management re sources . Training facilitators were employed by the health management organisation . Main outcome measures Primary outcomes were shared decision making , self efficacy , and generic health related quality of life measured at 12 months . Secondary outcomes were general health , social or role limitations , energy and vitality , psychological wellbeing , self care activity , and enablement . Results We r and omised 44 practice s and recruited 5599 patients , representing 43 % of the eligible population on the practice lists . 4533 patients ( 81.0 % ) completed the six month follow-up and 4076 ( 72.8 % ) the 12 month follow-up . No statistically significant differences were found between patients attending trained practice s and those attending control practice s on any of the primary or secondary outcomes . All effect size estimates were well below the prespecified threshold of clinical ly important difference . Conclusions An intervention to enhance self management support in routine primary care did not add noticeable value to existing care for long term conditions . The active components required for effective self management support need to be better understood , both within primary care and in patients ’ everyday lives . Trial registration Current Controlled Trials IS RCT N90940049 Previous studies about the association of multimorbidity and the health-related quality of life ( HRQOL ) in primary -care patients are limited because of their reliance on simple counts of diseases from a limited list of diseases and their failure to assess the severity of disease . We evaluated the association while taking into account the severity of the medical conditions based on the Cumulative Illness Rating Scale ( CIRS ) score , and controlling for potential confounders ( age , sex , household income , education , self-perception of economic status , number of people living in the same dwelling , and perceived social support ) . We r and omly selected 238 patients to construct quintiles of increasing multimorbidity ( CIRS ) . Patients completed the 36-item Medical Outcomes study question naire ( SF-36 ) to evaluate their HRQOL . Applying bivariate and multivariate linear regression analyses , we used the CIRS as either a continuous or a categorical ( quintiles ) variable . Use of the CIRS revealed a stronger association of HRQOL with multimorbidity than using a simple count of chronic conditions . Physical more than mental health deteriorated with increasing multimorbidity . Perceived social support and self-perception of economic status were significantly related to all scales of the SF-36 ( p < 0.05 ) . Increased multimorbidity adversely affected HRQOL in primary -care adult patients , even when confounding variables were controlled for OBJECTIVES To examine the impact of an interdisciplinary , collaborative practice intervention involving a primary care physician , a nurse , and a social worker for community-dwelling seniors with chronic illnesses . METHODS A concurrent , controlled cohort study of 543 patients in 18 private office practice s of primary care physicians was conducted . The intervention group received care from their primary care physician working with a registered nurse and a social worker , while the control group received care as usual from their primary care physician . The outcome measures included changes in number of hospital admissions , readmissions , office visits , emergency department visits , skilled nursing facility admissions , home care visits , and changes in patient self-rated physical , emotional , and social functioning . RESULTS From 1992 ( baseline year ) to 1993 , the two groups did not differ in service use or in self-reported health status . From 1993 to 1994 , the hospitalization rate of the control group increased from 0.34 to 0.52 , while the rate in the intervention group stayed at baseline ( P= .03 ) . The proportion of intervention patients with readmissions decreased from 6 % to 4 % , while the rate in the control group increased from 4 % to 9 % ( P=.03 ) . In the intervention group , mean office visits to all physicians fell by 1.5 visits compared with a 0.5-visit increase for the control group ( P=.003 ) . The patients in the intervention group reported an increase in social activities compared with the control group 's decrease ( P=.04 ) . With fewer hospital admissions , average per-patient savings for 1994 were estimated at $ 90 , inclusive of the intervention 's cost but exclusive of savings from fewer office visits . CONCLUSIONS This model of primary care collaborative practice shows potential for reducing utilization and maintaining health status for seniors with chronic illnesses . Future work should explore the specific benefit accruing from physician involvement in the collaborative practice team OBJECTIVE The aim of this study was to compare outcomes of use of a depression self-care toolkit with and without lay telephone coaching among primary care patients 40 years and older with depressive symptoms and comorbid chronic physical conditions . METHOD A single blind , individually r and omized , pragmatic trial of a depression self-care toolkit ( Toolkit ) with or without lay telephone coaching was conducted among primary care adults with depressive symptoms and comorbid chronic physical conditions . Eligible patients were r and omized to receive the Toolkit with ( intervention ) or without ( control ) telephone coaching provided by trained lay coaches . The primary outcome was depression severity [ Patient Health Question naire ( PHQ-9 ) ] at 6 months . Secondary outcomes were self-efficacy , satisfaction , and use of health services at 6 months . RESULTS A total of 223 patients were r and omized , and 172 ( 77.1 % ) completed 6-month follow-ups . PHQ-9 scores improved significantly in both groups over the 6-month follow-up ; the differences in PHQ-9 scores between intervention and control groups were statistically significant at 3 months [ effect size = 0.44 ; 95 % confidence interval ( CI ) = 0.16 - 0.72 ] but not at 6 months ( effect size = 0.24 ; 95 % CI = -0.01 to 0.60 ) . Patients with moderate depression severity ( PHQ-9 10 - 19 ) and high self-efficacy at baseline were most likely to benefit from the intervention . There was no significant effect of the intervention on the secondary outcomes . CONCLUSIONS The incremental value of lay telephone coaching of a Toolkit appears short-lived . Targeting of coaching to those with moderate depression severity may be indicated BACKGROUND Multiple hospital admissions , especially those related to chronic disease , represent a particular challenge to the acute health care sector in Australia . OBJECTIVE To determine whether a nurse-led chronic disease management model of transitional care reduced readmissions to acute care . DESIGN A quasi-experimental controlled trial . SETTING A large tertiary metropolitan teaching hospital . PARTICIPANTS 166 general medical patients aged > or = 65 years with either a history of readmissions to acute care or multiple medical comorbidities . INTERVENTION Implementation of a chronic disease management model of transitional care aim ed at improving patient management and reducing readmissions to acute care . MAIN OUTCOME MEASURES Readmission rates and emergency department presentation rates at 3- and 6-month follow up . Secondary outcome measures include quality of life , discharge destination , and primary health care service utilisation . RESULTS There was no difference in readmission rates , emergency department presentation rates , quality of life , discharge destination or primary health care service utilisation . The difficulties inherent in evaluating this type of multifactorial intervention are discussed and consideration is given to patient factors , the difficulty of influencing readmission rates , and local system issues . CONCLUSION The outcomes of this study reflect the tension that exists between implementing multifaceted integrated health service programs and attempting to evaluate them within complex and changing environments using robust research method ologies OBJECTIVE Self-management as a tool to manage chronic conditions has been well-described for majority population s. Limited studies exist on the potential benefit of self-management programs for African Americans with chronic conditions . The purpose was to demonstrate the feasibility , effectiveness and acceptability of a structured self-management program in African Americans with one or more chronic conditions . METHODS This pilot study involved an intervention-only arm of a six-week peer-led program aim ed at improving important self-management skills , including self-efficacy and physical activity . Participants were recruited from local churches and independent living senior centers , and trained lay leaders served as facilitators of the self-management program . RESULTS A total of 46 people participated in this program . Participants were mostly African American ( 96 % ) , female ( 91 % ) , with a mean age of 65 ( 11 ) , and 2.7 ( 1.5 ) chronic conditions . We found significant increases in pre- to postintervention self-efficacy ( P<.01 ) and self-reported walking for exercise ( P<0.05 ) . Self-rated health also had significant improvement ( P<.01 ) . Qualitative feedback revealed a desire for more support with transforming traditional foods and creative exercise strategies . CONCLUSIONS A st and ardized peer-led self-management course was effective at improving self-efficacy , walking for exercise and self-rated health in African Americans with a variety of common chronic conditions . Future self-management interventions should focus more on cultural interests and strengths such as spirituality , existing support networks for behavioral change , and retention strategies to achieve long-term lifestyle changes BACKGROUND Despite recognition of the benefits associated with well-controlled diabetes and hypertension , control remains suboptimal . Effective interventions for these conditions have been studied within academic setting s , but interventions targeting both conditions have rarely been tested in community setting s. We describe the design and baseline results of a trial evaluating a behavioral intervention among community patients with poorly-controlled diabetes and comorbid hypertension . METHODS Tailored Case Management for Diabetes and Hypertension ( TEACH-DM ) is a 24-month r and omized , controlled trial evaluating a telephone-delivered behavioral intervention for diabetes and hypertension versus attention control . The study recruited from nine community practice s. The nurse-administered intervention targets 3 areas : 1 ) cultivation of healthful behaviors for diabetes and hypertension control ; 2 ) provision of fundamentals to support attainment of healthful behaviors ; and 3 ) identification and correction of patient-specific barriers to adopting healthful behaviors . Hemoglobin A1c and blood pressure measured at 6 , 12 , and 24 months are co- primary outcomes . Secondary outcomes include self-efficacy , self-reported medication adherence , exercise , and cost-effectiveness . RESULTS Of 377 r and omized patients , 193 were allocated to the intervention and 184 to attention control . The cohort is balanced in terms of gender , race , education level , and income . The cohort 's mean baseline hemoglobin A1c and blood pressure are above goal , and mean baseline body mass index falls in the obese range . Baseline self-reported non-adherence is high for diabetes and hypertension medications . Trial results are pending . CONCLUSIONS If effective , the TEACH-DM intervention 's telephone-based delivery strategy and nurse administration make it well-suited for rapid implementation and broad dissemination in community setting A mental health enterprise may be described by either ( a ) rather general philosophical total mental health goals , or ( b ) highly diverse and individualized patient-therapist goals . Goals a. have not provided a workable framework for program evaluation . This paper proposes that evaluation be done in the framework of goals b. by setting up , before treatment , a measurable scale for each patient-therapist goal , and specifying , for each patient , a transformation of his overall goal attainment into a st and ardized T-score . This method , together with r and om assignment of patients to treatment modes , was devised to permit comparison of treatment modes within a program , but it also provides a good basis for a judgmental evaluation of the total program Patients with medically unexplained symptoms ( MUS ) often are a source of frustration for clinicians , and despite high quality biomedical attention and frequent diagnostic tests , they have poor health outcomes . Following upon progress in depression treatment approaches , we developed a multidimensional treatment protocol for deployment by primary care personnel . This multi-faceted intervention for MUS patients emphasized cognitive-behavioral principles , the provider-patient relationship , pharmacological management , and treating comorbid medical diseases . We deployed it in an HMO using nurse practitioners ( NP ) to deliver the intervention to 101 patients , while 102 controls continued to receive medical care from their usual primary care physician . Successful deployment of the intervention required training the NPs , continuing support for the NPs in their management of this difficult population , and establishing strong communication links with the HMO . This paper addresses the practical considerations of using primary care personnel to implement a complex intervention in primary care , and it includes a discussion of special challenges encountered as well as solutions developed to overcome them BACKGROUND Co-morbid depression in HIV-positive patients on anti-retroviral ( ART ) treatment poses a public health threat . It compromises treatment adherence and accelerates disease progression . This study aim ed to assess the feasibility of a group-based counselling intervention for depressed HIV-positive patients in primary health care ( PHC ) in South Africa using a task shifting approach . METHODS Using a r and omized control design , 76 HIV-positive patients with co-morbid depression were initially recruited . This reduced to 34 in the final cohort . Participants were assessed using the Patient Health Question naire ( PHQ9 ) , Hopkins Symptom Checklist ( HSCL-25 ) and Multidimensional Scale of Perceived Social Support ( MSPSS ) at baseline and 3-month follow-up . The intervention was adapted from a local group-based Interpersonal Therapy ( IPT ) intervention . Process evaluation interviews were held with the HIV counsellors who delivered the intervention and a sub- sample of participants . RESULTS Repeated measures ANOVA analysis showed significantly greater improvement on depression scores on the PHQ9 in the intervention group compared to the control group . A significant decline in the mean scores on the HSCL-25 was found for both groups although this was more pronounced for the intervention group . There was no significant improvement in the MSPSS scores . LIMITATIONS The small sample size of the final cohort affected the power of the study to detect significant differences between the intervention and control groups on the MSPSS . Longer term impact of the intervention is unknown . CONCLUSIONS These preliminary findings suggest that group-based counselling for depression in HIV-positive patients can potentially be effectively delivered by appropriately trained and supported lay HIV counsellors . The need for a larger trial is indicated Background : : Depression is associated with poor glycemic control , increased number of microvascular and macrovascular complications , functional impairment , mortality , and 4.5 times higher total health care costs in patients with diabetes . Shared medical appointments ( SMAs ) may be an effective method to attain national guideline recommendations for glycemic control in diabetes for patients with depression through peer support , counseling , problem solving , and improved access to care . Objective : To test the efficacy as assessed by attainment of a hemoglobin A1c ( A1C ) < 7 % of pharmacistted group SMA visits , Veterans Affairs Multidisciplinary Education in Diabetes and Intervention for Cardiac Risk Reduction in Depression ( VA-MEDIC-D ) , in patients with type 2 diabetes mellitus . Methods : This was a r and omized controlled trial of VA-MEDIC-D added to st and ard care versus st and ard care alone in depressed patients with diabetes with A1C > 6.5 % . VA-MEDIC-D consisted of 4 once-weekly , 2-hour sessions followed by 5 monthly 90-minute group sessions . Each SMA session consisted of multidisciplinary education and pharmacist-led behavioral and pharmacologic interventions for diabetes , lipids , smoking , and blood pressure . No pharmacologic interventions for depression were provided . The change in the proportion of participants who achieved an A1C < 7 % at 6 months was compared . Results : Compared to st and ard care ( n = 44 ) , a lower proportion of patients in VA-MEDIC-D ( n = 44 ) had systolic blood pressure ( SBP ) < 130 mm Hg at baseline , but were similar in other cardiovascular risk factors and psychiatric comorbidity . The change in the proportion of participants achieving an A1C < 7 % was greater in the VA-MEDIC-D arm than in the st and ard care arm ( 29.6 % vs 11.9 % ) , with odds ratio 3.6 ( 95 % CI 1.1 to 12.3 ) . VA-MEDIC-D participants also achieved significant reductions in SBP , low-density lipoprotein cholesterol , and non – high-density lipoprotein ( HDL ) cholesterol from baseline , whereas significant reductions were attained only in non – HDL cholesterol with st and ard care . There was no significant change in depressive symptoms for either arm . Conclusions : Pharmacist-led group SMA visits are efficacious in attainment of glycemic control in patients with diabetes and depression without change in depression symptoms Objectives : Depression and anxiety are commonly seen in patients with chronic pain which affects the patient ’s daily life functioning . Although considerable attention has been devoted to explain why depression and anxiety are frequent comorbid with chronic pain , little empirical work has been conducted on interventions that target depression and anxiety and chronic pain . The present study was design ed to test an individualized cognitive-behavioral treatment delivered through the internet for persons with chronic pain and emotional distress . Material s and Methods : A total of 52 patients with chronic pain and depression were included and r and omized to either treatment for 8 weeks or to a control group that participated in a moderated online discussion forum . Results : Intent-to-treat analyses showed significant decreases regarding depressive symptoms and pain disability in the treatment group . Results on the primary outcomes of depression and anxiety were in favor of the treatment group . Reductions were also found on pain catastrophizing . Discussion : One-year follow-up showed maintenance of improvements . We conclude that an individualized guided internet-delivered treatment based on cognitive-behavior therapy can be effective for persons with chronic pain comorbid emotional distress PURPOSE Many r and omized controlled trials ( RCTs ) exclude patients who have multiple comorbidities . The aim of this study was to illustrate the prevalence of comorbidities among patients followed up in primary care who would have met the inclusion criteria of selected RCTs focusing on treatment of a particular condition . We used hypertension as an example of a particular chronic condition . METHODS We used an existing data base of 980 patients ( 660 women ) that was representative of a population consulting primary care family doctors and that contained information about all chronic conditions . We r and omly selected 5 RCTs that focused on patients with hypertension . The inclusion and exclusion criteria used in each of the 5 RCTs were applied ( 1 study at a time ) to the patients in our data base . The patients from our data set who met the inclusion criteria of a given RCT were considered eligible for that RCT . RESULTS Of the patients from our data set who were eligible for each of the RCTs , 89 % to 100 % had multiple chronic conditions . The mean number of chronic conditions of patients eligible for each RCT ranged from 5.5 ± 3.3 to 11.7 ± 5.3 . CONCLUSIONS Results from this study suggest that RCTs targeting a chronic medical condition such as hypertension could find that , in a sample taken from family practice , most eligible patients have comorbid conditions . Whether these patients are sample d or excluded should be reported . Research results intended to be applied in medical practice should take the complex reality of effective treatment of these patients into consideration BACKGROUND There is a high prevalence of depression in patients with diabetes mellitus . Depression has been shown to be associated with poor self-management ( adherence to diet , exercise , checking blood glucose levels ) and high hemoglobin A1c ( HbA1c ) levels in patients with diabetes . OBJECTIVE To determine whether enhancing quality of care for depression improves both depression and diabetes outcomes in patients with depression and diabetes . DESIGN R and omized controlled trial with recruitment from March 1 , 2001 , to May 31 , 2002 . SETTING Nine primary care clinics from a large health maintenance organization . PARTICIPANTS A total of 329 patients with diabetes mellitus and comorbid major depression and /or dysthymia . Intervention Patients were r and omly assigned to the Pathways case management intervention ( n = 164 ) or usual care ( n = 165 ) . The intervention provided enhanced education and support of antidepressant medication treatment prescribed by the primary care physician or problem-solving therapy delivered in primary care . MAIN OUTCOME MEASURES Independent blinded assessment s at baseline and 3 , 6 , and 12 months of depression ( Hopkins Symptom Checklist 90 ) , global improvement , and satisfaction with care . Automated clinical data were used to evaluate adherence to antidepressant regimens , percentage receiving specialty mental health visits , and HbA1c levels . RESULTS When compared with usual care patients , intervention patients showed greater improvement in adequacy of dosage of antidepressant medication treatment in the first 6-month period ( odds ratio [ OR ] , 4.15 ; 95 % confidence interval [ CI ] , 2.28 - 7.55 ) and the second 6-month period ( OR , 2.90 ; 95 % CI , 1.69 - 4.98 ) , less depression severity over time ( z = 2.84 , P = .004 ) , a higher rating of patient-rated global improvement at 6 months ( intervention 69.4 % vs usual care 39.3 % ; OR , 3.50 ; 95 % CI , 2.16 - 5.68 ) and 12 months ( intervention 71.9 % vs usual care 42.3 % ; OR , 3.50 ; 95 % CI , 2.14 - 5.72 ) , and higher satisfaction with care at 6 months ( OR , 2.01 ; 95 % CI , 1.18 - 3.43 ) and 12 months ( OR , 2.88 ; 95 % CI , 1.67 - 4.97 ) . Although depressive outcomes were improved , no differences in HbA1c outcomes were observed . CONCLUSION The Pathways collaborative care model improved depression care and outcomes in patients with comorbid major depression and /or dysthymia and diabetes mellitus , but improved depression care alone did not result in improved glycemic control OBJECTIVE We developed a personalized intervention for depressed patients with COPD ( PID-C ) aim ed to mobilize patients to participate in the care of both conditions . We showed that PID-C reduced depressive symptoms and dyspnea-related disability more than usual care over 28 weeks . This study focused on untangling key therapeutic ingredients of PID-C. DESIGN R and omized controlled trial . SETTING Community . PARTICIPANTS 138 patients who received the diagnoses of COPD and major depression after screening 898 consecutive admissions for acute inpatient pulmonary rehabilitation . INTERVENTION Nine sessions of PID-C compared with usual care over 28 weeks . MEASUREMENTS Primary outcome measures were the 17-item Hamilton Depression Rating Scale and the Pulmonary Functional Status and Dyspnea Question naire-Modified . Other measures were adherence to rehabilitation exercise ( ≥2 hours per week ) and adherence to adequate antidepressant prescriptions . RESULTS Low severity of dyspnea-related disability and adherence to antidepressants predicted subsequent improvement of depression . Exercise and low depression severity predicted improvement of dyspnea-related disability . CONCLUSIONS PID-C led to an interacting spiral of improvement in both depression and disability in a gravely medically ill population with a 17 % mortality rate over 28 weeks and an expected deterioration in disability . The interrelationship of the course of depression and dyspnea-related disability underscores the need to target adherence to both antidepressants and chronic obstructive pulmonary disease rehabilitation . PID-C may serve as a care management model for depressed persons suffering from medical illnesses with a deteriorating course The objective of this study was to determine how well the Charlson index of comorbidity would predict mortality of critically ill patients ; and how the predictive ability of the index would compare with that of the comorbidity component ( Chronic Health Points ) of the APACHE II system . This prospect i ve cohort study included in its setting an intensive care unit ( ICU ) and intermediate ICU ( IICU ) in a teaching hospital . Patients included a previously assembled inception cohort of 201 patients consecutively admitted to either unit , followed until death or discharge from the hospital , excluding patients admitted after coronary artery bypass grafting , for planned dialysis , or transferred to the IICU from another intensive care unit . Main outcome measures were recorded as death in hospital versus survival at discharge . For each patient we had prospect ively obtained all data necessary to predict the probability of in-hospital death using the APACHE II system , and to classify comorbidity using the Charlson index . The Charlson index had significant ability to discriminate between patients who would live and who would die ( ROC curve area = 0.67 , SE = 0.05 ) . The Chronic Health Points component of APACHE II had no significant discriminating ability ( ROC area = 0.57 , SE = 0.05 ) , although the full APACHE II system was an excellent predictor ( area = 0.87 , SE = 0.04 ) . Logistic regression analyses suggested that the Charlson index could contribute significant ( p = 0.03 ) prognostic information to that obtained from the components of APACHE II other than Chronic Health , i.e. , acute physiological derangement , age , and reason for admission , but the Chronic Health Points component of APACHE II could not so contribute to the rest of APACHE II ( p = 0.19 ) . Our conclusion is that use of the detailed information about comorbidity captured by the Charlson index could improve prognostic predictions even for critically ill patients Carle 's Medicare Coordinated Care Demonstration care/disease management interventional components , based on the chronic care model , are described for elderly patients in 13 counties in Illinois . Patients enrolled in the program are diagnosed with chronic obstructive pulmonary disease , coronary artery disease , diabetes , atrial fibrillation , or congestive heart failure . Primary care teams are made up of a primary care physician , an advanced practice nurse , a nurse case manager , and a case assistant . The patient/family is the cornerstone of the intervention , which is evaluated using a prospect i ve , longitudinal r and omized treatment-control design BACKGROUND : The comorbidity of type 2 diabetes mellitus ( T2DM ) and depression is associated with poor glycemic control . Exercise has been shown to improve mood and glycemic control , but individuals with comorbid T2DM and depression are disproportionately sedentary compared to the general population and report more difficulty with exercise . Behavioral activation , an evidence -based depression psychotherapy , was design ed to help people with depression make gradual behavior changes , and may be helpful to build exercise adherence in sedentary population s. This pilot r and omized clinical trial will test the feasibility of a group exercise program enhanced with behavioral activation strategies among women with comorbid T2DM and depression . METHODS / DESIGN : Sedentary women with inadequately controlled T2DM and depression ( N=60 ) will be r and omly assigned to one of two conditions : exercise or usual care . Participants r and omized to the exercise condition will attend 38 behavioral activation-enhanced group exercise classes over 24 weeks in addition to usual care . Participants r and omized to the usual care condition will receive depression treatment referrals and print information on diabetes management via diet and physical activity . Assessment s will occur at baseline and 3- , 6- , and 9-months following r and omization . The goals of this pilot study are to demonstrate feasibility and intervention acceptability , estimate the re sources and costs required to deliver the intervention and to estimate the st and ard deviation of continuous outcomes ( e.g. , depressive symptoms and glycosylated hemoglobin ) in preparation for a fully-powered r and omized clinical trial . DISCUSSION : A novel intervention that combines exercise and behavioral activation strategies could potentially improve glycemic control and mood in women with comorbid type 2 diabetes and depression . TRIAL REGISTRATION : NCT01024790 BACKGROUND The prevalence , health care expenditures , and hospitalization experiences are important considerations among elderly population s with multiple chronic conditions . METHODS A cross-sectional analysis was conducted on a nationally r and om sample of 1 217 103 Medicare fee-for-service beneficiaries aged 65 and older living in the United States and enrolled in both Medicare Part A and Medicare Part B during 1999 . Multiple logistic regression was used to analyze the influence of age , sex , and number of types of chronic conditions on the risk of incurring inpatient hospitalizations for ambulatory care sensitive conditions and hospitalizations with preventable complications among aged Medicare beneficiaries . RESULTS In 1999 , 82 % of aged Medicare beneficiaries had 1 or more chronic conditions , and 65 % had multiple chronic conditions . Inpatient admissions for ambulatory care sensitive conditions and hospitalizations with preventable complications increased with the number of chronic conditions . For example , Medicare beneficiaries with 4 or more chronic conditions were 99 times more likely than a beneficiary without any chronic conditions to have an admission for an ambulatory care sensitive condition ( 95 % confidence interval , 86 - 113 ) . Per capita Medicare expenditures increased with the number of types of chronic conditions from $ 211 among beneficiaries without a chronic condition to $ 13 973 among beneficiaries with 4 or more types of chronic conditions . CONCLUSIONS The risk of an avoidable inpatient admission or a preventable complication in an inpatient setting increases dramatically with the number of chronic conditions . Better primary care , especially coordination of care , could reduce avoidable hospitalization rates , especially for individuals with multiple chronic conditions OBJECTIVE To compare the impact of group outpatient visits to traditional " physician-patient dyad " care among older chronically ill HMO members on health services utilization and cost , self-reported health status , and patient and physician satisfaction . DESIGN A 1-year r and omized trial . SETTING A group model HMO in the Denver Metropolitan area . PARTICIPANTS Three hundred twenty-one members aged 65 and older , r and omized to a group visit intervention ( n = 160 ) or to usual care ( n = 161 ) . INTERVENTION Patients with high health services utilization and one or more chronic conditions had monthly group visits with their primary care physician and nurse . Visits included health education , prevention measures , opportunities for socialization , mutual support , and for one-to-one consultations with their physician , where necessary . MEASUREMENTS Health services utilization and associated cost , health status , and patient and physician satisfaction . RESULTS Outcome measures obtained after a 1-year follow-up period showed that group participants had fewer emergency room visits ( P = .009 ) , visits to subspecialists ( P = .028 ) , and repeat hospital admissions per patient ( P = .051 ) . Group participants made more visits ( P = .021 ) and calls ( P = .038 ) to nurses than control group patients and fewer calls to physicians ( P = .019 ) . In addition , a greater percentage of group participants received influenza and pneumonia vaccinations ( P < .001 ) . Group participants had greater overall satisfaction with care ( P = .019 ) , and participating physicians reported higher levels of satisfaction with the groups than with individual care . No differences were observed between groups on self-reported health and functional status . Cost of care per member per month was $ 14.79 less for the group participants . CONCLUSIONS Group visits for chronically ill patients reduce repeat hospital admissions and emergency care use , reduce cost of care , deliver certain preventive services more effectively , and increase patient and physician satisfaction CONTEXT Patients with depression and poorly controlled diabetes mellitus , coronary heart disease ( CHD ) , or both have higher medical complication rates and higher health care costs , suggesting that more effective care management of psychiatric and medical disease control might also reduce medical service use and enhance quality of life . OBJECTIVE To evaluate the cost-effectiveness of a multicondition collaborative treatment program ( TEAMcare ) compared with usual primary care ( UC ) in out patients with depression and poorly controlled diabetes or CHD . DESIGN R and omized controlled trial of a systematic care management program aim ed at improving depression scores and hemoglobin A(1c ) ( HbA(1c ) ) , systolic blood pressure ( SBP ) , and low-density lipoprotein cholesterol ( LDL-C ) levels . SETTING Fourteen primary care clinics of an integrated health care system . PATIENTS Population -based screening identified 214 adults with depressive disorder and poorly controlled diabetes or CHD . INTERVENTION Physician-supervised nurses collaborated with primary care physicians to provide treatment of multiple disease risk factors . MAIN OUTCOME MEASURES Blinded assessment s evaluated depressive symptoms , SBP , and HbA(1c ) at baseline and at 6 , 12 , 18 , and 24 months . Fasting LDL-C concentration was assessed at baseline and at 12 and 24 months . Health plan accounting records were used to assess medical service costs . Quality -adjusted life-years ( QALYs ) were assessed using a previously developed regression model based on intervention vs UC differences in HbA(1c ) , LDL-C , and SBP levels over 24 months . RESULTS Over 24 months , compared with UC controls , intervention patients had a mean of 114 ( 95 % CI , 79 to 149 ) additional depression-free days and an estimated 0.335 ( 95 % CI , -0.18 to 0.85 ) additional QALYs . Intervention patients also had lower mean outpatient health costs of $ 594 per patient ( 95 % CI , -$3241 to $ 2053 ) relative to UC patients . CONCLUSIONS For adults with depression and poorly controlled diabetes , CHD , or both , a systematic intervention program aim ed at improving depression scores and HbA(1c ) , SBP , and LDL-C levels seemed to be a high-value program that for no or modest additional cost markedly improved QALYs . TRIAL REGISTRATION clinical trials.gov Identifier : OBJECTIVES To assess the feasibility , validity and responsiveness of an individualized measure-- goal attainment scaling-in long-term care . DESIGN Prospect i ve descriptive study . SETTING One academic and three community-based long-term care facilities . SUBJECTS 53 nursing-home patients seen in consultation between July 1996 and June 1997 . INTERVENTION Specialized geriatric medicine consultation . MAIN OUTCOME MEASURES Effect size and relative efficiency of the Barthel index , hierarchical assessment of balance and mobility , global deterioration scale , axis 8 ( behaviour ) of the brief cognitive rating scale , cumulative illness rating scale and the goal attainment scale . RESULTS Mean goal attainment scale at follow-up was 46+/-7 . The goal attainment scale was the most responsive measure , with an effect size of 1.29 and a relative efficiency of 53.7 . The goal attainment scale did not correlate well with the other measures ( -0.22 to 0.17 ) . CONCLUSION Goal attainment scaling is a feasible and responsive measure in long-term care . Although fewer problems in nursing-home patients than elderly in patients are susceptible to intervention , clinical ly important goals can be achieved in this population Background The impact of educational strategies in the management of adverse treatment effects and drug interactions in adult patients with epilepsy with comorbidities remains undetermined . Objective The EDU-COM study is a r and omised , pragmatic trial investigating the effect of a patient-tailored educational plan in patients with epilepsy with comorbidity . Methods 174 adult patients with epilepsy with chronic comorbidities , multiple-drug therapy and reporting at least one adverse treatment effect and /or drug interaction at study entry were r and omly assigned to the educational plan or usual care . The primary endpoint was the number of patients becoming free from adverse treatment events and /or drug interactions after a 6-month follow-up . The number of adverse treatment events and drug interactions , health-related quality of life ( HRQOL ) summary score changes and the monetary costs of medical contacts and drugs were assessed as secondary outcomes . Results The primary endpoint was met by 44.0 % of patients receiving the educational plan versus 28.9 % of those on usual care ( p=0.0399 ) . The control group reported a significantly higher risk not to meet successfully the primary endpoint at the end of the study : OR ( 95 % CI ) of 2.29 ( 1.03 to 5.09 ) . A separate analysis on drug adverse effects and drug interactions showed that the latter were more sensitive to the effect of educational treatment . Quality of life and costs were not significantly different in the two groups . Conclusions A patient-tailored educational strategy is effective in reducing drug-related problems ( particularly drug interactions ) in epilepsy patients with chronic comorbidities , without adding significant monetary costs . Registered at Clinical Trials.gov , identifier NCT01804322 , ( http://www . clinical trials.gov ) The authors describe a medical center-based r and omized trial aim ed at determining the feasibility and effectiveness of partnering patients and primary -care providers with an exercise health counselor . Study participants included 165 veterans age 70 years and older . The primary end point was change in physical activity at 3 and 6 months comparing patients receiving high-intensity physical activity counseling , attention control counseling , and usual care after receiving st and ardized clinic-based counseling . We noted a significant Group x Time interaction ( p = .041 ) for physical activity frequency and a similar effect for caloric expenditure ( p = .054 ) . Participants receiving high-intensity counseling and usual care increased physical activity over the short term , but those with usual care returned to baseline by the end of the study . The intervention was well received by practitioners and patients . We conclude that partnering primary -care providers with specialized exercise counselors for age- and health-appropriate physical activity counseling is effective BACKGROUND With a lifetime risk for major depressive disorder of up to 50 % , depression is a common comorbidity in multiple sclerosis but remains widely underdiagnosed and untreated . We investigated the potential of a fully automated , internet-based , cognitive behavioural therapy programme , Deprexis , to reduce depressive symptoms in patients with multiple sclerosis . METHODS For this r and omised controlled trial , we recruited patients from an outpatient clinic in Hamburg , Germany . Patients aged 18 - 65 years were eligible for inclusion if they had multiple sclerosis and self-reported depressive symptoms . By use of a computer-generated r and omisation sequence , we allocated 90 patients ( 1:1 ; no blocking or stratification ) to either the intervention group or a waitlist control group for 9 weeks . The primary endpoint was the Beck Depression Inventory ( BDI ) , as assessed by an intention-to-treat analysis . This trial is registered with Clinical Trials.gov , number NCT01663649 . FINDINGS 71 patients completed the trial : 35 patients in the intervention group and 36 patients in the control group . During the intervention , BDI scores decreased in the Deprexis group and increased in the control group , yielding a positive effect of Deprexis relative to the waitlist group ( mean group difference -4·02 points [ 95 % CI -7·26 to -0·79 ] , p=0·015 , effect size d=0·53 ) . Worsening of depressive symptoms from below to above the clinical cutoff ( BDI > 13 ) occurred in three ( 7 % ) of 45 patients in the control group and no patients in the Deprexis group . We noted no adverse events with respect to new occurrence of suicidal ideation during the trial . INTERPRETATION Psychological online-intervention programmes could be suitable for patients with multiple sclerosis who are unable to regularly attend therapeutic sessions because of mobility impairments . FUNDING European Union and the Deutsche Forschungsgemeinschaft BACKGROUND The quality of health care for older Americans with multiple chronic conditions is suboptimal . We design ed " Guided Care " ( GC ) to enhance quality of care by integrating a registered nurse , intensively trained in chronic care , into primary care practice s to work with physicians in providing comprehensive chronic care to 50 - 60 multimorbid older patients . METHODS We hypothesized that GC would improve the quality of health care for this population . In 2006 , we began a cluster-r and omized controlled trial of GC at eight practice s ( n = 49 physicians ) . Older patients of these practice s were eligible to participate if they were at risk for using health services heavily during the coming year . Teams of two to five physicians and their at-risk older patients were r and omized to either GC or usual care ( UC ) . Six months after baseline , participants rated the quality of their health care by answering vali date d closed-ended questions from telephone interviewers who were masked to group assignment . RESULTS Of the 13,534 older patients screened , 2391 ( 17.7 % ) were eligible to participate in the study , of which 904 ( 37.8 % ) gave informed consent and were cluster-r and omized . After 6 months , 93.8 % and 93.2 % of the GC and UC participants who remained alive and eligible completed telephone interviews . GC participants were more likely than UC participants to rate their care highly ( adjusted odds ratio = 2.0 , 95 % confidence interval , 1.2 - 3.4 , p = .006 ) , and primary care physicians were more likely to be satisfied with their interactions with chronically ill older patients and their families ( p < .05 ) . CONCLUSIONS GC improves important aspects of the quality of health care for multimorbid older persons . Additional data will become available as this trial continues BACKGROUND Effective new strategies that complement primary care are needed to reduce disability risks and improve self-management of chronic illness in frail older people living in the community . OBJECTIVE To evaluate the impact of a 1-year , senior center-based chronic illness self-management and disability prevention program on health , functioning , and healthcare utilization in frail older adults . DESIGN A r and omized controlled trial . SETTING A large senior center located in a northeast Seattle suburb . The trial was conducted in collaboration with primary care providers of two large managed care organizations . PARTICIPANTS A total of 201 chronically ill older adults seniors aged 70 and older recruited through medical practice s. INTERVENTION A targeted , multi-component disability prevention and disease self-management program led by a geriatric nurse practitioner ( GNP ) . MEASUREMENTS Self-reported Physical function , physical performance tests , health care utilization , and health behaviors . RESULTS Each of 101 intervention participants met with the GNP from 1 to 8 times ( median = 3 ) during the study year . The intervention group showed less decline in function , as measured by disability days and lower scores on the Health Assessment Question naire . Other measures of function , including the SF-36 and a battery of physical performance tests , did not change with the intervention . The number of hospitalized participants increased by 69 % among the controls and decreased by 38 % in the intervention group ( P = .083 ) . The total number of inpatient hospital days during the study year was significantly less in the intervention group compared with controls ( total days = 33 vs 116 , P = .049 ) . The intervention led to significantly higher levels of physical activity and senior center participation and significant reductions in the use of psychoactive medications . CONCLUSIONS This project provides evidence that a community-based collaboration with primary care providers can improve function and reduce inpatient utilization in chronically ill older adults . Linking organized medical care with complementary community-based interventions may be a promising direction for research and practice Background The rising prevalence of chronic conditions constitutes a major burden for patients and healthcare systems and is predicted to increase in the upcoming decades . Improving the self-management skills of patients is a strategy to steer against this burden . This could lead to better outcomes and lower healthcare costs . Health coaching is one method for enhancing the self-management of patients and can be delivered by phone . The effects of telephone-based health coaching are promising , but still inconclusive . Economic evaluations and studies examining the transferability of effects to different healthcare systems are still rare . Aim of this study is to evaluate telephone-based health coaching for chronically ill patients in Germany . Methods / Design The study is a prospect i ve r and omized controlled trial comparing the effects of telephone-based health coaching with usual care during a 4-year time period . Data are collected at baseline and after 12 , 24 and 36 months . Patients are selected based on one of the following chronic conditions : diabetes , coronary artery disease , asthma , hypertension , heart failure , COPD , chronic depression or schizophrenia . The health coaching intervention is carried out by trained nurses employed by a German statutory health insurance . The frequency and the topics of the health coaching are manual-based but tailored to the patients ’ needs and medical condition , following the concepts of motivational interviewing , shared decision-making and evidence -based-medicine . Approximately 12,000 insurants will be enrolled and r and omized into intervention and control groups . Primary outcome is the time until hospital readmission within two years after enrolling in the health coaching , assessed by routine data . Secondary outcomes are patient-reported outcomes like changes in quality of life , depression and anxiety and clinical values assessed with question naires . Additional secondary outcomes are further economic evaluations like health service use as well as costs and hospital readmission rates . The statistical analyses includes intention-to-treat and as-treated principles . The recruitment will be completed in September 2014 . Discussion This study will provide evidence regarding economic and clinical effects of telephone-delivered health coaching . Additionally , this study will show whether health coaching is an adequate option for the German healthcare system to address the growing burden of chronic diseases . Trial registration German Clinical Trials Register ( Deutsches Register Klinischer Studien ; DRKS ) DRKS00000584 OBJECTIVES To explore changes in mortality and hospital usage for chronically ill seniors enrolled in a multidisease care management program , Care Management Plus ( CMP ) . DESIGN Controlled clinical trial with seven intervention and six control clinics with additional patient-level matching . SETTING Intermountain Health Care , a large health system in Utah ; seven intervention and six control clinics . PARTICIPANTS Three thous and four hundred thirty-two senior patients ( > or=65 ) enrolled in Medicare . INTERVENTION The intervention employed nurse care managers supported by specialized information technology in primary care to manage chronically ill patients ( 2002 - 2005 ) . MEASUREMENTS Mortality and hospitalization data were collected from clinical records and Medicare billing . RESULTS One thous and one hundred forty-four intervention patients were matched to 2,288 controls . Average age was 76.2 ; average comorbidity score was 2.3+/-1.1 ; 75 % of patients had two or more chronic diseases . Survival analyses showed lower mortality and slightly more emergency department visits for care managed patients than for controls . In patients with diabetes mellitus , the intervention result ed in significantly lower mortality at 1 year ( 6.2 % , vs 10.6 % for controls ) and at 2 years ( 12.9 % vs 18.2 % ) . Hospitalization rate was lower ( 21.0 % , vs. 24.2 % for controls ) at 1 year and substantially more so at the 2-year follow-up . CONCLUSION CMP was successful in reducing death for all patients . For complex patients with diabetes mellitus in the intervention group , death and hospital usage were lower . Per clinic , hypothesized savings from decreased hospitalizations was $ 17,384 to $ 70,349 |
848 | 30,045,939 | Patients and carers expect their GPs to be competent in all aspects of palliative care .
They valued easy access to their GP , a multidisciplinary approach to care and well-coordinated and informed care .
They also wanted their care team to communicate openly , honestly and empathically , particularly as the patient deteriorated .
ACP and the involvement of GPs were important factors which contributed to patients being cared for and dying in their preferred place .
Patients and carers prefer a holistic approach to care .
This review shows that GPs have an important role in ACP and that their involvement facilitates dying in the place of preference . | BACKGROUND With an increasing ageing population in most countries , the role of general practitioners ( GPs ) and general practice nurses ( GPNs ) in providing optimal end of life ( EoL ) care is increasingly important .
OBJECTIVE To explore : ( 1 ) patient and carer expectations of the role of GPs and GPNs at EoL ; ( 2 ) GPs ' and GPNs ' contribution to advance care planning ( ACP ) and ( 3 ) if primary care involvement allows people to die in the place of preference . | The lay caregiving role is integral to advanced cancer care but places carers ' health at risk . A supportive General Practitioner ( GP ) can help primary lay carers manage their health , if they disclose their concerns . A Needs Assessment Tool for Caregivers ( NAT-C ) was developed for carers to self-complete and use as the basis of a GP consultation , then tested in a r and omised controlled trial . This paper reports a qualitative research study to determine the usefulness and acceptability of the NAT-C in the Australian primary care setting . Convenience sample s of 11 carers and 5 GPs were interviewed between September 2010 and December 2011 regarding their experiences with and perceptions of the NAT-C. Open-ended questions were used , and the transcripts were analysed qualitatively to identify themes and patterns . Three major themes were identified : ( a ) Acceptability of the intervention ; ( b ) Impact of the intervention on the GP-patient relationship ; and ( c ) Place of the intervention in advanced cancer care . This simple checklist was acceptable to carers , although some were uncertain about the legitimacy of discussing their own needs with their GP . Carer- patients could not be certain whether a GP would be willing or equipped to conduct a NAT-C-based consultation . Such consultations were acceptable to most GPs , although some already used a holistic approach while others preferred brief symptom-based consultations . Although the NAT-C was acceptable to most carers and GPs , supportive consultations take time . This raises organisational issues to be addressed so carers can seek and benefit from their GP 's support CONTEXT A clear underst and ing of what patients , families , and health care practitioners view as important at the end of life is integral to the success of improving care of dying patients . Empirical evidence defining such factors , however , is lacking . OBJECTIVE To determine the factors considered important at the end of life by patients , their families , physicians , and other care providers . DESIGN AND SETTING Cross-sectional , stratified r and om national survey conducted in March-August 1999 . PARTICIPANTS Seriously ill patients ( n = 340 ) , recently bereaved family ( n = 332 ) , physicians ( n = 361 ) , and other care providers ( nurses , social workers , chaplains , and hospice volunteers ; n = 429 ) . MAIN OUTCOME MEASURES Importance of 44 attributes of quality at the end of life ( 5-point scale ) and rankings of 9 major attributes , compared in the 4 groups . RESULTS Twenty-six items consistently were rated as being important ( > 70 % responding that item is important ) across all 4 groups , including pain and symptom management , preparation for death , achieving a sense of completion , decisions about treatment preferences , and being treated as a " whole person . " Eight items received strong importance ratings from patients but less from physicians ( P<.001 ) , including being mentally aware , having funeral arrangements planned , not being a burden , helping others , and coming to peace with God . Ten items had broad variation within as well as among the 4 groups , including decisions about life-sustaining treatments , dying at home , and talking about the meaning of death . Participants ranked freedom from pain most important and dying at home least important among 9 major attributes . CONCLUSIONS Although pain and symptom management , communication with one 's physician , preparation for death , and the opportunity to achieve a sense of completion are important to most , other factors important to quality at the end of life differ by role and by individual . Efforts to evaluate and improve patients ' and families ' experiences at the end of life must account for diverse perceptions of quality . JAMA . 2000;284:2476 - 2482 Background Due to a rising number of deaths from cancer and other chronic diseases a growing number of people experience complex symptoms and require palliative care towards the end of life . However , population -based data on the number of people receiving palliative care in Europe are scarce . The objective of this study is to examine , in four European countries , the number of people receiving palliative care in the last three months of life and the factors associated with receiving palliative care . Methods Cross-national retrospective study . Over two years ( 2009–2010 ) , GPs belonging to representative epidemiological surveillance networks in Belgium , the Netherl and s , Italy , and Spain registered weekly all deaths of patients ( ≥18 years ) in their practice s and the care they received in the last three months of life using a st and ardized form . Sudden deaths were excluded . Results We studied 4,466 deaths . GPs perceived to have delivered palliative care to 50 % of patients in Belgium , 55 % in Italy , 62 % in the Netherl and s , and 65 % in Spain ( p<.001 ) . Palliative care specialists attended to 29 % of patients in the Netherl and s , 39 % in Italy , 45 % in Spain , and 47 % in Belgium ( p<.001 ) . Specialist palliative care lasted a median ( inter-quartile range ) of 15 ( 23 ) days in Belgium to 30 ( 70 ) days in Italy ( p<.001 ) . Cancer patients were more likely than non-cancer patients to receive palliative care in all countries as were younger patients in Italy and Spain with regard to specialist palliative care . Conclusions Although palliative care is established in the countries studied , there are considerable differences in its provision . Two potentially underserved groups emerge non-cancer patients in all countries and older people in Italy and Spain . Future research should examine how differences in palliative care use relate to both patient characteristics and existing national health care policies OBJECTIVE Despite being ideally placed to provide care to patients with terminal illness , many general practitioners ( GPs ) are not involved in palliative care . This study aim ed to determine the level of participation of Australian urban GPs in palliative care , and to determine the main barriers facing them in providing this care . DESIGN Cross-sectional postal survey . PARTICIPANTS AND SETTING Between March and May 2007 a r and om sample of 500 GPs from southwestern and northern regions of Sydney were surveyed . MAIN OUTCOME MEASURES Involvement in palliative care ; personal and professional characteristics of the GPs related to the provision of palliative care ; GPs ' views on barriers to their involvement in palliative care ; GPs ' confidence levels across different issues in palliative medicine . RESULTS Response rate was 61 % and of these 25 % of GPs were not involved in palliative care . GPs not providing palliative care were more likely to be younger , have less GP experience , work less hours , be an employee rather than a practice owner , and educated overseas . Main barriers to GPs ' involvement in palliative care were lack of interest and knowledge , home visits , problems with after-hours care due to family and personal commitments . GPs felt least confident about psychosocial problems and technical aspects of palliative medicine . CONCLUSION About one quarter of GPs surveyed are not involved in palliative care . Strategies to increase GPs ' involvement should aim at increasing their knowledge and interest in palliative care . Innovations in service provider models are required to overcome the barriers to provision of after-hours care Objective To investigate the impact of advance care planning on end of life care in elderly patients . Design Prospect i ve r and omised controlled trial . Setting Single centre study in a university hospital in Melbourne , Australia . Participants 309 legally competent medical in patients aged 80 or more and followed for six months or until death . Interventions Participants were r and omised to receive usual care or usual care plus facilitated advance care planning . Advance care planning aim ed to assist patients to reflect on their goals , values , and beliefs ; to consider future medical treatment preferences ; to appoint a surrogate ; and to document their wishes . Main outcome measures The primary outcome was whether a patient ’s end of life wishes were known and respected . Other outcomes included patient and family satisfaction with hospital stay and levels of stress , anxiety , and depression in relatives of patients who died . Results 154 of the 309 patients were r and omised to advance care planning , 125 ( 81 % ) received advance care planning , and 108 ( 84 % ) expressed wishes or appointed a surrogate , or both . Of the 56 patients who died by six months , end of life wishes were much more likely to be known and followed in the intervention group ( 25/29 , 86 % ) compared with the control group ( 8/27 , 30 % ; P<0.001 ) . In the intervention group , family members of patients who died had significantly less stress ( intervention 5 , control 15 ; P<0.001 ) , anxiety ( intervention 0 , control 3 ; P=0.02 ) , and depression ( intervention 0 , control 5 ; P=0.002 ) than those of the control patients . Patient and family satisfaction was higher in the intervention group . Conclusions Advance care planning improves end of life care and patient and family satisfaction and reduces stress , anxiety , and depression in surviving relatives . Trial registration Australian New Zeal and clinical trials registry ACTRN12608000539336 BACKGROUND : Discussion s of end-of-life care should be held prior to acute , disabling events . Many barriers to having such discussion s during primary care exist . These barriers include time constraints , communication difficulties , and perhaps physicians ’ anxiety that patients might react negatively to such discussion s. OBJECTIVE : To assess the impact of discussion s of advance directives on patients ’ satisfaction with their primary care physicians and outpatient visits . DESIGN : Prospect i ve cohort study of patients enrolled in a r and omized , controlled trial of the use of computers to remind primary care physicians to discuss advance directives with their elderly , chronically ill patients . SETTING : Academic primary care general internal medicine practice affiliated with an urban teaching hospital . PARTICIPANTS : Six hundred eighty-six patients who were at least 75 years old , or at least 50 years old with serious underlying disease , and their 87 primary care physicians ( 57 residents , 30 faculty general internists ) participated in the study . MEASUREMENTS AND MAIN RESULTS : We assessed patients ’ satisfaction with their primary care physicians and visits via interviews held in the waiting room after completed visits . Controlling for satisfaction at enrollment and physician , patient , and visit factors , discussing advance directives was associated with greater satisfaction with the physician ( P=.052 ) . At follow-up , the strongest predictor of satisfaction with the primary care visit was having previously discussed advance directives with that physician ( P=.004 ) , with a trend toward greater visit satisfaction when discussion s were held during that visit ( P=.069 ) . The percentage of patients scoring a visit as “ excellent ” increased from 34 % for visits prior without advance directive discussion s to 51 % for visits with such discussion s ( P=.003 ) . CONCLUSIONS : Elderly patients with chronic illnesses were more satisfied with their primary care physicians and outpatient visits when advanced directives were discussed . The improvement in visit satisfaction was substantial and persistent . This should encourage physicians to initiate such discussion s to overcome communication barriers that might result in reduced patient satisfaction levels OBJECTIVE Late or non-referral of patients to specialist palliative care ( SPC ) services may affect patients ' and their carers ' quality of care . General practitioners ( GPs ) are key professionals in linking people with SPC . The aim of this article is to assess GPs ' perceptions and SPC referrals for their patients with advanced cancer and differences between metropolitan ( M GPs ) and non-metropolitan GPs ( NM GPs ) . METHOD Self-report survey mailed to a stratified r and om sample of 1,680 Australian GPs was used . RESULTS Thirty-one percent ( 469 ) of eligible GPs returned surveys . More M GPs than NM GPs reported referring > 60 % of their patients for SPC ( p = 0.014 ) ; and that a more comprehensive range of SPC services was available . The most frequently reported referral prompts were : presence of terminal illness ( M GPs , 71 % , NM GPs , 66 % , ns ( not significant ) ) ; future need for symptom control ( 69 % vs. 59 % , ns ) and uncontrolled physical symptoms ( 63 % vs. 54 % , ns ) . Reasons for not referring were : doctor 's ability to manage symptoms ( 62 % vs. 68 % , ns ) and the absence of symptoms ( 29 % vs. 18 % , p = 0.025 ) . Higher referral was associated with : having a palliative care physician or consultative service available ; agreeing that all patients with advanced cancer should be referred , and agreeing that with SPC , the needs of the family are better met . SIGNIFICANCE OF RESULTS Referrals for SPC were primarily disease-related rather than for psychological and emotional concerns . Measures are needed to encourage referrals based upon psychosocial needs as well as for physical concerns , and to support GPs caring for people with advanced cancer in areas with fewer comprehensive SPC services We surveyed primary care physicians about their involvement and perceived skills in palliative care . A survey instrument asked how frequently internal medicine and family practice physicians performed 10 palliative care items . Subjects rated their skills in each area . A majority of physicians always or frequently performed all 10 palliative care items , but fewer than 50 % of respondents adequately attended to the spiritual needs and economic problems of patients . Interest in palliative care was associated with an increased frequency in performing palliative care items ( P = 0.036 ) , while training in palliative care was associated with better perceived performance ( P = 0.05 ) . Only 36 % of respondents had received training in palliative care . Internists and family practitioners provide palliative care to patients , but feel their skills are lacking in certain areas . Training may improve care to patients at the end of life The objectives of this study were to establish the extent to which UK primary care has adopted recommended practice s on supportive and palliative care of adults with cancer , and to relate this to participation in national initiatives . We conducted a cross-sectional postal question naire survey of a r and om sample of UK general practice s. In total , 60.0 % of practice s ( 2096 of 3495 ) responded to the survey : 61.5 % reported involvement with the Gold St and ards Framework ( GSF ) ; 24.4 % with the Liverpool or other End of Life Care Pathway ; 12.3 % , with the Preferred Place of Care ( PPC ) initiative ; and 8.4 % with Advance Care Planning ( ACP ) . Participation in GSF contributed most to the variance in practice organization scores ; and practice organization scores contributed most to the variance in clinical care scores . Participation in ACP or PPC , and higher clinical care scores were associated with an increased likelihood of reported high rates of death at home for cancer patients . Our findings appear to support the role of national initiatives in improving the quality of end-of-life care delivery in general practice . A population -based study would be required to assess the effect of end of life care on clinical outcomes and patient or carer experience BACKGROUND Advance care planning ( ACP ) provides patients with the ability to make their decisions known about how they would like to be treated if they lose capacity . Medical practitioners have a key role to play in providing information on ACP to their patients . This research explores their knowledge and attitudes to advance care planning and how this affects their practice . AIM The objective of this study is to assess the NSW medical practitioners ' knowledge and self-reported practice of ACP . METHODS A postal survey of a r and om sample of 650 general practitioners plus 350 medical specialists from specialties most often involved in end-of-life decisions was conducted . Respondents ' work location post codes were subsequently used to assign respondents to one of the eight NSW Area Health Services . The main outcome measures were medical practitioners ' knowledge of and practice pertaining to ACP . RESULTS Thirty-four per cent of specialists ( n = 110 ) and 24 % of general practitioners ( n = 150 ) responded ; the majority of respondents had heard of all ACP options . However , respondents ' underst and ing of the uses and legal requirements of the relevant ACP options vary widely . CONCLUSIONS Respect for patient wishes expressed in advance directives is reassuringly high . The findings suggest significant misunderst and ing by medical practitioners of terminologies and systems around substitute decision-making for incompetent persons . Further education and st and ardisation of terminologies and systems across different jurisdictions would assist in addressing these issues . Low response rate , relating to only one legal jurisdiction , means results may not be generalisable This prospect i ve study was design ed to assess whether patients with terminal cancer , and their relatives , find that competent home care sufficiently maintains comfort and helps adjustment . A r and om sample from a home care service with readily available beds comprised 77 adults and their relatives who were able and willing to be interviewed separately each week . They were asked the nature and degree of current problems and regular assessment s were made of some qualities of life including mood , attitude to the condition , perceived help and preferred place of care . These patients had 90 % of their care at home ; 29 % died at home but 30 % were finally admitted for one to three days and 41 % for longer . In the final eight weeks , tolerable physical symptoms were volunteered by a mean of 63 % each week and psychological symptoms by 17 % . Some distress was felt by 11 % of patients ; this was usually from pain , depression , dyspnoea , anxiety or weakness , and generally did not persist . Relatives suffered grief , strain or their own ill health . Patients ' and relatives ' reports generally matched except for the strain on carers . Regular assessment s found that 64 % of patients thought death certain or probable , and 27 % thought it possible . Various proportions coped by optimism , fighting their disease , partial suppression or denial , but 50 % reached positive acceptance . Relatives were more aware and accepting . About three-quarters of patients and half the relatives were composed , often enjoying life . Serious depression affected 5 % of patients and anxiety 4 % , but relatives ' manifest depression in the later stages increased to 17 % and anxiety to 14 % . Many consciously disguised their feelings . Treatment was usually praised but realistic preference for home care fell steadily from 100 % to 54 % of patients and 45 % of relatives . At follow-up most relatives approved of where patients had received care and died |
849 | 31,719,846 | Overall , adverse events seemed to be similar between fibrate and placebo , but again based on the width of the confidence intervals , an important increase of adverse events can not be rule out .
Based on these findings , we are uncertain about the effects of statins for DR . | Evidence from observational studies have found a relationship between serum cholesterol and diabetic retinopathy ( DR ) .
Apart of the assumption that cholesterolemic control has benefits for patients with diabetes with or without retinopathy , the effects of lipid-lowering drugs have not been properly mapped and critically assessed so far .
The objective of this study was to evaluate the effects of statins and /or fibrates on prevention and progression of DR . | Background Diabetic retinopathy ( DR ) is a common microvascular complication of diabetes mellitus , and more than 75 % of patients who have had diabetes for more than 20 years will have some degree of DR . This disease is highly destructive to self-esteem and puts a high burden on public health and pension systems due to the effects that it has on people of working age . The current mainstay of treatment is laser photocoagulation , which causes impairment of vision and discomfort to patients . Thus , finding a systemic drug that could act on all microcirculation and prevent direct manipulation of the eyes would be highly desirable . Objective To assess the efficacy and safety of the drugs in the statin and /or fibrate groups for the prevention and treatment of DR . Methods In this systematic review , we will select r and omized controlled trials of fibrates or statins used for the treatment or prevention of DR . Our search strategy will include free text terms and controlled vocabulary ( eg , MeSH , Emtree ) for , “ diabetic retinopathy ” , “ statins ” , “ fibrates ” , “ hypolipidemic agents ” , and for drugs from both groups . Data bases that will be used include Medical Literature Analysis and Retrieval System/ PubMed , Embase , Cochrane Central Register of Controlled Trials , Latin American and Caribbean Center on Health Sciences Information , Clinical trials.gov , World Health Organization International Clinical Trials Registry Platform , and OpenGrey , and we will not have language or date limits . Two review authors will independently select eligible studies and assess the risk of bias using the Cochrane Collaboration ’s tool . We will report structured summaries of the included studies and , if possible , conduct meta-analyses . Results This is a protocol for a systematic review , therefore results are not available . We registered a short version of this protocol before progressing in the review and we are currently in the process of selecting the studies for inclusion . Conclusions Intensive glucose control and lowering blood pressure and lipids are mechanisms that protect macrocirculation in diabetic patients . Both macrovascular and microvascular events in diabetic patients appear to have a common pathway , starting with endothelial injury . Thus , prevention and treatment of microvascular events may benefit from the same interventions . In the review for which we have written this protocol , we will assess whether the use of lipid-lowering oral drugs of the statin and /or fibrate groups may prevent and /or retard progression of DR , with the added benefit of preserving visual acuity . Trial Registration PROSPERO A three-year trial of Atromid treatment in exudative diabetic retinopathy was carried out in twenty-three patients and twenty-five controls . In comparison with those of the controls the eyes of the Atromid-treated patients showed a highly significant decrease in hard waxy exu date s ( p = < 0.0001 ) which was not , however , accompanied by appreciable improvement in visual acuity . No improvement in the vascular retinal lesions occurred . The initial severity of the exudative lesions was not related to the fasting serum cholesterol or triglyceride levels ; there was also no correlation between the effect of Atromid on the exu date s and on these serum lipids . The way in which Atromid might influence exu date deposition and its possible use in the treatment of exudative diabetic retinopathy are discussed Background Synthesis of multiple r and omized controlled trials ( RCTs ) in a systematic review can summarize the effects of individual outcomes and provide numerical answers about the effectiveness of interventions . Filtering of search es is time consuming , and no single method fulfills the principal requirements of speed with accuracy . Automation of systematic review s is driven by a necessity to expedite the availability of current best evidence for policy and clinical decision-making . We developed Rayyan ( http://rayyan.qcri.org ) , a free web and mobile app , that helps expedite the initial screening of abstract s and titles using a process of semi-automation while incorporating a high level of usability . For the beta testing phase , we used two published Cochrane review s in which included studies had been selected manually . Their search es , with 1030 records and 273 records , were uploaded to Rayyan . Different features of Rayyan were tested using these two review s. We also conducted a survey of Rayyan ’s users and collected feedback through a built-in feature . Results Pilot testing of Rayyan focused on usability , accuracy against manual methods , and the added value of the prediction feature . The “ taster ” review ( 273 records ) allowed a quick overview of Rayyan for early comments on usability . The second review ( 1030 records ) required several iterations to identify the previously identified 11 trials . The “ suggestions ” and “ hints , ” based on the “ prediction model , ” appeared as testing progressed beyond five included studies . Post rollout user experiences and a reflexive response by the developers enabled real-time modifications and improvements . The survey respondents reported 40 % average time savings when using Rayyan compared to others tools , with 34 % of the respondents reporting more than 50 % time savings . In addition , around 75 % of the respondents mentioned that screening and labeling studies as well as collaborating on review s to be the two most important features of Rayyan . As of November 2016 , Rayyan users exceed 2000 from over 60 countries conducting hundreds of review s totaling more than 1.6 M citations . Feedback from users , obtained mostly through the app web site and a recent survey , has highlighted the ease in exploration of search es , the time saved , and simplicity in sharing and comparing include-exclude decisions . The strongest features of the app , identified and reported in user feedback , were its ability to help in screening and collaboration as well as the time savings it affords to users . Conclusions Rayyan is responsive and intuitive in use with significant potential to lighten the load of review ers PURPOSE To report additional ocular outcomes of intensive treatment of hyperglycemia , blood pressure , and dyslipidemia in the Action to Control Cardiovascular Risk in Diabetes ( ACCORD ) study . DESIGN Double 2 × 2 factorial , multicenter , r and omized clinical trials in people with type 2 diabetes who had cardiovascular disease or cardiovascular risk factors . In the glycemia trial , targets of intensive and st and ard treatment were : hemoglobin A1c < 6.0 % and 7.0 % to 7.9 % , respectively , and in the blood pressure trial : systolic blood pressures of < 120 and < 140 mmHg , respectively . The dyslipidemia trial compared fenofibrate plus simvastatin with placebo plus simvastatin . PARTICIPANTS Of the 3472 ACCORD Eye Study participants enrolled , 2856 had 4-year data ( 85 % of survivors ) . METHODS Eye examinations and fundus photographs were taken at baseline and year 4 . Photographs were grade d central ly for retinopathy severity and macular edema using the Early Treatment Diabetic Retinopathy Study ( ETDRS ) methods . MAIN OUTCOME MEASURES Three or more steps of progression on the ETDRS person scale or treatment of retinopathy with photocoagulation or vitrectomy . RESULTS As previously reported , there were significant reductions in the primary outcome in the glycemia and dyslipidemia trials , but no significant effect in the blood pressure trial . Results were similar for retinopathy progression by 1 , 2 , and 4 or more steps on the person scale and for ≥ 2 steps on the eye scale . In the subgroup of patients with mild retinopathy at baseline , effect estimates were large ( odds ratios , ∼0.30 ; P < 0.001 ) , but did not reach nominal significance for participants with no retinopathy or for those with moderate to severe retinopathy at baseline . CONCLUSIONS Slowing of progression of retinopathy by intensive treatment of glycemia was observed in ACCORD participants , whose average age and diabetes duration were 62 and 10 years , respectively , and who had cardiovascular disease or cardiovascular risk factors . The effect seemed stronger in patients with mild retinopathy . Similar slowing of progression was observed in patients treated with fenofibrate , with no effect observed with intensive blood pressure treatment . This is the second study to confirm the benefits of fenofibrate in reducing diabetic retinopathy progression , and fenofibrate should be considered for treatment of diabetic retinopathy INTRODUCTION Lipid-lowering drugs preserve vision and reduce the risk of hard exu date s in clinical ly-significant macular edema(CSME ) in diabetics with an abnormal lipid profile . But their role in reducing CSME in diabetics with a normal lipid profile is not yet known . OBJECTIVE To evaluate the role of atorvastatin in CSME in diabetics with a normal lipid profile . MATERIAL S AND METHODS A prospect i ve , r and omized clinical trial was carried out . Thirty CSME patients with a normal lipid profile were r and omly divided into Group A and B. Atorvastatin had been started in Group A four weeks prior to laser treatment . The main outcome measures were any improvement or deterioration in visual acuity and macular edema and hard exu date s at six months follow-up . STATISTICS Both the groups were compared using unpaired t test for quantitative parameters and chi-square test for qualitative parameters . A p value of less than 0.05 was taken as significant . RESULTS Visual acuity , macular edema and hard exu date s resolution was not significantly different in the two groups ( P = 0.14 , 0.62 , 0.39 respectively ) . CONCLUSION Atorvastatin does not affect treatment outcome in CSME with a normal lipid profile over a short term follow-up OBJECTIVE To evaluate the relationship between serum lipid levels , retinal hard exu date , and visual acuity in patients with diabetic retinopathy . DESIGN Observational data from the Early Treatment Diabetic Retinopathy Study . PARTICIPANTS Of the 3711 patients enrolled in the Early Treatment Diabetic Retinopathy Study , the first 2709 enrolled had serum lipid levels measured . MAIN OUTCOME MEASURES Baseline fasting serum lipid levels , best-corrected visual acuity , and assessment of retinal thickening and hard exu date from stereoscopic macular photographs . RESULTS Patients with elevated total serum cholesterol levels or serum low-density lipoprotein cholesterol levels at baseline were twice as likely to have retinal hard exu date s as patients with normal levels . These patients were also at higher risk of developing hard exu date during the course of the study . The risk of losing visual acuity was associated with the extent of hard exu date even after adjusting for the extent of macular edema . CONCLUSIONS These data demonstrate that elevated serum lipid levels are associated with an increased risk of retinal hard exu date in persons with diabetic retinopathy . Although retinal hard exu date usually accompanies diabetic macular edema , increasing amounts of exu date appear to be independently associated with an increased risk of visual impairment . Lowering elevated serum lipid levels has been shown to decrease the risk of cardiovascular morbidity . The observational data from the Early Treatment Diabetic Retinopathy Study suggest that lipid lowering may also decrease the risk of hard exu date formation and associated vision loss in patients with diabetic retinopathy . Preservation of vision may be an additional motivating factor for lowering serum lipid levels in persons with diabetic retinopathy and elevated serum lipid levels Besides hyperglycemia and hypertension , a recently recognized risk factor for diabetic retinopathy ( DR ) appears to be hyperlipidemia . While studies using earlier generation lipid lowering agents in DR were disappointing , a r and omized trial using HMG-CoA Reductase Inhibitors has strong rationale , though hitherto not attempted . The aim of the present study was to compare the HMG-CoA Reductase Inhibitor , simvastatin , with placebo in patients having DR in a double-blind r and omized placebo-controlled trial . Fifty patients with diabetes mellitus ( Type 1 and 2 ) with good glycemic control and hypercholesterolemia and having DR ( non- clinical ly significant macular edema and visual acuity 6/24 or better ) in either or both eyes were r and omized to simvastatin 20-mg per day or placebo , and were followed up for 180 days . On simvastatin therapy , total cholesterol and low-density lipoprotein cholesterol ( LDL-C ) decreased ( P < 0.001 , respectively ) , and the level of high-density lipoprotein cholesterol ( HDL-C ) increased ( P < 0.001 ) . VA improved in four patients using simvastatin , ( not statistically different from placebo group ) and worsening of VA occurred in seven patients in the placebo group and none in the simvastatin group ( P = 0.009 ) . Fundus fluorescein angiography and color fundus photograph showed improvement in one patient in the simvastatin group , while seven patients showed worsening in the placebo group ( P = 0.009 ) . The observations of the current study suggest that the HMG-CoA Reductase Inhibitor simvastatin significantly retards the progression of retinopathy in diabetic patients with hypercholesterolemia . The potential of this class of drugs for the primary prevention of DR and other microvascular complications needs to be explored further AIM Hyperlipidemia and diabetic retinopathy increase the risk of cardiovascular disease ( CVD ) . The st and ard versus intEnsive statin therapy for hypercholesteroleMic Patients with diAbetic retinopaTHY ( EMPATHY ) study examines whether intensive lipid-lowering therapy is superior to st and ard therapy in reducing the incidence of cardiovascular events in patients with hyperlipidemia and diabetic retinopathy , but without a history of coronary artery disease . METHODS Patients who had elevated low-density lipoprotein cholesterol ( LDL-C ) and diabetic retinopathy without a history of coronary artery disease were eligible for the study . Patients were r and omly assigned in a 1:1 ratio to receive intensive or st and ard therapy . Patients are being treated with monotherapy with 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor ( statin ) for a maximum of 5.5 years to achieve the following LDL-C target : ＜70 mg/dL for the intensive therapy group or ≥100 and ＜120 mg/dL for the st and ard therapy group . The primary endpoint is a composite of incidence of CVD and death from CVD . RESULTS Between May 2010 and October 2013 , 5,995 patients were assessed for eligibility , and 5,144 were assigned to the study treatment ( 2,571 and 2,573 in the intensive and st and ard therapy groups , respectively ) , and baseline data were analyzed from 5,107 ( 2,550 in the intensive therapy group and 2,557 in the st and ard therapy group ) . CONCLUSIONS This is the first study assessing the benefits of intensive statin therapy in patients with hypercholesterolemia and diabetic retinopathy in a primary prevention setting . Furthermore , this study evaluates the appropriateness of the treat-to-target approach because all patients are treated to achieve specific LDL-C targets by titrating statin therapy . CLINICAL TRIAL REGISTRATION NUMBER UMIN000003486 PURPOSE To determine the efficacy of the lipid-lowering drug atorvastatin in reducing retinal hard exu date s and subfoveal lipid migration after focal/grid laser photocoagulation in clinical ly significant macular edema in patients with diabetes with elevated serum lipids . DESIGN R and omized case trial . METHODS Thirty patients with type 2 diabetes with clinical ly significant macular edema , dyslipidemia , and hard exu date s of grade 4 and above were assessed in an institutional setting . All patients were subjected to strict metabolic control within 4 to 6 weeks of enrollment . In addition , 15 patients in group A received atorvastatin , a 3-hydroxy-3-methylglutaryl coenzyme A inhibitor ; 15 members of group B did not receive any lipid-lowering therapy . All received laser photocoagulation after a metabolic control period and were followed up for a minimum of 18 weeks . The outcome measures were reduction in hard exu date s , subfoveal lipid migration , status of macular edema , and visual acuity . RESULTS The study included 21 men and nine women with noninsulin-dependent diabetes mellitus who could achieve good metabolic control within 4 to 6 weeks of inclusion in the study . All patients had elevated serum lipids at baseline . Ten ( 66.6 % ) of 15 patients in treatment group A and two ( 13.3 % ) of 15 patients in control group B showed reduction in hard exu date s ( P = .007 ) . None of the patients in group A and five ( 33.3 % ) of 15 in group B showed subfoveal lipid migration after laser photocoagulation ( P = .04 ) . Regression of macular edema was seen in nine eyes in group A and five in group B ( P = .27 ) . None of the eyes in group A and three eyes in group B showed worsening of visual acuity ( P = .22 ) . CONCLUSION Oral atorvastatin therapy in patients with type 2 diabetes with dyslipidemia reduces the severity of hard exu date s and subfoveal lipid migration in clinical ly significant macular edema and could be an important adjunct in the management of clinical ly significant macular edema Although hyperlipidemia is associated with the development of diabetes complications , the effect of lipid reduction on microvascular complications is unknown . We initiated a 2-year , r and omized , double-blinded placebo-controlled pilot trial of simvastatin/diet vs. diet alone in Type 1 diabetic patients without overt nephropathy . Thirty-nine patients with LDL cholesterol 100 - 160 mg/dl , > 10 year duration of diabetes and an albumin excretion rate ( AER ) < 200 microg/min were recruited for study . The primary end-point was change in AER . Secondary end-points were change in ankle-brachial index , progression of retinopathy status , change in vibratory threshold , and development of new clinical neuropathy . Nineteen patients were treated with simvastatin and twenty with placebo . However , because of the lowering of drug initiation levels by the American Diabetes Association , the trial was terminated early with 2 subjects reaching 2 years , 17 reaching 18 months , 36 reaching 1 year , and all 6 months . Simvastatin significantly reduced total cholesterol ( mean on treatment 173.4 vs. 191.4 , P=.020 ) and LDL cholesterol ( mean on treatment 105.0 vs. 127.7 , P<.001 ) . Simvastatin therapy was associated with a slower rise in AER compared to placebo , though the result was not statistically significant ( median rate of change/month 0.004 vs. 0.029 ) . There was a trend towards slower progression of neuropathy as measured by vibratory threshold ( median change at 1 year 0.03 simvastatin vs. 0.94 , P=.07 ) . There was no difference in change in ankle-brachial index , clinical neuropathy status , or retinopathy status . In conclusion , treatment with simvastatin may have a beneficial effect on early nephropathy and diabetic neuropathy , justifying a fully powered trial . However , this would be difficult under current treatment guidelines We conducted a prospect i ve multicenter r and omized trial to determine both the feasibility of maintaining blood glucose control at differing levels and the effect of improved control on diabetic microangiopathy and albuminuria . Seventy patients with diabetes ( low C-peptide level ) with nonproliferative retinopathy were r and omly assigned to continuous subcutaneous insulin infusion or unchanged conventional injection treatment . At entry , both groups had similar demographic , clinical , and glycemic characteristics . Over the succeeding eight months , mean 24-hour glucose concentrations ( 175 + /- 9 mg per deciliter ) and glycosylated hemoglobin levels ( 10.0 + /- 0.3 per cent ) remained elevated during conventional treatment but fell to nearly normal levels ( 117 + /- 6 mg per deciliter and 8.1 + /- 0.2 per cent , respectively ) with continuous insulin infusion . The frequency of biochemical hypoglycemia ( less than 40 mg of blood glucose per deciliter ) was similar in both groups , but ketoacidosis occurred only during continuous infusion . The level of retinopathy , assessed from photographs , progressed in both groups . Continuous infusion was associated with slightly more deterioration , mainly because of the appearance of soft exu date s and intraretinal microvascular abnormalities . In contrast , elevated albumin-excretion rates fell during continuous infusion but not during conventional treatment . We conclude that maintenance of differing levels of blood glucose is feasible in a multicenter trial and that a nearly normal blood glucose level for eight months does not retard progression of , and may initially worsen , established retinopathy . These preliminary observations indicate the need for longer trials ( particularly of primary prevention ) BACKGROUND Type 2 diabetes is associated with a substantially increased risk of cardiovascular disease , but the role of lipid-lowering therapy with statins for the primary prevention of cardiovascular disease in diabetes is inadequately defined . We aim ed to assess the effectiveness of atorvastatin 10 mg daily for primary prevention of major cardiovascular events in patients with type 2 diabetes without high concentrations of LDL-cholesterol . METHODS 2838 patients aged 40 - 75 years in 132 centres in the UK and Irel and were r and omised to placebo ( n=1410 ) or atorvastatin 10 mg daily ( n=1428 ) . Study entrants had no documented previous history of cardiovascular disease , an LDL-cholesterol concentration of 4.14 mmol/L or lower , a fasting triglyceride amount of 6.78 mmol/L or less , and at least one of the following : retinopathy , albuminuria , current smoking , or hypertension . The primary endpoint was time to first occurrence of the following : acute coronary heart disease events , coronary revascularisation , or stroke . Analysis was by intention to treat . FINDINGS The trial was terminated 2 years earlier than expected because the prespecified early stopping rule for efficacy had been met . Median duration of follow-up was 3.9 years ( IQR 3.0 - 4.7 ) . 127 patients allocated placebo ( 2.46 per 100 person-years at risk ) and 83 allocated atorvastatin ( 1.54 per 100 person-years at risk ) had at least one major cardiovascular event ( rate reduction 37 % [ 95 % CI -52 to -17 ] , p=0.001 ) . Treatment would be expected to prevent at least 37 major vascular events per 1000 such people treated for 4 years . Assessed separately , acute coronary heart disease events were reduced by 36 % ( -55 to -9 ) , coronary revascularisations by 31 % ( -59 to 16 ) , and rate of stroke by 48 % ( -69 to -11 ) . Atorvastatin reduced the death rate by 27 % ( -48 to 1 , p=0.059 ) . No excess of adverse events was noted in the atorvastatin group . INTERPRETATION Atorvastatin 10 mg daily is safe and efficacious in reducing the risk of first cardiovascular disease events , including stroke , in patients with type 2 diabetes without high LDL-cholesterol . No justification is available for having a particular threshold level of LDL-cholesterol as the sole arbiter of which patients with type 2 diabetes should receive statins . The debate about whether all people with this disorder warrant statin treatment should now focus on whether any patients are at sufficiently low risk for this treatment to be withheld INTRODUCTION Diabetic retinopathy is the leading cause of vision loss or blindeness in working-age adults in the developed and developing countries . No curative treatments are available for diabetic retinopathy and the most common symptomatic treatment , laser photocoagulation , provides only partial and temporary relief from the progressive vascular damage caused by this disease . Etofibrate ( Lipo-Merz ) is an orally-administered treatment for lipid disorders that combines fibrate and nicotinic acid in a slow-release formulation . PATIENTS AND METHODS This report describes the results of a double-blind , r and omised , placebo-controlled study , performed to evaluate the efficacy and safety of etofibrat in patients with type 2 diabetes mellitus and concomitant diabetic retinopathy . They received either placebo or 1000 mg/day etofibrate for up to 12 months . Efficacy analyses were based on visual acuity assessment and blinded expert ratings of ocular fundus pathology , as well as laboratory analyses of serum lipid parameters . RESULTS The evaluable population comprised 296 patients , 148 in each treatment group , of whom 89 % completed the study and 73 % completed according to protocol . After 12 months of treatment , a significantly larger population of etofibrate-treated patients than placebo-treated patients showed improvements in ocular pathology ( 46 % versus 32 % , respectively , p < 0.001 ) ; similar findings were already apparent after 6 months of treatment ( 43 % versus 31 % , respectively p < 0.001 ) . Etofibrate treatment also produced significant improvements in total cholesterol , LDL-cholesterol and HDL-cholesterol in comparison to the placebo treatment group . Safety evaluations ( adverse events , laboratory parameters ) did not reveal any clinical ly significant adverse effects of etofibrate in comparison to placebo . CONCLUSION Etofibrate provides a safe and effective treatment for ocular pathology result ing from type 2 diabetes mellitus BACKGROUND Laser treatment for diabetic retinopathy is often associated with visual field reduction and other ocular side-effects . Our aim was to assess whether long-term lipid-lowering therapy with fenofibrate could reduce the progression of retinopathy and the need for laser treatment in patients with type 2 diabetes mellitus . METHODS The Fenofibrate Intervention and Event Lowering in Diabetes ( FIELD ) study was a multinational r and omised trial of 9795 patients aged 50 - 75 years with type 2 diabetes mellitus . Eligible patients were r and omly assigned to receive fenofibrate 200 mg/day ( n=4895 ) or matching placebo ( n=4900 ) . At each clinic visit , information concerning laser treatment for diabetic retinopathy-a prespecified tertiary endpoint of the main study -was gathered . Adjudication by ophthalmologists masked to treatment allocation defined instances of laser treatment for macular oedema , proliferative retinopathy , or other eye conditions . In a sub study of 1012 patients , st and ardised retinal photography was done and photographs grade d with Early Treatment Diabetic Retinopathy Study ( ETDRS ) criteria to determine the cumulative incidence of diabetic retinopathy and its component lesions . Analyses were by intention to treat . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N64783481 . FINDINGS Laser treatment was needed more frequently in participants with poorer glycaemic or blood pressure control than in those with good control of these factors , and in those with a greater burden of clinical microvascular disease , but the need for such treatment was not affected by plasma lipid concentrations . The requirement for first laser treatment for all retinopathy was significantly lower in the fenofibrate group than in the placebo group ( 164 [ 3.4 % ] patients on fenofibrate vs 238 [ 4.9 % ] on placebo ; hazard ratio [ HR ] 0.69 , 95 % CI 0.56 - 0.84 ; p=0.0002 ; absolute risk reduction 1.5 % [ 0.7 - 2.3 ] ) . In the ophthalmology sub study , the primary endpoint of 2-step progression of retinopathy grade did not differ significantly between the two groups overall ( 46 [ 9.6 % ] patients on fenofibrate vs 57 [ 12.3 % ] on placebo ; p=0.19 ) or in the subset of patients without pre-existing retinopathy ( 43 [ 11.4 % ] vs 43 [ 11.7 % ] ; p=0.87 ) . By contrast , in patients with pre-existing retinopathy , significantly fewer patients on fenofibrate had a 2-step progression than did those on placebo ( three [ 3.1 % ] patients vs 14 [ 14.6 % ] ; p=0.004 ) . An exploratory composite endpoint of 2-step progression of retinopathy grade , macular oedema , or laser treatments was significantly lower in the fenofibrate group than in the placebo group ( HR 0.66 , 95 % CI 0.47 - 0.94 ; p=0.022 ) . INTERPRETATION Treatment with fenofibrate in individuals with type 2 diabetes mellitus reduces the need for laser treatment for diabetic retinopathy , although the mechanism of this effect does not seem to be related to plasma concentrations of lipids The modified Airlie House classification of diabetic retinopathy has been extended for use in the Early Treatment Diabetic Retinopathy Study ( ETDRS ) . The revised classification provides additional steps in the grading scale for some characteristics , separates other characteristics previously combined , exp and s the section on macular edema , and adds several characteristics not previously grade d. The classification is described and illustrated and its reproducibility between grade rs is assessed by calculating percentages of agreement and kappa statistics for duplicate gradings of baseline color nonsimultaneous stereoscopic fundus photographs . For retinal hemorrhages and /or microaneurysms , hard exu date s , new vessels , fibrous proliferations , and macular edema , agreement was substantial ( weighted kappa , 0.61 to 0.80 ) . For soft exu date s , intraretinal microvascular abnormalities , and venous beading , agreement was moderate ( weighted kappa , 0.41 to 0.60 ) . A double grading system , with adjudication of disagreements of two or more steps between duplicate gradings , led to some improvement in reproducibility for most characteristics A double blind controlled trial has been made of clofibrate in the treatment of diabetic retinopathy . Fifty-six patients completed one year in the trial and form the basis for this paper . At the end of one year there was a significant reduction in the area of retina involved by hard exudation in the treated group . There were no significant effects on other retinal lesions . The improvement in retinal exu date s was not associated with any significant improvement in visual acuity In a study of retinopathy during one year of tight blood glucose control 45 type I ( insulin dependent ) diabetics without proliferative retinopathy were r and omised to receive either continuous subcutaneous insulin infusion , multiple insulin injections , or conventional insulin treatment ( controls ) . Near normoglycaemia was achieved with continuous infusion and multiple injections but not with conventional treatment . Blind evaluation of fluorescein angiograms performed three monthly showed progression of retinopathy in the control group , transient deterioration in the continuous infusion group , and no change in the multiple injection group . Half the patients receiving continuous infusion and multiple injections developed retinal cotton wool spots after three to six months . These changes regressed in all but four patients after 12 months . Control patients did not develop cotton wool spots . Patients who developed cotton wool spots are characterised by a larger decrement in glycosylated haemoglobin and blood glucose values , more frequent episodes of hypoglycaemia , a longer duration of diabetes , and more severe retinopathy at onset . A large and rapid fall in blood glucose concentration may promote transient deterioration of diabetic retinopathy Abstract Purpose : Fenofibrate reduced progression of diabetic retinopathy in two large r and omized studies . The effect of 135 mg fenofibric acid on diabetic macular edema ( DME ) was evaluated in subjects with existing DME . Methods : In this double-blind , r and omized , placebo-controlled study , 110 subjects with DME not requiring immediate photocoagulation or intraocular treatment with adequate diabetes and blood pressure control received either fenofibric acid or placebo once daily for 1 year . Total macula volume ( TMV ) and thickness were measured in the worse eye and all eligible eyes with time-domain optical coherence tomography at baseline and quarterly thereafter . Results : TMV decreased by −0.35 mm3 ( within-group difference ) after fenofibric acid treatment and by −0.11 mm3 after placebo . The between-group comparison of the change was −0.25 mm3 ( 95 % confidence interval , CI , −0.645–0.155 ; p = 0.227 , worse eye analysis ) . Weighted inner zone thickness and volume decreased by −18.7 µm and −0.13 mm3 , respectively , for within group difference after fenofibric acid and by −3.1 µm and −0.02 mm3 , respectively , after placebo . Considering all eligible eyes , thicknesses at central zone , mean inner zone , and entire retina decreased by −21.3 µm , −19.8 µm , and −20.4 µm , respectively , after fenofibric acid . No between-group difference in changes of these measurements was observed . Triglycerides decreased by 23 % after fenofibric acid ( vs 4 % after placebo , p = 0.001 ) and high-density lipoprotein cholesterol increased by 8 % ( vs 0.3 % , p = 0.014 ) . No safety concern was identified . Conclusion : Subjects treated with fenofibric acid had a modest improvement in TMV , although the study was probably underpowered to detect a benefit over placebo after 1 year |
850 | 31,910,415 | For RA in carious anterior upper primary teeth , a low level of evidence was found for higher failure rates of glass ionomer cement and composite fillings than composite strip crowns even if placed under general anaesthesia and especially compared to other crowns ( stainless steel and zirconia ) . | For an Organisation for Caries Research /European Federation of Conservative Dentistry consensus , this systematic review is aim ed to assess the question of how to manage the caries process in the case of early childhood caries ( ECC ) . | 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 Early childhood caries discloses a distinct clinical pattern , and the teeth most often involved are the maxillary central incisors , lateral incisors , and the maxillary and man-dibular first molars . The maxillary incisors are most severely affected , with deep carious lesions usually involving the pulp . Teeth that have been endodontically treated often have little coronal tooth tissue remaining and as such require a post to retain the core and restoration .This study evaluated and compared the efficacy of EverStick glass fiber-reinforced composite post with ParaPost Taper Lux in primary maxillary anterior teeth . Aim An in vivo study was conducted to evaluate and compare the longevity and failures of two fiber post systems in primary maxillary anterior teeth . Material s and methods A total of 60 severely mutilated primary maxillary anterior teeth from children aged 3 to 5 years were selected according to the inclusion criteria . These teeth were treated endodontically and were r and omly assigned into two groups with 30 sample s in each group , group I : EverStick glass fiber-reinforced composite post , group II : ParaPost Taper Lux post . The evaluation of dislodgment of posts , secondary caries , root fracture , and post fracture was carried out clinical ly and radiographically during every follow-up at 3 , 6 , 9 , and 12 months interval . Results Statistical tests ( Chi-square test , Fisher ’s exact probability test ) suggested that dislodgment of the posts was significant between the two groups at 6 , 9 , and 12 months follow-ups . But within the group during subsequent follow-up intervals , dislodgment of posts as a mode of failure was not statistically significant . However , clinical ly failures were seen in both the study groups . Conclusion Fiber post system has proved to be successful clinical ly in both primary and permanent teeth due to the mono-block effect with luting agent , post system , core material , and bonding to dentin . Thus , today the EverStick glass fiber post system provides a novel way of fabricating cost-effective and less time-consuming custom-made post in treating mutilated maxillary anteriors . How to cite this article Sawant A , Chunawalla Y , Morawala A , Kanchan NS , Jain K , Talathi R. Evaluation of Novel Glass Fiber-reinforced Composite Technique for Primary Anterior Teeth with Deep Carious Lesions : A 12-month Clinical Study . Int J Clin Pediatr Dent 2017;10(2):126 - 130 OBJECTIVE To compare the effectiveness of three applications of silver diammine fluoride ( SDF ) solution at yearly interval and three applications of SDF solution or sodium fluoride ( NaF ) varnish at weekly interval at baseline in arresting active caries in the primary teeth of preschool children . METHODS Children aged 3 - 4 years ( n = 371 ) who had at least one active caries lesion ( ICDAS codes 3 - 6 ) in their primary teeth were r and omly allocated into three groups : Group 1 - annual application of 30 % SDF solution ; Group 2 - three applications of 30 % SDF at weekly intervals ; and Group 3 - three applications of 5 % NaF varnish at weekly intervals . Follow-up examinations were performed every 6 mo nths by the same masked examiner . RESULTS After 30 months , 309 ( 83 % ) children with 1877 caries lesions remained in the study . For cavitated lesions ( ICDAS code 5 or 6 ) , the caries arrest rate of Group 1 ( 48 % ) was significantly higher than those of Group 2 ( 33 % ) and Group 3 ( 34 % ) , ( p < 0.001 ) . Results of multi-level survival analysis showed that the arrest times of cavitated lesions in both SDF groups ( Groups 1 and 2 ) were significantly shorter than that of the NaF varnish group . For moderate caries lesions without visible dentine ( ICDAS code 3 or 4 ) , the caries arrest rates were 45 % , 44 % and 51 % in Groups 1 , 2 and 3 , respectively ( p > 0.05 ) . Presence of plaque on caries lesion , tooth type and tooth surface type had an influence on caries arrest . CONCLUSION Over a 30-month period , annual applications of SDF solution is more effective than three weekly applications of NaF varnish or SDF solution at baseline in arresting active cavitated dentine caries lesions in primary teeth . CLINICAL SIGNIFICANCE As annual application of SDF solution was found to be more effective than 3 weekly applications of NaF varnish or SDF solution at baseline in arresting active cavitated dentine caries lesions , the former application protocol is preferred for young children who are available for regular caries arrest treatment Objective : We aim ed to evaluate the efficacy of oral hygiene instruction , fluoride varnish and casein phosphopeptide-amorphous calcium phosphate ( CPP-ACP ) for remineralizing white spot lesions ( WSL ) , and the effect of these on the dmft index in primary teeth . Subjects and Methods : In this 1-year , r and omized clinical trial , 140 children aged 12 - 36 months with WSL in the anterior maxillary teeth were selected and r and omly divided into 4 groups of 35 children each . Group 1 ( control ) received no preventive intervention . In group 2 , there was oral hygiene and dietary counseling . In group 3 , there was oral hygiene and the application of fluoride varnish at 4 , 8 and 12 months after baseline . In group 4 , there was oral hygiene and tooth mousse was applied by the parents twice a day over a 12-month period . At baseline and 4 , 8 and 12 months after the intervention , the size of WSL in millimeters and the dmft index were recorded . One hundred and twenty-two children completed the study . Data were analyzed using the repeated- measures ANOVA test . Results : In group 1 , the mean percent WSL area and dmft index values had increased significantly at 12 months after baseline ( p < 0.001 ) . The interventions led to significant decreases in the size of the WSL ; the greatest reduction was in group 4 ( 63 % ) followed by group 3 ( 51 % ) and group 2 ( 10 % ) after 12 months . The smallest increase in the dmft index was in group 4 ( 0.17 ) , followed by groups 3 ( 0.3 ) and 2 ( 0.42 ) . However , there were no significant differences between the groups ( p < 0.001 ) . Conclusions : Oral hygiene along with four fluoride varnish applications or constant CPP-ACP during the 12- month period reduced the size of WSL in the anterior primary teeth and caused a small increase in dmft index values 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 A pragmatic r and omised controlled trial comparing a minimally invasive approach based on atraumatic restorative treatment ( ART ) procedures ( test ) was tested against the st and ard-care approach ( control ) to treat early childhood caries ( ECC ) in a primary -care setting in Perth , W.A. , Australia . Parent/child dyads with ECC were allocated to the test or control group using stratified block r and omisation . Children were examined at baseline and follow-up by two calibrated examiners blinded to group allocation status . Dental therapists trained in ART provided treatment to the test group and dentists treated the control group . Restoration quality was evaluated at follow-up using the ART criteria . Data were analysed on an intention-to-treat basis ; test of proportions , Wilcoxon rank test and logistic regression , controlling for clustering of teeth , were used . Two hundred and fifty-four children were r and omised ( test = 127 and control = 127 ) . There was no statistically significant difference in age , sex and baseline caries experience between the test and control groups . At follow-up ( mean interval 11.4 months , SD 3.1 ) , 220 children were examined ( test = 115 and control = 105 ) and 597 teeth ( test = 417 and control = 180 ) were evaluated for restoration quality , of which 16.8 % ( test ) and 6.7 % ( control ) were judged to have failed ( required replacement ; p < 0.01 ) . Intention-to-treat , multiple logistic regression found multisurface restorations ( OR = 10.4 ) had significantly higher odds of failure , while referral for specialist paediatric care had significantly lower odds of restoration failure ( OR = 0.2 ) . The ART-based approach enabled more children and teeth to be treated , and multisurface restoration and treatment in a primary -care setting had higher odds of restoration failure AIM This r and omised clinical trial ( RCT ) compared the clinical outcomes of three aesthetic full-coronal restorations ( composite strip crowns , pre-veneered stainless steel crowns ( SSCs ) and pre-fabricated primary zirconia crowns ) in carious and traumatised primary maxillary incisors . MATERIAL S AND METHODS One hundred and twenty nine teeth in 39 children aged between 3 to 5 years were included . Children were r and omly assigned to one of three treatment groups using a permuted block r and omisation technique with a total of 43 teeth in each group . After trainee calibration , restorations were placed and evaluated after 6 months . Outcomes evaluated were restoration failure , tooth wear of opposing teeth and gingival health . RESULTS The retention rate was highest for zirconia crowns ( 100 % ) followed by pre-veneered SSCs ( 95 % ) . Strip crowns were the least retentive ( 78 % ) . Zirconia crowns showed low grade abrasion in four opposing teeth . Teeth restored with resin composite and pre-veneered SSC showed an increase in mean gingival index score , while corresponding values decreased in zirconia crowns . CONCLUSION Resin composite strip crown is a highly sensitive technique leading to lower retention rate . Pre-veneered stainless steel crowns showed increased incidence of facial veneer fracture . Zirconia crowns are highly retentive and biocompatible but cause low grade of abrasion of their opposing natural dentition at the 6-month follow-up This study compares the clinical characteristic evaluations of slot against dovetail class III composite restorations . Focusing on the primary anterior teeth of children aged 2 years 6 months to 5 years 3 months with the mean age of 4 years , thirty-six matched pairs of class III of slot and dovetail preparations were made by one investigator These preparations were evaluated for marginal adaptation , anatomic form , secondary caries and marginal discoloration after 6 , 12 , and 24 months by another investigator with the intra-examiner reliability of 0.95 - 1 ( Kappa Statistic ) . The results revealed no statistical significance in the difference of clinical characteristics between the two design s ( p > 0.05 ) 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 BACKGROUND An expert panel convened by the American Dental Association Council on Scientific Affairs and the Center for Evidence -Based Dentistry conducted a systematic review and formulated evidence -based clinical recommendations for the arrest or reversal of noncavitated and cavitated dental caries using nonrestorative treatments in children and adults . TYPES OF STUDIES REVIEW ED The authors conducted a systematic search of the literature in MEDLINE and Embase via Ovid , Cochrane CENTRAL , and Cochrane data base of systematic review s to identify r and omized controlled trials reporting on nonrestorative treatments for noncavitated and cavitated carious lesions . The authors used the Grading of Recommendations Assessment , Development and Evaluation approach to assess the certainty in the evidence and move from the evidence to the decisions . RESULTS The expert panel formulated 11 clinical recommendations , each specific to lesion type , tooth surface , and dentition . Of the most effective interventions , the panel provided recommendations for the use of 38 % silver diamine fluoride , sealants , 5 % sodium fluoride varnish , 1.23 % acidulated phosphate fluoride gel , and 5,000 parts per million fluoride ( 1.1 % sodium fluoride ) toothpaste or gel , among others . The panel also provided a recommendation against the use of 10 % casein phosphopeptide-amorphous calcium phosphate . CONCLUSIONS AND PRACTICAL IMPLICATION S Although the recommended interventions are often used for caries prevention , or in conjunction with restorative treatment options , these approaches have shown to be effective in arresting or reversing carious lesions . Clinicians are encouraged to prioritize use of these interventions based on effectiveness , safety , and feasibility |
851 | 24,999,397 | Conclusion There is evidence from the literature to suggest that there is a positive relationship between OCPD and excessive exercise in patients with AN . | Objective Obsessive-compulsive personality disorder ( OCPD ) traits and obsessive-compulsive disorder ( OCD ) are commonly associated with patients with Anorexia Nervosa ( AN ) .
The aim of this review was to systematic ally search the literature to examine whether OCPD and OCD are positively associated with excessive exercise in patients with AN . | This study was intended to establish the pathogenic significance of sport and exercise in the development of eating disorders . Hospitalized eating disordered patients and an age-matched control group were assessed . Historical and current physical activity data were collected . An indepth interview was also conducted to ascertain the age of onset of the diagnostic symptoms for eating disorders , and to determine whether : ( i ) exercising pre date d dieting ; ( ii ) patients had been involved in competitive athletics ; ( iii ) exercise was excessive ; and ( iv ) weight loss was inversely related to level of exercise . The results indicated that patients were more physically active than controls from adolescence onwards , and prior to the onset of the primary diagnostic criteria for anorexia nervosa . A content analysis of the interview data indicated that 78 % of patients engaged in excessive exercise , 60 % were competitive athletes prior to the onset of their disorder , 60 % reported that sport or exercise pre- date d dieting , and 75 % cl aim ed that physical activity levels steadily increased during the period when food intake and weight loss decreased the most . Together our results suggest that overactivity should not be routinely viewed as a secondary symptom in anorexia nervosa , equivalent to other behaviours . For a number of anorexic women , sport/exercise is an integral part of the pathogenesis and progression of self-starvation Anorexia nervosa ( AN ) and obsessive-compulsive disorder ( OCD ) are highly comorbid , and appear to share a common neurophysiological dysfunction that contributes to the obsessional thoughts and compulsive behaviours seen in both disorders . Obsessive-compulsive personality ( OCP ) traits are also important risk factors for AN . Since excessive exercise has also been associated with greater obsessionality , we hypothesised that AN patients with a hyperactive behavioural profile represent a phenotype more closely linked to OCD than their non-exercising counterparts . We examined prospect ively 50 female AN-Restrictor patients whom we classified as " excessive " or " non-excessive " based on their exercise status i ) at admission and ii ) over the lifetime of their illness . Vali date d measures of OCD symptoms and OCP traits were obtained at admission and after refeeding at discharge . On both classification methods , excessive exercisers had greater OCD symptoms and OCP traits than the non-excessive group , but did not differ on body mass index . OCD symptoms , but not OCP traits , decreased between admission and discharge . Findings support our prediction that AN patients with excessive physical activity constitute a subtype of the disorder with strong links to OCD . Indeed , this phenotype may be a culture-bound variant of OCD 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 BACKGROUND Anorexia nervosa is a disorder of unknown etiology with a high rate of relapse and no known treatment . Because anorexia nervosa shares some similarities with obsessive compulsive disorder , we hypothesized that a serotonin-specific medication might be useful in the treatment of this illness . METHOD We administered an open trial of fluoxetine to 31 patients with DSM-III-R anorexia nervosa . Most anorexics were started on fluoxetine treatment after inpatient weight restoration and then discharged from the hospital and followed up as out patients . RESULTS At the time of follow-up ( 11 + /- 6 months on fluoxetine ) , 29 of the 31 patients had maintained their weight at or above 85 % average body weight ( 97 % + /- 13 % average body weight for the group ) . We judged response as good in 10 , partial in 17 , and poor in 4 anorexics as measured by improvements in eating behavior , mood , and obsessional symptoms . Restrictor anorexics responded significantly better than bulimic and /or purging-type anorexics . CONCLUSION This open trial suggests that fluoxetine may help patients with anorexia nervosa maintain a healthy body weight as out patients . The reasons for the positive effects of fluoxetine are uncertain , but the agent may help by improving eating behavior and /or reducing obsessionality , depression , and anxiety . It is important to emphasize that this was not a double-blind , placebo-controlled study . Thus we can not be certain of the efficacy of fluoxetine and caution that fluoxetine should not be used as the sole treatment of anorexia nervosa at this time OBJECTIVE This study considered whether the prevalence and type of anxiety and psychoactive substance use disorder ( PSUD ) diagnoses differ between women with spectrum anorexia nervosa ( AN ) ( N=40 ) and women with major depressive disorder ( N = 58 ) participating in outpatient clinical trials . METHOD Anxiety and PSUD diagnoses ( according to criteria in the 3rd Rev. ed . of the Diagnostic and Statistical Manual of Mental Disorders ) were assessed using structured clinical interviews . Comparisons were made between AN subtypes ( restricting or binge eating/purging ) and by history of depression within the AN sample . RESULTS A high prevalence of obsessive-compulsive disorder ( OCD ) was found in women with AN . However , social phobia , simple phobia , and PSUD were significantly elevated in both women with depression and women with AN . Prevalences were similar for anxiety and PSUD diagnoses between AN subtypes . DISCUSSION Women with anorexia or depression were comparable in all respects , except for the elevated OCD prevalence in AN , emphasizing the need to use clinical comparison groups to avoid inadvertently attributing elevated prevalences of comorbid conditions to specific disorders In the present study , the structure of obsessive-compulsive symptoms was investigated by means of the Padua Inventory ( PI ) . Simultaneous Components Analysis on data from obsessive-compulsives ( n = 206 ) , patients with other anxiety disorders ( n = 222 ) , and a non clinical sample ( n = 430 ) revealed a five-factor solution . These factors are : ( I ) impulses ; ( II ) washing ; ( III ) checking ; ( IV ) rumination ; and ( V ) precision . Forty-one items were selected as measure of these factors . The reliability for the five subscales , assessing each of the five factors , was found to be satisfactory to excellent . Four subscales ( washing , checking , rumination and precision ) discriminated between panic disorder patients , social phobics and normals on the one h and and obsessive compulsives on the other . The Impulses subscale discriminated between obsessive-compulsives on the one h and and normals on the other , but not between obsessive-compulsives and social phobics or panic patients . Some evidence in support of the construct validity was found . The Padua Inventory-Revised ( 41-items ) appears to measure the structure of obsessive compulsive symptoms : The main types of behaviours and obsessions as seen clinical ly are assessed by this question naire , apart from obsessional slowness |
852 | 27,780,031 | Results Both pooled and subgroup meta-analyses in medication washout patients showed robust fractional anisotropy ( FA ) reductions in white matter of the right cerebellum hemispheric lobule , body of the corpus callosum ( CC ) and bilateral superior longitudinal fasciculus III ( SLF III ) , whereas FA reductions in the genu of the CC and right anterior thalamic projections were seen in only medication-naive patients .
Fibre tracking showed that the main tracts with observed FA reductions included the right cerebellar tracts , body of the CC , bilateral SLF III and arcuate fascicle .
Conclusion By excluding the confounding influences of current medication status , findings from the present study may provide a better underst and ing of the underlying neuropathology of MDD | Background Multiple meta-analyses of diffusion tensor imaging ( DTI ) studies have reported impaired white matter integrity in patients with major depressive disorder ( MDD ) .
However , owing to inclusion of medicated patients in these studies , it is difficult to conclude whether these reported alterations are associated with MDD or confounded by medication effects .
A meta- analysis of DTI studies on medication-free ( medication-naive and medication washout ) patients with MDD would therefore be necessary to disentangle MDD-specific effects . | BACKGROUND Functional neuroimaging studies implicate anterior cingulate and limbic dysfunction in major depressive disorder ( MDD ) and responsiveness to antidepressants . Diffusion tensor imaging ( DTI ) enables characterisation of white matter tracts that relate to these regions . AIMS To examine whether DTI measures of anterior cingulate and limbic white matter are useful prognostic biomarkers for MDD . METHOD Of the 102 MDD out- patients from the International Study to Predict Optimized Treatment for Depression ( iSPOT-D ) who provided baseline magnetic resonance imaging ( MRI ) data , 74 completed an 8-week course of antidepressant medication ( r and omised to escitalopram , sertraline or extended-release venlafaxine ) and were included in the present analyses . Thirty-four matched controls also provided DTI data . Fractional anisotropy was measured for five anterior cingulate-limbic white matter tracts : cingulum cingulate and hippocampus bundle , fornix , stria terminalis and uncinate fasciculus . ( Trial registered at Clinical Trials.gov : NCT00693849 . ) RESULTS A cross-vali date d logistic regression model demonstrated that altered connectivity for the cingulum part of the cingulate and stria terminalis tracts significantly predicted remission independent of demographic and clinical measures with 62 % accuracy . Prediction improved to 74 % when age was added to this model . CONCLUSIONS Anterior cingulate-limbic white matter is a useful predictor of antidepressant treatment outcome in MDD Diffusion Tensor magnetic resonance imaging and computational neuroanatomy are used to quantify postnatal developmental patterns of C57BL/6J mouse brain . Changes in neuronal organization and myelination occurring as the brain matures into adulthood are examined , and a normative baseline is developed , against which transgenic mice may be compared in genotype-phenotype studies . In early postnatal days , gray matter-based cortical and hippocampal structures exhibit high water diffusion anisotropy , presumably reflecting the radial neuronal organization . Anisotropy drops rapidly within a week , indicating that the underlying brain tissue becomes more isotropic in orientation , possibly due to formation of a complex r and omly intertwined web of dendrites . Gradual white matter anisotropy increase implies progressively more organized axonal pathways , likely reflecting the myelination of axons forming tightly packed fiber bundles . In contrast to the spatially complex pattern of tissue maturation , volumetric growth is somewhat uniform , with the cortex and the cerebellum exhibiting slightly more pronounced growth . Temporally , structural growth rates demonstrate an initial rapid volumetric increase in most structures , gradually tapering off to a steady state by about 20 days . Fiber maturation reaches steady state in about 10 days for the cortex , to 30 - 40 days for the corpus callosum , the hippocampus , and the internal and external capsules Background Due to a lack of evidence , there is no consistent age of onset to define early onset ( EO ) versus later onset ( LO ) major depressive disorder ( MDD ) . Fractional anisotropy ( FA ) , derived from diffusion tensor imaging ( DTI ) , has been widely used to study neuropsychiatric disorders by providing information about the brain circuitry , abnormalities of which might facilitate the delineation of EO versus LO MDD . Method In this study , 61 pairs of untreated , non-elderly , first-episode MDD patients and healthy controls ( HCs ) aged 18–45 years old received DTI scans . The voxel-based analysis method ( VBM ) , classification analysis , using the Statistical Package for the Social Sciences ( SPSS ) , and regression analyses were used to determine abnormal FA clusters and their correlations with age of onset and clinical symptoms . Results Classification analysis suggested in the best model that there were two subgroups of MDD patients , delineated by an age of onset of 30 years old , by which MDD patients could be divided into EO ( 18–29 years old ) and LO ( 30–45 years old ) groups . LO MDD was characterized by decreased FA , especially in the white matter ( WM ) of the fronto-occipital fasciculus and posterior limb of internal capsule , with a negative correlation with the severity of depressive symptoms ; in marked contrast , EO MDD showed increased FA , especially in the WM of the corpus callosum , corticospinal midbrain and inferior fronto-occipital fasciculus , while FA of the WM near the midbrain had a positive correlation with the severity of depressive symptoms . Conclusion Specific abnormalities of the brain circuitry in EO vs. LO MDD were delineated by an age of onset of 30 years old , as demonstrated by distinct abnormal FA clusters with opposite correlations with clinical symptoms . This DTI study supported the evidence of an exact age for the delineation of MDD , which could have broad multidisciplinary importance . Trial Registration Clinical Trials.gov BACKGROUND Neuroimaging studies have shown that major depressive disorder ( MDD ) is accompanied by structural and functional abnormalities in specific brain regions and connections ; yet , little is known about alterations of the topological organization of whole-brain networks in MDD patients . METHODS Thirty drug-naive , first-episode MDD patients and 63 healthy control subjects underwent a resting-state functional magnetic resonance imaging scan . The whole-brain functional networks were constructed by thresholding partial correlation matrices of 90 brain regions , and their topological properties ( e.g. , small-world , efficiency , and nodal central ity ) were analyzed using graph theory-based approaches . Nonparametric permutation tests were further used for group comparisons of topological metrics . RESULTS Both the MDD and control groups showed small-world architecture in brain functional networks , suggesting a balance between functional segregation and integration . However , compared with control subjects , the MDD patients showed altered quantitative values in the global properties , characterized by lower path length and higher global efficiency , implying a shift toward r and omization in their brain networks . The MDD patients exhibited increased nodal central ities , predominately in the cau date nucleus and default-mode regions , including the hippocampus , inferior parietal , medial frontal , and parietal regions , and reduced nodal central ities in the occipital , frontal ( orbital part ) , and temporal regions . The altered nodal central ities in the left hippocampus and the left cau date nucleus were correlated with disease duration and severity . CONCLUSIONS These results suggest that depressive disorder is associated with disruptions in the topological organization of functional brain networks and that this disruption may contribute to disturbances in mood and cognition in MDD patients OBJECTIVE The polymorphism BDNF val66met of the brain derived neurotrophic factor ( BDNF ) is common , may increase the risk for depression , and affects BDNF secretion , critical for neuronal survival , plasticity , neurogenesis , and synaptic connectivity . Our objectives were : 1 ) to test the hypothesis that BDNF(val/met ) status influences the remission rate of geriatric depression ; 2 ) to explore whether the relationship between BDNF allelic status to remission is influenced by the presence of microstructural white matter abnormalities . METHOD Non-demented older subjects with major depression had a 2-week placebo period , after which those with a Hamilton Depression Rating Scale ( HDRS ) of 18 or greater received escitalopram 10 mg daily for 12 weeks . Fractional anisotropy was determined in specific regions using the Reproducible Object Quantification Scheme ( ROQS ) software that operates on non-normalized data . RESULTS BDNF(met ) carriers were more likely to achieve remission than BDNF(val/val ) homozygotes after 12 weeks of treatment with escitalopram 10 mg daily . Microstructural abnormalities in the corpus callosum , left superior corona radiata , and right inferior longitudinal fasciculum were also associated with lower remission rate . However , there were no significant interactions between BDNF(val66met ) status and microstructural abnormalities in predicting remission . LIMITATIONS Small number of subjects , focus on a single BDNF polymorphism , fixed antidepressant dose . CONCLUSIONS Depressed older BDNF(met ) carriers had a higher remission rate than BDNF(val/val ) homozygotes . This effect was not related to microstructural white matter abnormalities , which predicted remission independently . We speculate that the relationship between BDNF(val66met ) and remission is due to different effects of BDNF in brain structures related to mood regulation This study was conducted to eluci date the effects of electroconvulsive therapy ( ECT ) on frontal white matter in late-life depressed patients . Diffusion tensor imaging was performed on 8 late-life depressed patients and 12 healthy age-matched controls . The patients were scanned before and after a course of ECT . Fractional anisotropy ( FA ) was determined in the frontal and temporal regions and the corpus callosum . A significant white matter FA reduction was found in widespread frontal and temporal brain regions in patients with depression before ECT treatment compared with controls . A significant increase in frontal white matter FA was seen following ECT treatment . A course of bilateral ECT ameliorated white matter integrity in frontal brain regions . This suggests a strong relationship with the antidepressant action of ECT BACKGROUND Repetitive transcranial magnetic stimulation ( rTMS ) is an effective treatment for treatment-resistant depression ( TRD ) , but its therapeutic mechanisms are unclear . White matter abnormalities are thought to cause network dysfunction underlying TRD . Diffusion tensor imaging ( DTI ) is an ideal tool for examining neural connections and the integrity of white matter . Few studies have used DTI to investigate the impact of rTMS on alterations of whiter matter in TRD . METHOD 30 young treatment-resistant unipolar depression patients ( 19 males and 11 females ) were enrolled in a double-blind , r and omized high-frequency ( 15 Hz ) rTMS treatment study . Seventeen patients were treated with real stimulation , and 13 were treated with sham stimulation . White-matter fractional anisotropy ( FA ) was evaluated using voxel-based analysis ( VBA ) of FA maps derived from DTI before and after treatment . Twenty-five age- and gender-matched subjects were examined as a control group . RESULTS In an exploratory VBA method , clusters of fifty voxels or greater that survived a family-wise error (FWE)-corrected threshold of p<0.05 were considered significant . The results revealed significantly reduced FA in the left middle frontal gyrus , with peak coordinates [ -18 46 -14 ] in TRD patients . This reduced FA was significantly improved after active rTMS treatment , but not sham stimulation . FA increases were correlated with decreased depressive symptoms . LIMITATIONS This study requires replication and further clarification in a larger patient population , and optimization of stimulation locations and methods . CONCLUSIONS These results suggest that the efficacy of rTMS on TRD is related to increased white-matter FA in the left middle frontal gyrus |
853 | 27,331,030 | Evidence suggests it is safe to monitor symptomatic rotator cuff tears , as tear size and symptoms are not correlated with pain , function , and /or ultimate outcome .
CONCLUSIONS complete rotator cuff tears may be effectively treated with injections , exercise in the short and intermediate terms respectively .
Negative effect of corticosteroids on rotator cuff tissue has not been demonstrated . | BACKGROUND rotator cuff tear affects many people .
Natural history , and evidence for non-operative treatment remains limited .
Our objective is to assess evidence available for the efficacy and morbidity of commonly used systemic medications , physiotherapy , and injections alongside evaluating any negative long-term effects . | BACKGROUND The purpose of this prospect i ve study was to report the long-term risks of rotator cuff tear enlargement and symptom progression associated with degenerative asymptomatic tears . METHODS Subjects with an asymptomatic rotator cuff tear in one shoulder and pain due to rotator cuff disease in the contralateral shoulder enrolled as part of a prospect i ve longitudinal study . Two hundred and twenty-four subjects ( 118 initial full-thickness tears , fifty-six initial partial-thickness tears , and fifty controls ) were followed for a median of 5.1 years . Vali date d functional shoulder scores were calculated ( visual analog pain scale , American Shoulder and Elbow Surgeons [ ASES ] , and simple shoulder test [ SST ] scores ) . Subjects were followed annually with shoulder ultrasonography and clinical evaluations . RESULTS Tear enlargement was seen in 49 % of the shoulders , and the median time to enlargement was 2.8 years . The occurrence of tear-enlargement events was influenced by the severity of the final tear type , with enlargement of 61 % of the full-thickness tears , 44 % of the partial-thickness tears , and 14 % of the controls ( p < 0.05 ) . Subject age and sex were not related to tear enlargement . One hundred subjects ( 46 % ) developed new pain . The final tear type was associated with a greater risk of pain development , with the new pain developing in 28 % of the controls , 46 % of the shoulders with a partial-thickness tear , and 50 % of those with a full-thickness tear ( p < 0.05 ) . The presence of tear enlargement was associated with the onset of new pain ( p < 0.05 ) . Progressive degenerative changes of the supraspinatus muscle were associated with tear enlargement , with supraspinatus muscle degeneration increasing in 4 % of the shoulders with a stable tear compared with 30 % of the shoulders with tear enlargement ( p < 0.05 ) . Nine percent of the shoulders with a stable tear showed increased infraspinatus muscle degeneration compared with 28 % of those in which the tear had enlarged ( p = 0.07 ) . CONCLUSIONS This study demonstrates the progressive nature of degenerative rotator cuff disease . The risk of tear enlargement and progression of muscle degeneration is greater for shoulders with a full-thickness tear , and tear enlargement is associated with a greater risk of pain development across all tear types . LEVEL OF EVIDENCE Prognostic Level II . See Instructions for Authors for a complete description of levels of evidence BACKGROUND Presently , there are no approved nonoperative therapies for the ongoing treatment of persistent shoulder pain . Preliminary data suggest that intra-articular sodium hyaluronate injections may be beneficial for the treatment of persistent shoulder pain result ing from various etiologies . The present study evaluated the efficacy and safety of sodium hyaluronate ( Hyalgan ; molecular weight , 500 to 730 kDa ) for these patients . METHODS Six hundred and sixty patients with persistent shoulder pain and limitation result ing from glenohumeral joint osteoarthritis , rotator cuff tear , and /or adhesive capsulitis who had had a failure of conventional therapy were enrolled in this double-blind , r and omized , phosphate-buffered saline solution-controlled study , and 456 patients completed twenty-six weeks of follow-up . Patients were r and omized to receive either five weekly intra-articular injections of sodium hyaluronate , three weekly intra-articular injections of sodium hyaluronate followed by two weekly intra-articular injections of saline solution , or five weekly intra-articular injections of saline solution . The main outcomes were improvement in terms of shoulder pain on movement at thirteen weeks after the initiation of treatment ( as assessed with use of a 100-mm visual analog scale ) and the treatment effect throughout twenty-six weeks . RESULTS For the overall intent-to-treat population , patients who were managed with sodium hyaluronate had greater pain relief than controls did ; significant differences were noted at Week 7 ( for the five-injection hyaluronate group ) , Week 17 ( for the three and five-injection hyaluronate groups ) , and Week 26 ( for the three-injection hyaluronate group ) . Analysis of the stratified population s clearly established that this effect was due to benefits experienced by the patients with osteoarthritis . The treatment effect through twenty-six weeks was significant in patients with osteoarthritis in the three-injection ( p = 0.003 ) and five-injection ( p = 0.002 ) groups , with no significant difference for either regimen in patients without osteoarthritis . The safety profile was very favorable , with no product-related serious adverse effects and no between-group differences for any reported adverse event . CONCLUSIONS Although the primary end point of this study ( that is , improvement in terms of shoulder pain at thirteen weeks ) was not achieved , the overall findings , including secondary end points , indicate that sodium hyaluronate ( 500 to 730 kDa ) is effective and well tolerated for the treatment of osteoarthritis and persistent shoulder pain that is refractory to other st and ard nonoperative interventions PURPOSE To assess the effectiveness of a specific nonoperative physical therapy program in treating atraumatic full-thickness rotator cuff tears using a multicenter prospect i ve cohort study design . MATERIAL S AND METHODS Patients with atraumatic full-thickness rotator cuff tears who consented to enroll provided data via question naire on demographics , symptom characteristics , comorbidities , willingness to undergo surgery , and patient-related outcome assessment s ( Short Form 12 score , American Shoulder and Elbow Surgeons score , Western Ontario Rotator Cuff score , Single Assessment Numeric Evaluation score , and Shoulder Activity Scale ) . Physicians recorded physical examination and imaging data . Patients began a physical therapy program developed from a systematic review of the literature and returned for evaluation at 6 and 12 weeks . At those visits , patients could choose 1 of 3 courses : ( 1 ) cured ( no formal follow-up scheduled ) , ( 2 ) improved ( continue therapy with scheduled re assessment in 6 weeks ) , or ( 3 ) no better ( surgery offered ) . Patients were contacted by telephone at 1 and 2 years to determine whether they had undergone surgery since their last visit . A Wilcoxon signed rank test with continuity correction was used to compare initial , 6-week , and 12-week outcome scores . RESULTS The cohort consists of 452 patients . Patient-reported outcomes improved significantly at 6 and 12 weeks . Patients elected to undergo surgery less than 25 % of the time . Patients who decided to have surgery generally did so between 6 and 12 weeks , and few had surgery between 3 and 24 months . CONCLUSION Nonoperative treatment using this physical therapy protocol is effective for treating atraumatic full-thickness rotator cuff tears in approximately 75 % of patients followed up for 2 years HYPOTHESIS The purpose of this cross-sectional study is to determine whether the duration of symptoms influences the features seen in patients with atraumatic , full-thickness rotator cuff tears . Our hypothesis is that an increasing duration of symptoms will correlate with more advanced findings of rotator cuff tear severity on magnetic resonance imaging , worse shoulder outcome scores , more pain , decreased range of motion , and less strength . METHODS We enrolled 450 patients with full-thickness rotator cuff tears in a prospect i ve cohort study to assess the effectiveness of nonoperative treatment and factors predictive of success . The duration of patient symptoms was divided into 4 groups : 3 months or less , 4 to 6 months , 7 to 12 months , and greater than 12 months . Data collected at patient entry into the study included ( 1 ) demographic data , ( 2 ) history and physical examination data , ( 3 ) radiographic imaging data , and ( 4 ) vali date d patient-reported measures of shoulder status . Statistical analysis included a univariate analysis with the Kruskal-Wallis test and Pearson test to identify statistically significant differences in these features for different duration s of symptoms . RESULTS A longer duration of symptoms does not correlate with more severe rotator cuff disease . The duration of symptoms was not related to weakness , limited range of motion , tear size , fatty atrophy , or vali date d patient-reported outcome measures . CONCLUSIONS There is only a weak relationship between the duration of symptoms and features associated with rotator cuff disease BACKGROUND The purpose s of this study were to identify changes in tear dimensions , shoulder function , and glenohumeral kinematics when an asymptomatic rotator cuff tear becomes painful and to identify characteristics of individuals who develop pain compared with those who remain asymptomatic . METHODS A cohort of 195 subjects with an asymptomatic rotator cuff tear was prospect ively monitored for pain development and examined annually for changes in various parameters such as tear size , fatty degeneration of the rotator cuff muscle , glenohumeral kinematics , and shoulder function . Forty-four subjects were found to have developed new pain , and the parameters before and after pain development were compared . The forty-four subjects were then compared with a group of fifty-five subjects who remained asymptomatic over a two-year period . RESULTS With pain development , the size of a full-thickness rotator cuff tear increased significantly , with 18 % of the full-thickness tears showing an increase of > 5 mm , and 40 % of the partial-thickness tears had progressed to a full-thickness tear . In comparison with the assessment s made before the onset of pain , the American Shoulder and Elbow Surgeons scores for shoulder function were significantly decreased and all measures of shoulder range of motion were decreased except for external rotation at 90 ° of abduction . There was an increase in compensatory scapulothoracic motion in relation to the glenohumeral motion during early shoulder abduction with pain development . No significant changes were found in external rotation strength or muscular fatty degeneration . Compared with the subjects who remained asymptomatic , the subjects who developed pain were found to have significantly larger tears at the time of initial enrollment . CONCLUSIONS Pain development in shoulders with an asymptomatic rotator cuff tear is associated with an increase in tear size . Larger tears are more likely to develop pain in the short term than are smaller tears . Further research is warranted to investigate the role of prophylactic treatment of asymptomatic shoulders to avoid the development of pain and loss of shoulder function Objective : Assess platelet rich plasma ( PRP ) injection for rotator cuff tendinopathy ( RCT ) . Design : Prospect i ve open label study with 1-year follow-up . Methods : Participants recruited from an outpatient sports medicine clinic had clinical ly and magnetic resonance image (MRI)—demonstrated RCT refractory to physical therapy and corticosteroid injection . They received one ultrasound-guided injection of 3.0 mL of 1 % xylocaine followed by 3.5 mL of PRP at the lesion and surrounding tendon . Primary outcome : 0—10 visual analog scale ( VAS ; baseline , 8 , 12 , and 52 weeks ) . Secondary outcomes : functional shoulder tests assessing rotator cuff strength and endurance ( at baseline and 8 and 12 weeks ) , MRI severity ( 1—5 points [ at baseline and 4 and 8 weeks ] ) , and patient satisfaction ( 52 weeks ) . Results : Eighteen participants with 19 assessed shoulders reported VAS pain score improvement from 7.5 ± 0.3 points to 0.5 ± 0.3 points by week 12 and 0.4 ± 0.2 ( P = .0001 ) points at week 52 . Functional outcomes significantly improved ; the largest effect was seen in the external rotation test : 33.5 ± 5.7 seconds to 62.6 ± 7.2 seconds at week 12 ( P = .0001 ) . MRI appearance improved by 1 to 3 points in 16 of 18 assessed shoulders . Seventeen participants were “ completely satisfied ” ( 12 ) or “ satisfied ” ( 5 ) . One participant was “ unsatisfied . ” Conclusions : A single ultrasound-guided , intralesional injection of PRP result ed in safe , significant , sustained improvement of pain , function , and MRI outcomes in participants with refractory RCT . R and omized multidisciplinary effectiveness trials that add ultrasound and vali date d clinical outcome measures are needed to further assess PRP for RCT Background : Patient activity level may be an important prognostic variable relating to outcomes in patients with shoulder disorders . Little is known about the predictors of activity level in patients with shoulder disorders . Hypothesis : Tear size and patient variables would be predictive of shoulder activity level in a cohort of patients who have selected initial nonoperative treatment for a symptomatic , atraumatic rotator cuff tear on magnetic resonance imaging ( MRI ) . Study Design : Cross-sectional study ; Level of evidence , 3 . Methods : Patients with an atraumatic rotator cuff tear on MRI were prospect ively enrolled in the Multicenter Orthopaedic Outcomes Network ( MOON ) shoulder study of nonoperative treatment . As part of routine data collection , these patients were asked to complete a previously vali date d shoulder activity scale . A regression analysis was performed to assess the association of shoulder activity level to rotator cuff tear characteristics , including tendon involvement and retraction , and patient factors such as age , sex , smoking , and occupation . Results : A total of 434 patients ( 220 male , 214 female ) with a mean age of 62.7 years ( range , 31 - 90 years ) completed the activity scale . Shoulder activity was not associated with severity of the rotator cuff tear , but it was negatively associated with age ( P = .0001 ) and female sex ( P = .001 ) . The only other factor associated with shoulder activity level in this cohort was occupation ( P = .0006 ) . Conclusion : Shoulder activity level in patients with an atraumatic rotator cuff tear confirmed on MRI is not associated with severity of the tear but is affected by age , sex , and occupation Thirty-one female Sprague-Dawley rats were used to determine the effects of subacromial corticosteroid injections on the rotator cuff . The injection technique was tested in 6 animals , which were excluded from the study . The remaining 25 rats were r and omly divided into three groups of 8 animals each ; a single rat received no injections . Every other week for 8 weeks , one shoulder in each rat was injected with methylprednisolone , betamethasone , or saline in a dosage equivalent to that used in humans . The supraspinatus and infraspinatus tendons were removed 10 days after the last injection and evaluated . There were no pathologic changes in the tendons injected with saline . In 43 % of the methylprednisolone-treated rats and 29 % of the betamethasone-treated rats , the tendons were abnormally soft and light-colored . In 43 % of the methylprednisolone group and 71 % of the betamethasone group , fragmentation of collagen bundles and inflammatory cell infiltration were evident . Subacromial injections of methylprednisolone or betamethasone repeated frequently can cause deleterious changes in the normal structure of the rat rotator cuff . In light of these findings , therapy for subacromial impingement syndrome of the shoulder with frequent , repeated steroid injections is potentially harmful To determine the prevalence of rotator cuff tears in asymptomatic shoulders we conducted a prospect i ve clinical and ultrasonographic study of 411 volunteers . We anticipated an age-dependent outcome and divided the patients into 4 age-groups . Overall , we found evidence of a rotator cuff tear in 23 % of the patients . In group 1 ( aged 50 to 59 years ) , 13 % ( 22 of 167 ) of the patients had tears ; in group 2 ( aged 60 to 69 years ) , 20 % ( 22 of 108 ) of the patients had tears ; in group 3 ( aged 70 to 79 years ) , 31 % ( 27 of 87 ) of the patients had tears ; and in group 4 ( age > 80 years ) , 51 % ( 25 of 49 ) of the patients had tears . An astonishingly high rate of rotator cuff tears in patients with asymptomatic shoulders was thus demonstrated with increasing patient age . At this stage it remains unclear , however , which parameters convert an asymptomatic rotator cuff tear into a symptomatic tear . As a result , rotator cuff tears must to a certain extent be regarded as " normal " degenerative attrition , not necessarily causing pain and functional impairment Major ruptures of the rotator cuff were repaired in 89 patients over a six-year period , using an approach through the split deltoid muscle and the bed of the excised outer centimetre of the clavicle . Review of these patients showed that poor results were associated with larger cuff defects , with more pre-operative steroid injections and with pre-operative weakness of the deltoid muscle . A r and omised prospect i ve study showed that repair followed by splinting in abduction gave no better results than repair followed by resting the arm at the side . Excision of the coraco-acromial ligament was associated with worse results than leaving its divided halves in situ . Follow-up showed that the results continued to improve for two years after operation ; their quality was maintained in patients less than 60 years old , but in those over 60 there was deterioration with time A r and omized study of two types of conservative treatment of 78 shoulders in 78 patients with rotator cuff tears was performed . Twenty-five milligrams of sodium hyaluronate ( SH ) was injected into shoulders in one group ( SH group ) and 2 mg of dexamethasone was injected in the other group ( steroid group ) . Injection of each drug was planned for once per week for 5 consecutive weeks . In the SH group , University of California at Los Angeles score before treatment was 13.6 + /- 2.6 points in 16 patients who did not require surgery ( satisfied patients ) and 12.8 + /- 3.5 points in 22 patients who required surgery ( unsatisfied patients ) ( not statistically significant ) . In the steroid group , University of California at Los Angeles score before treatment was 11.9 + /- 3.6 points for 15 satisfied patients and 12.6 + /- 3.9 points for 25 unsatisfied patients ( again , not statistically significant ) . In the SH group , the score at 4 weeks after treatment for satisfied patients increased to 27.6 + /- 3.1 points , whereas that for unsatisfied patients was 14.9 + /- 1.2 points ( P < .0001 ) . Similarly , in the steroid group , the score at 4 weeks after the treatment for satisfied patients increased to 26.5 + /- 2.0 points , whereas that for unsatisfied patients was 15.0 + /- 4.0 points ( P < .0001 ) . At 24 weeks after treatment , the score for satisfied patients was 26.2 + /- 3.1 points in the SH group and 25.3 + /- 2.5 points in the steroid group . The effective rate of the SH group was 39.5 % and that of the steroid group was 35 % . Therapeutic efficacy in the SH group was equivalent to that in the steroid group . In both groups , the rate of patients who engaged in manual labor was significantly higher in the group of unsatisfied patients than in that of satisfied patients . No adverse reaction to either treatment was observed . These results suggest that SH is an effective conservative treatment for patients with rotator cuff tears A prospect i ve , r and omized , controlled , double-blind clinical study was performed to determine the short-term efficacy of subacromial injection of corticosteroids for the treatment of subacromial impingement syndrome . Forty patients were r and omized to receive either six milliliters of 1 per cent lidocaine without epinephrine ( the control group ) or two milliliters containing forty milligrams of triamcinolone acetonide per milliliter with four milliliters of 1 per cent lidocaine without epinephrine ( the corticosteroid group ) . The patients were re-examined serially until completion of the study . Nineteen patients , whose mean age was fifty-six years ( range , thirty-two to eighty years ) , were r and omized to the corticosteroid group , and twenty-one patients , whose mean age was fifty-seven years ( range , thirty-two to eighty-one years ) , were r and omized to the control group . The mean duration of symptoms before the injection was eight months for both groups . Eighteen patients in the corticosteroid group and nineteen patients in the control group had moderate or severe pain before the injection . At the most recent follow-up evaluation , at a mean of thirty-three weeks for the corticosteroid group and twenty-eight weeks for the control group , three patients in the corticosteroid group had moderate or severe pain , compared with fifteen patients in the control group . The mean active range of forward elevation and external rotation improved by 24 and 11 degrees , respectively , for the corticosteroid group and by 10 and 5 degrees , respectively , for the control group . We concluded that subacromial injection of corticosteroids is an effective short-term therapy for the treatment of symptomatic subacromial impingement syndrome . The use of such injections can substantially decrease pain and increase the range of motion of the shoulder Background : Rotator cuff tears are the most frequent tendon injury in the adult population . However , the natural history of nonoperatively treated full-thickness tears is poorly defined . Knowledge of the expected evolution in tear size is important when considering nonoperative versus surgical care , especially in relatively young , active patients . Purpose : To evaluate the size change of nonoperatively treated full-thickness rotator cuff tears over 2 to 3 years ’ follow-up . Study Design : Case series ; Level of evidence , 4 . Methods : The authors prospect ively followed patients 60 years old or younger who had a full-thickness rotator cuff tear equal to or larger than 5 mm , as diagnosed by bilateral shoulder ultrasound , and who were treated nonoperatively . At 2 to 3 years after the index ultrasound examination , a repeat ultrasound examination was performed by the same ultrasonographer . Results of the follow-up ultrasound examinations of both shoulders were compared with those of the index ultrasound examinations for change in rotator cuff tear size . The correlations were examined between these changes and age , sex , history of initial trauma , size of tear on the index ultrasound , and current shoulder symptoms . Results : Fifty-one patients with 61 rotator cuff tears were evaluated . At a follow-up of 25 to 39 months ( mean , 29 ) , 49 % of the tears ( 30 tears ) increased in size , 43 % ( 26 tears ) had not changed , and 8 % ( 5 tears ) decreased in size . For 25 % ( 10 shoulders ) of initially intact shoulders ( 41 shoulders ) , a new full-thickness rotator cuff tear was diagnosed . No correlation was found between the change in tear size and age of the patient ( P = .85 ) , sex ( P = .93 ) , existence of a prior trauma ( P = .63 ) , size of tear at index ultrasound ( P = .62 ) , and bilateral tears ( P = 1.00 ) . There was a correlation between the existence of considerable pain at the time of the follow-up ultrasound and a clinical ly significant increase in tear size ( P = .002 ) . Conclusion : Full-thickness rotator cuff tears tend to increase in size in about half of patients aged 60 years or younger . Surgery should be initially considered in these patients to prevent a probable increase in size tear . Patients treated nonoperatively should be routinely monitored for tear size increase , especially if they remain symptomatic AIM The aim of this prospect i ve study was to evaluate the effect of corticosteroids intra-articular injections on pain in patients with rotator cuff tear ( RCT ) , and to identify predictors for pain outcomes . METHODS A total of 60 patients with RCT were enrolled . All patients underwent rehabilitation ; 20 patients received a single intra-articular injection of 40 mg triamcinolone acetonide and 20 patients had a repeat injection at a 21-day interval . Backward stepwise regression analysis was used to predict effectiveness and improvement of pain . The independent variables were age , sex , symptom duration , tear size , passive range of motion ( ROM ) , active ROM , non-steroidal anti-inflammatory drugs request , pain at rest , number of triamcinolone injections and severity of osteoarthritis at admission . RESULTS At 3 and 6 months , patients who received triamcinolone had higher effectiveness and improvement in pain during activities and pain at night than those of control group . At the 3-month interval post-therapy , active ROM was the only predictor for effectiveness in pain during activity , effectiveness in pain at night and improvement in pain at night . Six months after therapy , active ROM was a predictor for improvement in pain at night . Age was a predictor for effectiveness in pain at night , whereas tear size of RCT was a predictor for effectiveness and improvement in pain during activity . CONCLUSIONS Corticosteroids can relieve pain in RCT . Active ROM is the most important predictor of pain outcomes . This finding can be useful to physicians when deciding on the type of patients who might best benefit from intra-articular injections of corticosteroids Objective : To compare the effects of platelet-rich plasma injection with those of dry needling on shoulder pain and function in patients with rotator cuff disease . Design : A single-centre , prospect i ve , r and omized , double-blinded , controlled study . Setting : University rehabilitation hospital . Participants : Thirty-nine patients with a supraspinatus tendon lesion ( tendinosis or a partial tear less than 1.0 cm , but not a complete tear ) who met the inclusion criteria recruited between June 2010 and February 2011 . Intervention : Two dry needling procedures in the control group and two platelet-rich plasma injections in the experimental group were applied to the affected shoulder at four-week intervals using ultrasound guidance . Measurements : The Shoulder Pain and Disability Index , passive range of motion of the shoulder , a physician global rating scale at the six-month follow-up , adverse effects monitoring and an ultrasound measurement were used as outcome measures . Results : The clinical effect of the platelet-rich plasma injection was superior to the dry needling from six weeks to six months after initial injection ( P < 0.05 ) . At six months the mean Shoulder Pain and Disability Index was 17.7 ± 3.7 in the platelet-rich plasma group versus 29.5 ± 3.8 in the dry needling group ( P < 0.05 ) . No severe adverse effects were observed in either group . Conclusions : Autologous platelet-rich plasma injections lead to a progressive reduction in the pain and disability when compared to dry needling . This benefit is certainly still present at six months after treatment . These findings suggest that treatment with platelet-rich plasma injections is safe and useful for rotator cuff disease Abstract Introduction . Rotator cuff tears ( RCT ) are a common source of shoulder pain , with an incidence ranging between 5 % and 40 % . The influence of corticosteroid injections on the incidence of RCT remains unknown . The aim of this study was to estimate the incidence of full-thickness RCT 12 weeks after a subacromial corticosteroid injection in patients with shoulder pain . Patients and method . We made a prospect i ve , open-label study in patients with unilateral painful shoulder without previous local corticosteroid injection . Ultrasound assessment s were made at the first ( baseline ) and last ( Week 12 ) visits by an experienced radiologist . A rheumatologist did the clinical examination . Patients with full-thickness RCT at the first visit were excluded . All patients received a subacromial injection of triamcinolone acetate 40 mg . Results . One hundred and two patients with shoulder pain were initially evaluated : 49 ( 48 % ) were excluded due to full-thickness RCT on ultrasound assessment . Therefore , 53 patients completed the study ( 34 female , mean age 60.8 years , mean time of evolution 9.6 months ) . In the first ultrasound evaluation , 24 patients ( 45.3 % ) had a partial-thickness tear . At 12 weeks after the corticosteroid injection , 9 ( 17 % ) patients developed full-thickness RCT , 66.6 % of which occurred in patients with previous partial-thickness RCT . Corticosteroid injection significantly improved symptoms ( p = 0.0001 for pain VAS score ) and range of motion ( p = 0.002 for forward elevation and external rotation ) . Conclusions . Seventeen percent of patients with shoulder pain suffered a full-thickness RCT 12 weeks after subacromial corticosteroid injection . Corticosteroid injection is highly effective in improving clinical symptoms of rotator cuff tendinopathy at 12 weeks |
854 | 17,253,516 | Thus fewer failures occurred when using non-metal posts but the evidence is unreliable .
Our systematic review could not specify which type of post and core system should be used when two or three dentine walls remain . | BACKGROUND The foundation for the reconstruction of endodontically-treated teeth can be provided by a metal or a non-metal post and core system but no guidelines exist for choosing one or the other in particular clinical cases .
OBJECTIVES To assess the effectiveness of different post and core systems for the restoration of endodontically-treated teeth .
The primary objective of this review was to compare the clinical failure rates of the different types of posts . | This study reports a prospect i ve clinical trial comparing a carbon fibre reinforced carbon ( CFRC ) endodontic post with a conventional prefabricated post . Twenty-seven single rooted maxillary anterior teeth in 18 patients ( nine males and nine females ; age range 18 - 60 years ) were restored either with a CFRC post or a wrought precious alloy control . Cast type III gold alloy cores were used in conjunction with both post groups . The CRFC posts ( n = 16 ) were cemented with a composite luting agent and the conventional posts ( control ) were cemented with zinc phosphate . Four failures were recorded in the CFRC post group at 24 , 29 , 56 and 87 months , compared with one failure in the control group at 84 months . These results suggest that post-retained crowns utilizing a CFRC material and a composite resin luting agent do not perform as well as conventional wrought precious alloy posts AIMS AND METHODS The purpose of this retrospective , non-r and omised cohort study was to evaluate the success rate of 775 endodontically treated teeth depending on the restoration type . A total of 508 patients with 775 endodontically treated teeth were examined during at least 12 months . The radiographic controls , time span between root canal filling and definitive restoration , restoration material type , inserted post system type and the occurrence of possible endodontically as well as restorative post-operative complications were recorded . RESULTS 18.3 % of the 775 investigated teeth were incisors and canines , 33.5 % were premolars and 48.2 % molars . Pre-fabricated and casted metal post systems were used only in 15.6 % of the endodontically treated teeth ( 18.4 % incisors and canines , 44.8 % premolars , 36.8 % molars ) . 6.6 % of the teeth had endodontically related symptoms or severe complications , whereas in 13.2 % of the teeth restored with metal posts showed complications , such as root or crown fractures . The Cox-Regression analysis showed that teeth restored with a post system had a statistically significant higher failure rate ( p = 0.044 ) than those which had been restored without posts . CONCLUSIONS The results showed a high success rate for endodontically treated teeth when the final restoration was placed within a short period of time ( two weeks ) . A higher tooth loss was observed when metal post systems were employed suggesting that pre caution is recommended when these types of posts are inserted STATEMENT OF PROBLEM Crowns have been considered the restoration of choice for endodontically treated teeth , but their selection has been based primarily on anecdotal evidence . PURPOSE This study tested the hypothesis that crown placement ( coronal coverage ) is associated with improved survival of endodontically treated teeth when preaccess , endodontic , and restorative factors are controlled . MATERIAL AND METHODS A University of Iowa College of Dentistry treatment data base was used to identify permanent teeth that had undergone initial obturation between July 1 , 1985 , and December 31 , 1987 . Study patients were restricted to persons with at least 1 dental visit in each 2-year interval from 1985 to 1996 ; a simple r and om sample of 280 patients ( n = 400 teeth ) was selected . Dental charts , radiographs , and computerized data bases were examined to ascertain variables of interest and to verify study inclusion criteria . Kaplan-Meier survival estimates were generated for the 203 teeth that satisfied study inclusion criteria . Multivariate Cox proportional hazards regression models were developed , with st and ard errors adjusted to account for clustering of teeth within patients . RESULTS When tooth type and radiographic evidence of caries at access were controlled , the final Cox model showed that endodontically treated teeth not crowned after obturation were lost at a 6.0 times greater rate than teeth crowned after obturation ( 95 % confidence interval : 3.2 to 11.3 ) . CONCLUSION Within the limitations of this study , a strong association between crown placement and the survival of endodontically treated teeth was observed . These results may impact treatment planning if long-term tooth retention is the primary goal Through a st and ardized procedure using clinical examination , interviews , and dental history , this 2-year study documents 100 cases of tooth fracture in 98 patients . For comparison , pertinent information was also recorded for more than 2,000 teeth in a r and omly selected sample population . Two chief types of fracture were found : incomplete crown-root fractures and root fractures associated with earlier endodontic therapy BACKGROUND A prospect i ve study was started in 1995 to evaluate the success of carbon fibre reinforced epoxy resin ( CFRR ) posts used to restore endodontically treated teeth . All the teeth in the study had lost more than 50 % of their coronal structure . METHODS Fifty-nine carbon fibre Composiposts cemented with Metabond and built up with Core Paste cores were placed into the teeth of 47 patients . Each tooth received a full-coverage restoration ( porcelain fused to metal crown ) and was followed for 6.7 - 45.4 months ( average = 28.0 months , st and ard deviation = 10.7 ) . RESULTS Results for 52 teeth in 42 patients were analyzed . There were no fractures . The overall failure rate was 7.7 % and the cumulative survival rate was 89.6 % at the end of the follow-up period . The only statistically significant finding ( p = 0.04 ) was that posts in lower premolars were at higher risk of failure . CONCLUSION CFRR posts are among the most predictable systems available today . CFRR posts in the upper anterior teeth are associated with a higher success rate and longer life than those placed in premolars , especially lower premolars . This study contributes to the growing body of evidence that supports the use of CFRR posts in the restoration of endodontically treated teeth PURPOSE This study prospect ively evaluated the clinical performance of three types of translucent posts over a follow-up period of between 2 and 3 years . MATERIAL S AND METHODS Selected were 225 patients with one premolar in need of endodontic treatment , followed by restoration with a fiber post and porcelain crown . The sample was r and omly divided into three groups of 75 patients each . The same type of post was used in all patients within a group : group 1 = Aesthetic Plus ; group 2 = DT ; and group 3 = FRC Postec . For bonding the post , a light-curing adhesive ( One-Step ) and a dual-curing resin cement ( Duo-Link ) were applied in group 1 and 2 roots , whereas self-curing material s ( Excite DSC as adhesive and MultiLink as resin cement ) were used in group 3 . After 6 , 12 , and 24 months , patients were recalled , and a clinical and radiographic examination was performed . For some patients , 30-month follow-up data were also collected . RESULTS Debonding of the post occurrred in eight cases ( 3.5 % ) ; in another six cases , a recurrence of the periapical lesion was reported . CONCLUSION The statistical analysis did not reveal any significant difference in the survival rate of the tested posts , suggesting that all are equally and sufficiently reliable for clinical use PURPOSE In the present prospect i ve study , four different post- and -core systems were evaluated over a period of up to 10 years . MATERIAL S AND METHODS Fifty endodontically treated teeth in 31 patients were r and omized to one of four groups for post- and -core placement : Group 1 received conventional tapered cast posts and cores ( n = 14 ) ; group 2 received ParaPost system prefabricated gold posts with cast cores ( n = 13 ) ; group 3 received ParaPost system cast posts and cores ( n = 13 ) ; and group 4 received Radix-Anchor posts ( n = 10 ) . Clinical and radiologic evaluations were made . RESULTS One post and core in group 2 was functioning well 58 months after placement when the patient died . No posts and cores in groups 1 or 2 had been lost or had any complications , one in group 3 had been lost because of a root fracture after 108 months , and two in group 4 had been lost after 54 and 88 months , respectively , because of loss of retention . The final treatment result for 46 of the 49 remaining posts ( 30 patients ) was successful . The overall failure rate was 6 % . There were no statistically significant differences between the four groups . CONCLUSION If recommended procedures are strictly followed , posts and cores can serve as abutments for fixed single crowns with satisfactory long-term results OBJECTIVES The aim of this study is to provide prospect i ve clinical data for the survival of postendodontic reconstructions of teeth with varying degrees of hard tissue loss using tapered or parallel-sided post shapes . METHODS Eighty-three patients got 105 glass fibre reinforced posts of tapered ( Luscent Anchors , Dentatus , Sweden ) and parallel-sided , serrated ( FibreKor , Jeneric Pentron , USA ) post shape . A dual curing hybrid composite Compolute ( 3 M ESPE , Germany ) was used as luting material , EBS-Multi ( 3 M ESPE ) as adhesive system and Clearfil Core ( Kuraray , Japan ) for core built-up . The restorations were followed for a minimum of 24 months . The statistical analysis was performed on a r and om sub- sample of one restoration per subject . The Fisher exact test was used to compare frequencies of failures after 12 and 24 month . A Kaplan-Meier- analysis was used to analyse time-to-failure in both groups . Differences of survival time between post types were tested with the log-rank test . RESULTS 3.8 % of the restorations failed after 12 month , 12.8 % after 24 month , respectively . The main failure type observed was post fractures . All but one failed teeth could be restored . There was no difference in failure frequency between post types after 12 or 24 months . The log-rank test showed no differences in survival between the two types of post ( p=0.37 ) . CONCLUSION Parallel-sided and tapered glass fibre posts result after 2 years of clinical service in an equal rate of survival PURPOSE This prospect i ve clinical follow-up evaluated the acceptability of quartz fiber-reinforced epoxy posts used in endodontically treated teeth over a 30-month period . MATERIAL S AND METHODS In 132 patients , 180 endodontically treated teeth were restored using AEstheti-Plus quartz-fiber posts . The posts were luted with the All-Bond 2 adhesive system and C&B Resin Cement according to the manufacturer 's recommendations . The core was made with Core-Flo or Bis-Core , and all-ceramic crowns or metal-ceramic crowns were applied as final restorations . The parameters considered as clinical failure were displacement , detachment , or fracture of posts ; core or root fracture ; and crown or prosthesis decementation . Patients were reevaluated at 6 , 12 , 24 , and 30 months . RESULTS One cohesive failure involving a margin of the composite core was observed after 2 weeks , and two adhesive fractures were seen after 2 months . These failures were located between the cement and the dentin walls of the canals . All three failures occurred during removal of the temporary crown . The percentage of failures was thus 1.7 % over a 30-month period , but it was possible to successfully replace the restoration in all three failed cases . CONCLUSION Over a 30-month period , the rehabilitation of endodontically treated teeth using quartz-fiber posts showed good clinical results . No crown or prosthesis decementation was observed , and no post , core , or root fractures were recorded Prospect i ve clinical studies comparing the results of different types of restorations of endodontically treated teeth are lacking . This study compared the clinical success rate of endodontically treated premolars restored with fiber posts and direct composite to the restorations of premolars using amalgam . Premolars with Class II carious lesions were selected and r and omly assigned to one of two experimental groups : ( 1 ) restoration with amalgam or ( 2 ) restoration with fiber posts and composite . One hundred and nine teeth were included in Group 1 and 110 in Group 2 . Patients were recalled after 1 , 3 and 5 years . No statistically significant difference was found between the proportion of failed teeth in the two experimental groups . Significant differences were observed between the proportion of root fractures ( p=0.029 ) and caries ( p=0.047 ) , with more root fractures and less caries observed in the teeth restored with amalgam at the five-year recall . Within the limits of this study , it can be concluded that restorations with fiber posts and composite were found to be more effective than amalgam in preventing root fractures but less effective in preventing secondary caries STATEMENT OF PROBLEM Little information exists regarding the outcome of crown build-ups on endodontically treated teeth restored with metal-ceramic crowns or with only a direct-placed composite . PURPOSE The aim of this study was to evaluate the clinical success rate of endodontically treated premolars restored with fiber posts and direct composite restorations and compare that treatment with a similar treatment of full-coverage with metal-ceramic crowns . MATERIAL AND METHODS Subjects included in this study had one maxillary or m and ibular premolar for which endodontic treatment and crown build up was indicated and met specific inclusion /exclusion criteria . Only premolars with Class II carious lesions and preserved cusp structure were included . Subjects were r and omly assigned to 1 of the following 2 experimental groups : ( 1 ) teeth endodontically treated and restored with adhesive techniques and composite or ( 2 ) teeth endodontically treated , restored with adhesive techniques and composite , and then restored with full-coverage metal-ceramic crowns . Sixty teeth were included in the first group and 57 in the second . All restorations were performed by one operator . Causes of failure were categorized as root fracture , post fracture , post decementation , clinical and /or radiographic evidence of marginal gap between tooth and restoration , and clinical and /or radiographic evidence of secondary caries contiguous with restoration margins . Subjects were examined for the listed clinical and radiographic causes of failure by 2 calibrated examiners at intervals of 1 , 2 , and 3 years . Exact 95 % confidence intervals for the difference between the 2 experimental groups were calculated . RESULTS At the 1-year recall , no failures were reported . The only failure modes observed at 2 and 3 years were decementations of posts and clinical and /or radiographic evidence of marginal gap between tooth and restoration . There was no difference in the failure frequencies of the 2 groups ( 95 % confidence interval , -17.5 to 12.6 ) . There was no difference between the number of failures caused by post decementations and the presence of marginal gaps observed in the 2 groups ( 95 % confidence intervals , -9.7 to 16.2 and -17.8 to 9.27 ) . CONCLUSION Within the limitations of this study , the results upheld the research hypothesis that the clinical success rates of endodontically treated premolars restored with fiber posts and direct composite restorations after 3 years of service were equivalent to a similar treatment of full coverage with metal-ceramic crowns This study investigated how the absence of a ferrule affected the failure load of teeth that had been restored with bonded fiber posts and resin cores . There was a significant difference ( p < 0.001 ) between the ferrule and nonferrule groups ' load to failure . For the ferrule group , root fracture was the predominant mode of failure ; in the nonferrule group , debonding failures were predominant |
855 | 29,059,210 | Autonomic regulation tends to be consistent between insomniacs , as long as they are grouped according to their respective phenotype , as shown in the insomnia subgroup with objective ly short sleep duration .
Our hypothesis is that these differences in the expression of cardiovascular activity could be explained by the heterogeneity of the disorder .
Therefore , the determination of insomnia phenotypes , and the study of cardiovascular measures , rather than heart rate variability alone , will give more insight into the link between insomnia and cardiovascular regulation .
This study suggests that cardiovascular activity differs between insomniacs and controls . | BACKGROUND Insomnia disorder is a widespread sleep disorder with a prevalence of approximately 10 % .
Even though the link between insomnia and cardiovascular activity is not exactly clear , it is generally assumed that cardiovascular autonomic modifications could occur as a result of sleeplessness , or , alternatively , that autonomic alterations could be an expression of a hyper-arousal state .
This review investigates whether cardiovascular measures are different between insomniacs and controls . | BACKGROUND The powers of the low-frequency ( LF ) and high-frequency ( HF ) oscillations characterizing heart rate variability ( HRV ) appear to reflect , in their reciprocal relationship , changes in the state of the sympathovagal balance occurring during numerous physiological and pathophysiological conditions . However , no adequate information is available on the quantitative resolution of this methodology . METHODS AND RESULTS We studied 22 healthy volunteers ( median age , 46.5 years ) who were subjected after a rest period to a series of passive head-up tilt steps r and omly chosen from the following angles : 15 degrees , 30 degrees , 45 degrees , 60 degrees , and 90 degrees . From the continuous ECG , after appropriate analog-to-digital conversion , a personal computer was used to compute , with an autoregressive methodology , time and frequency domain indexes of RR interval variability . Spectral and cross-spectral analysis with the simultaneously recorded respiratory signal excluded its contribution to LF . Age was significantly correlated to variance and to the absolute values in milliseconds squared of very-low-frequency ( VLF ) , LF , and HF components . The tilt angle was correlated to both LF and HF ( expressed in normalized units [ nu ] ) and to the LF-to-HF ratio ( r = .78 , -.72 , and .68 ; respectively ) . Lower levels of correlation were found with HF ( in ms2 ) and RR interval . No correlation was present between tilt angle and variance , VLF , or LF ( in ms2 ) . Individual analysis confirmed that the use of nu provided the greatest consistency of results . CONCLUSIONS Spectral analysis of HRV , using nu or LF-to-HF ratio , appears to be capable of providing a noninvasive quantitative evaluation of grade d changes in the state of the sympathovagal balance OBJECTIVE To assess as whether insomniacs have higher nighttime blood pressure ( BP ) and a blunted day-to-night BP reduction , recognized markers of increased risk of cardiovascular morbidity and mortality . DESIGN Prospect i ve case-control study . SETTING University hospital-based sleep research laboratory . PARTICIPANTS Thirteen normotensive subjects with chronic primary insomnia ( 9 women , 42 + /- 7 y ) and 13 sex- and age-matched good sleepers . MEASUREMENTS AND RESULTS Subjects underwent 2-week sleep diary and 3 sleep studies to provide subjective and objective sleep variables , and 24-h beat-to-beat BP recording to provide daytime , night-time and day-to-night BP changes ([nighttime-daytime]/daytime)*100 ) ( BP dipping ) . Spectral analysis of the electroencephalogram ( EEG ) was also performed during sleep of night 3 to assess EEG activity in the beta frequency ( 16 - 32 Hz ) , a measure of brain cortical activation . Nighttime SBP was higher ( 111 + /- 15 vs 102 + /- 12 mm Hg , P < 0.01 ) and day-to-night SBP dipping was lower (-8 % + /- 6 % vs -15 % + /- 5 % , P < 0.01 ) in insomniacs than good sleepers . Insomniacs also had higher activity in EEG beta frequency ( P < 0.05 ) . Higher nighttime SBP and smaller SBP dipping were independently associated with increased EEG beta activity ( P < 0.05 ) . CONCLUSIONS Higher nighttime SBP and blunted day-to-night SBP dipping are present in normotensive subjects with chronic insomnia and are associated with a hyperactivity of the central nervous system during sleep . An altered BP profile in insomniacs could be one mechanism implicated in the link between insomnia and cardiovascular morbidity and mortality documented in epidemiological studies Entropy , as it relates to dynamical systems , is the rate of information production . Methods for estimation of the entropy of a system represented by a time series are not , however , well suited to analysis of the short and noisy data sets encountered in cardiovascular and other biological studies . Pincus introduced approximate entropy ( ApEn ) , a set of measures of system complexity closely related to entropy , which is easily applied to clinical cardiovascular and other time series . ApEn statistics , however , lead to inconsistent results . We have developed a new and related complexity measure , sample entropy ( SampEn ) , and have compared ApEn and SampEn by using them to analyze sets of r and om numbers with known probabilistic character . We have also evaluated cross-ApEn and cross-SampEn , which use cardiovascular data sets to measure the similarity of two distinct time series . SampEn agreed with theory much more closely than ApEn over a broad range of conditions . The improved accuracy of SampEn statistics should make them useful in the study of experimental clinical cardiovascular and other biological time series Objectives : The prevalence of insomnia is very high in our society . Although pharmacological treatment of insomnia is available , most hypnotics have been shown to alter sleep architecture and have many adverse effects . Gabapentin was originally design ed for antiepileptic therapy ; however , some studies reported that its use increases slow-wave sleep in healthy volunteers or patients . Our goal was to evaluate the benefits of gabapentin in the treatment of primary insomnia in patients . Methods : Eighteen patients with primary insomnia participated in the study . They received gabapentin treatment for at least 4 weeks . All patients received polysomnography , a biochemical blood test , and neuropsychological tests before and after the treatment period . All measures were analyzed with Student t test to examine the treatment effects of gabapentin , except that the measures of heart rate variability were analyzed with analysis of variance . Results : Polysomnographic study revealed increased sleep efficiency and slow-wave sleep , decreased wake after sleep onset , and spontaneous arousal index after gabapentin treatment . The biochemical blood test revealed decreased prolactin levels in the morning after treatment . Electroencephalographic power spectral analysis showed increased delta-2 and theta power in sleep stage 1 and decreased sigma activity power in sleep stages N2 and N3 after gabapentin treatment . Heart rate variability analyses also showed a significant increase in normalized high frequency percentage in sleep stages N2 and N3 and low frequency-high frequency ratio in sleep stage N2 after treatment . In addition , neuropsychological tests revealed the elevation of visual motor processing speed after gabapentin treatment . Conclusions : Gabapentin enhances slow-wave sleep in patients with primary insomnia . It also improves sleep quality by elevating sleep efficiency and decreasing spontaneous arousal . The results suggest that gabapentin may be beneficial in the treatment of primary insomnia STUDY OBJECTIVES To examine the joint effect of insomnia and objective short sleep duration on hypertension risk . DESIGN Representative cross-sectional study . SETTING Sleep laboratory . PARTICIPANTS 1,741 men and women r and omly selected from central Pennsylvania . INTERVENTIONS None . MEASUREMENTS Insomnia was defined by a complaint of insomnia with a duration > or = 1 year , while poor sleep was defined as a complaint of difficulty falling asleep , staying asleep , or early final awakening . Polysomnographic sleep duration was classified into 3 categories : > or = 6 h sleep ( top 50 % of the sample ) ; 5 - 6 h ( approximately the third quartile of the sample ) ; and < or = 5 h ( approximately the bottom quartile of the sample ) . Hypertension was defined based either on blood pressure measures or treatment . We controlled for age , race , sex , body mass index , diabetes , smoking , alcohol use , depression , sleep disordered breathing ( SDB ) , and sampling weight . RESULTS Compared to the normal sleeping and > 6 h sleep duration group , the highest risk of hypertension was in insomnia with < 5 h sleep duration group ( OR [ 95 % CI ] 5.1 [ 2.2 , 11.8 ] ) , and the second highest in insomnia who slept 5 - 6 hours ( OR 3.5 [ 1.6 , 7.9 ] P < 0.01 ) . The risk for hypertension was significantly higher , but of lesser magnitude , in poor sleepers with short sleep duration . CONCLUSIONS Insomnia with short sleep duration is associated with increased risk of hypertension , to a degree comparable to that of other common sleep disorders , e.g. , SDB . Objective sleep duration may predict the severity of chronic insomnia a prevalent condition whose medical impact has been apparently underestimated Background Clinical presentation phenotypes of obstructive sleep apnoea ( OSA ) and their association with comorbidity as well as impact on adherence to continuous positive airway pressure ( CPAP ) treatment have not been established . Methods A prospect i ve follow-up cohort of adult patients with OSA ( apnoea-hypopnoea index ( AHI ) of ≥5/h ) from 17 European countries and Israel ( n = 6,555 ) was divided into four clinical presentation phenotypes based on daytime symptoms labelled as excessive daytime sleepiness ( “ EDS ” ) and nocturnal sleep problems other than OSA ( labelled as “ insomnia ” ) : 1 ) EDS ( daytime+/nighttime- ) , 2 ) EDS/insomnia ( daytime+/nighttime+ ) , 3 ) non-EDS/non-insomnia ( daytime-/nighttime- ) , 4 ) and insomnia ( daytime-/nighttime+ ) phenotype . Results The EDS phenotype comprised 20.7 % , the non-EDS/non-insomnia type 25.8 % , the EDS/insomnia type 23.7 % , and the insomnia phenotype 29.8 % of the entire cohort . Thus , clinical presentation phenotypes with insomnia symptoms were dominant with 53.5 % , but only 5.6 % had physician diagnosed insomnia . Cardiovascular comorbidity was less prevalent in the EDS and most common in the insomnia phenotype ( 48.9 % vs. 56.8 % , p<0.001 ) despite more severe OSA in the EDS group ( AHI 35.0±25.5/h vs. 27.9±22.5/h , p<0.001 , respectively ) . Psychiatric comorbidity was associated with insomnia like OSA phenotypes independent of age , gender and body mass index ( HR 1.5 ( 1.188–1.905 ) , p<0.001 ) . The EDS phenotype tended to associate with higher CPAP usage ( 22.7 min/d , p = 0.069 ) when controlled for age , gender , BMI and sleep apnoea severity . Conclusions Phenotypes with insomnia symptoms comprised more than half of OSA patients and were more frequently linked with comorbidity than those with EDS , despite less severe OSA . CPAP usage was slightly higher in phenotypes with EDS INTRODUCTION Impaired heart rate variability ( HRV ) is associated with poor outcome in diabetic patients . The present prospect i ve study compared spectral components of HRV obtained by either fast Fourier transform ( FFT ) or autoregressive ( AR ) analyses in diabetic patients . METHODS Thirty patients ( 49+/-12 years ; 11 F/19 M ; 60 % with insulin-dependent type 1 diabetes ) underwent 24-h ambulatory electrocardiographic recordings which comprised a 10-min resting period at the onset ( n=30 ) and end ( n=12 ) of the monitoring . Spectral analysis was applied to 5-min sequences at rest , and the total power and power spectra integrated over the very low ( VLF ) , low ( LF ) , and high ( HF ) frequency b and s were obtained . RESULTS Fifteen patients had moderately depressed HRV and two patients had highly depressed HRV ( st and ard deviation of the RR intervals over 24-h<100 ms and < 50 ms , respectively ) . Both raw data and ln-transformed data were significantly different between FFT and AR . All spectra component were obtained in each patient using FFT . Using AR , the LF/HF ratio could not be estimated or was zero in 4 and 11 patients , respectively . The AR results were more sensitive than FFT results to minor changes ( + /-5 % ) in the timing of the onset of analysis . The day-to-day reproducibility of FFT was better than that of AR . Finally , using FFT , the LF/HF ratio , LFnu , and HFnu were essentially redundant ( nu = normalized units ) . CONCLUSIONS The spectral components of short-term HRV calculated by using the FFT and AR methods were not interchangeable and FFT analysis must be preferred in diabetic patients AIMS Heart rate variability has been proposed as an indicator of cardiovascular health . Since women have a lower cardiovascular risk , we hypothesized that there are gender differences in autonomic modulation . METHODS AND RESULTS In 276 healthy subjects ( 135 women , 141 men ) between 18 and 71 years of age , 24 h heart rate and heart rate variability were determined . All heart rate variability parameters , except for pNN50 and high frequency power , were higher in men . After adjustment for heart rate , we obtained gender differences for : the st and ard deviation ( P=0.049 ) , the st and ard deviation of the 5 min average ( P=0.047 ) , low frequency power ( absolute values , P=0.002 ; normalized units , P<0.001 ) and ratio low frequency/high frequency ( P<0.001 ) . There were no significant gender differences in heart rate variability parameters denoting vagal modulation . Gender differences were confined to age categories of less than 40 years of age . The majority of heart rate variability parameters decreased with age . Only in men , was a higher body mass index associated with a higher heart rate and with lower heart rate variability parameters ( P<0.001 ) . CONCLUSION Cardiac autonomic modulation as determined by heart rate variability , is significantly lower in healthy women compared to healthy men . We hypothesize that this apparently paradoxical finding may be explained by lower sympathetic activity ( low frequency power ) in women . This may provide protection against arrhythmias and against the development of coronary heart disease The adaptive effects of physical training on cardiovascular control mechanisms were studied in 11 subjects with mild hypertension . In these subjects we assessed the gain of the heart periodsystolic arterial pressure relationship in the unfit and the fit state by using 1 ) an open loop approach , whereby the gain is expressed by the slope of the regression of heart period as a function of systolic arterial pressure , during a phenylephrine-induced pressure rise and 2 ) a closed loop approach with proper simplification , whereby the gain is expressed by the index a , obtained through simultaneous spectral analysis of the spontaneous variabilities of heart period and systolic arterial pressure . Both methods indicated that training significantly increased the gain of the relationship between heart period and systolk arterial pressure at rest and reduced arterial pressure and increased heart period significantly . This gam was drastically reduced during bicycle exercise both in the unfit and fit state . In a second group of normotensive ( n = 7 ; systolic pressure , 133 ± 3 mm Hg ) and hypertensive ( n = 7 ; systolic pressure , 180 ± 10 mm Hg ) subjects undergoing 24 -hour diagnostic continuous ekctrocardiographic and high fidelity arterial pressure monitoring , the index a was significantly reduced in the hypertensive group at rest . Furthermore , when analyzed continuously over the entire 24-hour period , this index underwentminute-to-minute changes with lower values during the day and higher values during the night . We propose the index a as a quantitative indicator of the changes in the gain of baroreceptor mechanisms occurring with physical training in mild hypertension and during a 24-hour period in ambulatory subjects 1 . It is often assumed that the power in the low- ( around 0.10 Hz ) and high-frequency ( around 0.25 Hz ) b and s obtained by power spectral analysis of cardiovascular variables reflects sympathetic and vagal tone [ corrected ] respectively . An alternative model attributes the low-frequency b and to a resonance in the control system that is produced by the inefficiently slow time constant of the reflex response to beat-to-beat changes in blood pressure effected by the sympathetic ( with or without the parasympathetic ) arm(s ) of the baroreflex ( De Boer model ) . 2 . We have applied the De Boer model of circulatory variability to patients with varying baroreflex sensitivity to patients with varying baroreflex sensitivity and one normal subject , and have shown that the main differences in spectral power ( for both low and high frequency ) between and within subjects are caused by changes in the arterial baroreflex gain , particularly for vagal control of heart rate ( R-R interval ) and left ventricular stroke output . We have computed the power spectrum at rest and during neck suction ( to stimulate carotid baroreceptors ) . We stimulated the baroreceptors at two frequencies ( 0.1 and 0.2 Hz ) , which were both distinct from the controlled respiration rate ( 0.25 Hz ) , in both normal subjects and heart failure patients with either sensitive or poor baroreflex control . 3 . The data broadly confirm the De Boer model . The low-frequency ( 0.1 Hz ) peak in either R-R or blood pressure variability ) was spontaneously generated only if the baroreflex control of the autonomic outflow was relatively intact . ( ABSTRACT TRUNCATED AT 250 WORDS UNLABELLED Circadian Profile of Heart Rate Variability . INTRODUCTION Although heart rate variability ( HRV ) has been established as a tool to study cardiac autonomic activity , almost no data are available on the circadian patterns of HRV in healthy subjects aged 20 to 70 years . METHODS AND RESULTS We investigated 166 healthy volunteers ( 81 women and 85 men ; age 42 + /- 15 years , range 20 - 70 ) without evidence of cardiac disease . Time-domain HRV parameters were determined from 24-hour Holter monitoring and calculated as hourly mean values and mean 24-hour values . All volunteers were fully mobile , awoke around 7 A.M. , and had 6 to 8 hours of sleep . Circadian profiles of vagus-associated HRV parameters revealed a marked day-night pattern , with a peak at nighttime and a plateau at daytime . The characteristic nocturnal peak and the day-night amplitude diminished with aging by decade . Estimates of overall HRV ( geometric triangular index [ TI ] , SD of NN intervals [ SDNN ] ) and long-term components of HRV ( SD of the averages of NN intervals for all 5-min segments [ SDANN ] ) were low at nighttime and increased in the morning hours . There was a significant decline of 24-hour values of all HRV parameters ( P < 0.001 ) and a strong negative correlation ( P < 0.001 ) with increasing age . Mean 24-hour RR interval ( P < 0.001 ) , SDNN , mean SD of NN intervals for all 5-minute intervals ( SDNNi ) , and SDANN ( all P < 0.01 ) were significantly higher in men . Younger men also exhibited significantly higher values for vagus-associated parameters ( root mean square successive difference [ rMSSD ] , P < 0.05 ; SDNNi , P < 0.01 ) ; however , gender differences diminished with increasing age . CONCLUSION Normal aging is associated with a constant decline of cardiac vagal modulation due to a significant decrease of nocturnal parasympathetic activity . The significant gender-related difference of HRV decreases with aging . These findings emphasize the need to determine age- , gender- , and nycthemeral-dependent normal ranges for HRV assessment Healthy and medically compromised patients were studied to compare blood pressure and heart rate changes in response to stress of routine dental extraction s performed while they were under local anesthesia . Thirty-nine patients divided into American Society of Anesthesiologists ( ASA ) I and II groups were noninvasively monitored every 5 minutes . Systolic , diastolic , and mean arterial pressures and heart rate were recorded . Rate pressure products ( RPP ) and pressure rate ( PRQ ) quotients were calculated and compared in each group . Significant results were measures of RPP greater than 12,000 and PRQ less than one . Of the 24 patients in the ASA I category , 50 % demonstrated elevated RPP values , but only two of 24 had coincidental PRQ abnormalities . Of the 15 patients in the ASA II category , 80 % demonstrated elevated RPP values , but two of 15 had coincidental PRQ abnormalities . Patients in the ASA II category had a higher incidence of RPP and PRQ abnormalities , as was expected . However , it is not known which of these two measures is a more sensitive indicator of increased risk associated with stimulation of the sympathetic-adrenergic axis during oral surgery performed with patients under local anesthesia . Correlation studies with continuous Holter monitoring for ST-T wave changes on electrocardiography are forthcoming |
856 | 17,215,726 | Due to insufficient evidence , rivastigmine could not yet be recommended for the treatment of vascular dementia .
Memantine appeared to be safe and well tolerated but did not demonstrate effectiveness across all cognitive outcomes and clinical global measures .
Conclusion : Acetylcholinesterase inhibitors and NMDA receptor antagonists , in general , displayed promise as treatments for patients with vascular dementia and vascular cognitive impairment .
The most effective , evidence -based treatments were donepezil and galantamine | Objective : In patients with vascular dementia and vascular cognitive impairment , are acetylcholinesterase inhibitors ( donepezil , galantamine , and rivastigmine ) and N-methyl-d-aspartate ( NMDA ) receptor antagonists ( memantine ) effective in improving cognitive function over placebo ? | Background and Purpose — Based on the hypothesis of glutamate-induced neurotoxicity ( excitotoxicity ) in cerebral ischemia , this study examined the efficacy and tolerability of memantine , an uncompetitive N-methyl-d-aspartate antagonist , in the treatment of mild to moderate vascular dementia . Methods — In this multicenter , 28-week trial carried out in France , 321 patients received 10 mg/d memantine or placebo twice a day ; 288 patients were valid for intent-to-treat analysis . Patients had to meet the criteria for probable vascular dementia and have a Mini-Mental State ( MMSE ) score between 12 and 20 at inclusion . The 2 primary end points were the cognitive subscale of the Alzheimers Disease Assessment Scale ( ADAS-cog ) and the global Clinician ’s Interview Based Impression of Change ( CIBIC-plus ) . Results — After 28 weeks , the mean ADAS-cog scores were significantly improved relative to placebo . In the intention-to-treat population , the memantine group mean score had gained an average of 0.4 points , whereas the placebo group mean score had declined by 1.6 points , ie , a difference of 2.0 points ( 95 % confidence interval , 0.49 to 3.60 ) . The response rate for CIBIC-plus , defined as improved or stable , was 60 % with memantine compared with 52 % with placebo ( P = 0.227 , intention to treat ) . Among the secondary efficacy parameters , which were analyzed in the per- protocol subset , MMSE was significantly improved with memantine compared with deterioration with placebo ( P = 0.003 ) . The Gottfries-Brane-Steen Scale intellectual function subscore and the Nurses ’ Observation Scale for Geriatric Patients disturbing behavior dimension also showed differences in favor of memantine ( P = 0.04 and P = 0.07 , respectively ) . Memantine was well tolerated with a frequency of adverse events comparable to placebo . Conclusions — In patients with mild to moderate vascular dementia , memantine 20 mg/d improved cognition consistently across different cognitive scales , with at least no deterioration in global functioning and behavior . It was devoid of concerning side effects BACKGROUND The Consortium to Investigate Vascular Impairment of Cognition ( CIVIC ) is a Canadian , multi-centre , clinic-based prospect i ve cohort study of patients with Vascular Cognitive Impairment ( VCI ) . We report its organization and the impact of diagnostic criteria on the study of VCI . METHODS Nine memory disability clinics enrolled patients and recorded their usual investigations and care . A case report form included all vascular dementia ( VaD ) individual criteria for each of four sets ( National Institute of Neurological Disorders and Stroke ( NINDS-AIREN ) , Alzheimer 's Disease Diagnostic Treatment Centers ( ADDTC ) , the ICD-10 Classification of Mental and Behavioural Disorders ( ICD-10 ) , and the Diagnostic and Statistical Manual of Mental Disorders ( DSM-IV ) ) of consensus-based diagnostic criteria and for the Hachinski Ischemia Score ( HIS ) . Investigators , having completed the case report form , were asked to make a clinical judgement about the cognitive diagnosis based on the best available information , including neuroimaging . RESULTS Of 1,347 patients ( mean age 72 years ; 56 % women ) , 846 ( 63 % ) were diagnosed with dementia and 324 ( 24 % ) were diagnosed with VCI . The proportion of patients diagnosed with VaD by the diagnostic criteria was : 23.9 % ( n = 322 ) by DSM-IV , 10.2 % ( n = 137 ) by HIS , 4.3 % ( n = 58 ) by ICD-10 , 3.8 % ( n = 51 ) by ADTCC , and 3.6 % ( n = 48 ) by NINDS-AIREN . Judged against a clinical diagnosis of VaD , the sensitivity/specificity of each was : DSM-IV ( 0.77/0.80 ) ; HIS ( 0.41/0.92 ) ; ICD-10 ( 0.29/0.98 ) ; ADTCC ( 0.24/0.98 ) ; NINDS-AIREN ( 0.42/0.995 ) . Compared with a clinical diagnosis of VCI , sensitivities were lower for the diagnostic criteria , reflecting the exclusion of patients who did not have dementia . CONCLUSIONS Consensus-based criteria for VaD omit patients who do not meet dementia criteria that are modeled on Alzheimer 's disease . Even for patients who do , the proportion identified with VaD varies widely . Criteria based on empirical analyses need to be developed and vali date Objective : To evaluate the efficacy and tolerability of donepezil in patients with vascular dementia ( VaD ) . Methods : Patients ( n = 616 ; mean age , 75.0 years ) with probable or possible VaD , according to National Institute of Neurological Disorders and Stroke – Association Internationale pour la Recherche en l’Enseignement en Neurosciences criteria , were r and omized to receive donepezil 5 mg/day ( n = 208 ) , donepezil 10 mg/day ( after 5 mg/day for the first 28 days ) ( n = 215 ) , or placebo ( n = 193 ) for 24 weeks . Results : Seventy-six percent of the patients enrolled had probable VaD. A total of 75.3 % of the 10 mg donepezil group and 80.8 % of the 5 mg group completed the study compared with 83.4 % of the placebo group . Both donepezil-treated groups showed improvements in cognitive function on the Alzheimer ’s Disease Assessment Scale – cognitive subscale compared with placebo , with a mean endpoint treatment difference , as measured by the change from baseline score , of approximately 2 points ( donepezil 5 mg , −1.65 [ p = 0.003 ] ; 10 mg , −2.09 [ p = 0.0002 ] ) . Greater improvements on the Clinician ’s Interview-Based Impression of Change – plus version were observed with both donepezil groups than with the placebo group ( overall donepezil treatment vs placebo p = 0.008 ) ; 25 % of the placebo group showed improvement compared with 39 % ( p = 0.004 ) of the 5 mg group and 32 % ( p = 0.047 ) of the 10 mg group . Withdrawal rates due to adverse events were low ( placebo , 8.8 % ; donepezil 5 mg , 10.1 % ; 10 mg , 16.3 % ) . Conclusions : Donepezil-treated patients demonstrated significant improvements in cognition and global function compared with placebo-treated patients , and donepezil was well tolerated Little is known about progression , short of dementia , in vascular cognitive impairment . In the Canadian Study of Health and Aging , 149 participants ( 79.3 ± 6.7 years ; 61 % women ) were found to have vascular cognitive impairment , no dementia ( CIND ) . After 5 years , 77 participants ( 52 % ) had died and 58 ( 46 % ) had developed dementia . Women were at greater risk of dementia ( OR 2.1 , 1.0 to 4.5 ) . Of 32 participants alive without dementia , cognition had deteriorated in seven and improved in four . Half of those with vascular CIND developed dementia within 5 years , suggesting a target for preventive interventions Background and Purpose — Clinical observations suggest that patients with vascular dementia ( VaD ) may benefit from treatment with cholinesterase inhibitors . This study evaluated the efficacy and safety of donepezil for relieving symptoms of dementia in VaD. Methods — Patients ( n=603 ; mean age , 73.9 years ; 55.2 % men ) with probable ( 70.5 % ) or possible ( 29.5 % ) VaD , according to criteria of the National Institute of Neurological Disorders and Stroke ( NINDS ) and the Association Internationale pour la Recherche et l’Enseignement en Neurosciences ( AIREN ) , were r and omized to 24 weeks of treatment with donepezil 5 mg/d ( n=198 ) , donepezil 10 mg/d ( 5 mg/d for first 28 days ; n=206 ) , or placebo ( n=199 ) . Analyses were based on the intent-to-treat population . Results — At week 24 , both donepezil groups showed significant improvement in cognition versus placebo on the Alzheimer ’s Disease Assessment Scale – cognitive subscale ( mean change from baseline score effect size : donepezil 5 mg/d , −1.90 ; P = 0.001 ; donepezil 10 mg/d , −2.33 ; P < 0.001 ) . Significant improvements in patients ’ global function were seen versus placebo at week 24 ( observed cases ) , on the Clinician ’s Interview-Based Impression of Change – Plus version only for patients on donepezil 5 mg/d ( P = 0.014 ) , and on the Sum of the Boxes of the Clinical Dementia Rating only for patients on 10 mg/d ( P = 0.007 ) . Donepezil-treated patients showed significant benefits in activities of daily living over placebo on the Alzheimer ’s Disease Functional Assessment and Change Scale ( mean change from baseline score effect size at week 24 : donepezil 5 mg/d , −1.31 , P = 0.02 ; donepezil 10 mg/d , −1.31 , P = 0.02 ) . Donepezil was well tolerated . Withdrawal rates due to adverse events were relatively low ( placebo , 11.1 % ; donepezil 5 mg/d , 11.1 % ; donepezil 10 mg/d , 21.8 % ; P = 0.005 versus placebo ) . Conclusions — These data demonstrate that donepezil is an effective and well-tolerated treatment for VaD and show it may have an important place in the management of this condition |
857 | 20,496,065 | The findings indicated that there was acceptable inter-observer and intra-observer reliability and validity for different methods of assessing patellar height and the sulcus angle with X-ray , MRI and CT methods , and the tibial tubercle-trochlear groove ( TT-TG ) assessed using CT .
There was poor reliability or validity for the assessment of severity of trochlear dysplasia and the sulcus angle using US .
Conclusion There is insufficient evidence to determine the reliability , validity , sensitivity or specificity of tests such as the congruence angle , lateral patellar displacement , lateral patellar tilt , trochlear depth , boss height , the crossing sign or Wiberg patellar classification . | Objective To determine the discriminative validity and reliability of the evidence base using meta- analysis . | Data regarding validity of clinical and radiographic findings in diagnosing patellofemoral pain syndrome are inconclusive . We prospect ively assessed how sensitive and specific key patellofemoral physical examination tests are , and evaluated the prevalence of physical examination and radiographic findings . Sixty-one infantry soldiers with patellofemoral pain syndrome and 25 control subjects were evaluated . The sensitivity of the patellar tilt , active instability , patella alta , and apprehension tests was low ( less than 50 % ) ; specificity ranged between 72 % and 100 % . Although the prevalence of positive patellar tilt and active instability tests was significantly greater in subjects with patellofemoral pain syndrome , there were no significant differences between the groups in the results of the other two tests . Soldiers with patellofemoral pain syndrome presented with increased quadriceps angle , lateral and medial retinacular tenderness , patellofemoral crepitation , squinting patella , and reduced mobility of the patella . There were no differences between the groups in the prevalence of lower limb and foot posture alignment and knee effusion . Plain radiography showed increased patellar subluxation in soldiers with patellofemoral pain syndrome . Other radiographic measures ( sulcus angle , Laurin angle , Merchant angle , and Insall-Salvati index ) were similar in both groups . We provide evidence regarding the validity of clinical and radiographic features commonly used for diagnosing patellofemoral pain syndrome . Physical examinations were more useful than plain radiography . Level of Evidence : Diagnostic study , Level I. See the Guidelines for Authors for a complete description of levels of evidence Background The goals of this study were to ( 1 ) define the epidemiology of acute patellar dislocation , ( 2 ) determine the risk of subsequent patellar instability episodes ( subluxation and /or redislocation ) during the study period , and ( 3 ) identify risk factors for subsequent instability episodes . Study Design Prospect i ve cohort study . Methods The authors prospect ively followed 189 patients for a period of 2 to 5 years . Historical data , injury mechanisms , and physical and radiographic measurements were recorded to identify potential risk factors for poor outcomes . Results Risk was highest among females 10 to 17 years old . Patients presenting with a prior history of instability were more likely to be female ( P < .05 ) and were older than first-time dislocation patients ( P < .05 ) . Fewer first-time dislocators ( 17 % ) had episodes of instability during follow-up than patients with a previous history of instability ( 49 % ) ( P < .01 ) . After adjusting for demographics , patients with a prior history had 7 times higher odds of subsequent instability episodes during follow-up than first time dislocators ( adjusted odds ratio = 6.6 , P < .001 ) . Conclusions Patellar dislocators who present with a history of patellofemoral instability are more likely to be female , are older , and have greater risk of subsequent patellar instability episodes than first-time patellar dislocators . Risk of recurrent patellar instability episodes in either knee is much higher in this group than in first-time dislocators Different surgical techniques have been described to correct trochlear dysplasia , without clear descriptions of the various types of trochlear dysplasia . In describing trochlear dysplasia , there exist no clear criteria to distinguish between decreased trochlear depth ( heightened trochlea floor ) and flattened lateral and /or medial condylar height . The current study aims to build a data base of axial MRI measurements of normal and abnormal trochlear shape to create a foundation for the selection of the necessary surgical correction to more normal trochlear anatomy . We prospect ively examined 152 subjects : 30 patients with patellar instability due to trochlea dysplasia and 122 subjects without any symptoms or objective findings related to the patellofemoral joint . MRI was performed in both groups . The height of the medial and lateral condyle , and the center of the trochlea was measured on axial MR images . The height of these different locations was compared to the total width of the femoral condyle and expressed in percentages . The statistical analysis was conducted with the Student ’s t test at SPSS software . For intraobserver reliability 20 r and omly taken MRI were evaluated twice . The intraobserver reliability was determined by calculating the kappa values investigated parameter . In normal subjects , the height of the lateral condyle was 81 % of the width of the femoral condyle ( 100 units),the trochlear central height was 73 % , the medial condylar height was 76 % . In patients with patellar instability , the lateral condylar height was 82 % and showed no significant difference compared to the normal group ( P = 0.082 ) . The trochlear central ( 77 % ) and medial condylar height ( 79 % ) were significantly different ( P < 0.001 ) compared to the normal subjects . The location of pathology in patients with patellar instability was decreased lateral condylar height in five cases ( 16.6 % ) and decreased central /medial height in 25 cases ( 83.4 % ) . A height of the lateral condyle < 77 % was documented to be pathologic . There was also a significant difference ( P < 0.001 ) between males and females comparing the different heights of the trochlea to the total width of the femoral condyle . The result ant percentages of all three height measurements , the lateral , central , and medial heights , were greater in males than in females . The intraobserver reliability was perfect for all investigated parameters . In conclusion , ( 1 ) the presented measurement scheme on axial MRI is a reliable method to calculate the height of the trochlea in different locations , ( 2 ) a more objective assessment of the trochlear pathology is possible , ( 3 ) in five of six cases the pathology is located in the center and /or medial trochlea , and ( 4 ) in our series of patellofemoral instability patients , most would benefit from a deepening trochleaplasty as the surgical procedure of choice to correct dysplasia Objective Recent advances in surgical intervention for patellar instability have led to a need for long-term radiological monitoring . The aim of this study is to determine whether or not magnetic resonance imaging ( MRI ) or ultrasound ( US ) can replace computed tomography ( CT ) as the st and ard of care for the evaluation of the femoral sulcus . Material s and methods This was a prospect i ve study comparing the reliability of CT , magnetic resonance ( MR ) , and US for measuring the femoral sulcus in patients with patellar instability . Twenty-four patients were recruited to undergo a CT , MR , and US examination of each knee . Two observers independently measured femoral sulcus angles from subchondral bone and hyaline cartilage on two occasions . Intraclass correlations and generalizability coefficients were calculated to measure the reliability of each of the techniques . Thereafter , two observers measured the femoral sulcus angle from ultrasound images recorded by two independent operators to estimate interobserver and interoperator reliability . Results Forty-seven knees were examined with CT and US and 44 with MRI . The sulcus angle was consistently smaller when measured from subchondral bone compared to cartilage ( 5–7 ° ) . Interobserver reliability for CT , MR , and US measurements from subchondral bone were 0.87 , 0.80 , and 0.82 and from cartilage 0.80 , 0.81 , and 0.50 . Generalizability coefficients of measurements from subchondral bone for CT , MR , and US were 0.87 , 0.76 , and 0.81 and for cartilage 0.76 , 0.73 , and 0.05 . Most of the variability in the US occurred at image acquisition rather than measurement . Conclusion In patients with patellar instability , CT and MR are reliable techniques for measuring the femoral sulcus angle but US , particularly of the articular cartilage , is not . MR is therefore the most suitable tool for longitudinal studies of the femoral sulcus We prospect ively studied the characteristics and early recovery of an unselected population of patients who had acute first-time lateral patellar dislocation . The recovery program used st and ardized rehabilitation , emphasizing range of motion , muscle strength , and return of function . Patients returned to stressful activities including sports as tolerated when they regained full passive range of motion , had no effusion , and when quadriceps muscle strength was at least 80 % compared with the noninjured limb . Seventy-four patients met the enrollment criteria ; 37 men and 37 women . The average age was 19.9 years , and preinjury sports participation was similar to that of ligament-injury patients . Four percent of patients ( N 3 ) had a history of birth complications , 3 % ( N 2 ) had a history of lower extremity problems as an infant or child , and 9 % ( N 7 ) had a family history of patellar dislocation . Radiographs revealed a 50 % incidence ( N 37 ) of patella alta ; all patients demonstrated lateral patellar overhang . Patients regained range of motion ( mean , 0 ° to 132 ° ) by 6 weeks . Sports participation remained significantly reduced throughout the first 6 months after injury , with the greatest limitations in kneeling and squatting . At 6 months , 58 % of patients ( N 43 ) noted limitation in strenuous activities . The patients who had acute primary patellar dislocation were young and active . Most injuries occurred during sports , and few patients had abnormal physical features , contradicting any stereotype of an overweight , sedentary , adolescent girl whose patella dislocates with little or no trauma Minor degrees of malalignment of the patella and anatomical abnormalities including a flattened sulcus angle and an increased ratio between patellar tendon length and patellar length ( PT : P ) have been suggested as predisposing factors in the causation of chondromalacia patellae , as well as patellar instability . In order to confirm or refute this hypothesis a prospect i ve study has been performed comparing the congruence and sulcus angles and the PT : P ratio in a group of 35 patients with chondromalacia confirmed by arthroscopy and a group of 33 patients with instability , with those of a group of 50 knees in normal volunteers . While there was a statistically significant correlation between an increased sulcus and congruence angle and a high-riding patella in patients with instability , no correlation could be identified in patients with idiopathic chondromalacia This is a prospect i ve study of 431 patients ( 862 knees ) with patellofemoral pain , patellar dislocation , or other abnormalities of the knee joint . There were 217 asymptomatic knees with no contralateral problems for comparison . All patients had a history and physical and radiographic examination of both knees . The radiographs included st and ard anteroposterior views , axial views at 30 ° of knee flexion , and st and ing lateral views at 0 ° and 30 ° of flexion . The presence of patellar tilt or subluxation was noted on the axial view . The lateral view of the patella , with precise overlap of the posterior femoral condyles , allowed determination of relationships between the patella 's medial edge , median ridge , and lateral edge to assess patellar tilt . Sixty-two percent of patients with patellar dislocations demonstrated subluxation on the axial view , while 98 % demonstrated an abnormal lateral view . Eighteen percent of the control knees revealed evidence of subluxation on the axial view while 35 % demonstrated subluxation on the extended lateral view . The axial view demonstrated 62 % sensitivity for dislocation , while the lateral view taken in full extension demonstrated 98 % sensitivity . The specificity for previous dislocation was 82 % for the axial view and 93 % for the lateral flexed view . Given the high sensitivity of the lateral view for detecting prior patellar dislocation , a normal result on this view can virtually eliminate the question of previous dislocation . Also , with the high specificity of the axial view and lateral view with knee flexion , the two views combined can confirm a clinical impression of patellofemoral malalignment The present study compares the repeatability of patellofemoral malalignment ( PFM ) indices obtained by 20 degree flexion axial radiography ( AR ) and computerized tomography ( CT ) with 0 degree and 20 degree flexion of the knees in children and adolescents . Thirty-one patients with a mean age of 14.2 years ( range 8 to 19.2 years ) suffering from PFM were examined using these two radiographic techniques . The lateral patellofemoral angle ( LPA ) , the lateral patellar tilt ( LPT ) , and the lateral patellar displacement ( LPD ) were measured by by two different investigators on different occasions , and the agreement of these indices between CT and AR was evaluated according to Bl and and Altman 's statistical method . LPT and LPD obtained by AR were more reliable and repeatable than those obtained by CT . The quadriceps muscle contraction exacerbates PFM indices significantly with the knees in full extension ( P = 0.0001 ) . LPT and LPD measured at 20 degrees AR show reliably the two pathological components ( the patellar tilt and the lateral patellar displacement ) of PFM which are necessary for diagnosis and treatment planning . CT with quadriceps contractions is better in qualitative screening of more subtle cases of PFM |
858 | 28,723,532 | Meta-regression adjusting for confounders found no significant difference in oncologic outcomes between SRP and nonsurgical salvage modalities .
SBT , SCT , and SHIFU appeared to have better continence outcomes than SRP .
Oncologic outcomes are comparable for SRP and all three nonsurgical salvage modalities .
We found no significant differences in toxicity outcomes among modalities ; however , SRP appears to be associated with worse rates of urinary incontinence than SBT , SCT , and SHIFU .
Oncologic and toxicity outcomes appear to be similar ; however , all nonsurgical salvage modalities may be associated with better continence outcomes | CONTEXT In the absence of r and omised controlled trials comparing the oncologic , toxicity , and functional outcomes of salvage radical prostatectomy ( SRP ) , salvage high-intensity focused ultrasound ( SHIFU ) , salvage brachytherapy ( SBT ) , and salvage cryotherapy ( SCT ) , controversy exists as to the optimal salvage modality in radiorecurrent prostate cancer .
OBJECTIVE We carried out a meta-regression analysis to determine whether there is a difference in oncologic , toxicity , and functional outcomes using data from original publications of salvage modalities in the postradiation setting . | Despite improvements in treatment of localized prostate cancer , local recurrence remains a significant problem . A total of 46 patients with proven local cancer recurrence following external beam radiotherapy entered a prospect i ve clinical trial using ultrasound-guided cryosurgery to ablate the residual prostate gl and . Persistent complications included one urethra – rectal fistula , incontinence ( 2 ) , retention ( 3 ) , and treatment induced erectile dysfunction ( 7 ) . Using the PSA definitions for biochemical failure as PSA ⩾0.3 ng/ml , the Kaplan – Meier plots showed the incidence of patients to be free of biochemical recurrence at 51 and 44 % at 1 and 2 y , respectively . For a PSA ⩾1.0 , the values at 1 and 2 y were 72 and 58 % PURPOSE Few patients with locally recurrent prostate cancer after external beam ( EB ) or interstitial ( I ) radiotherapy ( RT ) are considered c and i date s for salvage radical prostatectomy ( RP ) due to high reported rates of major complications and urinary incontinence . We report the morbidity associated with salvage RP in 100 consecutive patients . MATERIAL S AND METHODS From 1984 to 2003 salvage RP was performed for recurrent prostate cancer following EBRT in 58 cases , and IRT in 42 ( 28 retropubic ) and ( 14 transperineal ) . Clinical information was obtained from a prospect i ve data base . RESULTS Since 1993 , the major complication rate has decreased significantly ( 13 % vs 33 % , p = 0.02 ) , including the rectal injury rate ( 2 % vs 15 % , p = 0.01 ) . Compared with retropubic IRT and /or pre-radiotherapy pelvic lymph node dissection the risk of major complications following EBRT or transperineal IRT was significantly less ( OR 0.2 , p = 0.006 ) . At 5 years an estimated 39 % of patients were dry and 68 % required 1 pad daily or less . A total of 23 patients with moderate-severe incontinence underwent artificial sphincter placement . The anastomotic stricture rate was 30 % . The 5-year potency rate was 28 % following unilateral or bilateral nerve sparing RP and 45 % in previously potent patients . CONCLUSIONS Due to patient selection the major complication rate after salvage RP has improved significantly with time and it is similar to that of st and ard RP . Rates of anastomotic stricture and moderate to severe incontinence are higher than those observed after st and ard RP . However , most patients recover reasonable urinary continence and a substantial number of select patients recover potency . The acceptable morbidity profile of salvage RP following EBRT and transperineal IRT should persuade more physicians to consider patients for this potentially curative procedure Objectives In this study , we evaluate the outcomes of salvage cryotherapy for locally recurrent prostate cancer within the COLD ( cryo online data ) Registry . Furthermore , we assess the results of salvage cryotherapy ( with intermediate follow-up ) stratified by pre-treatment prostate-specific antigen ( PSA ) levels to determine which patients may best be suited for treatment . Methods The COLD registry was developed as a prospect i ve , central ly collected data base among patients undergoing salvage cryoablation for locally recurrent prostate cancer following primary prostate radiotherapy with curative intent . Of the patients undergoing salvage cryotherapy ( without neoadjuvant hormonal ablative therapy ) , complete medical records were available in 156 patients , with their mean follow-up being 3.8 years ( 0.9–12.7 years ) . The treatment outcomes of salvage cryotherapy were assessed using the Phoenix definition ( nadir PSA + 2 ng/ml ) of biochemical failure . Results Of our entire study population , the biochemical disease-free survival ( bDFS ) rates at 1 , 2 , and 3 years were 89.0 , 73.7 , and 66.7 % , respectively . Stratification of our patients into two subgroups is based on their pre-treatment total serum PSA values < 5 and ≥5 ng/ml , and bDFS rates at 3 years for these two subgroups were 78.3 and 52.9 % , respectively . A Kaplan – Meier analysis of bDFS stratified by these same pre-treatment PSA values revealed that the subset of patients with a PSA ≥ 5 ng/ml had statistically significant poorer bDFS rates ( P = 0.01 ) . Conclusions Salvage prostate cryotherapy is a potentially curative local salvage therapy . The importance of early referral when patients have a pre-treatment PSA < 5 ng/ml is essential to optimize treatment outcomes The authors prospect ively evaluated the late gastrointestinal ( GI ) and genitourinary ( GU ) toxicity and prostate‐specific antigen ( PSA ) control of magnetic resonance imaging (MRI)‐guided brachytherapy used as salvage for radiation therapy ( RT ) failure PURPOSE Radiation Therapy Oncology Group protocol 85 - 31 was design ed to evaluate the effectiveness of adjuvant and rogen suppression , using goserelin , in unfavorable prognosis carcinoma of the prostate treated with definitive radiotherapy ( RT ) . METHODS AND MATERIAL S Eligible patients were those with palpable primary tumor extending beyond the prostate ( clinical Stage T3 ) or those with regional lymphatic involvement . Patients who had undergone prostatectomy were eligible if penetration through the prostatic capsule to the margin of resection and /or seminal vesicle involvement was documented histologically . Stratification was based on histologic differentiation , nodal status , acid phosphatase status , and prior prostatectomy . The patients were r and omized to either RT and adjuvant goserelin ( Arm I ) or RT alone followed by observation and application of goserelin at relapse ( Arm II ) . In Arm I , the drug was to be started during the last week of RT and was to be continued indefinitely or until signs of progression . RESULTS Between 1987 and 1992 , when the study was closed , 977 patients were entered : 488 to Arm I and 489 to Arm II . As of July 2003 , the median follow-up for all patients was 7.6 years and for living patients was 11 years . At 10 years , the absolute survival rate was significantly greater for the adjuvant arm than for the control arm : 49 % vs. 39 % , respectively ( p = 0.002 ) . The 10-year local failure rate for the adjuvant arm was 23 % vs. 38 % for the control arm ( p < 0.0001 ) . The corresponding 10-year rates for the incidence of distant metastases and disease-specific mortality was 24 % vs. 39 % ( p < 0.001 ) and 16 % vs. 22 % ( p = 0.0052 ) , respectively , both in favor of the adjuvant arm . CONCLUSION In a population of patients with unfavorable prognosis carcinoma of the prostate , and rogen suppression applied as an adjuvant after definitive RT was associated not only with a reduction in disease progression but in a statistically significant improvement in absolute survival . The improvement in survival appeared preferentially in patients with a Gleason score of 7 - 10 PURPOSE A positive post-irradiation prostatic biopsy associated with an increasing prostate specific antigen level but no palpable evidence of local progression may identify a subgroup of patients who could be cured by salvage surgical therapy . MATERIAL S AND METHODS Between 1967 and 1992 , 132 patients underwent salvage surgery , including radical retropubic prostatectomy in 79 , anterior exenteration in 38 , total exenteration in 5 and bilateral pelvic lymphadenectomy only in 10 . RESULTS The 10-year cancer-specific survival rate in the prostatectomy group was 72 % . Local control was equivalent among the surgical groups . Radical retropubic prostatectomy patients with negative surgical margins and nonaneuploid tumors demonstrated a significant survival advantage . Adjuvant hormonal therapy improved the disease-free survival rate in patients with nonaneuploid tumors . CONCLUSIONS Radical retropubic prostatectomy can achieve excellent survival with low morbidity in select patients . Patients with clinical stage T2 or less disease and with prostate specific antigen detected cancers ( 52 % and 75 % , respectively ) had pathological stage T2 disease . Thus , by using modern diagnostic techniques patients can be identified who may be cured with salvage surgery PURPOSE We review our 20-year experience with salvage radical prostatectomy to determine prognostic variables predictive of oncological control of radiorecurrent prostate cancer . Using a st and ardized question naire we also evaluate outcome data regarding the long-term sexual and urinary effects of salvage radical prostatectomy . MATERIAL S AND METHODS Between 1983 and 2002 salvage radical prostatectomy was performed in 51 patients with locally recurrent prostate cancer following definitive radiotherapy . Clinical information was obtained from a prospect i ve data base . Quality of life data were collected using the UCLA Prostate Cancer Index , a vali date d , patient administered instrument . RESULTS At 5 years 47 % of patients were progression-free without and rogen deprivation therapy . Among patients with pT2 disease 100 % were progression-free at 5 years , compared with 35 % of patients with pT3N0 disease or higher and 0 % of patients with node positive ( pTxN+ ) disease ( p < 0.001 ) . Preoperative PSA 5.0 ng/ml or less was predictive of organ confined disease , and strongly associated with prolonged progression-free and overall survival ( p < 0.001 and 0.01 , respectively ) . Mean urinary function scores for patients with or without an artificial urinary sphincter compared favorably with scores reported after st and ard , nonsalvage prostatectomy . Sexual dysfunction was nearly uniform in patients undergoing st and ard salvage radical prostatectomy but implantation of a penile prosthesis was associated with a clinical ly significant improvement in sexual function . CONCLUSIONS When initiated early in the course of recurrent disease , salvage radical prostatectomy provides excellent oncological control of radiorecurrent prostate cancer without the need for and rogen ablation . Implantation of an artificial urinary sphincter and inflatable penile prosthesis devices in patients with postoperative urinary incontinence or erectile dysfunction results in significantly improved quality of life parameters INTRODUCTION Prostate cancer recurrence following primary radiation is common . If the recurrence remains localized to the prostate gl and , surgical removal may result in long-term local control or cure . Despite the well-established oncological outcomes , salvage prostatectomy is infrequently performed or reported . We present our experience with salvage prostatectomy at a Canadian centre . METHODS We identified all patients undergoing salvage prostatectomy at the Vancouver General Hospital between 1995 and 2010 from a prospect ively recorded and maintained prostate cancer data base . Details regarding initial presentation , delivery of radiotherapy , clinical features at the time of recurrence , as well as oncological and functional outcomes , were collected . Information regarding postoperative morbidity was collected prospect ively and confirmed by retrospective chart review . RESULTS Over a 15-year period , salvage prostatectomy was successfully completed in 21 patients . With a median follow-up period of 68 months ( range : 2 - 122 ) , 9 ( 43 % ) patients experienced a biochemical recurrence , with most failing within the first 2 years of surgery . There were 3 deaths in the cohort , all from prostate cancer , giving a prostate cancer specific and overall survival of 86 % . The main postoperative morbidity was bladder neck contracture , occurring in 40 % . One patient each developed a recto-urethral fistula and osteitis pubis . Physician-recorded data regarding continence was available in 13 ( 62 % ) . Of these 13 patients , 10 ( 85 % ) men were recorded as dry or using 1 pad per day . CONCLUSIONS This is the first Canadian centre to report that salvage prostatectomy can be performed with favourable oncological and functional outcomes PURPOSE Salvage radical prostatectomy is associated with a higher complication rate than radical prostatectomy without prior radiotherapy but the magnitude of the increase is not well delineated . MATERIAL S AND METHODS A total of 3,458 consecutive patients underwent open radical prostatectomy and 98 underwent open salvage radical prostatectomy from January 1999 to June 2007 . Data were collected from prospect i ve surgical and institutional morbidity data bases , and retrospectively from billing records and medical records . Medical and surgical complications were captured , grade d by the modified Clavien classification and classified by time of onset . RESULTS Median followup after salvage radical prostatectomy and radical prostatectomy was 34.5 and 45.5 months , respectively . Patients with salvage had significantly higher median age , modified Charlson comorbidity score , clinical and pathological stage , and Gleason score . They were less likely to have organ confined disease and more likely to have seminal vesicle invasion and nodal metastasis . There was no significant difference in median operative time , blood loss or transfusion rate . The salvage group had a higher adjusted probability of medical and surgical complications , including urinary tract infection , bladder neck contracture , urinary retention , urinary fistula , abscess and rectal injury . Only 1 of 4 potent patients with salvage prostatectomy who underwent bilateral nerve sparing recovered erection adequate for intercourse . The 3-year actuarial recovery of continence was 30 % ( 95 % CI 19 - 41 ) . CONCLUSIONS Medical and surgical complications of prostatectomy are significantly increased in the setting of prior radiotherapy . Underst and ing the magnitude of this increased risk is important for patient counseling PURPOSE We report the toxicity and biochemical tumor control outcome of a prospect i ve Phase II study using high-dose-rate brachytherapy ( HDR ) alone as a salvage therapy for recurrent disease after external beam radiotherapy ( EBRT ) . METHODS Forty-two patients with biopsy-proven recurrence were enrolled on a Phase II study of salvage HDR monotherapy using iridium-192 . Median pretreatment EBRT dose was 8100 cGy ( 6840–8640 cGy ) and the median time from completion of EBRT to salvage HDR was 73 months . The protocol prescription dose of 3200 cGy was delivered in four fractions over 30 hours in a single insertion . Median followup after salvage HDR was 36 months ( 6–67 months ) . RESULTS The actuarial prostate-specific antigen biochemical relapse-free survival and distant metastases-free survival rates at 5 years were 68.5 % and 81.5 % , respectively . Cause-specific survival was 90.3 % . Late genitourinary Grade 1 and 2 toxicities were found in 38 % and 48 % , respectively , and one patient developed Grade 3 urinary incontinence . Late Grade 1 and 2 gastrointestinal toxicity was noted in 17 % and 8 % of patients , respectively . Three patients ( 7 % ) developed Grade 2 late urinary toxicity ( urethral stricture ) , which were corrected with urethral dilatation , and one patient developed Grade 3 urinary incontinence . No Grade 4 toxicities were observed . CONCLUSIONS Genitourinary toxicity was the most commonly encountered toxicity observed after salvage HDR but severe toxicities were uncommon . Salvage HDR is an effective and well-tolerated modality for locally recurrent prostate cancer and should be considered even for patients who have previously been treated with ultra-high dose levels of EBRT |
859 | 15,674,906 | The primary outcome was a significant reduction in depression .
Depression is common among patients with heart failure . | BACKGROUND Heart failure is a common and growing health problem .
Depression is prevalent among these patients and is associated with an increased risk of mortality , in some , but not all , studies .
Depression may increase the risk of recurrent cardiac events and death , either through direct pathophysiological mechanisms such as thrombogenesis or ventricular arrhythmias , or through behavioural mechanisms .
Depressed patients are less likely to adhere to their medication regimen and modify their lifestyle appropriately , thereby increasing the likelihood of recurrent cardiac events and death .
The effects of psychological interventions for depression in terms of reducing depression and improving prognosis in patients with heart failure are unknown .
OBJECTIVES To assess the effects of psychological interventions for depression in people with heart failure on depression and quality of life , morbidity , and mortality in these patients . | Three hundred eleven employees of the National Institutes of Health volunteered to take 1 gm of ascorbic acid or lactose placebo in capsules three times a day for nine months . At the onset of a cold , the volunteers were given an additional 3 gm daily of either a placebo or ascorbic acid . One hundred ninety volunteers completed the study . Dropouts were defined as those who missed at least one month of drug ingestion . They represented 44 % of the placebo group and 34 % of those taking ascorbic acid . Analysis of these data showed that ascorbic acid had at best only a minor influence on the duration and severity of colds , and that the effects demonstrated might be explained equally well by a break in the double blind CONTEXT Depression and low perceived social support ( LPSS ) after myocardial infa rct ion ( MI ) are associated with higher morbidity and mortality , but little is known about whether this excess risk can be reduced through treatment . OBJECTIVE To determine whether mortality and recurrent infa rct ion are reduced by treatment of depression and LPSS with cognitive behavior therapy ( CBT ) , supplemented with a selective serotonin reuptake inhibitor ( SSRI ) antidepressant when indicated , in patients enrolled within 28 days after MI . DESIGN , SETTING , AND PATIENTS R and omized clinical trial conducted from October 1996 to April 2001 in 2481 MI patients ( 1084 women , 1397 men ) enrolled from 8 clinical centers . Major or minor depression was diagnosed by modified Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition criteria and severity by the 17-item Hamilton Rating Scale for Depression ( HRSD ) ; LPSS was determined by the Enhancing Recovery in Coronary Heart Disease Patients ( ENRICHD ) Social Support Instrument ( ESSI ) . R and om allocation was to usual medical care or CBT-based psychosocial intervention . INTERVENTION Cognitive behavior therapy was initiated at a median of 17 days after the index MI for a median of 11 individual sessions throughout 6 months , plus group therapy when feasible , with SSRIs for patients scoring higher than 24 on the HRSD or having a less than 50 % reduction in Beck Depression Inventory scores after 5 weeks . MAIN OUTCOME MEASURES Composite primary end point of death or recurrent MI ; secondary outcomes included change in HRSD ( for depression ) or ESSI scores ( for LPSS ) at 6 months . RESULTS Improvement in psychosocial outcomes at 6 months favored treatment : mean ( SD ) change in HRSD score , -10.1 ( 7.8 ) in the depression and psychosocial intervention group vs -8.4 ( 7.7 ) in the depression and usual care group ( P<.001 ) ; mean ( SD ) change in ESSI score , 5.1 ( 5.9 ) in the LPSS and psychosocial intervention group vs 3.4 ( 6.0 ) in the LPSS and usual care group ( P<.001 ) . After an average follow-up of 29 months , there was no significant difference in event-free survival between usual care ( 75.9 % ) and psychosocial intervention ( 75.8 % ) . There were also no differences in survival between the psychosocial intervention and usual care arms in any of the 3 psychosocial risk groups ( depression , LPSS , and depression and LPSS patients ) . CONCLUSIONS The intervention did not increase event-free survival . The intervention improved depression and social isolation , although the relative improvement in the psychosocial intervention group compared with the usual care group was less than expected due to substantial improvement in usual care patients CONTEXT Significant symptoms of depression are common in the older community-dwelling population . Although depressive symptoms and disability may commonly occur in the same person , whether depressive symptoms contribute to subsequent functional decline has not been eluci date d. OBJECTIVE To determine whether depressive symptoms in older persons increase the risk of subsequent decline in physical function as measured by objective performance-based tests . DESIGN A 4-year prospect i ve cohort study . SETTING The communities of Iowa and Washington counties , Iowa . PARTICIPANTS A total of 1286 persons aged 71 years and older who completed a short battery of physical performance tests in 1988 and again 4 years later . MAIN OUTCOME MEASURES Baseline depressive symptoms were assessed by the Center for Epidemiological Studies Depression Scale . Physical performance tests included an assessment of st and ing balance , a timed 2.4-m ( 8-ft ) walk , and a timed test of 5 repetitions of rising from a chair and sitting down . RESULTS After adjustment for baseline performance score , health status , and sociodemographic factors , increasing levels of depressive symptoms were predictive of greater decline in physical performance over 4 years ( odds ratio for decline in those with depressed mood vs those without , 1.55 ; 95 % confidence interval [ CI ] , 1.02 - 2.34 ) . Even among those at the high end of the functional spectrum , who reported no disability , the severity of depressive symptoms predicted subsequent decline in physical performance ( odds ratio for decline , 1.03 ; 95 % CI , 1.00 - 1.08 ) . CONCLUSIONS This study provides evidence that older persons who report depressive symptoms are at higher risk of subsequent physical decline . These results suggest that prevention or reduction of depressed mood could play a role in reducing functional decline in older persons The purpose of this study was to evaluate the effect of stress management training on quality of life , functional capacity , and heart rate variability in elderly patients with New York Heart Association class I-III congestive heart failure ( CHF ) . While substantial research exists on stress management training for patients with coronary heart disease , there are few data on the value of psychosocial training on patients with CHF . Thirty-three multiethnic patients ( mean age , 66+/-9 years ) were assigned through incomplete r and omization to one of two treatment groups or a wait-listed control group . The 14 participants who completed the treatment attended eight training sessions during a 10-week period . The training consisted of 75-minute sessions adapted from the Freeze-Frame stress management program developed by the Institute of HeartMath . Subjects were assessed at baseline and again at the completion of the training . Depression , stress management , optimism , anxiety , emotional distress , and functional capacity were evaluated , as well as heart rate variability . Significant improvements ( p<0.05 ) were noted in perceived stress , emotional distress , 6-minute walk , and depression , and positive trends were noted in each of the other psychosocial measures . The 24-hour heart rate variability showed no significant changes in autonomic tone . The authors noted that CHF patients were willing study participants and their emotional coping and functional capacity were enhanced . This program offers a simple and cost-effective way to augment medical management of CHF . Given the incompleteness of CHF medical management and the exploding interest in complementary medical intervention , it seems imperative that further work in psychosocial treatment be undertaken 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 & NA ; Previous research has documented high rates of noncompliance to prescribed medical therapy in patients recovering from myocardial infa rct ion ( MI ) . This study was undertaken to determine if patients who subsequently drop out of a structured cardiac rehabilitation program could be prospect ively distinguished from those who remain in the program based upon their initial baseline characteristics . Thirty‐five consecutive patients with recent MIs underwent comprehensive physical and psychological assessment s at entry into the program , and were followed for a period of 1 year . The 14 patients who dropped out of the program could be distinguished from the compliers on the basis of their reduced left ejection fraction assessed by first pass radionuclide angiography at rest and during peak exercise . In addition , their psychological profiles assessed by the MMPI indicated the dropouts were more depressed , hypochondriacal , anxious , and introverted and had lower ego strength than those who remained in the program . Statistical analysis further indicated that psychological variables were associated with noncompliance independently of physical status . These findings suggest that MI patients who are unlikely to adhere to this form of medical therapy may be prospect ively identified based upon their initial physical and psychological characteristics OBJECTIVE To determine if the diagnosis of major depression in patients hospitalized following myocardial infa rct ion ( MI ) would have an independent impact on cardiac mortality over the first 6 months after discharge . DESIGN Prospect i ve evaluation of the impact of depression assessed using a modified version of the National Institute of Mental Health Diagnostic Interview Schedule for major depressive episode . Cox proportional hazards regression was used to evaluate the independent impact of depression after control for significant clinical predictors in the data set . SETTING A large , university-affiliated hospital specializing in cardiac care , located in Montreal , Quebec . PATIENTS All consenting patients ( N = 222 ) who met established criteria for MI between August 1991 and July 1992 and who survived to be discharged from the hospital . Patients were interviewed between 5 and 15 days following the MI and were followed up for 6 months . There were no age limits ( range , 24 to 88 years ; mean , 60 years ) . The sample was 78 % male . PRIMARY OUTCOME MEASURE Survival status at 6 months . RESULTS By 6 months , 12 patients had died . All deaths were due to cardiac causes . Depression was a significant predictor of mortality ( hazard ratio , 5.74 ; 95 % confidence interval , 4.61 to 6.87 ; P = .0006 ) . The impact of depression remained after control for left ventricular dysfunction ( Killip class ) and previous MI , the multivariate significant predictors of mortality in the data set ( adjusted hazard ratio , 4.29 ; 95 % confidence interval , 3.14 to 5.44 ; P = .013 ) . CONCLUSION Major depression in patients hospitalized following an MI is an independent risk factor for mortality at 6 months . Its impact is at least equivalent to that of left ventricular dysfunction ( Killip class ) and history of previous MI . Additional study is needed to determine whether treatment of depression can influence post-MI survival and to assess possible underlying mechanisms A relationship between cigarette smoking and major depressive disorder was suggested in previous work involving nonr and omly selected sample s. We conducted a test of this association , employing population -based data ( n = 3213 ) collected between 1980 and 1983 in the St Louis Epidemiologic Catchment Area Survey of the National Institute of Mental Health . A history of regular smoking was observed more frequently among individuals who had experienced major depressive disorder at some time in their lives than among individuals who had never experienced major depression or among individuals with no psychiatric diagnosis . Smokers with major depression were also less successful at their attempts to quit than were either of the comparison groups . Gender differences in rates of smoking and of smoking cessation observed in the larger population were not evident among the depressed group . Furthermore , the association between cigarette smoking and major depression was not ubiquitous across all psychiatric diagnoses . Other data are cited indicating that when individuals with a history of depression stop smoking , depressive symptoms and , in some cases , serious major depression may ensue To determine whether participating in physical activity affects psychological well-being in an adolescent population , 147 adolescents completed self-reports of exercise and psychological stress and well-being . Analysis revealed that those who reported greater physical activity also reported less stress and lower levels of depression . Adolescents who experienced a higher incidence of life events also demonstrated a strong association between stress and anxiety/depression/hostility . To investigate the effects of exercise training on psychological well-being , adolescents were assigned to either high or moderate intensity aerobic training , flexibility training or a control group . The training groups met twice per week for 25 - 30 min . Aerobic fitness levels , heart rate , blood pressure and self-report of stress and well-being were measured prior to and following 10 weeks of training . Post-training fitness measures confirmed the effectiveness of the high intensity aerobic exercise and between groups differences for physiological and some psychological measures were found . Subjects undergoing high intensity exercise reported significantly less stress than subjects in the remaining three groups . The relationship between stress and anxiety/depression/hostility for the high intensity group was considerably weakened at the end of the training period . For the remaining subjects , however , this relationship was , if anything , strengthened . This experiment provides evidence to suggest that in an adolescent population , high intensity aerobic exercise has positive effects on well-being The frequency of ventricular premature complexes and the degree of impairment of left ventricular ejection fraction are major predictors of cardiac mortality and sudden death in the year after acute myocardial infa rct ion . Recent studies have implicated psychosocial factors , including depression , the interaction of social isolation and life stress , and type A-B behavior pattern , as predictors of cardiac events , controlling for known parameters of disease severity . However , results tend not to be consistent and are sometimes contradictory . The present investigation was design ed to test the predictive association between biobehavioral factors and clinical cardiac events . This evaluation occurred in the context of a prospect i ve clinical trial , the Cardiac Arrhythmia Pilot Study ( CAPS ) . Five-hundred two patients were recruited with greater than or equal to 10 ventricular premature complexes/hour or greater than or equal to 5 episodes of nonsustained ventricular tachycardia , recorded 6 to 60 days after a myocardial infa rct ion . Baseline behavioral studies , conducted in approximately 66 % of patients , included psychosocial question naires of anxiety , depression , social desirability and support , and type A-B behavior pattern . In addition , blood pressure and pulse rate reactivity to a portable videogame was assessed . The primary outcome was scored on the basis of mortality or cardiac arrest . Results indicated that the type B behavior pattern , higher levels of depression and lower pulse rate reactivity to challenge were significant risk factors for death or cardiac arrest , after adjusting statistically for a set of known clinical predictors of disease severity . The implication of these results for future research relating behavioral factors to cardiac endpoints is discussed OBJECTIVES We sought to examine whether depressive symptoms are associated with poorer prognosis in patients with heart failure . BACKGROUND Depression is an established risk factor for poor outcome in patients with coronary heart disease ( CHD ) . Little is known of its role in patients with heart failure . METHODS We prospect ively followed 391 patients > or = 50 years of age who met criteria for decompensated heart failure on hospital admission . The outcome of the study was death or decline in activities of daily living ( ADL ) at six months , relative to baseline . Depressive symptoms were measured at baseline by means of the Geriatric Depression Scale , Short-Form , with 6 to 7 symptoms , 8 to 10 symptoms and > or = 11 symptoms indicating mild , moderate and severe levels of depressive symptoms , respectively . RESULTS There was a strong and grade d association between the severity of depressive symptoms at baseline and the rate of the combined end point of either functional decline or death at six months . After adjustment for demographic factors , medical history , baseline functional status and clinical severity , patients with > or = 11 depressive symptoms , compared with those with < 6 depressive symptoms , had an 82 % higher risk of either functional decline or death , whereas the intermediate levels of depressive symptoms showed intermediate risk ( p = 0.003 for trend ) . A similar grade d association was found for functional decline and death separately ; however , after multivariate analysis , the association with mortality was less strong and no longer statistically significant . CONCLUSIONS An increasing number of depressive symptoms is a negative prognostic factor for patients with heart failure , just as it is for patients with CHD PURPOSE To compare the effects of a multimodal nonpharmacologic intervention to digoxin and to placebo in patients with congestive heart failure receiving background therapy with angiotensin-converting enzyme inhibitors . DESIGN R and omized , parallel assignment to three treatment groups of 20 patients with congestive heart failure ( New York Heart Association Class II and III ) . INTERVENTION Nonpharmacologic treatment program included the following : ( 1 ) graduated exercise training , three to five times per week ; ( 2 ) structured cognitive therapy and stress management ; and ( 3 ) dietary intervention aim ed at salt reduction and weight reduction in the overweight . Digoxin was titrated to achieve a blood level between 0.8 and 2.0 ng/ml . Placebo and digoxin were administered in a r and omized , double-blind fashion . RESULTS Echocardiographic ejection fraction improved ( p < 0.05 ) in the digitalis group ( change = + 4.4 + /- 6.5 ) compared with both placebo ( change = -3.2 + /- 3.9 ) and nonpharmacologic therapy ( change = -3.2 + /- 3.9 ) . The nonpharmacologic treatment program was well tolerated by all patients and result ed in significant improvement ( p < 0.05 ) in exercise tolerance ( digoxin = + 51 + /- 50 s , placebo = + 91 + /- 76 , nonpharmacologic therapy = + 182 + /- 139 ) , as well as Beck Depression Inventory score ( digoxin = + 1.2 + /- 4.4 , placebo = + 2.0 + /- 4.2 , nonpharmacologic therapy = -5.0 + /- 4.2 ) , Hamilton Scale scores of anxiety ( digoxin = + 3.0 + /- 6.8 , placebo = + 6.0 + /- 2.6 , nondrug therapy = -5.2 + /- 5.4 ) , and depression ( digoxin = + 1.0 + /- 4.9 , placebo = + 5.0 + /- 5.0 , nonpharmacologic therapy = -6.6 + /- 10.1 ) . In addition , weight loss was significantly greater with nonpharmacologic therapy ( digoxin = + 0.32 + /- 1.76 kg ; placebo = -1.35 + /- 1.44 kg ; nonpharmacologic therapy = -4.37 + /- 4.50 kg ) compared with both digoxin and placebo . CONCLUSIONS Nonpharmacologic therapy improved functional capacity , body weight , and mood state in patients with congestive heart failure . In contrast , digoxin improved ejection fraction without corresponding changes in exercise tolerance or quality of life |
860 | 30,356,547 | Conclusion HIIT-based running plans ( 2 to 3 HIIT sessions per week , combining HIIT and CR runs ) show athletic performance improvements in endurance runners by improving maximal oxygen uptake and running economy along with muscular and metabolic adaptations . | Objective This systematic review aim ed to critically analyze the literature to determine how high-intensity intermittent training ( HIIT ) affects recreational endurance runners in the short- and long-term . | The purpose of this study was to test the hypothesis that athletes having a slower oxygen uptake ( V̇O2 ) kinetics would benefit more , in terms of time spent near V̇O2max , from an increase in the intensity of an intermittent running training ( IT ) . After determination of V̇O2max , vV̇O2max ( i.e. the minimal velocity associated with V̇O2max in an incremental test ) and the time to exhaustion sustained at vV̇O2max ( Tlim ) , seven well-trained triathletes performed in r and om order two IT sessions . The two IT comprised 30-s work intervals at either 100 % ( IT100 % ) or 105 % ( IT105 % ) of vV̇O2max with 30-s recovery intervals at 50 % of vV̇O2max between each repeat . The parameters of the V̇O2 kinetics ( td1 , τ1 , A1 , td2 , τ2 , A2 , i.e. time delay , time constant and amplitude of the primary phase and slow component , respectively ) during the Tlim test were modelled with two exponential functions . The highest V̇O2 reached was significantly lower ( P<0.01 ) in IT100 % run at 19.8 ( 0.9 ) km.h−1 [ 66.2 ( 4.6 ) ml.min−1.kg−1 ] than in IT105 % run at 20.8 ( 1.0 ) km.h−1 [ 71.1 ( 4.9 ) ml.min−1.kg−1 ] or in the incremental test [ 71.2 ( 4.2 ) ml.min−1.kg−1 ] . The time sustained above 90 % of V̇O2max in IT105 % [ 338 ( 149 ) s ] was significantly higher ( P<0.05 ) than in IT100 % [ 168 ( 131 ) s ] . The average Tlim was 244 ( 39 ) s , τ1 was 15.8 ( 5.9 ) s and td2 was 96 ( 13 ) s. τ1 was correlated with the difference in time spent above 90 % of V̇O2max ( r=0.91 ; P<0.01 ) between IT105 % and IT100 % . In conclusion , athletes with a slower V̇O2 kinetics in a vV̇O2max constant-velocity test benefited more from the 5 % rise of IT work intensity , exercising for longer above 90 % of V̇O2max when the IT intensity was increased from 100 to 105 % of vV̇O2max The objective of this study was to analyze the effect of two different high-intensity interval training ( HIT ) programs on selected aerobic physiological indices and 1500 and 5000 m running performance in well-trained runners . The following tests were completed ( n=17 ) : ( i ) incremental treadmill test to determine maximal oxygen uptake ( VO2 max ) , running velocity associated with VO2 max ( vVO2 max ) , and the velocity corresponding to 3.5 mmol/L of blood lactate concentration ( vOBLA ) ; ( ii ) submaximal constant-intensity test to determine running economy ( RE ) ; and ( iii ) 1500 and 5000 m time trials on a 400 m track . Runners were then r and omized into 95 % vVO2 max or 100 % vVO2 max groups , and undertook a 4 week training program consisting of 2 HIT sessions ( performed at 95 % or 100 % vVO2 max , respectively ) and 4 submaximal run sessions per week . Runners were retested on all parameters at the completion of the training program . The VO2 max values were not different after training for both groups . There was a significant increase in post-training vVO2 max , RE , and 1500 m running performance in the 100 % vVO2 max group . The vOBLA and 5000 m running performance were significantly higher after the training period for both groups . We conclude that vOBLA and 5000 m running performance can be significantly improved in well-trained runners using a 4 week training program consisting of 2 HIT sessions ( performed at 95 % or 100 % vVO2 max ) and 4 submaximal run sessions per week . However , the improvement in vVO2 max , RE , and 1500 m running performance seems to be dependent on the HIT program at 100 % vVO2 max Context : A high number of recreational runners sustain a running-related injury each year . To reduce injury risk , alterations in running form have been suggested . One simple strategy for running stride frequency or length has been commonly advocated . Objective : To characterize how running mechanics change when stride frequency and length are manipulated . Data Sources : In January 2012 , a comprehensive search of PubMed , CINAHL Plus , SPORTD iscus , PEDro , and Cochrane was performed independently by 2 review ers . A second search of the data bases was repeated in June 2012 to ensure that no additional studies met the criteria after the initial search . Study Selection : Inclusion criteria for studies were an independent variable including manipulation of stride frequency or length at a constant speed with outcome measures of running kinematics or kinetics . Study Design : Systematic review . Level of Evidence : Level 3 . Data Extraction : Two review ers independently appraised each article using a modified version of the Quality Index , design ed for assessing bias of nonr and omized studies . Results : Ten studies met the criteria for this review . There was consistent evidence that increased stride rate result ed in decreased center of mass vertical excursion , ground reaction force , shock attenuation , and energy absorbed at the hip , knee , and ankle joints . All but 1 study had a limited number of participants , with several method ological differences existing among studies ( eg , overground and treadmill running , duration of test conditions ) . Although speed was held constant during testing , it was individually self-selected or fixed . Most studies used only male participants . Conclusion : Despite procedural differences among studies , an increased stride rate ( reduced stride length ) appears to reduce the magnitude of several key biomechanical factors associated with running injuries The purpose of this study was to examine physiological strain and muscular performance responses of well trained athletes during two intermittent running exercise protocol s at the velocity associated with VO2max . Ten national level middle-distance runners ( VO2max 69.4+/-5.1 ; mean+/-SD ) performed in r and om order two 28 min treadmill running exercises : 14 bouts of 60 s runs with 60 s rest ( IR60 ) and 7 bouts of 120 s runs with 120 s rest between each run ( IR120 ) . During IR120 peak oxygen uptake ( 12 % ) , peak heart rate ( 3 % ) and peak blood lactate ( 79 % ) were significantly higher than during IR60 ( P < 0.001 ) and almost the same as in the VO2max test . In IR120 the relative aerobic energy release calculated on the basis of the accumulated oxygen deficit during the running bouts was significantly higher than in IR60 ( 81.5+/-2.7 vs. 70.2+/-2.6 % , P<0.001 ) likewise the sum oxygen consumption during the 14 min running ( P < 0.001 ) , while during the 14 min recovery it was as much lower ( P < 0.001 ) . There were no changes either during or between the IR60 and IR120 protocol s with regard to the muscular performance parameters , stride length or height of maximal vertical jumps . In conclusion , during intermittent running at the velocity associated with VO2max doubling the duration of work and rest bouts from 60 s to 120s increased the physiological strain of well trained athletes to the same level as at exhaustion in the VO2max test but the muscular performance variables were not influenced PURPOSE To quantify the relationship between total training load and running performance during the most important competitions of the season ( national cross-country championships , 4.175- and 10.130-km races ) . METHODS Eight well-trained , subelite endurance runners ( age ( mean+/-SD ) : 23+/-2 yr ; VO2max : 70.0+/-7.3 mL.kg.min ) performed a maximal cardiorespiratory exercise test before the training period to determine ventilatory threshold ( VT ) and respiratory compensation threshold ( RCT ) . Heart rate was continuously recorded using telemetry during each training session over a 6-month macrocycle , design ed to achieve peak performance during the aforementioned cross-country races , lasting from late August to the time that these races were held , that is , mid-February . This allowed us to quantify the total cumulative time spent in three intensity zones calculated as zone 1 ( low intensity , lower than the VT ) ; zone 2 ( moderate intensity , between VT and RCT ) ; and zone 3 ( high intensity , above the RCT ) . RESULTS Total training time in zone 1 ( 4581+/-979 min ) was significantly higher ( P<0.001 ) than that accumulated in zones 2 ( 1354+/-583 min ) and 3 ( 487+/-154 min ) . Total time in zone 2 was significantly higher than time in zone 3 ( P<0.05 ) . A correlation coefficient of r=-0.79 ( P=0.06 ) and r=-0.97 ( P=0.008 ) was found between the total training time spent in zone 1 and performance time during the short and long cross-country races , respectively . CONCLUSIONS Our findings suggest that total training time spent at low intensities might be associated with improved performance during highly intense endurance events , especially if the event duration is approximately 35 min . Interventional studies ( i.e. , improving or reducing training time in zone 1 ) are needed to corroborate our findings and to eluci date the physiological mechanisms behind them Beneficial systemic effects of regular physical exercise have been demonstrated to reduce risks of a number of age-related disorders . Antioxidant capacity adaptations are amongst these fundamental changes in response to exercise training . However , it has been cl aim ed that acute physical exercise performed at high intensity ( > 60 % of maximal oxygen uptake ) may result in oxidative stress , due to reactive oxygen species being generated excessively by enhanced oxygen consumption . The aim of this study was to evaluate the effect of high-intensity discontinuous training ( HIDT ) , characterized by repeated variations of intensity and changes of redox potential , on oxidative damage . Twenty long-distance masters runners ( age 47.8±7.8 yr ) on the basis of the individual values of gas exchange threshold were assigned to a different 8-weeks training program : continuous moderate-intensity training ( MOD , n = 10 ) or HIDT ( n = 10 ) . In both groups before ( PRE ) and after ( POST ) training we examined the following oxidative damage markers : thiobarbituric acid reactive substances ( TBARS ) as marker of lipid peroxidation ; protein carbonyls ( PC ) as marker of protein oxidation ; 8-hydroxy-2-deoxy-guanosine ( 8-OH-dG ) as a biomarker of DNA base modifications ; and total antioxidant capacity ( TAC ) as indicator of the overall antioxidant system . Training induced a significant ( p<0.05 ) decrease in resting plasma TBARS concentration in both MOD ( 7.53±0.30 and 6.46±0.27 µM , PRE and POST respectively ) and HIDT ( 7.21±0.32 and 5.85±0.46 µM , PRE and POST respectively ) . Resting urinary 8-OH-dG levels were significantly decreased in both MOD ( 5.50±0.66 and 4.16±0.40 ng mg−1creatinine , PRE and POST respectively ) and HIDT ( 4.52±0.50 and 3.18±0.34 ng mg−1creatinine , PRE and POST respectively ) . Training both in MOD and HIDT did not significantly modify plasma levels of PC . Resting plasma TAC was reduced in MOD while no significant changes were observed in HIDT . In conclusion , these results suggest that in masters runners high-intensity discontinuous does not cause higher level of exercise-induced oxidative stress than continuous moderate-intensity training , inducing similar beneficial effects on redox homeostasis This study compared running velocity , physiological responses , and perceived exertion during self-paced interval training bouts differing only in work bout duration . Twelve well-trained runners ( nine males , three females , 28+/-5 years , VO2 max 65+/-6 mL min(-1 ) kg(-1 ) ) performed preliminary testing followed by four " high-intensity " interval sessions ( Latin squares , 1 session week(-1 ) over 4 weeks ) consisting of 24 x 1 , 12 x 2 , 6 x 4 , or 4 x 6-min running bouts with a 1:1 work-to-rest interval ( total session duration 48 min ) . The average running velocity decreased ( 93 % , 88 % , 86 % , 84 % vVO2 max , P < 0.01 ) with increasing work duration . Peak VO2 averaged about 92+/-4 % of VO2 max for 2- , 4- , and 6-min intervals compared with only 82+/-5 % for 1-min bouts ( P < 0.001 ) . Six of 12 athletes achieved their highest average VO2 and heart rate during 4-min intervals . The average RPEpeak ( rating scale of perceived exertion ) was approximately 17+/-1 for all four interval sessions . RPE increased by 2 - 4 U during an interval training session . The mean lactate concentration was similar across sessions ( 4.3+/-1.1 - 4.6+/-1.5 mmol L(-1 ) ) . Under self-paced conditions , well-trained runners perform " high-intensity " intervals at an RPE of approximately 17 , independent of interval duration . The optimal interval duration for eliciting a high physiological load is 3 - 5 min under these training conditions . Increases in RPE during an interval bout are not associated with increasing blood lactate concentration The magnitude of improvement in peak oxygen uptake ( V(o)(2peak ) ) ) and performance to an exercise training regime is related to the V(o)(2 ) of prior accumulated exercise training bouts . However , it is unclear whether constant rate training ( CRT ) or interval training ( INT ) preferentially alters the V(o)(2 ) of running exercise . Therefore , the purpose of this study was to compare the acute V(o)(2 ) response to constant , and interval training sessions . Consequently , this study compared the mean average V(o)(2 ) of 17 moderately trained participants to a 20-min CRT and two different 20min INT treadmill runs . Participants completed three treatments ( twice ) in r and om order over 3 weeks . In 1min INT participants completed 10x1min efforts at the velocity corresponding to V(o)(2peak ) ( V(peak ) ) interspersed with 10x1min efforts at 0.5V(peak ) . In the 2min INT , participants completed 5x2min efforts at the V(peak ) interspersed with 5x2min efforts at 0.5 at V(peak ) . In CRT participants ran at a velocity equivalent to the mean velocity of INT ( 75 % V(peak ) ) . Mean average V(o)(2 ) for 2min INT , 1min INT and CRT were , respectively , 3200+/-661 ; 3076+/-6041 ; 2909+/-584mlmin(-1 ) . Both INT sessions result ed in a significantly higher mean average V(o)(2 ) than CRT . Furthermore , 2min INT result ed in 90 % of V(o)(2peak ) being exceeded more frequently than 1min INT . We conclude that INT serves as a more potent stimulus for improvement in V(o)(2peak ) and subsequent endurance performance than CRT 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 compare the effectiveness of three very short interval training sessions ( 15 - 15 s of hard and easier runs ) run at an average velocity equal to the critical velocity to elicit VO2 max for more than 10 minutes . We hypothesized that the interval with the smallest amplitude ( defined as the ratio between the difference in velocity between the hard and the easy run divided by the average velocity and multiplied by 100 ) would be the most efficient to elicit VO2 max for the longer time . The subjects were middle-aged runners ( 52 + /- 5 yr , VO2 max of 52.1 + /- 6 mL x min(-1 ) x kg(-1 ) , vVO2 max of 15.9 + /- 1.8 km x h(-1 ) , critical velocity of 85.6 + /- 1.2 % vVO2 max ) who were used to long slow distance-training rather than interval training . They performed three interval-training ( IT ) sessions on a synthetic track ( 400 m ) whilst breathing through the COSMED K4b2 portable metabolic analyser . These three IT sessions were : A ) 90 - 80 % vVO2 max ( for hard bouts and active recovery periods , respectively ) , the amplitude= ( 90 - 80/85 ) 100=11 % , B ) 100 - 70 % vVO2 max amplitude=35 % , and C ) 60 x 110 % vVO2 max amplitude = 59 % . Interval training A and B allowed the athlete to spend twice the time at VO2 max ( 14 min vs. 7 min ) compared to interval training C. Moreover , at the end of interval training A and B the runners had a lower blood lactate than after the procedure C ( 9 vs. 11 mmol x l(-1 ) ) . In conclusion , short interval-training of 15s-15s at 90 - 80 and 100 - 70 % of vVO2 max proved to be the most efficient in stimulating the oxygen consumption to its highest level in healthy middle-aged long-distance runners used to doing only long slow distance-training PURPOSE The purpose of this systematic review was to examine the link between training characteristics ( volume , duration , frequency , and intensity ) and running related injuries . METHODS A systematic search was performed in PubMed , Web of Science , Embase , and SportD iscus . Studies were included if they examined novice , recreational , or elite runners between the ages of 18 and 65 . Exposure variables were training characteristics defined as volume , distance or mileage , time or duration , frequency , intensity , speed or pace , or similar terms . The outcome of interest was Running Related Injuries ( RRI ) in general or specific RRI in the lower extremity or lower back . Method ological quality was evaluated using quality assessment tools of 11 to 16 items . RESULTS After examining 4561 titles and abstract s , 63 articles were identified as potentially relevant . Finally , nine retrospective cohort studies , 13 prospect i ve cohort studies , six case-control studies , and three r and omized controlled trials were included . The mean quality score was 44.1 % . Conflicting results were reported on the relationships between volume , duration , intensity , and frequency and RRI . CONCLUSION It was not possible to identify which training errors were related to running related injuries . Still , well supported data on which training errors relate to or cause running related injuries is highly important for determining proper prevention strategies . If method ological limitations in measuring training variables can be resolved , more work can be conducted to define training and the interactions between different training variables , create several hypotheses , test the hypotheses in a large scale prospect i ve study , and explore cause and effect relationships in r and omized controlled trials . LEVEL OF EVIDENCE 2a The present study examined the effect of training by the 10 - 20 - 30 concept on performance , blood pressure ( BP ) , and skeletal muscle angiogenesis as well as the feasibility of completing high-intensity interval training in local running communities . One hundred sixty recreational runners were divided into either a control group ( CON ; n = 28 ) , or a 10 - 20 - 30 training group ( 10 - 20 - 30 ; n = 132 ) replacing two of three weekly training sessions with 10 - 20 - 30 training for 8 weeks and performance of a 5-km run ( 5-K ) and BP was measured . VO2max was measured and resting muscle biopsies were taken in a subgroup of runners ( n = 18 ) . 10 - 20 - 30 improved 5-K time ( 38 s ) and lowered systolic BP ( 2 ± 1 mmHg ) . For hypertensive subjects in 10 - 20 - 30 ( n = 30 ) , systolic and diastolic BP was lowered by 5 ± 4 and 3 ± 2 mmHg , respectively , which was a greater reduction than in the non-hypertensive subjects ( n = 102 ) . 10 - 20 - 30 increased VO2max but did not influence muscle fiber area , distribution or capillarization , whereas the expression of the pro-angiogenic vascular endothelial growth factor ( VEGF ) was lowered by 22 % . No changes were observed in CON . These results suggest that 10 - 20 - 30 training is an effective and easily implemented training intervention improving endurance performance , VO2max and lowering BP in recreational runners , but does not affect muscle morphology and reduces muscle VEGF PURPOSE To analyze the acute physiological response to aerobic short-interval training ( AESIT ) at various high-intensity running speeds . A minor anaerobic glycolytic energy supply was aim ed to mimic the characteristics of slow continuous runs . METHODS Eight trained male runners ( maximal oxygen uptake [ VO(2max ) ] 55.5 ± 3.3 mL · kg(-1 ) · min(-1 ) ) performed an incremental treadmill exercise test ( increments : 0.75 km · h(-1 ) · min(-1 ) ) . Two lactate turn points ( LTP1 , LTP2 ) were determined . Subsequently , 3 r and omly assigned AESIT sessions with high-intensity running-speed intervals were performed at speeds close to the speed ( v ) at VO(2max ) ( vVO(2max ) ) to create mean intensities of 50 % , 55 % , and 60 % of vLTP1 . AESIT sessions lasted 30 min and consisted of 10-s work phases , alternated by 20-s passive recovery phases . RESULTS To produce mean velocities of 50 % , 55 % , and 60 % of vLTP1 , running speeds were calculated as 18.6 ± 0.7 km/h ( 93.4 % vVO(2max ) ) , 20.2 ± 0.6 km/h ( 101.9 % vVO(2max ) ) , and 22.3 ± 0.7 km/h ( 111.0 % vVO(2max ) ) , which gave a mean blood lactate concentration ( La ) of 1.09 ± 0.31 mmol/L , 1.57 ± 0.52 mmol/L , and 2.09 ± 0.99 mmol/L , respectively . La at 50 % of vLTP1 was not significantly different from La at vLTP1 ( P = .8894 ) . Mean VO(2 ) was found at 54.0 % , 58.5 % , and 64.0 % of VO(2max ) , while at the end of the sessions VO(2 ) rose to 71.1 % , 80.4 % , and 85.6 % of VO(2max ) , respectively . CONCLUSION The results showed that AESIT with 10-s work phases alternating with 20 s of passive rest and a running speed close to vVO(2max ) gave a systemic aerobic metabolic profile similar to slow continuous runs PURPOSE To examine the kinematic adjustments that runners make during an exhaustive run and to look at the effects these adjustments have on shock and shock attenuation . METHODS Ten recreational runners ran to volitional exhaustion on a treadmill at a velocity equal to their average 3200-m running velocity at maximal effort ( average time : 15.7 + /- 1.7 min ) . Head and leg accelerometers , a knee electrogoniometer , and a rearfoot electrogoniometer were attached to each subject . The data were sample d at 1000 Hz at the start , middle , and end of the run . RESULTS The knee became significantly more flexed at heel impact ( start : 164.9 + /- 2.3 degrees ; end : 160.5 + /- 2.9 degrees ; P < 0.05 ) . The rearfoot angle became more inverted at impact ( start : 12.2 + /- 1.6 degrees ; end : 13.6 + /- 1.9 degrees ; P < 0.05 ) . These kinematic changes result ed in a lower extremity that that had a lower effective mass during the impact . This decreased effective mass allowed the leg to accelerate more easily ; thus , peak leg impact accelerations ( start : 6.11 + /- 0.96 g ; end : 7.38 + /- 1.05 g ; P < 0.05 ) and impact attenuation ( start : 74.5 + /- 5.4 % ; end : 77.5 + /- 4.1 % ; P < 0.05 ) increased during the progression of the run . CONCLUSIONS The increase in peak impact accelerations at the leg was not considered an increased injury risk because of the decreased effective mass . The altered kinematics may have result ed in increased metabolic costs during the latter stages of the exhaustive run BACKGROUND AND PURPOSE Assessment of the quality of r and omized controlled trials ( RCTs ) is common practice in systematic review s. However , the reliability of data obtained with most quality assessment scales has not been established . This report describes 2 studies design ed to investigate the reliability of data obtained with the Physiotherapy Evidence Data base ( PEDro ) scale developed to rate the quality of RCTs evaluating physical therapist interventions . METHOD In the first study , 11 raters independently rated 25 RCTs r and omly selected from the PEDro data base . In the second study , 2 raters rated 120 RCTs r and omly selected from the PEDro data base , and disagreements were resolved by a third rater ; this generated a set of individual rater and consensus ratings . The process was repeated by independent raters to create a second set of individual and consensus ratings . Reliability of ratings of PEDro scale items was calculated using multirater kappas , and reliability of the total ( summed ) score was calculated using intraclass correlation coefficients ( ICC [ 1,1 ] ) . RESULTS The kappa value for each of the 11 items ranged from.36 to.80 for individual assessors and from.50 to.79 for consensus ratings generated by groups of 2 or 3 raters . The ICC for the total score was.56 ( 95 % confidence interval=.47-.65 ) for ratings by individuals , and the ICC for consensus ratings was.68 ( 95 % confidence interval=.57-.76 ) . DISCUSSION AND CONCLUSION The reliability of ratings of PEDro scale items varied from " fair " to " substantial , " and the reliability of the total PEDro score was " fair " to " good . The aim of this study was to compare the effects of two high-intensity , treadmill interval-training programs on 3000-m and 5000-m running performance . Maximal oxygen uptake ( V̇O2max ) , the running speed associated with V̇O2max ( vV̇O2max ) , the time for which vV̇O2max can be maintained ( Tmax ) , running economy ( RE ) , ventilatory threshold ( VT ) and 3000-m and 5000-m running times were determined in 27 well-trained runners . Subjects were then r and omly assigned to three groups ; ( 1 ) 60 % Tmax , ( 2 ) 70 % Tmax and ( 3 ) control . Subjects in the control group continued their normal training and subjects in the two Tmax groups undertook a 4-week treadmill interval-training program with the intensity set at vV̇O2max and the interval duration at the assigned Tmax . These subjects completed two interval-training sessions per week ( 60 % Tmax = six intervals/session , 70 % Tmax group = five intervals/session ) . Subjects were re-tested on all parameters at the completion of the training program . There was a significant improvement between pre- and post-training values in 3000-m time trial ( TT ) performance in the 60 % Tmax group compared to the 70 % Tmax and control groups [ mean ( SE ) ; 60 % Tmax=17.6 ( 3.5 ) s , 70 % Tmax = 6.3 ( 4.2 ) s , control=0.5 ( 7.7 ) s ] . There was no significant effect of the training program on 5000-m TT performance [ 60 % Tmax=25.8 ( 13.8 ) s , 70 % Tmax=3.7 ( 11.6 ) s , control=9.9 ( 13.1 ) s ] . Although there were no significant improvements in V̇O2max , vV̇O2max and RE between groups , changes in V̇O2max and RE were significantly correlated with the improvement in the 3000-m TT . Furthermore , VT and Tmax were significantly higher in the 60 % Tmax group post- compared to pre-training . In conclusion , 3000-m running performance can be significantly improved in a group of well-trained runners , using a 4-week treadmill interval training program at vV̇O2max with interval duration s of 60 % Tmax The aims of this study were to determine if there are significant kinematic changes in running pattern after intense interval workouts , whether duration of recovery affects running kinematics , and whether changes in running economy are related to changes in running kinematics . Seven highly trained male endurance runners ( VO 2max = 72.3 + /- 3.3 ml kg -1 min -1 ; mean + /- s ) performed three interval running workouts of 10 X 400 m at a speed of 5.94 + /- 0.19 m s -1 ( 356 + /- 11.2 m min -1 ) with a minimum of 4 days recovery between runs . Recovery of 60 , 120 or 180 s between each 400 m repetition was assigned at r and om . Before and after each workout , running economy and several kinematic variables were measured at speeds of 3.33 and 4.47 m s -1 ( 200 and 268 m min -1 ) . Speed was found to have a significant effect on shank angle , knee velocity and stride length ( P ≪ 0.05 ) . Correlations between changes pre- and post-test for VO 2 ( ml kg -1 min -1 ) and several kinematic variables were not significant ( P > 0.05 ) at both speeds . In general , duration of recovery was not found to adversely affect running economy or the kinematic variables assessed , possibly because of intra-individual adaptations to fatigue PURPOSE To investigate the effect of rest duration on self-selected intensity , physiological responses , and RPE during a st and ardized , high-intensity interval training prescription . SUBJECTS Nine well-trained male runners ( VO(2max ) 71 + /- 4 mL.kg(-1).min(-1 ) ) performed three treadmill interval training sessions running at constant 5 % incline . Six 4-min work bouts with either 1- , 2- , or 4-min recovery periods were performed in each session . Sessions were prescribed as " high-intensity " workouts with the goal being to achieve the highest possible average running speed for the work intervals . Subjects regulated their work and rest intensity based on these instructions . In a fourth interval session , subjects self-selected recovery time in response to a fixed intensity . RESULTS Running velocity increased slightly ( 14.7 + /- 0.7 vs 14.4 + /- 0.8 km.h(-1 ) , P = 0.02 ) when rest increased from 1 to 2 min , but showed no further increase with a 4-min rest ( 14.7 + /- 0.6 km.h(-1 ) . Work VO(2 ) was slightly higher with a 2-min rest duration compared with 1 and 4 min ( 66.2 + /- 4.2 vs 65.1 + /- 4.2 and 64.9 + /- 4.7 mL.kg(-1).min(-1 ) , P < 0.05 ) . Peak blood lactate was similar ( 6.2 + /- 2.6 , 6.8 + /- 2.9 , 6.2 + /- 2.6 mmol . L(-1 ) ) across conditions , whereas peak RPE was slightly lower during the 4-min rest condition ( 17.1 + /- 1.3 , 17.7 + /- 1.5 , 16.8 + /- 1.5 , P < 0.05 ) . With self-selected recovery time and no knowledge of elapsed time , the average rest duration was 118 + /- 23 s. CONCLUSIONS Under self-paced conditions , varying rest duration in a range of 1 to 4 min had limited impact on performance during repeated 4-min high-intensity exercise bouts . Approximately 120 s of active recovery may provide an appropriate balance between intracellular restitution and maintenance of high VO(2 ) on-kinetics The aim of this study was to compare the effects of two high-intensity interval training ( HIT ) programmes on maximal oxygen uptake ( .VO(2max ) ) , the lactate threshold ( LT ) and 3000 m running performance in moderately trained male runners . .VO(2max ) , the running speed associated with .VO(2max ) ( V.VO(2max ) ) , the time for which V.VO(2max ) can be maintained ( T(max ) ) , the running speed at LT ( v(LT ) ) and 3000 m running time ( 3000 mTT ) were determined before and following three different training programmes performed for 10 weeks . Following the pre-test , 17 moderately trained male runners ( V O(2max)=51.6+/-2.7ml kg(-1)min(-1 ) ) were divided into training groups based on their 3000 mTT ( Group 1 , G(1 ) , N=6 , 8 x 60 % of T(max ) at V.VO(2max ) , 1:1 work : recovery ratio ; Group 2 , G(2 ) , N=6 , 12 x 30s at 130 % V.VO(2max ) , 4.5 min recovery ; control group , G(CON ) , N=5 , 60 min at 75 % V.VO(2max ) ) . G(1 ) and G(2 ) performed two HIT sessions and two 60 min recovery run sessions ( 75 % V.VO(2max ) ) each week . Control subjects performed four 60 min recovery run sessions ( 75 % V.VO(2max ) ) each week . In G(1 ) , significant improvements ( p<0.05 ) following HIT were found in .VO(2max ) ( + 9.1 % ) , V.VO(2max ) ( + 6.4 % ) , T(max ) ( 5 % ) , v(LT ) ( + 11.7 % ) and 3000 mTT ( -7.3 % ) . In G(2 ) , significant improvements ( p<0.05 ) following HIT were found in .VO(2max ) ( + 6.2 % ) , V.VO(2max)(+7.8 % ) , T(max ) ( + 32 % ) and 3000 mTT ( -3.4 % ) , but not in v(LT ) ( + 4.7 % ; p=0.07 ) . No significant changes in these variables were found in G(CON ) . The present study has shown that 3000 m running performance , .VO(2max ) , V.VO(2max ) , T(max ) and v(LT ) can be significantly enhanced using different HIT programmes in moderately trained runners , but that changes in performance and physiological variables may be more profound using prolonged HIT at intensities of V.VO(2max ) with interval duration s of 60 % T(max ) |
861 | 30,408,162 | Results show differences between the three clinical studies regarding outcome measurement and intensity of the interventions .
Investigators describe more successful quitters at the end of the intervention programme than among controls .
Intensive alcohol cessation interventions offered for four to eight weeks to participants undergoing all types of surgical procedures to achieve complete alcohol cessation before surgery probably reduced the number of postoperative complications .
The included participants may represent a selective group , as they could have been more motivated and /or more interested in participating in clinical research or otherwise different , and effects may have been overestimated for both intervention and control groups in these studies . | BACKGROUND Risky consumption of alcohol is a global problem .
More than 3.3 million deaths annually are associated with risky use of alcohol , and global alcohol consumption continues to increase .
People who have high alcohol consumption often require planned and emergency surgical procedures .Risky drinking is associated with increased postoperative complications such as infections , cardiopulmonary complications , and bleeding episodes .
Alcohol causes disorders of the liver , pancreas , and nervous system .
Stopping consumption of alcohol can normalize these organ systems to some degree and may reduce the occurrence of complications after surgery .
This review was first published in 2012 and was up date d in 2018 .
OBJECTIVES To assess the effects of perioperative alcohol cessation interventions on rates of postoperative complications and alcohol consumption .
AUTHORS ' CONCLUSIONS This systematic review assessed the efficacy of perioperative alcohol cessation interventions for postoperative complications and alcohol consumption . | AIMS ( i ) To evaluate the effect of receiving one of two brief interventions in reducing alcohol consumption among general hospital patients compared with usual care . ( ii ) To assess whether a brief intervention of self-efficacy enhancement was superior to a self-help booklet in reducing alcohol consumption . DESIGN A three-arm cluster r and omized controlled trial . SETTING Seven general medical , six general surgical , one dermatology and two otolaryngology wards of a large teaching hospital covering a large urban and rural area . PARTICIPANTS A total of 215 of 789 in- patients aged 18 - 75 years , who screened positive for alcohol consumption in excess of national recommended limits according to a 7-day retrospective drinking diary . INTERVENTIONS Participants were allocated to receive one of three interventions : ( i ) face-to-face self-efficacy enhancement ; ( ii ) a self-help booklet ; or ( iii ) usual care . MEASUREMENTS The primary outcome measure was change in reported alcohol consumption at 6-month follow-up as measured by a 7-day retrospective drinking diary . Secondary outcomes were change in : number of alcohol drinking days in last week ; the maximum units of alcohol consumed on any one day in last week ; and Drinking Refusal Self-efficacy Expectancy Question naire score . FINDINGS Compared to the usual care group the self-efficacy enhancement group ( -10.1 units 95 % CI -16.1 to -4.1 ) and the self-help booklet group ( -10.0 units 95 % CI -16.0 to -3.9 ) had greater reductions in self-reported weekly alcohol consumption . There was no evidence that self-efficacy enhancement was superior to the self-help booklet ( P = 0.96 ) . CONCLUSIONS Brief interventions delivered in hospital offer simple means of helping heavy drinkers to reduce their alcohol consumption Background Patients with hazardous alcohol intake are overrepresented in emergency departments and surgical wards . These patients have an increased risk of postoperative complications with prolonged hospital stays and admissions to intensive care unit after surgery . In elective surgery , preoperative alcohol cessation interventions can reduce postoperative complications , but no studies have investigated the effect of alcohol cessation intervention at the time of acute fracture surgery . This protocol describes a r and omised clinical trial that aims to evaluate the effect of a new gold st and ard programme for alcohol cessation intervention in the perioperative period regarding postoperative complications , alcohol intake and cost-effectiveness . Methods / Design Patients with hazardous alcohol intake undergoing ankle fracture surgery will be recruited into the trial from multiple orthopaedic wards at university hospitals in Denmark , Sweden and Norway . Included patients will be r and omly allocated to either st and ard care or the gold st and ard programme aim ed at complete alcohol abstinence before , during and 6 weeks after surgery . It includes a structured patient education programme and weekly interventions meetings at the orthopaedic outpatient clinic . Furthermore , patients are provided with thiamine and B-vitamins , alcohol withdrawal prophylaxis and treatment , and disulfiram to support abstinence . Alcohol intake is biochemically vali date d ( blood , urine and breath tests ) at the weekly intervention meetings and follow-up visits . Follow-up assessment s will be conducted 6 weeks and 3 , 6 , 9 and 12 months after surgery for all patients . The effect of the gold st and ard programme will be assessed comparing the outcome measures between the intervention and control group at each follow-up point . Discussion The study will provide new knowledge about how to prevent alcohol-related postoperative complications at the time of acute fracture surgery . If effective , the results will be a benefit for the clinical course , patients and society alike . Trial registration The protocol is registered in Clinical Trials.gov ( I d : NCT00986791 ) PURPOSE The proximate use of illicit drugs or alcohol ( substance use ) is the most common precipitator of facial injuries among socioeconomically disadvantaged population s. Reducing these risky behaviors could minimize adverse health sequelae and potential reinjury . The objective of our study was to test whether a culturally competent , personalized motivational intervention incorporated into surgical care could significantly reduce existing substance use behaviors in facial injury patients . PATIENTS AND METHODS Substance-using subjects ( n = 218 ) presenting with facial injuries to a level 1 trauma center were r and omly assigned to either a personalized motivational intervention ( PMI ) condition or a health-information ( HI ) control condition . After a brief assessment of the individual 's substance use severity and willingness to change these behaviors , both groups attended 2 counseling sessions with a trained interventionist . The PMI subjects ( n = 118 ) received individualized , motivational interventions , whereas the HI subjects ( n = 100 ) received only general health information . Both groups were reassessed at 6 and 12 months postinjury , and changes in substance-use patterns were measured to assess the effects of intervention . RESULTS The PMI and HI groups were closely matched on their sociodemographic and substance use characteristics . Subjects in the PMI group showed statistically significant declines in drug use at both the 6- and 12-month assessment s. The intervention 's effect on lowering illicit drug use was greatest at the 6-month assessment but had weakened by the 1-year follow-up . The efficacy of the PMI was moderated by an individual 's initial drug use severity ; individuals with greater drug use dependency at baseline were seen to have larger intervention effects , as did individuals who were most aware of their drug problem and willing to change their substance use behaviors . Unlike illicit drug use , changes in alcohol use did not differ significantly between the intervention and control groups , irrespective of an individuals ' recognition of the alcohol problem or willingness to take steps to address it . CONCLUSION A culturally competent , motivational intervention integrated into the care of vulnerable patients with facial injury can reduce illicit drug use behaviors . Subgroups of injured patients appear to benefit most from such personalized motivational interventions . A better articulation of target population s , intervention content , and delivery would allow for directed interventions and an appropriate focusing of limited time and health care re sources Abstract Objective : To evaluate the influence of preoperative abstinence on postoperative outcome in alcohol misusers with no symptoms who were drinking the equivalent of at least 60 g ethanol/day . Design : R and omised controlled trial . Setting : Copenhagen , Denmark . Subjects : 42 alcoholic patients without liver disease admitted for elective colorectal surgery . Interventions : Withdrawal from alcohol consumption for 1month before operation ( disulfiram controlled ) compared with continuous drinking . Main outcome measures : Postoperative complications requiring treatment within the first month after surgery . Perioperative immunosuppression measured by delayed type hypersensitivity ; myocardial ischaemia and arrhythmias measured by Holter tape recording ; episodes of hypoxaemia measured by pulse oximetry . Response to stress during the operation were assessed by heart rate , blood pressure , serum concentration of cortisol , and plasma concentrations of glucose , interleukin 6 , and catecholamines . Results : The intervention group developed significantly fewer postoperative complications than the continuous drinkers ( 31 % v 74 % , P=0.02 ) . Delayed type hypersensitivity responses were better in the intervention group before ( 37 mm2 v 12 mm2 , P=0.04 ) , but not after surgery ( 3 mm2 v 3 mm2 ) . Development of postoperative myocardial ischaemia ( 23 % v 85 % ) and arrhythmias ( 33 % v 86 % ) on the second postoperative day as well as nightly hypoxaemic episodes ( 4 v 18 on the second postoperative night ) occurred significantly less often in the intervention group . Surgical stress responses were lower in the intervention group ( P≤0.05 ) . Conclusions : One month of preoperative abstinence reduces postoperative morbidity in alcohol abusers . The mechanism is probably reduced pre clinical organ dysfunction and reduction of the exaggerated response to surgical stress We have compared 2 % lignocaine 3.5 ml with 0.5 % hyperbaric bupivacaine 3 ml in a r and omized , double-blind study in 30 patients undergoing subarachnoid anaesthesia for transurethral surgery . A sensory level of T10 was produced more quickly ( P = 0.0001 ) and maximum height reached sooner ( P = 0.0002 ) with lignocaine , although there was a greater reduction in systolic arterial pressure ( P = 0.03 ) and a trend towards slower heart rates ( P = 0.056 ) . Return of full sensory and motor function occurred earlier with lignocaine ( P = 0.00005 and P = 0.02 ) Objectives We compared the effectiveness of the Gold St and ard Programme ( a comprehensive smoking cessation intervention commonly used in Denmark ) with other face-to-face smoking cessation programmes in Denmark after implementation in real life , and we identified factors associated with successful quitting . Design Prospect i ve cohort study . Setting A total of 423 smoking cessation clinics from different setting s reported data from 2001 to 2013 . Participants In total , 82 515 patients were registered . Smokers ≥15 years old and attending a programme with planned follow-up were included . Smokers who did not want further contact , who intentionally were not followed up or who lacked information about the intervention they received were excluded . A total of 46 287 smokers were included . Interventions Various real-life smoking cessation interventions were identified and compared : The Gold St and ard Programme , Come & Quit , crash courses , health promotion counselling ( brief intervention ) and other interventions . Main outcome Self-reported continuous abstinence for 6 months . Results Overall , 33 % ( 11 184 ) were continuously abstinent after 6 months ; this value was 24 % when non-respondents were considered smokers . The follow-up rate was 74 % . Women were less likely to remain abstinent , OR 0.83 ( CI 0.79 to 0.87 ) . Short interventions were more effective among men . After adjusting for confounders , the Gold St and ard Programme was the only intervention with significant results across sex , increasing the odds of abstinence by 69 % for men and 31 % for women . In particular , compliance , and to a lesser degree , mild smoking , older age and not being disadvantaged were associated with positive outcomes for both sexes . Compliance increased the odds of abstinence more than 3.5-fold . Conclusions Over time , Danish smoking cessation interventions have been effective in real life . Compliance is the main predictor of successful quitting . Interestingly , short programmes seem to have relatively strong effects among men , but the absolute numbers are very small . Only the comprehensive Gold St and ard Programme works across sexes Patients admitted to an emergency surgical ward were screened for alcohol problems and r and omized between an extensive alcohol counseling and a brief assessment followed by feedback of risky alcohol consumption . Some 165 patients were assessed for risk consumption and followed up 6 to 12 months , and it was found that patients in both interventions significantly reduced the amount they drank per occasion although they drank as often as before . The patients had also moved to a stage more ready to change . No differences in effect were found between the interventions . A brief assessment with feedback about risk consumption can be done on an emergency surgical ward by the surgical staff with a few hours of training and may reduce risky alcohol consumption significantly Background : Although alcohol use disorders ( AUDs ) have enormous public health consequences , the rate of diagnosis of AUDs remains unsatisfactorily low . The primary aim of this study was to compare the detection of AUDs by anesthesiologists in a large preoperative assessment clinic to that by computerized self- assessment of the Alcohol Use Disorder Identification Test . Secondary outcome measures were to compare the actions taken by anesthesiologists upon a finding of an AUD . Methods : One thous and five hundred fifty-six patients were included . Before preoperative assessment , patients were asked to complete the Alcohol Use Disorder Identification Test ( positive scores : men ≥ 8 , women ≥ 5 ) using a computer . The authors performed a retrospective chart analysis of the anesthesiologists ’ actions upon a finding of an AUD . The anesthesiologists were blinded to the results of the computer-based assessment and to the subsequent chart analysis . Results : The prevalence rate of AUDs determined by the anesthesiologists was 6.9 % ( 107 of 1,556 ) , whereas the proportion of patients positive for an AUD using the computerised Alcohol Use Disorder Identification Test was 18.1 % ( 282 of 1,556 ) ( P < 0.001 ) . The detection rate by the anesthesiologists of AUDs among men was significantly higher than among women ( P < 0.001 ) as well as in the elderly compared with younger patients ( P < 0.001 ) . Action taken by anesthesiologists was mainly based on evaluating quantity of alcohol consumption . Conclusion : The computer-based self- assessment increases detection rates of AUDs in busy setting s such as a preoperative assessment clinic . Prevalence rates of AUDs are underestimated . Best- practice guidelines for detection of AUDs are not implemented in the daily clinical routine . Barrier analysis is urgently required Background : Preoperative alteration of T cell – mediated immunity as well as an altered immune response to surgical stress were found in long-term alcoholic patients . The aim of this study was to evaluate perioperative T cell – mediated immune parameters as well as cytokine release from whole blood cells after lipopolysaccharide stimulation and its association with postoperative infections . Methods : Fifty-four patients undergoing elective surgery of the aerodigestive tract were included in this prospect i ve observational study . Long-term alcoholic patients ( n = 31 ) were defined as having a daily ethanol consumption of at least 60 g and fulfilling the Diagnostic and Statistical Manual of Mental Disorders for either alcohol abuse or alcohol dependence . The nonalcoholic patients ( n = 23 ) were defined as drinking less than 60 g ethanol/day . Blood sample s to analyze the immune status were obtained on morning before surgery and on the morning of days 1 , 3 , and 5 after surgery . Results : Basic patient characteristics did not differ between groups . Before surgery , the T helper 1:T helper 2 ratio ( Th1 : Th2 ) was significantly lower ( P < 0.01 ) , whereas plasma interleukin 1β and lipopolysaccharide-stimulated interleukin 1ra from whole blood cells were increased in long-term alcoholic patients . After surgery , a significant suppression of the cytotoxic lymphocyte ratio ( Tc1:Tc2 ) , the interferon γ : interleukin 10 ratio from lipopolysaccharide-stimulated whole blood cells , and a significant increase of plasma interleukin 10 was observed . Long-term alcoholics had more frequent postoperative infections compared with nonalcoholic patients ( 54%vs . 26 % ; P = 0.03 ) . Conclusions : T helper cell – mediated immunity was significantly suppressed before surgery and possibly led to inadequate cytotoxic lymphocyte and whole blood cell response in long-term alcoholic patients after surgery . This altered cell-mediated immunity might have accounted for the increased infection rate in long-term alcoholic patients after surgery Background Over the past 20 years evidence has accumulated confirming the immunomodulatory role of the appendix in ulcerative colitis ( UC ) . This led to the idea that appendectomy might alter the clinical course of established UC . The objective of this body of research is to evaluate the short-term and medium-term efficacy of appendectomy to maintain remission in patients with UC , and to establish the acceptability and cost-effectiveness of the intervention compared to st and ard treatment . Methods / Design These paired phase III multicenter prospect i ve r and omised studies will include patients over 18 years of age with an established diagnosis of ulcerative colitis and a disease relapse within 12 months prior to r and omisation . Patients need to have been medically treated until complete clinical ( Mayo score <3 ) and endoscopic ( Mayo score 0 or 1 ) remission . Patients will then be r and omised 1:1 to a control group ( maintenance 5-ASA treatment , no appendectomy ) or elective laparoscopic appendectomy plus maintenance treatment . The primary outcome measure is the one year cumulative UC relapse rate - defined both clinical ly and endoscopically as a total Mayo-score ≥5 with endoscopic subscore of 2 or 3 . Secondary outcomes that will be assessed include the number of relapses per patient at 12 months , the time to first relapse , health related quality of life and treatment costs , and number of colectomies in each arm . Discussion The ACCURE and ACCURE-UK trials will provide evidence on the role and acceptability of appendectomy in the treatment of ulcerative colitis and the effects of appendectomy on the disease course . Trial registration NTR2883 ; IS RCT BACKGROUND Because 40 % of motor vehicle fatalities in the United States are alcohol-related , interventions delivered by trauma clinicians targeted to reduce drinking are of particular importance to public health . The objective of this study was to test the effectiveness of hospital-based brief intervention strategies to reduce alcohol consumption and other health-related outcomes in the year after an alcohol-related vehicular injury . Brief interventions are clinical ly based strategies including assessment and direct feedback about drinking alcohol , goal setting , behavioral modification techniques , and the use of a self-help manual . METHODS The study was a r and omized controlled trial of two types of brief intervention with a 12-month follow-up . Participants with alcohol-related vehicular injury who were admitted to Level I trauma centers were eligible for enrollment . Enrolled participants were r and omized to a control , simple advice , or brief counseling condition . Primary outcome variables were alcohol consumption ( st and ard drinks/month , binges/month ) , adverse driving events ( driving citations , traffic crashes ) , and changes in health status ( hospital and emergency department admissions ) . RESULTS The study enrolled 187 participants at baseline and retained 100 across 12 months . Participants had a significant decrease in alcohol consumption and traffic citations at 12 months as compared with baseline . Mean st and ard drinks/month declined from 56.80 ( SD 63.89 ) at baseline to 32.10 ( SD 53.20 ) at 12 months . Mean binges/month declined from 5.79 ( SD 6.98 ) at baseline to 3.21 ( SD 6.17 ) at 12 months . There were no differences in alcohol consumption , adverse driving events , or health status by condition . CONCLUSIONS Whether the reductions in alcohol consumption and traffic citations were a result of the crash , hospitalization for injury , screening for alcohol use , or combination of these factors is difficult to determine . Further work is needed to underst and the mechanisms involved in reductions of health-related outcomes and the role of brief intervention in this population AIM To assess the effectiveness of a tailored pre-operative intervention for excessive alcohol consumption in reducing post-operative complications and alcohol consumption thereafter . METHODS Patients scheduled for elective surgery requiring at least overnight hospitalisation were screened for alcohol misuse . Consenting , eligible participants with > or = 7 days to surgery at the time of screening were offered an intervention and those with < 7 days to surgery were provided usual care . RESULTS Over a period of 2 years and 10 months , 3139 patients were screened to recruit 136 participants . Baseline analysis revealed a mean age of 53 ( + /-15.8 ) years and a mean consumption of 71 g/day ( + /-48.1 ) . The intervention group ( n = 45 ) did not differ significantly from controls ( n = 91 ) in age , consumption , and number of current smokers , but there were significantly more women in the control group . There was no difference between the groups in major or minor complications experienced , or length of stay after controlling for age , gender , and baseline consumption . At 6-month follow-up there was a significant reduction in drinking for the entire study population . CONCLUSION The study did not demonstrate any beneficial effect of the pre-operative intervention on post-operative complications . The relatively short time to surgery , intervention by a non-member of the surgical team , challenges to recruitment and reduced consumption in the control group may have limited the ability of the study to detect a significant effect of the intervention Perioperative low-dose ethanol infusion is a feasible option for stress reduction and prophylaxis of alcoholism-associated complications . Because alcohol has inhibitory effects on hemostasis , our study focused on the effect of perioperative low-dose ethanol infusion on bleeding complications , defined as transfused blood units and reoperations , in alcoholic patients undergoing major surgery . We included 44 long-term alcoholic patients scheduled for tumor resection of the aerodigestive and gastrointestinal tract . Patients were r and omly assigned to the ethanol or control group . Ethanol infusion ( 0.5 g ethanol/kg body weight/24 hours ) started before surgery and was continued until the postoperative Day 3 . Regarding all patients , there was no statistically significant difference in the amount of transfused blood between the ethanol and control groups . However , the effect of ethanol infusion on bleeding complications depended on the site of surgery . Ethanol infusion result ed in an increased number of transfused blood units in gastrointestinal patients and a decreased number of transfused units in patients undergoing tumor resection of the aero-digestive tract . In conclusion , perioperative ethanol infusion in long-term alcoholic patients with tumor resections of the aerodigestive tract is an option for stress reduction without increased risk for blood transfusion . In contrast , ethanol infusion in patients with tumor resections in the gastrointestinal tract could increase the risk for bleeding complications OBJECTIVE Alcoholism is the leading risk factor for injury . The authors hypothesized that providing brief alcohol interventions as a routine component of trauma care would significantly reduce alcohol consumption and would decrease the rate of trauma recidivism . METHODS This study was a r and omized , prospect i ve controlled trial in a level 1 trauma center . Patients were screened using a blood alcohol concentration , gamma glutamyl transpeptidase level , and short Michigan Alcoholism Screening Test ( SMAST ) . Those with positive results were r and omized to a brief intervention or control group . Reinjury was detected by a computerized search of emergency department and statewide hospital discharge records , and 6- and 12-month interviews were conducted to assess alcohol use . RESULTS A total of 2524 patients were screened ; 1153 screened positive ( 46 % ) . Three hundred sixty-six were r and omized to the intervention group , and 396 to controls . At 12 months , the intervention group decreased alcohol consumption by 21.8+/-3.7 drinks per week ; in the control group , the decrease was 6.7+/-5.8 ( p = 0.03 ) . The reduction was most apparent in patients with mild to moderate alcohol problems ( SMAST score 3 to 8) ; they had 21.6+/-4.2 fewer drinks per week , compared to an increase of 2.3+/-8.3 drinks per week in controls ( p < 0.01 ) . There was a 47 % reduction in injuries requiring either emergency department or trauma center admission ( hazard ratio 0.53 , 95 % confidence interval 0.26 to 1.07 , p = 0.07 ) and a 48 % reduction in injuries requiring hospital admission ( 3 years follow-up ) . CONCLUSION Alcohol interventions are associated with a reduction in alcohol intake and a reduced risk of trauma recidivism . Given the prevalence of alcohol problems in trauma centers , screening , intervention , and counseling for alcohol problems should be routine Retrospective studies suggest that there is an increased postoperative morbidity among alcohol misusers . We have prospect ively studied the risk of alcohol intake among patients undergoing surgery . We investigated 15 symptom-free subjects who required colorectal surgery and who were drinking at least 60 g of alcohol per day . These patients were matched for sex , nutrition , age , weight , cardiovascular and pulmonary disease , diagnosis , anaesthesia , and surgery to 15 control subjects who were consuming below 25 g of alcohol daily . Those drinking at least 60 g of alcohol per day developed more postoperative complications than controls ( 67 % vs 20 % , p less than 0.05 ) and hospital stay was prolonged ( 20 vs 12 days , p less than 0.05 ) . Preoperatively , alcohol misusers had reduced left ventricular ejection fraction ( median , 54 % vs 68 % , p less than 0.01 ) . Delayed hypersensitivity responses were smaller in the alcohol group before ( 53 mm2 vs 78 mm2 , p less than 0.05 ) and after ( 18 mm2 vs 55 mm2 , p less than 0.01 ) surgery . Alcohol misusers had longer bleeding times during the first postoperative week ( p less than 0.01 ) . Surgical stress responses , as assessed by changes in plasma cortisol and catecholamines , were higher among alcoholics ( p less than 0.05 ) . Postoperative morbidity is increased in symptom-free alcohol misusers . The mechanism is probably sub clinical cardiac insufficiency , immunosuppression , and decreased haemostatic function . Preoperative alcohol consumption may be a more important risk factor than previously thought RATIONALE Postoperative pneumonia is three to four times more frequent in patients with alcohol use disorders followed by prolonged intensive care unit ( ICU ) stay . Long-term alcohol use leads to an altered perioperative hypothalamus-pituitary-adrenal ( HPA ) axis and immunity . OBJECTIVES The aim of this study was to evaluate HPA intervention with low-dose ethanol , morphine , or ketoconazole on the neuroendocrine-immune axis and development of postoperative pneumonia in long-term alcoholic patients . METHODS In this r and omized , double-blind controlled study , 122 consecutive patients undergoing elective surgery for aerodigestive tract cancer were included . Long-term alcohol use was defined as consuming at least 60 g of ethanol daily and fulfilling the Diagnostic and Statistical Manual of Mental Disorders IV criteria for either alcohol abuse or dependence . Nonalcoholic patients were included but only as a descriptive control . Perioperative intervention with low-dose ethanol ( 0.5 g/kg body weight per day ) , morphine ( 15 mug/kg body weight per hour ) , ketoconazole ( 200 mg four times daily ) , and placebo was started on the morning before surgery and continued for 3 d after surgery . Blood sample s to analyze the neuroendocrine-immune axis were obtained on the morning before intervention and on Days 1 , 3 , and 7 after surgery . MEASUREMENTS AND MAIN RESULTS In long-term alcoholic patients , all interventions decreased postoperative hypercortisolism and prevented impairment of the cytotoxic T-lymphocyte type 1:type 2 ratio . All interventions decreased the pneumonia rate from 39 % to a median of 5.7 % and shortened intensive care unit stay by 9 d ( median ) compared with the placebo-treated long-term alcoholic patients . CONCLUSIONS Intervention at the level of the HPA axis altered the immune response to surgical stress . This result ed in decreased postoperative pneumonia rates and shortened intensive care unit stay in long-term alcoholic patients We studied 120 injured male patients of working age who were heavy drinkers or alcoholics , obtaining seven points or more in the Michigan Alcoholism Screening Test ( MAST ) . They were r and omly allocated either to an intervention group ( IG ) or to a control group ( CG ) . In addition to the MAST interview , the consumption of alcohol during the previous week prior to hospital admission was calculated and laboratory measures ( serum GGT , ASAT and ALAT ) were obtained . Counselling of the patients in the IG was carried out by a trained assistant nurse and a physician . Forty-nine patients in IG and 40 patients in CG were re-examined after 6 months . In the IG 45 % and in the CG 20 % of the patients were improved ( Chi square test , P less than 0.05 ) . Improvement criteria were a decrease in alcohol consumption by at least one-third and decrease of S-GGT by at least 20 % during the follow-up period . In respect to the laboratory measures the groups were identical at the beginning of the study and after 6 months ' follow-up . Our results are encouraging and suggest that the assessment of heavy drinking should be a routine in the treatment of alcohol-related injuries and that education and counselling must be intensive to be effective AIM To evaluate the effectiveness of a brief motivational intervention on alcohol consumption and misuse in young males with alcohol-related face injury . DESIGN R and omized controlled trial . SETTING Oral and maxillofacial surgery out-patient clinic in an urban teaching hospital . PARTICIPANTS One hundred and fifty-one participants were r and omized to motivational intervention and control conditions . INTERVENTIONS Control was treatment as usual . The intervention was treatment as usual plus a one-session brief motivational intervention administered by a nurse . MEASUREMENTS Three sets of measurements were taken at baseline , 3-month and 1-year follow-up . Collateral measurements were also taken at 1-year follow-up . Primary outcome measures were total alcohol consumption , typical weeks consumption and days abstinent in preceding 3 months . Other outcome measures included the Alcohol Use Disorders Identification Test , a short form of the Alcohol Problems Question naire , and a measure of satisfaction with social relationships . RESULTS There was a significant decrease in 84-day total alcohol consumption across the year ( P < 0.006 ) and further , a significant effect for the motivational intervention was demonstrated ( P < 0.029 ) . This pattern was repeated for days abstinent and alcohol consumption in a typical week as well as alcohol-related problems . There was a significantly greater reduction in the percentage of hazardous drinkers in the motivational intervention group ( from 60 % to 27 % , P < 0.009 ) compared to the control group ( from 54 % to 51 % , NS ) . CONCLUSION A proportion of young men change their alcohol consumption following alcohol-related injury . A nurse-led psychological intervention adds significantly to the proportion and magnitude of response BACKGROUND A substantial number of trauma center admissions are related to driving under the influence ( DUI ) ; however , there has been no prior report of brief intervention ( BI ) after injury reducing subsequent DUI arrests . The hypothesis of this study was that injured patients receiving BI would have a lower risk of DUI arrest within 3 years of discharge than those receiving st and ard care ( SC ) . METHODS This prospect i ve , r and omized clinical trial r and omly allocated patients involved in motor vehicle collisions to receive SC or a BI regarding alcohol use . The primary outcome measure was DUI arrest within 3 years of hospital discharge . DUI arrests were documented by matching demographic information to state traffic safety data . RESULTS After r and omization ( N = 126 ) , BI and SC groups were similar in age , prior DUI arrests , and alcohol screening score . BI sessions lasted an average of 30 minutes and were performed by either a social worker or a trauma surgeon . Approximately one in six participants ( n = 21 , 16.7 % ) had a DUI arrest within 3 years of hospital discharge . Within 3 years of hospital discharge , 14 of 64 patients ( 21.9 % ) in the SC group had an arrest for DUI compared with only 7 of 62 patients ( 11.3 % ) who received the BI . Multivariate analysis demonstrated that BI was the strongest protective factor against DUI arrest ( odds ratio [ OR ] , 0.32 ; 95 % confidence interval < or = CI ] , 0.11 - 0.96 ) . Prior number of DUIs ( OR , 1.43 ; 95 % CI , 1.03 - 2.01 ) and age ( OR , 0.94 ; 95 % CI , 0.88 - 0.99 ) were also associated with DUI arrest post-hospitalization , but alcohol screening score ( OR , 1.06 ; 95 % CI , 0.99 - 1.13 ) was not . The absolute risk reduction implies that only nine patients would need to receive a BI to prevent one DUI arrest . CONCLUSION Patients who receive BI during a trauma center admission are less likely to be arrested for DUI within 3 years of discharge . BI represents a viable intervention to reduce DUI after trauma center admission AIMS To estimate the incremental cost , cost-effectiveness and benefit-cost ratio of incorporating a significant other ( SO ) into motivational intervention for alcohol misuse . DESIGN We obtained economic data from the one year with the intervention in full operation for patients in a recent r and omized trial . SETTING The underlying trial took place at a major urban hospital in the United States . PARTICIPANTS The trial r and omized 406 ( 68.7 % male ) eligible hazardous drinkers ( 196 during the economic study ) admitted to the emergency department or trauma unit . INTERVENTION The motivational interview condition consisted of one in-person session featuring personalized normative feedback . The significant other motivational interview condition comprised one joint session with the participant and SO in which the SO 's perspective and support were elicited . MEASUREMENTS We ascertained activities across 445 representative time segments through work sampling ( including staff idle time ) , calculated the incremental cost in per patient of incorporating an SO , expressed the results in 2014 US$ , incorporated quality and mortality effects from a closely related trial and derived the cost per quality -adjusted life-year ( QALY ) gained . FINDINGS From a health system perspective , the incremental cost per patient of adding an SO was $ 341.09 [ 95 % confidence interval ( CI ) = $ 244.44 - 437.74 ] . The incremental cost per year per hazardous drinker averted was $ 3623 ( CI = $ 1777 - 22,709 ) , the cost per QALY gained $ 32,200 ( CI = $ 15,800 - 201,700 ) , and the benefit-cost ratio was 4.73 ( 95 % CI = 0.7 - 9.66 ) . If adding an SO into the intervention strategy were concentrated during the hours with highest risk or in a trauma unit , it would become even more cost-beneficial . CONCLUSIONS Using criteria established by the World Health Organization ( cost-effectiveness below the country 's gross domestic product per capita ) , incorporating a significant other into a patient 's motivational intervention for alcohol misuse is highly cost-effective |
862 | 31,615,461 | Perceived facilitators of the uptake of HIVST were autonomy and self-empowerment , privacy , confidentiality , convenience , opportunity to test , including couples HIV testing , and ease of use .
Actual HIVST users expressed preference of oral-fluid self-testing because of ease of use , and that it is less invasive and painless compared to finger-stick/whole blood-based HIV tests .
Lack of clear instructions on how to use self-test kits , and existing different products of HIVST increases rates of user errors . | More than 40 % of adults in Sub-Saharan Africa are unaware of their HIV status .
HIV self-testing ( HIVST ) is a novel approach with a potential to increase uptake of HIV testing and linkage to care for people who test HIV positive .
We explored HIV stakeholder ’s perceptions about factors that enable or deter the uptake of HIV self-testing and experiences of self-testing of adult users in Africa .
This systematic review of qualitative evidence included articles on qualitative studies published or made available between January 1998 to February 2018 on perspectives of key stakeholders , including HIV policymakers , HIV experts , health care providers , and adult men and women ( 18 years and above ) about factors that enable or deter the uptake of HIV self-testing and experiences of self-testing among adult users . | Objectives : The current study identifies young people 's preferences for HIV self-testing ( HIVST ) delivery , determines the relative strength of preferences and explores underlying behaviors and perceptions to inform youth-friendly services in southern Africa . Design : A mixed methods design was adopted in Malawi and Zimbabwe and includes focus group discussion s , in-depth interviews and discrete choice experiments . Methods : The current study was conducted during the formative phase of cluster-r and omized trials of oral-fluid HIVST distribution . Young people aged 16–25 years were purposively selected for in-depth interviews ( n = 15 ) in Malawi and 12 focus group discussion s ( n = 107 ) across countries . Representative sample s of young people in both countries ( n = 341 ) were administered discrete choice experiments on HIVST delivery , with data analyzed to estimate relative preferences . The qualitative results provided additional depth and were triangulated with the quantitative findings . Results : There was strong concordance across methods and countries based on the three triangulation parameters : product , provider and service characteristics . HIVST was highly accepted by young people , if provided at no or very low cost . Young people expressed mixed views on oral-fluid tests , weighing perceived benefits with accuracy concerns . There was an expressed lack of trust in health providers and preference for lay community distributors . HIVST addressed youth-specific barriers to st and ard HIV testing , with home-based distribution considered convenient . Issues of autonomy , control , respect and confidentiality emerged as key qualitative themes . Conclusion : HIVST services can be optimized to reach young people if products are provided through home-based distribution and at low prices , with respect for them as autonomous individuals Abstract Introduction : In the era of ambitious HIV targets , novel HIV testing models are required for hard-to-reach groups such as men , who remain underserved by existing services . Pregnancy presents a unique opportunity for partners to test for HIV , as many pregnant women will attend antenatal care ( ANC ) . We describe the views of pregnant women and their male partners on HIV self-test kits that are woman-delivered , alone or with an additional intervention . Methods : A formative qualitative study to inform the design of a multi-arm multi-stage cluster-r and omized trial , comprised of six focus group discussion s and 20 in-depth interviews , was conducted . ANC attendees were purposively sample d on the day of initial clinic visit , while men were recruited after obtaining their contact information from their female partners . Data were analysed using content analysis , and our interpretation is hypothetical as participants were not offered self-test kits . Results : Providing HIV self-test kits to pregnant women to deliver to their male partners was highly acceptable to both women and men . Men preferred this approach compared with st and ard facility-based testing , as self-testing fits into their lifestyles which were characterized by extreme day-to-day economic pressures , including the need to raise money for food for their household daily . Men and women emphasized the need for careful communication before and after collection of the self-test kits in order to minimize the potential for intimate partner violence although physical violence was perceived as less likely to occur . Most men stated a preference to first self-test alone , followed by testing as a couple . Regarding interventions for optimizing linkage following self-testing , both men and women felt that a fixed financial incentive of approximately USD$2 would increase linkage . However , there were concerns that financial incentives of greater value may lead to multiple pregnancies and lack of child spacing . In this low-income setting , a lottery incentive was considered overly disappointing for those who receive nothing . Phone call reminders were preferred to short messaging service . Conclusions : Woman-delivered HIV self-testing through ANC was acceptable to pregnant women and their male partners . Feedback on additional linkage enablers will be used to alter pre-planned trial arms Background HIV self-testing ( HIVST ) has been found to be highly effective , but no cost analysis has been undertaken to guide the design of affordable and scalable implementation strategies . Methods Consecutive HIV self-testers and facility-based testers were recruited from participants in a community cluster-r and omised trial ( IS RCT N02004005 ) investigating the impact of offering HIVST in addition to facility-based HIV testing and counselling ( HTC ) . Primary costing studies were undertaken of the HIVST service and of health facilities providing HTC to the trial population . Costs were adjusted to 2014 US$ and INT$. Recruited participants were asked about direct non-medical and indirect costs associated with accessing either modality of HIV testing , and additionally their health-related quality of life was measured using the EuroQol EQ-5D . Results A total of 1,241 participants underwent either HIVST ( n = 775 ) or facility-based HTC ( n = 446 ) . The mean societal cost per participant tested through HIVST ( US$ 9.23 ; 95 % CI : US$ 9.14-US$9.32 ) was lower than through facility-based HTC ( US$ 11.84 ; 95 % CI : US$ 10.81 - 12.86 ) . Although the mean health provider cost per participant tested through HIVST ( US$ 8.78 ) was comparable to facility-based HTC ( range : US$ 7.53-US$10.57 ) , the associated mean direct non-medical and indirect cost was lower ( US$ 2.93 ; 95 % CI : US$ 1.90-US$3.96 ) . The mean health provider cost per HIV positive participant identified through HIVST was higher ( US$ 97.50 ) than for health facilities ( range : US$ 25.18-US$76.14 ) , as was the mean cost per HIV positive individual assessed for anti-retroviral treatment ( ART ) eligibility and the mean cost per HIV positive individual initiated onto ART . In comparison to the facility-testing group , the adjusted mean EQ-5D utility score was 0.046 ( 95 % CI : 0.022 - 0.070 ) higher in the HIVST group . Conclusions HIVST reduces the economic burden on clients , but is a costlier strategy for the health provider aim ing to identify HIV positive individuals for treatment . The provider cost of HIVST could be substantially lower under less restrictive distribution models , or if costs of oral fluid HIV test kits become comparable to finger-prick kits used in health facilities We evaluated performance , accuracy , and acceptability parameters of unsupervised oral fluid ( OF ) HIV self-testing ( HIVST ) in a general population in western Kenya . In a prospect i ve validation design , we enrolled 240 adults to perform rapid OF HIVST and compared results to staff administered OF and rapid fingerstick tests . All reactive , discrepant , and a proportion of negative results were confirmed with lab ELISA . Twenty participants were video-recorded conducting self-testing . All participants completed a staff administered survey before and after HIVST to assess attitudes towards OF HIVST acceptability . HIV prevalence was 14.6 % . Thirty-six of the 239 HIVSTs were invalid ( 15.1 % ; 95 % CI 11.1–20.1 % ) , with males twice as likely to have invalid results as females . HIVST sensitivity was 89.7 % ( 95 % CI 73–98 % ) and specificity was 98 % ( 95 % CI 89–99 % ) . Although sensitivity was somewhat lower than expected , there is clear interest in , and high acceptability ( 94 % ) of OF HIV self-testing Objective To evaluate HIV self-testing performance and results interpretation among female sex workers ( FSWs ) in Kampala , Ug and a , who performed unassisted HIV self-testing . Methods In October 2016 , 104 participants used an oral HIV self-test while under observation by research assistants . Participants were not assisted on HIV self-test use prior to or during testing , and were only given the manufacturer ’s pictorial and written instructions to guide them . Research assistants recorded if participants completed and /or had difficulties with steps in the HIV self-testing process on a prespecified checklist . R and omly drawn , used HIV self-tests were interpreted by FSWs . We calculated the concordance between FSWs ’ interpretations of self-test results with those indicated in the manufacturer ’s instructions . Results Only 33 % ( 34/104 ) of participants completed all of the key steps in the HIV self-testing process , and the majority ( 86 % , 89/104 ) were observed having difficulties with at least one of these steps . Misinterpretation of HIV self-test results were common among FSWs : 23 % ( 12/56 ) of FSWs interpreted HIV-negative self-test results as HIV positive and 8 % ( 3/37 ) of FSWs interpreted HIV-positive self-test results as HIV negative . The concordance between FSWs ’ interpretations of self-test results and that indicated in the instructions was 73 % ( 95 % CI 56 % to 86 % ) for HIV-positive self-tests and 68 % ( 95 % CI 54 % to 80 % ) for HIV-negative self-tests . Conclusions FSWs in Kampala , who performed unassisted HIV self-testing , skipped steps in the HIV self-testing process and had difficulties correctly interpreting self-test results . Training on use and interpretation of HIV self-tests may be necessary to prevent errors in the HIV self-testing process and to avoid the negative consequences of false-positive and false-negative HIV self-test results among FSWs . Trial registration number NCT02846402 |
863 | 31,767,988 | Modest exchange of carbohydrates for fats in mixed meals significantly reduces PPG and PPI and increases PPTG responses .
The quantitative relationships derived here may be applied to predict responses , and to design and optimize meal macronutrient compositions in dietary intervention studies | Varying the macronutrient composition of meals alters acute postpr and ial responses , but the effect sizes for specific macronutrient exchanges have not been quantified by systematic review s. Therefore the aim is to quantify the effect size of exchanging fat for carbohydrates in mixed meals on postpr and ial glucose ( PPG ) , insulin ( PPI ) , triglycerides ( PPTG ) , and free fatty acids ( PPFFA ) responses by performing a systematic review and meta- analysis of r and omized controlled trials . | BACKGROUND Substitution of dietary polyunsaturated for saturated fat has long been recommended for the primary prevention of cardiovascular disease ( CVD ) , but only a few prospect i ve cohort studies have provided support for this advice . METHODS We assessed the association of dietary linoleic and total polyunsaturated fatty acid ( PUFA ) intake with cardiovascular and overall mortality in a population -based cohort of 1551 middle-aged men . Dietary fat composition was estimated with a 4-day food record and serum fatty acid composition . RESULTS During the 15-year follow-up , 78 men died of CVD and 225 of any cause . Total fat intake was not related to CVD or overall mortality . Men with an energy-adjusted dietary intake of linoleic acid ( relative risk [ RR ] 0.39 ; 95 % confidence interval [ CI ] , 0.21 - 0.71 ) and PUFA ( RR , 0.38 ; 95 % CI , 0.20 - 0.70 ) in the upper third were less likely to die of CVD than men with intake in the lower third after adjustment for age . Multivariate adjustment weakened the association somewhat . Mortality from CVD was also lower for men with proportions of serum esterified linoleic acid ( RR , 0.42 ; 95 % CI , 0.21 - 0.80 ) and PUFA ( RR , 0.25 ; 95 % CI , 0.12 - 0.50 ) in the upper vs lower third , with some attenuation in multivariate analyses . Serum and to a lesser extent dietary linoleic acid and PUFA were also inversely associated with overall mortality . CONCLUSIONS Dietary polyunsaturated and more specifically linoleic fatty acid intake may have a substantial cardioprotective benefit that is also reflected in overall mortality . Dietary fat quality seems more important than fat quantity in the reduction of cardiovascular mortality in men OBJECTIVE To examine the predictive capability of a 1-h vs 2-h postload glucose value for cardiovascular morbidity and mortality . DESIGN Prospect i ve , population -based cohort study ( Malmö Preventive Project ) with subject inclusion 1974 - 1992 . METHODS 4934 men without known diabetes and cardiovascular disease , who had blood glucose ( BG ) measured at 0 , 20 , 40 , 60 , 90 and 120 min during an OGTT ( 30 g glucose per m2 body surface area ) , were followed for 27 years . Data on cardiovascular events and death were obtained through national and local registries . Predictive capabilities of fasting BG ( FBG ) and glucose values obtained during OGTT alone and added to a clinical prediction model comprising traditional cardiovascular risk factors were assessed using Harrell 's concordance index ( C-index ) and integrated discrimination improvement ( IDI ) . RESULTS Median age was 48 ( 25th-75th percentile : 48 - 49 ) years and mean FBG 4.6 ± 0.6 mmol/L. FBG and 2-h postload BG did not independently predict cardiovascular events or death . Conversely , 1-h postload BG predicted cardiovascular morbidity and mortality and remained an independent predictor of cardiovascular death ( HR : 1.09 , 95 % CI : 1.01 - 1.17 , P = 0.02 ) and all-cause mortality ( HR : 1.10 , 95 % CI : 1.05 - 1.16 , P < 0.0001 ) after adjusting for various traditional risk factors . Clinical risk factors with added 1-h postload BG performed better than clinical risk factors alone , in predicting cardiovascular death ( likelihood-ratio test , P = 0.02 ) and all-cause mortality ( likelihood-ratio test , P = 0.0001 ; significant IDI , P = 0.0003 ) . CONCLUSION Among men without known diabetes , addition of 1-h BG , but not FBG or 2-h BG , to clinical risk factors provided incremental prognostic yield for prediction of cardiovascular death and all-cause mortality Purpose The purpose of this study is to compare the glycemic and insulinemic responses following the ingestion of recently developed diabetes-specific enteral formulas versus a st and ard and a high-fat formula . Methods Fifteen type 2 diabetes patients were selected to participate in a r and omized , double-blind , crossover study . Two enteral formulas ( 47 energy percent [ En% ] carbohydrate , 34En% fat , and 4 g fiber/200 mL ) were defined with either isomaltulose ( formula 1 ) or sucromalt ( formula 2 ) as the main carbohydrate source . For comparison , an isoenergetic diabetes-specific , high-fat ( 33En% carbohydrate , 50En% fat , 2.9 g fiber/200 mL ) and a st and ard formula ( 55En% carbohydrate , 30En% fat , 2.8 g fiber/ 200 mL ) were tested . Results Ingestion of formulas 1 and 2 and the high-fat formula result ed in an attenuated blood glucose response when compared with the st and ard formula ( P < .05 ) . In accordance , peak plasma glucose concentrations were significantly lower when compared with the st and ard formula ( 189 ± 3.6 mg/dL [ 10.5 ± 0.2 mmol/L ] , 196.2 ± 3.6 mg/dL [ 10.9 ± 0.2 mmol/L ] , 187.2 ± 3.6 mg/dL [ 10.4 ± 0.2 mmol/L ] , and 237.6 ± 3.6 mg/dL [ 13.2 ± 0.2 mmol/L ] , respectively ) . Plasma insulin responses were lower after consumption of the newly developed and high-fat formulas . Ingestion of the high-fat formula result ed in a greater postpr and ial triglyceride response ( P < .05 ) . Conclusions Diabetes-specific enteral formulas rich in slowly digestible carbohydrate sources can be equally effective in attenuating the postpr and ial blood glucose response as low-carbohydrate , high-fat enteral formulas without elevating the plasma triglyceride response Glycaemic index ( GI ) is used as an indicator to guide consumers in making healthier food choices . We compared the GI , insulin index ( II ) , and the area under the curve for blood glucose and insulin as glucose ( GR ) and insulin responses ( IR ) of a newly developed liquid nutritional formula with one commercially available liquid product with different types of carbohydrates . We then evaluated the glucose and insulin responses of two test foods with comparable energy density and protein percentage but presented in different food forms ( liquid vs. solid ) . Fourteen healthy women participated in the study . GI , II , GR , and IR were assessed after ( independent ) consumption of two liquid products and a solid breakfast meal . The two liquid foods showed comparable GI , whilst the liquid form appeared to produce lower median GI ( 25 vs. 54 ) , and II ( 52 vs. 98 ) values compared to the solid breakfast ( p < 0.02 ) . The median GR and IR for solid breakfast were respectively 44 % and 45 % higher compared to the liquid product ( p < 0.02 ) . Liquid formulas with different carbohydrate qualities produced comparable glucose responses , while foods with comparable energy density and protein percentage but different food form elicited differential effects on GI , II , GR , and IR . Nutrient quality and food form need to be taken into consideration when developing low GI products to manage glycaemic responses Background : The potential confounding effect of different amounts and proportions of macronutrients across eating patterns on meal or dietary glycemic index ( GI ) and glycemic load ( GL ) value determinations has remained partially unaddressed . Objective : The study aim ed to determine the effects of different amounts of macronutrients and fiber on measured meal GI and GL values . Design : Four studies were conducted during which participants [ n = 20 - 22 ; women : 50 % ; age : 50 - 80 y ; body mass index ( in kg/m2 ) : 25 - 30 ) ] received food challenges containing different amounts of the variable nutrient in a r and om order . Added to the st and ard 50 g available carbohydrate from white bread was 12.5 , 25 , or 50 g carbohydrate ; 12.5 , 25 , or 50 g protein ; and 5.6 , 11.1 , or 22.2 g fat from rice cereal , tuna , and unsalted butter , respectively , and 4.8 or 9.6 g fiber from oat cereal . Arterialized venous blood was sample d for 2 h , and measured meal GI and GL and insulin index ( II ) values were calculated by using the incremental area under the curve ( AUCi ) method . Results : Adding carbohydrate to the st and ard white-bread challenge increased glucose AUCi ( P < 0.0001 ) , measured meal GI ( P = 0.0066 ) , and mean GL ( P < 0.0001 ) . Adding protein ( 50 g only ) decreased glucose AUCi ( P = 0.0026 ) , measured meal GI ( P = 0.0139 ) , and meal GL ( P = 0.0140 ) . Adding fat or fiber had no significant effect on these variables . Adding carbohydrate ( 50 g ) , protein ( 50 g ) , and fat ( 11.1 g ) increased the insulin AUCi or II ; fiber had no effect . Conclusions : These data indicate that uncertainty in the determination of meal GI and GL values is introduced when carbohydrate-containing foods are consumed concurrently with protein ( equal amount of carbohydrate challenge ) but not with carbohydrate- , fat- , or fiber-containing foods . Future studies are needed to evaluate whether this uncertainty also influences the prediction of average dietary GI and GL values for eating patterns . This trial was registered at clinical trials.gov as NCT01023646 The glycaemic index ( GI ) concept was originally introduced to classify different sources of carbohydrate (CHO)-rich foods , usually having an energy content of > 80 % from CHO , to their effect on post-meal glycaemia . It was assumed to apply to foods that primarily deliver available CHO , causing hyperglycaemia . Low-GI foods were classified as being digested and absorbed slowly and high-GI foods as being rapidly digested and absorbed , result ing in different glycaemic responses . Low-GI foods were found to induce benefits on certain risk factors for CVD and diabetes . Accordingly it has been proposed that GI classification of foods and drinks could be useful to help consumers make ' healthy food choices ' within specific food groups . Classification of foods according to their impact on blood glucose responses requires a st and ardised way of measuring such responses . The present review discusses the most relevant method ological considerations and highlights specific recommendations regarding number of subjects , sex , subject status , inclusion and exclusion criteria , pre-test conditions , CHO test dose , blood sampling procedures , sampling times , test r and omisation and calculation of glycaemic response area under the curve . All together , these technical recommendations will help to implement or reinforce measurement of GI in laboratories and help to ensure quality of results . Since there is current international interest in alternative ways of expressing glycaemic responses to foods , some of these methods are discussed Elevated postpr and ial blood glucose levels constitute a global epidemic and a major risk factor for prediabetes and type II diabetes , but existing dietary methods for controlling them have limited efficacy . Here , we continuously monitored week-long glucose levels in an 800-person cohort , measured responses to 46,898 meals , and found high variability in the response to identical meals , suggesting that universal dietary recommendations may have limited utility . We devised a machine-learning algorithm that integrates blood parameters , dietary habits , anthropometrics , physical activity , and gut microbiota measured in this cohort and showed that it accurately predicts personalized postpr and ial glycemic response to real-life meals . We vali date d these predictions in an independent 100-person cohort . Finally , a blinded r and omized controlled dietary intervention based on this algorithm result ed in significantly lower postpr and ial responses and consistent alterations to gut microbiota configuration . Together , our results suggest that personalized diets may successfully modify elevated postpr and ial blood glucose and its metabolic consequences . VIDEO ABSTRACT Few studies have examined short term responses to the different contents of carbohydrate or fat in the meal , although long term effects of the high fat meal have been considered as compound risk factor for metabolic disorders . The aim of this study was to investigate the postpr and ial changes of plasma glucose , insulin and lipids upon intakes of high carbohydrate or high fat meal in young healthy women . Subjects were r and omly assigned to either the high carbohydrate meal ( HCM , 75 % carbohydrate , n=13 ) or the high fat meal ( HFM , 60 % fat , n=12 ) groups . The meals were prepared as isocaloric typical Korean menu . Blood sample s were obtained prior to and 30 , 60 , 90 , 120 , 180 and 240 minute after the meal . There were no significant differences on fasting blood parameters including glucose , insulin , lipids concentrations between the groups prior to the test . The HCM had higher blood glucose and insulin concentrations , reached the peak at 30 min and maintained for 240 min compared to the HFM ( P<0.05 ) . The HFM had higher plasma triglyceride ( TG ) and free fatty acid ( FFA ) concentrations , reached the peak at 120 min and maintained for 240 min compared to the HCM ( P<0.05 ) . It is concluded that macronutrients content in the meal may be an important determinant of postpr and ial substrate utilization in healthy women BACKGROUND AND AIMS Previous evidence suggests that dietary fat could influence the composition and size of triacylglycerols-rich lipoproteins ( TRL ) . In a controlled intervention study on healthy subjects , we evaluated the influence of 3 dietary interventions , with different types of fat on postpr and ial TRL particle size and number . METHODS AND RESULTS Volunteers followed three different diets for four weeks each , according to a r and omized crossover design . Western diet : 15 % protein , 47 % carbohydrates ( CHO ) , 38 % fat ( 22 % saturated fatty acid ( SFA ) ) ; Mediterranean diet : 15 % protein , 47 % CHO , 38 % fat ( 24 % monounsaturated fatty acid ( MUFA ) ) ; high CHO enriched with ALNA diet : 15 % protein , 55 % CHO , < 30 % fat ( 8 % polyunsaturated fatty acid ( PUFA ) ) . After a 12-h fast , volunteers consumed a breakfast with 1 g fat and 7 mg cholesterol per kg body weight and a fat composition similar to that consumed in each of the diets : Butter meal : 35 % SFA ; Olive oil meal : 36 % MUFA ; Walnut meal : 16 % PUFA , 4 % α-linolenic acid . Tryglicerides ( TG ) in TRL ( large and small TRL ) were determined by ultracentrifugation and size and number of lipoprotein particles were measured with Nuclear Magnetic Resonance Spectroscopy at different time points . The olive oil meal reduced the number of total TRL postpr and ial particles compared with the other meals ( P=0.002 ) . Moreover , the olive oil meal also increased the TRL particle size compared with the walnut meal ( P=0.001 ) . CONCLUSION Our data showed that short-term intake of the Mediterranean diet and the acute intake of an olive oil meal lead to the formation of a reduced number and higher-size TRL particle compared with other fat sources . These novel findings have implication s for underst and ing the postpr and ial lipoprotein mechanisms , and could favour the lower cardiovascular risk in Mediterranean countries Healthy male volunteers consumed hot lunches consisting of cooked white rice , fried chicken fillet , raisins , bigarreaus ( sweet cherries ) and curry sauce with carbohydrate : fat ratios of either 0.77 or 2.04 , and polysaccharide : ( mono + di)saccharide ratios ( P : MD ) varying between 5.3 and 0.95 . Before and at various time intervals after the start of the meal , blood sample s were analysed for glucose , insulin , triacylglycerol ( TG ) , free glycerol ( FG ) , free fatty acids ( FFA ) and cholesterol . Elevated postpr and ial glucose and insulin peaks were induced by the meals containing a larger amount of carbohydrate . The type of carbohydrate in the meal appeared to have little or no effect on the peak maximum . A small second glucose peak was seen at 2 h after the meals with P : MD greater than 3.1 . The TG concentration in the blood showed a similar and rapid rise . After the meal containing the largest amount of simple sugars , the TG curve levelled off 1 h after the start of the meal and then remained at a nearly constant level ( 1.5 mM ) . In contrast , a larger amount of complex carbohydrates induced a TG concentration which rapidly rose to a maximum of 1.75 mM , and subsequently decreased slowly to somewhat below that of the simple sugar-rich meal at 4 h. The postpr and ial curves after the fat-rich meals showed a continuous rise of TG up to a maximum of about 2 mM at 2 h , and a subsequent slow decrease . FG and FFA all showed a rapid drop immediately after the start of the consumption of the meals , followed by a rebound at 1 h. The postpr and ial curves of total cholesterol , as well as the areas below the curve of both total cholesterol and free , unesterified cholesterol were lower after the carbohydrate-rich meals than after the fat-rich meals . This is attributed to the larger amount of cholesterol in the fat-rich meals We investigated the effects of high-monounsaturated fatty acid ( MUFA ) versus high-carbohydrate enteral formula on post-pr and ial plasma glucose concentration and insulin response in Japanese patients with type 2 diabetes mellitus and healthy Japanese volunteers . Ten healthy volunteers aged 20.8 ± 1.2 years and 12 diabetic patients with good glycaemic control ( glycosylated haemoglobulin < 7 % ) aged 58.6 ± 7.7 years were r and omly assigned to take high-MUFA or high-carbohydrate formula after a 12-h overnight fast . The patients switched to the other formula after 7 days . Post-pr and ial plasma glucose and insulin response were significantly lower in all subjects after taking high-MUFA formula compared with high-carbohydrate formula . No differences were observed in free fatty acids , triglycerides and plasma glucagon between the two diet groups . In conclusion , a high-MUFA enteral formula suppresses post-pr and ial hyperglycaemia without exaggerated insulin secretion compared with a high-carbohydrate enteral diet in patients with type 2 diabetes and healthy subjects Importance Recent guidelines have recommended nonfasting for routine testing of lipid levels based on comparisons of nonfasting and fasting population s. However , no previous study has examined the association of cardiovascular outcomes with fasting vs nonfasting lipid levels measured in the same individuals . Objective To compare the association of nonfasting and fasting lipid levels with prospect ively ascertained coronary and vascular outcomes and to evaluate whether a strategy of using nonfasting instead of fasting lipid level measurement would result in misclassification of risk for individuals undergoing evaluation for initiation of statin therapy . Design , Setting , and Participants This post hoc prospect i ve follow-up of a r and omized clinical trial included 8270 of 10 305 participants from the Anglo-Sc and inavian Cardiac Outcomes Trial-Lipid Lowering Arm ( ASCOT-LLA ) with nonfasting and fasting lipid levels measured 4 weeks apart ( including 6855 participants with no prior vascular disease ) ( median follow-up , 3.3 years ; interquartile range , 2.8 - 3.6 years ) . Data were collected from February 1 , 1998 , to December 31 , 2002 , and analyzed from February 1 , 2016 , to November 30 , 2018 . Multivariable Cox models , adjusted for cardiovascular risk factors , were calculated for 40-mg/dL ( 1-mmol/L ) higher values of nonfasting and fasting lipids . Main Outcomes and Measures The trial 's primary end point consisted of major coronary events ( nonfatal myocardial infa rct ion [ MI ] and fatal coronary heart disease [ 212 events ] ) . Secondary analyses examined atherosclerotic cardiovascular disease ( ASCVD ) events ( including MI , stroke , and ASCVD death [ 351 events ] ) . Results Among the 8270 participants ( 82.1 % male ; mean [ SD ] age , 63.4 [ 8.5 ] years ) , nonfasting sample s had modestly higher triglyceride levels and similar cholesterol levels compared to fasting sample s. Associations of nonfasting lipid levels with coronary events were similar to those for fasting lipid levels . For example , adjusted hazard ratios ( HRs ) per 40-mg/dL of low-density lipoprotein cholesterol were 1.32 ( 95 % CI , 1.08 - 1.61 ; P = .007 ) for nonfasting levels and 1.28 ( 95 % CI , 1.07 - 1.55 ; P = .008 ) for fasting levels . For the primary prevention group , adjusted HRs were 1.42 ( 95 % CI , 1.13 - 1.78 ; P = .003 ) for nonfasting levels and 1.37 ( 95 % CI , 1.11 - 1.69 ; P = .003 ) for fasting levels . Results were consistent by r and omized treatment arm ( atorvastatin calcium , 10 mg/d , or placebo ) and similar for ASCVD events . Concordance of fasting and nonfasting lipid levels for classifying participants into appropriate ASCVD risk categories was high ( 94.8 % ) . Conclusions and Relevance Measurement of nonfasting and fasting lipid levels yields similar results in the same individuals for association with incident coronary and ASCVD events . These results suggest that routine measurement of nonfasting lipid levels may help facilitate ASCVD risk screening and treatment , including consideration of when to initiate statin therapy |
864 | 28,733,092 | CONCLUSION Exercise training could be effective in reducing sympathetic nerve activity in patients with heart failure . | OBJECTIVE To determine the effects of exercise training on sympathetic nerve activity in heart failure patients . | ABSTRACT Objective To analyze respiratory mechanics and hemodynamic alterations in an experimental model of chronic heart failure ( CHF ) following myocardial infa rct ion . Method Twenty-seven male adult Wistar rats were r and omized to CHF group ( n=12 ) or Sham group ( n=15 ) . Ten weeks after coronary ligation or sham surgery , the animals were anesthetized and su bmi tted to respiratory mechanics and hemodynamic measurements . Pulmonary edema as well as cardiac remodeling were measured . Results The CHF rats showed pulmonary edema 26 % higher than the Sham group . The respiratory system compliance ( Crs ) and the total lung capacity ( TLC ) were lower ( 40 % and 27 % , respectively ) in the CHF rats when compared to the Sham group ( P<0.01 ) . There was also an increase in tissue resistance ( Gti ) and elastance ( Hti ) ( 28 % and 45 % , respectively ) in the CHF group . Moreover , left ventricular end-diastolic pressure was higher ( 32 mmHg vs 4 mmHg , P<0.01 ) , while the left ventricular systolic pressure was lower ( 118 mmHg vs 130 mmHg , P=0.02 ) in the CHF group when compared to the control . Pearson ’s correlation coefficient showed a negative association between pulmonary edema and Crs ( r=–0.70 , P=0.0001 ) and between pulmonary edema and TLC ( r=–0.67 , P=0.0034 ) . Pulmonary edema correlated positively with Gti ( r=0.68 , P=0.001 ) and Hti ( r=0.68 , P=0.001 ) . Finally , there was a strong positive relationship between pulmonary edema and heart weight ( r=0.80 , P=0.001 ) . Conclusion Rats with CHF present important changes in hemodynamic and respiratory mechanics , which may be associated with alterations in cardiopulmonary interactions Background —Although heart failure is common among women with coronary disease , the risk factors for developing heart failure have not been well studied . We determined the risk factors for developing heart failure among postmenopausal women with established coronary disease . Methods and Results —This is a prospect i ve cohort study using data from the Heart and Estrogen/progestin Replacement Study ( HERS ) , a r and omized , blinded , placebo-controlled trial of 4.1 years ’ duration , and subsequent open-label observational follow-up for 2.7 years ( HERS II ) , performed at 20 US clinical centers between 1993 and 2000 . Of the 2763 postmenopausal women with established coronary disease in the HERS trial , we studied the 2391 women with no heart failure at baseline by self-report and physical examination . The primary outcome of this analysis was incident heart failure defined by hospital admission or death from heart failure . During the 6.3±1.4-year follow-up , 237 women ( 10 % ) developed heart failure . Nine predictors were identified : diabetes ( defined as a self-reported history of diabetes on treatment ) , atrial fibrillation , myocardial infa rct ion , creatinine clearance < 40 mL/min , systolic blood pressure > 120 mm Hg , current smoking , body mass index > 35 kg/m2 , left bundle-branch block , and left ventricular hypertrophy . R and omization to estrogen/progestin was not associated with heart failure ( hazard ratio=1.0 ; 95 % CI , 0.7 to 1.3 ) . Diabetes was the strongest risk factor ( adjusted hazard ratio=3.1 ; 95 % CI , 2.3 to 4.2 ) . Diabetic women with elevated body mass index or depressed creatinine clearance were at highest risk , with annual incidence rates of 7 % and 13 % , respectively . Among diabetic women , hyperglycemia was associated with heart failure risk ( adjusted hazard ratio=3.0 ; 95 % CI , 1.2 to 7.5 for fasting glucose > 300 mg/dL compared with fasting glucose 80 to 150 mg/dL ) . Conclusions —We identified 9 predictors of heart failure in postmenopausal women with coronary disease . Diabetes was the strongest risk factor , particularly when poorly controlled or with concomitant renal insufficiency or obesity BACKGROUND The effect of home-based exercise training on neurovascular control in heart failure patients is unknown . AIMS To test the hypothesis that home-based training would maintain the reduction in muscle sympathetic nerve activity ( MSNA ) and forearm vascular resistance ( FVR ) acquired after supervised training . METHODS AND RESULTS Twenty-nine patients ( 54+/-1.9 years , EF<40 % ) were r and omised into two groups : untrained control ( n=12 ) and exercise trained ( n=17 ) . Both groups underwent assessment of Quality of Life ( QoL ) , MSNA , and forearm blood flow . The exercise group underwent a 4-month supervised training program followed by 4 months of home-based training . After the initial 4 months of training , patients in the exercise group showed a significant increase in peak VO(2 ) and reduction in MSNA , compared to the untrained group , but this was not maintained during 4 months of home-based training . In contrast , the decrease in FVR ( 56+/-3 vs. 46+/-4 vs. 40+/-2 U , p=0.008 ) and the improvement in QOL that were achieved during supervised training were maintained during home-based training . CONCLUSIONS Home-based training following supervised training is a safe strategy to maintain improvements in QoL and reduction in FVR in chronic heart failure patients , but is an inadequate strategy to maintain fitness as estimated by peak VO(2 ) or reduction in neurohumoral activation 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 Stratification of the severity of heart failure has major prognostic and therapeutic implication s. OBJECTIVES The goal of this study was to test the hypothesis that exercise training reduces resting sympathetic neural activation in patients with chronic advanced heart failure . BACKGROUND Exercise training in heart failure has been shown to be beneficial , but its mechanisms of benefit remain unknown . METHODS Sixteen New York Heart Association class II to III heart failure patients , age 35 to 60 years , ejection fraction < or = 40 % were divided into two groups : 1 ) exercise-trained ( n = 7 ) , and 2 ) sedentary control ( n = 9 ) . A normal control exercise-trained group was also studied ( n = 8) . The four-month supervised exercise training program consisted of three 60 min exercise sessions per week , at heart rate levels that corresponded up to 10 % below the respiratory compensation point . Muscle sympathetic nerve activity ( MSNA ) was recorded directly from peroneal nerve using the technique of microneurography . Forearm blood flow was measured by venous plethysmography . RESULTS Baseline MSNA was greater in heart failure patients compared with normal controls ; MSNA was uniformly decreased after exercise training in heart failure patients ( 60 + /- 3 vs. 38 + /- 3 bursts/100 heart beats ) , and the mean difference in the change was significantly ( p < 0.05 ) greater than the mean difference in the change in sedentary heart failure or trained normal controls . In fact , resting MSNA in trained heart failure patients was no longer significantly greater than in trained normal controls . In heart failure patients , peak VO(2 ) and forearm blood flow , but not left ventricular ejection fraction , increased after training . CONCLUSIONS These findings demonstrate that exercise training in heart failure patients results in dramatic reductions in directly recorded resting sympathetic nerve activity . In fact , MSNA was no longer greater than in trained , healthy controls |
865 | 19,007,996 | TRD is associated with poorer clinical outcome , particularly among those who require multiple antidepressant medications . | BACKGROUND Treatment-resistant depression ( TRD ) is relatively common and accounts for a large proportion of the overall burden caused by depression .
We conducted a systematic review of outcome studies of TRD in order to summarise findings on the longer term outcome of TRD and make recommendations . | There have been no systematic follow-up studies of depressed patients with documented refractoriness to antidepressants treated with lithium augmentation . To assess their longitudinal course , 66 ( 88 % ) of an original cohort of 75 such patients were followed in a retrospective , naturalistic design for 29.0 + /- SD 15.3 months . At follow-up , 29 % had poor , 23 % fair , and 48 % good outcomes . An acute marked positive response to lithium augmentation predicted a good subsequent course . Acute partial and non-responders had a less benign outcome despite subsequent treatments . These findings indicate that outcomes of patients with documented refractory depression are heterogeneous . There is a suggestion that an acute marked response to lithium augmentation is sustained regardless of the duration of taking lithium , but this must be regarded as speculative BACKGROUND Treatment-resistant depression ( TRD ) is a long-term , disabling illness . We report on the characteristics and outcomes of a large cohort of patients with a level of treatment resistance that is very substantial and who were treated for 2 years with st and ard care . METHOD This 2-year prospect i ve , multicenter , observational study ( patients enrolled from January 2001 through July 2004 ) tracked the outcomes of 124 patients with treatment-resistant , nonpsychotic major depressive disorder ( N = 109 ) or bipolar depressed phase disorder ( N = 15 ) who received treatment as usual ( TAU ) ( i.e. , any therapeutic regimen agreed to by patients and psychiatrists , including medications , electroconvulsive therapy [ ECT ] , and psychotherapy ) . Treatments could be adjusted , started , and stopped as necessary . The primary outcome , treatment response , was defined a priori as > or = 50 % improvement from baseline as measured by the 30-item Inventory of Depressive Symptomatology-Self-Report ( IDS-SR-30 ) . Remission was defined as an IDS-SR-30 score of < or = 14 . The Medical Outcomes Study ( MOS ) 36-item Short Form Health Survey ( SF-36 ) was used to monitor quality -of-life changes . RESULTS The 12- and 24-month IDS-SR-30 response rates were 11.6 % ( 13/112 ) and 18.4 % ( 19/103 ) , respectively . Of the 13 responders at 12 months , only 5 were responders at 24 months . The 12- and 24-month IDS-SR-30 remission rates were 3.6 % ( 4/112 ) and 7.8 % ( 8/103 ) , respectively . Only 1 of the 4 12-month remitters was also a remitter at 24 months . The SF-36 indicated globally poor quality of life in this sample . CONCLUSIONS Despite the wide range of treatment options available for depression , the response rates , remission rates , and quality -of-life results in this study show that most patients with a substantial degree of treatment resistance continue to have significant symptomatology and functional disability when receiving TAU BACKGROUND This paper describes the Household Survey from the National Survey of Psychiatric Morbidity . This covered a sample drawn at r and om from the population of Britain , with the exception of the Highl and s and Isl and s of Scotl and . METHODS The Postcode Address file was used as the sampling frame . Nearly 13000 adults aged 16 - 65 were selected for interview , of whom 10108 ( 79.4 % ) were successfully interviewed . Eight per cent could not be contacted and 13 % refused interview . Psychiatric assessment was carried out by lay interviewers using the CIS-R. Subjects were also screened for psychosis , and screen-positive individuals were examined by psychiatrists using SCAN . RESULTS Sixteen per cent of subjects scored above the st and ard cut-off of 12 on the CIS-R. The overall 1-week prevalence of neurotic disorder was 12.3 % in males and 19.5 % in females . Unmarried and post-marital groups had high rates of disorder , as did single parents and people living on their own . Respondents in Social Class I had notably lower rates of neurotic disorder than the remainder of the sample . Unemployment was strongly associated with disorder . Subjects living in urban areas had a higher overall prevalence , but there was no significant variation by region . Black respondents had higher rates of disorders that were entirely explained by their age , family type and social class . Individual neurotic disorders were all significantly commoner in women , with the exception of panic disorder . The 1-year prevalence of functional psychoses was 4 per 1000 , with no sex difference . Alcohol and drug dependence was considerably more prevalent in men . CONCLUSIONS For the first time , the survey provides data on the prevalence and correlates of psychiatric disorder on a nationwide sample that can be used to inform equitable and effective national psychiatric services OBJECTIVE Selective serotonin reuptake inhibitors ( SSRIs ) are widely used to treat depression , but the rates , timing , and baseline predictors of remission in " real world " patients are not established . The authors ' primary objectives in this study were to evaluate the effectiveness of citalopram , an SSRI , using measurement-based care in actual practice , and to identify predictors of symptom remission in out patients with major depressive disorder . METHOD This clinical study included out patients with major depressive disorder who were treated in 23 psychiatric and 18 primary care " real world " setting s. The patients received flexible doses of citalopram prescribed by clinicians for up to 14 weeks . The clinicians were assisted by a clinical research coordinator in the application of measurement-based care , which included the routine measurement of symptoms and side effects at each treatment visit and the use of a treatment manual that described when and how to modify medication doses based on these measures . Remission was defined as an exit score of < or=7 on the 17-item Hamilton Depression Rating Scale ( HAM-D ) ( primary outcome ) or a score of < or=5 on the 16-item Quick Inventory of Depressive Symptomatology , Self-Report ( QIDS-SR ) ( secondary outcome ) . Response was defined as a reduction of > or=50 % in baseline QIDS-SR score . RESULTS Nearly 80 % of the 2,876 out patients in the analyzed sample had chronic or recurrent major depression ; most also had a number of comorbid general medical and psychiatric conditions . The mean exit citalopram dose was 41.8 mg/day . Remission rates were 28 % ( HAM-D ) and 33 % ( QIDS-SR ) . The response rate was 47 % ( QIDS-SR ) . Patients in primary and psychiatric care setting s did not differ in remission or response rates . A substantial portion of participants who achieved either response or remission at study exit did so at or after 8 weeks of treatment . Participants who were Caucasian , female , employed , or had higher levels of education or income had higher HAM-D remission rates ; longer index episodes , more concurrent psychiatric disorders ( especially anxiety disorders or drug abuse ) , more general medical disorders , and lower baseline function and quality of life were associated with lower HAM-D remission rates . CONCLUSIONS The response and remission rates in this highly generalizable sample with substantial axis I and axis III comorbidity closely resemble those seen in 8-week efficacy trials . The systematic use of easily implemented measurement-based care procedures may have assisted in achieving these results OBJECTIVE This study investigated the influence of incomplete recovery from first lifetime major depressive episodes on long-term outcome . METHOD After their first lifetime major depressive episode , patients were divided into asymptomatic ( N=70 ) and residual subthreshold depressive symptom ( N=26 ) recovery groups and compared on longitudinal course during up to 12 years of prospect i ve naturalistic follow-up . RESULTS Patients with residual subthreshold depressive symptoms during recovery had significantly more severe and chronic future courses . Those with residual symptoms relapsed to major and minor depressive episodes faster and had more recurrences , shorter well intervals , and fewer symptom-free weeks during follow-up than asymptomatic patients . CONCLUSIONS Resolution of major depressive episodes with residual subthreshold depressive symptoms , even the first lifetime episode , appears to be the first step of a more severe , relapsing , and chronic future course . When ongoing subthreshold symptoms continue after major depressive episodes , the illness is still active , and continued treatment is strongly recommended CONTEXT There are no studies of the natural history of major depressive disorder that lack prevalence and clinic biases . OBJECTIVES To estimate risk factors for first lifetime onset and parameters of chronicity following the first episode , including duration , recovery , and recurrence , and to search for predictors of each parameter . DESIGN Prospect i ve population -based cohort study with 23 years of follow-up . SETTING East Baltimore , Maryl and , an urban setting . PARTICIPANTS Probability sample of 3481 adult household residents in 1981 , including 92 with first lifetime onset of major depressive disorder during the course of the follow-up , and 1739 other participants followed up for at least 13 years . OUTCOME MEASURES Diagnostic Interview Schedule and Life Chart Interview . RESULTS Female participants showed higher risk of onset of disorder , longer duration of episodes , and a nonsignificant tendency for higher risk of recurrence . Sex was not related to recovery . The median episode length was 12 weeks . About 15 % of 92 individuals with first episodes did not have a year free of episodes , even after 23 years . About 50 % of first episode participants recovered and had no future episodes . The evolution of the course was relatively stable from first to later episodes . Individuals with 1 or 2 short alleles of the serotonin transporter gene were at higher risk for an initial episode , but experienced episodes of shorter duration . There were few strong predictors of recovery or recurrence . CONCLUSIONS Major depressive disorder is unremitting in 15 % of cases and recurrent in 35 % . About half of those with a first-onset episode recover and have no further episodes Eighty-nine consecutive admissions with primary depressive illness were prospect ively ascertained and diagnosed in 1965 - 66 by R. E. Kendell , who also allocated each a position on a neurotic-psychotic continuum on the basis of previous discriminant function analysis . In 1983 - 84 , 94 % of the survivors were personally interviewed by a psychiatrist blind to index admission data . Operational outcome criteria were employed and longitudinal data were established for 98 % of the series . Mortality risk was doubled overall , and increased sevenfold for women under 40 years at index admission . Less than one-fifth of the survivors had remained well , and over one-third of the series suffered unnatural death or severe chronic distress and h and icap . Patients whose index episode marked their first psychiatric contact had a 50 % chance of readmission within their lifetime , but those with previous admissions had a 50 % chance of readmission within three years . Readmissions occurred even after 12 years of being symptom-free , and conversely patients recovered after as long as 15 years of illness . There was a high incidence of other disorders ( schizoaffective disorder , alcoholism , schizophrenia ) , and only four patients showed pure recurrent unipolar histories . Patients at the psychotic end of the continuum were more likely to be readmitted and to have very poor outcomes BACKGROUND To investigate the mortality rates in affective disorders due to unnatural and natural causes with respect to illness subtype and social-demographic features . METHODS Mortality data were determined from a prospect i ve study of 354 out patients with affective disorders during a follow-up period of 5 years . Death from natural and unnatural causes was compared to sex- and age-specific expectations in the general population . St and ardized mortality rates ( SMR ) in diagnostic subgroups and the influence of social-demographic features were investigated . RESULTS The observed 30 deaths represented nearly three times ( SMR , 2.9 ) the number expected on the basis of age- and sex-st and ardized reference population rates . Death from natural causes occurred with the same rate as expected ( SMR , 1.0 ) , death from unnatural causes was 28.8 times higher than expected . Women with affective disorders had a considerable high risk to die from unnatural causes ( SMR , 47.1 ) . A significant excess of unnatural death was found in all subtypes of affective disorders , particularly in recurrent major depressive episodes ( SMR , 46.7 ) . LIMITATIONS The sample was restricted in size . Therefore subgroup differences and multiple relationships of risk factors could not be analyzed with high statistical power . CONCLUSIONS The results corroborate earlier findings of excess mortality in major affective disorders and strengthen the view that suffering from recurrent major depression confers per se an important biological risk for suicide . Natural causes of death in affective disorders are comparable to expectations from reference population s. Social-demographic characteristics may contribute to an additional risk of premature death by suicide , particularly in women BACKGROUND Previous reports have described the effects of vagus nerve stimulation plus treatment as usual ( VNS+TAU ) during open trials of patients with treatment-resistant depression ( TRD ) . To better underst and these effects on long-term outcome , we compared 12-month VNS+TAU outcomes with those of a comparable TRD group . METHODS Admission criteria were similar for those receiving VNS+TAU ( n = 205 ) or only TAU ( n = 124 ) . In the primary analysis , repeated- measures linear regression was used to compare the VNS+TAU group ( monthly data ) with the TAU group ( quarterly data ) according to scores of the 30-item Inventory of Depressive Symptomatology-Self-Report ( IDS-SR(30 ) ) . RESULTS The two groups had similar baseline demographic data , psychiatric and treatment histories , and degrees of treatment resistance , except that more TAU participants had at least 10 prior major depressive episodes , and the VNS+TAU group had more electroconvulsive therapy before study entry . Vagus nerve stimulation plus treatment as usual was associated with greater improvement per month in IDS-SR(30 ) than TAU across 12 months ( p < .001 ) . Response rates according to the 24-item Hamilton Rating Scale for Depression ( last observation carried forward ) at 12 months were 27 % for VNS+TAU and 13 % for TAU ( p < .011 ) . Both groups received similar TAU ( drugs and electroconvulsive therapy ) during follow-up . CONCLUSIONS This comparison of two similar but nonr and omized TRD groups showed that VNS+TAU was associated with a greater antidepressant benefit over 12 months BACKGROUND There is still a relative paucity of information about the long-term course of depression . METHODS Consecutive patients admitted to a teaching hospital psychiatry unit with symptoms of depression , previously assessed at 6 months and 2 , 5 and 15 years after index admission , were review ed at 25 years ( N = 49 , including eight informants of deceased prob and s , of an original 145 with major depression ( DEPs ) ) . Prospect i ve psychiatric ( N = 22 ) and retrospective surgical ( N = 50 ) control groups assessed after 25 years were used for comparison . RESULTS A further decade of follow-up confirmed the chronicity of depression . Of depressed patients ( DEPs ) followed for the full 25-year-period only 12 % of the 49 original DEPs recovered and remained continuously well , 84 % experienced recurrences , 2 % experienced an unremitting course and another 2 % died by suicide . Note that in the first 15-year-period 6 % ( 9/145 DEPs ) committed suicide , a further 38 died and 32 were lost to follow-up . They experienced an average of three episodes of depression over the 25 years . In the decade since the 15-year follow-up , 27 % improved in clinical outcome ( including four of five previously chronically depressed patients ) , 55 % remained unchanged and 18 % worsened ; and the number of episodes per year declined . Patients initially diagnosed with neurotic or endogenous depression had similar long-term outcomes . The criteria for a current DSM-III-R disorder were met by 37 % of DEPs , including 11 % with depression or dysthymia . On the global assessment of functioning scale 78 % of the DEPs had some impairment compared to 62 % of psychiatric controls and 40 % of surgical controls . CONCLUSION Even after 25 years , severe depressive disorders appear to have poor long-term outcomes . Patients with chronic outcomes over 15 years can improve when followed over longer periods BACKGROUND The long-term course of depression in patients who present for treatment carries prognostic and therapeutic implication s. This study presents prospect i ve data on the time to recovery from an episode of major depressive disorder of 5 years ' duration among patients followed up since 1978 in the National Institutes of Mental Health Collaborative Program on the Psychobiology of Depression . METHODS Survival analysis was used to examine the 10-year course of the 431 prob and s with major depressive disorder with a specific focus on the 35 prob and s who were observed to be continuously ill for the first 5 years . Univariate analytic techniques were used to describe the demographic and clinical variables in the group that recovered and the group that did not . By study design , somatic treatment was assessed but not controlled by the investigators . RESULTS By year 10 , 93 % ( Kaplan-Meier estimate ) of prob and s had recovered from their intake episode of major depressive disorder . In those ill for the first 5 years , 38 % had recovered within the next 5 years . Shorter duration of illness prior to intake and being married were associated with the group that recovered . Pharmacological treatment dosages averaged 100 mg of imipramine hydrochloride equivalent in the chronically ill group . CONCLUSIONS Despite lengthy periods of illness , people continued to recover from major depressive disorder for up to 10 years of prospect i ve follow-up . Few demographic and clinical variables distinguished those who recovered from those who did not . Treatment , as observed in this naturalistic study , was at a low level despite lengthy illness |
866 | 27,268,103 | A positive effect on completion was noted in intervention studies that used short regimens and social interventions ; mixed results were found for intervention studies that used DOT or incentives .
Conclusion LTBI treatment completion can be improved by using shorter regimens and social interventions . | Background Latent tuberculosis infection ( LTBI ) control relies on high initiation and completion rates of preventive treatment to preclude progression to tuberculosis disease .
Specific interventions may improve initiation and completion rates .
The objective was to systematic ally review data on determinants of initiation , adherence and completion of LTBI treatment , and on interventions to improve initiation and completion . | BACKGROUND Few studies have examined predictors of latent tuberculosis infection ( LTBI ) treatment completion in inner city population s in the United States . OBJECTIVE To assess LTBI treatment completion rates and predictors in an inner city cohort . METHODS Data from control groups of two sequentially conducted r and omized controlled trials of LTBI treatment were analyzed for treatment completion rates . Participants in Study A ( n = 191 ) , conducted in 1996 - 1999 , self administered daily isoniazid ( INH ) for 6 - 12 months , while participants in Study B ( n = 123 ) , conducted in 2002 - 2005 , self administered daily INH for 9 months . RESULTS Overall , 44.6 % of participants completed therapy , with significantly higher completion rates in Study B than Study A ( 37.0 % vs. 56.1 % , P = 0.001 ) . Marriage and alcohol use were significant predictors of completion ( aOR = 2.153 , 95%CI 1.301 - 3.562 ) and non-completion ( aOR = 0.530 , 95%CI 0.320 - 0.877 ) , respectively ; multivariate analysis indicated increased completion among married persons of foreign birth and among alcohol users who were homeless . Knowledge of and attitudes to tuberculosis were not significant predictors . CONCLUSIONS The design provided an opportunity to assess predictors of LTBI treatment completion in this inner city population . Social circumstances were the strongest predictors of treatment completion , suggesting that tangible social services may be more effective than educational programs in encouraging treatment completion BACKGROUND Drug users are at increased risk for latent tuberculosis infection ( LTBI ) and also at increased risk for noncompletion of medication regimens for treatment of LTBI or tuberculosis disease . Directly observed therapy ( DOT ) provided by outreach workers , the use of incentives , or both have been suggested as a means to increase adherence . OBJECTIVE To compare the independent and combined effects of monetary incentives and outreach worker provision of DOT for LTBI treatment in a sample of active drug users . METHODS The research design was a r and omized controlled trial in a community outreach program setting . Participants consisted of a volunteer sample of 163 active injection drug and crack cocaine users placed on twice weekly DOT . Condition 1 of the interventions consisted of provision of DOT by an outreach worker at a location chosen by the participant ( active outreach ) and a $ 5 per visit incentive . Condition 2 was comprised of active outreach with no monetary incentive , and Condition 3 , provision of DOT at the study community site and a $ 5 per visit incentive . The main outcome measures were percentage of medication taken as prescribed and completion of medication regimen . RESULTS The percentage of prescribed medication taken was higher for those who received incentives , either with ( 71 % ) or without ( 68 % ) active outreach , compared to those who received active outreach alone ( 13 % ) . Only 4 % of participants assigned to Condition 2 completed treatment , compared to 53 % of Condition 1 participants , and 60 % of Condition 3 participants . CONCLUSIONS Monetary incentives were clearly superior to active outreach . Active outreach in combination with monetary incentives did not increase adherence over incentives alone BACKGROUND Cases of severe and fatal liver injury were reported after a 2-month course of rifampin-pyrazinamide therapy was recommended in 2000 as an alternative to isoniazid for treatment of latent tuberculosis infection . We estimated rates of rifampin-pyrazinamide-associated liver injury and compared these with historical rates for isoniazid . METHODS We conducted a survey of state and city tuberculosis programs and other health care setting s in the United States where rifampin-pyrazinamide was prescribed . The number of rifampin-pyrazinamide therapy initiations was collected , as well as the number of occurrences of ( 1 ) asymptomatic aspartate aminotransferase serum concentration > 5 times the upper limit of normal , ( 2 ) symptomatic hepatitis ( in which the patient was not hospitalized ) , ( 3 ) hospitalization for liver injury , ( 4 ) death with liver injury , and ( 5 ) treatment completion . We also search ed a national pharmacy cl aims data base ( Verispan ) . Rates of these events were calculated . RESULTS Among 139 programs , 110 ( 79 % ) responded ; 87 ( 79 % ) had initiated rifampin-pyrazinamide therapy for a total of 8087 patients between January 2000 and June 2002 . Rates per 1000 rifampin-pyrazinamide therapy initiations during this period were 25.6 ( 95 % confidence interval [ CI ] , 22.3 - 29.3 ) for asymptomatic aspartate aminotransferase level > 5 times the upper limit of normal and 18.7 ( 95 % CI , 15.9 - 21.9 ) for hepatitis . Seven fatalities and 23 hospitalizations occurred , with rates of 0.9 ( 95 % CI , 0.4 - 1.9 ) and 2.8 ( 95 % CI , 1.8 - 4.3 ) per 1000 rifampin-pyrazinamide therapy initiations , respectively . Of 8087 patients , 64 % completed rifampin-pyrazinamide therapy . The Verispan search revealed 1 rifampin-pyrazinamide-associated hospitalization ( 2.9 hospitalizations per 1000 rifampin-pyrazinamide therapy initiations ; 95 % CI , 0.1 - 18.4 ) and no deaths . Articles on the use of isoniazid therapy for latent tuberculosis infection that were published after 1990 reported fatality rates of 0.0 - 0.3 deaths per 1000 persons . CONCLUSIONS Rates of liver injury , hospitalization , and death associated with rifampin-pyrazinamide therapy exceed rates reported for isoniazid therapy . Because earlier r and omized trials of rifampin-pyrazinamide lacked adequate statistical power to detect fatal events , the Centers for Disease Control and Prevention recommends that rifampin-pyrazinamide generally should not be used for treatment of latent tuberculosis infection SETTING Few studies have examined strategies for optimizing adherence to latent tuberculosis infection ( LTBI ) treatment programs in homeless population s. OBJECTIVES 1 ) To compare the effectiveness of an intervention program employing nurse case management and incentives ( NCMI ) vs. a control program with st and ard care and incentives on completion of LTBI treatment ; and 2 ) to compare the impact of the two programs on tuberculosis ( TB ) knowledge among participants . DESIGN A prospect i ve , two-group site-r and omized design conducted among 520 homeless adults residing in the Skid Row region of Los Angeles from 1998 to 2003 , assessing completion rates of a 6-month isoniazid ( INH ) treatment program and change in TB knowledge . RESULTS Using intent-to-treat analysis , 62 % of participants in the intervention program , compared with 39 % of controls , completed the full 6-month course of LTBI treatment with INH . Logistic regression modeling revealed that intervention participants had three times greater odds of completing INH treatment than controls . TB knowledge improved in both programs , but the increase was greater among the intervention participants ( P < 0.001 ) . CONCLUSIONS Nurse case management combined with education , incentives , and tracking dramatically improves both adherence to LTBI treatment and TB knowledge in homeless persons compared to a st and ard approach of outreach and incentives BACKGROUND A 9-month course of isoniazid monotherapy is currently recommended for the treatment of latent tuberculosis infection ( LTBI ) and has been shown to be effective in both children and adults . Reduced compliance with this regimen has forced physicians to explore shorter regimens . The aim of this study was to compare 3- and 4-month combination regimens of isoniazid plus rifampin with a 9-month regimen of isoniazid monotherapy for the treatment of LTBI in children . METHODS This prospect i ve , r and omized , controlled study was conducted over an 11-year period ( 1995 - 2005 ) . In period 1 ( 1995 - 1998 ) , 232 patients received isoniazid therapy for 9 months ( group A ) , and 238 patients received isoniazid and rifampin for 4 months ( group B ) . In period 2 ( 1999 - 2002 ) , 236 patients were treated with isoniazid and rifampin for 4 months ( group C ) , and 220 patients received the same regimen for 3 months ( group D ) . All patients were observed for > or = 3 years . RESULTS Overall compliance with treatment was good , but patients who received isoniazid monotherapy were less compliant than were those who received short-course combination therapy ( P=.011 , for group A vs. group B ; P=.510 , for group C vs. group D ) . No patient in any group developed clinical disease during the follow-up period . New radiographic findings suggestive of possible active disease were more common in patients who received isoniazid monotherapy ( 24 % ) than in those treated with shorter regimens ( 11.8 % , 13.6 % , and 11 % for groups B , C , and D , respectively ; P=.001 for group A vs. group B ; P=.418 for group C vs. group D ) . Serious drug-related adverse effects were not detected . CONCLUSIONS Short-course treatment with isoniazid and rifampin for 3 - 4 months is safe and seems to be superior to a 9-month course of isoniazid monotherapy Background Treatment of latent tuberculosis infection ( LTBI ) is a key component in U.S. tuberculosis control , assisted by recent improvements in LTBI diagnostics and therapeutic regimens . Effectiveness of LTBI therapy , however , is limited by patients ’ willingness to both initiate and complete treatment . We aim ed to evaluate the demographic , medical , behavioral , attitude-based , and geographic factors associated with LTBI treatment initiation and completion of persons presenting with LTBI to a public health tuberculosis clinic . Methods Data for this prospect i ve cohort study were collected from structured patient interviews , self-administered question naires , clinic intake forms , and U.S. census data . All adults ( > 17 years ) who met CDC guidelines for LTBI treatment between January 11 , 2008 and May 6 , 2009 at Wake County Health and Human Services Tuberculosis Clinic in Raleigh , North Carolina were included in the study . In addition to traditional social and behavioral factors , a three-level medical risk variable ( low , moderate , high ) , based on risk factors for both progression to and transmission of active tuberculosis , was included for analysis . Clinic distance and neighborhood poverty level , based on percent residents living below poverty level in a person ’s zip code , were also analyzed . Variables with a significance level < 0.10 by univariate analysis were included in log binomial models with backward elimination . Models were used to estimate risk ratios for two primary outcomes : ( 1 ) LTBI therapy initiation ( picking up one month ’s medication ) and ( 2 ) therapy completion ( picking up nine months INH therapy or four months rifampin monthly ) . Results 496 persons completed medical interviews and question naires addressing social factors and attitudes toward LTBI treatment . 26 % persons initiated LTBI therapy and 53 % of those initiating completed therapy . Treatment initiation predictors included : a non-employment reason for screening ( RR 1.6 , 95 % CI 1.0 - 2.5 ) , close contact to an infectious TB case ( RR 2.5 , 95 % CI 1.8 - 3.6 ) , regular primary care(RR 1.4 , 95 % CI 1.0 - 2.0 ) , and history of incarceration ( RR 1.7 , 95 % CI 1.0 - 2.8 ) . Persons in the “ high ” risk category for progression/transmission of TB disease had higher likelihood of treatment initiation ( p < 0.01 ) , but not completion , than those with lower risk . Conclusions Investment in social support and access to regular primary care may lead to increased LTBI therapy adherence in high-risk population Context Guidelines from the American Thoracic Society and Centers for Disease Control and Prevention for treating latent tuberculosis infection advocate 2 months of rifampin plus pyrazinamide as an effective alternative to 6 to 9 months of isoniazid or 4 months of rifampin . However , case reports have described severe liver injury in patients who were receiving the 2-month regimen . Contribution This nonr and omized , open-label trial found that the risk for grade 3 or 4 liver injury was higher in patients taking 2 months of rifampin plus pyrazinamide ( 7.7 % ) than in patients taking 6 months of isoniazid ( 1 % ) . Clinical Implication s If clinicians use the short-course regimen , they should vigilantly follow patients ' liver enzyme levels . The Editors As rates of tuberculosis cases in the United States have decreased ( 1 , 2 ) , the focus of prevention and control efforts has shifted toward identification and treatment of persons with latent tuberculosis infection who are at increased risk for developing tuberculosis . This approach was endorsed in a recent report from the Institute of Medicine ( 3 ) . Isoniazid given for at least 6 months has been the st and ard therapy for latent tuberculosis infection for decades , but its use has been limited by toxicity , especially hepatitis ( 4 - 6 ) , and by poor adherence to treatment ( 7 ) . A 2-month course of rifampin and pyrazinamide has been shown to be effective and well tolerated as treatment of latent tuberculosis infection in HIV-infected persons ( 8 - 10 ) . Guidelines from the American Thoracic Society and Centers for Disease Control and Prevention ( 11 ) offer three main regimens for treatment of latent tuberculosis infection : isoniazid for 6 to 9 months , rifampin for 4 months , or rifampin and pyrazinamide for 2 months . However , there is relatively little experience with use of rifampin plus pyrazinamide to treat latent tuberculosis infection in persons without HIV infection , and case reports of severe hepatitis causing five deaths have raised concerns about the safety of the regimen ( 12 , 13 ) . We therefore conducted a multicenter , prospect i ve , open-label trial comparing daily treatment with rifampin and pyrazinamide for 2 months with daily treatment with isoniazid for 6 months in nonHIV-infected adults with latent tuberculosis infection ( the Short-Course Rifampin and Pyrazinamide for Tuberculosis Infection [ SCRIPT ] study ) . Our primary goals were to compare risk for toxicity , particularly hepatotoxicity , and completion of therapy . We also investigated whether persons with latent tuberculosis infection who were older than 35 years of age , a group known to have increased rates of hepatitis while taking isoniazid ( 5 ) , would have fewer adverse events while taking rifampin plus pyrazinamide than while taking isoniazid . Methods Patients All adults older than 17 years of age who had a positive tuberculin skin test ( as defined by American Thoracic Society/Centers for Disease Control and Prevention criteria [ 11 ] ) and in whom active tuberculosis was excluded and treatment of latent tuberculosis infection would ordinarily be recommended ( for example , persons with close contact to an infectious case or those with a medical risk factor , such as diabetes ) were eligible for the study . In addition , we enrolled foreign-born persons older than 35 years of age who had been in the United States for fewer than 6 years . These latter patients were not included in the American Thoracic Society/Centers for Disease Control and Prevention guidelines when the study was begun . Before being invited to participate , all patients who met initial criteria for enrollment were asked about previous liver disease , current medications and illnesses , previous gout , and risk factors for HIV infection . Liver enzymes ( alanine aminotransferase [ ALT ] , aspartate aminotransferase , and alkaline phosphatase ) , bilirubin , and creatinine were measured . Testing for and counseling about HIV infection were recommended for patients whose HIV status was not known , and a urine pregnancy test was performed for all women of childbearing age . During their baseline visit , patients underwent a review of symptoms that included history of nausea , vomiting , jaundice , abdominal pain , weight loss , arthralgia , headache , and neuropathy . Exclusion criteria were pregnancy , HIV infection , serum creatinine concentration more than twice the upper limit of normal , serum aspartate aminotransferase or ALT level more than three times the upper limit of normal , and a history of gout . Institutional review boards at each site approved the study , and written informed consent was obtained from all patients . Design Persons who met study criteria and agreed to participate were allocated in alternate weeks to receive rifampin ( 600 mg/d ) plus pyrazinamide ( 20 mg/kg of body weight daily ) for 2 months or isoniazid ( 300 mg/d ) for 6 months ( the recommended minimum duration when the study started [ 14 ] ) . Tables were used to st and ardize weight-based dosing of pyrazinamide to the closest 250 mg . At each site , the allocation during the first week of patient enrollment was determined by a coin toss . For the remainder of the trial , allocation to treatment regimen was alternated weekly . This systematic allocation design was chosen for ease of implementation in busy public health tuberculosis clinics in San Francisco , Boston , and Atlanta . Serum levels of liver enzymes and bilirubin were measured in all patients after 1 month of treatment . Patients receiving isoniazid had repeated liver enzyme testing at 3 months . Patients receiving rifampin and pyrazinamide also had a complete blood count and measurement of uric acid and creatinine after 1 month of treatment . All treatment was self-administered , and specific incentives , financial or otherwise , were not provided . All patients received monthly supplies of medication and were instructed to take medication daily and return in 1 month ( or sooner if any of the symptoms mentioned previously occurred ) . At each visit , patients were evaluated for signs and symptoms of adverse events by tuberculosis control nurses and evaluated for adherence to treatment . Hepatotoxicity was based on the World Health Organization classification and was defined as grade 1 for any serum ALT level of 51 to 125 U/L , or 1.25 to 2.5 times normal ; grade 2 for any serum ALT level of 126 to 250 U/L , or 2.6 to 5.0 times normal ; grade 3 for any serum ALT level of 251 to 500 U/L , or 5.1 to 10.0 times normal ; and grade 4 for any serum ALT level greater than 500 U/L , or > 10 times normal , or greater than 250 U/L if accompanied by compatible symptoms ( 15 ) . At the 1-month evaluation in recipients of rifampin plus pyrazinamide or the 3-month evaluation in isoniazid recipients , patients who had grade 1 or 2 liver injury continued to take study medication and had repeated liver enzyme testing in 2 weeks . In patients with grade 3 hepatotoxicity , treatment with study drugs was stopped and not resumed unless another cause of hepatitis could be found ( such as alcohol abuse ) . Treatment with study drugs was permanently discontinued in patients with grade 4 hepatotoxicity . Outcomes Primary end points were development of any adverse event , especially grade 3 or 4 hepatotoxicity , and completion of the prescribed amount of treatment . Adverse events were determined on the basis of interviews and by laboratory examination when indicated . Completion of the regimen was defined as taking at least 80 % of prescribed medication . Statistical Analysis A sample of 540 patients was calculated to provide 80 % power in two-sided tests , with an value of 0.05 , to detect an increase in the expected incidence of hepatotoxicity of any grade ( the primary end point ) from 15 % in the isoniazid group to 25 % in the rifampin plus pyrazinamide group . The first patient was enrolled on 15 February 1999 . A scheduled interim analysis of the first 313 patients that was performed in July 2000 indicated no statistically significant differences between the two groups in terms of adverse events or completion of therapy . Enrollment continued until October 2000 . Between-regimen comparisons of hepatotoxicity , other adverse events , and completion were based on the treatment initially assigned , without regard to the duration of treatment actually received . In an initial analysis of treatment effects on hepatotoxicity , the Fisher exact test was used to compare the proportion of patients with ALT values greater than 250 U/L among 411 participants who had liver enzyme testing at 1 or 3 months . Confirmatory analyses were then used to vali date the initial result . Because the study was not r and omized , treatment assignment was potentially confounded by imbalances in baseline covariates between the two treatment groups . In addition , grade 3 or 4 hepatotoxicity was uncommon . Therefore , to adjust for potential confounding , the initial exact analysis of hepatotoxicity was repeated with stratification by quintile of a propensity score that was estimated by using a multivariable logistic model for treatment assignment ( 16 , 17 ) . Furthermore , liver enzyme values were missing for 78 of 282 ( 27.7 % ) patients in the isoniazid group and 100 of 307 ( 32.6 % ) patients in the rifampin plus pyrazinamide group . To correct for this possible source of bias , we used multiple imputation . Specifically , the odds ratio for treatment was estimated in each of 10 data sets with imputed values for the missing liver enzyme tests by using logistic models to adjust for the propensity score as a continuous covariate . In the final step , a summary odds ratio estimate was calculated by using st and ard methods ( 18 , 19 ) . In a further analysis , treatment-by-site interaction was examined in an exact analysis that was stratified by site . We also used logistic models to assess possible violations of independence due to clustering by site by comparing model-based st and ard errors with robust st and ard errors that accounted for within-site correlation . Finally , more common outcomes , including BACKGROUND Treatment of latent TB infection ( LTBI ) is essential for preventing TB in North America , but acceptance and completion of this treatment have not been systematic ally assessed . METHODS We performed a retrospective , r and omized two-stage cross-sectional survey of treatment and completion of LTBI at public and private clinics in 19 regions of the United States and Canada in 2002 . RESULTS At 32 clinics that both performed tuberculin skin testing and offered treatment , 123 ( 17.1 % ; 95 % CI , 14.5%-20.0 % ) of 720 subjects tested and offered treatment declined . Employees at health-care facilities were more likely to decline ( odds ratio [ OR ] , 4.74 ; 95 % CI , 1.75 - 12.9 ; P = .003 ) , whereas those in contact with a patient with TB were less likely to decline ( OR , 0.19 ; 95 % CI , 0.07 - 0.50 ; P = .001 ) . At 68 clinics starting treatment regardless of where skin testing was performed , 1,045 ( 52.7 % ; 95 % CI , 48.5%-56.8 % ) of 1,994 people starting treatment failed to complete the recommended course . Risk factors for failure to complete included starting the 9-month isoniazid regimen ( OR , 2.08 ; 95 % CI , 1.23 - 3.57 ) , residence in a congregate setting ( nursing home , shelter , or jail ; OR , 2.94 ; 95 % CI , 1.58 - 5.56 ) , injection drug use ( OR , 2.13 ; 95 % CI , 1.04 - 4.35 ) , age > or= 15 years ( OR , 1.49 ; 95 % CI , 1.14 - 1.94 ) , and employment at a health-care facility ( 1.37 ; 95 % CI , 1.00 - 1.85 ) . CONCLUSIONS Fewer than half of the people starting treatment of LTBI completed therapy . Shorter regimens and interventions targeting residents of congregate setting s , injection drug users , and employees of health-care facilities are needed to increase completion OBJECTIVES We sought to determine the efficacy of coaching Latino adolescents with latent tuberculosis infection to adhere to isoniazid treatment . METHODS Participants ( n = 286 ) were r and omly assigned to adherence coaching , attention control , or usual care groups . Adherence was measured via interviews and vali date d with urine assays . RESULTS Coaching result ed in significant increases in adherence compared with attention and usual care groups . Bicultural adolescents were more likely to be adherent than those most or least acculturated . Age and risk behavior were negatively related to adherence . CONCLUSIONS Coaching can increase Latino adolescents ' adherence to treatment for latent tuberculosis infection and should contribute to tuberculosis control for adolescents at high risk of contracting the disease SETTING Nine public health care centres in four Spanish cities . OBJECTIVE To evaluate the efficacy and safety of 2 months of rifampicin ( R ) plus pyrazinamide ( Z ) therapy ( 2RZ ) compared with a 6-month course of isoniazid therapy ( 6H ) for treating latent tuberculosis infection ( LTBI ) . DESIGN Multicentered , r and omised , comparative and prospect i ve trial conducted in HIV-seronegative contacts of infectious pulmonary TB cases . RESULTS Of 352 individuals , 199 received 6H and 153 2RZ ; 73 % of contacts receiving 6H and 71 % receiving 2RZ completed treatment ( P = 0.73 ) . Treatment interruption due to hepatotoxicity ( ALT/AST > 5 times upper limit of normal ) was observed in 10 % of contacts in the 2RZ group and in 2.5 % of the 6H group ( P = 0.007 ) . This higher than expected rate of hepatotoxicity in the 2RZ arm led to premature termination of the study . Severe or fatal liver injury was not detected . Liver function tests normalised after discontinuation of treatment . We conclude that the use of RZ should only be considered when other regimens are unsuitable and intensive monitoring of liver function is feasible There is little published information regarding treatment completion , safety , and efficacy of rifampin administered daily for 4 months-a recommended alternative to 9 months of isoniazid for therapy of latent tuberculosis infection . In an open-label r and omized trial at a university-affiliated respiratory hospital , consenting patients whose treating physician had recommended therapy for latent tuberculosis infection were r and omized to daily self-administered rifampin for 4 months or daily self-administered isoniazid for 9 months . Of 58 patients r and omized to rifampin , 53 ( 91 % ) took 80 % of doses , and 50 ( 86 % ) took more than 90 % of doses within 20 weeks compared with 44 ( 76 % ) and 36 ( 62 % ) who took 80 and 90 % , respectively , of doses of isoniazid within 43 weeks ( relative risks : 80 % of doses , 1.2 [ 95 % confidence interval : 1.02 , 1.4 ] ; 90 % of doses , 1.4 [ 1.1 , 1.7 ] ) . Adverse events result ed in permanent discontinuation of therapy for two ( 3 % ) patients taking rifampin , and for eight ( 14 % ) patients taking isoniazid . Three patients developed drug-induced hepatitis -- all were taking isoniazid . Total costs of therapy were significantly higher for isoniazid . In conclusion , completion of therapy was significantly better with 4 months of rifampin and major side effects were somewhat lower . Further studies are needed to assess the safety and efficacy of the 4-month rifampin regimen PURPOSE Assess the costs and cost-effectiveness of an incentive-based tuberculosis ( TB ) program design ed to promote adolescents ' compliance with treatment for latent TB infection ( LTBI ) . METHODS R and omized controlled trial . Adolescents between the ages of 11 and 19 years who were referred to one of two participating clinics after being screened for TB and receiving a positive diagnosis indicating LTBI ( n = 794 ) were assigned to one of four groups : usual care , peer counseling , contingency contracting , and combined peer counseling/contingency contracting . Primary outcome variables were completion of isoniazid preventive therapy ( IPT ) , total treatment costs , and lifetime TB-related costs per quality -adjusted life year ( QALY ) in each of the four study groups ( three treatment , one control ) . Cost effectiveness was evaluated using a five-stage Markov model and a Monte Carlo simulation with 10,000 trials . RESULTS Average costs were 199 dollars for usual care ( UC ) , 277 dollars for peer counseling ( PC ) , 326 dollars for contingency contracting ( CC ) , and 341 dollars for PC + CC combined . The differences among these groups were all significant at the p = .001 level . Only the PC + CC group improved the rate of IPT completion ( 83.8 % ) relative to usual care ( 75.9 % ) ( p = .051 ) , with an overall incremental CE ratio of 209 dollars per QALY relative to usual care . CONCLUSION Incentives combined with peer counseling are a cost-effective strategy for helping adolescents to complete care when combined with peer counseling SETTING San Diego , California public health department tuberculosis clinic . OBJECTIVE To evaluate the effectiveness of a behavioral intervention ( the Treasure Chest ) that employed the behavior modification techniques of self-monitoring and positive reinforcement to increase adherence to therapy for latent tuberculosis infection ( LTBI ) in children . DESIGN A retrospective study utilizing a historical comparison group . The treatment adherence of children who attended San Diego County TB Control Program ( SDCTBCP ) clinics with positive tuberculin skin tests who were started on LTBI treatment prior to Treasure Chest program implementation ( n=841 ) was compared to that of SDCTBCP children enrolled in the Treasure Chest program ( n=741 ) . RESULTS Logistic regression analysis demonstrated that children who participated in the Treasure Chest program were 2.4 times more likely to complete therapy than those who did not receive the intervention . CONCLUSION The Treasure Chest intervention is effective in increasing adherence to LTBI therapy in children OBJECTIVE The purpose of this study was to examine the effect of a cultural intervention ( CI ) on increasing adherence to latent tuberculosis infection ( LTBI ) therapy among Latino immigrants . DESIGN AND SAMPLE This clinical study used a preexperimental design . A nonprobability sample of 86 Latino immigrant clients who were starting LTBI therapy were enrolled in the intervention . The comparison group was an historical sample of 131 clients ' records r and omly selected from the previous year . INTERVENTION The CI , design ed by the principal investigator , was delivered by 2 Spanish-speaking interventionist nurses at each of 9 clinic visits . The intervention was based on Latino cultural values and included 5 components . MEASURES The patients ' adherence was measured by a self-report of the number of pills taken . RESULTS The findings of this study were that clients in the CI group took a significantly greater number of doses of INH than those in the historical sample . CONCLUSIONS Using a CI to increase adherence to LTBI therapy shows promise for public health nursing practice SETTING R and omised trial comparing 9 months of isoniazid with 4 months of rifampicin for the treatment of high-risk tuberculin skin test positive subjects in Rio de Janeiro , Brazil . OBJECTIVES To compare QuantiFERON ® -TB Gold In-Tube ( QFT-GIT ) responses before and 1 , 4 and 9 months after starting treatment for latent tuberculous infection ( LTBI ) according to adherence to one of the two regimens . DESIGN Participants in the trial were invited to undergo serial QFT-GIT . Within-subject differences at different time points were analysed as quantitative responses and categorised as positive or negative using different cut-off points . RESULTS Of 215 participants , 118 completed treatment , of whom 58 underwent all three tests ; and 97 did not complete treatment , of whom 10 underwent all tests . After 1 month of treatment , there was no significant difference in QFT-GIT response between the groups . After 4 and 9 months , reversions were more frequent in non-adherent subjects . Marked within-subject fluctuations were observed . No cut-off point could be established at which QFT-GIT responses were consistently positive or associated with adherence or type of treatment . CONCLUSION Frequent within-subject variability in QFT-GIT responses , not associated with LTBI treatment , makes it difficult for clinicians to interpret QFT-GIT conversions and reversions PURPOSE To determine the effect of several interventions on adherence to tuberculosis preventive therapy . METHODS We conducted a r and omized trial with a factorial design comparing strategies for improving adherence to isoniazid preventive therapy in 300 injection drug users with reactive tuberculin tests and no evidence of active tuberculosis . Patients were assigned to receive directly observed isoniazid preventive therapy twice weekly ( Supervised group , n = 99 ) , daily self-administered isoniazid with peer counseling and education ( Peer group , n = 101 ) , or routine care ( Routine group , n = 100 ) . Patients within each arm were also r and omly assigned to receive an immediate or deferred monthly $ 10 stipend for maintaining adherence . The endpoints of the trial were completing 6 months of treatment , pill-taking as measured by self-report or observation , isoniazid metabolites present in urine , and bottle opening as determined by electronic monitors in a subset of patients . RESULTS Completion of therapy was 80 % for patients in the Supervised group , 78 % in the Peer group , and 79 % in the Routine group ( P = 0.70 ) . Completion was 83 % ( 125 of 150 ) among patients receiving immediate incentives versus 75 % ( 112 of 150 ) among patients with deferred incentives ( P = 0.09 ) . The proportion of patients who were observed or reported taking at least 80 % of their doses was 82 % for the Supervised arm of the study , compared with 71 % for the Peer arm and 90 % for the Routine arm . The proportion of patients who took 100 % of doses was 77 % for the Supervised arm ( by observation ) , 6 % for the Peer arm ( by report ) , and 10 % for the Routine arm ( by report ; P < 0.001 ) . Direct observation showed the median proportion of doses taken by the Supervised group was 100 % , while electronic monitoring in a subset of patients showed the Peer group ( n = 27 ) took 57 % of prescribed doses and the Routine group ( n = 32 ) took 49 % ( P < 0.001 ) . Patients in the Routine arm overreported adherence by twofold when data from electronic monitoring were used as a gold st and ard . There were no significant differences in electronically monitored adherence by type of incentive . CONCLUSION Adherence to isoniazid preventive therapy by injection drug users is best with supervised care . Peer counseling improves adherence over routine care , as measured by electronic monitoring of pill caps , and patients receiving peer counseling more accurately reported their adherence . More widespread use of supervised care could contribute to reductions in tuberculosis rates among drug users and possibly other high-risk groups BACKGROUND Adherence to treatment of persons with latent tuberculosis infection after release from jail has been poor . METHODS A r and omized controlled trial was conducted at the San Francisco City and County Jail , San Francisco , Calif. Subjects undergoing therapy for latent tuberculosis infection who spoke either English or Spanish were r and omly allocated to receive education every 2 weeks while in jail ; an incentive if they went to the San Francisco County Tuberculosis Clinic within 1 month of release ; or usual care . The main outcome measures were completion of a visit to the tuberculosis clinic within 1 month of release and completion of therapy . RESULTS Of 558 inmates enrolled , 325 were released before completion of therapy . Subjects in either intervention group were significantly more likely to complete a first visit than were control subjects ( education group , 37 % ; incentive group , 37 % ; and controls , 24 % ) ( adjusted odds ratio based on pooled results for the education and incentive groups , 1.85 ; 95 % confidence interval , 1.04 - 3.28 ; P = .02 ) . Those in the education group were twice as likely to complete therapy compared with controls ( adjusted odds ratio , 2.2 ; 95 % confidence interval , 1.04 - 4.72 ; P = .04 ) . Of those who went to the tuberculosis clinic after release , subjects in the education group were more likely to complete therapy ( education group , 65 % [ 24/37 ] ; incentive group , 33 % [ 14/42 ] ; and control group , 48 % [ 12/25 ] ; P = .02 ) . CONCLUSIONS Education or the promise of an incentive improved initial follow-up . Education was superior to an incentive for the completion of therapy . Fairly modest strategies provided in jail can improve adherence . Further links between jail health services and community care should be explored OBJECTIVE To assess the effectiveness of a peer-based intervention on adherence to and completion of latent tuberculous infection ( LTBI ) treatment . METHODS Patients prescribed self-administered LTBI treatment were enrolled in a r and omized controlled trial of an experimental , peer-based adherence support intervention . Primary outcomes were treatment adherence and completion . Adherence was assessed through self-report , electronic monitoring devices and clinic visits . RESULTS Of 250 participants , 70 % were male ; 71 % were Black and 20 % Latino ; the mean age was 40 years ; 67 % were foreign-born and 39 % were married . No significant baseline differences were noted between the intervention groups . Treatment completion was 61 % in the intervention group compared to 57 % in the controls ( P = 0.482 ) . The corresponding completion rate for other clinic patients was 44 % . Foreign birth , marriage and history of mental illness were associated with non-completion of treatment after controlling for the intervention group ; increased completion rates were found among foreign-born married persons and older participants . A substantial difference in adherence rates was observed between the intervention groups . Adherence among non-completers decreased early , while adherence among completers remained constant . CONCLUSIONS The peer-based intervention was not significantly associated with LTBI treatment completion , but was associated with greater adherence . Findings suggest the importance of interventions to support adherence that target early non-adherence with LTBI treatment , particularly in the first 2 months , when there is a substantial risk of default SETTING Community-based population of homeless adults living in San Francisco , California . OBJECTIVE To compare the effect of cash and non-cash incentives on 1 ) adherence to treatment for latent tuberculosis infection , and 2 ) length of time needed to look for participants who missed their dose of medications . DESIGN Prospect i ve , r and omized clinical trial comparing a 5 dollar cash or a 5 dollar non-cash incentive . All participants received directly observed preventive therapy and st and ardized follow-up per a predetermined protocol . Completion rates and amount of time needed to follow up participants was measured . RESULTS Of the 119 participants , 102 ( 86 % ) completed therapy . There was no difference between the cash and non-cash arms . Completion was significantly higher among males ( OR 5.65 , 95%CI 1.36 - 23.40 , P = 0.02 ) and persons in stable housing at study entry ( OR 4.86 , 95%CI 1.32 - 17.94 , P = 0.02 ) . No substance use or mental health measures were associated with completion . Participants in the cash arm needed significantly less follow-up to complete therapy compared to the non-cash arm ( P = 0.03 ) . In multivariate analysis , non-cash incentive , use of crack cocaine , and no prior preventive therapy were associated with more follow-up time . CONCLUSION Simple , low cost incentives can be used to improve adherence to TB preventive therapy in indigent adults OBJECTIVES To compare the tolerance , adherence and effectiveness of two approaches for the treatment of latent tuberculosis infection ( LTBI ) : 6 months of isoniazid ( 6H ) vs. 3 months of isoniazid plus rifampicin ( 3RH ) . POPULATION Immigrants with LTBI . METHODS Participants were enrolled in a controlled , r and omised clinical trial in Barcelona , Spain , from April 2001 to April 2005 . Monthly follow-up was done to assess tolerance , side effects and adherence . Effectiveness was evaluated at 5 years . RESULTS In the 590 subjects enrolled , the rate of adherence was greater in the 3RH than in the 6H arm ( 72 % vs. 52.4 % , P = 0.001 ) . No differences between study arms were observed with respect to hepatotoxicity or side effects . Variables associated with non-adherence were diagnosis by screening ( OR 1.88 , 95%CI 1.26 - 2.82 , P = 0.001 ) , illegal immigration status ( OR 1.48 , 95%CI 1.01 - 2.15 , P = 0.03 ) , unemployment ( OR 1.91 , 95%CI 1.28 - 2.85 , P = 0.0008 ) , illiteracy ( OR 1.73 , 95%CI 1.04 - 2.88 , P = 0.02 ) , lack of family support ( OR 3.7 , 95%CI 2.54 - 5.4 , P = 0.001 ) and the 6-month treatment regimen ( OR 2.45 , 95%CI 1.68 - 3.57 , P = 0.0001 ) . None of the patients who completed either treatment developed tuberculosis . CONCLUSIONS The 3RH regimen facilitates adherence to LTBI treatment and offers a safe , well-tolerated and effective alternative The objective was to test whether theoretical variables predict adherence to treatment for latent tuberculosis infection in high-risk Latino adolescents . 286 Latino adolescents , age 13 - 18 years , were recruited from 10 middle/high schools in San Diego County , San Diego , USA . Participants completed a baseline interview and up to 9 monthly interviews . The cumulative number of pills consumed in 9 months was regressed on 16 independent variables , entered hierarchically in seven blocks . The final model accounted for 25 % of the variance in adherence to isoniazid ( INH ) , F ( 16 , 230)=4.69 , p<0.001 . Adherence counseling ( + ) , age ( - ) , grade s ( + ) , being bicultural ( + ) , and risk behaviors ( - ) were significantly related to adherence . Learning theories presume that adherence to medical regimens requires social support and freedom from physical and social barriers . Results support these theories . Future studies should explore additional precepts in order to identify additional predictors and to maximize adherence to INH among Latino adolescents and other high-risk population s. Doing so should decrease the risk of active TB among high-risk racial/ethnic and foreign-born population Substance abuse is associated with high risk for tuberculosis ( TB ) and poor adherence to medication regimens . This study compared completion rates for isoniazid ( INH ) preventive therapy for injection drug users ( IDUs ) r and omly assigned to methadone treatment combined with directly observed preventive treatment ( DOPT ) versus those assigned to routine TB clinic referral without methadone treatment . One hundred and eleven opioid-dependent patients with latent TB were assigned to one of three 6-month treatment conditions : st and ard methadone treatment including substance abuse counseling combined with daily INH DOPT ( n=37 ) ; minimal methadone treatment without counseling , also combined with daily INH DOPT ( n=35 ) ; or routine care referral to TB clinic for monthly INH supplies without DOPT and without methadone treatment ( n=39 ) . INH completion rates were 77.1 % for minimal methadone and 59.5 % for st and ard methadone , as compared with only 13.5 % for routine care ( P<0.0001 ) . Mean duration of INH treatment retention was 5.7 , 5.0 and 1.6 months , respectively ( P<0.0001 ) . TB incidence at 4-year follow-up was 0 of 54 subjects who completed preventive therapy versus 2 of 57 who failed to complete . One of these two had been assigned to routine care , and the other to minimal methadone . In conclusion , INH retention time and completion rates were significantly improved by methadone treatment combined with observed INH , whether or not substance abuse counseling was provided . The results of this study indicate that methadone treatment offers clear public health benefits when it is used to deliver preventive medical services In a multicenter , prospect i ve , r and omized , open-label study of isoniazid-preventive therapy ( IPT ) for latent tuberculosis infection , illegal immigrants from countries where tuberculosis is highly endemic were enrolled at two clinical sites in Northern Italy . Of 208 eligible subjects , 82 received supervised IPT at a dose of 900 mg twice weekly for 6 mo ( Regimen A ) , 73 received unsupervised IPT 900 mg twice weekly for 6 mo ( Regimen B ) , and 53 received unsupervised IPT 300 mg daily for 6 mo ( Regimen C ) . Supervised IPT was delivered at either one tuberculosis clinic or one migrant clinic . The probability of completing a 26-wk regimen was 7 , 26 , and 41 % in Regimens A , B , and C , respectively ( p < 0.005 , Log- rank test calculated using Kaplan-Meier plots ) . The mean time to dropout was 3 . 8 , 6 , and 6.2 wk in Regimens A , B , and C , respectively ( p = 0.003 for regimen A versus either Regimens B or C ) . Treatment was stopped in five subjects ( 2.4 % ) because of adverse events . The rate of completion of preventive therapy for latent tuberculosis infection among illegal immigrants was low . Supervised , clinic-based administration of IPT significantly reduced adherence . Alternative strategies to implement preventive therapy in illegal immigrants are clearly required BACKGROUND Treatment of latent Mycobacterium tuberculosis infection is an essential component of tuberculosis control and elimination . The current st and ard regimen of isoniazid for 9 months is efficacious but is limited by toxicity and low rates of treatment completion . METHODS We conducted an open-label , r and omized noninferiority trial comparing 3 months of directly observed once-weekly therapy with rifapentine ( 900 mg ) plus isoniazid ( 900 mg ) ( combination-therapy group ) with 9 months of self-administered daily isoniazid ( 300 mg ) ( isoniazid-only group ) in subjects at high risk for tuberculosis . Subjects were enrolled from the United States , Canada , Brazil , and Spain and followed for 33 months . The primary end point was confirmed tuberculosis , and the noninferiority margin was 0.75 % . RESULTS In the modified intention-to-treat analysis , tuberculosis developed in 7 of 3986 subjects in the combination-therapy group ( cumulative rate , 0.19 % ) and in 15 of 3745 subjects in the isoniazid-only group ( cumulative rate , 0.43 % ) , for a difference of 0.24 percentage points . Rates of treatment completion were 82.1 % in the combination-therapy group and 69.0 % in the isoniazid-only group ( P<0.001 ) . Rates of permanent drug discontinuation owing to an adverse event were 4.9 % in the combination-therapy group and 3.7 % in the isoniazid-only group ( P=0.009 ) . Rates of investigator-assessed drug-related hepatotoxicity were 0.4 % and 2.7 % , respectively ( P<0.001 ) . CONCLUSIONS The use of rifapentine plus isoniazid for 3 months was as effective as 9 months of isoniazid alone in preventing tuberculosis and had a higher treatment-completion rate . Long-term safety monitoring will be important . ( Funded by the Centers for Disease Control and Prevention ; PREVENT TB Clinical Trials.gov number , NCT00023452 . ) Context Isoniazid is hepatotoxic and must be taken for 9 months by patients with latent tuberculosis infection . Contribution In this trial comparing 4 months of rifampin therapy with 9 months of isoniazid therapy , patients who took rifampin had fewer adverse events and were more likely to complete treatment . Caution The investigators did not compare efficacy of the 2 treatments . Implication These safety and adherence data justify a larger trial to compare the efficacy of rifampin and isoniazid for latent tuberculosis infection . The Editors After detection and treatment of active tuberculosis cases , the next priority in tuberculosis control is the diagnosis and treatment of persons with latent tuberculosis infection ( LTBI ) who are at increased risk for active tuberculosis . Treatment of such individuals can provide individual and public health benefits ( 14 ) . The current recommended st and ard therapy in most countries is 9 months of isoniazid therapy ( 4 , 5 ) . The drug has more than 90 % efficacy if taken the entire 9 months ( 6 ) , but completion rates under routine practice conditions are about 50 % or less ( 79 ) . Another important disadvantage of isoniazid therapy is the occurrence of serious adverse events , particularly drug-induced hepatitis ( 10 ) . Drug-induced hepatitis was not recognized as a complication of isoniazid therapy in early trials involving more than 50000 participants ( 11 ) , but it was a frequent and potentially severe problem after isoniazid was recommended for tuberculosis prevention in 1970 ( 12 ) and was subsequently used more widely ( 13 , 14 ) . This complication makes close monitoring necessary , increasing costs . These problems have stimulated considerable interest in finding shorter and safer regimens for the treatment of LTBI ( 15 ) . One alternative , 2 months of daily rifampinpyrazinamide , was recommended in 2000 ( 4 ) on the basis of evidence from several trials ( 1618 ) . However , subsequent reports of severe and fatal hepatotoxicity ( 19 , 20 ) have rendered this regimen unacceptable for most patients . The remaining recommended alternative is 4 months of daily rifampin , but published outcome information is limited and systematic review s on this regimen have not been done . In the only published trial that compared 3 months of daily rifampin therapy with 6 months of daily isoniazid therapy in 332 patients , efficacy and safety were similar ( 21 ) . In 2 uncontrolled case series , 6 months of daily rifampin was well tolerated in 49 homeless persons in Boston ( 22 ) and in 157 high school students in California ( 23 ) . Two nonr and omized studies have described better treatment completion and less hepatotoxicity with 4 months of rifampin than with 9 months of isoniazid under program conditions ( 8 , 9 ) . However , rifampin has been reported to cause other problemsnotably drug interactions ( 24 ) , a flu-like syndrome ( 24 ) , and rare hematologic problems ( immune-mediated thrombocytopenia and anemia ) ( 25 ) . Also , development of drug resistance is a theoretical concern . Given the experience with isoniazid and 2 months of rifampinpyrazinamide , both of which were thought to be safe on the basis of early studies but caused deaths when used more widely , we design ed a multicenter , r and omized trial to compare the frequency of serious adverse events and treatment completion rates in patients given 4 months of daily rifampin or 9 months of daily isoniazid for LTBI . Methods Setting , Study Sample , and R and omization This open-label trial was conducted at 9 university-affiliated hospitals : 7 in Canada and 1 each in Saudi Arabia and Brazil . We considered patients to be eligible if they were age 18 years or older and had a documented tuberculin skin test that met the criteria for a positive result ( 5 ) and if their primary treating physician initially recommended isoniazid for LTBI following national or international guidelines ( 4 , 26 , 27 ) . Patients were ineligible if they were contacts of isoniazid- or rifampin-resistant cases ( 28 ) , were allergic to isoniazid or rifamycins , or were taking concomitant medications that had clinical ly significant potential drug interactions that could not be easily managed . To ensure a realistic assessment of adverse events , we considered all other adults eligible , regardless of age or additional risk factors for adverse events , as long as their treating physician felt that therapy for LTBI was indicated . A Web-based program verified eligibility and r and omly assigned participants ( by using a r and om-number generator ) , after they signed informed consent , to 4 months of daily rifampin ( 10 mg per kg of body weight , up to 600 mg/d ) or 9 months of daily isoniazid ( 5 mg/kg , up to 300 mg/d ) in blocks of varying size , stratified by center . A team at the University of Sherbrooke , Sherbrooke , Quebec , Canada , prepared the Web-based program and allocation sequence . Study personnel in the different centers enrolled and registered participants , obtained consent , verified assignment , and administered treatment . All study participants signed informed consent before r and omization . Institutional review boards in each participating institution approved the study . Processes and Outcomes Patients were followed in routine fashion by their usual treating physician , who made all management decisions , including discontinuation of therapy . By study protocol , all patients had blood tests ( complete blood count , liver aminotransferase levels [ aspartate aminotransferase and alanine aminotransferase ] , and bilirubin level ) before and after 1 and 2 months of therapy and were seen every month for the first 4 months of therapy and ( for those receiving 9 months of isoniazid ) at physician discretion every 6 weeks thereafter . Adverse events could be detected at any time throughout the course of therapy . When the treating physician suspected an adverse event and therapy was suspended , investigations , including blood tests , were performed according to study protocol . The treating physician decided whether to discontinue , rechallenge with , or restart the study therapy , although the protocol specified that participants with grade 3 or 4 adverse events ( Appendix Table 1 ) were not to be rechallenged . When all investigations were complete , and if therapy was permanently discontinued in response to the event , the patient 's clinical course and results of investigations and rechallenge ( if any ) were made available to a 3-member independent review panel who were blinded to study drug . If therapy was resumed ( for example , after resolution of a grade 1 or 2 adverse event ) and the event did not recur , the patient 's information was not review ed by the panel . Appendix Table 1 . Grading System for Adverse Events Used by Independent Panel Each review panel member had substantial experience and expertise in clinical and epidemiologic aspects of tuberculosis , and each independently judged the type and severity of the adverse events and its likely relationship to the study drug . We grade d adverse events as recommended by the National Cancer Institute Common Terminology Criteria for Adverse Events , version 2.0 ( 29 ) ( Appendix Table 1 ) . Liver aminotransferase levels that increased to 5 to 10 or 3 to 10 times the upper limit of normal in the presence of compatible symptoms met criteria for grade 3 hepatotoxicity , whereas those that exceeded 10 times the upper limit of normal met criteria for grade 4 toxicity ( 30 ) . In the event of disagreement , panel members re- review ed the information ; if disagreement remained , the majority opinion was used . The study 's primary outcome was the frequency of grade 3 or 4 adverse events that result ed in study drug discontinuation and were judged by the review panel to be probably related to the drug ( Appendix Table 1 ) . The study 's secondary outcome was on-time treatment completion , defined as taking more than 80 % of doses within a maximum of 150 days for 4 months of rifampin or 301 days ( 43 weeks ) for 9 months of isoniazid . Doses taken were measured with the Medical Event Monitoring System , an electronic device in the pill container cap that recorded the date and time of bottle opening ( APREX Corporation , Fremont , California ) . Other secondary outcomes included grade 1 or 2 adverse events that were judged by the independent panel to be probably study drugrelated and result ed in permanent discontinuation of therapy and changes in liver aminotransferase levels and leukocyte and platelet counts before and 1 and 2 months after beginning treatment . Statistical Analysis We initially calculated a trial sample size by assuming that the frequency of serious adverse events would be significantly higher with rifampin . We calculated that 630 patients per group would provide 90 % power ( 2-sided = 0.05 ) to detect a difference between frequency of adverse events of 9 % and 4 % in the rifampin and isoniazid groups , respectively . This estimate also accounted for an anticipated 15 % dropout rate during therapy . Because we were unsure about the actual frequency of adverse events with rifampin , we also noted that 630 patients per group provided 80 % power to detect a statistically significant difference between rates of adverse events in the 2 groups if the event rates were 2 % and 5 % in the rifampin and isoniazid groups , respectively , and the dropout rate was 15 % . To ensure safety of study participants , we planned 3 interim analyses for when 25 % , 50 % , and 75 % of the planned total sample size had been r and omly assigned . The data safety and monitoring board , blinded to the identity of the 2 groups , review ed the overall rate of serious adverse events in each group . If the rate was significantly higher in 1 group , then the results were unblinded and the data safety and monitoring board made a decision , based on clinical judgment and statistical input , about stopping or continuing the trial . We used an value of 0.01 to account for multiple testing ( 31 ) . We reported summary baseline liver function test results for each group as the ratio of each patient 's test result to the upper |
867 | 28,276,567 | Severe stroke was associated with the greatest disutility among AF outcomes and most patients value the stroke prevention efficacy of therapy more than other attributes .
Patients ' therapy preferences usually align with their values when individualised risk information is presented , although divergence from this is common .
Patients value the attributes of NOACs but frequently do not prefer NOACs over warfarin when all therapy-related attributes are considered .
In conclusion , patients ' values and preferences for SPAF antithrombotic therapy are heterogeneous and there is no substitute for directly clarifying patients ' individual values and preferences . | Guidelines recommend that patients ' values and preferences should be considered when selecting stroke prevention therapy for atrial fibrillation ( SPAF ) .
However , doing so is difficult , and tools to assist clinicians are sparse .
We performed a narrative systematic review to provide clinicians with insights into the values and preferences of AF patients for SPAF antithrombotic therapy .
RESEARCH QUESTIONS 1 ) What are patients ' AF and SPAF therapy values and preferences ?
2 ) How are SPAF therapy values and preferences affected by patient factors ?
3 ) How does conveying risk information affect SPAF therapy preferences ?
and 4 ) What is known about patient values and preferences regarding novel oral anticoagulants ( NOACs ) for SPAF ? | Warfarin is an anticoagulant medication that is challenging to manage . Dabigatran has been approved by the FDA for stroke and systemic embolism prevention in non-valvular atrial fibrillation as an alternative to warfarin . Dabigatran does not require routine monitoring , has an established dose , and lacks many of the drug , herbal , and food interactions that afflict warfarin . To evaluate patients ’ satisfaction with their current warfarin treatment and their opinion on switching to a newly marketed medication ( dabigatran ) through a brief survey . Two separate surveys were administered to ( 1 ) evaluate the patients ’ opinion of their warfarin therapy and ( 2 ) evaluate their thoughts on switching to a newer anticoagulant . Responses were recorded on a rating scale of 1–5 ; 1 being the least and 5 being the highest . Study was conducted at the Georgia Regents Health System ( GRHS ) pharmacy-based anticoagulation clinic . Two hundred sixty patients on warfarin treatment were enrolled . Patients expressed high satisfaction with warfarin treatment ( 4.7 ± 0.78 ) . However , a vast majority of the patients were willing to switch to an agent that : requires less frequent follow-up visits ( 3.9 ± 1.35 ) ; lacks interaction with food and /or beverage ( 4.1 ± 1.25 ) ; is as efficacious as warfarin ( 3.7 ± 1.38 ) . Patients expressed that out-of-pocket cost would be a major barrier to switch to this new medication ( 1.3 ± 0.58 ) . Patients are satisfied with their warfarin treatment but willing to consider a new anticoagulant . Cost was highlighted as the most significant barrier . Efficacy , dietary freedom and less frequent visits are the major factors affecting the patients ’ decision Introduction Reporting r and omised controlled trials is a key element in order to disseminate research findings . The CONSORT statement was introduced to improve the reporting quality . We assessed the adherence to the CONSORT statement of r and omised controlled trials published 2011 in the top ten ranked journals of critical care medicine ( ISI Web of Knowledge 2011 , Thomson Reuters , London UK ) . Methods Design . We performed a retrospective cross sectional data analysis . Setting . This study was executed at the University Hospital of RWTH , Aachen . Participants . We selected the following top ten listed journals according to ISI Web of Knowledge ( Thomson Reuters , London , UK ) critical care medicine ranking in the year 2011 : American Journal of Respiratory and Critical Care Medicine , Critical Care Medicine , Intensive Care Medicine , CHEST , Critical Care , Journal of Neurotrauma , Resuscitation , Pediatric Critical Care Medicine , Shock and Minerva Anestesiologica . Main outcome measures . We screened the online table of contents of each included journal , to identify the r and omised controlled trials . The adherence to the items of the CONSORT Checklist in each trial was evaluated . Additionally we correlated the citation frequency of the articles and the impact factor of the respective journal with the amount of reported items per trial . Results We analysed 119 r and omised controlled trials and found , 15 years after the implementation of the CONSORT statement , that a median of 61,1 % of the checklist-items were reported . Only 55.5 % of the articles were identified as r and omised trials in their titles . The citation frequency of the trials correlated significantly ( rs = 0,433 ; p<0,001 and r = 0,331 ; p<0,001 ) to the CONSORT statement adherence . The impact factor showed also a significant correlation to the CONSORT adherence ( r = 0,386 ; p<0,001 ) . Conclusion The reporting quality of r and omised controlled trials in the field of critical care medicine remains poor and needs considerable improvement BACKGROUND Noncompliant patients might be at risk of thromboembolism because of the short half-life and rapid offset of dabigatran etexilate . The assessment and management of dabigatran noncompliance should be optimized . METHODS AND RESULTS A total of 150 nonvalvular atrial fibrillation patients receiving dabigatran were prospect ively enrolled and followed for drug compliance and persistence . Noncompliance was identified by question naires and interviews . The hemoclot thrombin inhibitor ( HTI ) assay was used for monitoring the plasma dabigatran levels . Sixteen patients were noncompliant ( 10.7 % ) . None of the clinical characteristics were significantly relevant to noncompliance after multivariate analysis . The dabigatran plasma level based on HTI was the only independent predictor of noncompliance ( odds ratio : 0.97 per ng/mL , P = 0.003 ) . The prothrombin time ( PT ) , international normalized ratio of PT ( INR [ PT ] ) , and activated partial thromboplastin time did not differ between compliant and noncompliant patients . During the follow-up , the persistent prescription of dabigatran was noted in 75 % of noncompliant patients without improvement in compliance . The drug discontinuation rate was higher in the noncompliant than compliant patients ( 6.7 % vs. 25 % , P = 0.035 ) . None of the patients in either group received warfarin after discontinuing dabigatran . CONCLUSIONS The assessment and management of dabigatran noncompliance is generally ignored in clinical practice . The measurement of dabigatran plasma levels by HTI could be a reliable and simple method to identify noncompliant patients CONTEXT Decision aids are tools design ed to help patients participate in the clinical decision-making process . OBJECTIVE To determine whether use of an audiobooklet ( AB ) decision aid explaining the results of a clinical trial affected the decision-making process of study participants . DESIGN R and omized controlled trial conducted from May 1997 to April 1998 . SETTING Fourteen centers that participated in the Stroke Prevention in Atrial Fibrillation ( SPAF ) III trial . PARTICIPANTS A total of 287 patients from the SPAF III aspirin cohort study , in which patients with atrial fibrillation and a relatively low risk of stroke received 325 mg/d of aspirin and were followed up for a mean of 2 years . INTERVENTION At the end of SPAF III , participants were r and omized to be informed of the study results with usual care plus use of an AB ( AB group ) vs usual care alone ( control group ) . The AB included pertinent information to help patients decide whether to continue taking aspirin or switch to warfarin . MAIN OUTCOME MEASURES Patients ' ability to make choices regarding antithrombotic therapy , and 6-month adherence to these decisions . Their knowledge , expectations , decisional conflict ( the amount of uncertainty about the course of action to take ) , and satisfaction with the decision-making process were also measured . RESULTS More patients in the AB group made a choice about antithrombotic therapy than in the control group ( 99 % vs 94 % ; P = .02 ) . Patients in the AB group were more knowledgeable and had more realistic expectations about the risk of stroke and hemorrhage ( in the AB group , 53%-80 % correctly estimated different risks ; in the control group , 16%-28 % gave correct estimates ) . Decisional conflict and satisfaction were similar for the 2 groups . After 6 months , a similar percentage of patients were still taking their initial choice of antithrombotic therapy ( 95 % vs 93 % ; P = .44 ) . CONCLUSIONS For patients with atrial fibrillation who had participated in a major clinical trial , the use of an AB decision aid improved their underst and ing of the benefits and risks associated with different treatment options and helped them make definitive choices about which therapy to take . Further studies are necessary to evaluate the acceptability and impact of decision aids in other clinical setting BACKGROUND Warfarin reduces the risk of stroke in patients with atrial fibrillation but increases the risk of hemorrhage and is difficult to use . Dabigatran is a new oral direct thrombin inhibitor . METHODS In this noninferiority trial , we r and omly assigned 18,113 patients who had atrial fibrillation and a risk of stroke to receive , in a blinded fashion , fixed doses of dabigatran--110 mg or 150 mg twice daily -- or , in an unblinded fashion , adjusted-dose warfarin . The median duration of the follow-up period was 2.0 years . The primary outcome was stroke or systemic embolism . RESULTS Rates of the primary outcome were 1.69 % per year in the warfarin group , as compared with 1.53 % per year in the group that received 110 mg of dabigatran ( relative risk with dabigatran , 0.91 ; 95 % confidence interval [ CI ] , 0.74 to 1.11 ; P<0.001 for noninferiority ) and 1.11 % per year in the group that received 150 mg of dabigatran ( relative risk , 0.66 ; 95 % CI , 0.53 to 0.82 ; P<0.001 for superiority ) . The rate of major bleeding was 3.36 % per year in the warfarin group , as compared with 2.71 % per year in the group receiving 110 mg of dabigatran ( P=0.003 ) and 3.11 % per year in the group receiving 150 mg of dabigatran ( P=0.31 ) . The rate of hemorrhagic stroke was 0.38 % per year in the warfarin group , as compared with 0.12 % per year with 110 mg of dabigatran ( P<0.001 ) and 0.10 % per year with 150 mg of dabigatran ( P<0.001 ) . The mortality rate was 4.13 % per year in the warfarin group , as compared with 3.75 % per year with 110 mg of dabigatran ( P=0.13 ) and 3.64 % per year with 150 mg of dabigatran ( P=0.051 ) . CONCLUSIONS In patients with atrial fibrillation , dabigatran given at a dose of 110 mg was associated with rates of stroke and systemic embolism that were similar to those associated with warfarin , as well as lower rates of major hemorrhage . Dabigatran administered at a dose of 150 mg , as compared with warfarin , was associated with lower rates of stroke and systemic embolism but similar rates of major hemorrhage . ( Clinical Trials.gov number , NCT00262600 . BACKGROUND Edoxaban is a direct oral factor Xa inhibitor with proven antithrombotic effects . The long-term efficacy and safety of edoxaban as compared with warfarin in patients with atrial fibrillation is not known . METHODS We conducted a r and omized , double-blind , double-dummy trial comparing two once-daily regimens of edoxaban with warfarin in 21,105 patients with moderate-to-high-risk atrial fibrillation ( median follow-up , 2.8 years ) . The primary efficacy end point was stroke or systemic embolism . Each edoxaban regimen was tested for noninferiority to warfarin during the treatment period . The principal safety end point was major bleeding . RESULTS The annualized rate of the primary end point during treatment was 1.50 % with warfarin ( median time in the therapeutic range , 68.4 % ) , as compared with 1.18 % with high-dose edoxaban ( hazard ratio , 0.79 ; 97.5 % confidence interval [ CI ] , 0.63 to 0.99 ; P<0.001 for noninferiority ) and 1.61 % with low-dose edoxaban ( hazard ratio , 1.07 ; 97.5 % CI , 0.87 to 1.31 ; P=0.005 for noninferiority ) . In the intention-to-treat analysis , there was a trend favoring high-dose edoxaban versus warfarin ( hazard ratio , 0.87 ; 97.5 % CI , 0.73 to 1.04 ; P=0.08 ) and an unfavorable trend with low-dose edoxaban versus warfarin ( hazard ratio , 1.13 ; 97.5 % CI , 0.96 to 1.34 ; P=0.10 ) . The annualized rate of major bleeding was 3.43 % with warfarin versus 2.75 % with high-dose edoxaban ( hazard ratio , 0.80 ; 95 % CI , 0.71 to 0.91 ; P<0.001 ) and 1.61 % with low-dose edoxaban ( hazard ratio , 0.47 ; 95 % CI , 0.41 to 0.55 ; P<0.001 ) . The corresponding annualized rates of death from cardiovascular causes were 3.17 % versus 2.74 % ( hazard ratio , 0.86 ; 95 % CI , 0.77 to 0.97 ; P=0.01 ) , and 2.71 % ( hazard ratio , 0.85 ; 95 % CI , 0.76 to 0.96 ; P=0.008 ) , and the corresponding rates of the key secondary end point ( a composite of stroke , systemic embolism , or death from cardiovascular causes ) were 4.43 % versus 3.85 % ( hazard ratio , 0.87 ; 95 % CI , 0.78 to 0.96 ; P=0.005 ) , and 4.23 % ( hazard ratio , 0.95 ; 95 % CI , 0.86 to 1.05 ; P=0.32 ) . CONCLUSIONS Both once-daily regimens of edoxaban were noninferior to warfarin with respect to the prevention of stroke or systemic embolism and were associated with significantly lower rates of bleeding and death from cardiovascular causes . ( Funded by Daiichi Sankyo Pharma Development ; ENGAGE AF-TIMI 48 Clinical Trials.gov number , NCT00781391 . ) Background : Decision aids have been shown to be useful in selected situations to assist patients in making treatment decisions . Important features such as the format of decision aids and their graphic presentation of data on benefits and harms of treatment options have not been well studied . Methods : In a r and omized trial with a 3 × 2 factorial design , we investigated the effects of decision aid format ( decision board , decision booklet with audiotape , or interactive computer program ) and graphic presentation of data ( pie graph or pictogram ) on patients ' comprehension and choices of 3 treatments for anticoagulation , identified initially as “ treatment A ” ( warfarin ) , “ treatment B ” ( acetylsalicylic acid ) and “ treatment C ” ( no treatment ) . Patients aged 65 years or older without known atrial fibrillation and not currently taking warfarin were included . The effect of blinding to the treatment name was tested in a before – after comparison . The primary outcome was change in comprehension score , as assessed by the Atrial Fibrillation Information Question naire . Secondary outcomes were treatment choice , level of satisfaction with the decision aid , and decisional conflict . Results : Of 102 eligible patients , 98 completed the study . Comprehension scores ( maximum score 10 ) increased by an absolute mean of 3.1 ( p < 0.01 ) after exposure to the decision aid regardless of the format or graphic presentation . Overall , 96 % of the participants felt that the decision aid helped them make their treatment choice . Unblinding of the treatment name result ed in 36 % of the participants changing their initial choice ( p < 0.001 ) . Interpretation : The decision aid led to significant improvement in patients ' knowledge regardless of the format or graphic representation of data . Revealing the name of the treatment options led to significant shifts in declared treatment preferences Background : Although warfarin has been extensively studied in clinical trials , little is known about rates of hemorrhage attributable to its use in routine clinical practice . Our objective was to examine incident hemorrhagic events in a large population -based cohort of patients with atrial fibrillation who were starting treatment with warfarin . Methods : We conducted a population -based cohort study involving residents of Ontario ( age ≥ 66 yr ) with atrial fibrillation who started taking warfarin between Apr. 1 , 1997 , and Mar. 31 , 2008 . We defined a major hemorrhage as any visit to hospital for hemorrage . We determined crude rates of hemorrhage during warfarin treatment , overall and stratified by CHADS2 score ( congestive heart failure , hypertension , age ≥ 75 yr , diabetes mellitus and prior stroke , transient ischemic attack or thromboembolism ) . Results : We included 125 195 patients with atrial fibrillation who started treatment with warfarin during the study period . Overall , the rate of hemorrhage was 3.8 % ( 95 % confidence interval [ CI ] 3.8%–3.9 % ) per person-year . The risk of major hemorrhage was highest during the first 30 days of treatment . During this period , rates of hemorrhage were 11.8 % ( 95 % CI 11.1%–12.5 % ) per person-year in all patients and 16.7 % ( 95 % CI 14.3%–19.4 % ) per person-year among patients with a CHADS2 scores of 4 or greater . Over the 5-year follow-up , 10 840 patients ( 8.7 % ) visited the hospital for hemorrhage ; of these patients , 1963 ( 18.1 % ) died in hospital or within 7 days of being discharged . Interpretation : In this large cohort of older patients with atrial fibrillation , we found that rates of hemorrhage are highest within the first 30 days of warfarin therapy . These rates are considerably higher than the rates of 1%–3 % reported in r and omized controlled trials of warfarin therapy . Our study provides timely estimates of warfarin-related adverse events that may be useful to clinicians , patients and policy-makers as new options for treatment become available Objective : To determine the efficacy of a computerised decision aid in patients with atrial fibrillation making decisions on whether to take warfarin or aspirin therapy . Design : Two-armed open exploratory r and omised controlled trial . Setting : Two research clinics deriving participants from general practice s in Northeast Engl and . Participants : 109 patients with atrial fibrillation aged over 60 . Interventions : Computerised decision aid applied in shared decision-making clinic compared to evidence -based paper guidelines applied as direct advice . Main outcome measures : Primary outcome measure was the decision conflict scale . Secondary outcome measures included anxiety , knowledge , decision-making preference , treatment decision , use of primary and secondary care services and health outcomes . Results : Decision conflict was lower in the computerised decision aid group immediately after the clinic ; mean difference −0.18 ( 95 % CI −0.34 to −0.01 ) . Participants in this group not already on warfarin were much less likely to start warfarin than those in the guidelines arm ( 4/16 , 25 % compared to the guidelines group 15/16 , 93.8 % , RR 0.27 , 95 % CI 0.11 to 0.63 ) . Conclusions : Decision conflict was lower immediately following the use of a computerised decision aid in a shared decision-making consultation than immediately following direct doctor-led advice based on paper guidelines . Furthermore , participants in the computerised decision aid group were significantly much less likely to start warfarin than those in the guidelines arm . The results show that such an approach has a positive impact on decision conflict comparable to other studies of decision aids , but also reduces the uptake of a clinical ly effective treatment that may have important implication s for health outcomes BACKGROUND Given the greater uncertainty surrounding probability estimates associated with qualitative ( use of words or phrases ) descriptions , the use of quantitative ( numerical ) information to communicate the risks and benefits of therapies is recommended but the impact of its use in decision aids is unexplored . OBJECTIVE Using stroke prevention in atrial fibrillation as an example , to compare the impact of quantitative vs. qualitative descriptions of probability risk estimates in decision aids on the clinical decision-making process . DESIGN R and omized trial with a 2 x 2 factorial design . SUBJECTS A total of 198 volunteers aged 60 - 80 years . SETTING Outpatient clinics of a university-affiliated , tertiary-care teaching hospital . METHODS Participants were asked to imagine that they had atrial fibrillation , and using a decision aid , were then r and omized to two ways of receiving pertinent risk information regarding the probability of stroke and major bleeding when taking warfarin , aspirin or no therapy : ( 1 ) quantitatively , in which the 2-year probabilities of stroke and major haemorrhage were presented both numerically and graphically with 100 faces ( e.g. 8 of 100 ) , and ( 2 ) qualitatively in which these probabilities were presented with the use of verbal phrases ( e.g. very low , moderate ) . OUTCOME MEASURES Primary : decisional conflict . Secondary : participants ' choices , knowledge and expectations of outcomes using qualitative and quantitative scales . RESULTS Participants review ing quantitative risk information scored better on the informed subscale of the decisional conflict scale ( P < 0.05 ) and , as expected , were better able to estimate numerically their chance of stroke and bleeding when taking warfarin , aspirin or no medication . For the low risk arm , there were no significant differences in treatment choices for the qualitative and quantitative groups . For the moderate risk arm , treatment choices between the two groups were significantly different ( P = 0.01 ) , with those in the quantitative group more likely to make an actual choice and to choose therapies at the extremes of effectiveness ( warfarin and no treatment ) . There were no significant differences between the quantitative and qualitative groups in their ability to rank-order their stroke risk when taking warfarin , aspirin and no treatment , overall knowledge about atrial fibrillation and its treatment , and other dimensions of decisional conflict ( all P-values > 0.05 ) . CONCLUSIONS For participants without the disease in question , this study found that providing sufficient quantitative risk information makes them feel more informed , which sometimes affects their treatment choices . Further studies are necessary to confirm these findings for patients making actual clinical decisions BACKGROUND Multiple antithrombotic agents are available for stroke prevention in atrial fibrillation ( AF ) . A decision aid can assist patients in making informed decisions that best serves their needs . OBJECTIVE To vali date a decision aid to assist patients in choosing between antithrombotic agents ( antiplatelets , warfarin , direct-acting oral anticoagulants ( DOACs ) ) for AF . METHODS Patients ( 60years or older ) were recruited for this prospect i ve study . The decision aid presented descriptions related to AF , then charts portraying important outcomes for comparisons between 1 ) no treatment , aspirin and anticoagulants , 2 ) warfarin versus DOACs , and 3 ) DOAC versus DOAC . The primary outcome was confidence in making treatment decisions . The secondary outcomes included change in knowledge scores , ratings of clarity , helpfulness and comprehensiveness . RESULTS Eighty-one patients ( mean age 75.2 [ SD 7.5 ] , 77 % taking an anticoagulant ) participated . After using the decision aid , mean decisional conflict score was low at 7.2 [ SD 10.8 ] on a scale from 1 to 100 . Mean knowledge score ( total possible 10 ) improved from 7.4 [ SD 1.7 ] to 9.3 [ SD 1.0 ] ( p<0.001 ) . The mean helpfulness score in making a treatment choice was high at 6.2 [ SD 0.9 ] on a scale from 1 to 7 . No participant found the decision aid difficult to underst and . Information in the decision aid was rated as good or excellent in terms of clarity and comprehensiveness . CONCLUSIONS Our decision aid addresses a key medication safety gap - assisting patients to participate in shared decisions about anticoagulation . Future research is required to evaluate how decision aids influence actual choices and clinical outcomes BACKGROUND Anticoagulants are effective in preventing stroke in those with atrial fibrillation , but most patients remain untreated . AIM To investigate the prevalence of disability , cognitive impairment , and problems with compliance in a representative sample of the elderly with atrial fibrillation , and to determine whether they would want treatment and how they would like services to be arranged . METHOD In a survey of a r and om sample of 4843 elderly subjects , those with atrial fibrillation were identified using electrocardiograms . Views on treatment were obtained using a structured interview . Disability was assessed using the Office of Population Censuses and Surveys Disability Scale and cognitive status using the Mini Mental State Examination . General practitioners were asked , via question naire , for their views on each subject 's compliance . RESULTS Two hundred and seven elderly people with atrial fibrillation were identified . Almost all subjects expressed a willingness to undertake treatment to prevent stroke and preferred blood testing performed outside of hospital . Disability ( 82.7 % ) , cognitive impairment ( 25.7 % ) , and problems with compliance ( 25.0 % ) were common , but the prevalence of these difficulties was not substantially different from the general elderly population , and in many cases they could be overcome ( e.g. only 10 % of subjects had problems with compliance and no-one who could help them to comply ) . CONCLUSIONS Most elderly people with atrial fibrillation would accept treatment to prevent stroke . Disability , cognitive impairment , and problems with compliance may make it difficult to treat this patient group . An increase in the use of anticoagulants should be accompanied by the development of services appropriate to this frail population Since the introduction of new oral anticoagulants ( NOACs ) , besides vitamin-K antagonists , an additional option for stroke prevention of patients with atrial fibrillation ( AF ) is available . The objective of this study was to assess AF patients ’ preferences with regard to the attributes of these different treatment options . We conducted a multicenter study among r and omly selected physicians . Preferences were assessed by computer-assisted telephone interviews . We used a discrete-choice-experiment ( DCE ) with four convenience-related treatment dependent attributes ( need of bridging : yes/no , interactions with food/nutrition : yes/no , need of INR controls/dose adjustment : yes/no ; frequency of intake : once/twice daily ) and one comparator attribute ( distance to practitioner : < 1 km/>15 km ) . Preferences measured in the interviews were analyzed descriptively and based on a conditional logit regression model . A total of 486 AF patients ( age : 73.9 ± 8.2 years ; 43.2 % female ; mean CHA2DS2-VASc : 3.7 ± 1.6 ; current medication : 48.1 % rivaroxaban , 51.9 % VKA ) could be interviewed . Regardless of type of medication , patients significantly preferred the attribute levels ( in order of patients ’ importance ) “ once daily intake ” ( Level : once = 1 vs. twice = 0 ; Coefficient = 0.615 ; p < 0.001 ) , “ bridging necessary ” ( yes = 1 vs. no = 0 ; −0.558 ; p < 0.001 ) , “ distance to practitioner of ≤1 km ( > 15 km = 0 vs. ≤1 km = 1 ; 0.494 ; p < 0.001 ) , “ interactions with food/nutrition ” ( yes = 1 vs. no = 0 ; −0.332 ; p < 0.001 ) and “ need of INR controls/dose adjustment ” ( yes = 1 vs. no = 0 ; −0.127 ; p < 0.001 ) . In our analyses , “ once daily frequency of intake ” was the most important OAC-attribute for patients ’ choice followed by “ no bridging necessary ” and “ no interactions with food/nutrition ” . Thus , patients with AF seem to prefer treatment options which are easier to administer Abstract Objective : To determine and compare physicians ' and patients ' thresholds for how much reduction in risk of stroke is necessary and how much risk of excess bleeding is acceptable with antithrombotic treatment in people with atrial fibrillation . Design : Prospect i ve observational study . Setting : Tertiary and peripheral referral centres in Nova Scotia , Canada . Participants : 63 physicians who were treating patients with atrial fibrillation and 61 patients at high risk for atrial fibrillation . Main outcome measures : Participants underwent a face to face interview with a probability trade-off tool . Thresholds were determined for the minimum reduction in risk of stroke necessary and the maximum increase in risk of excess bleeding acceptable for treatment with aspirin and warfarin in people with atrial fibrillation . Results : The minimum number of strokes that needed to be prevented in 100 patients over two years for warfarin to be justified was significantly lower for patients than for physicians ( 1.8 ( SD 1.9 ) v 2.5 ( 1.6 ) , P=0.009 ) , whereas for aspirin there was no difference between patients and physicians ( 1.3 ( 1.3 ) v 1.6 ( 1.5 ) , P=0.29 ) . The maximum number of excess bleeds acceptable in 100 patients over two years for use of warfarin and aspirin was significantly higher for patients than for physicians ( warfarin 17.4 ( 7.1 ) v 10.3 ( 6.1 ) ; aspirin 14.7 ( 8.5 ) v 6.7 ( 6.2 ) ; P<0.001 for both comparisons ) . Conclusions : Patients at high risk for atrial fibrillation placed more value on the avoidance of stroke and less value on the avoidance of bleeding than did physicians who treat patients with atrial fibrillation . The views of the individual patient should be considered when decisions are being made about antithrombotic treatment for people with atrial fibrillation . What is already known on this topic Several observational studies have shown an apparent underuse of antithrombotic drugs in patients with atrial fibrillation , despite evidence of efficacy What this study adds There is considerable variability between physicians and patients in their weighing up of the potential outcomes associated with atrial fibrillation and its treatment For anticoagulation treatment to be acceptable patients required less reduction in risk of stroke and were more tolerant of an increase in risk of bleeding than physicians Physicians varied considerably in how much risk of bleeding they thought was acceptable for a given reduction in risk of stroke associated with antithrombotic BACKGROUND Warfarin sodium is a highly efficacious drug , but proper levels of anticoagulation are difficult to maintain . Conflicting data exist on the influence of patient adherence on anticoagulation control . METHODS We performed a prospect i ve cohort study at 3 anticoagulation clinics to determine the effect of adherence on anticoagulation control . Patients treated with warfarin with a target international normalized ratio of 2.0 to 3.0 were monitored with electronic Medication Event Monitoring System ( MEMS ) medication bottle caps . Detailed information was collected on other factors that might alter warfarin response . RESULTS Among 136 participants observed for a mean of 32 weeks , 92 % had at least 1 missed or extra bottle opening ; 36 % missed more than 20 % of their bottle openings ; and 4 % had more than 10 % extra bottle openings . In multivariable analyses , there was a significant association between underadherence and underanticoagulation . For each 10 % increase in missed pill bottle openings , there was a 14 % increase in the odds of underanticoagulation ( P<.001 ) ; participants with more than 20 % missed bottle openings ( 1 - 2 missed days each week ) had more than a 2-fold increase in the odds of underanticoagulation ( adjusted odds ratio , 2.10 ; 95 % confidence interval , 1.48 - 2.96 ) . Participants who had extra pill bottle openings on more than 10 % of days had a statistically significant increase in overanticoagulation ( adjusted odds ratio , 1.73 ; 95 % confidence interval , 1.09 - 2.74 ) . CONCLUSION Patients have substantial difficulties maintaining adequate adherence with warfarin regimens , and this poor adherence has a significant effect on anticoagulation control OBJECTIVE To examine the cost-effectiveness of prescribing warfarin sodium in patients who have nonvalvular atrial fibrillation ( NVAF ) with or without additional stroke risk factors ( a prior stroke or transient ischemic attack , diabetes , hypertension , or heart disease ) . DESIGN Decision and cost-effectiveness analyses . The probabilities for stroke , hemorrhage , and death were obtained from published r and omized controlled trials . The quality -of-life estimates were obtained by interviewing 74 patients with atrial fibrillation . Costs were estimated from literature review , phone survey , and Medicare reimbursement . PATIENTS In the base case , the patients were 65 years of age and good c and i date s for warfarin therapy . INTERVENTIONS Treatment with warfarin , aspirin , or no therapy in the decision analytic model . MAIN OUTCOME MEASURES Quality -adjusted survival and marginal cost-effectiveness of warfarin as compared with aspirin or no therapy . RESULTS For patients with NVAF and additional risk factors for stroke , warfarin therapy led to a greater quality -adjusted survival and to cost savings . For patients with NVAF and one additional risk factor , warfarin therapy cost $ 8000 per quality -adjusted life-year saved . For 65-year-old patients with NVAF alone , warfarin cost about $ 370,000 per quality -adjusted life-year saved , as compared with aspirin therapy . However , for 75-year-old patients with NVAF alone , prescribing warfarin cost $ 110,000 per quality -adjusted life-year saved . For patients who were not prescribed warfarin , aspirin was preferred to no therapy on the basis of both quality -adjusted survival and cost in all patients , regardless of the number of risk factors present . CONCLUSIONS Treatment with warfarin is cost-effective in patients with NVAF and one or more additional risk factors for stroke . In 65-year-old patients with NVAF but no other risk factors for stroke , prescribing warfarin instead of aspirin would affect quality -adjusted survival minimally but increase costs significantly BACKGROUND Because most strokes cause neurological impairment rather than death , stroke prophylaxis may improve quality of life more than length of life . Thus , an underst and ing of how stroke and stroke prophylaxis affect quality of life is central to clinical decision making for many patients . METHODS We elicited quality -of-life estimates , known as utilities , for 3 degrees of severity of anticipated stroke-mild , moderate , and major- and for stroke prophylaxis with either warfarin sodium or aspirin therapy . We used the time tradeoff and st and ard gamble methods to elicit these utilities from 83 patients who had atrial fibrillation . RESULTS Seventy patients completed the interview successfully . Their utilities for stroke ranged from worse than death ( < 0 ) to as good as current health ( 1.0 ) . The median utilities for mild , moderate , and major stroke were 0.94 , 0.07 , and 0.0 , respectively . Although the median utilities decreased with increasing severity of stroke ( P < .001 ) , there was high interpatient variability within each degree of stroke severity . For example , 7 subjects ( 10 % ) rated a major stroke above 0.5 , while 58 subjects ( 83 % ) rated it as equal to or worse than death . In contrast to the stroke utilities , the median utilities for warfarin and aspirin therapy were high-0.997 and 1.0 , respectively . However , the interpatient variability for warfarin therapy was also important : 11 patients ( 16 % ) with atrial fibrillation rated the utility of warfarin therapy so low that their quality -adjusted life expectancy would be greater with aspirin . CONCLUSION Patients ' utilities for stroke prophylaxis and anticipated stroke vary substantially . Many patients view the quality of life with major stroke as tantamount to or worse than death . These findings highlight the relevance of incorporating patient preferences when choosing stroke prophylaxis OBJECTIVE To investigate the effect of patients ' preferences in the treatment of atrial fibrillation by using individualized decision analysis in which probability and utility assessment s are combined into a decision tree . DESIGN Observational study based on interviews with patients . SETTING 8 general practice s in Avon , Engl and . PARTICIPANTS 260 r and omly selected patients aged 70 to 85 years with atrial fibrillation . MAIN OUTCOME MEASURES Patients ' treatment preferences regarding anticoagulation treatment ( warfarin sodium ) after individualized decision analysis ; comparison of these preferences with treatment guidelines on the basis of comorbidity and absolute risk and compared with current prescription . RESULTS Of 195 eligible patients , 97 participated in decision making using decision analysis . Among these 97 , the decision analysis indicated that 59 ( 61 % ; 95 % confidence interval , 50%-71 % ) would prefer anticoagulation treatment , considerably fewer than those who would be recommended treatment according to guidelines . There was marked disagreement between the decision analysis and guideline recommendations ( kappa > or = 0.25 ) . Of 38 patients whose decision analysis indicated a preference for anticoagulation , 17 ( 45 % ) were being prescribed warfarin ; on the other h and , 28 ( 47 % ) of 59 patients were not being prescribed warfarin , although the results of their decision analysis suggested they wanted to be . CONCLUSIONS In the context of shared decision making , individualized decision analysis is valuable in a sizable proportion of elderly patients with atrial fibrillation . Taking account of patients ' preferences would lead to fewer prescriptions for warfarin than under published recommendations . Decision analysis as a shared decision-making tool should be evaluated in a r and omized controlled trial The Canadian Cardiovascular Society ( CCS ) published the complete set of 2010 Atrial Fibrillation ( AF ) Guidelines in the January , 2011 issue of the Canadian Journal of Cardiology . During its deliberations , the CCS Guidelines Committee engaged to a timely review of future evidence , with periodic composition of focused up date s to address clinical ly important advances . In 2011 , results were published from 3 pivotal AF trials : the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonist for Prevention of Stroke and Embolism Trial in Atrial Fibrillation ( ROCKET-AF ) , the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation ( ARISTOTLE ) study , and the Permanent Atrial Fibrillation Outcome Study Using Dronedarone on Top of St and ard Therapy ( PALLAS ) , comparing dronedarone with placebo in patients with permanent AF and additional cardiovascular disease risk-factor burden . Each of these large r and omized trials provided clear results with major implication s for AF management . Other important evidence that has emerged since the 2010 Guidelines includes findings about prediction instruments for AF-associated stroke and bleeding risk , stroke risk in paroxysmal-AF patients , risk-benefit considerations related to oral anticoagulation in patients with chronic kidney disease , and risk/benefit considerations in the use of antiplatelet agents , alone and in combination with each other or with oral anticoagulants , in AF patients . The Guidelines Committee judged that this extensive and important new evidence required focused updating of the 2010 Guidelines with respect to stroke prevention and rate/rhythm control . This report presents the details of the new recommendations , along with the background and rationale OBJECTIVES To design a tool for nonvalvular atrial fibrillation ( NVAF ) to inform individuals of their individual stroke and bleeding risks , assist in clarifying priorities , and promote communication . DESIGN Clustered r and omized controlled trial . SETTING Primary care clinics . PARTICIPANTS Individuals with NVAF ( N = 135 ) . INTERVENTION Completion of tool before regularly scheduled visit . MEASUREMENTS Primary outcomes included the 100-point informed and values clarity subscales of the decisional conflict scale ( lower scores indicate individual is more informed and has greater clarity ) . Secondary outcomes included knowledge , patient-clinician communication , and change in treatment . RESULTS Sixty-nine individuals were enrolled in the intervention group and 66 in the control group . After their visit , intervention participants had lower scores on the informed ( mean difference = -11.9 , 95 % confidence interval ( CI ) = -21.1 to -2.7 ) and values clarity subscales ( mean difference = -14.6 , 95 % CI = -22.6 to -6.6 ) . Greater proportions of intervention participants knew medications for reducing stroke risk ( 61 % vs 31 % , P < .001 ) and side effects ( 49 % vs 37 % , P = .07 ) . Stroke ( 71 % vs 12 % ) and bleeding risk ( 69 % vs 20 % ) were discussed more frequently in the intervention than control group ( P < .001 ) . Five intervention participants expressed a preference for medication that was not concordant with their current treatment plan . There was no change in treatment plan in either group . CONCLUSION The tool was effective in improving perceived and actual knowledge and values clarity and in increasing physician-patient communication but did not change treatment OBJECTIVE To determine the minimal clinical ly important difference ( MCID ) of warfarin therapy for the treatment of nonvalvular atrial fibrillation from the perspective of patients using 2 different elicitation methods . DESIGN All patients completed 2 face-to-face interviews , which were 2 weeks apart . For each interview , they were r and omized to receive 1 of 2 elicitation methods : ping-ponging or starting at the known efficacy . SETTING The practice s of 2 university-affiliated family medicine centers ( 8 physicians each ) , 14 community-based family physicians , and 2 cardiologists . PATIENTS Sixty-four patients with nonvalvular atrial fibrillation who were initiated with warfarin therapy at least 3 months before the study . INTERVENTION During each interview , the patients ' MCIDs were determined by using ( 1 ) a pictorial flip chart to describe atrial fibrillation ; the consequences of a minor stroke , a major stroke , and a major bleeding episode ; the chance of stroke if not taking warfarin ; the chance of a major bleeding episode if taking warfarin ; examples of the inconvenience , minor side effects , and costs of warfarin therapy ; and then ( 2 ) 1 of the 2 elicitation methods to determine their MCIDs ( the smallest reduction in stroke risk at which the patients were willing to take warfarin ) . Patients ' knowledge of their stroke risk , acceptability of the interview process , and factors determining their preferences were also assessed . MAIN RESULTS Given a baseline risk of having a stroke in the next 2 years , if not taking warfarin , of 10 of 100 , the mean MCID was 2.01 of 100 ( 95 % confidence interval , 1.60 - 2.42 ) . Fifty-two percent of the patients would take warfarin for an absolute decrease in stroke risk of 1 % over 2 years . Before eliciting their MCIDs , patients showed poor knowledge of their stroke risk , which improved afterward . The interview process was well accepted by the patients . The MCID using the ping-ponging elicitation method was 1.015 of 100 smaller compared with use of the starting at the known efficacy method ( P = .01 ) . CONCLUSIONS We were able to determine the MCID of warfarin therapy for the prevention of stroke from the perspective of patients with nonvalvular atrial fibrillation . Their MCIDs were much smaller than those that have been implied by some experts and clinicians . The interview process , using the flip chart approach , appeared to improve the patients ' knowledge of their disease and its consequences and treatment . The method used to elicit the patients ' MCIDs can have a clinical ly important effect on patient responses . The method used in our study can be generalized to other conditions and , thus , could be helpful in 3 ways : ( 1 ) from a clinical decision-making perspective , it could facilitate patient-physician communication ; ( 2 ) it could clarify the patient perspective when interpreting the results of previously completed trials ; and ( 3 ) it could be used to derive more clinical ly relevant sample sizes for r and omized treatment trials BACKGROUND Real-world data on patients ' and physicians ' values related to the use of oral anticoagulant ( OAC ) therapy for stroke prevention in patients with nonvalvular atrial fibrillation are currently lacking . We sought to assess the values , preferences , and experience of patients who receive OAC therapy , and of physicians who prescribe OAC therapy . METHODS A national survey of r and omly selected patients ( n = 266 ) and physicians ( n = 178 ) was conducted between May and September 2014 . Each was asked to evaluate the importance of individual OAC attributes and identify which of 2 medication profiles they would prefer ( individual attributes were progressively modified to determine which were the most valued and /or influenced treatment choice ) . Medication adherence and prescription practice was also assessed . RESULTS The preferences of patients and physicians regarding OAC therapy differed but largely focused on characteristics related to safety and , to a lesser extent , efficacy . When based solely on the basis of the attribute profile ( blinded to the specific agent ) , physicians were more likely to select apixaban ( 61 % ) , whereas patients showed no significant preference among apixaban , rivaroxaban , and warfarin . Despite this , 49 % of physicians spontaneously stated rivaroxaban as their preferred agent ( vs 25 % apixaban ) . Patients prescribed and taking once daily medications ( rivaroxaban or warfarin ) showed better compliance with their OAC therapy ( approximately 30 % of twice daily medications being taken once daily , with significantly more missed doses compared with once daily medications ) . CONCLUSIONS Real-world prescriptions do not reflect reported values , which suggests that other factors influence patient-physician decision-making around OAC therapy . Data on self-reported adherence to OAC therapy and discordance in the use of OACs from prescribed regimens are concerning and warrant further investigation Abstract Objective : To investigate the impact of patients ' preferences for the treatment of atrial fibrillation , by using individualised decision analysis combining probability and utility assessment s into a decision tree . Design : Observational study based on interviews with patients . Setting : Eight general practice s in Avon . Participants : 260 r and omly selected patients aged 70–85 years with atrial fibrillation . Main outcome measures : Patients ' treatment preferences regarding anticoagulation treatment ( warfarin ) after individualised decision analysis ; comparison of these preferences with treatment guidelines on the basis of comorbidity and absolute risk and compared with current prescription . Results : Of 195 eligible patients , 97 participated in decision making using decision analysis . Among these 97 , the decision analysis indicated that 59 ( 61 % ; 95 % confidence interval 50 % to 71 % ) would prefer anticoagulation treatment — considerably fewer than those who would be recommended treatment according to guidelines . There was marked disagreement between the decision analysis and guideline recommendations ( kappa = 0.25 or less ) . Of 38 patients whose decision analysis indicated a preference for anticoagulation , 17 ( 45 % ) were being prescribed warfarin ; on the other h and , 28 ( 47 % ) of 59 patients were not being prescribed warfarin although the results of their decision analysis suggested they wanted to be . Conclusions : In the context of shared decision making , individualised decision analysis is valuable in a sizeable proportion of elderly patients with atrial fibrillation . Taking account of patients ' preferences would lead to fewer prescriptions for warfarin than under published guideline recommendations . Decision analysis as a shared decision making tool should be evaluated in a r and omised controlled trial BACKGROUND Vitamin K antagonists are highly effective in preventing stroke in patients with atrial fibrillation but have several limitations . Apixaban is a novel oral direct factor Xa inhibitor that has been shown to reduce the risk of stroke in a similar population in comparison with aspirin . METHODS In this r and omized , double-blind trial , we compared apixaban ( at a dose of 5 mg twice daily ) with warfarin ( target international normalized ratio , 2.0 to 3.0 ) in 18,201 patients with atrial fibrillation and at least one additional risk factor for stroke . The primary outcome was ischemic or hemorrhagic stroke or systemic embolism . The trial was design ed to test for noninferiority , with key secondary objectives of testing for superiority with respect to the primary outcome and to the rates of major bleeding and death from any cause . RESULTS The median duration of follow-up was 1.8 years . The rate of the primary outcome was 1.27 % per year in the apixaban group , as compared with 1.60 % per year in the warfarin group ( hazard ratio with apixaban , 0.79 ; 95 % confidence interval [ CI ] , 0.66 to 0.95 ; P<0.001 for noninferiority ; P=0.01 for superiority ) . The rate of major bleeding was 2.13 % per year in the apixaban group , as compared with 3.09 % per year in the warfarin group ( hazard ratio , 0.69 ; 95 % CI , 0.60 to 0.80 ; P<0.001 ) , and the rates of death from any cause were 3.52 % and 3.94 % , respectively ( hazard ratio , 0.89 ; 95 % CI , 0.80 to 0.99 ; P=0.047 ) . The rate of hemorrhagic stroke was 0.24 % per year in the apixaban group , as compared with 0.47 % per year in the warfarin group ( hazard ratio , 0.51 ; 95 % CI , 0.35 to 0.75 ; P<0.001 ) , and the rate of ischemic or uncertain type of stroke was 0.97 % per year in the apixaban group and 1.05 % per year in the warfarin group ( hazard ratio , 0.92 ; 95 % CI , 0.74 to 1.13 ; P=0.42 ) . CONCLUSIONS In patients with atrial fibrillation , apixaban was superior to warfarin in preventing stroke or systemic embolism , caused less bleeding , and result ed in lower mortality . ( Funded by Bristol-Myers Squibb and Pfizer ; ARISTOTLE Clinical Trials.gov number , NCT00412984 . ) |
868 | 17,347,953 | In patients with MN , nephrotic syndrome and normal renal function , methylprednisolone and chlorambucil or cyclophosphamide for 6 months alternately increase the probability of nephritic syndrome remission ( evidence from SR ) and long-term renal protection ( evidence from RCT ) .
Other drugs ( ACTH and cyclosporine ) are associated with nephrotic syndrome remission , but there is no evidence of significant effects on renal function ( evidence from RCT ) .
In patients with impaired renal function , association of corticosteroids and cytotoxic agents is proven to cause a short-term delay of renal damage progression , even though benefits are counterbalanced by complications ( evidence from RCT ) . | BACKGROUND The current 3rd edition of the Italian Society of Nephrology guidelines has been drawn up to summarize evidence of key intervention issues on the basis of systematic review s ( SR ) of r and omized trials ( RCT ) or RCT data only .
In the present guideline , evidence of interventions for idiopathic membranous nephropathy ( MN ) is presented . | To assess whether chlorambucil or cyclophosphamide may have a better therapeutic index in patients with idiopathic membranous nephropathy , we compared two regimens based on a 6-mo treatment , alternating every other month methylprednisolone with chlorambucil or methylprednisolone with cyclophosphamide . Patients with biopsy-proven membranous nephropathy and with a nephrotic syndrome were r and omized to be given methylprednisolone ( 1 g intravenously for 3 consecutive days followed by oral methylprednisolone , 0.4 mg/kg per d for 27 d ) alternated every other month either with chlorambucil ( 0.2 mg/kg per d for 30 d ) or cyclophosphamide ( 2.5 mg/kg per d for 30 d ) . The whole treatment lasted 6 mo ; 3 mo with corticosteroids and 3 mo with one cytotoxic drug . Among 87 patients followed for at least 1 yr , 36 of 44 ( 82 % ; 95 % confidence interval [ CI ] , 67.3 to 91.8 % ) assigned to methylprednisolone and chlorambucil entered complete or partial remission of the nephrotic syndrome , versus 40 of 43 ( 93 % ; 95 % CI , 80.9 to 98.5 % ) assigned to methylprednisolone and cyclophosphamide ( P = 0.116 ) . Of patients who attained remission of the nephrotic syndrome , 11 of 36 in the chlorambucil group ( 30.5 % ) and 10 of 40 in the cyclophosphamide group ( 25 % ) had a relapse of the nephrotic syndrome between 6 and 30 mo . The reciprocal of plasma creatinine improved in the cohort groups followed for 1 yr for both treatment groups ( P < 0.01 ) and remained unchanged when compared with basal values in the cohort groups followed for 2 and 3 yr . Six patients in the chlorambucil group and two in the cyclophosphamide group did not complete the treatment because of side effects . Four patients in the chlorambucil group but none in the cyclophosphamide group suffered from herpes zoster . One patient per group developed cancer . It is concluded that in nephrotic patients with idiopathic membranous nephropathy both treatments may be effective in favoring remission and in preserving renal function for at least 3 yr BACKGROUND We conducted a pilot trial to compare the effectiveness and safety of 2 different treatments in patients with membranous nephropathy and nephrotic syndrome . METHODS To vali date the hypothesis that the 2 treatments were equivalent , patients with biopsy-proven membranous nephropathy and nephrotic syndrome were r and omly assigned to methylprednisolone alternated with a cytotoxic drug every other month for 6 months ( group A ) or to intramuscular synthetic adrenocorticotropic hormone administered twice a week for 1 year ( group B ) . RESULTS The primary outcome measure is cumulative number of remissions as a first event . Fifteen of 16 patients in group A and 14 of 16 patients in group B entered complete or partial remission as a first event . After a median follow-up of 24 months ( interquartile range , 15 to 25 months ) , there were 4 complete remissions and 8 partial remissions in group A versus 8 complete remissions and 6 partial remissions in group B. Median proteinuria decreased from protein of 5.1 g/d ( interquartile range , 4.0 to 7.3 g/d ) to 2.1 g/d ( interquartile range , 0.4 to 3.8 g/d ; P = 0.004 ) in group A and 6.0 g/d ( interquartile range , 4.4 to 8.5 g/d ) to 0.3 g/d ( interquartile range , 0.2 to 1.9 g/d ; P = 0.049 ) in group B. Two patients from each group interrupted treatment because of side effects or inefficacy . CONCLUSION Most nephrotic patients with membranous nephropathy responded to either treatment . Proteinuria was significantly decreased with both methylprednisolone and cytotoxic agents or prolonged administration of synthetic adrenocorticotropic hormone , without significant differences between these 2 therapies In this retrospective non-r and omized study we review ed the outcome for 41 patients with membranous nephropathy older than 65 years at onset and followed for at least 1 year . Twelve of the patients never received any specific treatment ( group A ) , 15 were treated with a 6-month course of methylprednisolone alternated to chlorambucil every other month ( group B ) , and 14 received corticosteroids alone for 3 - 12 months ( group C ) . At the end of a mean follow-up of 92 + /- 61 months in group A , 53 + /- 35 in group B , and 38 + /- 25 in group C there were significantly more remissions of nephrotic syndrome in group B than in group A ( P = 0.035 ) or in group C ( P = 0.010 ) . Moreover patients in group B spent a significantly longer period without nephrotic syndrome than patients in group A ( P = 0.000 ) and C ( P = 0.000 ) . Three patients in group A and one in group B died . During the follow-up six patients of group A , two of group B , and five of group C developed renal function deterioration . In patients followed for at least 5 years the mean plasma creatinine increased from a basal of 112 + /- 29 to 239 + /- 287 mumol/l at the 5th year in group A and from 113 + /- 14 to 124 + /- 30 mumol/l in group B. The mean urine protein excretion remained unchanged in group A ( basal 4.6 + /- 2.3 versus 4.8 + /- 5.7 g/day at 5 years ) while it decreased in group B ( from a basal of 6.8 + /- 3.5 to 1.1 + /- 0.4 g/day at 5 years ) . ( ABSTRACT TRUNCATED AT 250 WORDS Patients with various forms of glomerulonephritis , but excluding those with minimal glomerular changes , were admitted to a controlled trial of a regimen which combined azathioprine in a dosage of 2·5 mg/kg/day with prednisone in a dosage of 20 mg/day ( adults ) or 0·5 mg/kg/day ( children ) . Of 149 patients included , 32 of them under the age of 15 , 72 were r and omly allocated to the “ treatment ” group and 77 to the “ control ” group . There was no evidence of benefit from the treatment group as a whole ; and the mortality was in fact higher in the treated group Patients with membranous glomerulonephritis ( MGN ) , impaired renal function and the nephrotic syndrome are at high risk of developing renal failure . Twenty-six such patients were studied with serum creatinine concentrations exceeding 135 microM , and 24-hour urine protein excretion of at least 3.5 g/day to determine the potential benefit of cyclophosphamide therapy . Cyclophosphamide ( mean 1.5 mg/kg/day ) was given to nine patients for 23 + /- 4 months . These patients were compared with 17 concurrent controls . The two groups did not differ in clinical or laboratory features at the time of biopsy or start of treatment or its equivalent . Six of the nine cyclophosphamide treated patients and 15 of the 17 controls had received prednisone therapy . The total follow-up was 49 + /- 10 months in the treated group and 50 + /- 6 months in the controls . At last observation , serum creatinine values exceeded 400 microM in eight controls ( 4 on dialysis ) and in none of the treated patients . The mean serum creatinine level was significantly lower ( P less than 0.02 ) in the treated group ( 173 + /- 24 microM ) than in controls ( 433 + /- 71 0.02 ) in the treated group ( 173 + /- 24 microM ) than in controls ( 433 + /- 71 microM ) . The mean serum albumin level and 24-hour urine protein excretion both improved significantly with treatment as compared with controls . There were four complete remissions , five partial remissions and no patient with persistent nephrotic syndrome after treatment . In the controls , there were no complete remissions , six partial remissions and 11 patients had persistent nephrotic syndrome ( P less than 0.001 ) . Thus , cyclophosphamide therapy appears to be of benefit in patients with MGN , the nephrotic syndrome and impaired renal function Because of the high rate of spontaneous remission , treatment of membranous nephropathy with prednisolone and chlorambucil is still controversial . The aim of this study was to give this therapy only to those patients at risk of developing renal insufficiency and to test the efficacy of a low-dose therapeutic regimen . Seventeen patients with more than 10 g protein excretion per day ( mean 16.9 ) and /or a deterioration in renal function ( mean serum creatinine , 162 μmol/l ) were included . Serum total protein , serum lipids , proteinuria , serum creatinine , and blood pressure were measured , along with the diuretic and antihypertensive medication . The observation time before the start of treatment was 27 ± 27 months . Steroids were given during months 1 , 3 , and 5 ( methylprednisolone 3 × 500 mg intravenously ) prednisolone 0.5 mg/kgBW daily per os for 1 week , then tapered by 0.1 mg/kg BW/week for 1 month . Chlorambucil was given during months 2 , 4 , and 6 at a dose of 0.12 mg/kgBW daily . At the end of treatment proteinuria had significantly decreased ( mean of all patients , 7.8 ± 1.4 g/d ) in all patients . Six months after the end of treatment proteinuria was significantly lower than at baseline in 14 of 17 patients . Hypoproteinemia and hyperlipidemia had improved ; diuretic and antihypertensive medication were reduced . Elevated serum creatinine decreased in 7 of 9 patients ( pretreatment , 227 ± 39 μmol/1 ; 6 months , 176 ± 28 μmol/l ) . Nonresponders with respect to serum creatinine responded with respect to proteinuria . Regarding adverse effects , two patients complained of dyspepsia while taking steroids ; during chlorambucil treatment two patients experienced nausea and lack of appetite , and one developed leukopenia ( 1600/μl ) . Chlorambucil was stopped and cell counts normalized 2 weeks later . We conclude that low-dose prednisolone/chlorambucil is both safe and efficient in the majority of patients with severe membranous nephropathy Controlled trial of cyclophosphamide in idiopathic membranous nephropathy . We evaluated cyclophosphamide treatment in a controlled prospect i ve study of 22 adult patients with clinical ly and histologically defined idiopathic membranous nephropathy . By r and om assignment , 11 patients received no drug and 11 patients received cyclophosphamide orally , 1.5 to 2.5 mg/kg/day ( mean , 1.8 ) , for one year . Before treatment , the two groups were similar in age and sex distributions , duration of illness , blood pressure , degree of proteinuria , renal function and histologic staging . After treatment , a downward trend in proteinuria was noted , with no significant difference in the quantity and rate of decrease between groups . Renal function ( C in and C PAH ) was stable in all patients , with no difference between groups . On comparing pretreatment and one-year renal biopsy specimens in eight patients in each group , regardless of treatment or clinical outcome , the appearance of the renal lesions remained the same or progressed in terms of basement membrane thickening and incorporation of subepithelial deposits , and immunofluorescence with IgG and C3 remained positive in glomerular capillaries . Cyclophosphamide dosage was decreased in five patients because of recurrent leukopenia ; no other major toxicity was observed . Beyond one year of treatment , renal function has decreased in two of eight patients in the no-drug group and in one of seven patients in the cyclophosphamide-treated group . We conclude that treatment with cyclophosphamide for one year did not have a favorable effect on proteinuria , renal function or morphologic aspects of the glomerular lesion . Essai controle du cyclophosphamide dans la nephropathie membraneuse idiopathique . Nous avons evalue le traitement par le cyclophosphamide dans une etude prospect i ve controlee de 22 malades adultes atteints de nephropathie membraneuse idiopathique cliniquement et anatomiquement definie . Au hasard , onze malade n'ont recu aucun traitement et onze autres ont eu du cyclophosphamide par voie orale a raison de 1,5 a 2,5 mg/kg par jour ( 1,8 en moyenne ) pendant un an . Avant le traitement les deux groupes etaient semblables en distribution d'âge et de sexe , duree de la maladie , pression arterielle , importance de la proteinurie , fonction renale et etat histologique . Apres traitement , une tendance a la diminution de la proteinurie a ete observee sans difference significative entre les groupes dans le debit de proteine ou la vitesse de diminution . La fonction renale ( C in et C PAH ) etait stable chez tous les malades , sans difference entre les groupes . La comparaison des biopsies avant traitement et apres un an chez huit malades de chaque groupe , independamment du traitement ou de l'evolution clinique , a montre que les lesions renales sont restees les memes ou ont progresse , sous la forme d'un epaississement de la membrane basale et de l'incorporation de depots sous-epitheliaux , et que l'immunofluorescence avec IgG et C3 reste positive dans les capillaires glomerulaires . La posologie du cyclophosphamide a ete diminuee chez cinq malades en raison d'une leucopenie recidivante ; aucune autre toxicite majeure n'a ete observee . Au-dela d'un an de traitement , la fonction renale a diminue chez deux des huit malades du groupe ne recevant pas de medicament et chez l'un des sept malades du groupe traite par le cyclophosphamide . Nous concluons que le traitement par le cyclophosphamide pendant un an n'a pas eu d'effet favorable sur la proteinurie , la fonction renale ou les lesions histologiques glomerulaires We have assessed the medium-term effect of a short course of high-dose , alternate-day prednisolone on adult nephrotic patients with membranous nephropathy , using a r and omized , prospect i ve , double-blind , controlled trial . Patients were entered over the period 1981 to 1984 and were observed for a minimum of three years . One hundred and seven adult patients who had not previously received immunosuppressive treatment were included in the trial . One hundred and sixty further patients , excluded from the trial , but with membranous nephropathy were identified , followed and assessed retrospectively at the end of the trial . At 36 months there was no significant difference between control and treatment groups in plasma creatinine , creatinine clearance or 24-h excretion of protein . At between three and six months serum albumin concentrations were higher and protein excretions lower in the treatment group compared to controls . No significant benefit was therefore observed on renal function in the medium term Patients with nephrotic syndrome ( NS ) are believed to be at increased risk of atherosclerosis and coronary heart disease ( CHD ) , although existing evidence for this association has not been persuasive . The risk of CHD among 142 persons with NS documented by protein-uria > or = 3.5 g daily was compared with that among 142 matched controls r and omly selected from the membership of a large Northern California health plan . Controls were matched for sex , year of birth , and presence in the health plan when the referent case was diagnosed . No diabetics were included in this study . Mean follow-up for nonfatal CHD events was 5.6 years for NS subjects and 11.2 years for controls . Among the NS subjects myocardial infa rct ion ( MI ) developed in 11 , and there were 58 deaths , seven because of CHD . Among the controls , there were four MIs and 10 deaths , three because of CHD . In matched-pair analysis , there were 11 MIs among NS subjects and none among controls [ P = 0.001 , lower bound of 95 % confidence interval for relative risk ( CI ) , 2.8 ] . In an unmatched analysis adjusted for hypertension and smoking at diagnosis of NS , the relative risk of MI was 5.5 ( 95 % CI 1.6 to 18.3 ) and the relative risk of coronary death was 2.8 ( 95 % CI 0.7 to 11.3 ) . Omitting data of NS subjects with minimal change disease and systemic lupus erythematosus yielded similar results . These data suggest that persons with NS are at increased risk of CHD We conducted a prospect i ve r and omized study in which patients with biopsy-confirmed idiopathic membranous nephropathy were assigned to receive either a six-month course of prednisone given on alternate days ( 45 mg per square meter of body-surface area ; n = 81 ) or no specific treatment ( n = 77 ) . The mean duration of follow-up was 48 months . Patients in the prednisone group ( median age , 46 years ) entered with a mean disease duration of 15 months , a median creatinine clearance of 1.2 ml per second per 1.73 m2 ( range , 0.25 to 2.6 ) , and a median rate of urinary protein excretion of 6.8 g per day ( 0.3 to 26 ) . The annual change in the corrected creatinine clearance at six months did not differ between the prednisone group and the control group ( 0.10 vs. 0.06 ml per second ; P = 0.8 ) , or at the last follow-up evaluation ( -0.07 vs. -0.02 ml per second ; P = 0.2 ; 95 percent confidence interval on the difference , -0.03 to 0.13 ) . The proportion of patients with complete remission of proteinuria was also similar in the groups at 6 and 12 months and after a mean of 48 months . Outcomes were similar in the two groups with respect to progression to renal failure ( 3 vs. 4 patients ) , death ( 3 vs. 1 patient ) , complete remission of proteinuria at 36 months ( 16 vs. 19 patients ) , and a decline of 25 percent or more in the creatinine clearance at 60 months ( 32 vs. 25 percent of patients ) . A multivariate analysis , which adjusted for differences at entry in sex distribution , urinary protein excretion , and creatinine concentration , as well as other prognostic variables , failed to provide an explanation for the lack of effect of prednisone . We conclude that a six-month course of therapy in which prednisone is given on alternate days is of no benefit to patients with idiopathic membranous nephropathy BACKGROUND Defining the most appropriate treatment for patients with idiopathic membranous nephropathy is a matter of controversy . The course of the disorder is often benign , and the immunosuppressive regimens used in some patients have uncertain benefits and substantial risks . We studied the natural history of idiopathic membranous nephropathy in patients who received only symptomatic therapy . METHODS We prospect ively studied 100 consecutive patients ( 68 men and 32 women ; mean [ + /- SD ] age , 51 + /- 17 years ) with biopsy-proved idiopathic membranous nephropathy . The patients received diuretic or antihypertensive drugs as needed , but no glucocorticoid or immunosuppressive drugs . We examined the patients and measured their urinary protein excretion and serum creatinine concentrations every 6 months for a mean of 52 months . RESULTS Twenty-four ( 65 percent ) of the 37 patients followed for at least five years had complete or partial remission of proteinuria ; in 6 others ( 16 percent ) , end-stage renal disease developed , and they required dialysis . As calculated by the Kaplan-Meier method , the estimated probability ( + /- the st and ard error of the estimate ) of retaining adequate kidney function was 88 + /- 5 percent after five years and 73 + /- 7 percent after eight years . The prognosis was poorer in men and in patients over 50 years of age , but not in patients with the nephrotic syndrome , hypertension , or hypercholesterolemia . CONCLUSIONS Most untreated patients with idiopathic membranous nephropathy maintain renal function for prolonged periods and are likely to have spontaneous remission . These results do not support the use of glucocorticoids and immunosuppressive drugs in patients with idiopathic membranous nephropathy BACKGROUND Previous studies have shown that short-term treatment with adrenocorticotrophic hormone ( ACTH ) has a strong and rapid lipid-lowering effect . In this long-term study of nephrotic patients with idiopathic membranous nephropathy , the influence of ACTH on the serum lipoprotein profile and glomerular function as well as the dose-effect relationship was investigated . METHODS Fourteen patients received ACTH intramuscularly at increasing doses during 56 days . Serum concentrations of lipids , lipoproteins , and apolipoproteins as well as variables of glomerular function were analyzed , and the side-effects were recorded . ACTH treatment , in the estimated optimal dosage , was then continued in five patients with severe steroid-resistant nephrotic syndrome . In these five patients , the total treatment period was 12 months , and the follow-up time after discontinuing treatment was 18 months . RESULTS Taking both the statistically significant therapeutic effects and the modest side-effects into consideration , the optimal dosage of ACTH was estimated to be 1 mg twice per week . At that dose , reductions by 30 to 60 % in the serum concentrations of cholesterol , triglycerides , apolipoprotein B , and lipoprotein(a ) were observed , whereas the serum concentrations of high-density lipoprotein cholesterol and apolipoprotein AI rose by 30 to 40 % . In addition , the urinary albumin excretion decreased by 90 % , and the glomerular filtration rate increased by 25 % . Deterioration was observed in all cases when ACTH was discontinued after a treatment duration of 56 days . However , the five patients in whom ACTH therapy was resumed were still in remission 18 months after discontinuance of treatment . CONCLUSIONS In nephrotic patients with idiopathic membranous nephropathy , treatment with ACTH 1 mg twice per week was associated with significant long-term improvements in serum lipoprotein pattern and glomerular function 40 patients with idiopathic membranous glomerulonephritis were r and omized to receive either no treatment or a regime of cyclophosphamide for 6 months , and warfarin and dipyridamole for two years . During the two years of the trial there was no significant deterioration in renal function in either group . A significantly greater improvement in urinary protein excretion was , however , observed at all time points in the treatment group . Plasma albumin was also significantly higher in the treatment group at 18 and 24 months . As progressive deterioration in renal function in membranous glomerulonephritis is associated with persistent heavy proteinuria these results suggest a beneficial effect of treatment Sixty-seven adults with idiopathic membranous nephropathy and the nephrotic syndrome were r and omly assigned to symptomatic treatment only or to a six-month course of methylprednisolone alternated with chlorambucil every other month . Patients were followed for one to seven years . At the end of follow-up ( mean of 31.4 + /- 18.2 months for the treated group and 37.0 + /- 22.0 for the control group ) 23 of 32 treated patients were in complete or partial remission , as compared with 9 of 30 control patients ( P = 0.001 ) . Twelve of the treated patients were in complete remission , as compared with only two of the controls . In the treated group there were no changes in renal function during follow-up , whereas in the control group the reciprocal of the plasma creatinin level , which is proportional to the creatinine clearance , decreased significantly ( P = 0.00017 ) after two years of follow-up . Side effects were minimal in all treated patients except two , who were dropped from the study because of peptic ulcer and gastric intolerance to chlorambucil . We conclude that steroid and chlorambucil treatment for six months favors remission of the nephrotic syndrome in adults with idiopathic membranous nephropathy and can preserve renal function for at least some years In most patients with membranous nephropathy , the disease follows a benign course ; only one fourth of the patients develop renal insufficiency [ 1 - 4 ] . Results of r and omized clinical trials assessing the efficacy of corticosteroids [ 5 - 7 ] and chlorambucil [ 8 , 9 ] in patients with membranous nephropathy and normal renal function are controversial . Because in most untreated patients renal function remains normal and spontaneous remissions of proteinuria develop , it does not seem justified to use potentially toxic immunosuppressive drugs in these patients . Such treatment should be limited to patients at risk for disease progression [ 10 ] . It is well known that patients with membranous nephropathy and established renal insufficiency are at high risk for developing end-stage renal disease [ 11 ] . Uncontrolled studies in patients with deteriorating renal function have shown beneficial effects of intravenous pulses of methylprednisolone followed by oral prednisone [ 12 ] , of prednisone and cyclophosphamide [ 13 - 15 ] , of prednisone and chlorambucil [ 16 ] , and of prednisone combined with azathioprine [ 17 ] . In a pilot study , we observed that chlorambucil and prednisone reversed the deterioration of renal function in some patients with membranous nephropathy [ 18 ] . Both chlorambucil and cyclophosphamide have major side effects . In patients with lupus nephritis , it has been shown that the use of intravenous pulses of cyclophosphamide is effective and is associated with fewer side effects than is daily oral cyclophosphamide [ 19 ] . We therefore did a r and omized trial comparing the efficacy of chlorambucil , methylprednisolone , and prednisone with pulses of cyclophosphamide and methylprednisolone in patients with membranous nephropathy and deteriorating renal function . Our data show that treatment with chlorambucil can retard progression of renal failure , whereas monthly intravenous cyclophosphamide is ineffective . Methods Patient Selection To be eligible for the study , patients were required to have a nephrotic syndrome with biopsy-proven membranous nephropathy and deteriorating renal function . Exclusion criteria were as follows : age younger than 18 years , serum creatinine levels lower than 150 mol/L , evidence for secondary types of membranous nephropathy ( such as malignancy , hepatitis infection , positive test results for anti-DNA antibodies , or the use of drugs that could induce membranous nephropathy ) , child wish , diabetes mellitus , or clinical evidence of renal vein thrombosis . Renal biopsy specimens were taken from all patients at presentation and were re-evaluated by one investigator . Histologic staging was done according to the criteria of Ehrenreich and Churg [ 20 ] . All patients gave informed consent . Study Design and Intervention Patients were r and omly assigned to one of two treatment protocol s. Patients assigned to receive chlorambucil were given three cycles of treatment with steroids ( intravenous pulses of methylprednisolone , 1 g on 3 consecutive days , followed by oral prednisone , 0.5 mg/kg of body weight per day for 27 days ) , and each cycle was followed by 1 month of treatment with oral chlorambucil ( 0.15 mg/kg per day ) . We used a lower dose of chlorambucil than that used by Ponticelli and colleagues [ 9 ] because in our previous study using chlorambucil at 0.2 mg/kg per day , leukopenia developed in more than half of the patients [ 18 ] . Patients assigned to receive cyclophosphamide were given intravenous pulses of cyclophosphamide , 750 mg/m2 , at monthly intervals for 6 months . They also received three intravenous pulses of methylprednisolone of 1 g for 3 consecutive days every 2 months . Cyclophosphamide was administered under forced saline diuresis . All patients received intravenous metoclopramide or ondansetron to avoid or reduce symptoms of nausea and vomiting . The patients received diuretics and antihypertensive drugs if required . Clinical examinations , biochemical profiles , and full blood counts were done at weekly intervals during immunosuppressive therapy and at regular intervals thereafter . The trial was stopped when the serum creatinine levels doubled . For calculations of renal survival , renal death was defined as a doubling of the serum creatinine level or the start of renal replacement therapy . We have used the reciprocal of serum creatinine ( 1000/serum creatinine level ) to assess the effect of the therapeutic interventions on the progression of renal insufficiency . Changes in this ratio parallel changes in endogenous creatinine clearance ( [ urinary creatinine concentration x V]/serum creatinine , where V = 24-h urine volume ) because in a given patient , creatinine excretion ( urinary creatinine concentration x V ) is generally constant over time . For calculations , 1000 mol/L ( 8.85 mg/dL ) was taken as the creatinine level in patients who received hemodialysis . Complete remission was defined as a reduction of proteinuria to less than 0.3 g/24 h , and partial remission was defined as when proteinuria ranged between 0.3 and 3.0 g/24 h. To correct for inappropriate 24-hour urine collection s , the amount of urinary protein per 10 mmol of creatinine ( protein-creatinine index ) was used for calculation . At the start of the therapy , an interim analysis was planned after 20 patients were enrolled . By the end of 1992 , we became aware of the study of Falk and colleagues [ 21 ] , which showed no additional benefit of intravenous pulses of cyclophosphamide plus steroid treatment . Analysis of our patients ' data also showed no effect of treatment with pulses of cyclophosphamide . It therefore seemed unjustified to continue the study protocol , and no more patients were enrolled . Statistical Analysis Results are given as the mean SD or as the median with range . Average changes in time from baseline values are given with 95 % confidence intervals . Changes in serum creatinine levels were compared using repeated measures of analysis of variance . The Gehan log-rank test was used for survival analysis . The Wilcoxon test was used for all other statistical comparisons . A probability value of less than 0.05 was considered statistically significant . Results Clinical Findings Between June 1989 and November 1992 , 20 patients met the entrance criteria of the study and were r and omly assigned to either treatment regimen . Two of the 20 patients ( 1 from each treatment group ) immediately withdrew after assignment . One had to receive regular dialysis before treatment with methylprednisolone and cyclophosphamide had begun , and the other became psychotic 2 weeks after starting prednisone treatment . Because these 2 patients received neither chlorambucil nor cyclophosphamide , their data are not used for analysis . Of the remaining 18 patients , 9 were assigned to receive chlorambucil and 9 to receive cyclophosphamide . The clinical details are given in Table 1 . All patients but 1 were men , and all had a nephrotic syndrome ( proteinuria , 3.5 g/d ) and renal insufficiency . In the 6 months before the start of treatment , the serum creatinine levels of patients in the chlorambucil group increased from a mean of 146 69 mol/L to 260 112 mol/L ; in the cyclophosphamide group , the levels increased from 141 87 mol/L to 218 85 mol/L ( P > 0.2 between the two groups ) . Six patients in the chlorambucil group and 5 patients in the cyclophosphamide group had been treated previously with short-term , high-dose prednisone according to a previously published schedule [ 5 ] . In the group assigned to receive chlorambucil , 7 of the 9 patients received antihypertensive treatment consisting of one drug ( 3 patients received an angiotensin-converting enzyme inhibitor and 4 patients , a -blocker ) , and in the group assigned to receive cyclophosphamide , 5 of the 9 patients received an antihypertensive drug , an angiotensin-converting enzyme inhibitor . Patients were followed for 6 to 36 months after the start of immunosuppressive therapy . Table 1 . Clinical Characteristics of Patients at Study Entry Pathologic Findings In both treatment groups , six patients had stage I or II membranous nephropathy . In the chlorambucil group , two patients had stage III nephropathy . The biopsy specimen of one patient could not be re-evaluated . Three of the patients treated with pulse cyclophosphamide had stage III nephropathy . Response to Immunosuppressive Therapy The course of renal function as reflected by 1000/serum creatinine for the individual patients is shown in Figures 1 and 2 . During the 6 months of treatment , the serum creatinine level had decreased in all patients treated with chlorambucil by an average of 74 mol/L ( range , 19 to 175mol/L ; P = 0.003 ) . In contrast , we observed an uninterrupted increase of the serum creatinine level in seven of the nine patients treated with cyclophosphamide , with an average increase of 79 mol/L ( range , 67 to 204 mol/L ; P = 0.02 ; difference between both groups , P < 0.001 ) . The difference in the course of the serum creatinine level between the treatment groups was already apparent 3 months after therapy was started ( P = 0.02 compared with the baseline creatinine level ) , and it persisted during the subsequent years of follow-up . Renal survival differed significantly between the two treatment groups ( P = 0.03 ) in favor of the patients treated with chlorambucil . Both groups had similar increases of serum albumin levels and decreases of proteinuria and serum cholesterol levels ( Table 2 ) . Table 2 . Changes in Biochemical Variables from Baseline during the First Year after Start of Treatment * Figure 1 . Renal function as shown by 1000/serum creatinine level in individual patients treated with chlorambucil , methylprednisolone , and prednisone . Figure 2 . Renal function as shown by 1000/serum creatinine level in individual patients treated with intravenous pulses of cyclophosphamide and methylprednisolone . Follow-up Follow-up data for each patient are given in Table 3 . In the chlorambucil group , one patient had a complete remission of proteinuria , and three had a partial remission of proteinuria after Seventy-two adults with the nephrotic syndrome without renal insufficiency had a membranous type of renal histology on biopsy . These patients were r and omly allocated to at least eight weeks of alternate-day treatment with prednisone or placebo in a multicenter study . Deterioration of glomerular filtration rate was significantly more rapid in placebo-treated than in prednisone-treated patients , and ultimately 10 of 38 given placebo but only one of 34 given prednisone were in renal failure ( creatinine more than 5 mg per deciliter [ 440 mumol per liter ] ) or dead ( P less than 0.02 ) . In male patients and in those with nonselective initial proteinuria , there was a trend ( not reaching statistical significance ) toward more rapid deterioration of renal function . Age , admission blood pressure , serum creatinine , daily total protein excretion , and severity of histologic changes did not predict the subsequent course . We conclude that a short course of alternate-day prednisone therapy was beneficial in our group of patients with idiopathic membranous nephropathy OBJECTIVE To determine if deterioration in renal function could be ameliorated by adding cyclophosphamide to corticosteroid therapy in patients with progressive membranous glomerulopathy . DESIGN R and omized , controlled treatment trial . Patients were followed for a mean of 29.2 + /- 17.1 months . SETTING Collaborative network of 120 university and private- practice nephrologists . PARTICIPANTS Patients with membranous glomerulopathy whose renal function deteriorated ( as evidence d by doubling of the serum creatinine level , a 50 % fall in the glomerular filtration rate , or a sustained serum creatinine level of greater than 2.0 mg/dL [ reciprocal creatinine value , 0.5 ] , or whose nephrotic range proteinuria persisted in association with morbid complications . Of 156 patients with biopsy-proven membranous glomerulopathy , 36 became eligible for r and omization . Twenty-six of these 36 patients were r and omly assigned to receive one of the two treatments . INTERVENTIONS Pulse methylprednisolone , oral corticosteroids , and 6 months of intravenous cyclophosphamide or alternate-day corticosteroid therapy alone . MAIN RESULTS At entry , no statistical differences were found between the treatment groups in duration of renal disease , age , gender , serum creatinine level , 24-hour urine protein excretion , or biopsy stage . The groups showed no difference in mean arterial blood pressure during follow-up . Four of the 13 patients receiving corticosteroids alone and 4 of the 13 patients receiving corticosteroids plus intravenous cyclophosphamide progressed to end-stage renal disease during follow-up . Reciprocal creatinine values tested at 6-month intervals showed no statistical differences between treatment groups at any time point . The log of the 24-hour protein excretion values showed no statistical differences between treatment groups after treatment . The power to detect a substantial improvement in renal function , defined as a doubling of the reciprocal of the serum creatinine , at the 0.05 significance level was 0.92 . CONCLUSIONS Combination therapy with intravenous cyclophosphamide and corticosteroids , when compared with corticosteroid therapy alone , does not improve renal function in patients with progressive membranous glomerulopathy We conducted a controlled trial to investigate the long-term effects of treatment with methylprednisolone and chlorambucil in patients with idiopathic membranous nephropathy . We have previously reported that after a mean of 31 months , treated patients did better . We now report the results of a longer follow-up . Eighty-one patients with proteinuria ( greater than or equal to 3.5 g per day ) and biopsy-proved membranous nephropathy were r and omly assigned to receive either supportive therapy alone or a six-month course of corticosteroids alternated with chlorambucil ( 0.2 mg per kilogram of body weight per day ) every other month . Methylprednisolone was first given intravenously in three pulses ( 1 g per day ) and was then given orally ( 0.4 mg per kilogram per day ) for 27 days . The patients were followed for 2 to 11 years ( median , 5 ) . Two patients in the control group and one in the treatment group died . At the last follow-up visit , 9 of 39 patients assigned to the control group ( 23 percent ) and 28 of 42 patients assigned to the treatment group ( 67 percent ) did not have the nephrotic syndrome . At five years there were more remissions of the nephrotic syndrome in treated patients than in controls ( 22 of 30 vs. 10 of 25 ; P = 0.026 ) . Compared with base-line values , the mean reciprocal of the plasma creatinine level declined significantly in the control group ( 33 percent ; P = 0.0002 ) but not in the treatment group ( 6 percent ; P not significant ) . Plasma creatinine increased by 50 percent or more in 19 controls ( 49 percent ) and in 4 treated patients ( 10 percent ) . We conclude that a six-month course of methylprednisolone and chlorambucil can bring about sustained remission of the nephrotic syndrome and help to preserve renal function in patients with idiopathic membranous nephropathy BACKGROUND A clinical trial of cyclosporine in patients with steroid-resistant membranous nephropathy ( MGN ) was conducted . Although MGN remains the most common cause of adult-onset nephrotic syndrome , its management is still controversial . Cyclosporine has been shown to be effective in cases of progressive MGN , but it has not been used in controlled studies at an early stage of the disease . METHODS We conducted a r and omized trial in 51 biopsy-proven idiopathic MGN patients with nephrotic-range proteinuria comparing 26 weeks of cyclosporine treatment plus low-dose prednisone to placebo plus prednisone . All patients were followed for an average of 78 weeks , and the short- and long-term effects on renal function were assessed . RESULTS Seventy-five percent of the treatment group versus 22 % of the control group ( P < 0.001 ) had a partial or complete remission of their proteinuria by 26 weeks . Relapse occurred in 43 % ( N = 9 ) of the cyclosporine remission group and 40 % ( N = 2 ) of the placebo group by week 52 . The fraction of the total population in remission then remained almost unchanged and significant different between the groups until the end of the study ( cyclosporine 39 % , placebo 13 % , P = 0.007 ) . Renal function was unchanged and equal in the two groups over the test medication period . In the subsequent follow-up , renal insufficiency , defined as doubling of baseline creatinine , was seen in two patients in each group , but remained equal and stable in all of the other patients . CONCLUSION This study suggests that cyclosporine is an effective therapeutic agent in the treatment of steroid-resistant cases of MGN . Although a high relapse does occur , 39 % of the treated patients remained in remission and were subnephrotic for at least one-year post-treatment , with no adverse effect on filtration function BACKGROUND AND METHODS Treatment with methylprednisolone and chlorambucil may protect renal function and increase the chance of remission of the nephrotic syndrome in patients with idiopathic membranous nephropathy . To determine whether similar results might be obtained with methylprednisolone alone , we compared the effects of methylprednisolone and chlorambucil with those of methylprednisolone alone in 92 patients with the nephrotic syndrome caused by idiopathic membranous nephropathy . The patients were r and omly assigned to receive either alternating one-month courses of methylprednisolone and then chlorambucil for a total of six months ( group 1 ) or methylprednisolone alone for six months at the same cumulative dosage ( group 2 ) . RESULTS Four of the 45 patients in group 1 ( 9 percent ) and 1 of the 47 in group 2 ( 2 percent ) stopped treatment because of side effects . At one , two , and three years , the percentage of patients who did not have the nephrotic syndrome was significantly higher in group 1 than in group 2 . It was 58 , 54 , and 66 percent , respectively , in group 1 , as compared with 26 , 32 , and 40 percent in group 2 ( P = 0.002 , 0.029 , and 0.011 ) . By year 4 , the difference was no longer statistically significant : 62 percent of the patients in group 1 and 42 percent of those in group 2 did not have the nephrotic syndrome ( P = 0.102 ) . The patients in group 1 were in remission longer than those in group 2 ( P = 0.008 ) . CONCLUSIONS In patients with the nephrotic syndrome caused by idiopathic membranous nephropathy , treatment with methylprednisolone and chlorambucil for six months induces an earlier remission of the nephrotic syndrome than methylprednisolone alone , but the difference may diminish with time A multi-centre controlled trial of steroid treatment of the nephrotic syndrome was carried out on 125 patients . Of these , 64 were controls and 61 received prednisone in a recommended dose range of 20 - 30 mg./24 hours . The actual initial dose averaged 29 mg./24 hours . Treatment was continued for a variable period , but not less than six months . More than 10 mg./24 hours was given on average for 12 months to all patients , and for longer periods to some . Patients were classified , on the basis of biopsy specimens , into three groups : A , minimal change ; B , membranous nephropathy ; and C , proliferative glomerulonephritis . In groups B and C prednisone did not have any strikingly favourable effect on proteinuria or on renal function as compared with the control group . In group A , however , prednisone reduced proteinuria to a striking and statistically significant extent . It had little if any effect on long-term renal function in any group . The death rate was higher in the combined prednisone groups ( 17/61 ) than in the control groups ( 12/64 ) . This difference was not statistically significant , but there was a significantly higher number of deaths from cardiovascular disease in the prednisone group , whereas the numbers of deaths from renal failure were not significantly different in the two groups In a controlled double-blind trial five patients with the nephrotic syndrome due to idiopathic membranous glomerulonephritis received azathioprine , 2.5 mg/kg-d , while four others received placebo . After 1 year of treatment there was no significant difference between the two groups with regard to the changes in leukocyte count , values for hemoglobin , serum creatinine , blood urea nitrogen or serum albumin , 24-hour excretion of protein in the urine , or creatinine clearance . In this study azathiprine appeared not to be useful in the treatment of idiopathic membranous glomerulonephritis We treated patients with idiopathic membranous nephropathy ( iMGN ) and renal insufficiency , using : ( i ) ( n = 15 ) monthly cycles of steroids ( 1 g methyl-prednisolone i.v . on three consecutive days , followed by oral prednisone 0.5 mg/kg/day months 1 , 3 and 5 ) and chlorambucil ( 0.15 mg/kg/day months 2 , 4 and 6 ) ; or ( ii ) ( n = 17 ) oral cyclophosphamide ( 1.5 - 2.0 mg/kg/day for 1 year ) and steroids in a comparable dose . The groups were comparable in age , renal function and levels of proteinuria . During the 6 months preceding treatment , serum creatinine levels increased from 148 + /- 50 to 219 + /- 73 mumol/l in the chlorambucil group and from 164 + /- 86 to 274 + /- 126 mumol/l in the cyclophosphamide group . Median ( range ) follow-ups were : chlorambucil 38 months ( 8 - 71 ) ; cyclophosphamide 26 months ( 5 - 68 ) ( NS ) . Renal function improved in both groups , but the improvement was short-lived in the chlorambucil group ; 12 months after starting treatment , mean serum creatinine was 6.3 mumol/l lower in the chlorambucil group and 121 mumol/l lower in the cyclophosphamide group ( p < 0.01 ) . Four chlorambucil-treated patients developed ESRD , and five needed a second course of therapy , whereas only one cyclophosphamide-treated patient developed ESRD ( p < 0.05 ) . Remissions of proteinuria occurred more frequently after cyclophosphamide treatment ( 15/17 vs. 5/15 ; p < 0.01 ) . Side-effects necessitated interruption of treatment in six patients on cyclophosphamide and in 11 on chlorambucil ( p < 0.05 ) . In our patients , oral cyclophosphamide was better tolerated than oral chlorambucil . The suggested greater efficacy of the oral cyclophosphamide regimen needs to be ascertained by longer follow-up Patients of idiopathic membranous nephropathy ( MGN ) were r and omly assigned to received steroid and cyclophosphamide every other month ( Gr-I ) and steroid alone ( Gr-II ) . Of 36 patients in Gr . I , 33 patients achieved complete remissions , 2 had relapsing course with remission on further courses of therapy and only one has reached end stage renal failure . In contrast , of the 35 patients in Gr . II , 15 ( P < 0.001 ) achieved complete remission , 7 are in partial remission , 5 have no response , another 5 have deterioration of renal function of which two required dialysis , and 3 have relapsing course after the initial remission . Mean follow up period was 46 + /- 10.2 months . We conclude that steroid and cyclophosphamide every other month is highly effective in achieving remission in patients with membranous nephropathy |
869 | 28,124,828 | Life review is a worthwhile intervention for reducing depression and hopelessness , and improving quality of life , well-being and specific memory in older adults . | AIM The present study aim ed to evaluate the effects of life review interventions on psychosocial outcomes among older adults . | Objective : The aim of this study is to evaluate the effectiveness of life review ( LR ) based on specific positive events in non-depressed older adults taking part in an active aging program . Method : Fifty-five older adults were r and omly assigned to an experimental group or an active control ( AC ) group . A six-session individual training of LR based on specific positive events was carried out with the experimental group . The AC group undertook a “ media workshop ” of six sessions focused on learning journalistic techniques . Pre-test and post-test measures included life satisfaction , depressive symptoms , experiencing the environment as rewarding , and autobiographical memory ( AM ) scales . Results : LR intervention decreased depressive symptomatology , improved life satisfaction , and increased specific memories . Discussion : The findings suggest that practice in AM for specific events is an effective component of LR that could be a useful tool in enhancing emotional well-being in active aging programs , thus reducing depressive symptoms Surviving events that have posed a serious threat to life can result in major psychological problems during the recovery period . Younger patients , with years of life ahead of them , are at risk of depression and loss of self-esteem following their ordeal , despite their physical recovery . Traditional forms of counselling and psychotherapy following traumatic events can sometimes carry a stigma and be viewed as ' disease centred ' . Reminiscence and life review therapies , used until now , with the elderly , appear to have valuable transferable benefits to younger survivors of critical illness . Life review and reminiscent interventions are holistic and person centred , techniques resonating with the essence of critical care nursing . Life review and reminiscence can be used therapeutically from an early stage to help minimize the negative psychological effects of being critically ill The purpose of this r and omized , controlled trial was to test the efficacy of a community-based intervention , the Life Story Workshop , on depressive symptoms , operationalized as depression subscale scores on the Brief Symptom Inventory 18 , in adults age 60 and older . Thirty-three men and women were r and omly assigned to one of two groups : an intervention group that attended 2-hour workshops once a week for 10 weeks or a wait-list control group . The intervention provided an opportunity for older participants to reflect on , write , and share stories about their lived and current lives . The depression subscale of the Brief Symptom Inventory 18 was administered before and after the workshops . Mean depression scores were compared using Welch 's t test . A significant improvement was measured for the intervention group compared with the control group ( p = .03 ) . This research supports the Life Story Workshop as an effective intervention for improving depressive symptoms in older adults OBJECTIVE This study was aim ed at evaluating whether a Life Review Group Program ( LRGP ) improved the self-esteem and life satisfaction in the elderly . METHODS This r and omized , controlled trial consisted of 75 elderly males from a Veterans ' Home in Northern Taiwan , 36 of whom were in the experimental group and 39 of whom were in the control group . The subjects in the experimental group participated in an 8-week LRGP . Data were collected before and after the LRGP and again 1 month after the end of the program . RESULTS The study subjects had a mean age of 78.13 years . The generalized estimating equation was used to compare alterations in the self-esteem and life satisfaction of the elderly before and after the intervention . The alterations in self-esteem and life satisfaction in the experimental group after the LRGP were significantly improved compared to the control group . One month after the LRGP was completed , the self-esteem and life satisfaction of the experimental group continued to improve when compared with pre-intervention levels . CONCLUSIONS Based on these results , the LRGP can potentially improve the self-affirmation , confidence , and self-esteem of the elderly and promote short-term life satisfaction . The results of this study provide a model for clinical evidence -based therapy , serving as a reference for related studies and evaluation of health-promoting programs , as well as improving the health and quality of care of the elderly BACKGROUND France has high rates of psychotropic drug consumption and suicide in the elderly population , but it has not yet been possible to determine whether this is due to exceptionally high morbidity rates . AIMS To describe the first longitudinal population study of psychiatric disorder undertaken in France , and to estimate current and lifetime prevalences and age of onset of psychiatric disorder . METHOD A study group of 1873 non-institutionalised persons aged 65 years and over was r and omly recruited from the Montpellier district electoral rolls . The Mini International Neuropsychiatric Interview was used to assess current and lifetime symptoms . Cases identified by the application of DSM-IV criteria were re-examined by a clinical panel . RESULTS Forty-six per cent of the study population had experienced a mental disorder in their lifetime , and 3.7 % had made a suicide attempt . Lifetime prevalence of major depression was 26.5 % and 30 % for anxiety disorders . Current prevalence rates were 14.2 % for anxiety disorders , 10.7 % for phobia , 3 % for major depression and 1.7 % for psychosis . CONCLUSIONS Results show very high rates of lifetime but not current major depression . Rates of current phobia and suicidal ideation in the very elderly are also high compared with other studies . The rates reported are likely to be underestimates This study examined the underlying variables of selected reminiscing processes to determine those that contributed to well-being . Two hundred and forty subjects r and omly selected from nursing homes and high-rises participated in one of 10 different reminiscing modalities for eight weeks . Measures of life satisfaction ( LSI-A ) , psychological well being ( ABS ) , self-esteem ( SES ) , and depression ( BDI ) were given pre- and postintervention to determine the most therapeutic treatment modalities . Results showed the most therapeutic way to reminisce was through a structured , evaluative life review performed on an individual basis . Thus , three variables contributed to successful reminiscing : individuality ( one-to-one reminiscing ) , evaluation ( a personal valuing of events ) , and structure ( covering the whole life span ) People living with AIDS ( PLWA ) are confronted with uncertainty and their own mortality at an earlier than expected age . Life review , an intervention that has the potential to increase life satisfaction in the elderly experiencing transition points in their lives , may have a similar effect when used with PLWA . Therefore , the purpose of this feasibility study was to explore the use of life review in a sample of 20 PLWA through a r and omized controlled trial of its effectiveness in decreasing depressive symptoms and in increasing self esteem , quality of life , and purpose in life . Compared to the control group , the treatment group had an improved overall quality of life and self-esteem over 12 months , less depressive symptoms over 12 months , and a greater purpose in life at 3 months . The effects that were seen were mainly small to medium effects . The findings from this feasibility study suggest the potential value of life review to enhance quality of life , purpose in life , and self-esteem , and to decrease depressive symptoms in PLWA . Further research is needed with a larger sample and with other groups such as PLWA experiencing virologic failure Background : The objective of this study was to evaluate the mid-term efficacy of life review activities on the quality of life ( QOL ) of the elderly by conducting a r and omized controlled trial , and to identify the factors that should be taken into consideration when conducting life review activities . Methods : Written consent was obtained from 80 of the 97 eligible elderly persons . After r and omly assigning them to two groups , an intervention group and a control group , group life review activities were conducted in the intervention group and discussion activities about health were conducted in the control group . In both the intervention group and the control group , life satisfaction , self-esteem , depression , and hopelessness were evaluated using self-rating scales at three points : at baseline , immediately after completion of the 8 weeks of sessions , and 3 months after completion of the intervention . Results : Repeated measures analysis of covariance showed significant differences between the two groups in the changes in scores for depression ( p = 0.04 ) and hopelessness ( p = 0.04 ) . Regarding the factors that were associated with depression and hopelessness , 3 months after completion of the intervention , depression and hopelessness of a more severe nature at baseline and having greater unresolved conflicts in the past were extracted by multiple regression analysis . Conclusions : The results suggested that group life review activities have a role in assisting the developmental stage of old age and supporting mental health , and have mid- to long-term effectiveness in maintaining and improving the QOL of the elderly Background and aims : As life expectancy rises worldwide and the population grows older , psychopathology in older adults becomes a significant public health concern and intervention methods acquire renewed importance . The aim of the present study was to assess the efficacy of Life Review as an intervention strategy in working with older women with depressive symptoms , specifically through promotion of the specificity of autobiographical memories . Methods : Twenty-two participants were r and omly assigned to experimental or control conditions . Intervention consisted of four individual sessions of Life Review , structured along 14 questions aim ed at prompting autobiographical memory specificity . Participants in the control condition did not receive intervention . Results : Results indicated a significant change in the experimental group , appearing as the reduction of depressive symptoms ( t(20)=3.58 , p<0.05 ) and an increase in life satisfaction ( t(20)=−3.83 , p<0.05 ) , as well as a significant increase in the specificity ( t(20)=−3.46 , p<0.05 ) and positivity ( t(20)=−4.23 , p<0.05 ) of autobiographical memories . All variables reached high effect sizes , with an effect size of r=0.64 regarding depressive symptoms . Conclusions : Results suggest that Life Review is a valuable tool for use with older adults , and that promotion of specific autobiographical memories is a mechanism through which the strategy attains its effectiveness OBJECTIVE We examined the effects of engaging in the occupation-based intervention of life review through writing on expressed depressive symptoms as measured with the Geriatric Depression Scale in older adults residing in senior residences . METHOD The study design was a r and omized controlled trial that took place in four senior residences in New York City . Forty-five participants ( 23 treatment , 22 wait-list control ) ≥ 65 yr old participated in the 8-wk , once-weekly autobiographical writing workshop , Share Your Life Story ( Sierpina , 2002 ) . RESULTS Depressive symptoms were significantly less prevalent for the treatment group than for the control group after the 8-wk life review program ( repeated- measures analysis of variance p = .03 ) . CONCLUSION The results suggest that the Share Your Life Story writing workshop is an effective occupation-based intervention for occupational therapists to use with older adults who reside in senior residences This pilot study sought to determine if the use of Life Review Therapy would result in lower levels of depression and higher degrees of life satisfaction in individuals with right hemisphere cerebral vascular accidents ( CVAs ) . Fourteen subjects in a southern rehabilitation center were r and omly assigned to either an experimental or control group . The experimental group received three one-hour sessions of Life Review Therapy and the control group viewed three one-hour sessions of neutral video with a follow-up discussion . Following the third session of each group , subjects were administered the Zung Scale for Depression and the Life Satisfaction Index — Form Z. A one-way ANOVA revealed a significantly lower level of depression ( p < .01 ) and a significantly higher degree of life satisfaction ( p < .01 ) in the Life Review Therapy group The aim of this study was to examine the efficacy of life review based on autobiographical retrieval practice for treating depressed older adults . Forty-three adults aged 65 - 93 with clinical ly significant depressive symptomatology and no dementia were r and omly assigned to treatment or to no treatment . The results indicated significant differences between experimental and control groups after 4 weeks of autobiographical retrieval practice . At posttest , those in the treatment condition showed fewer depressive symptoms , less hopelessness , improved life satisfaction , and retrieval of more specific events . The findings suggest that practice in autobiographical memory for specific events may be among the components of life review that account for its effectiveness and could be a useful tool in psychotherapy with older adults OBJECTIVES To study the onset and compare risk factors for pure depression ( DEP ) , pure anxiety ( ANX ) , and comorbid anxiety-depression ( ANXDEP ) in the aging population . DESIGN Prospect i ve study with 3-year intervals over a 9-year period . SETTING Data of the Longitudinal Aging Study Amsterdam were used , which is a population -based study among older adults ( 55 - 85 years at baseline ) . PARTICIPANTS Older adults free of depression and anxiety at baseline ( N = 1,712 ) . MEASUREMENTS Clinical ly relevant levels of depression and anxiety were measured with the Center for Epidemiologic Studies Depression scale > or = 16 and Hospital Anxiety and Depression Scale > or = 7 , respectively . A broad range of potential sociodemographic , health , and psychosocial risk factors for anxiety and /or depression were examined by using polytomous logistic regression analyses . RESULTS Within 9 years , 184 subjects ( 10.8 % ) developed DEP , 93 ( 5.4 % ) ANX , and 103 ( 6.0 % ) ANXDEP . Concerning sociodemographics , higher age and lower educational level were predictors for DEP . Health indicators were predictive for DEP and ANXDEP but not for ANX . Depressive symptoms at baseline were predictive for DEP , whereas initial anxiety symptoms were predictive for ANX and ANXDEP . Neuroticism increased the risk of DEP and ANXDEP . Mixed effects of psychosocial variables were found : DEP was associated with recent widowhood , whereas ANX and ANXDEP were associated with other life events such as having an ill partner . CONCLUSION Although onset of ANXDEP demonstrated communality in risk factors , comparing risk factors associated with DEP and ANX revealed more differences than similarities . This underlines the need to distinguish anxiety from depression in preventive strategies The aim of this experiment was to examine the efficacy of life review based on autobiographical retrieval practice for treating depression in older adults . Thirty-seven clinical ly depressed older adults aged 64 - 83 , who were also receiving pharmacological treatment , were r and omly assigned to life review therapy or to a placebo condition with supportive therapy . Results indicated decreased depression for both conditions , with no significant differences between the two therapies . There was some indication of greater gain in production of specific memories among those in life review therapy . Patients who produced higher numbers of specific memories decreased their depression scores at a faster rate BACKGROUND . Although there is substantial evidence for the efficacy of life review therapy as an early treatment of depression in later life , its effectiveness in natural setting s has not been studied . The present study evaluates an intervention based on life review and narrative therapy in a large multi-site , pragmatic r and omized controlled trial ( RCT ) . METHOD . Life review therapy was compared with care as usual . The primary outcome was depressive symptoms ; secondary outcomes were anxiety symptoms , positive mental health , quality of life , and current major depressive episode ( MDE ) . To identify groups for whom the intervention was particularly effective , moderator analyses were carried out ( on sociodemographic variables , personality traits , reminiscence functions , clinical ly relevant depressive and anxiety symptoms , and past MDEs ) . RESULTS . Compared with care as usual ( n=102 ) , life review therapy ( n=100 ) was effective in reducing depressive symptoms , at post-treatment ( d=0.60 , B= -5.3 , p<0.001 ) , at 3-month follow-up ( d=0.50 , B= -5.0 , p<0.001 ) and for the intervention also at 9-month follow-up ( t=5.7 , p<0.001 ) . The likelihood of a clinical ly significant change in depressive symptoms was significantly higher [ odds ratio ( OR ) 3.77 , p<0.001 at post-treatment ; OR 3.76 , p<0.001 at the 3-month follow-up ] . Small significant effects were found for symptoms of anxiety and positive mental health . Moderator analyses showed only two significant moderators , the personality trait of extraversion and the reminiscence function of boredom reduction . CONCLUSIONS . This study shows the effectiveness of life review therapy as an early intervention for depression in an ecologically valid context , supporting its applicability to a broad target group . The intervention is also effective in reducing anxiety symptoms and strengthening positive mental health Life- review therapy has been recognized as an effective therapeutic approach for depression in older adults . Additionally , the use of new media is becoming increasingly common in psychological interventions . The aim of this study was to investigate a life- review therapy in a face-to-face setting with additional computer use . This study explored whether a six-week life- review therapy with computer supplements from the e-mental health Butler system constitutes an effective approach to treat depression in older adults aged 65 and over . A total of 36 participants with elevated levels of depressive symptoms were r and omized to a treatment group or a waiting-list control group and completed the post- assessment . Fourteen individuals in the intervention group completed the follow-up assessment . Analyses revealed significant changes from pre- to post-treatment or follow-up for depression , well-being , self-esteem , and obsessive reminiscence , but not for integrative reminiscence and life satisfaction . Depressive symptoms decreased significantly over time until the three-month follow-up in the intervention group compared to the control group ( pre to post : d = 1.13 ; pre to follow-up : d = 1.27 ; and group × time effect pre to post : d = 0.72 ) . Furthermore , the therapy led to an increase in well-being and a decrease in obsessive reminiscence among the participants in the intervention group from pre-treatment to follow-up ( well-being : d = 0.70 ; obsessive reminiscence : d = 0.93 ) . Analyses further revealed a significant but small group × time effect regarding self-esteem ( d = 0.19 ) . By and large , the results indicate that the life- review therapy in this combined setting could be recommended for depressive older adults There is little evidence to support the efficacy of the life storybook creation process , which incorporates the use of narratives , in mediating depression levels . The study aim ed to examine the effects of the life storybook creation process on depressive symptoms among older community-dwelling Chinese adults in Singapore . A r and omised controlled trial was conducted from January 2011 to March 2012 . Twenty-six Chinese aged over 60 years , who were able to communicate in Chinese and /or English , and with mild to severe depression were r and omly allocated to either the life storybook ( intervention ) group ( n = 14 ) or the non-life storybook ( control ) group ( n = 12 ) . Subjects in the intervention group were interviewed on a one to one basis on five sessions over 8 weeks . Depressive symptoms were measured using the Geriatric Depression Scale . Generalised estimating equations were used to examine the effects of the intervention on the elderly peoples ' depression level . Significant reductions in depression scores were found in the intervention group from baseline ( mean 7.9 [ SD 3.0 ] ) to week 8 ( 2.5 [ 1.7 ] , χ(2 ) = 15.25 , P < 0.001 ) . At week 8 , the intervention group showed a lower level of depression than the control ( χ(2 ) = 4.33 , P = 0.037 ) . This study supports the life storybook creation process as an effective intervention for depressed older Chinese adults living in the community . The findings suggest that this intervention may enhance the quality of care provided by healthcare providers as the therapeutic relationship between provider and client is being established BACKGROUND Empirical data suggest that life review is an effective psychospiritual intervention . However , it has not been applied to Chinese patients with advanced cancer , and its effects on this population remain unknown . OBJECTIVE The aim of the study was to determine the effect of a life review program on quality of life among Chinese patients with advanced cancer . METHODS In this prospect i ve r and omized controlled trial , a total of 80 patients were r and omly assigned to the life review program group and the control group . The 3-weekly life review program included review ing a life and formulating a life review booklet . Outcome data were assessed by a collector who was blinded to group assignment before and immediately after the program and at a 3-week follow-up . RESULTS Significantly better scores in overall quality of life , support , negative emotions , sense of alienation , existential distress , and value of life were found in the life review group immediately after the program and at the 3-week follow-up . CONCLUSION This study provides additional data on the potential role of a life review in improving quality of life , particularly psychospiritual well being ; it also indicates that the life review program could enable Chinese patients with advanced cancer to express their views on life and death . IMPLICATION S FOR PRACTICE The life review program offers advanced cancer patients an opportunity to integrate their whole life experiences and discuss end-of-life issues , which lays the ground for further active intervention in their psychospiritual distress . The program could be integrated into daily home care to enhance the psychospiritual well-being of Chinese patients with advanced cancer |
870 | 27,213,715 | However , this did not translate to a clinical ly meaningful reduction in opioid-induced adverse events .
Adverse events occurred at similar rates with IV paracetamol or IV propacetamol and placebo .
Meta- analysis did not demonstrate clinical ly meaningful differences between IV paracetamol/propacetamol and active comparators for any adverse event .
Low to very low quality evidence demonstrates that both formulations are associated with few adverse events , although patients receiving IV propacetamol have a higher incidence of pain on infusion than both placebo and IV paracetamol | BACKGROUND This is an up date d version of the original Cochrane review published in Issue 10 , 2011 .
Paracetamol ( acetaminophen ) is the most commonly prescribed analgesic for the treatment of acute pain .
It may be administered orally , rectally , or intravenously .
The efficacy and safety of intravenous ( IV ) formulations of paracetamol , IV paracetamol , and IV propacetamol ( a prodrug that is metabolized to paracetamol ) , compared with placebo and other analgesics , is unclear .
OBJECTIVES To assess the efficacy and safety of IV formulations of paracetamol for the treatment of postoperative pain in both adults and children . | Background : Intravenous acetaminophen injection ( paracetamol ) is marketed in Europe for the management of acute pain . A repeated-dose , r and omized , double-blind , placebo-controlled , three-parallel group study was performed to evaluate the analgesic efficacy and safety of intravenous acetaminophen as compared with its prodrug ( propacetamol ) and placebo . Propacetamol has been available in many European countries for more than 20 yr . Methods : After orthopedic surgery , patients reporting moderate to severe pain received either 1 g intravenous acetaminophen , 2 g propacetamol , or placebo at 6-h intervals over 24 h. Patients were allowed “ rescue ” intravenous patient-controlled analgesia morphine . Pain intensity , pain relief , and morphine use were measured at selected intervals . Safety was monitored through adverse event reporting , clinical examination , and laboratory testing . Results : One hundred fifty-one patients ( intravenous acetaminophen : 49 ; propacetamol : 50 ; placebo : 52 ) received at least one dose of study medication . The intravenous acetaminophen and propacetamol groups differed significantly from the placebo group regarding pain relief from 15 min to 6 h ( P < 0.05 ) and median time to morphine rescue ( intravenous acetaminophen : 3 h ; propacetamol : 2.6 h ; placebo : 0.8 h ) . Intravenous acetaminophen and propacetamol significantly reduced morphine consumption over the 24-h period : The total morphine doses received over 24 h were 38.3 ± 35.1 mg for intravenous acetaminophen , 40.8 ± 30.2 mg for propacetamol , and 57 . 4 ± 52.3 mg for placebo , corresponding to decreases of −33 % ( 19 mg ) and −29 % ( 17 mg ) for intravenous acetaminophen and propacetamol , respectively . Drug-related adverse events were reported in 8.2 % , 50 % ( most of them local ) , and 17.3 % of patients treated with intravenous acetaminophen , propacetamol , and placebo , respectively . Conclusion : Intravenous acetaminophen , 1 g , administered over a 24-h period in patients with moderate to severe pain after orthopedic surgery provided rapid and effective analgesia and was well tolerated Background A multimodal and preventative approach to providing postoperative analgesia is becoming increasingly popular for children and adults , with the aim of reducing reliance on opioids . We conducted a prospect i ve , r and omized double-blind study to compare the analgesic efficacy of intravenous paracetamol and dipyrone in the early postoperative period in school-age children undergoing lower abdominal surgery with spinal anesthesia . Methods Sixty children scheduled for elective lower abdominal surgery under spinal anesthesia were r and omized to receive either intravenous paracetamol 15 mg/kg , dipyrone 15 mg/kg or isotonic saline . The primary outcome measure was pain at rest , assessed by means of a visual analog scale 15 min , 30 min , 1 h , 2 h , 4 h and 6 h after surgery . If needed , pethidine 0.25 mg/kg was used as the rescue analgesic . Time to first administration of rescue analgesic , cumulative pethidine requirements , adverse effects and complications were also recorded . Results There were no significant differences in age , sex , weight , height or duration of surgery between the groups . Pain scores were significantly lower in the paracetamol group at 1 h ( P = 0.030 ) and dipyrone group at 2 h ( P = 0.010 ) when compared with placebo . The proportion of patients requiring rescue analgesia was significantly lower in the paracetamol and dipyrone groups than the placebo group ( vs. paracetamol P = 0.037 ; vs. dipyrone P = 0.020 ) . Time to first analgesic requirement appeared shorter in the placebo group but this difference was not statistically significant , nor were there significant differences in pethidine requirements , adverse effects or complications . Conclusion After lower abdominal surgery conducted under spinal anesthesia in children , intravenous paracetamol appears to have similar analgesic properties to intravenous dipyrone , suggesting that it can be used as an alternative in the early postoperative period . Trial registration Clinical Trials.gov . Identifier : NCT01858402 BACKGROUND This study assessed the analgesic efficacy , side effects , and time to extubation of intravenous paracetamol when administered as an adjuvant to intravenous meperidine after major surgery in intensive care unit ( ICU ) . MATERIAL Patients were r and omized postoperatively into 2 groups in ICU . Patients received either 100 mL of serum saline intravenous ( IV ) every 6 hours and IV meperidine ( n = 20 group M ) or IV paracetamol 1 g every 6 hours and IV meperidine ( n = 20 , group MP ) into a peripheral vein for 24 hours . Behavioral Pain Scale ( BPS ) is used until extubation , and visual analog score ( VAS ) is used after extubation . When BPS and VAS values were more than 4 , meperidine , 1 mg/kg IV , was administered and noted in 2 groups . Pain scores , total meperidine consumption , time to extubation , sedation scores , and side effects are 24-hour postoperatively noted . RESULTS Behavioral Pain Scale and VAS scores are significantly lower in group paracetamol-meperidine at 24 hours ( P < .05 ) . In group MP , postoperative meperidine consumption ( 76.75 ± 18.2 mg vs. 198 ± 66.4 mg ) and extubation time ( 64.3 ± 40.6 min vs. 204.5 ± 112.7 min ) were lower than in group M ( P < .01 ) . In addition to , postoperative nausea-vomiting and sedation scores were significantly lower in group MP when compared with group M ( P < .05 ) . CONCLUSION We have demonstrated important clinical benefits by the addition of 4 g/d of paracetamol to meperidine after major surgery . This benefit has been shown in a range of patients under routine clinical conditions and therefore has important practical consequences in ICU . These data suggest that intravenous paracetamol is a useful component of the multimodal analgesia model , especially after major surgery OBJECTIVES The purpose of the present study was to determine the efficacy of intravenous ( iv ) paracetamol and iv lornoxicam on postoperative analgesia and the reduction in tramadol consumption . METHODS Sixty patients ( ASA class 1 - 2 , age : 18 - 72 years ) undergoing thyroidectomy were enrolled in the study , and were r and omized into three groups : Group L received 8 mg of iv lornoxicam , Group P received 1 g iv paracetamol and Group C received 100 cc of iv saline solution . All patients received st and ard general anesthesia . The postoperative salvage analgesic consumption was recorded at 0 - 6 , 6 - 12 and 12 - 24 hour ( h ) intervals . Pain scores were evaluated with a visual analogue scale at 15 min , and 1 , 2 , 4 , 6 , 8 , 12 , 18 , and 24 h postoperatively . RESULTS The time to first analgesic requirement was approximately 127.5 min in Group L , 162.3 in Group P and 35.5 min in Group C , and the time was found to be significantly prolonged in Group L and Group P. Pain scores were significantly lower in Group P and Group L at 15 min , and 1 , 8 , 12 , and 18 h. Twenty-four hour analgesic consumption was significantly lower in Group P and Group L compared to Group C. Supplemental analgesics requirement was as follows : 100 % in Group C , 50 % in Group L and 55 % in Group P. The degree of satisfaction with postoperative pain management was excellent in 90 % in Groups L and P , versus in only 30 % in Group C. CONCLUSION Administration of iv lornoxicam and iv paracetamol following thyroid surgery decreased the postoperative pain scores and opioid requirement , as well as the incidence of nausea and vomiting , while also prolonging the time to the first analgesic supplement BACKGROUND The purpose of this r and omized double-blind study was to compare the efficacy and safety of propacetamol 2 g ( an i.v . acetaminophen 1 g formulation ) administered as a 2-min bolus injection ( n=50 ) or a 15-min infusion ( n=50 ) with oral acetaminophen 1 g ( n=50 ) or placebo ( n=25 ) for analgesia after third molar surgery in patients with moderate to severe pain after impacted third molar removal . METHODS All patients were evaluated for efficacy during the initial 6 h period after treatment administration ( T(0 ) ) and for safety during the entire week after T(0 ) . RESULTS The onset of analgesia after propacetamol was shorter ( 3 min for bolus administration , 5 min for 15-min infusion ) than after oral acetaminophen ( 11 min ) . Active treatments were significantly better for all parameters ( pain relief , pain intensity , patient 's global evaluation , duration of analgesia ) than placebo ( P<0.05 ) . Adverse events were more frequent after propacetamol , especially pain at the injection site . Propacetamol bolus result ed in a much higher incidence of local adverse events than the infusion ( propacetamol bolus 90 % vs propacetamol infusion 52 % ) with no clinical ly significant benefits in terms of analgesic efficacy . CONCLUSION I.V. propacetamol , administered as a 15-min infusion , is a fast-acting analgesic agent . It is more effective in terms of onset of analgesia than a similar dose of oral acetaminophen Background In recent years , intravenously ( IV ) administered acetaminophen has become one of the most common perioperative analgesics . Despite its now-routine use , IV acetaminophen ’s analgesic comparative efficacy has never been compared with that of ketamine , a decades-old analgesic familiar to obstetricians , gynecologists , and anesthesiologists alike . This doubleblind clinical trial aim ed to evaluate the analgesic effects of ketamine and IV acetaminophen on postoperative pain after abdominal hysterectomy . Methods Eighty women aged 25–70 years old and meeting inclusion and exclusion criteria were r and omly allocated into two groups of 40 to receive either IV acetaminophen or ketamine intraoperatively . Postoperatively , each patient had patient-controlled analgesia . Pain and sedation ( Ramsay Sedation Scale ) were documented based on the visual analog scale in the recovery room and at 4 hours , 6 hours , 12 hours , and 24 hours after the surgery . Hemodynamic changes , adverse medication effects , and the need for breakthrough meperidine were also recorded for both groups . Data were analyzed by repeated- measures analysis of variance . Results Visual analog scale scores were significantly lower in the IV acetaminophen group at each time point ( P<0.05 ) , and this group required significantly fewer doses of breakthrough analgesics compared with the ketamine group ( P=0.039 ) . The two groups had no significant differences in terms of adverse effects . Conclusion Compared with ketamine , IV acetaminophen significantly improved postoperative pain after abdominal hysterectomy BACKGROUND Intravenous administration is the route of choice for drug therapy in the immediate postoperative period . Propacetamol ( ProAPAP ) , an injectable prodrug of paracetamol requiring reconstitution , has demonstrated efficacy in managing acute pain and fever . However , it has been associated with pain at the injection site . A stable , ready-to-use formulation of paracetamol solution infused intravenously ( IV-APAP ) has been developed and might be associated with less pain at the injection site compared with ProAPAR . OBJECTIVE The objective of this study was to assess the tolerability and efficacy of a single dose of IV APAP 1 g compared with those of a single dose of ProAPAP 2 g in patients with moderate to severe pain after minor gynecologic surgery . METHODS This single-dose , r and omized , double-blind , active-controlled,2-parallel-group study was conducted at 23 hospitals and outpatient clinics in France . After minor gynecologic surgery , patients reporting moderate to severe pain were r and omized to receive a single 15-minute infusion of IV-APAP 1 g or ProAPAP 2 g ( bioeyuivalent doses ) . Tolerability was monitored using local and systemic adverse event ( AE ) reporting , clinical examination including vital sign measurement , and patients ' ratings of acceptability of the infusion . Efficacy end points included pain intensity at 0 , 1 , 2 , 4 , and 6 hours ; median time to rescue medication ( defined as the time at which 50 % of patients requested rescue medication ) ; and percentage of patients requesting rescue medication . Patients ' satisfaction with the study drugs was assessed using patient 's global evaluation ( PGE ) and the percentage of patients willing to receive the treatment again . RESULTS Of the 163 women who were r and omized , 161 received the study medication . The IV-APAP group comprised 80 patients ( mean [ SD ] age , 38.3 [ 12.8 ] years [ range , 18.0 - 69.0 years ] ; mean [ SD ] weight , 61.1 [ 11.0 ] kg [ range , 49.0 - 90.0 kg ] ) , and the ProAPAP group comprised 81 patients ( mean [ SD ] age , 33.9 [ 12.0 ] years [ range , 18.0 - 67.0 years ] ; mean [ SD ] weight , 61.6 [ 10.2 ] kg [ range , 42.0 - 95.5 kg ] ) ; the difference in mean age between the 2 groups was statistically significant ( P < 0.05 ) . The incidence of local treatment-emergent AEs ( TEAEs ) was significantly lower in the IV-APAP group compared with that in the ProAPAP group ( 7.5 % vs 38.3 % ; P < 0.001 ) . No between-group differences in the incidence of systemic TEAEs was found . All patients in the IV-APAP group found the infusion tolerable , compared with 95 % of patients in the ProAPAP group . The median time to rescue medication was not evaluated because < 50 % of the patients in each group requested it . No significant differences in mean pain intensity score or percentage of patients requesting rescue medication were found between the 2 groups at any time point . The percentages of patients in the IV-APAP and ProAPAP groups who rated the study medication as good or excellent on the PGE ( 83.6 % vs 75.6 % ; P < 0.05 ) and who were willing to receive the same treatment again ( 96.0 % vs 81.0 % ; P = 0.005 ) were significantly higher with IV-APAP compared with ProAPAP . CONCLUSION In these patients with moderate to severe pain after minor gynecologic surgery , a single dose of IV-APAP was associated with better local tolerability , similar analgesic efficacy , and greater patient satisfaction compared with a single bioequivalent dose of ProAPAP BACKGROUND Propacetamol is widely used in the management of postoperative pain . It decreases morphine requirements but its effect on the incidence of morphine-related adverse effects remains unknown . METHODS Patients ( 550 ) were r and omly assigned to receive propacetamol or a placebo over the first 24 h after operation in a blinded study . Intravenous morphine titration was performed , after which morphine was administered s.c . every 4 h according to their pain score . Pain was assessed using a visual analogue scale ( VAS ) . The primary end-point was the incidence of morphine-related adverse effects . The main secondary end-points were morphine requirements and VAS score . RESULTS After morphine titration , the VAS score and the number of patients with pain relief did not differ between groups . Morphine requirements were decreased in the propacetamol group ( 21 vs 14.5 mg , P<0.001 ) but the incidence of morphine-related adverse effects did not differ between groups ( 42 vs 46 % , not significant ) . In patients with moderate pain ( n=395 ) , morphine requirements decreased by 37 % ( P<0.001 ) and the percentage of patients requiring no morphine was greater ( 21 vs 8 % , P=0.002 ) in the propacetamol group . In patients with severe pain ( n=155 ) , morphine requirements decreased by 18 % ( P=0.04 ) in the propacetamol group and the number of patients who did not require morphine ( 3 vs 8 % ) did not differ significantly . CONCLUSIONS Although propacetamol induced a small morphine-sparing effect , it did not change the incidence of morphine-related adverse effects in the postoperative period . Moreover , no benefit could be demonstrated in patients with severe postoperative pain Study Design A r and omized , double-blinded controlled trial . Purpose Postoperative pain relief especially using analgesic drugs with minimal side effects has considerable clinical importance . This study aim ed to examine the effect of intravenous paracetamol on pain relief after lumbar discectomy as a major surgery . Overview of Literature Patients undergoing lumbar discectomy experience a high degree of lumbar pain . Some authors emphasize the use of intravenous paracetamol to improve postoperative pain and increase patients ' satisfaction following this surgery . Methods Fifty-two patients scheduled for lumbar discectomy were r and omly allocated into two groups : a group that received intravenous paracetamol ( 1 g/100 mL normal saline ) within the last 20 minutes of surgery as the case group ( n=24 ) and a group that received sodium chloride 0.9 % 100 mL as the control group ( n=28 ) . Postoperative pain was assessed at 1 , 6 , 12 , 18 , and 24 hours after surgery by a visual analogue scale ( VAS ) . The dosage of the administered opioid ( morphine ) , as well as drug-related side effects within the first 24 hours after surgery were also recorded . Results The mean VAS score was significantly lower in the paracetamol group than the controls for all of the assessed time points . Although the dose of the administered morphine was numerically lower in the paracetamol group , this difference was not statistically significant ( 5.53±4.49 mL vs. 7.85±4.17 mL ) . Conclusions Intravenous paracetamol as a non-opioid analgesic can relieve postoperative pain in patients undergoing lumbar discectomy ; however , its use alone may not represent the best regimen for reducing the needed dose of opioids after operation In order to compare the morphine‐sparing effect , analgesic efficacy and tolerance of nefopam and propacetamol given at their highest recommended doses , 120 patients undergoing elective hepatic resection were r and omly assigned to receive postoperative intravenous patient‐controlled analgesia with morphine alone , or in combination with nefopam ( 20 mg.4 h‐1 ) or propacetamol ( 2 g.6 h‐1 ) . Compared with the control group ( 43 [ 7–92 ] mg ) , median [ range ] cumulative morphine consumption for 24 h after the study started was halved in the nefopam group ( 21 [ 3–78 ] mg , p < 0.001 ) and 20 % lower in the propacetamol group ( 35 [ 6–84 ] mg , p = 0.15 ) . Analgesia was superior in the nefopam group despite the lower morphine consumption . Adverse effects were comparable in the three groups , except for significantly more nausea in the control group ( 39 % vs. 17 and 26 % in the nefopam and propacetamol groups , respectively ) and more sweating in the nefopam group ( 17 % vs. 0 and 3 % in the control and propacetamol groups , respectively ) . Overall patient satisfaction was better ( p < 0.001 ) in patients given nefopam ( 97 % ) than those receiving morphine alone ( 82 % ) or propacetamol ( 74 % ) Postoperative pain can have a significant effect on patient recovery . An underst and ing of patient attitudes and concerns about postoperative pain is important for identifying ways health care professionals can improve postoperative care . To assess patients ’ postoperative pain experience and the status of acute pain management , we conducted a national study by using telephone question naires . A r and om sample of 250 adults who had undergone surgical procedures recently in the United States was obtained from National Family Opinion . Patients were asked about the severity of postsurgical pain , treatment , satisfaction with pain medication , patient education , and perceptions about postoperative pain and pain medications . Approximately 80 % of patients experienced acute pain after surgery . Of these patients , 86 % had moderate , severe , or extreme pain , with more patients experiencing pain after discharge than before discharge . Experiencing postoperative pain was the most common concern ( 59 % ) of patients . Almost 25 % of patients who received pain medications experienced adverse effects ; however , almost 90 % of them were satisfied with their pain medications . Approximately two thirds of patients reported that a health care professional talked with them about their pain . Despite an increased focus on pain management programs and the development of new st and ards for pain management , many patients continue to experience intense pain after surgery . Additional efforts are required to improve patients ’ postoperative pain experience Background : The purpose of the present study was to determine the post-operative analgesic effects of preemptive intravenous ( iv ) paracetamol and the amount of reduction in tramadol ( Contramal ® ) consumption . Material s and Methods : Following local research ethics committee approval , ASAI-II , 300 patients were assigned in a r and omized manner into three groups : Group I ( preemptive ) received iv paracetamol 1 g/100 mL 10 min before skin inscision and 100 mL of saline solution at the end of the operation , Group II ( post-operative ) received 100 mL of saline solution 10 min before skin inscision and iv paracetamol 1 g/100 mL at the end of the operation and Group III ( placebo ) received 100 mL of saline solution 10 min before skin insicision and 100 mL of saline solution at the end of the operation as well . The time to first analgesic requirement use and 24 h total analgesic consumption were recorded . Visual analog scale ( VAS ) pain scores were obtained from all patients at 15 , 30 , min 1 , 2 , 4 , 6 , 8 , 12 and 24 h after the end of the operation . Results : Time to first analgesic requirement was significantly longer in Group I and Group II , compared to Group III ( P < 0.05 ) . Time to first analgesic requirement was significantly longer in Group I compared to Group II ( P < 0.05 ) . Total analgesic consumption and postoperative VAS pain scores recorded were significantly lower in Group I and II , compared to Group III . Total analgesic consumption and postoperative VAS pain scores recorded were significantly lower in Group I compared to Group II ( P < 0.05 ) . Conclusion : In conclusion , preemptive iv paracetamol provided effective and reliable pain control after cholecystectomy surgeries and reduced post-operative pain scores , the need for and use of supplementary opioids and the time to first request of analgesics Background and objective Paracetamol has a well established pharmacological profile , but its postoperative efficacy is in question . This double-blind , placebo-controlled study was design ed to compare the efficacy of intravenous paracetamol with other intravenous non-opioids as part of a multimodal concept for perioperative pain therapy . Methods Patients undergoing minor-to-intermediate surgery under general anaesthesia were r and omly assigned to receive infusions of paracetamol ( 1 g every 6 h ) , dipyrone ( 1 g every 6 h ) , parecoxib ( 40 mg every 12 h ) separated by infusions of physiological saline 0.9 % , or placebo ( 0.9 % saline every 6 h ) , respectively , for at least 48 h as part of a multimodal pain concept . Patient-controlled piritramide was administered as rescue medication . Dependent variables were recorded 1 , 6 , 18 , 30 and 42 h after extubation and 1 week after surgery . Surgical and associated pain was scored as the primary outcome on a visual analogue scale . Additionally , time to first dose and total piritramide dosage , satisfaction , respiratory depression , nausea , vomiting , sedation , itching and sweating were recorded . Results A total of 196 patients were recruited . The efficacy of paracetamol was similar to that of the other non-opioid analgesics . Surgical pain was reduced with all non-opioids compared to placebo ; there was no effect on associated pain . Piritramide dosage and incidence of side effects were not reduced . Conclusion Intravenous paracetamol has equivalent efficacy to non-opioids dipyrone and parecoxib that improves postoperative pain therapy when used as part of a multimodal concept after minor-to-intermediate surgery The common adverse effects of traditional nonsteroidal antiinflammatory drugs on renal function include reductions in renal blood flow , glomerular filtration rate , and sodium and potassium excretion , mainly via inhibition of renal cyclooxygenase . We design ed the present study to determine the effects of IV paracetamol or parecoxib on renal function in elderly patients undergoing orthopedic surgery . Seventy-five patients ( 76 ± 8 yr , mean ± sd ) undergoing hip replacement or surgery of the femoral shaft completed this r and omized and placebo-controlled study . After their arrival in the postanesthesia care unit , patients received an initial dose of the study medication , paracetamol 1000 mg IV ( n = 25 ) , parecoxib 40 mg IV ( n = 25 ) , or saline IV ( n = 25 ) ; subsequent doses were administered for the next 3 days . Opioids were provided as rescue medication . Blood and urine sample s were collected before and after surgery , and markers of renal function were determined . During the first 2 h after the initial dose of parecoxib , creatinine clearance was slightly diminished ( 125 ± 83 to 86 ± 45 mL/min , P < 0.05 ) , whereas no significant decrease of creatinine clearance was observed in the placebo and paracetamol groups . After all treatments , sodium and potassium excretion as well as urine albumin and & agr;-1-microglobulin were transiently increased ( group differences : not signicifant ) . In conclusion , glomerular and tubular functions were transiently affected in all patients after orthopedic surgery ; however , the differences between the treatment groups were small and not clinical ly relevant . Further studies are warranted to determine adverse renal effects of longer-lasting therapy with these drugs , especially in patients with renal impairment or concomitant diseases Purpose The concept of balanced analgesia suggests that a combination of analgesic drugs may enhance analgesia and reduce side effects after surgery . This study evaluated the effect of the combination of propacetamol ( Prodafalgan ) and ketoprofen ( Profenid ) after surgery of a hemiated disc of the lumbar spine . Methods After r and omization . 60 patients received : placebo ( group 1 ) ; 2 g propacetamol ( group 2 ) ; 50 mg ketoprofen ( group 3 ) ; or a combination of 2 g propacetamol and 50 mg ketoprofen ( group 4 ) . Drugs were administered every six hours for two days after surgery . The patients used morphine with patient controlled analgesia pumps ( bolus 1 mg ; lock out time 10 min ) and were evaluated with a visual analogue scale ( VAS ) at rest and movement every six hours for two days . Side effects were noted . Results The patient characteristics and surgery were identical for each of the four groups . The VAS scores throughout the study were lower in group 4 than in groups 1 , 2 and 3 both at rest ( P < 0.05 ) and on movement ( P < 0.01 ) . The cumulative dose of morphine at 48 hr was lower in group 4 than in group 1 ( 23.4 ± 5 mg vs 58.9 ± 9 mg ; P < 0.01 ) or group 2 ( 23.4 ± 5 mg vs 43.4 ± 6.6 mg ; P < 0.05 ) and similar to that in group 3 ( 34.2 ± 4.5 mg ) . The incidence of side effects was similar in all groups . Conclusion The combination of propacetamol and ketoprofen reduced pain scores both at rest and on movement . The drug combination did not reduce the morphine consumption and incidence of side effects . RésuméButLe concept d’analgésie balancée suggère que I’association de drogues analgésiques en postopératoire peut permettre d’améliorer I’analgésie et réduire les effets secondaires . Cette étude a évalué I’intérêt d’une association de propacetamol ( Prodafalgan ) et de ketoprofen ( Profenid ) pour I’analgésie après chirurgie d’une hernie discale lombaire . MéthodesAprès r and omisation 60 patients ont reçu : un placebo ( groupe 1 ) ; 2 g de propacetamol ( groupe 2 ) ; 50 mg de ketoprofen ( groupe 3 ) ; où I’association de 2 g de propacetamol et 50 mg de ketoprofen ( groupe 4 ) . Les produits analgésiques ont été administrés toutes les six heures pendant 48 h. Les patients utilisaient de la morphine grâce à une pompe d’analgésie autocontrôlée pendant 48 h ( bolus 1 mg ; période réfractaire 10 mm ) et la douleur était évaluée par échelle visuelle analogique toutes les six heures au repos et au mouvement . Les effets secondaires étaient notés toutes les six heures . Result atsLes patients et la chirurgie étaient similaires dans les quatre groupes . Les scores d’EVA etaient plus bas pendant les 48 heures de I’étude dans le groupe 4 par rapport à ceux des groupes 1 , 2 et 3 au repos ( P < 0.05 ) comme au mouvement ( P < 0.01 ) . Les doses cumulées de morphine étaient significativement plus basses à 48 h dans le groupe 4 par rapport au groupe 1 ( 23.4 ± 5 mg vs 58.9 ± 9 mg ; P < 0.01 ) . groupe 2 ( 23.4 ± 5 mgvs 43.4 ± 6.6 mg ; P < 0.05 ) et pas significativement différentes de celles du groupe 3 ( 34.2 ± 4.5 mg ) . L’incidence des effets secondaires était similaire dans tous les groupes . Conclusion L’association de propacetamol et ketoprofen a réduit les scores de douleur au repos et au mouvement par rapport aux groupes traités par une seule drogue analgésique . Lassociation propacetamol-ketoprofen n’a pas significativement réduit la consommation de morphine et les effets secondaires Iiés à la morphine BACKGROUND Following laparoscopic cholecystectomy , an effective post-operative pain control is necessary , at least during the first 24 hours . We present a r and omized , double-blind trial on the effect of the combined use of intravenous parecoxib , and metamizol or paracetamol on piritramide consumption using a patient-controlled analgesia ( PCA ) pump in patients recovering from laparoscopic cholecystectomy . METHODS 120 patients were r and omly allocated to four patient groups treated with normal saline or one of non-opioid analgesics ( parecoxib 40 mg twice daily , metamizol 1 g three times daily , paracetamol 1 g three times daily ) in addition to piritramide using the PCA pump . Beginning in the post-anesthesia care unit ( PACU ) , patients were asked every 2 h for 6 hours and afterwards once every 6 h to quantify their pain experience at rest while piritramide consumption was recorded . RESULTS In all groups , piritramide consumption was high in PACU . Only metamizol significantly reduced piritramide consumption compared to the others upon discharge from PACU . Overall , cumulative piritramide consumption was slightly lower in the metamizol group and higher in the NaCl group ; however , these findings were statistically not significant . VAS scores were highest upon arrival in PACU and dropped almost continuously after surgery . A significantly lower postoperative pain intensity was only found in the parecoxib group at 24 h after surgery compared to the metamizol group . CONCLUSION The efficacy of tested additive medications on piritramide consumption and pain relief is weak and there is no clear-cut difference between the non-opioid drugs used BACKGROUND Intravenous acetaminophen has been approved in Europe and elsewhere for the treatment of acute pain and fever , and was recently approved by the US Food and Drug Administration ( FDA ) for the management of mild to moderate pain , the management of moderate to severe pain with adjunctive opioid analgesics , and the reduction of fever . OBJECTIVE The aim of this work was to evaluate the analgesic efficacy and safety of repeated doses of 2 dosing regimens of intravenous acetaminophen compared with placebo over 24 hours in subjects with moderate to severe pain after abdominal laparoscopic surgery . METHODS This double-blind , placebo-controlled , parallel-group study was conducted at 17 sites in the United States and enrolled adult subjects ( aged 18 - 80 years ) who were r and omized to 4 groups ( IV acetaminophen 1000 mg [ 100 mL ] q6h ; IV acetaminophen 650 mg [ 65 mL ] q4h ; IV placebo 100 mL q6h ; or IV placebo 65 mL q4h ) , each given as a 15-minute infusion after surgery for 24 hours . An open-label extension was offered to all subjects who remained in the hospital beyond the study period . Two subjects ( 1 in the placebo 100 mL q6h group and 1 in the IV acetaminophen 1000 mg q6h group ) were enrolled in the open-label extension and were eligible to receive unblinded IV acetaminophen 1000 mg . Before r and omization , the choice of opioid for patient-controlled analgesia ( PCA ) rescue was left to the investigator ; however , acetaminophen-containing products , NSAIDs , and aspirin were not allowed . The morning after abdominal laparoscopic surgery procedure , subjects ' PCA was withheld until pain intensity ( PI ) was moderate ( 2 ) or severe ( 3 ) on a categorical scale ( range , 0 - 3 ) and between 40 and 70 mm , inclusive , on a 100-mm visual analog scale , at which point they were r and omized . After the first dose of study medication , intravenous rescue was restricted to morphine or hydromorphone , and oral rescue was restricted to morphine or oxycodone immediate-release tablets . Efficacy analyses were performed using the modified intent-to-treat ( mITT ) population , defined as all r and omized subjects who received ≥ 1 complete dose of study medication before requesting rescue medication , and who had ≥ 1 completed PI/pain relief ( PR ) assessment after baseline . The primary efficacy end point was the weighted sum of PI differences over 24 hours ( SPID24 ) using an ANCOVA model . Time to meaningful PR was documented after the first dose of study medication using a double-stopwatch method : at T0 , 2 stopwatches were started , and subjects were instructed to stop the first stopwatch when they felt perceptible PR and the second when it became meaningful . Safety was assessed via spontaneous adverse event ( AE ) reporting and laboratory tests . RESULTS A total of 349 subjects were screened before elective surgery for eligibility . Of these , 244 subjects were r and omized to a study arm ( IV acetaminophen 1000 mg [ n = 92 ] ; IV acetaminophen 650 mg [ n = 42 ] ; IV placebo 100 mL [ n = 43 ] ; or IV placebo 65 mL [ n = 67 ] ) and included in the ITT population , of whom 81.1 % ( 198/244 ) were women and 87.3 % ( 213/244 ) were white ; the mean ( SD ) age was 46.2 ( 12.51 ) years ( range , 18 - 78 years ) , and the mean weight was 174.3 ( 35.7 ) lb ( range , 103 - 284 lb ) . There was an allocation error in the contract research organization 's program linking group assignment and kit r and omization ; therefore , the original r and omization procedure was replaced with a modified r and omization schedule created by an independent biostatistician under the supervision of the FDA . The mITT population included 241 subjects ; of these , 227 completed 24 hours of treatment . Four subjects withdrew before completing treatment because of AEs ( 1 subject in the placebo group because of fever and 3 in the IV acetaminophen 1000 mg q6h group because of infusion-site pain [ n = 1 ] or infiltration [ n = 2 ] ) , 8 because of withdrawal of consent , 2 because of early discharge from the hospital , and 2 for other reasons . Only 2 subjects participated in the elective open-label extension . Both intravenous acetaminophen dosing regimens were associated with significantly reduced SPID24 compared with placebo ( 1000 mg q6h , P < 0.007 ; 650 mg q4h , P < 0.019 ) . Among the mITT population , SPID24 ( using nonimputed data after first rescue : 1000 mg q6h , P < 0.001 ; 650 mg q4h , P = 0.020 ) , sum of PR scores over 24 hours ( 1000 mg q6h , P < 0.001 ; 650 mg q4h , P = 0.003 ) and 12 hours ( 1000 mg q6h , P < 0.001 ; 650 mg q4h , P = 0.001 ) , and subjects ' global evaluations at 24 hours ( 1000 mg q6h , P < 0.001 ; 650 mg q4h , P = 0.005 ) were statistically significant in favor of both acetaminophen dosing regimens compared with the combined placebo group . Time to meaningful PR ( by double stopwatch method ) after the first dose was significantly shorter among subjects who received IV acetaminophen 1000 mg compared with subjects in the placebo 100 mL group ( median of 24.9 vs 53.9 minutes , respectively ) . The most common overall AEs ( ie , those that occurred in > 10 % of any group ) were constipation , flatulence , nausea , and headache . The frequency of treatment-emergent AEs ( TEAEs ) across the treatment groups was not statistically significant . Most TEAEs were deemed to be unrelated to study medication . There were 6 subjects with serious TEAEs ( 1 [ 0.9 % ] in the IV acetaminophen 1000 mg group , 3 [ 7.0 % ] in the IV acetaminophen 650 mg group , and 2 [ 1.8 % ] in the placebo group ) . There was 1 ( 2.3 % ) related hepatic TEAE ( transaminase increased ) in the placebo group . CONCLUSION Both regimens of intravenous acetaminophen ( 1000 mg q6h and 650 mg q4h ) were associated with statistically significant analgesic efficacy compared with placebo and were well tolerated in these adults after abdominal laparoscopic surgery . Clinical Trials.gov identifier : NCT00564486 To compare the analgesic efficacy and tolerance of propacetamol and morphine , 80 patients in good clinical condition were included in a prospect i ve , parallel , r and omized double blind trial after elective surgery expected to elicit light to moderate postoperative pain . At the end of general anesthesia , 40 patients received 30 mg/kg propacetamol and 40 0.2 mg/kg morphine , as a 15-min intravenous infusion . The groups were similar for age , weight and duration of anesthesia . Supplemental analgesia had to be given in 7 cases from the propacetamol group vs. 2 cases from the morphine group . The postoperative pain , evaluated 7 times during 4 h from the end of infusion with a visual analog scale , revealed a modest advantage for morphine at 0.5 and 4 h ( p = 0.05 ) . The respiratory rate was slightly lower after morphine ( p = 0.02 ) . No significant differences were observed in blood oxygen saturation , blood pressure , heart rate , body temperature and vigilance evaluated by the trailmaking test . Nausea was present in 4 cases under propacetamol and 3 under morphine , and pruritus in 2 and 7 cases , respectively . In conclusion , propacetamol may represent an alternative to morphine for pain prevention after mildly to moderately painful surgery in situations where the use of opioids is unsuitable We conducted this double-blinded , r and omized study to assess the analgesic effect of repeated administrations of paracetamol , administered as propacetamol , an injectable prodrug formulation of paracetamol , and to compare this with the analgesic effects of morphine . Patients experiencing moderate to severe pain after elective surgical removal of bone-impacted third-molar teeth under general anesthesia were r and omly assigned to receive IV propacetamol 2 g ( n = 31 ) , IM morphine 10 mg ( n = 30 ) , or placebo ( n = 34 ) . Five hours later , the treatments were readministered at half of the previous dosages . St and ard measures of analgesia were collected repeatedly for 10 h. Propacetamol and morphine were significantly more effective than placebo in all primary measures of analgesia over 5 h after the first administration and globally over 10 h ( first and second administrations ) . After the first dose , 21 of the 34 patients in the placebo group required rescue medication , compared with 6 of the 31 in the propacetamol group ( P < 0.0009 ) and 4 of the 30 in the morphine group ( P < 0.0001 ) . No statistically or clinical ly significant differences were found between propacetamol and morphine for any sum or peak measures of analgesia . No serious adverse events were reported ; adverse events were significantly less frequent in the propacetamol group than in the morphine group ( P < 0.027 ) . Propacetamol administered IV in repeated doses ( 2 g followed by 1 g ) has a significant analgesic effect that is indistinguishable from that of morphine administered IM ( 10 mg followed by 5 mg ) after dental surgery , with better tolerability & 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 Background and objective : Enteral acetaminophen ( paracetamol ) has limited analgesic efficacy due to its delayed absorption and sub‐therapeutic plasma concentration . Intravenous ( i.v . ) acetaminophen solves this issue and could thus provide adequate analgesia as a single agent . We compared intraoperative i.v . acetaminophen with intramuscular ( i.m . ) meperidine with regard to postoperative analgesia and readiness for discharge in paediatric patients undergoing day care dental restoration . Methods : Forty children were r and omized , in this double‐blind study , to receive acetaminophen 15 mg kg−1 i.v . ( Group A ) or meperidine 1 mg kg−1 i.m . ( Group M ) after anaesthesia induction and before surgery . All patients received midazolam 0.5 mg kg−1 orally 30 min preoperatively and fentanyl 1 μg kg−1 i.v . immediately after induction . Anaesthesia was induced with either sevoflurane inhalation or propofol 3 mg kg−1 i.v . and was maintained with sevoflurane . Postoperatively , the objective pain scale , Ramsay sedation score , and Aldrete score were determined every 5 min until readiness for recovery room discharge ( defined as achieving an Aldrete score of 10 ) . Results : Group A had slightly higher pain scores during early recovery compared with Group M ( estimated marginal means : 3 ± SEM 0.4 vs. 2 ± SEM 0.4 , respectively ( 95 % CI for difference : 0.4 , 2.6 ) , P = 0.012 for F‐test ) . In contrast , Ramsay scores were higher in Group M than in Group A during assessment period ( estimated marginal means : 4 ± SEM 0.3 vs. 2 ± SEM 0.4 , respectively ( 95 % CI for difference : −2.3 , −0.3 ) , P = 0.013 for F‐test ) . Group A patients achieved an Aldrete score of 10 sooner than those in Group M ( 5 ± SEM 2 vs. 16 ± SEM 4 min , respectively ( 95 % CI for difference : −9 , −14 ) , P = 0.009 ) . Conclusion : Compared with i.m . meperidine , intraoperative i.v . acetaminophen result ed in slightly higher pain scores but earlier readiness for recovery room discharge in paediatric patients undergoing dental restoration . The potential economic benefit of early recovery room discharge needs to be further explored We assessed the analgesic efficacy of IV propacetamol and ketorolac in a double-blinded , placebo-controlled study involving patients undergoing total hip or knee replacement procedures . On the first morning after major joint replacement surgery , 164 patients experiencing moderate-to-severe pain were r and omly assigned to receive an IV infusion of propacetamol ( 2 g ) , ketorolac ( 15 or 30 mg ) , or placebo ( saline ) . Patient-controlled analgesia with morphine was made available as a “ rescue ” analgesic on patient ’s request during the 6-h postdosing evaluation period . The median time to onset of analgesia with propacetamol ( 8 [ 95 % confidence interval 6,10 ] min ) was shorter than ketorolac 15 mg ( 14 [ 7,16 ] min ) , and placebo ( 16 [ 8 ; not estimable ] min ) although the differences did not reach statistical significance . However , compared with ketorolac 30 mg , propacetamol had a shorter duration of analgesia ( 3.5 [ 2;5.4 ] vs 6 [ 3.3 ; not estimable ] h ) . Analysis of pain intensity and pain relief scores demonstrated that propacetamol produced a significantly greater improvement in pain relief than saline from 45 min until 5 h after the injection . Propacetamol was not significantly different from ketorolac 15 mg and 30 mg with respect to the main analgesic efficacy variables during the 6-h assessment period . The most frequently reported adverse event with propacetamol was injection site pain ( 28 % vs 19 % for ketorolac 15 mg , 29 % for ketorolac 30 mg , and 10 % for placebo , respectively ) . In conclusion , propacetamol ( 2 g IV ) possesses a similar analgesic efficacy to ketorolac ( 15 or 30 mg IV ) after total hip or knee replacement surgery OBJECTIVES The aim of this study was to assess the analgesic efficacy and safety of nonsteroidal anti-inflammatory drugs ( NSAIDs ) , administered as intramuscular diclofenac in comparison with intravenous paracetamol after transurethral resection of the prostate ( TURP ) . MATERIAL S AND METHODS Fifty men , aged 55 to 75 years , undergoing TURP at our hospital were included in this study . Patients were divided r and omly and prospect ively into two groups ( 25 patients in each group ) . Group I ( NSAID ) received 75 mg of diclofenac i.m . at the end of the operation followed by 75 mg of diclofenac i.m . for 24 hours ( 75 mg x 2 once a day = 150 mg/24 h ) postoperatively . The other group ( Group II ) consisted of patients who received 1g/100 mL i.v . paracetamol 15 minutes twice daily as postoperative analgesia . Postoperative pain scores were evaluated at 30 minutes , 1 , 2 , 4 and 6 hours after administration of each analgesic , using a visual analogue scale ( VAS ) . Furthermore , preoperative and postoperative hemoglobin ( Hb ) levels and hemostatic variables ( bleeding time , prothrombine time and the international normalized ratio , i.e. the ratio of a patient 's prothrombin time to a normal [ control ] sample ) were recorded in all patients . RESULTS The pain score changes during a 4 hour period between the two groups was similar ( p = 0.162 ) . Thirty minutes after surgery , pain scores were high ( > 3 cm ) in both groups and without differences between groups ( p = 0.11 ) but 6 hours after surgery , pain scores were significantly higher with paracetamol compared to diclofenac ( p < 0.05 ) . No significant difference was observed between the groups regarding the amount of resected tissue , operating time , preoperative-postoperative Hb levels and hemostatic variables . In the both groups , no patient required blood transfusion postoperatively . CONCLUSIONS NSAIDs are not a contraindication to TURP and should be used for the control of postoperative pain if indicated Paracetamol , a central ly acting inhibitor of cyclooxygenase , has less gastrointestinal and platelet-inhibiting side effects and is clinical ly better tolerated than nonsteroidal anti-inflammatory drugs . Therefore , it will be ideally suited for postoperative pain relief . In this prospect i ve , double-blind , r and omized , placebo-controlled study , we evaluated the analgesic efficacy , opioid-sparing effect and effects on opioid-related adverse effects of intravenous ( IV ) paracetamol in combination with IV morphine after lumbar laminectomy and discectomy . Forty patients were divided into 2 groups ( n=20 each ) to receive either paracetamol 1 g ( group 1 ) or 0.9 % NaCl 100 ml ( group 2 ) at the end of the operation and at 6-hour intervals over 24 hours . IV patient-controlled analgesia with morphine was used as a rescue analgesic in both groups . Pain was evaluated at rest and on movement at the 1st , 2nd , 4th , 6th , 12th , 18th , and 24th hours using a visual analog scale . Hemodynamic parameters , morphine usage , patient satisfaction , and probable side effects were also evaluated . Pain scores at rest and on movement at the 12th , 18th , and 24th hours were significantly lower in group 1 ( P<0.001 ) . Morphine consumption was not statistically significantly different between the groups ( P>0.05 ) . Vomiting in group 2 was significantly higher ( P=0.027 ) . Significantly more patients in the paracetamol group rated their pain management as excellent ( 45 % vs. 5 % ) . Although repeated IV paracetamol usage after lumbar laminectomy and discectomy did not demonstrate a significant opioid-sparing effect , it did decrease visual analog scale scores at certain evaluation times and incidence of vomiting and increase patient satisfaction Study Design . A r and omized , placebo-controlled , double-blind study to evaluate the effect of intravenously ( IV ) administered acetaminophen on postoperative pain in children and adolescents undergoing surgery for idiopathic scoliosis or spondylolisthesis . Objective . To evaluate effectiveness of IV-administered acetaminophen on postoperative analgesia , opioid consumption , and acetaminophen concentrations after major spine surgery in adolescents . Summary of Background Data . Scoliosis surgery is associated with severe postoperative pain , most commonly treated with IV-administered opioids . Nonsteroidal anti-inflammatory drugs ( NSAIDs ) , as adjuvant to opioids , improve analgesia and reduce the need for opioids . However , by inhibiting cyclo-oxygenase enzymes peripherally , NSAIDs may inhibit bone healing . Acetaminophen , a central ly acting analgesic , does not have the adverse effects of NSAIDs and has improved analgesia in children after another orthopedic surgery . Methods . In an institutional review board approved study , 36 American Society of Anesthesiology patient classification I to III patients of 10 to 18 years of age were analyzed . Acetaminophen 30 mg/kg , administered IV or 0.9 % NaCl was administered at the end of scoliosis or spondylolisthesis surgery , and thereafter twice at 8-hour intervals . Timed blood sample s for acetaminophen determination were taken between 0.25 and 20 hours after the first dose . All patients received st and ard propofol-remifentanil anesthesia . Pain scores ( visual analogue scale [ VAS ] , 0–10 ) , opioid consumption , and adverse effects were recorded . Results . In the surgical ward , 7 ( 39 % ) patients in the acetaminophen and 13 ( 72 % ) in the placebo group had a VAS pain score 6 or more ( P < 0.05 ) . There were fewer hours with VAS score 6 or more in the acetaminophen group compared with the placebo group ( 8.7 % vs. 17.8 % of the hours , P < 0.05 ) . There was no difference in oxycodone consumption during the 24-hour follow-up between the 2 groups . Conclusion . IV-administered acetaminophen 90 mg/kg/day , adjuvant to oxycodone , did improve analgesia , but did not diminish oxycodone consumption during 24 hours after major spine surgery in children and adolescents . All acetaminophen concentrations were in nontoxic levels BACKGROUND We assessed the analgesic efficacy of parecoxib , acetaminophen , and the combination of both compared with placebo in patients undergoing elective thyroid or parathyroid surgery . METHODS We r and omized 140 patients to receive one of the following i.v . treatments using a double-blinded double-dummy technique : placebo , 80 mg 24 h(-1 ) parecoxib , 5 g 24 h(-1 ) acetaminophen , or 80 mg parecoxib plus 5 g acetaminophen . We provided rescue analgesia with piritramide delivered by a patient-controlled analgesia device . We measured opioid consumption and pain intensity over 24 h after operation . RESULTS Patient characteristic data , anaesthetic , and surgical characteristics of the patients in the four groups were similar . Parecoxib , acetaminophen , and the combination significantly reduced opioid requirements during 24 h after surgery [ mean ( sd ) 12.5 ( 10.9 ) mg for parecoxib , 14.2 ( 12.3 ) mg for acetaminophen , and 11.9 ( 10.7 ) mg for combination ] compared with placebo [ 23.5 ( 15.3 ) mg , P<0.05 ] . However , the combination of parecoxib and acetaminophen did not have any advantage over individual drugs in terms of opioid consumption in our trial ( P>0.05 ) . CONCLUSIONS Parecoxib and acetaminophen effectively reduce postoperative opioid requirements after thyroid or parathyroid surgery . The combination of these drugs is not associated with a further reduction in opioid consumption Background Although opioids are the main choice for acute postoperative pain control , many side effects have been reported for them . NSAIDs and paracetamol have been used extensively as alternatives , and it seems that they are more effective for minor to moderate pain control postoperatively when have been used alone or in combination with opioids . As laparoscopic cholecystectomy poses moderate pain postoperatively , this study was planned to assess whether paracetamol is able to provide effective analgesia as a sole analgesic at least in the first few hours post operatively . Objectives We evaluated the effect of intravenous Paracetamol on postoperative pain in patients undergoing laparoscopic cholecystectomy . Patients and Methods This is a r and omized double- blind clinical trial study . 30 patients ASA class I , aged 18 to 50 years , c and i date for laparoscopic cholecystectomy were recruited , and r and omly divided into two equal groups . Group A ( paracetamol group ) received 1 gr paracetamol and group B received placebo ten minutes after the induction of anesthesia . 0.1 mg/Kg Morphine was administered intravenously based on patients compliant and pain score > 3 . Pain score and the opioids consumption were recorded in the first six hours postoperative . Patient 's pain was measured by the VAS ( Visual Analog Scale ) . Results The pain score was lower in group A ( P= 0.01 ) , but the morphine consumption showed no significant difference between the groups ( P= 0.24 ) during the first 6 hours postoperatively . Conclusions Although paracetamol ( 1gr ) has caused a better pain relief quality but it is not a suitable analgesic for moderate pain control in acute phase after surgery alone Purpose The aim of the study was to compare the efficacy of parecoxib for postoperative analgesia after endoscopic turbinate and sinus surgery with the prodrug of acetaminophen , proparacetamol . Material s and Methods Fifty American Society of Anesthesiology ( ASA ) physical status I-II patients , receiving functional endoscopic sinus surgery ( FESS ) and endoscopic turbinectomy , were investigated in a prospect i ve , r and omized , double-blind manner . After local infiltration with 1 % mepivacaine , patients were r and omly allocated to receive intravenous ( IV ) administration of either 40 mg of parecoxib ( n = 25 ) or 2 g of proparacetamol ( n = 25 ) 15 min before discontinuation of total IV anaesthesia with propofol and remifentanil . A blinded observer recorded the incidence and severity of pain at admission to the post anaesthesia care unit ( PACU ) at 10 , 20 , and 30 min after PACU admission , and every 1 h thereafter for the first 6 postoperative h. Results The area under the curve of VAS ( AUCVAS ) calculated during the study period was 669 ( 28 - 1901 ) cm·min in the proparacetamol group and 635 ( 26 - 1413 ) cm·min in the parecoxib group ( p = 0.34 ) . Rescue morphine analgesia was required by 14 patients ( 56 % ) in the proparacetamol group and 12 patients ( 48 % ) in the parecoxib ( p ≥ 0.05 ) , while mean morphine consumption was 5 - 3.5 mg and 5 - 2.0 mg in the proparacetamol groups and parecoxib , respectively ( p ≥ 0.05 ) . No differences in the incidence of side effects were recorded between the 2 groups . Patient satisfaction was similarly high in both groups , and all patients were uneventfully discharged 24 h after surgery . Conclusion In patients undergoing endoscopic nasal surgery , prior infiltration with local anaesthetics , parecoxib administered before discontinuing general anaesthetic , is not superior to proparacetamol in treating early postoperative pain OBJECTIVES Paracetamol is primarily thought to be a cyclooxygenase inhibitor acting through the central nervous system . Indirect effects of paracetamol are through the serotoninergic system as a non-opioid analgesic . In this study , total abdominal hysterectomy patients were given intravenous ( iv ) paracetamol 1 g preoperatively or intraoperatively to assess its postoperative analgesic effects . METHODS 90 patients undergoing total abdominal hysterectomy were enrolled into the study . Patients were r and omized into three groups : in Group I , iv paracetamol 1 g was given 30 minutes prior to induction . In Group II , iv paracetamol 1 g was given prior to skin closure . Group III served as the control group and received saline as placebo . Postoperatively , all patients received morphine via patient-controlled analgesia pump . Postoperatively , rest and activity pain scores , sedation scores , hemodynamic parameters , postoperative morphine consumption , side effects , patient satisfaction , and total hospital stay were recorded . RESULTS In the control group , at rest and movement pain scores and total morphine consumption via patient-controlled analgesia were higher than in Groups I and II . When Groups I and II were compared , total morphine consumption was much greater in Group II . Intravenous paracetamol intraoperatively and postoperatively did not result in any hemodynamic effects . CONCLUSION In total abdominal hysterectomy , preemptive iv paracetamol 1 g provided good quality postoperative analgesia , with decreased consumption of morphine and minimal side effects Background : Opioids have been traditionally used for postoperative pain control , but they have some unpleasant side effects such as respiratory depression or nausea . Some other analgesic drugs like non-steroidal anti-inflammatory drugs ( NSAIDs ) are also being used for pain management due to their fewer side effects . Objectives : The aim of our study was to compare the analgesic effects of paracetamol , an intravenous non-opioid analgesic and morphine infusion after elective laparotomy surgeries . Patients and Methods : This r and omized clinical study was performed on 157 ASA ( American Society of Anesthesiology ) I-II patients , who were scheduled for elective laparotomy . These patients were managed by general anesthesia with TIVA technique in both groups and 150 patients were analyzed . Paracetamol ( 4 g/24 hours ) in group 1 and morphine ( 20 mg/24 hours ) in group 2 were administered by infusion pump after surgery . Postoperative pain evaluation was performed by visual analog scale ( VAS ) during several hours postoperatively . Meperidine was administered for patients complaining of pain with VAS > 3 and repeated if essential . Total doses of infused analgesics , were recorded following the surgery and compared . Analysis was performed on the basis of VAS findings and meperidine consumption . Results : There were no differences in demographic data between two groups . Significant difference in pain score was found between the two groups , in the first eight hours following operation ( P value = 0.00 ) , but not after 12 hours ( P = 0.14 ) .The total dose of rescue drug ( meperidine ) and number of doses injected showed a meaningful difference between the two groups ( P = 0.00 ) . Also nausea , vomiting and itching showed a significant difference between the two groups and patients in morphine group , experienced higher levels of them . Conclusions : Paracetamol is not enough for postoperative pain relief in the first eight hour postoperatively , but it can reduce postoperative opioid need and is efficient enough for pain management as morphine after the first eight hours following surgery Background The aim of this study was to compare the efficacy of ketorolac , paracetamol , and paracetamol plus morphine on pain relief after thyroidectomy . Methods Eighty patients were r and omly allocated to one of the 4 groups : normal saline ( group C ) , ketorolac 30 mg ( group K ) , paracetamol 1 g ( group P ) , and paracetamol 700 mg plus morphine 3 mg ( group PM ) . Each regimen was administered intravenously ( IV ) 30 min . before the end of surgery . If pain was not relieved , patients received an IV bolus of pethidine hydrochloride 25 mg . Pain intensity using a visual analogue scale ( VAS ) was recorded at 0.5 , 1 , 2 , 4 , and 6 hr after the end of surgery . Results VAS at 0.5 and 1 hr after the end of surgery were significantly lower in group K , group P , and group PM than in group C ( P < 0.05 ) . The number of patients receiving pethidine hydrochloride at 0.5 and 1 hr after the end of surgery was significantly lower in group K , group P , and group PM than in group C ( P < 0.05 ) . There was no significant difference among the groups in the incidences of adverse events associated with study medications and patient satisfaction ( P > 0.05 ) . Conclusions Paracetamol 1 g IV possesses a similar analgesic efficacy to ketorolac 30 mg IV after thyroidectomy . Paracetamol may represent an alternative to ketorolac for pain prevention after mildly to moderately painful surgery in situations where the use of NSAIDs is unsuitable STUDY OBJECTIVE To compare postoperative pain scores and rescue analgesic use in patients who received acetaminophen preoperatively or during skin closure versus those who received a placebo . DESIGN R and omized , double-blind clinical trial . SETTING University-based , tertiary-care hospital . PATIENTS 75 adult , ASA physical status 1 and 2 undergoing lower extremity orthopedic surgery . INTERVENTIONS Patients were r and omized to three groups . The control group received 100 mL of intravenous ( IV ) normal saline as a placebo . The preventive acetaminophen group received 100 mL of IV normal saline plus 15 mg/kg of acetaminophen prior to skin closure . The preemptive acetaminophen group received 15 mg/kg of IV acetaminophen combined with 100 mL of normal saline half an hour preoperatively . MEASUREMENTS Pain was scored with the verbal rating scale and assessed 5 minutes before spinal anesthesia , and 6 , 12 , 18 , and 24 hours after surgery . Total rescue meperidine consumption by each patient during the first 24 hours after surgery was also recorded . MAIN RESULTS Pain scores were lower in both preemptive and preventive acetaminophen groups at 6 hours after surgery than in the placebo group ( P < 0.001 ) . There were no differences in pain scores after 6 hours between the preemptive and preventive groups . Total analgesic consumption 24 hours after surgery was lowest in the preemptive acetaminophen group ( P < 0.01 ) . Average time to initial analgesic requirement was slightly longer in the preemptive and preventive acetaminophen groups than the control group ( P < 0.01 ) . CONCLUSION In patients undergoing lower extremity surgery with spinal anesthesia , both preventive and preemptive acetaminophen may enhance analgesia and decrease postoperative analgesic consumption UNLABELLED We assessed the relative morphine consumption in a combined analgesic regimen ( on-dem and morphine plus the nonopioids propacetamol or ketorolac ) after gynecologic surgery . Two hundred women r and omly received two i.v . doses of propacetamol 2 g or ketorolac 30 mg in a double-blinded , double-dummy trial . Patients were monitored for 12 h , and the following efficacy variables were assessed : total dose of morphine , pain intensity , and global efficacy . Safety and tolerability were evaluated by the occurrence of adverse events , especially the presence and intensity of gastrointestinal symptoms . Hemostatic variables were measured 30 and 60 min after the first infusion ; arterial blood pressure , heart and respiratory rates , sedation scores , and renal and hepatic function were also assessed . Total morphine requirements were not significantly different between the propacetamol ( 10.6 + /- 4.8 mg ) and ketorolac ( 10.2 + /- 4.4 mg ) groups . The evolution of pain intensity and the global efficacy also showed similar patterns in the two groups : 70.2 % of patients in the propacetamol group rated the efficacy as " good/ excellent " compared with 68.2 % in the ketorolac group . There were no clinical ly significant changes in vital signs or laboratory values and no observed differences between the two groups , although ketorolac slightly , but not significantly , prolonged the bleeding time . Epigastric pain was present in 9 % and 15 % of patients receiving propacetamol and ketorolac , respectively . There were two adverse events in the propacetamol group and four in the ketorolac group . Propacetamol demonstrates an efficacy similar to that of ketorolac and has an excellent tolerability after gynecologic surgery . IMPLICATION S Propacetamol and ketorolac , combined with patient-controlled analgesia morphine , show similar analgesic efficacy after gynecologic surgery . Morphine consumption and pain scores were comparable in the two studied groups . Propacetamol is as effective as ketorolac and has an excellent tolerability after gynecologic surgery Abstract A previously established relationship for deriving dichotomous from continuous information in r and omised controlled trials ( RCTs ) of analgesics has been tested using an independent data set . Individual patient information from 18 RCTs of parallel‐group design in acute postoperative pain ( after abdominal , gynaecological and oral surgery ) was used to calculate the percentage of the maximum possible pain relief score ( % maxTOTPAR ) and the proportion of patients with > 50%maxTOTPAR for the different treatments . The relationship between the measures was investigated in 85 treatments with over 3400 patients . In 80 of 85 treatments ( 94 % ) agreement between calculated and actual number of patients with > 50%maxTOTPAR was within four patients per treatment and in 72 ( 85 % ) was within three ( average of 40 patients per treatment , range 21–58 patients ) . Summing the positive and negative differences between actual and calculated numbers of patients with > 50%maxTOTPAR gave an average difference of 0.30 patients per treatment arm . Reports of RCTs of analgesics frequently describe results of studies in the form of mean derived indices , rather than using discontinuous events , such as number or proportion of patients with 50 % pain relief . Because mean data inadequately describe information with a non‐normal distribution , combining mean data in systematic review s may compromise the results . Showing that dichotomous data can reliably be derived from mean data in acute pain studies enables data published as means to be used for quantitative systematic review s which require data in dichotomous form Background and objective : The combination of non‐opioid analgesic drugs , though widely used , has been rarely evaluated . The aim of this study was to compare the efficacy of propacetamol and the non‐steroidal analgesic drug ketoprofen , alone or in combination , on pain relief after thyroid surgery performed using remifentanil . Methods : Ninety‐seven patients were r and omly allocated to one of the three groups : propacetamol 2 g ( 32 ) , ketoprofen 100 mg ( 33 ) and propacetamol 2 g + ketoprofen 100 mg ( 32 ) . Each regimen was administered intravenously ( i.v . ) 30 min before the end of surgery and then every 6 h. If pain was not relieved , patients received an i.v . bolus of tramadol 100 mg . Tramadol consumption and pain intensity using a visual analogue scale was recorded at 1 , 2 , 8 and 14 h after the end of surgery . Results : Pain scores were significantly higher with propacetamol compared with ketoprofen 2 h after surgery ( 35 ± 3.7 , 21 ± 2.6 , respectively ; P < 0.01 ) . The number of patients receiving tramadol was higher with propacetamol alone compared with the two other groups , 1 h ( 14/32 , 4/33 , 2/32 , respectively ; P > 0.01 ) and 2 h ( 24/32 , 6/33 , 8/32 , respectively ; P < 0.01 ) after surgery . There was no difference between ketoprofen alone and ketoprofen plus propacetamol , and there was no difference between the three groups from the 8th hour onward . Conclusions : In the immediate postoperative period after thyroid surgery performed using remifentanil , the concomitant use of propacetamol and ketoprofen does not improve analgesia compared with ketoprofen alone BACKGROUND Enteral acetaminophen , when used alone , is not very effective for postoperative analgesia because of delayed absorption and sub-therapeutic plasma concentrations . In contrast , i.v . acetaminophen is devoid of these shortcomings and could potentially provide adequate postoperative analgesia as a single agent . This r and omized double-blind study compared the analgesic effects of i.v . acetaminophen and i.m . meperidine in paediatric patients undergoing tonsillectomy . METHODS Eighty children undergoing tonsillectomy were r and omized to receive either acetaminophen 15 mg kg(-1 ) i.v . ( acetaminophen group ) or meperidine 1 mg kg(-1 ) i.m . ( meperidine group ) , intraoperatively . Anaesthesia was induced with either sevoflurane inhalation or propofol , and was maintained with sevoflurane . After operation , the objective pain scale ( OPS ) , Ramsay sedation score and Aldrete score were recorded every 5 min , and nurses ' satisfaction was determined on a 7-point scale ( 1 - 7 ) . RESULTS On admission to the recovery room , OPS scores were 3.1 ( sem 0.3 ) for the acetaminophen group and 2.1 ( sem 0.3 ) for the meperidine group ( P=0.147 ) ; however , Ramsay sedation scores were 3 ( sem 0.2 ) and 4 ( sem 0.3 ) for the acetaminophen and meperidine groups , respectively ( P<0.05 ) . Patients in the meperidine group continued to be more se date d 5 min after arrival in recovery ( P<0.05 ) . Acetaminophen group patients achieved an Aldrete score of 10 min sooner than those in the meperidine group [ median ( IQR ) time : 15 ( 0 - 20 ) min vs 25 ( 15 - 30 ) min , respectively , P=0.005 ] . Adjusted nurse satisfaction scores were similar in both groups [ 6.1 ( sem 0.2 ) vs 5.7 ( sem 0.2 ) min , P=0.311 ] . CONCLUSION Compared with i.m . meperidine , i.v . acetaminophen provided adequate analgesia , less sedation and earlier readiness for recovery room discharge among paediatric patients undergoing tonsillectomy The benefit of combining non-opioid analgesics with neuraxial opioids for analgesia after caesarean delivery has not been clearly established . Larger doses of paracetamol or cyclooxygenase-2 inhibitors have not been evaluated . A r and omised , double blind , double-dummy , parallel group placebo-controlled clinical trial was conducted among women having elective caesarean delivery under spinal anaesthesia , followed by pethidine patient-controlled epidural analgesia . Patients received placebos ( group C ) ; intravenous parecoxib 40 mg then oral celecoxib 400 mg at 12 hours ( group PC ) ; intravenous paracetamol 2 g then oral 1 g six-hourly ( group PA ) ; or these regimens combined ( group PCPA ) . The primary outcome was 24-hour postoperative patient-controlled epidural pethidine use and the main secondary outcome was postoperative pain . One hundred and thirty-eight women were recruited but 27 subsequently met exclusion criteria , leaving 111 who were r and omised , allocated and analysed by intention-to-treat ( n=23 , 30 , 32 and 26 in groups C , PC , PA and PCPA respectively ) . There were no differences between groups for pethidine consumption , based on either intention-to-treat ( median 365 , 365 , 405 and 360 mg in groups C , PC , PA and PCPA respectively , P=0.84 ) or per protocol analysis ( 17 major violations ) . Dynamic pain scores did not differ between groups but requirement for , and dose of , supplementary oral tramadol was least in group PCPA ( incidence 23 % versus 48 % , 70 % and 58 % in groups C , PC and PA respectively , P=0.004 ) . The addition of regular paracetamol , cyclooxygenase-2 inhibitors or both to pethidine patient-controlled epidural post-caesarean analgesia did not provide a pethidine dose-sparing effect during the first 24 hours BACKGROUND A new intravenous ( i.v . ) formulation of paracetamol and propacetamol ( prodrug of paracetamol ) were compared to determine tolerance and relative analgesic efficacy during the first 6 h after inguinal hernia repair performed under general anesthesia combined with ilioinguinal block in children . METHODS A total of 183 ASA I or II in- patients , aged 1 - 12 years , admitted for unilateral inguinal hernia repair were r and omized to receive in a double-blind design either i.v . paracetamol 15 mg.kg(-1 ) ( n = 95 ) or propacetamol 30 mg.kg(-1 ) ( n = 88 ) for postoperative pain relief as soon as pain intensity was greater than 30 on a 100 mm visual analog scale . All patients were evaluated for efficacy and tolerance . Efficacy was evaluated between 15 min and 6 h after the start of the 15 min infusion . RESULTS The most frequently reported adverse event was injection site pain , which was significantly reduced in the new formulation group ( i.v . paracetamol 14.7 % vs propacetamol 33.0 % of children , P = 0.005 ) . No significant difference was obtained between treatments on pain relief ( PR ) , pain intensity difference ( PAID ) from baseline , and objective pain scale intensity difference ( OPSD ) . Also , treatment effects did not differ significantly for maximum values and weighted sums of PR , PAID ( investigator and child rated ) , OPSD , time to first request for rescue medication , proportion of children requesting rescue medication , and investigators ' global treatment satisfaction . CONCLUSION A single infusion of i.v . paracetamol 15 mg.kg(-1 ) produced analgesia similar to a single infusion of propacetamol 30 mg.kg(-1 ) following inguinal hernia repair in children . Paracetamol i.v . 15 mg.kg(-1 ) was better tolerated at the injection site than propacetamol BACKGROUND Intravenous ( IV ) acetaminophen provides rapid and effective analgesia in the postoperative and inpatient setting s. The utility and efficacy of acetaminophen is well established ; however , due to chronic excessive dosing of over-the-counter acetaminophen products and prescription opioid combination products result ing in the potential for hepatic toxicity , concerns remain about acetaminophen safety . In order to evaluate the safety of IV acetaminophen 1,000 mg q6h or 650 mg q4h with repeated dosing for 5 days , a r and omized , open-label study assessed the safety and tolerability of repeated doses used to treat acute pain or fever in 213 adult in patients was conducted . METHODS Subjects were r and omized ( 3:3:1 ) to receive IV acetaminophen ( 1,000 mg q6h or 650 mg q4h ) or st and ard-of-care treatment for pain or fever . Safety was assessed according to spontaneous reports of adverse events ( AEs ) and clinical ly meaningful changes from baseline laboratory parameters . RESULTS Overall , IV acetaminophen was shown to be safe and well tolerated in adult in patients when given as repeated doses for up to 5 days . Owing to the comorbidities in the study population , the frequency of AEs reported was high . However , the majority of treatment-emergent adverse events ( TEAEs ) were unrelated to treatment , and only 8 % of the study population withdrew because of TEAEs . No major hepatic issues associated with IV acetaminophen warranted concern , and most hepatic events were likely related to underlying medical conditions or recent trauma/surgery . CONCLUSIONS Consistent with the tolerability and safety results , both treatment groups ( 1,000 mg q6h and 650 mg q4h ) demonstrated statistically significantly better ratings for the Subject Global Evaluations for the level of satisfaction with side effects related to study treatments as compared with the control group . The findings from this trial support the use of IV acetaminophen as a safe therapy in adult patients The aim of this study was to compare the analgesic efficacy of three different postoperative treatments after supratentorial craniotomy . Sixty-four patients were allocated prospect ively and r and omly into three groups : paracetamol ( the P group , n = 8) , paracetamol and tramadol ( the PT group , n = 29 ) , and paracetamol and nalbuphine ( the PN group , n = 27 ) . General anesthesia was st and ardized with propofol and remifentanil using atracurium as the muscle relaxant . One hour before the end of surgery , all patients received 30 mg/kg propacetamol intravenously then 30 mg/kg every 6 hours . Patients in the PT group received 1.5 mg/kg tramadol 1 hour before the end of surgery . For patients in the PN group , 0.15 mg/kg nalbuphine was injected after discontinuation of remifentanil , because of its & mgr;-antagonist effect . Postoperative pain was assessed in the fully awake patient after extubation ( hour 0 ) and at 1 , 2 , 4 , 8 , and 24 hours using a visual analog scale ( VAS ) . Additional tramadol ( 1.5 mg/kg ) or 0.15 mg/kg nalbuphine was administered when the VAS score was ≥ 30 mm . Analgesia was compared using the Mantha and Kaplan – Meier methods . Adverse effects of the drugs were also measured . The three groups were similar with respect to the total dose of remifentanil received ( 0.27 ± 0.1 & mgr;g/kg/min ) . In all patients , extubation was obtained within 6 ± 3 minutes after remifentanil administration . Postoperative analgesia was ineffective in the P group ; therefore , inclusion s in this group were stopped after the eighth patient . Postoperative analgesia was effective in the two remaining groups because VAS scores were similar , except at hour 1 , when nalbuphine was more effective ( P = .001 ) . Nevertheless , acquiring such a result dem and ed significantly more tramadol than nalbuphine ( P < .05 ) . More cases of nausea and vomiting were observed in the PT group but the difference was not significant ( P < .06 ) . In conclusion , pain after supratentorial neurosurgery must be taken into account , and paracetamol alone is insufficient in bringing relief to the patient . Addition of either tramadol or nalbuphine to paracetamol seems necessary to achieve adequate analgesia , with , nevertheless , a larger dose of tramadol to fulfill this objective The efficiency of paracetamol used in the balanced multimodal analgesia after thoracotomy still remains unclear . The prospect i ve study covered 75 adult patients operated on the chest . The patients were r and omized to 3 groups . They all received epidural autoanalgesia with a mixture of fentanyl ( 2 microg/ml ) in 0.2 % ropivacaine solution and intramuscular injections of ketorolac , 30 mg , every 8 hours . In Group 1 ( n = 25 ) , paracetamol was intravenously injected in a dose of 4 g daily . In Group 2 ( n = 23 ) , rectal paracetamol was used in an equipotential dose . In Group 3 ( n = 24 ) , paracetamol was not given . Within the first 24 postoperative hours , the severity of the pain syndrome and the incidence of adverse reactions of analgesia were estimated in all the patients . The obtained data were compared using Student 's t-test and x2 test , by taking into account Bonferroni 's correction . The p values of < 0.0017 were determined as statistically significant . The resting VAS did not differ between the groups . In cough , the severity of the pain syndrome was significantly less in Group 1 than in Groups 2 and 3 . The use of the epidural mixture of ropivacaine and fentanyl required for adequate analgesia within the first 24 hours after surgery was much less in Groups 1 and 2 than that in Group 3 . The high incidence of skin itch ( 20 % ) and urinary retention ( 8 % ) was observed in Group 3 ( p < 0.017 ) . No difference was found between the groups in the development of dyspepsia . The use of paracetamol in the postoperative multimodal analgesic therapy program after thoracotomy reduces the daily dose of epidurally administered ropivacaine and fentanyl with evident up grade of analgesia quality , and the incidence of opioid-induced adverse reactions OBJECTIVES A new , ready-to-use solution for injection of paracetamol ( Perfalgan 10 mg/ml ) without previous reconstitution has been developed . The aim of the study was to determine the serum concentration profiles of paracetamol after 15 min infusion of Perfalgan 0.5 g and 1 g doses and to demonstrate the bioequivalence between Perfalgan 1 g dose and a marketed reference formulation for injection , propacetamol 2 g ( Pro-Dafalgan 2 g ) equivalent to 1 g of paracetamol . The secondary objective was to evaluate local tolerance , and clinical and biological safety . METHODS The study was performed in 24 healthy , male volunteers , according to an open-label , r and omized , single-dose , 3-period crossover design , with a 1-week washout period between the doses . Blood sample s were taken prior to each administration and at 18 time points within the 24-hour period following the beginning of each infusion . Serum concentrations of paracetamol were determined by vali date d high-performance liquid chromatography with UV detection . From serum concentration-time data , a non-compartmental pharmacokinetic analysis was performed to calculate Cmax , tmax , AUC(inf ) , t(1/2 ) , MRT , Cl(T ) and Vd . Log-transformed AUC(inf ) and Cmax were tested for bioequivalence . The local pain intensity at infusion site was assessed using a 4-point categorical scale from 0 ( none ) to 3 ( severe ) . The clinical and biological safety was evaluated by physical examination with measurements of vital signs and ECG and laboratory tests including hematology and biochemistry . RESULTS After infusion of 0.5 g and I g of the new paracetamol solution , C(max ) and AUC(inf ) increased proportionally with dosage . After dose correction to 1 g of paracetamol , the mean ( + /- SD ) Cmax ratio was 0.98 + /- 0.24 and 0.94 + /- 0.08 for AUC ratio . Identical t(max ) was observed for the 2 paracetamol dosages and 90 % confidence intervals for t(1/2 ) , MRT , Cl(T ) and V(d ) were within the acceptable interval 0.8 - 1.25 . The calculated 90 % confidence intervals of the new solution ( Perfalgan 1 g ) to marketed solution ( propacetamol 2 g ) ratios were 1.11 - 1.31 ( point estimate 1.20 ) for C(max ) and 1.10 - 1.16 ( point estimate 1.13 ) for AUC(inf ) . These values were within the acceptable bioequivalence intervals of 0.75 to 1.33 for Cmax and 0.80 - 1.25 for AUC(inf ) . Application site disorders were the most frequently observed adverse events but local pain at infusion site was less reported by subjects after Perfalgan ( 2 % ) compared to propacetamol ( 20 % ) . The clinical and biological safety was good and equivalent for the 3 treatments . CONCLUSION After administration of paracetamol solution for injection 0.5 g and 1 g , the pharmacokinetics of paracetamol is linear . All results indicate that 1 g of paracetamol administered as Perfalgan 10 mg/ml is bioequivalent to propacetamol 2 g with a better local safety Background : Combined analgesic regimens have been suggested to improve the treatment of postoperative pain . The aim of our study was to evaluate the analgesic efficacy and tolerability of propacetamol , in combination with morphine Tonsillectomy in adults is associated with significant postoperative pain . Intravenous paracetamol injection ( Perfalgan ) is marketed for the management of acute pain . This prospect i ve placebo-controlled study was performed to evaluate the analgesic efficacy and safety of intravenous paracetamol in 76 adult patients undergoing elective st and ard bipolar diathermy tonsillectomy . After tonsillectomy was performed under general anesthesia , the patients were r and omized to receive either intravenous paracetamol 1 g ( Perfalgan ) ( n = 38 ) or 0.9 % normal saline as a placebo ( n = 38 ) at 6-h intervals . No other analgesic medication was permitted for postoperative pain during the study . Need for rescue analgesic during the first 24 h after surgery as well as all adverse events were recorded . The intravenous paracetamol group differed significantly from the placebo group regarding pain relief and median time to pethidine rescue . Intravenous paracetamol significantly reduced pethidine consumption over the 24-h period . The worst pain after surgery was also more severe in the placebo group than that in the paracetamol group . There was no significant difference between groups in the incidence of adverse events . Intravenous paracetamol administered regularly in adult patients with moderate to severe pain after tonsillectomy provided rapid and effective analgesia and was well tolerated We compared the efficacy and side effects of propacetamol ( P ) , an injectable prodrug of acetaminophen , 2 g and tramadol ( T ) , a weak synthetic opioid , 1.5 mg.kg-1 , given intravenously following thyroidectomy . 80 patients were r and omly assigned to blindly receive one dose of P or T on request in the PACU . Residual pain was treated with i.v . PCA morphine . Pain and patient satisfaction were assessed with Visual Analog Scales . Demographic and peroperative data were comparable in both groups . Although the morphine consumption was comparable ( p = 0.71 ) , the decrease in VAS pain scores was significantly higher following tramadol ( p = 0.03 ) . More patients complained of nausea and vomiting ( p = 0.01 ) during the first two hours following injection of tramadol , but there was no difference throughout the whole study . Oversedation was not observed in any group . We conclude that a single dose of tramadol provides a better quality of analgesia than propacetamol during the first six hours after thyroidectomy , but fails to ensure optimal analgesia , since VAS pain scores failed to fall below 3 despite the use of supplemental morphine Background : Diclofenac and paracetamol have different mechanisms and sites of action . Therefore , we tested if their combination is more effective for analgesia after tonsillectomy than either drug alone with respect to rescue analgesic consumption and visual analog scale values Inadequate control of postoperative pain after orthopedic procedures may trigger complications that increase morbidity . Multimodal analgesia is used to manage pain effectively after surgical procedures and reduce the need for rescue analgesia . Intravenous ( IV ) acetaminophen ( OFIRMEV ; Cadence Pharmaceuticals , Inc. ) , an analgesic that has been studied and used in the multimodal management of acute pain after major orthopedic procedures , combines the safety seen with oral and rectal formulations with a preferred route of administration . Two double-blind , r and omized , placebo-controlled clinical trials were conducted ( total 130 patients ) to determine the efficacy and safety of single-dose IV acetaminophen in patients following total hip arthroplasty . Although both studies were stopped prematurely , overlap in patient population s , study design , and method ologies in the single-dose phase of these studies allowed for analysis of their results to be presented concurrently . Both trials demonstrated IV acetaminophen having greater efficacy than placebo in terms of primary endpoints [ pain intensity differences from T0.5 to T3 ( P < 0.05 in both studies ) ] . The use of IV acetaminophen also reduced the need for rescue opioid consumption , with patients receiving IV acetaminophen consuming , on average , less than half the amount of rescue medication as those receiving placebo . IV acetaminophen was effective in treating moderate-to-severe pain after total hip arthroplasty and reduced the need for rescue opioid consumption Abstract Acetaminophen is widely used for pain management as an alternative to NSAIDs and selective COX‐2 inhibitors , but its action at a molecular level is still unclear . We evaluated acetaminophen ’s effect on PG release and the expression patterns of genes related to PG production in a clinical model of tissue injury and acute inflammation . Subjects ( 119 out patients ) received either 1000 mg acetaminophen , 50 mg rofecoxib ( a selective COX‐2 inhibitor ) , 30 mg ketorolac ( a dual COX‐1/COX‐2 inhibitor ) , or placebo before the surgical removal of two impacted m and ibular third molars . Microdialysis was used to collect inflammatory transu date from the surgical site for measurement of PGE2 and TXB2 levels at the site of injury . Biopsies were collected to investigate the expression patterns of genes related to PG production at baseline prior to surgery and at 3 or 24 h following surgery . PGE2 release was suppressed by ketorolac , rofecoxib and acetaminophen compared to placebo at 3 h coincident with increased COX‐2 gene expression in biopsies collected from the surgical site . TXB2 release was suppressed only by ketorolac . COX‐2 gene expression remained elevated at 24 h with continued ketorolac and acetaminophen treatment . COX‐1 gene expression was significantly down‐regulated at 24 h by ketorolac , rofecoxib and acetaminophen . Acetaminophen suppression of PGE2 without inhibiting TXB2 release , when COX‐2 gene expression is up‐regulated , suggests that acetaminophen is a selective COX‐2 inhibitor in vivo . The up‐regulation of COX‐2 gene and down‐regulation of COX‐1 gene expression suggests that acetaminophen may result in changes in COX‐derived prostanoids with repeated doses The analgesic efficacy and safety of propacetamol , an injectable prodrug of acetaminophen , ( paracetamol ) were studied in 87 children ( 36 boys , 51 girls ; age 6 - 13 ; mean age 9.5 years ) immediately after limb surgery . Using a double-blind , r and omized , parallel group design , the effects of a single IV infusion of 30 mg.kg-1 propacetamol ( i.e. 15 mg.kg-1 acetaminophen ) were compared with a single injection of placebo ( PL ) . Efficacy was assessed on pain scores rated on a four-point verbal scale , a five-point visual scale ( faces ) and on a four-point relief verbal scale before administration ( T0 ) and 0.25 , 0.5 , 1 , 2 , 3 , 4 , 5 , 6 h after administration . At the end the global efficacy was rated by the physician on a five-point verbal scale . Propacetamol was statistically superior to placebo on all assessment criteria . Seven side-effects were recorded : five in the propacetamol group and two in the placebo group . 30 mg.kg-1 propacetamol provided a significantly greater analgesic effect than placebo in children after orthopaedic surgery UNLABELLED Tonsillectomy is associated with severe postoperative pain for which , several drugs are employed for management . OBJECTIVE In this double-blind , placebo-controlled study we aim ed to evaluate the efficacy of intravenous paracetamol and dipyrone when used for post-tonsillectomy analgesia in children . METHOD 120 children aged 3 - 6 yr , undergoing tonsillectomy with or without adenoidectomy and /or ventilation tube insertion were r and omized to receive intraoperative infusions of paracetamol ( 15 mg/kg ) , dipyrone ( 15 mg/kg ) or placebo ( 0.9 % NaCl ) . Evaluation was carried out at 0.25 , 0.50 , 1 , 2 , 4 , 6h postoperatively . Pethidine 0.25 mg/kg was utilized as rescue analgesic . Cumulative pethidine requirement was the primary outcome . Pain intensity measurement , pain relief , sedation level , nausea and vomiting , postoperative bleeding and any other adverse effects were noted . RESULTS No significant difference was found in pethidine requirement between paracetamol and dipyrone groups . Cumulative pethidine requirement was significantly less in paracetamol and dipyrone groups vs. placebo . No significant difference was observed between groups in postoperative pain intensity scores throughout the study . CONCLUSION Intravenous paracetamol is found to have a similar analgesic efficacy as intravenous dipyrone and they both help to reduce the opioid requirement for postoperative analgesia in pediatric day-case tonsillectomy OBJECTIVES /HYPOTHESIS Endoscopic sinus surgery ( ESS ) is increasingly performed by otorhinolaryngologists . However , the early recovery and pain management after ESS is still largely unexplored . In the present study , we have evaluated the incidence and severity of pain and the efficacy and safety of acetaminophen ( paracetamol ) for pain management in patients undergoing ESS . STUDY DESIGN The authors conducted a prospect i ve , double-blind , placebo-controlled clinical trial . METHODS Seventy-four patients with ESS were r and omized to receive either 1 g intravenous acetaminophen ( Perfalgan ) ( n = 36 ) or 0.9 % normal saline as a placebo ( n = 38 ) after ESS was performed under local anesthesia . No other analgesic medication was permitted during the study . Need for rescue analgesic during the first 4 hours after surgery as well as all adverse events were recorded . RESULTS Most patients , 27 of 38 ( 71 % ) , in the placebo group needed rescue analgesics but significantly fewer patients in the acetaminophen group required rescue analgesia , i.e. , only nine of 36 ( 25 % ) patients needed oxycodone . The worst pain after surgery was also more severe in the placebo group than that in the acetaminophen group . There was no significant difference between groups in the incidence of adverse events . The most common adverse events were vomiting , nausea , and headache . CONCLUSIONS ESS is associated with significant postoperative pain . Acetaminophen provides adequate pain relief in most patients who have undergone ESS . However , the analgesic efficacy of acetaminophen alone is insufficient in some patients , and hence all patients with ESS must be followed closely to identify those patients in need of more efficient analgesia during the early phase of recovery We compared an acetaminophen ( paracetamol ) 1 g ( n = 51 ) formulation for infusion with propacetamol 2 g ( n = 51 ) and placebo ( n = 50 ) in a r and omized , controlled , double-blind , parallel group trial in patients with moderate-to-severe pain after third molar surgery . Treatment efficacy was assessed in house for 6 h after starting the 15-min infusion . Significant effects versus placebo ( P < 0.01 ) were obtained with both active treatments on pain relief , pain intensity difference on a 100-mm visual analog scale , and on a categorical scale ( except for propacetamol at 6 h ) . No significant differences were noted between active groups except at 1 h. Six-hour weighted sums of primary assessment s showed significantly better efficacy than placebo ( P < 0.0001 ) and no difference between active treatments . Median stopwatch time to onset of pain relief for active treatment was 6–8 min after infusion start . Active treatments showed comparable efficacy with a significantly longer duration of analgesia and better patients ’ global evaluation compared with placebo . The incidence of patients reporting local pain at the infusion site was significantly less frequent after IV acetaminophen or placebo ( 0 % ) in comparison with propacetamol ( 49 % ) . In conclusion , acetaminophen 1 g and propacetamol 2 g were superior to placebo regarding analgesic efficacy , with a more frequent incidence of local pain at the infusion site for propacetamol Background : We compared the analgesic effects of intravenous ( IV ) paracetamol with that of dexketoprofen on postoperative pain and morphine consumption during the first 24 hour after a lumbar disk surgery . Methods : This prospect i ve , placebo-controlled , double blind study investigated the analgesic effects of IV paracetamol and dexketoprofen on postoperative pain , morphine consumption , and morphine-related side effects after a lumbar disk surgery . Sixty American Society of Anesthesiologists 1 or 2 status patients scheduled for elective lumbar disk surgery under general anesthesia were included in the study . Patients were treated using patient-controlled analgesia with morphine for 24 hours after a lumbar disk surgery and r and omized to receive IV paracetamol 1 g , dexketoprofen 50 mg , or isotonic saline ( placebo ) . The primary endpoint was pain intensity measured by the visual analogue scale , and secondary endpoints were morphine consumption and related side effects . Results : Pain intensity was lower in the dexketoprofen group ( P=0.01 ) but not in the paracetamol group ( P=0.21 ) when compared with the control group . Cumulative morphine consumption and morphine-related side effects did not reveal significant differences between the groups . Conclusions : The study showed that pain intensity during 24 hours after the lumbar disk surgery was significantly lowered by dexketoprofen , but not with paracetamol , as a supplemental analgesic to morphine patient-controlled analgesia when compared with controls Postoperative pain management after cardiac surgery has been mainly based on parenteral opioids . However , because opioids have numerous side effects , coadministration of non-opioid analgesics has been introduced as a method of reducing opioid dose . In this prospect i ve , r and omized , double-blinded study , we evaluated the efficacy of propacetamol , an IV administered prodrug of acetaminophen ( paracetamol ) , as an adjunctive analgesic after cardiac surgery . Seventy-nine patients scheduled for elective coronary artery bypass grafting were r and omized to receive either propacetamol 2 g ( n = 40 ) or placebo ( n = 39 ) IV in 6-h intervals for 72 h. From the time of extubation , patients had access to an opioid ( oxycodone ) via a patient-controlled analgesia device . Pain was evaluated on a visual analog scale four times daily , whereas respiratory function tests ( forced vital capacity , forced expiratory volume in 1 s , peak expiratory flow , and arterial blood gas measurements ) were performed once a day . The prespecified primary efficacy variable ( cumulative oxycodone consumption at the end of the 72-h postoperative period ) was 123.5 mg ( 51.3 mg ) ( mean [ sd ] ) in the propacetamol group and 141.8 mg ( 57.5 mg ) in the placebo group ( difference in mean , 18.3 mg = 13 % ; 95 % confidence interval , 6.1–42.7 mg;P = 0.15 ) . Pain scores did not differ between the groups at rest ( P = 0.65 ) or during a deep breath ( P = 0.72 ) . The groups were also similar in terms of pulmonary function tests , postoperative bleeding , and hepatic function tests , and no significant differences were noted in the incidences of adverse effects . After completion of the study , a post hoc analysis was also performed analyzing the first 24 h as split into 6-h intervals . This analysis showed a significantly ( P = 0.036 ) smaller consumption of oxycodone in the propacetamol group at 24 h ( 47.1 mg [ 20.7 mg ] versus 57.9 mg [ 23.9 mg ] ; difference in mean , 10.8 mg ; 95 % confidence interval , 0.7–20.9 mg ) . In conclusion , propacetamol did not enhance opioid-based analgesia in coronary artery bypass grafting patients , nor did it decrease cumulative opioid consumption or reduce adverse effects within 3 days after surgery . However , post hoc analysis showed that oxycodone requirement was reduced within the first 24 h in the propacetamol group The analgesic efficacy and safety of propacetamol ( Pro-Dafalgan ) , an injectable prodrug of acetaminophen , in combination with morphine administered by patient-controlled analgesia ( PCA ) were studied in 60 patients ( 56 men , 4 women ; age 18 - 40 years ; mean age , 26 years ) after knee ligamentoplasty . Using a double-blind , r and omized , parallel-group design , the effects of four ( every 6 hr ) intravenous injections of 2 g propacetamol (= 1 g acetaminophen ) were compared with four injections of placebo ( PL ) in the recovery room immediately after surgery . Efficacy was assessed over 24 hr by automatic recording on the PCA device of the cumulative dose of morphine and the number of boluses requested . It was also assessed on pain scores rated on a five-point verbal scale and a visual analogue scale before administration , at 1 , 2 , 3 , and 4 hr , and then every 2 hr until the 24th hr after administration . A five-point global efficacy scale was also administered . Any side effects were recorded throughout the duration of the study , and the ability to tolerate the drug was assessed by recording arterial pressure , cardiac and respiratory frequency , and sedation at the same assessment times as the pain scores . The 24-hr morphine consumption was significantly decreased in the propacetamol group ( number of 1 mg boluses : 14.7 + /- 11.3 versus 23.2 + /- 13.8 , P = 0.01 ; PCA usage : 26.4 + /- 12.3 mg versus 34.6 + /- 15.4 mg , P = 0.03 ; PCA usage + titration : 34.5 + /- 12.7 mg versus 43.1 + /- 15.9 mg , P = 0.02 ) . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Paracetamol is widely used to treat postoperative pain and is well known for its morphine-sparing effect . Therefore , the effect of morphine-paracetamol combination can be synergistic , additive , or infra-additive . The primary aim of our study is to define the median effective analgesic doses ( ED₅₀s ) of paracetamol , morphine , and the combination of both . Also , the nature of the interaction for postoperative pain after moderately painful surgery using an up- and -down method and isobolographic analysis was determined . METHODS Ninety patients , undergoing moderately painful surgery , were included in one of the three groups . Determination of the median ED₅₀s was performed by the Dixon and Mood up- and -down method . Initial doses were 1.5 g and 5 mg , with dose adjustment intervals of 0.5 g and 1 mg , in the paracetamol and morphine groups , respectively . The initial doses of paracetamol and morphine were 1.5 g and 3 mg , in the paracetamol-morphine combination group with dose adjustment intervals of 0.25 g for paracetamol and 0.5 mg for morphine . Analgesic efficacy was defined as a reduction to or <3 on a 0 - 10 numeric rating scale , 45 min after the beginning of drug administration . Isobolographic analysis was used to define the nature of their interaction . RESULTS The median ED₅₀s of paracetamol and morphine were 2.1 g and 5 mg , respectively . The median ED₅₀ of the combination was 1.3 g for paracetamol and 2.7 mg for morphine . CONCLUSIONS Our study showed that the combination of the paracetamol and morphine produces an additive analgesic effect . Clinical trial registration NCT01366313 Background The aim of this prospect i ve , r and omized , double-blind study was to determine the more effective supplemental analgesic , paracetamol or lornoxicam , for postoperative pain relief after lower abdominal surgery . Methods Sixty patients scheduled for lower abdominal surgery under general anesthesia were r and omly allocated to receive either isotonic saline ( control group ) , intravenous paracetamol 1 g every 6 h ( paracetamol group ) , or lornoxicam 16 mg then 8 mg after 12 h ( lornoxicam group ) . Additionally pain was treated postoperatively with morphine patient-controlled analgesia . Postoperative pain scores measured by the verbal pain score ( VPS ) , morphine consumption , and the incidence of side effects were measured at 1 , 2 , 4 , 8 , 12 , and 24 h postoperatively . Results Morphine consumption at 12 and 24 h was significantly lower in the lornoxicam group ( 19.25 ± 5.7 mg and 23.1 ± 6.5 mg ) than in the paracetamol group ( 23.4 ± 6.6 mg and 28.6 ± 7.6 mg ) . Both treatment groups had less morphine consumption than the control group ( 28.5 ± 5 mg and 38.1 ± 6.6 mg ) at 12 and 24 h , respectively . Additionally , VPS was reduced in the paracetamol and the lornoxicam groups compared with the control group both at rest and on coughing . Further analysis revealed that VPS in the lornoxicam group was significantly lower than that in the paracetamol group only during coughing . Drug-related side effects were comparable in all groups . Conclusions Lornoxicam is superior to paracetamol for postoperative analgesia after lower abdominal surgery . However , paracetamol could be an alternative supplemental analgesic whenever an NSAID is unsuitable . Trial Registration : clinical trials.gov.identifier : NCT01564680 We sought to determine the analgesic efficacy , opioid-sparing effects , and tolerability of propacetamol , an injectable prodrug of acetaminophen , in combination with morphine administered by patient-controlled analgesia ( PCA ) after spinal fusion surgery . Forty-two patients undergoing spinal stabilization surgery were r and omized into two groups , which were given either an IV placebo or an IV injection of 2 g propacetamol every 6 h for 3 days after surgery . The postoperative opioid analgesic requirement was assessed with a PCA device used to self-administer morphine . Pain relief was evaluated by a visual analog pain scale and by verbal rating scores of pain relief at 8-h intervals for up to 72 h after surgery . The cumulative dose of morphine at 72 h was smaller in the Propacetamol group than in the Placebo group ( 60.3 ± 20.5 vs 112.2 ± 39.1 mg;P < 0.001 ) . The pain scores were significantly lower in the Propacetamol group measured at two intervals of the study , although visual analog scale pain intensity scores were smaller than 3 in both groups . Most patients in the Placebo group obtained a greater degree of sedation on postoperative Day 3 ( P < 0.05 ) . This study demonstrates the usefulness of propacetamol as an adjunct to PCA morphine in the treatment of postoperative pain after spinal fusion Background and Objectives A multimodal approach to postcesarean pain management may enhance analgesia and reduce side effects after surgery . This study evaluates the postoperative analgesic effects of propacetamol and /or diclofenac in parturients undergoing elective cesarean delivery under spinal anesthesia . Methods After r and omization , 80 healthy parturients received the following : placebo ( group M ) , 100 mg diclofenac rectally every 8 hours ( group MD ) , 2 g propacetamol intravenously every 6 hours ( group MP ) , or a combination of 2 g propacetamol and 100 mg diclofenac ( group MDP ) as described above . Drugs were administered for 24 hours after surgery . Postoperative pain was controlled with a patient controlled analgesia pump , using morphine . The visual analog scale ( VAS ) at rest and on coughing , as well as the morphine consumption , were evaluated at 2 , 6 , and 24 hours postoperatively . Also , the side effects experienced after undergoing the different regimens were compared . Results The patients ’ characteristics did not differ significantly between the 4 groups . VAS score at 2 hours , both at rest and on coughing were lower in group MDP and MD compared with group M ( P < .05 ) . At 24 hours , there was still a tendency toward lower pain scores in the groups MDP and MD ; however , this difference was only statistically significant at rest between the MDP group and the MP and M groups . Morphine consumption at 2 , 6 , and 24 hours was lower in the MDP and MD groups compared with the MP and M groups ( P < .05 ) . The morphine-sparing effect was higher in groups MDP and MD compared with group MP ( 57 % and 46 % , respectively , v 8.2 % , P < .05 ) . The incidence of side effects was similar in all groups . However , the power of the study was too low to permit an evaluation of potential side effects . Conclusion Diclofenac after cesarean delivery improves analgesia and has a highly significant morphine-sparing effect . We were unable to demonstrate significant morphine-sparing effect of propacetamol or additive effect of propacetamol and diclofenac in this group of patients OBJECTIVE To compare the postoperative analgesic efficacy and safety of the non-addictive propacetamol hydrochloride ( Pro-Bufferin ) injection and dolantin in a prospect i ve , r and omized , double blind and controlled clinical trial . METHODS After the pain intensity was assessed when the patients were undergone thoracic and abdominal selective surgery became fully conscious , 40 consecutive patients with moderate to severe postoperative pain ( equivalent to Pain Grade I and II of American Anesthesia Association classification ) were r and omized into the study against the control groups . The two groups were similar for age , sex , height/weight , disease categories , operation categories , anesthesia methods and duration , vital signs , hepatorenal function , and blood cell count ( P = 0.06 - 0.93 ) . In the study group , 2 g propacetamol in 100 ml normal saline ( NS ) intravenously with 1.0 ml NS intramuscularly as the placebo control to dolantin were administered . In the control group , 1.6 g mannitose in 100 ml NS intravenously as the placebo control to propacetamol with 50 mg dolantin ( 1.0 ml ) intramuscularly as the positive control to propacetamol were administered . The intensity change of postoperative pain was then evaluated 10 times with visual analog scale and verbal describing scale during 6 h from the beginning of propacetamol infusion . Vital signs and adverse reactions were also documented . After all data were put into the computer , the blinding codes were decoded and the statistic analysis was then made . RESULTS There was no significant difference ( P = 0.93 ) about the area under the curve of " Pain Relieve Score vs. Time " . The " starting to effect " time ( 15 - 30 min ) , analgesic duration ( 6 h ) and the percentage of excellent or good analgesic effect ( 90 % ) in the two groups were the same . Adverse reactions did n't reached the statistic different level ( P = 0.35 ) . CONCLUSIONS Propacetamol HCL injection 2 g intravenously could be an alternative to dolantin 50 mg intramuscularly for moderate to severe postoperative pain with its advantage of being non-addictive Our aim was to compare the analgesic affects of paracetamol and the non-steroidal anti-inflammatory drug ( NSAID ) diclofenac sodium for the relief of postoperative pain in patients having bimaxillary osteotomy . Thirty patients were r and omly allocated into two groups ( n = 15 in each ) using sealed envelopes . The first group was given paracetamol 1 g intravenously and the second diclofenac sodium 75 mg intramuscularly . The analgesics were given during the last 15 min of the operation while the mucosa was being sutured . The number of requests for further analgesia , and the amount of analgesia given postoperatively ( as diclofenac sodium ) were recorded . The intensity of postoperative pain was recorded on a visual analogue scale ( VAS ) , and postoperative requests for analgesia , haemodynamic variables ( systolic blood pressure and heart rate ) , and complications were compared . The groups were comparable . A single dose of diclofenac or paracetamol effectively decreases the intensity of postoperative pain after bimaxillary osteotomy Context Strabismus surgery is one of the most common ophthalmic surgical procedures in children and is associated with significant postoperative nausea and vomiting ( PONV ) . Objective We evaluated the effect of intravenous paracetamol on PONV in children after strabismus surgery . Design Prospect i ve , placebo-controlled , r and omised double-blind study . Setting University hospital . Patients Ninety children , between 2 and 14 years scheduled for strabismus surgery , were recruited . Eighty-six completed the study . Interventions After induction of anaesthesia , intravenous dexamethasone 0.1 mg kg−1 was administered to all . The patients were enrolled to receive either intravenous physiological saline ( group S ) or paracetamol 15 mg kg−1 ( group P ) . Main outcome measure Incidence of PONV in the first 24 h postoperatively . Results General and clinical characteristics of the children were similar in both groups . PONV during the first 24 h was significantly higher in group S in comparison with group P ( group S vs. group P , 33 vs. 14.6 % , respectively , P = 0.038 for nausea ; 24.4 vs. 7.3 % , respectively , P = 0.030 for vomiting ) . The number of analgesic administrations during the first 24 h was higher in group S compared with group P ( 1.31 ± 0.85 and 0.73 ± 0.6 , respectively , P = 0.001 ) . The repeat number of postoperative analgesic administrations was significantly different between groups during the first 24 h ( P = 0.005 ) , but during 24–48 h was not significant . Conclusion Intraoperative administration of intravenous paracetamol decreases the incidence of PONV during the first 24 h in children after strabismus surgery BACKGROUND AND METHODS From the time that Sinatra et al. ( Anesthesiology . 2005;102:822 ) was published to FDA apaproval of intravenous ( IV ) acetaminophen , an exp and ed analysis of the original raw study data became necessary for the regulatory su bmi ssion . The following analyses were conducted : ( 1 ) sum of pain intensity differences over 24 hours ( SPID24 ) using currently accepted imputation methods to account for both missing data and the effects of rescue ; ( 2 ) efficacy results after the first 6 hours ; ( 3 ) effects of gender , race/ethnicity , age , weight , surgical site , ASA Class , and serotonin antagonists ; and ( 4 ) a stepwise regression analysis of why adverse events of nausea and vomiting were numerically ( although not statistically ) higher in the IV acetaminophen group compared with placebo . RESULTS Sum of pain intensity differences over 24 hours using a 0- to 100-mm visual analog scale was statistically significantly ( P < 0.001 ) in favor of IV acetaminophen ( n = 49 ) compared with placebo ( n = 52 ) . Time to rescue was found to be 3.9 and 2.1 hours , respectively , for total hip and knee arthroplasty compared with 0.8 hours for the placebo group . Rescue medication consumption , requests , and actual administration were all significantly lower in the IV acetaminophen group compared with placebo for each dosing interval , except in the 6- to 12-hours interval where a numerical trend was observed . Analysis of various subset variables demonstrated similar efficacy for each variable . A stepwise regression analysis demonstrated that AE reports of nausea and vomiting were most likely due to prer and omization events , particularly opioid consumption and presence of nausea prior to r and omization . CONCLUSION Repeated-dose 24-hours end points were found to be as robust as previously published results . IV acetaminophen efficacy and safety appeared to be unaffected by specific subset variables . INTRODUCTION . The main action of paracetamol ( acetaminophen ) is presumed to be in the central nervous system . The central nervous system penetration of paracetamol has been described in children with intracranial pathologies but not in children with an intact blood-brain barrier . OBJECTIVE . We investigated the cerebrospinal fluid penetration of paracetamol in 32 healthy children , aged 3 months to 12 years , who were undergoing surgery in the lower body using spinal anesthesia . MATERIAL S AND METHODS . In this open-label prospect i ve study , children were given a single intravenous injection of paracetamol ( 15 mg/kg ) . Cerebrospinal fluid and venous blood sample s were obtained between 5 minutes and 5 hours after injection . Paracetamol concentrations were determined from the cerebrospinal fluid and plasma by using a fluorescence polarization immunoassay . RESULTS . Paracetamol was detected in cerebrospinal fluid from the earliest sample at 5 minutes , although in this sample paracetamol concentration was below the limit of quantification of 1.0 mg/L. Subsequent paracetamol concentrations in cerebrospinal fluid ranged between 1.3 and 18 mg/L ( median : 7.2 mg/L ) , plasma concentrations ranged between 2.4 and 33 mg/L , and cerebrospinal fluid/plasma ratios ranged between 0.06 and 2.0 . The highest CSF paracetamol concentration was detected at 57 minutes . CONCLUSIONS . Paracetamol permeates readily into the cerebrospinal fluid of children . This fast and extensive transfer enables the rapid central analgesic and antipyretic action of intravenous paracetamol Background : Paracetamol ; a cyclooxygenase inhibitor ; acts through the central nervous system as well as serotoninergic system as a nonopioid analgesic . A prospect i ve , double-blinded , and r and omized-controlled study was carried out to compare the efficacy of preoperative 1 g intravenous ( iv ) paracetamol with placebo in providing postoperative analgesia in head-neck cancer surgery . Material s and Methods : From 2008 February to 2009 December , 80 patients for palliative head-neck cancer surgery were r and omly divided into ( F ) and ( P ) Group receiving ivplacebo and iv paracetamol , respectively , 5 min before induction . Everybody received fentanyl before induction and IM diclofenac for pain relief at8 hourly for 24 h after surgery . Visual analogue scale ( VAS ) and amount of fentanyl were measured for postoperative pain assessment ( 24 h ) . Results and Statistical analysis : The mean VAS score in 1st , 2nd postoperative hour , and fentanyl requirement was less and the need for rescue analgesic was delayed in ivparacetamol group which were all statistically significant . Paracetamol group had a shorter surgical intensive care unit ( SICU ) and hospital stay which was also statistically significant . Conclusion : The study demonstrates the effectiveness of ivparacetamol as preemptive analgesic in the postoperative pain control after head-neck cancer surgery and earlier discharge from hospital OBJECTIVES In a r and omized , double-blind trial , the synergistic action of intravenous parecoxib , metamizol or paracetamol on postoperative piritramide consumption was compared in patients recovering from total thyroidectomy during the first 24 h while evaluating pain intensity and patient satisfaction . METHODS 120 patients were r and omly allocated to four patient groups treated with normal saline and /or one of non-opioid analgesics ( parecoxib 40 mg twice daily , metamizol 1 g three times daily , paracetamol 1 g three times daily ) in addition to piritramide using the PCA pump . Beginning in the recovery room ( PACU ) , patients were asked every 2 h for 6 hours and afterwards once every 6 h to quantify their pain experience and patient satisfaction while piritramide consumption was recorded . RESULTS Upon arrival in the PACU piritramide consumption was high and decreased thereafter significantly in all groups ( P < 0.05 ) . There were no significant differences between groups in incremental and cumulative piritramide consumption during the investigation . Also , VAS scores were high upon arrival in the PACU and dropped in all groups continuously after surgery : At 2 h and 4 h after surgery they were significantly lower in parecoxib group compared with NaCl ( P < 0.01 ) . For overall patient satisfaction , no significant differences were observed . Pain relief scores at 24 h were significantly higher in parecoxib group as compared to metamizol and paracetamol ( P < 0.01 ) . Mild PONV was observed frequently in all groups and was treated with metoclopramide . CONCLUSION There is no clear-cut difference between the non-opioid drugs used , even though parecoxib seems to be superior in regard to VAS scores and piritramide consumption . However , the clinical significance is debatable ABSTRACT Objective : To assess clinical efficacy of IV paracetamol 1 g and IV dipyrone 1 g on a 24.h dosing schedule in this r and omised , double-blinded study of 40 ASA I – III ( American Society of Anesthesiologists classification of physical status ) patients undergoing surgery for breast cancer . Research design and methods : General anaesthesia using remifentanil and propofol was performed for surgery . The patients were r and omly allocated to two groups , receiving infusions of paracetamol 1 g/100 mL ( Para Group ) or of dipyrone 1 g/100 mL ( Dipy Group ) 30 min before arrival in the recovery area and every 6 h up to 24 h postoperatively . All patients had unrestricted access to opioid rescue medication via an IV patient-controlled analgesia ( PCA ) device . Main outcome measures : The primary variables for clinical equivalence were the differences between the mean values for pain scores at rest and pain scores on coughing over 30 h postoperatively . The equivalence margin was determined as ±10 mm on the visual analogue scale ( VAS ) . Results : Regarding pain scores at rest , the 90 % CI of the mean differences between the treatment groups over 30 h postoperatively was found to be within the predefined equivalence margin [ + 7.5/–6.2 ] , and the CI values for pain scores on coughing [ + 7.3/–9.0 ] were similar . The two groups did not differ in cumulative opioid rescue consumption ( Dipy-Group 14.8 ± 17.7 mg vs. Para Group 12.1 ± 8.8 mg , p = 0.54 ) nor in piritramide loading dose ( Dipy Group 0.95 ± 2.8 mg vs. Para Group 1.3 ± 2.8 mg , p = 0.545 ) . Five patients in the Dipy Group experienced hypotension in contrast to none in the Para Group ( p = 0.047 ) . There were no significant between-treatment differences for other adverse events , patient satisfaction scores ( p = 0.4 ) or quality of recovery scores ( p = 0.3 ) . Conclusion : IV paracetamol 1 g is clinical ly equivalent to IV dipyrone 1 g for postoperative analgesia after surgery for breast cancer A r and omised controlled trial was conducted to investigate efficacy of paracetamol and dexketoprofen trometamol for perineal pain relief after perineal repair . Subjects were r and omly assigned to receive two doses of either 50 mg of intravenous dexketoprofen trometamol via slow i.v . infusion ( Group I , n = 49 ) or 1,000 mg of paracetamol via intravenous infusion ( Group II , n = 46 ) . The main outcome measure was a VAS ( visual analogue scale ) for pain recorded at 1 h ( VAS 1 ) . A total of 82 patients were included in the final analysis ( Group I , n = 41 ; Group II , n = 41 ) . There was no difference among groups in terms of pain scores at the beginning ( VAS 0 ) . The pain was decreased in 70 % of the patients in Group I and in 62 % of the patients in Group II ( p = 0.502 ) . Both paracetamol and dexketoprofen are effective in perineal pain relief after episiotomy or perineal tear repair The newly injectable cyclooxygenase-2 selective nonsteroidal antiinflammatory drug , parecoxib , has never been compared with propacetamol , a parenteral formulation of acetaminophen . In this prospect i ve , r and omized , double-blind , double-dummy study , we r and omly assigned 182 patients scheduled for initial inguinal hernia repair under general anesthesia to receive a single injection of 40 mg parecoxib or 2 injections of 2 g propacetamol within the first 12 h after surgery . The study variables were morphine consumption , pain at rest and while coughing , and patient satisfaction throughout the first 12 h postoperatively . For statistical analysis , we used the Student ’s t-test , & khgr;2 , and covariance analysis . Total morphine consumption did not differ between the two groups . Pain was less intense in the parecoxib group at rest ( P = 0.035 ) but did not differ for pain while coughing . The incidence of side effects was similar . Significantly more patients in the parecoxib group rated their pain management as good or excellent ( 87 % versus 70 % in the propacetamol group , P = 0.001 ) . Within the first 12 h after inguinal hernia repair in adult patients , a single injection of parecoxib 40 mg compares favorably with 2 injections of propacetamol 2 Background : Despite the widespread use of paracetamol for many years , the analgesic serum concentrations of paracetamol are unknown . Therefore the correlation between serum paracetamol concentrations and the analgesic effect was studied In 12 healthy volunteers , paracetamol pharmacokinetics were compared following administration of 1 g propacetamol HCl given intravenously over a 15-min period and 500 mg paracetamol given orally . Mean + /- SD total AUC ( microgram/ml.h ) following the iv formulation was significantly ( P < 0.01 ) greater than following oral paracetamol ( 25.53 + /- 4.27 vs 21.04 + /- 4.49 ) corresponding to a mean oral bioavailability of paracetamol of 82.2 + /- 9.4 % . Between 1 and 2 h after administration , paracetamol plasma concentrations became very similar following both formulations . In another study , 2 g propacetamol HCl was given both as a 15-min infusion and as a 2-min bolus injection to six healthy volunteers . Contrary to mild to moderate local discomfort experienced during the 2-min bolus injection , the 15-min infusion was well tolerated without any complaints reported In this study , postoperative analgesic effects of intravenous paracetamol administration in lumbar discectomy patients were evaluated . After the approval of ethic committee , 90 patients undergoing lumbar disc hernia operation r and omly divided into 3 groups . After st and art general anesthesia , patients in group I received 1 gr i.v . paracetamol infusion 15 minutes before the induction , patients in group II received i.v . Paracetamol infusion started 15 minutes before the end of surgery . i.v morphine via PCA is used for postoperative analgesia maintenance and patients pain scores were assessed with VAS at 0 . , 1 . , 2 . , 3 . , 6 . , 12 . and 24 . hours . First analgesic requirement time , total morphine consumption and side effects were recorded . In group I and II , VAS scores , 24 h morphine consumption and first morphine requirement times were significantly different comparing to group III . As a result , we think that in lumbar discectomy cases preoperative administration of 1 gr paracetamol has no preemptive analgesic effect OBJECTIVES In this study , the effects and side effects of intravenous paracetamol application , combined with patient-controlled intravenous tramadol analgesia , were investigated in elective cesarean operations for postoperative pain control and its tramadol-sparing effect . METHODS Fifty ASA I-II patients scheduled for cesarean operation were enrolled in this study . Patients were r and omly divided into two groups : group I served as a control group , with saline administration ( 100 ml ) 15 min before the end surgery and every 6 h for 24 h , whereas group II received paracetamol ( 1 g/100 ml ) at the stated time points . All patients received a st and ard anesthetic protocol . At the end of surgery , all patients received tramadol i.v . via a PCA ( patient-controlled analgesia ) device . Pain and sedation scores were assessed at 1 , 3 , 6 , 12 and 24 h postoperatively . RESULTS Tramadol consumption and adverse effects were noted in the first 24 hours following surgery . The pain scores were significantly lower in the paracetamol group when compared with the control group ( p<0.05 ) . The cumulative tramadol consumption was lower in the paracetamol group than the control group ( p<0.05 ) . No significant difference was observed in sedation scores and nausea-vomiting scores between the groups ( p>0.05 ) . CONCLUSION We conclude that paracetamol is a safe and effective treatment option in post-cesarean pain for combination with tramadol , as it produces effective analgesia and reduces tramadol consumption Abstract Background and methods Minimally invasive parathyroidectomy requires limited analgesia and short recovery times . The preferred post-operative analgesic regimen for this patient population has not been established but non-narcotic components would be quite appropriate . The aim of the study was to determine whether intravenous ( IV ) acetaminophen ( 1 g ) or ketorolac ( 30 mg ) provide better pain control after parathyroidectomy . A parallel , r and omized , double blind , comparative study was completed on 180 patients scheduled for outpatient parathyroidectomy utilizing general anesthesia . Patients were r and omized to a blinded administration of either intravenous acetaminophen 1 g or ketorolac 30 mg intra-operatively . Upon arrival but before premedication , baseline pain scores were assessed in all patients . A consecutive series of postoperative pain scores were collected every 15 min using a 10 cm visual analog pain scale ( VAS ) upon arrival to the post anesthesia care unit ( PACU ) until discharge by blinded study personnel . Other data collected included : anesthesia time , surgical time , time to discharge , supplemental morphine and postoperative side effects . Results Overall mean postoperative VAS scores were not significantly different between the two treatment groups ( p = 0.07 ) . However , ketorolac produced significantly lower pain scores compared with acetaminophen in the later postoperative periods ( 3.9 ± 1.9 vs. 4.8 ± 2.4 at 45 min , p = 0.009 ; 3.4 ± 1.7 vs. 4.5 ± 2.1 at 60min , p = 0.04 ; and 3.2 ± 2.1 vs. 4.4 ± 2.1 at 75 min , p = 0.03 ) . Supplemental morphine was administered to 3 patients in the ketorolac group and 9 patients in the acetaminophen group but total consumption was not significantly different between groups ( p = 0.13 ) . The occurrence of nausea was significantly lower in the ketorolac group compared with the IV acetaminophen group ( 3.4 % vs. 14.6 % , respectively ; p = 0.02 ) . The overall incidence of morphine supplementation , vomiting , headache , muscular pain , dizziness , and drowsiness were not significantly different when compared between the treatment groups . Conclusions Both postoperative regimens provided adequate analgesia but patients receiving ketorolac intraoperatively had significantly lower pain scores at later recovery time points and significantly lower occurrences of nausea . Implication s The large volume of patients undergoing parathyroidectomies at our facility warranted a study to develop a st and ardized postoperative analgesic regimen . We conclude both medications can be utilized safely in this patient population , but there is a slight advantage in pain control with the usage of ketorolac for minimally invasive parathyroidectomies |
871 | 28,287,319 | Findings demonstrate that green tea appears to be an effective chemopreventive agent , particularly in those with high- grade prostate intraepithelial neoplasia .
However , evidence of efficacy in the treatment of PCa is currently lacking . | This systematic review aim ed to assess the clinical benefits of green tea consumption on the progression and prevention of prostate cancer ( PCa ) . | Prostate cancer incidence was prospect ively studied among 7999 men of Japanese ancestry who were first examined between 1965 and 1968 and then followed through 1986 . During this surveillance period , 174 incident cases of prostate cancer were recorded . Prostate cancer was not associated with any measure of socioeconomic status , including amount of education , type of occupation , and type of residence . There was also no relationship with the number of children , as a surrogate measure of sexual activity . Increased consumption of rice and tofu were both associated with a decreased risk of prostate cancer , while consumption of seaweeds was associated with an increased risk of prostate cancer . There was no relationship between prostate cancer and the intake of various nutrients , including total fat and total protein . Etiological implication s of these associations are discussed , but more research is needed on these dietary factors and the subsequent development of prostate cancer before any firm conclusions can be drawn Green and black tea have shown promise in the chemoprevention of prostate cancer . The objective of this study was to determine the bioavailability and bioactivity of tea polyphenols ( PP ) and theaflavins in human serum and human and mouse tissues . A decaffeinated black tea diet was administered to C57BL/6 mice . PPs and theaflavins were found in the small and large intestine , liver , and prostate in conjugated and free forms . The relative prostate bioavailability of theaflavin was 70 % higher than that of epigallocatechin gallate ( EGCG ) . In the second mouse study , a green tea ( GT ) diet was administered followed by the control diet for 1 - 5 d. Epicatechin ( EC ) , EGCG , and epicatechin gallate ( ECG ) concentrations in prostate tissue were significantly decreased after 1 d of consuming the control diet . Epigallocatechin gallate ( EGC ) , however , did not decrease significantly . For the human study , 20 men scheduled for surgical prostatectomy were r and omly assigned to consume 1.42 L daily of GT , BT , or a caffeine-matched soda control ( SC ) for 5 d before radical prostatectomy . Tea PPs were greater in prostate sample s from men consuming BT and GT than in men consuming SC ( P = 0.0025 ) . Although tea PP were not detectable in serum , ex vivo LNCaP prostate cancer cell proliferation was less when cells were grown in media containing patient serum collected after BT ( P < 0.001 ) and GT ( P = 0.025 ) consumption relative to baseline serum This is the first human study to show that tea polyphenols and theaflavins are bioavailable in the prostate where they may be active in the prevention of prostate cancer The purpose of this study was to determine the effects of short-term supplementation with the active compounds in green tea on serum biomarkers in patients with prostate cancer . Twenty-six men with positive prostate biopsies and scheduled for radical prostatectomy were given daily doses of Polyphenon E , which contained 800 mg of (−)-epigallocatechin-3-gallate ( EGCG ) and lesser amounts of (−)-epicatechin , (−)-epigallocatechin , and (−)-epicatechin-3-gallate ( a total of 1.3 g of tea polyphenols ) , until time of radical prostatectomy . Serum was collected before initiation of the drug study and on the day of prostatectomy . Serum biomarkers hepatocyte growth factor ( HGF ) , vascular endothelial growth factor ( VEGF ) , insulin-like growth factor (IGF)-I , IGF binding protein-3 ( IGFBP-3 ) , and prostate-specific antigen ( PSA ) were analyzed by ELISA . Toxicity was monitored primarily through liver function enzymes . Changes in serum components were analyzed statistically using the Wilcoxon signed rank test . Cancer-associated fibroblasts were treated with EGCG , and HGF and VEGF protein and mRNA levels were measured . HGF , VEGF , PSA , IGF-I , IGFBP-3 , and the IGF-I/IGFBP-3 ratio decreased significantly during the study . All of the liver function tests also decreased , five of them significantly : total protein , albumin , aspartate aminotransferase , alkaline phosphatase , and amylase . The decrease in HGF and VEGF was confirmed in prostate cancer – associated fibroblasts in vitro . Our results show a significant reduction in serum levels of PSA , HGF , and VEGF in men with prostate cancer after brief treatment with EGCG ( Polyphenon E ) , with no elevation of liver enzymes . These findings support a potential role for Polyphenon E in the treatment or prevention of prostate cancer Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more The incidence of prostate cancer is much lower in Asian than Western population s. Given that environmental factors such as dietary habits may play a major role in the causation of prostate cancer and the high consumption of green tea in Asian population s , this low incidence may be partly due to the effects of green tea . The JPHC Study ( Japan Public Health Center-based Prospect i ve Study ) was established in 1990 for cohort I and in 1993 for cohort II . The subjects were 49,920 men aged 40 - 69 years who completed a question naire that included their green tea consumption habit at baseline and were followed until the end of 2004 . During this time , 404 men were newly diagnosed with prostate cancer , of whom 114 had advanced cases , 271 were localized , and 19 were of an undetermined stage . Green tea was not associated with localized prostate cancer . However , consumption was associated with a dose-dependent decrease in the risk of advanced prostate cancer . The multivariate relative risk was 0.52 ( 95 % confidence interval : 0.28 , 0.96 ) for men drinking 5 or more cups/day compared with less than 1 cup/day ( p(trend ) = 0.01 ) . Green tea may be associated with a decreased risk of advanced prostate cancer Pre clinical , epidemiologic , and prior clinical trial data suggest that green tea catechins ( GTC ) may reduce prostate cancer risk . We conducted a placebo-controlled , r and omized clinical trial of Polyphenon E ( PolyE ) , a proprietary mixture of GTCs , containing 400 mg (−)-epigallocatechin-3-gallate ( EGCG ) per day , in 97 men with high- grade prostatic intraepithelial neoplasia ( HGPIN ) and /or atypical small acinar proliferation ( ASAP ) . The primary study endpoint was a comparison of the cumulative one-year prostate cancer rates on the two study arms . No differences in the number of prostate cancer cases were observed : 5 of 49 ( PolyE ) versus 9 of 48 ( placebo ) , P = 0.25 . A secondary endpoint comparing the cumulative rate of prostate cancer plus ASAP among men with HGPIN without ASAP at baseline , revealed a decrease in this composite endpoint : 3 of 26 ( PolyE ) versus 10 of 25 ( placebo ) , P < 0.024 . This finding was driven by a decrease in ASAP diagnoses on the Poly E ( 0/26 ) compared with the placebo arm ( 5/25 ) . A decrease in serum prostate-specific antigen ( PSA ) was observed on the PolyE arm [ −0.87 ng/mL ; 95 % confidence intervals ( CI ) , −1.66 to −0.09 ] . Adverse events related to the study agent did not significantly differ between the two study groups . Daily intake of a st and ardized , decaffeinated catechin mixture containing 400 mg EGCG per day for 1 year accumulated in plasma and was well tolerated but did not reduce the likelihood of prostate cancer in men with baseline HGPIN or ASAP . Cancer Prev Res ; 8(10 ) ; 879–87 . © 2015 AACR Purpose Tea is one of the most commonly consumed beverages worldwide . To date , observational data from prospect i ve cohort studies investigating the relationship between green and black tea intake and prostate cancer risk are sparse and equivocal . In a population -based , prospect i ve cohort study of Chinese men in Singapore , we investigated the relationship between green and black tea intake and prostate cancer risk . Methods Tea consumption data for 27,293 men were collected at baseline ( between 1993 and 1998 ) using a vali date d food frequency question naire . After an average of 11.2 years of follow-up , 298 men had developed prostate cancer . Proportional hazards regression methods were used to assess the associations between tea intake and prostate cancer risk . Results There was no association between daily green tea intake and prostate cancer risk , compared with no green tea intake [ hazard ratio ( HR ) = 1.08 ; 95 % confidence interval ( CI ) 0.79 , 1.47 ] . For black tea , a statistically significant positive association and trend were observed for daily intake compared with no black tea intake ( HR = 1.41 , 95 % CI 1.03 , 1.92 ; p for trend < 0.01 ) Conclusions Few prospect i ve data are available from population s that have both a high level and wide range of black and green tea intake ; this study represents a unique opportunity to evaluate their individual effects on prostate cancer risk . Our findings support the notion that green tea intake does not protect against prostate cancer and that black tea intake may increase prostate cancer risk Compelling pre clinical and pilot clinical data support the role of green tea polyphenols in prostate cancer prevention . We conducted a r and omized , double-blind , placebo-controlled trial of polyphenon E ( enriched green tea polyphenol extract ) in men with prostate cancer scheduled to undergo radical prostatectomy . The study aim ed to determine the bioavailability of green tea polyphenols in prostate tissue and to measure its effects on systemic and tissue biomarkers of prostate cancer carcinogenesis . Participants received either polyphenon E ( containing 800 mg epigallocatechin gallate ) or placebo daily for 3 to 6 weeks before surgery . Following the intervention , green tea polyphenol levels in the prostatectomy tissue were low to undetectable . Polyphenon E intervention result ed in favorable but not statistically significant changes in serum prostate-specific antigen , serum insulin-like growth factor axis , and oxidative DNA damage in blood leukocytes . Tissue biomarkers of cell proliferation , apoptosis , and angiogenesis in the prostatectomy tissue did not differ between the treatment arms . The proportion of subjects who had a decrease in Gleason score between biopsy and surgical specimens was greater in those on polyphenon E but was not statistically significant . The study 's findings of low bioavailability and /or bioaccumulation of green tea polyphenols in prostate tissue and statistically insignificant changes in systemic and tissue biomarkers from 3 to 6 weeks of administration suggests that prostate cancer preventive activity of green tea polyphenols , if occurring , may be through indirect means and /or that the activity may need to be evaluated with longer intervention duration s , repeated dosing , or in patients at earlier stages of the disease . Cancer Prev Res ; 5(2 ) ; 290–8 . © 2011 AACR In a prospect i ve study of 19 561 Japanese men , green-tea intake was not associated with a lower risk of prostate cancer ( 110 cases ) , the multivariate hazard ratio for men drinking ⩾5 cups compared with < 1 cup per day being 0.85 ( 95 % confidence interval 0.50–1.43 , trend P=0.81 ) PURPOSE To evaluate the efficacy and toxicity of green tea , prescribed as an alternative complementary ( CAM ) formulation on hormone refractory prostate cancer ( HRPC ) . METHODS Patients with HRCP were prescribed green tea extract capsules at a dose level of 250 mg twice daily . Efficacy and toxicity were evaluated during monthly visits . The primary endpoint was prostate-specific antigen ( PSA ) or measurable disease progression after a minimum of 2 months of therapy . RESULTS Nineteen patients were enrolled into the study . The treatment was generally well tolerated . Twelve patients reported at least one side effect ; only two of these were of moderate or severe grade . Primary toxicity was related to gastrointestinal irritation or caffeine intake . Four patients did not complete the minimum 2 months of therapy because of : intolerance ( two patients ) , physician stoppage ( one patient ) , death from cerebrovascular accident ( one patient ) . Fifteen patients completed at least 2 months of therapy . Nine of these patients had progressive disease within 2 months of starting therapy . Six patients developed progressive disease after additional 1 to 4 months of therapy . CONCLUSION Green tea , as CAM therapy , was found to have minimal clinical activity against hormone refractory prostate cancer Background and aims . It has been hypothesized that some aspect of a traditional ‘ Asian ’ diet , that is low in animal products and high in soya , may be associated with a reduced risk of prostate cancer . This study aim ed to examine the association between dietary intake and prostate cancer risk among 18,115 men in Hiroshima and Nagasaki , Japan , using prospect i ve data from the Life Span Study . Methods : Subjects completed a food-frequency question naire at baseline ( 1963 , 1965 and /or 1979 ) and were followed for incident prostate cancer until the end of 1996 . During this time , 196 incident prostate cancer cases were identified after 252,602 person-years of observation . Poisson regression was used to calculate incidence rates for each dietary factor after adjustment for age , calendar period , city of residence , radiation dose and education level . Results : Fish intake was significantly associated with an increased risk of prostate cancer ; men who consumed fish more than four times per week had a 54 increased risk of developing prostate cancer compared with men who ate fish less than twice per week ( RR=1.54 ; 95 CI , 1.03–2.31 ) . No other food items , including soya products , were significantly associated with prostate cancer risk . Conclusions : These data suggest that dietary factors may not be strong determinants of prostate cancer in these Japanese men , although the increased risk associated with a high consumption of fish warrants further study The significance of drinking green tea in prevention of two of the main lifestyle-related diseases , cancer and cardiovascular disease , was demonstrated in terms of a prospect i ve cohort study on a total of 8,552 general residents in Saitama Prefecture , Japan . On the basis of the follow-up study , we revealed decreased relative risk of cancer incidence for those consuming over 10 cups a day , compared with those consuming below 3 cups : 0.54 ( 95 % confidence interval , 0.22 - 1.34 ) for men , 0.57 ( 0.34 - 0.98 ) for women , and 0.59 ( 0.35 - 0.98 ) for both sexes . Furthermore , a significant delay in cancer onset was associated with increased consumption of green tea . Next , decreased relative risk of death from cardiovascular disease was 0.58 ( 0.34 - 0.99 ) for men , 0.82 ( 0.49 - 1.38 ) for women , and 0.72 ( 0.60 - 1.04 ) for members of both sexes consuming over 10 cups a day . Finally , we evaluated the life-prolonging effects of drinking green tea on cumulative survival , using the life table Evidence from both epidemiological and experimental observations have fueled the belief that the high consumption of fruits and vegetables rich in carotenoids may help prevent cancer and heart disease in humans . Because of its well-documented antioxidant and antigenotoxic properties , the carotenoid beta-carotene ( betaCT ) gained most of the attention in the early 1980s and became one of the most extensively studied cancer chemopreventive agents in population -based trials supported by the National Cancer Institute . However , the results of three r and omized lung cancer chemoprevention trials on betaCT supplementation unexpectedly contradicted the large body of epidemiological evidence relating to the potential benefits of dietary carotenoids . Not only did betaCT show no benefit , it was associated with significant increases in lung cancer incidence , cardiovascular diseases , and total mortality . These findings aroused widespread scientific debate that is still ongoing . It also raised the suspicion that betaCT may even possess co-carcinogenic properties . In this review , we summarize the current data on the co-carcinogenic properties of betaCT that is attributed to its role in the induction of carcinogen metabolizing enzymes and the over-generation of oxidative stress . The data presented provide convincing evidence of the harmful properties of this compound if given alone to smokers , or to individuals exposed to environmental carcinogens , as a micronutrient supplement . This has now been directly verified in a medium-term cancer transformation bioassay . In the context of public health policies , while the benefits of a diet rich in a variety of fruits and vegetables should continue to be emphasized , the data presented here point to the need for consideration of the possible detrimental effects of certain isolated dietary supplements , before mass cancer chemoprevention clinical trials are conducted on human subjects . This is especially important for genetically predisposed individuals who are environmentally or occupationally exposed to mutagens and carcinogens , such as those found in tobacco smoke and in industrial setting The inhibitory activity of tea against tumorigenesis has been demonstrated in many animal models and has been suggested by some epidemiological studies . Such activity has generally been attributed to tea catechins . To underst and the bioavailability of tea catechins in humans , we gave 18 individuals different amounts of green tea and measured the time-dependent plasma concentrations and urinary excretion of tea catechins . After taking 1.5 , 3.0 , and 4.5 g of decaffeinated green tea solids ( dissolved in 500 ml of water ) , the maximum plasma concentration ( Cmax ) of (-)-epigallocatechin-3-gallate ( EGCG ) was 326 ng/ml , the Cmax of (-)-epigallocatechin ( EGC ) was 550 ng/ml , and the Cmax of (-)-epicatechin ( EC ) was 190 ng/ml . These Cmax values were observed at 1.4 - 2.4 h after ingestion of the tea preparation . When the dosage was increased from 1.5 to 3.0 g , the Cmax values increased 2.7 - 3.4-fold , but increasing the dose to 4.5 g did not increase the Cmax values significantly , which suggested a saturation phenomenon . The half-life of EGCG ( 5.0 - 5.5 h ) seemed to be higher than the half-life of EGC or EC ( 2.5 - 3.4 h ) . EGC and EC , but not EGCG , were excreted in the urine . Over 90 % of the total urinary EGC and EC was excreted within 8 h. When the tea dosage was increased , the amount of EGC and EC excretion seemed to increase , but a clear dose-response relationship was not observed . The present study provides basic pharmacokinetic parameters of green tea catechins in humans ; these parameters may be used to estimate the levels of these compounds after drinking tea |
872 | 10,796,445 | There was no differences between the two for outcomes of global improvement , relapse and leaving the study early . | BACKGROUND Anti-psychotic drugs are usually given orally but compliance with medication given by this route may be difficult to quantify .
The development of depot injections in the 1960s gave rise to extensive use of depots as a means of long-term maintenance treatment .
Perphenazine decanoate and enanthate are depot antipsychotics that belong to the phenothiazine family and have a piperazine ethanol side chain .
OBJECTIVES To assess the effects of depot perphenazine decanoate and enanthate versus placebo , oral anti-psychotics and other depot antipsychotic preparations for people with schizophrenia in terms of clinical , social and economic outcomes .
REVIEW ER 'S CONCLUSIONS Depot perphenazine is in clinical use in the Nordic countries , Belgium , Portugal and the Netherl and s. At a conservative estimate a quarter of a million people suffer from schizophrenia in those countries and could be treated with depot perphenazine . | We monitored fluphenazine plasma levels in 39 schizophrenic patients who participated in a 2-year double-blind comparison of 5 mg and 25 mg of fluphenazine decanoate ( FD ) administered every 14 days . We investigated the relationship between log-transformed plasma levels at 3 , 6 , and 9 months and subsequent psychotic exacerbations with logistic regression and survival analysis . Using logistic regression , the relationship was nonsignificant at 3 months ( chi-square = .21 , df = 1 , p = .65 ) , but significant at 6 months ( chi-square = 4.38 , df = 1 , p = .04 ) and 9 months ( chi-square = 8.98 , df = 1 , p = .003 ) . Using survival analysis with fluphenazine levels as a covariate ( Cox models ) , we also found significant relationships between the fluphenazine plasma level and the risk of exacerbations at 6 months ( chi-square = 3.77 , df = 1 , p = .052 ) and 9 months ( chi-square = 12.21 , df = 1 , p = .0005 ) , but not at three months ( chi-square = 0.87 , df = 1 , p = .65 ) . These findings suggest that the measurement of fluphenazine plasma levels may be helpful in decision-making about the dosage of FD A modification of an earlier rating scale for extrapyramidal system disturbance is described , and evidence for the validity and reliability of the scale is presented . The usefulness of the scale in studies of neuroleptic drugs is discussed . By its application it is possible to quantify extrapyramidal side effects and to separate them into four principal factors |
873 | 26,642,962 | Evidence demonstrated that individuals with MM still engaged in sunbathing , indoor tanning , and reported sunburns .
Moreover , survivors reported inadequate levels of both sun protection and skin self-examinations . | Purpose This systematic review was conducted to evaluate and summarize the existing literature on prevalence of ultraviolet radiation ( UVR ) exposure , sun protection , and screening behaviors among individuals diagnosed with malignant melanoma ( MM ) . | BACKGROUND Although some evidence indicates that early detection protects against the development of lethal melanoma , no r and omized clinical trials have been conducted to measure the efficacy of early detection ( or screening ) in preventing death from this disease . Since melanoma incidence in the United States is relatively rare , a r and omized clinical trial to test the efficacy of screening would be extremely expensive . PURPOSE As an alternative to a r and omized clinical trial , we conducted a population -based , case-control study to investigate whether early detection through skin self-examination ( SSE ) is associated with a decreased risk of lethal melanoma ( includes the presence of advanced disease with distant metastases in addition to death from melanoma ) . METHODS SSE ( conducting a careful , deliberate , and purpose ful examination of the skin ) was assessed in all subjects by use of a structured question naire and personal interviews . The major exposure variable , SSE , was defined following focus-group interviews with melanoma patients and healthy control subjects . The final study population consisted of 1199 Caucasian residents of the state of Connecticut enrolled from January 15 , 1987 , through May 15 , 1989 ; 650 individuals were newly diagnosed with cutaneous melanoma , and the remaining 549 individuals were age- and sex-frequency matched control subjects from the general population . During the study interviews , nevi on the arms and backs of subjects were counted . In 5 years of follow-up ( through March 1994 ) , 110 lethal cases of melanoma were identified . The study design allowed separate estimation of the impact of SSE on reduced melanoma incidence ( primary prevention ) and survival among incident cases ( secondary prevention ) . Odds ratios ( ORs ) were used to measure the associations between SSE and melanoma and between SSE and lethal melanoma . RESULTS SSE , practice d by only 15 % of all subjects , was associated with a reduced risk of melanoma incidence ( adjusted OR = 0.66 ; 95 % confidence interval [ CI ] = 0.44 - 0.99 ; comparing case patients with control subjects ) . The data indicated further that SSE may reduce the risk of advanced disease among melanoma patients ( unadjusted risk ratio = 0.58 ; 95 % CI = 0.31 - 1.11 ) ; however , longer follow-up is required to confirm this latter estimate . If both estimates are correct , they suggest , in combination , that SSE may reduce mortality from melanoma by 63 % ( adjusted OR = 0.37 ; 95 % CI = 0.16 - 0.84 ; comparing lethal cases with general population controls ) . CONCLUSIONS AND IMPLICATION S SSE may provide a useful and inexpensive screening method to reduce the incidence of melanoma . SSE may also reduce the development of advanced disease . The results of this study need to be replicated before strategies to increase the practice of SSE are further developed and promoted BACKGROUND In epidemiologic studies , sunscreen use is associated with increased risk of cutaneous melanoma , basal cell skin cancer , and higher numbers of nevi . It has been proposed that sunscreens may encourage prolonged sun exposure because they delay sunburn occurrence . We examined whether , under habitual conditions of sunscreen use , the sun-protection factor ( SPF ) had an influence on sun-exposure duration . METHODS Before the 1997 summer holidays , we r and omly assigned 87 French and Swiss participants who were 18 - 24 years of age to receive an SPF 10 or an SPF 30 sunscreen . Neither medical personnel nor study participants were aware of their sunscreen assignment . Participants were asked to complete daily records of their sun exposure . To avoid influencing the recreational sun-exposure habits of the study participants , no recommendation was made about sun exposure or sun protection . Furthermore , participants were told that the trial end point was the number of pigmented skin lesions before and after the holidays . One subject was lost to follow-up . All statistical tests were two-sided . RESULTS The SPF 10 ( n = 44 ) and SPF 30 ( n = 42 ) groups had equivalent mean holiday duration s ( 19.4 days versus 20.2 days ) and mean quantities of sunscreen used ( 72.3 g versus 71.6 g ) . The mean cumulative sun exposures for the two groups were 58.2 hours and 72.6 hours , respectively ( P = .011 ) . The mean daily duration s of sunbathing were 2.6 and 3.1 hours , respectively ( P = .0013 ) , and , for outdoor activities , they were 3.6 and 3.8 hours , respectively ( P = .62 ) . There was no difference in sunburn experience between the two groups . CONCLUSIONS Use of higher SPF sunscreen seems to increase the duration of recreational sun exposure of young white Europeans Prospect theory suggests that people respond differentially to factually equivalent messages depending on how these messages are framed ( A. Tversky & D. Kahneman , 1981 ) . A. J. Rothman and P. Salovey ( 1997 ) relied on prospect theory to predict that messages highlighting potential " gains " should promote prevention behaviors such as sunscreen use best . This experiment compared the effectiveness of 4 differently framed messages ( 2 highlighting gains , 2 highlighting losses ) to persuade 217 beach-goers to obtain and use sunscreen . Attitudes and intentions were measured before and immediately following the delivery of the framed information , and after completing the question naire participants were given a coupon redeemable for a small bottle of sunscreen later that same day . People who read either of the 2 gain-framed brochures , compared with those who read either of the 2 loss-framed brochures , were significantly more likely to ( a ) request sunscreen , ( b ) intend to repeatedly apply sunscreen while at the beach , and ( c ) intend to use sunscreen with a sun protection factor of 15 or higher OBJECTIVE To examine the role of partner assistance in learning and implementation of an intervention design ed to promote skin self-examination ( SSE ) behaviors in persons at risk of developing melanoma . DESIGN R and omized controlled trial with immediate and 4-month follow-up visits . SETTING Clinical offices in the ambulatory care area of a hospital . Patients The study included 130 participants and their cohabiting partners drawn from a melanoma registry . Intervention The subjects were r and omly assigned to receive the intervention either as solo learning or as dyadic learning . The intervention consisted of a 10-minute demonstration of the ABCDE ( asymmetry of shape , border irregularity , color variegation , diameter > or = 6 mm , and evolution of the lesion ) rule and skills training . MAIN OUTCOME MEASURES Behavioral measures included self-reported performance of SSE and use of a body map design ed to record areas of concern found during SSE . Intentions , along with attitudinal measures such as perceived importance of SSE and self-efficacy in performing SSE , were also assessed at the 4-month follow-up visit . RESULTS The participants in the dyadic learning group were significantly more likely to report engaging in SSE behaviors ( P<.05 ) . The dyadic learning group also exhibited greater intentions to perform future SSE ( P<.01 ) , higher perceived importance of SSE ( P<.01 ) , and higher perceived self-efficacy ( P<.01 ) . CONCLUSION Dyadic learning may be more effective than solo learning in regard to interventions design ed to teach and promote health behaviors , such as SSE Background Skin cancer is the most prevalent yet most preventable cancer in the US . While protecting oneself from ultraviolet radiation ( UVR ) can largely reduce risk , rates of unprotected sun exposure remain high . Because the desire to be tan often outweighs health concerns among sunbathers , very few interventions have been successful at reducing sunbathing behavior . Sunless tanning ( self-tanners and spray tans ) , a method of achieving the suntanned look without UVR exposure , might be an effective supplement to prevention interventions . Methods and Design This cluster r and omized trial will examine whether a beach-based intervention that promotes sunless tanning as a substitute for sunbathing and includes sun damage imaging and sun safety recommendations is superior to a question naire only control group in reducing sunbathing frequency . Female beach visitors ( N = 250 ) will be recruited from 2 public beaches in eastern Massachusetts . Beach site will be the unit of r and omization . Follow-up assessment will occur at the end of the summer ( 1-month following intervention ) and 1 year later . The primary outcome is average sunbathing time per week . The study was design ed to provide 90 % power for detecting a difference of .70 hours between conditions ( st and ard deviation of 2.0 ) at 1-year with an intra-cluster correlation coefficient of 0.01 and assuming a 25 % rate of loss to follow-up . Secondary outcomes include frequency of sunburns , use of sunless tanning products , and sun protection behavior . Discussion Interventions might be improved by promoting behavioral substitutes for sun exposure , such as sunless tanners , that create a tanned look without exposure to UVR.Trial registration Abstract Objective : Whole-body skin self-examination ( SSE ) with presentation of suspicious lesions to a physician may improve early detection of melanoma . The aim of this study was to establish the prevalence and determinants of SSE in a high-risk population in preparation for a community-based r and omised controlled trial of screening for melanoma . Methods : A telephone survey reached 3110 residents older than 30 years ( overall response rate of 66.9 % ) r and omly selected from 18 regional communities in Queensl and , Australia . Results : Overall , 804 ( 25.9 % ) participants reported whole-body SSE within the past 12 months and 1055 ( 33.9 % ) within the past three years . Whole-body SSE was associated in multivariate logistic regression analysis with younger age ( < 50 years ) ; higher education ; having received either a whole-body skin examination , recommendation or instruction on SSE by a primary care physician ; giving skin checks a high priority ; concern about skin cancer and a personal history of skin cancer . Conclusion : Overall , the prevalence of SSE in the present study is among the highest yet observed in Australia , with about one-third of the adult population reporting whole-body SSE in the past threeyears . People over 50 years , who are at relatively higher risk for skin cancer , currently perform SSE less frequently than younger people BACKGROUND Melanoma is a major public health problem for which early detection may reduce mortality . Since melanoma is generally asymptomatic , this requires skin examination . We sought to evaluate the extent to which the general public has their skin examined by themselves , their partners , or health care providers and the frequency of these examinations . METHODS R and om-digit-dial survey of adult Rhode Isl and ers . RESULTS Only 9 % performed a thorough skin examination ( TSE ) at least once every few months , although over half of the sample reported conducting skin self-examination " deliberately and systematic ally . " Participants were more likely to perform TSE if they were women and if their health care provider had asked them to examine their skin . Most participants reported that their health care provider never or rarely looked at the areas of their skin in which melanoma is most likely to arise . CONCLUSIONS The reported frequency of skin self-examination depends critically on the manner of inquiry . TSE by self or a partner is uncommon , and health care providers do not routinely examine the areas of the skin on which melanomas commonly arise BACKGROUND Thorough skin self-examination ( TSSE ) has substantial potential to reduce melanoma mortality by early detection . METHODS We interviewed 2,126 patients before a scheduled routine visit with a primary care physician , at which participation in a r and omized trial was offered as part of the Check-It-Out Project . We asked about skin examination behavior and related issues . RESULTS By our a priori definition of TSSE , 18 % of participants performed this activity , but other definitions led to widely varying estimates of 12 % to 38 % . Using a partner to assist in the examination was strongly associated with TSSE . That partner was generally the spouse , and wives were more likely to assist their husb and s in these examinations than the reverse . The availability of a wall mirror was a particularly important predictor of TSSE performance . Visual impairment also affected performance . CONCLUSIONS Estimates of TSSE performance vary substantially with the questions used to elicit this information . Partners , particularly spouses , appear to play a critical role in the conduct of TSSE , and wives appear more often and more effectively engaged in this process . Appropriate circumstances , such as availability of a wall mirror , are also important factors . These findings can be used to design interventions to increase TSSE performance with the ultimate aim of reducing melanoma mortality |
874 | 30,402,547 | This review showed that Carie-care ™ reduces pain during caries treatment but requires a longer time for effective treatment than conventional methods .
Local anesthesia was not required in the Chemo-mechanical caries removal ( CMCR ) group .
In addition , dental anxiety decreased compared to the control group , and co-operation was more positive . | Chemo-mechanical caries removal methods are known to be more effective compared with conventional methods in pain reduction .
Carie-care ™ , a chemo-mechanical caries removal agent , was introduced in 2010 but a systematic review of its efficacy has not yet been performed .
The purpose of this study was to investigate the effectiveness of Carie-care ™ on the outcomes of treatment of caries in children and adolescents .
The primary outcome was pain while the secondary outcomes included complete caries removal ( CCR ) , time , need for local anesthesia and behavioral response changes . | BACKGROUND The issue of dental fear and anxiety still poses a significant problem in treating children . Various caries management protocol s have been tried to make the dental visit more compatible to the child patients . AIM The aim of the study was to evaluate and compare the behavioral and physiological responses to chemo-mechanical caries removal ( CMCR ) and conventional drilling method ( CDM ) . MATERIAL S AND METHODS A total of 20 children with an age range of 7 to 11 years with bilateral frank carious lesions were included in this study . They were r and omized into two groups : Group A -- treated with CDM first followed by CMCR and Group B -- treated with CMCR first followed by CDM . The physiological signs ( pulse , blood pressure and oxygen saturation ) were noted prior to treatment , during treatment , post treatment and 5 min after treatment . The behavioral responses were assessed by face , legs , activity , cry , and consolability scale and facial image scale . The participants were interviewed about pain , discomfort , taste , smell , preference and overall experience after every procedure . The pediatric dentist filled in details about patient behavior , time utilized and need for local anesthesia . The results were statistically analyzed using t-test and Chi-square test appropriately ( SPSS version 11 ) . RESULTS There was no significant difference in any of the physiological parameters assessed between the two groups . Discomfort was significantly more ( P < 0.025 ) in the CDM group than CMCR group . The time taken by the dentist was significantly lesser ( P < 0.01 ) in the CDM group . CONCLUSION Techniques which enhance the behavioral response in children should be considered for a better pediatric dental practice PURPOSE The purpose of this controlled clinical trial was to compare the working time for caries removal in primary teeth , the need for local anesthesia and patient cooperation , when the chemomechanical Carisolv or the conventional mechanical method were used . METHODS The sample consisted of primary teeth of children who had occlusal or buccal carious lesions into dentin . High speed and /or low speed were used as the conventional mechanical method of caries removal . The efficiency in caries removal was judged on the basis of clinical criteria . Length of working time , need of local anesthesia , and level of patient cooperation were recorded for both methods . Statistical analysis was performed using the student 's t test and chi-square test . RESULTS Working time with the chemomechanical method was much more prolonged than with the mechanical method ( P < .001 ) , but it did not negatively affect children 's cooperation . Furthermore , the chemomechanical method reduced the need for administration of local anesthesia for Class V cavity preparations . CONCLUSIONS The chemomechanical method , although more prolonged , is effective in caries removal in primary teeth , does not influence children 's cooperation and may reduce the need of local anesthesia in Class V restorations The aim of the present study was to assess pain and the need for anesthesia during chemomechanical caries removal with Papacarie gel and the traditional method ( low-speed bur ) in pediatric patients . A r and omized , controlled , clinical trial with a “ split-mouth ” design was carried out involving 20 children ( 10 girls and 10 boys ) aged four to seven years . Forty primary teeth ( two per child ) were r and omly allocated to either Group 1 ( G1 : chemomechanical caries removal with Papacarie gel ) or Group 2 ( G2 : removal of carious dentin with low-speed bur ) . A face scale was used to classify the sensation of pain during the procedure ( 1 : absence of pain ; 2 : mild pain ; 3 : moderate pain ; 4 : moderately intense pain ; 5 : intense pain ; and 6 : extremely intense pain ) . Statistical analysis of the data was performed using the Wilcoxon-Mann-Whitney ( U ) test . Pain scores were higher in G2 , with statistically significant differences in comparison to G1 ( U = 148.0 ; W = 358.0 ; P = 0.041 ) . Chemomechanical caries removal with Papacarie provides a lesser degree of pain in comparison to conventional caries removal and does not require the use of local anesthesia . The clinical trial registration number is NCT01811420 Background : Chemomechanical caries removal is an effective alternative to the traditional rotary drilling method . The advantages of chemomechanical techniques in terms of the need for anesthesia , pain perception and patient preference are systematic ally review ed and a meta- analysis of the time required for caries removal is reported . Method : R and omized controlled studies of comparison of chemomechanical techniques with conventional rotary drill were selected from a systematic search of st and ard biomedical data bases , including the PubMed and Cochrane clinical trials . Non-repeated search results were screened for relevance and risk of bias assessment , followed by methodology assessment . Statistical models were applied to the outcome parameters - time required , pain perception , need of anesthesia and patient preference - extracted from the studies . Results : Out of the 111 non-repeated search results , 26 studies receiving a low bias score were selected for the review , and 16 r and omized clinical trials of rotary and Carisolv techniques were considered for meta- analysis . Meta- analysis by fixed effect as well as r and om effect models indicate that Carisolv takes more time ( 3.65 ± 0.05 and 4.09 ± 0.29 min ) than rotary drill ( 8.65 ± 0.09 and 8.97 ± 0.66 min ) method . Advantages of reduced pain ( 14.67 for Carisolv vs. 6.76 for rotary drill ) , need for anesthesia ( 1.59 % vs. 10.52 % ) outweigh the longer time requirement and make it the preferred ( 18.68 % vs. 4.69 % ) method . Conclusion : Chemomechanical techniques st and out as a minimally invasive and preferred method based on the meta-analyses . Evaluation of pain experienced using robust methods is needed to strengthen the evidence for their use The purpose of this study was to evaluate the clinical efficiency and patient acceptance of the chemomechanical caries removal agent Carisolv ™ in deciduous teeth . Contralateral primary molars of sixteen 7– to 9–year – old patients ( 32 teeth ) were treated with the air – motor and with Carisolv , respectively . Patients replied to a pre– and a postoperative question naire . Complete caries removal ( CCR ) was accomplished in all air – motor sessions . It was not achieved within the time limit of 15 min in 6 ( 37.5 % ) Carisolv sessions . Air – motor CCR time ranged between 6 and 18 s ( mean : 11.81 s ) . Carisolv CCR time , where accomplished within 15 min , ranged between 6 min 46 s and 13 min 57 s ( mean : 6 min 51 s ) . Preoperatively , the majority of the children reported disliking the drilling , and that they would visit the dentist more often and prefer sitting in the chair longer if they could avoid it . Postoperatively , the majority of the children reported disliking the taste of Carisolv , estimated Carisolv to have taken longer , would not recommend it to their friends , and preferred the air – motor . In conclusion , Carisolv , although a step forward in terms of solution volume required , is not in a position to replace rotary instruments for caries removal : it did not remove decay completely in one third of our sample ; it was much slower than the air – motor ; it had a chlorine taste/odor our patients disliked Prevalence , characteristics and consequences of dental anxiety in a r and omly selected sample of 645 Danish adults were explored in telephone interviews . Participation rate was 88 % . Demographics , fear of specific procedures , negative dentist contacts , general fear tendency , treatment utilization and perceived oral conditions were explored by level of dental anxiety using a modified Dental Anxiety Scale ( DAS ) . A Seattle fear survey item and a summary item from the Dental Fear Survey ( DFS ) were also included for fear description comparisons . Correlation between these indices ( DAS-DFS : rs = 0.72 ; DAS-Seattle item : rs = 0.68 ) aided semantic validation of DAS anxiety intensity levels . Extreme dental anxiety ( DAS > or = 15 ) was found in 4.2 % of the sample and 6 % reported moderate anxiety ( DAS scores 14 - 12 ) . Bivariate ( B ) and logistic regression ( L ) odds ratios ( OR ) showed that high dental anxiety was associated with gender , education and income , but not with age . Extreme dental anxiety for dentate subjects was characterized by fear of drilling ( ORL = 38.7 ) , negative dentist contacts ( ORL = 9.3 ) , general fear tendency ( ORL = 3.4 ) , avoidance of treatment ( ORL = 16.8 ) and increased oral symptoms ( ORB = 4.4 ) . Moderate dental anxiety was also related to drilling ( ORL = 22.3 ) , but with less avoidance due to anxiety ( ORL = 6.8 ) compared with low fear subjects AIM To evaluate and compare the efficacy of chemo mechanical ( carie care ) caries removal method with rotary and h and excavation by assessing the amount of time taken , the pain response experienced by the children and the amount of residual caries left out . STUDY DESIGN Twenty patients between the age groups of 5 - 7 years were selected and caries removal was done by airotor h and instruments and cariecare gel . The efficacy , time taken and pain threshold was evaluated during caries removal . RESULTS significant results were obtained when inter group comparison were made . CONCLUSION it was concluded that cariecare was efficient in caries removal and can be used as an alternative for the airotor in management of dental caries especially in children BACKGROUND Conventional methods of caries removal are commonly associated with pain , fear and discomfort . Chemomechanical methods were introduced to instill a positive dental attitude . Agents like GK-101 , Caridex , Carisolv did not prove effective alternatives owing to their high cost , need of special instruments and taste of chlorine . A new chemomechanical agent , Papacarie ® , has been introduced to overcome these deficiencies . OBJECTIVE This study was aim ed to compare the effectiveness and tolerance of Papacárie ® with the conventional method . METHOD 25 children with at least two primary teeth with broad cavitated occlusal or cervical lesion were selected . One carious tooth from each patient was r and omly treated with each of Papacarie ® and conventional drilling method , one after the other . Time taken for caries excavation , child 's pain perception , change in anxiety levels , microbial flora and child 's preference of treatment were recorded separately for both the methods . RESULT Although the mean time taken for caries removal by the Papacarie ® method was slightly longer ( P≯0.05 ) but it led to reduction in pain and anxiety ( p<0.05 ) . The viable bacterial counts were significantly reduced by either of the two methods ( P < 0 � 0001 ) . More patients preferred Papacarie ® over conventional method of treatment ( P<0.05 ) . CONCLUSION Papacárie ® method seems to be a better alternative to conventional method of caries removal The aim of this study was to evaluate the efficacy , comfort and efficiency of removing dentin caries using only h and instruments . The Carisolv ™ system for caries removal consisting of a solvent gel and a set of specially design ed h and instruments ( chemo – mechanical ) was compared to the use of conventional spoon excavators ( mechanical ) . This was a clinical r and omised controlled trial where the two techniques were compared in the same individual . The outcome variables were : complete caries removal ; pain during caries removal ; anaesthesia requested by the patient during caries removal ; time taken to remove caries . Sixty – six individuals , each with a pair of similar cavities in permanent teeth were selected . After caries removal , a ‘ blinded ’ evaluator assessed the clinical status of the cavity , with the use of a probe . The times for caries removal of the chemo – mechanical and mechanical methods were respectively : 9.2±3.8 and 8.6±3.8 min ( p>0.05 ) . There were 4 cavities arguably presenting signs of caries after cavity preparation in the 66 cavities treated with the mechanical method and 7 in the 66 chemo – mechanical cavities ( p>0,05 ) . Some pain/discomfort was reported by 21 ( 32 % ) participants when the chemo – mechanical method was used , compared with 43 ( 65 % ) when the mechanical method was used ( p<0.05 ) . During the chemo – mechanical and the mechanical treatment , 2 ( 3 % ) and 5 ( 8 % ) patients , respectively , requested local anaesthesia ( p>0.05 ) . The chemo – mechanical method appeared to be more comfortable for most patients |
875 | 25,364,885 | Network meta- analysis showed that SNRIs ( SMD , -1.36 [ CrI , -1.77 to -0.95 ] ) , topical capsaicin ( SMD , -0.91 [ CrI , -1.18 to -0.08 ] ) , TCAs ( SMD , -0.78 [ CrI , -1.24 to -0.33 ] ) , and anticonvulsants ( SMD , -0.67 [ CrI , -0.97 to -0.37 ] ) were better than placebo for short-term pain control .
Several medications may be effective for short-term management of painful diabetic neuropathy , although their comparative effectiveness is unclear . | BACKGROUND Multiple treatments for painful diabetic peripheral neuropathy are available .
PURPOSE To evaluate the comparative effectiveness of oral and topical analgesics for diabetic neuropathy . | A double blind placebo controlled trial was performed to evaluate the effects of the aldose reductase inhibitor , ponalrestat , on symptomatic diabetic neuropathy . After a 4-week placebo run-in phase , 60 patients were 2:1 r and omized to receive either 600 mg ponalrestat or placebo once daily over 12 months . Forty-six patients , 30 of whom were treated with ponalrestat and 16 with placebo , completed the study . Motor and sensory nerve conduction , thermal and vibration sensation thresholds , heart rate variation at rest , E/I ratio , pupillary dilation velocity and pupillary reflex latency were determined at baseline and after 6 and 12 months . Neuropathic symptom scores were assessed every 3 months . Among the fifteen nerve function parameters studied , only trends in favour of ponalrestat were noted for heart rate variation and E/I ratio after 6 months ( P = 0.06 ) , but no significant differences between the groups could be demonstrated during the study . No adverse reactions were observed . It is concluded that one-year treatment with ponalrestat has no beneficial effects on symptoms or electrophysiological parameters in diabetic neuropathy One hundred and ninety patients with symptomatic diabetic peripheral neuropathy took part in a double blind multicentre trial of either placebo or tolrestat 200 mg once daily for 6 months . Painful and paraesthetic symptoms , vibration sensory threshold , and nerve conduction velocity ( NCV ) were assessed as efficacy end-points during the trial . There was an equally marked improvement of painful symptoms during the trial in the tolrestat and placebo groups . A difference in the improvement of paraesthetic symptoms was found however in favour of the placebo group at 24 weeks ( p less than 0.02 ) . The deterioration in mean vibration threshold of the tolrestat group was less than placebo at 24 weeks at all 3 sites measured , and reached significance at the carpal site ( p less than 0.05 ) . Significant improvements in median motor NCV and in the mean NCV of the four motor nerves were also seen in tolrestat treated patients at 24 weeks compared to placebo ( p less than 0.05 ) . In addition , significant changes in favour of tolrestat were seen when the number of motor nerves per patient with NCV increased during the trial was analysed ( p less than 0.001 ) . Concordance analysis of patients with increased mean motor NCV and improvement in painful symptoms demonstrated a positive effect for tolrestat compared to placebo ( p less than 0.02 ) . Mild reversible elevations of hepatic transaminases were seen in a few patients treated with tolrestat , with no other significant adverse effects . Tolrestat may therefore be helpful in diabetic peripheral neuropathy , where there is little opportunity for therapeutic intervention apart from effort to achieve normoglycaemic control Background There are few repeated dose-controlled trials of N-methyl-d-aspartate glutamate receptor antagonists in patients with neuropathic pain . The authors sought to evaluate two low-affinity N-methyl-d-aspartate antagonists using a novel two-stage design . Methods The authors studied patients with painful diabetic neuropathy ( DN ) and postherpetic neuralgia ( PHN ) in two crossover trials : ( 1 ) efficacy trial ( dextromethorphan vs. memantine vs. active placebo [ lorazepam ] ) and ( 2 ) dose – response trial of the preferred active drug in responders from the first study ( 0%vs . 25%vs . 50%vs . 100 % of each patient 's maximally tolerated dose ) . Pain intensity was measured on a 20-point scale . Results Nineteen of 23 DN patients and 17 of 21 PHN patients completed the efficacy trial . Median doses for DN and PHN were 400 and 400 mg/day dextromethorphan , 55 and 35 mg/day memantine , and 1.8 and 1.2 mg/day lorazepam . In the efficacy trial , among patients with DN , dextromethorphan reduced pain intensity by a mean of 33 % from baseline , memantine reduced pain intensity by a mean of 17 % , and lorazepam reduced pain intensity by a mean of 16 % ; the proportions of subjects achieving greater than moderate pain relief were 68 % with dextromethorphan , 47 % with memantine , and 37 % with lorazepam . Mean reductions in pain intensity in patients with PHN were 6 % with dextromethorphan , 2 % with memantine , and 0 % with lorazepam . No comparison with placebo reached statistical significance in the efficacy trial . In the 10 DN subjects who responded to dextromethorphan , there was a significant dose – response effect on pain intensity ( P = 0.035 ) , with the highest dose significantly better than that of lorazepam ( P = 0.03 ) . Conclusions Dextromethorphan is effective in a dose-related fashion in selected patients with DN . This was not true of PHN , suggesting a difference in pain mechanisms . Selective approaches to pain-relevant N-methyl-d-aspartate receptors are warranted Background Peripheral diabetic neuropathy affects between 20 % and 45 % of patients with diabetes . Objective To ascertain the effect of lacosamide on pain associated with peripheral diabetic neuropathy . Methods One hundred nineteen patients with a 1 to 5-year history of pain attributed to diabetic neuropathy and a score of ≥4 on the Likert pain scale entered the multicenter , r and omized , double-blind , placebo-controlled trial . Lacosamide ( N=60 ) titrated from 100 to 400 mg/d or maximum tolerated dose and placebo ( N=59 ) were the trial interventions . Primary efficacy criterion was change in pain score on the 11-point Likert pain scale . Secondary assessment s included Short-Form McGill Pain and Short-Form-36 Quality of Life Question naires , sleep/activity interference , pain intensity , Patient and Clinical Global Impression of Change , and Profile of Mood . Patients receiving at least 1 dose of medication underwent safety evaluation . Results Ninety-four patients ( lacosamide 46 ; placebo 48 ) completed the trial . Lacosamide had significantly ( P=0.039 ) better pain relief versus placebo ( primary outcome ) . Improvements were also seen in secondary outcome measures . Adverse events occurred in 52 lacosamide and 44 placebo patients . Common adverse events , occurring in ≥5 % of patients , were headache ( lacosamide 18 % , placebo 22 % ) , dizziness ( lacosamide 15 % , placebo 8 % ) , and nausea ( lacosamide 12 % , placebo 7 % ) . Five lacosamide and 3 placebo patients withdrew for adverse events . Discussion Lacosamide seems to attenuate pain in diabetic neuropathy in doses up to 400 mg/d and improves quality of life issues Abstract Aims / Introduction : Duloxetine has been suggested to exert analgesic effects by activating the descending inhibitory system through inhibition of serotonin ( 5‐HT ) and noradrenaline ( NA ) reuptake . This r and omized controlled trial investigated the efficacy and safety of duloxetine in Japanese patients with diabetic neuropathic pain ( DNP ) . Material s and Methods : Duloxetine 40 or 60 mg/day or placebo was given orally once daily for 12 weeks . The primary efficacy measure was weekly mean 24‐h average pain severity score on the 11‐point Numerical Rating Scale . Results : At 12 weeks vs baseline , the 24‐h average pain score ( adjusted mean ± SE ) was significantly improved in the combined duloxetine ( −2.47 ± 0.18 ) and duloxetine 40 mg ( −2.41 ± 0.21 ) and 60 mg groups ( −2.53 ± 0.21 ) as compared with the placebo group ( −1.61 ± 0.18 ) . Duloxetine also exerted significant improvements over the placebo in nearly all secondary outcome measures including 24‐h worst pain , night pain , Brief Pain Inventory ( BPI ) pain scores , Patient ’s Global Impression of Improvement ( PGI‐I ) and health outcome measures , namely , various BPI interference scores . The incidence of adverse events ( AE ) was higher in the duloxetine groups than in the placebo group ( duloxetine overall , 84.8 % ; duloxetine 40 mg , 84.7 % ; duloxetine 60 mg , 84.9 % ; placebo , 73.7 % ) . Most AE were mild or moderate in severity , and resolved or relieved . There were no clinical ly significant safety concerns . Conclusions : Duloxetine 40 or 60 mg/day showed superiority over the placebo at reducing pain scores in patients with DNP . Duloxetine is safe , efficacious and clinical ly useful in the management of DNP . This trial was registered with Clinical Trials.gov ( no. NCT‐00552175 ) . ( J Diabetes Invest , doi : 10.1111/j.2040‐1124.2010.00073.x , 2010 OBJECTIVE We conducted an 8-wk controlled study with topical 0.075 % capsaicin in subjects with chronic severe painful diabetic neuropathy who were unresponsive or intolerant to conventional therapy . Capsaicin is an alkaloid found in capsicum peppers and produces desensitization to noxious thermal , chemical , and mechanical stimuli when applied topically . RESEARCH DESIGN AND METHODS In 22 r and omly assigned subjects , either capsaicin or vehicle cream was applied to painful areas 4 times/day . Pain measurements were recorded at baseline and at 2-wk intervals for 8 wk . RESULTS Capsaicin treatment was more beneficial than vehicle treatment in the overall clinical improvement of pain status , as measured by physician 's global evaluation ( P = 0.038 ) and by a categorical pain severity scale ( P = 0.057 ) . Decrease in mean pain intensity by a visual analogue scale was 16 % in capsaicin-treated and 4.1 % in vehicle-treated subjects . Mean pain relief on visual analogue scale was 44.6 and 23.2 % , respectively . In a follow-up open-label study , approximately 50 % of subjects reported improved pain control or were cured , and 25 % each were unchanged or worse . A burning sensation at the application site was noted by some subjects but both its magnitude and duration decreased with time . CONCLUSIONS Results from this preliminary study suggest that topical 0.075 % capsaicin may be of value in subjects with diabetic neuropathy and intractable pain AIMS To compare the efficacy and safety of lamotrigine and amitriptyline in controlling chronic painful peripheral neuropathy in diabetic patients . METHODS A r and omized , double-blind , crossover , active-control , clinical trial with variable dose titration was carried out ( n = 53 ) . Amitriptyline orally , at doses of 10 , 25 and 50 mg at night-time , each dose for 2 weeks , and lamotrigine orally , at doses of 25 , 50 and 100 mg twice daily , each dose for 2 weeks , by optional titration were used . There was a placebo washout period for 2 weeks between the two drugs . Assessment for pain relief , overall improvement and adverse events were carried out . RESULTS Good , moderate and mild pain relief were noted in 19 ( 41 % ) , six ( 13 % ) and seven ( 15 % ) patients on lamotrigine and 13 ( 28 % ) , five ( 11 % ) and 15 ( 33 % ) patients on amitriptyline , respectively , by patient 's global assessment of efficacy and safety . Patient and physicians global assessment , McGill pain question naire and Likert pain scale showed no significant difference between the treatments , although improvement with both treatments was seen from 2 weeks . Of the 44 adverse events reported , 33 ( 75 % ) were with amitriptyline , sedation being the commonest [ in 19 ( 43 % ) patients ] . Lamotrigine caused adverse events in 11 ( 25 % ) , of which rash in three ( 7 % ) and elevations of creatinine in four ( 9 % ) were the most common . The preferred lamotrigine dose was 25 mg twice daily . CONCLUSIONS As there are few differences between the two treatments in efficacy , lamotrigine 25 mg twice daily might be the first choice as it is associated with fewer adverse effects in our population An 8-week double-blind , multicenter , parallel study compared the safety and efficacy of topical capsaicin and oral amitriptyline in patients with painful diabetic neuropathy involving the feet . Two hundred thirty-five patients were r and omized to treatment with either capsaicin cream or amitriptyline capsules . Capsaicin-treated patients received inactive capsules , and amitriptyline-treated patients applied vehicle cream . A visual analogue scale of pain intensity and measurements of interference by pain with functional activities were recorded at onset and at 2-week intervals . A visual analogue scale of pain relief and physicians ' global evaluation assessed changes in pain status from baseline . Topical capsaicin and oral amitriptyline produced equal and statistically significant improvements in pain over the course of the study . By the end of week 8 , 76 % of patients in each group experienced less pain , with a mean reduction in intensity of more than 40 % . By the end of the study , the interference with daily activities by pain had diminished significantly ( P = .001 ) in both groups , including improvements in sleeping and walking . No systemic side effects were observed in patients treated with topical capsaicin . Most patients receiving amitriptyline experienced at least one systemic side effect , ranging from somnolence ( 46 % ) to neuromuscular ( 23 % ) and cardiovascular ( 9 % ) adverse effects . Topically applied capsaicin is an equally effective but considerably safer alternative to amitriptyline for relief of the pain of diabetic neuropathy Objectives – To evaluate the efficacy and tolerability of topiramate in patients with painful diabetic polyneuropathy OBJECTIVE The objective of this study was to evaluate the efficacy of venlafaxine HCl in the symptomatic treatment of painful peripheral diabetic neuropathy ( PPDN ) among patients with type 2 diabetes mellitus ( DM ) . DESIGN This study was design ed as a prospect i ve , r and omized , and controlled trial . SETTING This study was conducted at the Dicle University Medical Faculty ( Diyarbakir , Turkey ) . PATIENTS Sixty type 2 DM out patients ( 47 females and 13 males ) with PPDN who had a minimum visual analog scale ( VAS ) score of 40 mm were enrolled in this study . INTERVENTIONS Patients r and omized to the treatment group ( n=30 ) received venlafaxine HCl , whereas those r and omized to the control group ( n=30 ) received a combination of vitamins B(1 ) and B(6 ) tablets . MEASURES Severity of pain was measured by VAS , Short-Form McGill Pain Question naire , and numerical analog scale scores at admission and at the second , fourth , and eighth weeks of the study . Polyneuropathy was supported by electromyelography . OUTCOME In the treatment group , severity of pain was measured as 70.0+/-13.0 in the VAS , as 24.9+/-6.2 in the Short-Form McGill Pain Question naire , and as 7.2+/-1.1 in the numerical analog scale . In the control group , it was measured as 73.0+/-8.0 in the VAS , as 26.8+/-6.2 in the Short-Form McGill Pain Question naire , and as 7.4+/-0.8 in the numerical analog scale ( P>.05 ) . RESULTS The most common form of PPDN was distal symmetrical sensorimotor polyneuropathy in both groups ( 46.8 % vs. 50.0 % ) . At the end of the study , there was a significant difference in severity of pain between the groups . In the treatment group , scores were 8.5+/-5.2 and 3.1+/-1.6 in the Short-Form McGill Pain Question naire and numerical analog scale , respectively ; in the control group , these were 20.5+/-7.0 and 5.5+/-1.6 , respectively ( P<.001 ) . CONCLUSIONS Venlafaxine HCl is a safe and well-tolerable analgesic drug in the symptomatic treatment of PPDN ; however , it has minimal adverse effects . It showed its efficacy markedly in the second week of therapy & NA ; The aim of this study was to examine the efficacy and safety of duloxetine , a balanced and potent dual reuptake inhibitor of serotonin and norepinephrine , in the management of diabetic peripheral neuropathic pain . Serotonin and norepinephrine are thought to inhibit pain via descending pain pathways . In a 12‐week , multicenter , double‐blind study , 457 patients experiencing pain due to polyneuropathy caused by Type 1 or Type 2 diabetes mellitus were r and omly assigned to treatment with duloxetine 20 mg/d ( 20 mg QD ) , 60 mg/d ( 60 mg QD ) , 120 mg/d ( 60 mg BID ) , or placebo . The diagnosis was confirmed by a score of at least 3 on the Michigan Neuropathy Screening Instrument . The primary efficacy measure was the weekly mean score of the 24‐h Average Pain Score , which was rated on an 11‐point ( 0–10 ) Likert scale ( no pain to worst possible pain ) and computed from diary scores between two site visits . Duloxetine 60 and 120 mg/d demonstrated statistically significant greater improvement compared with placebo on the 24‐h Average Pain Score , beginning 1 week after r and omization and continuing through the 12‐week trial . Duloxetine also separated from placebo on nearly all the secondary measures including health‐related outcome measures . Significantly more patients in all three active‐treatment groups achieved a 50 % reduction in the 24‐h Average Pain Score compared with placebo . Duloxetine treatment was considered to be safe and well tolerated with less than 20 percent discontinuation due to adverse events . Duloxetine at 60 and 120 mg/d was safe and effective in the management of diabetic peripheral neuropathic pain An 8-week , double-blind , vehicle-controlled study was conducted to determine the effectiveness of topical capsaicin 0.075 % cream in relieving pain associated with diabetic neuropathy . Patients were selected who experienced moderate to very severe pain , which interfered with sleep or activities on a daily basis , and who were unresponsive or intolerant to conventional therapy . The results after 8 weeks showed a statistically significant difference in favor of the capsaicin-treated patients , with 90 % of these patients improved . The results of this study indicate that topical capsaicin 0.075 % cream is safe and effective in managing painful diabetic neuropathy OBJECTIVE Chronic diabetic peripheral neuropathic pain ( DPNP ) is difficult to treat , with treatment regimens often inadequate at controlling pain and limited by side effects and drug tolerance . Secondary parameters , such as quality of sleep and mood , may also be important for successful DPNP management . The objectives of this study were to compare the analgesic efficacy of pregabalin , amitriptyline , and duloxetine , and their effect on polysomnographic sleep , daytime functioning , and quality of life in patients with DPNP . RESEARCH DESIGN AND METHODS This was a double-blind , r and omized , parallel group investigation of type 1 and 2 diabetic subjects with DPNP . Each treatment group had a single-blind , 8-day , placebo run-in followed by 14 days of lower-dose and 14 days of higher-dose medication . At the end of each dose titration period , subjective pain , sleep , and daytime functioning were assessed during a 2-day residential period . RESULTS All medications reduced pain when compared with placebo , but no one treatment was superior to any other . For sleep , pregabalin improved sleep continuity ( P < 0.001 ) , whereas duloxetine increased wake and reduced total sleep time ( P < 0.01 and P < 0.001 ) . Despite negative effects on sleep , duloxetine enhanced central nervous system arousal and performance on sensory motor tasks . There were no significant safety findings ; however , there was a significantly higher number of adverse events in the pregabalin treatment group . CONCLUSIONS There was no significant difference in analgesic efficacy between amitriptyline , duloxetine , and pregabalin . However , there were significant differences in the secondary parameters , which may be of relevance when deciding the optimal treatment for DPNP OBJECTIVE The purpose of this study was to evaluate the efficacy of fidarestat , a novel aldose reductase ( AR ) inhibitor , in a double-blind placebo controlled study in patients with type 1 and type 2 diabetes and associated peripheral neuropathy . RESEARCH DESIGN AND METHODS A total of 279 patients with diabetic neuropathy were treated with placebo or fidarestat at a daily dose of 1 mg for 52 weeks . The efficacy evaluation was based on change in electrophysiological measurements of median and tibial motor nerve conduction velocity , F-wave minimum latency , F-wave conduction velocity ( FCV ) , and median sensory nerve conduction velocity ( forearm and distal ) , as well as an assessment of subjective symptoms . RESULTS Over the course of the study , five of the eight electrophysiological measures assessed showed significant improvement from baseline in the fidarestat-treated group , whereas no measure showed significant deterioration . In contrast , in the placebo group , no electrophysiological measure was improved , and one measure significantly deteriorated ( i.e. , median nerve FCV ) . At the study conclusion , the fidarestat-treated group was significantly improved compared with the placebo group in two electrophysiological measures ( i.e. , median nerve FCV and minimal latency ) . Subjective symptoms ( including numbness , spontaneous pain , sensation of rigidity , paresthesia in the sole upon walking , heaviness in the foot , and hypesthesia ) benefited from fidarestat treatment , and all were significantly improved in the treated versus placebo group at the study conclusion . At the dose used , fidarestat was well tolerated , with an adverse event profile that did not significantly differ from that seen in the placebo group . CONCLUSIONS The effects of fidarestat-treatment on nerve conduction and the subjective symptoms of diabetic neuropathy provide evidence that this treatment alters the progression of diabetic neuropathy There has been a recent growth in the use of Bayesian methods in medical research . The main reasons for this are the development of computer intensive simulation based methods such as Markov chain Monte Carlo ( MCMC ) , increases in computing power and the introduction of powerful software such as WinBUGS . This has enabled increasingly complex models to be fitted . The ability to fit these complex models has led to MCMC methods being used as a convenient tool by frequentists , who may have no desire to be fully Bayesian . Often research ers want ' the data to dominate ' when there is no prior information and thus attempt to use vague prior distributions . However , with small amounts of data the use of vague priors can be problematic . The results are potentially sensitive to the choice of prior distribution . In general there are fewer problems with location parameters . The main problem is with scale parameters . With scale parameters , not only does one have to decide the distributional form of the prior distribution , but also whether to put the prior distribution on the variance , st and ard deviation or precision . We have conducted a simulation study comparing the effects of 13 different prior distributions for the scale parameter on simulated r and om effects meta- analysis data . We varied the number of studies ( 5 , 10 and 30 ) and compared three different between- study variances to give nine different simulation scenarios . One thous and data sets were generated for each scenario and each data set was analysed using the 13 different prior distributions . The frequentist properties of bias and coverage were investigated for the between- study variance and the effect size . The choice of prior distribution was crucial when there were just five studies . There was a large variation in the estimates of the between- study variance for the 13 different prior distributions . With a large number of studies the choice of prior distribution was less important . The effect size estimated was not biased , but the precision with which it was estimated varied with the choice of prior distribution leading to varying coverage intervals and , potentially , to different statistical inferences . Again there was less of a problem with a larger number of studies . There is a particular problem if the between- study variance is close to the boundary at zero , as MCMC results tend to produce upwardly biased estimates of the between- study variance , particularly if inferences are based on the posterior mean . The choice of ' vague ' prior distribution can lead to a marked variation in results , particularly in small studies . Sensitivity to the choice of prior distribution should always be assessed Neuropathic pain treatment remains unsatisfactory despite a substantial increase in the number of trials . This EFNS Task Force aim ed at evaluating the existing evidence about the pharmacological treatment of neuropathic pain . Studies were identified using first the Cochrane Data base then Medline . Trials were classified according to the aetiological condition . All class I and II controlled trials ( according to EFNS classification of evidence ) were assessed , but lower‐class studies were considered in conditions that had no top level studies . Only treatments feasible in an outpatient setting were evaluated . Effects on pain symptoms/signs , quality of life and comorbidities were particularly search ed for . Most of the r and omized controlled trials included patients with postherpetic neuralgia ( PHN ) and painful polyneuropathies ( PPN ) mainly caused by diabetes . These trials provide level A evidence for the efficacy of tricyclic antidepressants , gabapentin , pregabalin and opioids , with a large number of class I trials , followed by topical lidocaine ( in PHN ) and the newer antidepressants venlafaxine and duloxetine ( in PPN ) . A small number of controlled trials were performed in central pain , trigeminal neuralgia , other peripheral neuropathic pain states and multiple‐aetiology neuropathic pains . The main peripheral pain conditions respond similarly well to tricyclic antidepressants , gabapentin , and pregabalin , but some conditions , such as HIV‐associated polyneuropathy , are more refractory . There are too few studies on central pain , combination therapy , and head‐to‐head comparison . For future trials , we recommend to assess quality of life and pain symptoms or signs with st and ardized tools Background : Painful neuropathy is one of the most common long‐term complications of diabetes mellitus and often proves difficult to relieve . Methods : Patients with diabetic neuropathy with moderate or greater pain for at least 3 months , were evaluated for efficacy , safety and health‐related quality of life ( QOL ) while receiving controlled‐release ( CR ) oxycodone ( OxyContin ® ) or active placebo . Patients underwent washout from all opioids 2–7 days before r and omization to 10 mg CR oxycodone or active placebo ( 0.25 mg benztropine ) q12h . The dose was increased , approximately weekly , to a maximum of 40 mg q12h CR oxycodone or 1 mg q12h benztropine , with crossover to the alternate treatment after a maximum of 4 weeks . Acetaminophen , 325–650 mg q4‐6h prn was provided as rescue . Results : Thirty‐six patients were evaluable for efficacy ( 21 men , 15 women , mean age 63.0±9.4 years ) . CR oxycodone result ed in significantly lower ( P=0.0001 ) mean daily pain ( 21.8±20.7 vs. 48.6±26.6 mm VAS ) , steady pain ( 23.5±23.0 vs. 47.6±30.7 mm VAS ) , brief pain ( 21.8±23.5 vs. 46.7±30.8 mm VAS ) , skin pain ( 14.3±20.4 vs. 43.2±31.3 mm VAS ) , and total pain and disability ( 16.8±15.6 vs. 25.2±16.7 ; P=0.004 ) . Scores from 6 of the 8 SF‐36 domains and both summary scales , St and ardized Physical Component ( P=0.0002 ) and St and ardized Mental Component ( P=0.0338 ) were significantly better during CR oxycodone treatment . The number needed to treat to obtain one patient with at least 50 % pain relief is 2.6 and clinical effectiveness scores favoured treatment with CR oxycodone over placebo ( P=0.0001 ) . Conclusion : CR oxycodone is effective and safe for the management of painful diabetic neuropathy and improves QOL Background and objective : Opioid treatment has played a limited role in the management of diabetic neuropathy , in part because of concerns about the responsiveness of neuropathic pain to opioid treatment . This controlled study evaluated the efficacy and safety of controlled-release ( CR ) oxycodone in subjects with moderate to severe pain due to diabetic neuropathy . Methods : This multicenter , r and omized , double-blind , placebo-controlled , parallel-group study included 159 subjects with moderate to severe pain due to diabetic neuropathy . Treatment began with either one 10-mg tablet of CR oxycodone ( n = 82 ) or identical placebo ( n = 77 ) every 12 hours . Doses could be increased every 3 days to a maximum of 6 tablets ( 60 mg CR oxycodone ) every 12 hours . Treatment lasted up to 6 weeks . The primary efficacy variable was overall average daily pain intensity during study days 28 to 42 . Results : At an average ( SD ) dose of 37 ( 21 ) mg per day ( range 10 to 99 mg/d ) , CR oxycodone provided more analgesia than placebo ( p= 0.002 ) in the intent-to-treat cohort . From days 28 to 42 , overall average daily pain intensity ( least squares mean ±SE ) , rated in subject diaries on a numeric scale of 0 ( no pain ) to 10 ( pain as bad as you can imagine ) , was 4.1 ± 0.3 in subjects given CR oxycodone and 5.3 ± 0.3 in placebo-treated subjects . Overall , 80 ( 96 % ) of 82 subjects given CR oxycodone and 52 ( 68 % ) of 77 subjects who received placebo reported adverse events . The most common adverse events in the CR oxycodone group were opioid related . Conclusions : In this 6-week trial , CR oxycodone was effective for the treatment of moderate to severe pain due to diabetic neuropathy . Adverse events were typical of opioid-related side effects Objectives The aims of this multicenter , r and omized , placebo-controlled , double-blind trial were to confirm the efficacy of lacosamide at a daily dose of 400 mg/d and to explore the efficacy , safety , and tolerability of lacosamide 200 mg/d and 600 mg/d in the treatment of painful diabetic neuropathy . Methods The trial consisted of a 2-week run-in period , a 6-week titration phase , and a 12-week maintenance phase , during which patients received placebo or fixed doses of lacosamide 200 , 400 , or 600 mg/d . No back titration was allowed during the trial . The primary efficacy criterion was the change in Likert pain score from baseline to the average over the last 4 weeks of the maintenance phase in the intent-to-treat population . Results The lacosamide 400 mg/d group demonstrated statistically significant improvement in Likert pain score over placebo for the primary efficacy measure . At the end of treatment , 58 % of patients in the lacosamide 400 mg/d treatment group achieved at least a 2-point or 30 % reduction in Likert pain score , compared with 46 % of placebo-treated patients . The lacosamide 200 mg/d group separated from placebo , but failed to show statistical significance for any of the primary or secondary outcome measures . The lacosamide 600 mg/d group was significantly more efficacious than placebo in the observed cases but not in the intent-to-treat population . This was probably secondary to a relatively high-premature withdrawal rate due to adverse events that occurred during the titration phase in that group . Overall lacosamide at daily doses of 200 to 400 mg was well tolerated , with 8 % of patients discontinuing due to an adverse event from the 200 mg/d group and 23 % from the 400 mg/d group compared with 9 % in the placebo group . Discontinuations due to adverse events were highest in the 600 mg/d group ( 40 % ) . The most common adverse events consisted of dizziness , nausea , tremor , headache , and fatigue . Somnolence , cognitive and behavioral side effects , weight change , and edema were notably low . Discussion Safety and efficacy analyses indicated that lacosamide 400 mg/d provided an optimal balance between efficacy and side effects in patients with painful diabetic neuropathy Twelve patients with severe , painful diabetic neuropathy in the lower extremities were treated with imipramine and placebo in a fixed-dose , double-blind , crossover study of five plus five weeks . Seven patients experienced notable improvement while receiving imipramine and none while receiving placebo . The rating of specific symptoms at the end of each treatment period showed a beneficial effect of imipramine on pain , paresthesia , dysesthesia , numbness , and nocturnal aggravation . The plasma levels of imipramine and its metabolite desipramine were significantly higher in patients who benefited from imipramine treatment Painful diabetic peripheral neuropathy ( DPN ) is common , is associated with significant reduction in quality of life and poses major treatment challenges to the practising physician . Although poor glucose control and cardiovascular risk factors have been proven to contribute to the aetiology of DPN , risk factors specific for painful DPN remain unknown . A number of instruments have been tested to assess the character , intensity and impact of painful DPN on quality of life , activities of daily living and mood . Management of the patient with DPN must be tailored to individual requirements , taking into consideration the co-morbidities and other factors . Pharmacological agents with proven efficacy for painful DPN include tricyclic anti-depressants , the selective serotonin and noradrenaline re-uptake inhibitors , anti-convulsants , opiates , membrane stabilizers , the anti-oxidant alpha-lipoic acid and topical agents including capsaicin . Current first-line therapies for painful DPN include tricyclic anti-depressants , the serotonin and noradrenaline re-uptake inhibitor duloxetine and the anti-convulsants pregabalin and gabapentin . When prescribing any of these agents , other co-morbidities and costs must be taken into account . Second-line approaches include the use of opiates such as synthetic opioid tramadol , morphine and oxycodone-controlled release . There is a limited literature with regard to combination treatment . In extreme cases of painful DPN unresponsive to pharmacotherapy , occasional use of electrical spinal cord stimulation might be indicated . There are a number of unmet needs in the therapeutic management of painful DPN . These include the need for r and omized controlled trials with active comparators and data on the long-term efficacy of agents used , as most trials have lasted for less than 6 months . Finally , there is a need for appropriately design ed studies to investigate non-pharmacological approaches Background : Using identical methods , three simultaneous placebo-controlled trials of topiramate for painful diabetic neuropathy ( PDN ) did not reach significance . This independent yet concurrent placebo-controlled trial used different methods to assess topiramate efficacy and tolerability in PDN . Methods : This 12-week , multicenter , r and omized , double-blind trial included 323 subjects with PDN and pain visual analog ( PVA ) score of at least 40 on a scale from 0 ( no pain ) to 100 ( worst possible pain ) . Topiramate ( n = 214 ) or placebo ( n = 109 ) was titrated to 400 mg daily or maximum tolerated dose . Short-acting rescue analgesics were permitted only during the first 6 weeks . Results : Baseline characteristics were comparable between groups except for mean body weight ( topiramate , 101.4 kg ; placebo , 95.7 kg ; p = 0.028 ) . Twelve weeks of topiramate treatment reduced PVA scale score ( from 68.0 to 46.2 mm ) more effectively than placebo ( from 69.1 to 54.0 mm ; p = 0.038 ) . Fifty percent of topiramate-treated subjects and 34 % of placebo-treated subjects responded to treatment , defined as > 30 % reduction in PVA scale score ( p = 0.004 ) . Topiramate monotherapy also reduced worst pain intensity ( p = 0.003 vs placebo ) and sleep disruption ( p = 0.020 vs placebo ) . Diarrhea , loss of appetite , and somnolence were the most commonly reported adverse events in the topiramate group . Topiramate reduced body weight ( −2.6 vs + 0.2 kg for placebo ; p < 0.001 ) without disrupting glycemic control . Conclusions : Topiramate monotherapy reduced pain and body weight more effectively than placebo in patients with painful diabetic neuropathy AIMS To compare the efficacy and safety of pregabalin and amitriptyline in alleviating pain associated with diabetic peripheral neuropathy . METHODS A r and omized , double-blind , crossover , active-control , clinical trial with variable dose titration was carried out ( n = 51 ) . Amitriptyline orally , at doses of 10 , 25 and 50 mg at night-time and pregabalin orally , at doses of 75 , 150 and 300 mg twice daily , by optional titration was used . Each drug treatment was of 5 weeks . There was a placebo washout period for 3 weeks between the two drugs . Assessment for pain relief , overall improvement and adverse events were carried out . RESULTS Good , moderate and mild pain relief were noted in 21 ( 48 % ) , 6 ( 13 % ) and 7 ( 15 % ) patients on pregabalin and 15 ( 34 % ) , 5 ( 11 % ) and 12 ( 27 % ) patients on amitriptyline , respectively , by patient 's global assessment of efficacy and safety . Patient and physician 's global assessment , McGill pain question naire , Likert pain scale and Patient Global Impression of Change showed no significant difference between the treatments , although improvement with both treatments was seen from the first week . Of the 52 adverse events reported , 34 ( 65.4 % ) were with amitriptyline , drowsiness being the commonest [ in 19 ( 43 % ) patients ] . Pregabalin caused adverse events in 18 ( 25 % ) , of which drowsiness was the most common in nine ( 20 % ) patients . The preferred pregabalin dose was 150 mg twice daily . CONCLUSIONS As there are few differences between the two treatments in efficacy , pregabalin 150 mg twice daily might be the alternative choice as it is associated with fewer adverse effects in our population A double-blind , r and omized , placebo-controlled crossover trial of the aldose reductase inhibitor sorbinil was undertaken in 15 patients ( age 35–68 yr ) with chronic painful diabetic neuropathy . Treatment was evaluated by subjective pain responses , clinical examination , vibration perception threshold , motor and sensory nerve electrophysiology , and cardiovascular reflex tests of autonomie nerve function . Among the many measurements , only pain , tendon reflex scores , and sural sensory potential amplitude improved significantly during sorbinil administration , while scores of clinical sensory examination deteriorated . Four patients experienced an idiosyncratic reaction that rapidly recovered on discontinuing the drug . This study suggests that aldose reductase inhibitor treatment with sorbinil may have an effect on symptomatic diabetic neuropathy in man BACKGROUND Reports of gabapentin use in diabetic peripheral neuropathy pain stimulate a need for controlled trials to determine its comparative efficacy to the therapeutic st and ard of amitriptyline hydrochloride . OBJECTIVE To determine the efficacy of gabapentin compared with amitriptyline in treating diabetic peripheral neuropathy pain . DESIGN Prospect i ve , r and omized , double-blind , double-dummy , crossover study . SETTING Veterans Affairs San Diego Healthcare System , Ambulatory Care Clinic . PATIENTS Twenty-eight veterans were referred by their primary care providers . Two patients withdrew before r and omization because of no neuropathic pain after washout ; a third withdrew for unexpected surgery that required analgesics . Three patients withdrew because of adverse effects and 1 for protocol violation . INTERVENTIONS Patients with stable glycemic control and neuropathic pain r and omized to 6 weeks of therapy with gabapentin , 900 to 1800 mg/d , or amitriptyline hydrochloride , 25 to 75 mg/d , with a 1-week washout before crossover . MAIN OUTCOME MEASURES Pain relief measured by pain scale with verbal descriptors and global pain score assessment at treatment end . RESULTS Participants and investigators were blinded throughout . Mean dosages were of gabapentin , 1565 mg/d , and of amitriptyline hydrochloride , 59 mg/d . Sixty-five percent of patients reached maximum dose with gabapentin and 54 % with amitriptyline . Mean score diary analysis showed pain relief with gabapentin and amitriptyline was not significantly different ( P = .26 ) . Global data were obtained from 21 of 25 enrolled patients who completed the study . Moderate or greater pain relief was experienced in 11 ( 52 % ) of 21 patients with gabapentin and 14 ( 67 % ) of 21 patients with amitriptyline . There were no significant period or carry-over effects ( P = .35 ) . CONCLUSIONS Although both drugs provide pain relief , mean pain score and global pain score data indicate no significant difference between gabapentin and amitriptyline . Gabapentin may be an alternative for treating diabetic peripheral neuropathy pain , yet does not appear to offer considerable advantage over amitriptyline and is more expensive . Larger trials are necessary to define gabapentin 's place in treating diabetic peripheral neuropathy pain UNLABELLED This was a 6-week , r and omized , double-blind , multicenter study evaluating the efficacy of pregabalin in the treatment of painful diabetic neuropathy . Two hundred forty-six men and women with painful diabetic neuropathy received pregabalin ( 150 or 600 mg/day by mouth ) or placebo . The primary efficacy variable was mean pain score at the end of treatment . Efficacy results indicate that pregabalin 600 mg/day significantly decreased mean pain score to 4.3 ( vs 5.6 for placebo , P = .0002 ) and increased the proportion of patients who had a > or = 50 % decrease from baseline pain ( 39 % vs 15 % for placebo , P = .002 ) . Pregabalin also significantly reduced sleep interference , past week and present pain intensity , sensory and affective pain scores , and bodily pain and decreased by > or = 50 % the number of patients describing their pain as gnawing , sickening , fearful , and punishing-cruel . More patients receiving pregabalin 600 mg/day than placebo showed improvement , as rated on the Clinical and Patient Global Impression of Change scales , 73 % vs 45 % and 85 % vs 47 % , respectively . Pregabalin 150 mg/day was essentially no different from placebo . Dizziness was the most common side effect . These study results show pregabalin 600 mg/day to be safe and effective in reducing the pain and other associated symptoms of painful diabetic neuropathy . PERSPECTIVE Painful diabetic peripheral neuropathy is a challenging neuropathic pain syndrome . This r and omized controlled trial demonstrates that pregabalin , a new drug that interacts with the alpha2-delta protein subunit of the voltage-gated calcium channel , is an efficacious and safe treatment for the pain of this condition UNLABELLED The efficacy and tolerability of oral lacosamide ( 200 , 400 , and 600 mg/day ) was evaluated in patients with painful diabetic neuropathy in a double-blind , r and omized , placebo-controlled trial . The primary target dose to be confirmed was lacosamide 400 mg/day . Efficacy was assessed by changes in pain scale scores from baseline , with changes over the last 4 weeks of the 12-week maintenance period regarded as the primary endpoint . Endpoint reductions in mean pain score were higher with all doses of lacosamide , reaching the level of significance with 400 mg/day ( P = .05 ) . Over the treatment period ( titration + maintenance ) , pain relief was significantly higher than placebo with lacosamide 400 ( P = .02 ) and 600 mg/day ( P = .03 ) . Lacosamide had an early-onset effect with significant reductions over placebo during the titration period . Nonparametric and mixed-model analysis approaches gave similar results , supporting significant efficacy at 400 mg/day . Secondary criteria such as Patient 's Global Impression of Change , responder rates , and pain-free days provided additional support . Adverse events included dizziness , nausea , and headache . Incidence of cognitive and behavioral adverse events was low . This trial suggests that lacosamide has beneficial effects and may be a suitable treatment option for patients with diabetic neuropathic pain . PERSPECTIVE This study presents efficacy and safety results of a phase 3 , double-blind , placebo-controlled trial of the anticonvulsant drug lacosamide in patients with painful diabetic neuropathy . Lacosamide treatment at a dose of 400 mg/day reduced diabetic neuropathic pain with a favorable safety and tolerability profile that may be suitable for patients with diabetes Sixteen of nineteen patients completed a r and omised double-blind crossover trial to assess the effect of oral mexiletine ( 10 mg/kg bodyweight daily ) on the symptoms and signs of chronic painful diabetic neuropathy . The median age of the sixteen patients was 50 years ( range 30 - 64 ) . Assessment with a five-item clinical symptom scale showed significant improvement during the mexiletine phase compared with the placebo phase . Pain was reduced during mexiletine but not during placebo , as assessed by a visual analogue rating scale . Mexiletine treatment had no effect on tendon reflexes , vibration threshold levels , beat-to-beat variation in heart rate during deep breathing , and postural blood pressure response . Mild side-effects were seen in three of the sixteen patients during mexiletine treatment OBJECTIVE : To evaluate the efficacy and safety of mexiletine in the symptomatic treatment of diabetic peripheral neuropathy ( DPN ) . METHODS : In this prospect i ve , double-blind study , 29 patients were r and omized to receive mexiletine 600 mg/d or matching placebo for 3 weeks . A four-item symptom score ( FIS ) , which rated pain , dysesthesias , paresthesias , and nightly exacerbations of symptoms , and a 100-mm visual analog scale ( VAS ) , which rated pain intensity , were completed by patients before and after treatment . At the end of treatment independent patient and investigator global assessment s were made . Patients reported adverse effects after 1 and 3 weeks of treatment . RESULTS : Treatment groups were similar at baseline . The difference between the median changes in FIS scores ( mexiletine = 5.5 , placebo = 2 ) was not statistically significant . Overall symptom response was similar in both treatment groups as demonstrated by both global assessment s ( p = 0.19 ) . The mean change in VAS score from baseline to posttreatment was determined for both groups and the difference between these mean scores was 16.5 mm ( 95 % CI , −7.1 to 40.2 mm ) ( p = 0.16 ) . Inadequate statistical power ( 1 — β = 0.40 ) may have result ed from small sample size , small magnitude of effect , or variability in the measured effect . Adverse effects were more common in the mexiletine group , though not statistically significant . One patient receiving mexiletine was hospitalized for palpitations . CONCLUSIONS : Because of conflicting reports of mexiletine 's efficacy in the treatment of symptomatic DPN , this drug should be reserved for patients unresponsive or intolerant to st and ard therapy , without evidence of heart disease , and with sensations of burning , heat , formication , or stabbing pain OBJECTIVE To study the effectiveness and safety aspects of sodium valproate in the management of painful neuropathy in patients of type 2 diabetes mellitus . MATERIAL AND METHODS A r and omized double-blind placebo controlled trial of sodium valproate was done in type 2 diabetic patients to assess its efficacy and safety in the management of painful neuropathy . We screened 60 patients but eight patients could not complete the study ; hence , the present study was done on 52 patients . Each patient was assessed by clinical examination , pain score by short form of the McGill pain question naire ( SF-MPQ ) and electrophysiological examination , which included motor and sensory nerve conduction velocity , amplitude and H-reflex initially and at the end of 1 month of treatment . RESULTS Significant improvement was noticed in the pain score of patients receiving sodium valproate in comparison to patients receiving placebo at the end of 1 month ( P < 0.05 ) . The changes in electrophysiological data were not significant . The drug was well tolerated by all patients except one who developed a raised aspartate transaminase (AST)/alanine transaminase ( ALT ) level after 15 days of treatment . CONCLUSION Sodium valproate is a well-tolerated drug and provides significant subjective improvement in painful diabetic neuropathy . These data provide a basis for future trials of longer duration in a larger group of patients BACKGROUND Various drugs are effective in the management of painful diabetic neuropathy , but none is completely satisfactory . We previously found sodium valproate to be effective and safe in a short-term study . AIM To test the effectiveness and safety of sodium valproate in the management of painful diabetic neuropathy over 3 months . DESIGN R and omized double-blind placebo-controlled study . METHODS Consecutive attending patients with type 2 diabetes mellitus with painful neuropathy were asked to participate in the trial : 48 agreed . Five were excluded : three with HbA(1c ) > 11 , one with too low a pain level and one who withdrew consent . The remaining 43 were given either drug ( group A ) or placebo ( group B ) . Each patient was assessed clinical ly . Quantitative assessment of pain was done by McGill Pain Question naire , Visual Analogue Score and Present Pain Intensity , at the beginning of the study , after 1 month and after 3 months . Motor and sensory nerve conduction velocities were measured initially and after 3 months . Liver function tests and other adverse drug-related effects were assessed periodically . RESULTS Of the 43 patients , four dropped out : one in group A and three in group B. There was significant improvement in pain score in group A , compared to group B , at 3 months ( p < 0.001 ) . Changes in electrophysiological data were not significant . The drug was well-tolerated by all patients , except one , who had raised serum AST and ALT levels after 1 month of treatment , and whose treatment was discontinued . DISCUSSION Sodium valproate is well-tolerated , and provides significant subjective improvement in painful diabetic neuropathy Abstract To assess the efficacy and tolerability of lamotrigine in pain associated with diabetic neuropathy , two replicate r and omized , double‐blind , placebo‐controlled studies were conducted . Patients ( n = 360 per study ) with painful diabetic neuropathy were r and omized to receive lamotrigine 200 , 300 , or 400 mg daily or placebo during the 19‐week treatment phase , including a 7‐week dose‐escalation phase and a 12‐week , fixed‐dose maintenance phase . The mean reduction in pain‐intensity score from baseline to week 19 ( primary endpoint ) was greater ( p ⩽ 0.05 ) in patients receiving lamotrigine 400 mg than placebo in Study 2 ( observed scores , −2.7 versus −1.6 on a 0‐ to 10‐point scale ) . This finding was not replicated in Study 1 . Lamotrigine 200 and 300 mg did not significantly differ from placebo at week 19 in either study . Lamotrigine 300 and 400 mg were only occasionally more effective than placebo for secondary efficacy endpoints . The 200‐mg dose did not separate from placebo . In a post hoc analysis of pooled data including only patients who reached their target dose , lamotrigine 400 mg conferred greater ( p ⩽ 0.05 ) mean reduction in pain‐intensity score from baseline to week 19 than placebo ( −2.5 for 300 mg and −2.7 for 400 mg versus −2.0 for placebo ) . Adverse events were reported in 71–82 % of lamotrigine‐treated patients compared with 63–70 % of placebo‐treated patients . The most common adverse events with lamotrigine were headache and rash . Compared with placebo , lamotrigine ( 300 and 400 mg daily ) was inconsistently effective for pain associated with diabetic neuropathy but was generally safe and well tolerated Objective : Pregabalin , an alpha2-delta lig and with analgesic , anxiolytic , and anticonvulsant activity , has been evaluated for treatment of neuropathic pain . The authors assessed the efficacy and tolerability of pregabalin ( 75 , 300 , 600 mg/day ) vs placebo in patients with diabetic peripheral neuropathy ( DPN ) . Methods : Patients with a 1- to 5-year history of DPN and average weekly pain score of ≥4 on an 11-point numeric pain-rating scale were enrolled in a 5-week , double-blind , multicenter , placebo-controlled study . Patients ( n = 338 ) were r and omized to receive one of three doses of pregabalin or placebo TID . Pregabalin 600 mg/day was titrated over 6 days ; lower doses were initiated on day 1 . Results : Patients in the 300- and 600-mg/day pregabalin groups showed improvements in endpoint mean pain score ( primary efficacy measure ) vs placebo ( p = 0.0001 ) . Improvements were also seen in weekly pain score , sleep interference score , patient global impression of change , clinical global impression of change , SF-McGill Pain Question naire , and multiple domains of the SF-36 Health Survey . Improvements in pain and sleep were seen as early as week 1 and were sustained throughout the 5 weeks . Responders ( patients with ≥50 % reduction in pain compared to baseline ) were 46 % ( 300 mg/day ) , 48 % ( 600 mg/day ) , and 18 % ( placebo ) . Pregabalin was well tolerated with a low discontinuation rate . The most common adverse events were dizziness and somnolence . Conclusions : In patients with diabetic peripheral neuropathy , pregabalin demonstrated early and sustained improvement in pain and a beneficial effect on sleep , which were confirmed by positive patient global impression . Pregabalin was well tolerated at all doses Seven published , r and omized , placebo-controlled clinical trials with pregabalin have shown robust efficacy for relief of neuropathic pain from DPN and PHN . An investigation of the efficacy and safety of twice daily pregabalin enrolled 395 adults with painful DPN for > or = 1 year in a 12-week , double-blind , placebo-controlled trial . Patients were r and omized to placebo , 150 , 300 , or 600 mg/day pregabalin ( n = 96 , 99 , 99 , and 101 ) . Primary efficacy measure was change from baseline in endpoint mean pain score from patients ' daily pain diaries . Secondary efficacy measures included pain-related sleep-interference scores , Patient and Clinical Global Impressions of Change ( PGIC , CGIC ) , and the EuroQOL Health Utilities Index ( EQ-5D ) . Statistically significant reduction in pain was observed in patients receiving pregabalin 600 mg/day , and 46 % of patients treated with 600 mg/day pregabalin reported > or = 50 % improvement in mean pain scores from baseline ( vs 30 % of placebo patients , p = 0.036 ) . Number needed to treat to achieve such response was 6.3 . Pregabalin 600 mg/day was significantly superior to placebo in improving pain-related sleep-interference scores ( p = 0.003 ) , PGIC ( p = 0.021 ) , and CGIC ( p = 0.009 ) . ( Neither pregabalin 150 nor 300 mg/day separated from placebo on these measures , largely because of an atypically large placebo response in one country representing 42 % of patients . ) All pregabalin dosages were superior to placebo in improving EQ-5D utility scores ( all p > or = 0.0263 vs placebo ) . Pregabalin was well tolerated at all dosages ; adverse events were generally mild to moderate . Number needed to harm ( discontinuation because of adverse events ) was 10.3 for pregabalin 600 mg/day Objective To evaluate the safety and efficacy of gabapentin and venlafaxine in the treatment of painful diabetic neuropathy in patients whose pain did not improve with gabapentin monotherapy . Methods ( 1 ) A r and omized , double-blind , placebo-controlled , 8-week clinical trial comparing gabapentin versus placebo to define a patient population whose pain did not improve with monotherapy ; ( 2 ) a second 8-week trial comparing gabapentin plus venlafaxine with gabapentin plus placebo ; ( 3 ) a third uncontrolled 8-week trial of patients who did not improve on gabapentin monotherapy and then received venlafaxine in addition to gabapentin . Results ( 1 ) Gabapentin-treated patients showed statistically significant improvement in pain reduction as well as improvement in quality of life and mood disturbance when compared with placebo-treated patients ; ( 2 ) patients who received gabapentin plus venlafaxine showed significant improvement in pain reduction , mood disturbance , and quality of life when compared with patients treated with gabapentin plus placebo ; ( 3 ) patients who received gabapentin plus venlafaxine showed significant improvement in pain reduction , mood disturbance , and quality of life . Conclusions ( 1 ) Gabapentin is efficacious in the treatment of painful diabetic neuropathy ; ( 2 ) and ( 3 ) in patients who do not respond to gabapentin monotherapy , the addition of venlafaxine is also efficacious Objective : To study the efficacy of lamotrigine in relieving the pain associated with diabetic neuropathy . Methods : The authors r and omly assigned 59 patients to receive either lamotrigine ( titrated from 25 to 400 mg/day ) or placebo over a 6-week period . Primary outcome measure was self-recording of pain intensity twice daily with a 0 to 10 numerical pain scale ( NPS ) . Secondary efficacy measures included daily consumption of rescue analgesics , the McGill Pain Question naire ( MPQ ) , the Beck Depression Inventory ( BDI ) , the Pain Disability Index ( PDI ) , and global assessment of efficacy and tolerability . Results : Twenty-four of 29 patients ( 83 % ) receiving lamotrigine and 22 of 30 ( 73 % ) patients receiving placebo completed the study . Daily NPS in the lamotrigine-treated group was reduced from 6.4 ± 0.1 to 4.2 ± 0.1 and in the control group from 6.5 ± 0.1 to 5.3 ± 0.1 ( p < 0.001 for lamotrigine doses of 200 , 300 , and 400 mg ) . The results of the MPQ , PDI , and BDI remained unchanged in both groups . The global assessment of efficacy favored lamotrigine treatment over placebo , and the adverse events profile was similar in both groups . Conclusions : Lamotrigine is effective and safe in relieving the pain associated with diabetic neuropathy Objectives : In controlled trials of analgesics for the treatment of neuropathic pain , the primary outcome variable is most often a measure of global pain intensity . However , because neuropathic pain is associated with a variety of pain sensations , the effects of analgesic treatments on different sensations could go undetected if specific pain qualities are not assessed . This study sought to evaluate the utility of assessing the multiple components of neuropathic pain in an analgesic clinical trial . Methods : One hundred fifty-nine subjects with diabetes-related foot pain were r and omly assigned to receive an active analgesic ( controlled-release oxycodone ) or matching placebo for 6 weeks . A multidimensional measure of neuropathic pain , the Neuropathic Pain Scale ( NPS ) , was administered before , during , and after study treatment . Results : Relative to placebo , the opioid analgesic produced statistically significantly greater decreases in global pain intensity , pain unpleasantness , and sharp , dull , and deep pain sensations . Responder analyses indicated a higher rate of responding to the opioid condition , relative to placebo , for intense , unpleasant , deep , and surface pain . The opioid analgesic did not significantly reduce hot , cold , itchy , or sensitive pain sensations compared with placebo in either analysis . Conclusions : These findings support the utility of the NPS for characterizing the multidimensional nature of the neuropathic pain experience and for detecting changes in neuropathic pain with treatment & NA ; A r and omized , double‐blind , placebo‐controlled , parallel‐group , multicenter , 8‐week trial ( with subsequent open‐label phase ) evaluated the effectiveness of pregabalin in alleviating pain associated with diabetic peripheral neuropathy ( DPN ) . For enrollment , patients must have had at baseline : 1‐ to 5‐year history of DPN pain ; pain score ≥40 mm ( Short‐Form McGill Pain Question naire [ SF‐MPQ ] visual analogue scale ) ; average daily pain score of ≥4 ( 11‐point numerical pain rating scale [ 0=no pain , 10=worst possible pain ] ) . One hundred forty‐six ( 146 ) patients were r and omized to receive placebo ( n=70 ) or pregabalin 300 mg/day ( n=76 ) . Primary efficacy measure was endpoint mean pain score from daily patient diaries ( 11‐point numerical pain rating scale ) . Secondary measures included SF‐MPQ scores ; sleep interference scores ; Patient and Clinical Global Impression of Change ( PGIC and CGIC ) ; Short Form‐36 ( SF‐36 ) Health Survey scores ; and Profile of Mood States ( POMS ) scores . Safety assessment included incidence and intensity of adverse events , physical and neurological examinations , and laboratory evaluations . Pregabalin produced significant improvements versus placebo for mean pain scores ( P<0.0001 ) ; mean sleep interference scores ( P<0.0001 ) ; total SF‐MPQ score ( P<0.01 ) ; SF‐36 Bodily Pain subscale ( P<0.03 ) ; PGIC ( P=0.001 ) ; and Total Mood Disturbance and Tension – Anxiety components of POMS ( P<0.03 ) . Pain relief and improved sleep began during week 1 and remained significant throughout the study ( P<0.01 ) . Pregabalin was well tolerated despite a greater incidence of dizziness and somnolence than placebo . Most adverse events were mild to moderate and did not result in withdrawal . Pregabalin was safe and effective in decreasing pain associated with DPN , and also improved mood , sleep disturbance , and quality of life OBJECTIVE Assess efficacy and safety of duloxetine , a selective serotonin and norepinephrine reuptake inhibitor , on the reduction of pain severity , in patients with diabetic peripheral neuropathic pain ( DPNP ) . METHODS This was a multicenter , parallel , double-blind , r and omized , placebo-controlled trial that enrolled 348 patients with pain due to peripheral neuropathy caused by type 1 or type 2 diabetes mellitus . Patients ( N = 116 per group ) were r and omly assigned to receive duloxetine 60 mg once daily ( QD ) , duloxetine 60 mg twice daily ( BID ) , or placebo , for 12 weeks . The primary outcome measure was the weekly mean score of 24-hour average pain severity evaluated on an 11-point Likert scale . Secondary outcome measures and safety were evaluated . RESULTS Compared with placebo-treated patients , both duloxetine-treated groups improved significantly more ( P < 0.001 ) on the 24-hour average pain score . Duloxetine demonstrated superiority to placebo in all secondary analyses of the primary efficacy measure . A significant treatment effect for duloxetine was observed in most secondary measures for pain . Discontinuations due to adverse events were more frequent in the duloxetine 60 mg BID- ( 12.1 % ) versus the placebo- ( 2.6 % ) treated group . Duloxetine showed no adverse effects on diabetic control , and both doses were safely administered and well tolerated . CONCLUSIONS In this clinical trial , duloxetine 60 mg QD and duloxetine 60 mg BID were effective and safe in the management of DPNP OBJECTIVE To investigate the efficacy and safety of mexiletine in the treatment of painful diabetic neuropathy . RESEARCH DESIGN AND METHODS A total of 216 insulin-treated diabetes patients with painful diabetic neuropathy were r and omly allocated to three dosages of mexiletine or placebo . The Visual Analog Scale ( VAS ) for pain/discomfort was scored each day during daytime and nighttime , and sleeping disturbances were also recorded by the patients . Plasma levels of mexiletine and 24-h electrocardiogram ( ECG ) mapping were assessed before and during the 3-week study period . RESULTS A significant reduction in sleep disturbances and pain during nighttime was observed in the group of patients taking the highest dosages ( 675 mg/day ) of mexiletine compared with the other groups . No significant correlation was found between plasma concentration of mexiletine and the therapeutic effect or adverse events . No serious adverse events were seen . The 24-h ECG mapping did not disclose onset of significant arrhythmias in any patient . CONCLUSIONS Mexiletine in a dosage of 675 mg daily can reduce pain caused by diabetic neuropathy , and the effect of this drug appears to have a rapid onset BACKGROUND Duloxetine , a selective serotonin and noradrenaline reuptake inhibitor , has been shown to be effective in treatment of diabetic peripheral neuropathic pain and approved for the management of patients with diabetic peripheral neuropathic pain ( DPNP ) in the United States , European Union , and many other countries . This study assessed the efficacy and safety of duloxetine in Chinese patients with diabetic peripheral neuropathic pain . METHODS This double-blind , r and omized , placebo-controlled , flexible-dose study treated adult patients with diabetic peripheral neuropathic pain and baseline Brief Pain Inventory ( BPI ) 24-hour average pain severity ratings ≥ 4 with duloxetine 60 mg to 120 mg once daily or placebo for 12 weeks . Dose adjustments of duloxetine or matching placebo were based upon investigator 's judgment of clinical response . Change from baseline to endpoint in BPI average pain was the primary efficacy outcome . Secondary outcome measures included BPI-severity and -Interference , Patient Global Impression of Improvement , Clinical Global Impressions of Severity , EuroQol : 5 Dimensions , Athens Insomnia Scale , and safety measures . RESULTS Of 215 patients r and omized , 88.4 % and 82.1 % of patients in placebo and duloxetine groups , respectively , completed the study . Mean change from baseline to endpoint in BPI average pain was not statistically different between the treatment groups ( P = 0.124 ) . Duloxetine- treated patients showed significantly greater pain reduction compared with those in placebo group at weeks 1 , 2 , and 4 ( P = 0.004 , P = 0.009 , and P = 0.006 , respectively ) , but not at weeks 8 ( P = 0.125 ) and 12 ( P = 0.107 ) . Duloxetine-treated patients experienced statistically significant improvement in Patient Global Impression of Improvement , Clinical Global Impression of Severity , area under the curve for pain relief , BPI-severity pain right now , and BPI-interference walking ability . Patients treated with duloxetine 120 mg once daily showed significantly greater pain reduction on the Brief Pain Inventory average pain score relative to placebo . Duloxetine-treated patients reported nausea , somnolence , anorexia , and dysuria significantly more than placebo . CONCLUSIONS Although the primary study endpoint was not achieved , the overall observed response pattern suggests the efficacy of duloxetine in the treatment of Chinese patients with diabetic peripheral neuropathic pain . The safety profile for duloxetine is similar to that reported in other global trials Summary The effect of imipramine on symptomatic peripheral diabetic neuropathy in 9 patients was examined in a double-blind cross-over study against placebo . The dose of imipramine was adjusted to yield optimal plasma levels of imipramine plus desipramine of 300–750 nM.Imipramine had a clear benificial effect on the symptoms of the neuropathy , whereas no changes in a range of neurophysiological measurements was detected . Despite some adverse effects , especially of an anticholinergic nature , the patients generally preferred imipramine to placebo Background : Serotonin ( 5-HT ) and norepinephrine ( NE ) are involved in pain modulation via descending inhibitory pathways in the brain and spinal cord . Objective : To assess the efficacy of duloxetine , a dual reuptake inhibitor of 5-HT and NE , on the reduction of pain severity , as well as secondary outcome measures in patients with diabetic peripheral neuropathic pain ( DPNP ) . Methods : In this double-blind study , patients with DPNP and without comorbid depression were r and omly assigned to treatment with duloxetine 60 mg once daily ( QD ) , duloxetine 60 mg twice daily ( BID ) , or placebo for 12 weeks . The primary outcome measure was the weekly mean score of 24-hour average pain severity on the 11-point Likert scale . Secondary measures and health outcome measures were also assessed . Results : Duloxetine 60 mg QD and 60 mg BID demonstrated improvement in the management of DPNP and showed rapid onset of action , with separation from placebo beginning at week 1 on the 24-hour average pain severity score . For all secondary measures for pain ( except allodynia ) , mean changes showed an advantage of duloxetine over placebo , with no significant difference between 60 mg QD and 60 mg BID . Clinical Global Impression of Severity and Patient ’s Global Impression of Improvement evaluation demonstrated greater improvement on duloxetine- vs placebo-treated patients . Duloxetine showed no notable interference on diabetic controls , and both doses were safely administered . Conclusions : This study confirms previous findings that duloxetine at 60 mg QD and 60 mg BID is effective and safe in the management of diabetic peripheral neuropathic pain In a double‐blind placebo‐controlled trial the effect of Sorbinil ( 250 mg daily ) on diabetic neuropathy was examined . After a 2‐month run‐in placebo period ( with three major assessment s ) 21 patients were r and omized to Sorbinil and 10 to placebo , and all were studied for a further 12 months with neurophysiological measurements at 3‐month intervals of nerve conduction velocity in multiple nerves , autonomic function tests , vibration thresholds as well as clinical examination and an extensive self‐ assessment of symptoms . Two subjects on Sorbinil treatment developed a hypersensitivity reaction and were withdrawn . Metabolic control and severity of neuropathy was not significantly different between groups . There were no changes in symptoms as judged by self‐ assessment scores . No patient entered the trial with neuropathic ulcers but ulceration developed in 4 patients during Sorbinil treatment and in 1 of the placebo group . No beneficial effect of Sorbinil was demonstrated on either the clinical manifestation or on the neurophysiological measurements made in these neuropathic diabetic patients over 12 months of treatment Anticonvulsant drugs are commonly used in neuropathic pain . There is anecdotal evidence of an analgesic effect of the anticonvulsant lamotrigine in neuropathic pain , but this is verified by few r and omised controlled trials . This r and omised , double-blind , placebo controlled trial of examined the effect of lamotrigine in a dose increasing to 200 mg in 100 patients with neuropathic pain . Eight patients failed to attend for review , 18 withdrew early and 74 provided results . There was no statistical difference in age , sex or duration pre-treatment pain in the two groups . Total pain , the character of the pain , sensitivity , numbness , paraesthesia , sleep , mobility , mood , quality of life and analgesic consumption were measured . There was a correlation between burning and numbness ( P<0 . 01 ) , shooting pain and total pain ( P<0.01 ) and between analgesic consumption and mobility ( P<0.05 ) throughout the study period . There were no correlation between any other measured variable . There was no significant change in any variable measured over the eight week period when lamotrigine was used . It is concluded that at the dose used and using the dose escalation regime described , lamotrigine had no effect on either pain , component pain symptoms or quality of life variables OBJECTIVE To compare amitriptyline and maprotiline in the treatment of painful polyneuropathy in diabetics and nondiabetics . DESIGN A double-blind , crossover trial of treatment with amitriptyline , maprotiline , and placebo . Treatment was given in r and omized order for periods of 4 weeks . Each period was separated by a 1-week washout . The final dose was 75 mg/day for both amitriptyline and maprotiline . PATIENTS Thirty-seven patients with diabetic and nondiabetic painful polyneuropathy . OUTCOME MEASURES The treatment effects were assessed by daily ratings of pain intensity on a 10-step verbal scale ( 0 = no pain and 10 = worst thinkable pain ) and at the end of each treatment period by a global rating of the analgesic effect on a 5-step verbal scale ( pain relief scale ) . For the assessment of depression , the Comprehensive Psychopathological Rating Scale ( CPRS ) was used . RESULTS Using the global assessment of pain relief at the end of each treatment period , 22 of 33 patients reported reduced pain on amitriptyline treatment compared with 14 of 33 patients on maprotiline treatment and 8 patients on placebo treatment ( p < .0001 and p < .05 for amitriptyline and maprotiline , respectively , against placebo ) . Amitriptyline was slightly better than maprotiline ( p < .05 ) [ tested by repeated measures analysis of variance ( ANOVA ) ] . The order in which treatments occurred and the diagnosis of diabetes or nondiabetes did not have any significant effect on the global rating of pain relief . The mean values of the daily ratings of pain intensity showed that pain was more severe in the evenings than in the mornings and that diabetic patients reported worse pain than nondiabetics at baseline . The mean values of pain reduction as assessed with the 10-step verbal scale during the 4th week of treatment showed that amitriptyline and maprotiline were significantly better than placebo in relieving the pain ( p < .0001 and p < .01 , respectively , post hoc test according to Scheffé ) . However , there was no significant difference between the pain reduction of amitriptyline compared with maprotiline when assessing pain reduction with the 10-step verbal scale during the 4th treatment week . Nor was there a significant difference between diabetics and nondiabetics with regard to the effect of the drugs . The clinical effect was not significantly correlated to plasma concentration of either amitriptyline and its active metabolite nortriptyline or maprotiline in the global or daily assessment s. The effect of treatment was not correlated to any particular pain quality nor to the intensity of pain . Depression was noted in three patients who completed the medication trial , but the effect of treatment of pain and depression did not clearly correlate . The adverse side effects of amitriptyline and maprotiline were common , and in 5 patients the medication had to be discontinued because of severe side effects . CONCLUSION From the present results and the literature , it is concluded that tricyclic antidepressants with a pharmacologic profile similar to amitriptyline are the most effective drugs in the treatment of polyneuropathy pain in both diabetic and nondiabetic patients The effect of treatment with the aldose reductase inhibitor , Ponalrestat * , was studied in 30 diabetic patients with established peripheral and autonomic neuropathy . After a 4-week placebo run-in phase , patients were r and omised to 16 weeks active or placebo treatment in a double-blind , parallel-group trial . Changes in neuropathy were assessed using vibration perception thresholds , heart rate responses to deep breathing , pulse and blood pressure changes on st and ing and the patients ' subjective scoring of peripheral and autonomic neuropathic symptoms . In addition , circulating neuropeptides and the responses of circulating gut peptides to an oral glucose tolerance test were studied . There was a significant improvement in the mean vibration perception threshold over the four sites studied in the ponalrestat treated group . There were no significant changes in the other indices of neuropathy , including heart rate variability , blood pressure responses to st and ing or symptom scores , though there were trends towards improvement . There were no significant changes in the levels of the circulating neuropeptides or in the responses of the circulating gut peptides to oral glucose tolerance test . No clinical ly important side-effects attributable to ponalrestat were observed . We conclude that ponalrestat improves some of the parameters of diabetic neuropathy and is likely to be of value in the treatment of this condition & NA ; Although amitriptyline relieves pain in many patients with painful diabetic neuropathy , side effects often preclude effective treatment . Desipramine has the least anticholinergic and sedative effects of the first generation tricyclic antidepressants . We compared a 6 week course of desipramine ( mean dose , 201 mg/day ) to active placebo in 20 patients with painful diabetic neuropathy in a double‐blind crossover trial . Pain relief with desipramine was statistically significant in weeks 5 and 6 . Eleven patients reported at least moderate relief with desipramine , compared to 2 with placebo . Pain relief tended to be greater in depressed patients , but relief was also observed in patients who did not show an antidepressant effect . We conclude that desipramine relieves pain in many patients with painful diabetic neuropathy , offering an alternative for patients unable to tolerate amitriptyline . Blockade of norepinephrine reuptake , an action shared by desipramine , amitriptyline , and other antidepressants proven effective in neuropathic pain , may mediate this analgesic effect & NA ; To evaluate the efficacy and safety of 6 weeks of venlafaxine extended‐release ( ER ) ( 75 mg and 150–225 mg ) treatment in patients with painful diabetic neuropathy . This multicenter , double‐blind , r and omized , placebo‐controlled study included 244 adult out patients with metabolically stable type 1 or 2 diabetes with painful diabetic neuropathy . Primary efficacy measures were scores on the daily 100 mm Visual Analog Pain Intensity ( VAS‐PI ) and Pain Relief ( VAS‐PR ) scales . Secondary efficacy measures included the Clinical Global Impressions – Severity of Illness and the Clinical Global Impressions – Improvement , Patient Global Rating of Pain Relief , and percentage of patients achieving 50 % reduction in pain intensity . Baseline pain intensity was 68.7 mm ( moderately severe ) . At week 6 , the percentage reduction from baseline in VAS‐PI was 27 % ( placebo ) , 32 % ( 75 mg ) , and 50 % ( 150–225 mg ; P<0.001 vs placebo ) . Mean VAS‐PR scores in the 150–225 mg group were significantly greater than placebo at week 6 ( 44 vs 60 mm ; P<0.001 ) . The number needed to treat ( NNT ) for 50 % pain intensity reduction with venlafaxine ER 150–225 mg was 4.5 at week 6 . Nausea and somnolence were the most common treatment‐emergent adverse events . Seven patients on venlafaxine had clinical ly important ECG changes during treatment . Venlafaxine ER appears effective and safe in relieving pain associated with diabetic neuropathy . NNT values for higher dose venlafaxine ER are comparable to those of tricyclic antidepressants and the anticonvulsant gabapentin Abstract Objective : Painful diabetic peripheral neuropathy ( DPN ) may not be adequately managed with available therapeutic options . This phase III , r and omized-withdrawal , placebo-controlled trial evaluated the safety and efficacy of tapentadol extended release ( ER ) for relieving painful DPN . Research design and methods : Patients ( n = 588 ) with at least a 3-month history of opioid and /or non-opioid analgesic use for DPN , dissatisfaction with current treatment , and an average pain intensity score of at least 5 on an 11-point numerical rating scale ( NRS ; 0 = ‘ no pain , ’ 10 = ‘ pain as bad as you can imagine ’ ) were titrated to an optimal dose of tapentadol ER ( 100–250 mg bid ) during a 3-week open-label phase . Subsequently , patients ( n = 395 ) with at least a 1-point reduction in pain intensity were r and omized 1:1 to receive placebo or the optimal fixed dose of tapentadol ER determined during the open-label phase for a 12-week double-blind phase . Clinical trial registration : NCT00455520 . Main outcome measures : The primary efficacy outcome was the change in average pain intensity from r and omization , determined by twice-daily NRS measurements . Safety was assessed throughout the study . Results : The least-squares mean difference between groups in the change in average pain intensity from the start of double-blind treatment to week 12 was −1.3 ( 95 % confidence interval , −1.70 to −0.92 ; p < 0.001 , tapentadol ER vs. placebo ) . A total of 60.5 % ( 356/588 ) of patients reported at least a 30 % improvement in pain intensity from the start to the end of the open-label titration phase ; of the patients who were r and omized to tapentadol ER , 53.6 % ( 105/196 ) reported at least a 30 % improvement from pre-titration to week 12 of the double-blind phase . The most common treatment-emergent adverse events that occurred during double-blind treatment with tapentadol ER included nausea , anxiety , diarrhea , and dizziness . Potential limitations of this study are related to the enriched enrollment r and omized-withdrawal trial design , which may result in a more homogeneous patient population during double-blind treatment and may present a risk of unblinding because of changes in side effects from the open-label to the double-blind phase . Conclusions : Compared with placebo , tapentadol ER 100–250 mg bid provided a statistically significant difference in the maintenance of a clinical ly important improvement in pain12 and was well-tolerated by patients with painful DPN & NA ; The effect of the selective serotonin reuptake inhibitor paroxetine on diabetic neuropathy symptoms was examined in comparison to imipramine and placebo in a r and omised , double‐blind , cross‐over study . Paroxetine was given as a fixed dose of 40 mg/day , while the dose of imipramine was adjusted to yield optimal plasma levels of imipramine plus desipramine of 400–600 nM. Paroxetine significantly reduced the symptoms of neuropathy as measured by both observer‐ and self‐rating , but was somewhat less effective than imipramine . However , patients showing a weaker response to paroxetine than to imipramine had lower plasma concentrations of paroxetine than patients with similar response to the 2 drugs . On imipramine 5 patients dropped out because of intolerable side effects and 4 of 19 patients completing the study reported withdrawal symptoms after discontinuing imipramine . On paroxetine no patients dropped out due to side effects and no withdrawal symptoms were reported . Self‐rating showed no depressive symptoms at baseline , and no changes during the study . Neither paroxetine nor imipramine caused changes in objective measures of peripheral nerve function . In conclusion , 40 mg paroxetine/day significantly reduced the symptoms in peripheral diabetic neuropathy and it was suggested that by dose adjustment on the basis of drug level monitoring , paroxetine may become as effective as imipramine . Paroxetine was devoid of the often disturbing autonomic side effects limiting the use of imipramine in several patients & NA ; Pregabalin binds with high affinity to the alpha2‐delta subunit protein of voltage‐gated calcium channels and , thereby , reduces release of excitatory neurotransmitters . This 12‐week r and omised , double‐blind , multicentre , placebo‐controlled , parallel‐group study evaluated the efficacy and safety of pregabalin in patients with chronic postherpetic neuralgia ( PHN ) or painful diabetic peripheral neuropathy ( DPN ) . Patients were r and omised to placebo ( n=65 ) or to one of two pregabalin regimens : a flexible schedule of 150 , 300 , 450 , and 600 mg/day with weekly dose escalation based on patients ' individual responses and tolerability ( n=141 ) or a fixed schedule of 300 mg/day for 1 week followed by 600 mg/day for 11 weeks ( n=132 ) . Both flexible‐ and fixed‐dose pregabalin significantly reduced endpoint mean pain score ( primary outcome ) versus placebo ( P=0.002 , P<0.001 ) and were significantly superior to placebo in improving pain‐related sleep interference ( P<0.001 ) . The most common adverse events ( AEs ) for pregabalin‐treated patients were dizziness , peripheral oedema , weight gain ( not affecting diabetes control ) , and somnolence . These results are consistent with previous studies ' demonstrating pregabalin 's efficacy , tolerability , and safety for treatment of chronic neuropathic pain associated with DPN or PHN . Pregabalin dosing aim ed at optimal balance of efficacy and tolerability provides significant pain relief and may reduce risks for AEs and therapy discontinuation In this multicentre , placebo-controlled , 16-week trial , the efficacy and safety of oxcarbazepine monotherapy in patients with neuropathic pain of diabetic origin was evaluated . Eligible patients had a 6-month to 5-year history of neuropathic pain symptoms of diabetic origin and a pain rating of > or = 50 units on the visual analogue scale ( VAS ) . Oxcarbazepine was initiated at a dose of 300 mg/day and titrated to a maximum dose of 1800 mg/day . In total , 146 patients ( oxcarbazepine , n=69 ; placebo , n=77 ) were r and omized . After 16 weeks , oxcarbazepine-treated patients experienced a significantly larger decrease in the average change in VAS score from baseline compared with placebo ( -24.3 vs. -14.7 units , respectively ; p=0.01 ) . The reduction from baseline in mean VAS score for oxcarbazepine-treated patients was of a greater magnitude than placebo as early as week 2 ( -8.0 vs. -4.7 ; p<0.05 ) . A significantly greater proportion of oxcarbazepine-treated patients experienced a > 50 % reduction from baseline in VAS score at the end of treatment compared with placebo ( 35.2 % vs. 18.4 % , respectively ; p=0.0156 ; number needed to treat=6.0 ) . Global assessment of therapeutic effect rating was improved in more oxcarbazepine patients than placebo patients ( 48 % vs. 22 % , respectively ; p=0.0025 ) . Patients on oxcarbazepine were awakened less frequently due to pain than patients on placebo . Most adverse events were mild to moderate in severity , transient , and in line with the known tolerability profile of oxcarbazepine . These observations suggest that oxcarbazepine monotherapy , pending additional trials , may be efficacious and may provide clinical ly meaningful pain relief in patients with neuropathic pain of diabetic origin OBJECTIVE To prove the efficacy of mexiletine in painful diabetic neuropathy . RESEARCH DESIGN AND METHODS Treatment was provided in three dosages . For pain measurements , a VAS and McGill 's verbal rating scale were chosen . Ninety-five patients were included in the study . RESULTS A global assessment of the VAS among patients showed no differences between mexiletine treatment and placebo . The total evaluation ( PRIT ) of the McGill scale fell just below the level of significance . More specific exploratory evaluations of subclasses of the McGill scale , representing different degrees of pain , gave remarkable differences between mexiletine and placebo in sensory and miscellaneous items . In special subgroups , which were formed according to types and courses of complaints compiled at the beginning of this evaluation , the substantial advantages of the mexiletine treatment were shown with both the VAS and the McGill scale . CONCLUSIONS Evidence strongly indicates that , in particular , those patients with stabbing or burning pain , heat sensations , or formication will benefit most by mexiletine therapy . Concerning the dosage , a medium regimen of 450 mg/day seems to be appropriate . With an increase in the antiarryhthmic dosage level , the efficacy does not rise proportionally . Mexiletine proved to be a safe therapy with negligible side effects at the medium dose range , even < placebo ; and remarkably , no cardiovascular side effects were noted . Further studies should avoid global assessment s and pay more attention to the variety of complaints and quality of life OBJECTIVE To evaluate efficacy and safety of lacosamide compared with placebo in painful diabetic polyneuropathy . RESEARCH DESIGN AND METHODS Diabetic patients with at least moderate neuropathic pain were r and omized to placebo or lacosamide 400 ( in a slow or st and ard titration ) or 600 mg/day over 6-week titration and 12-week maintenance periods . Primary efficacy criterion was intra-individual change in average daily Numeric Pain Rating Scale score from baseline to the last 4 weeks . RESULTS For the primary end point , pain reduction was numerically but not statistically greater with lacosamide compared with placebo ( 400 mg/day , P = 0.12 ; 600 mg/day , P = 0.18 ) . Both doses were significantly more effective compared with placebo over the titration ( P = 0.03 , P = 0.006 ) , maintenance ( P = 0.01 , P = 0.005 ) , and entire treatment periods ( P = 0.03 , P = 0.02 ) . Safety profiles between titration schemes were similar . CONCLUSIONS Lacosamide reduced neuropathic pain and was well tolerated in diabetic patients , but the primary efficacy criterion was not met , possibly due to an increased placebo response over the last 4 weeks |
876 | 30,561,254 | Conclusions There is increased risk of death following application of paclitaxel-coated balloons and stents in the femoropopliteal artery of the lower limbs . | Background Several r and omized controlled trials ( RCT s ) have already shown that paclitaxel-coated balloons and stents significantly reduce the rates of vessel restenosis and target lesion revascularization after lower extremity interventions . | Purpose : To evaluate the safety and efficacy of the novel Passeo-18 Lux paclitaxel-coated balloon compared with the Passeo-18 uncoated balloon in patients with symptomatic de novo or restenotic femoropopliteal lesions . Methods : Sixty patients ( 34 men ; mean age 70.7±10.1 years ) in 5 European centers were enrolled in the BIOLUX P-I trial ( Clinical Trials.gov identifier NCT01056120 ) and r and omized 1:1 to either the paclitaxel-coated balloon or the uncoated balloon . The primary endpoint was late lumen loss at 6 months . Secondary endpoints were binary restenosis at 6 months , clinical ly driven target lesion revascularization ( TLR ) , change in ankle-brachial index and Rutherford classification , and major adverse events at 6 and 12 months . Results : At 6 months , patients treated with paclitaxel-coated balloons had a significantly lower late lumen loss ( 0.51±0.72 vs. 1.04±1.00 mm , p=0.033 ) and binary restenosis ( 11.5 % vs. 34.6 % , p=0.048 ) than the control group . Correspondingly , clinical ly driven TLR was lower in the paclitaxel-coated balloon group at 12 months [ 15.4 % vs. 41.7 % ( p=0.064 ) for the intention-to-treat population and 16.0 % vs. 52.9 % , ( p=0.020 ) for the as-treated population ] . No death and one minor amputation were observed compared with two deaths and two minor amputations in the control group . No major amputations or thrombosis were reported . Conclusion : The Passeo-18 Lux paclitaxel-coated balloon has been proven to be safe and effective in patients with femoropopliteal lesions , with superior performance outcomes compared with treatment with an uncoated balloon Background —Peripheral percutaneous transluminal angioplasty is fraught with a substantial risk of restenosis and reintervention . A drug-eluting balloon ( DEB ) based on a novel coating was compared with uncoated balloons in patients undergoing femoro-popliteal percutaneous transluminal angioplasty . Methods and Results — Patients with symptomatic femoro-popliteal atherosclerotic disease undergoing percutaneous transluminal angioplasty were r and omized to paclitaxel-coated IN.PACT Pacific or uncoated Pacific balloons . The primary end point was late lumen loss at 6 months assessed by blinded angiographic corelab quantitative analyses . Secondary end points were binary restenosis and Rutherford class change at 6 months , and target lesion revascularization plus major adverse clinical events ( major adverse events = death , target limb amputation , or target lesion revascularization ) at 6 and 12 months . Eighty-five patients ( 91 cases = interventional procedures ) were r and omized in 3 hospitals ( 44 to DEB and 47 to uncoated balloons ) . Average lesion length was 7.0±5.3 and 6.6±5.5 cm for DEB and control arm , respectively . Procedural success was obtained in all cases . Six-month quantitative angiography showed that DEB were associated with significantly lower late lumen loss ( −0.01 mm [ 95 % CI , −0.29 ; 0.26 ] versus 0.65 mm [ 0.37 ; 0.93 ] , P=0.001 ) and fewer binary restenoses ( 3 [ 8.6 % ] versus 11 [ 32.4 % ] , P=0.01 ) . This translated into a clinical ly relevant benefit with significantly fewer major adverse events for DEB versus uncoated balloons up to 12 months ( 3 [ 7.1 % ] versus 15 [ 34.9 % ] , P<0.01 ) as well as target lesion revascularizations ( 3 [ 7.1 % ] versus 12 [ 27.9 % ] , P=0.02 ) . Conclusions —Use of IN.PACT Pacific DEB is associated with significant reductions in late lumen loss and restenoses at 6 months , and re interventions after femoro-popliteal percutaneous transluminal angioplasty up to 1 year of follow-up . Clinical Trial Registration —URL http://www . clinical trials.gov . Unique identifier : NCT01083030 BACKGROUND Evidence from large , r and omized , controlled peripheral artery disease trials reporting long-term outcomes using drug-coated balloons ( DCBs ) is limited . Previously , the DCB showed favorable 1-year outcomes compared with conventional percutaneous transluminal angioplasty ( PTA ) , yet durability of the treatment effect with DCBs remains unknown . OBJECTIVES This study sought to investigate the longer-term outcomes of a paclitaxel-eluting DCB compared to PTA for femoropopliteal lesions . METHODS We enrolled 331 patients with symptomatic ( Rutherford 2 to 4 ) femoropopliteal lesions up to 18 cm in length . Patients were r and omly assigned in a 2:1 ratio to treatment with DCB or PTA . The 24-month assessment s included primary patency , freedom from clinical ly driven target lesion revascularization ( CD-TLR ) , major adverse events , and quality of life and functional outcomes as assessed by the EuroQOL-5D quality -of-life question naire , walking impairment question naire , and 6-min walk test . RESULTS At 24 months , patients treated with DCB showed significantly higher primary patency when compared with PTA ( 78.9 % vs. 50.1 % ; p < 0.001 ) . The rates of CD-TLR were 9.1 % and 28.3 % ( p < 0.001 ) for the DCB and PTA groups , respectively . The overall mortality rate in the DCB group was 8.1 % versus 0.9 % in the PTA group ( p = 0.008 ) . There were no device- or procedure-related deaths and no major amputations in either group through 24-month follow-up . The rate of vessel thrombosis was low ( 1.5 % DCB vs. 3.8 % PTA ; p = 0.243 ) , with no new events reported between 1 and 2 years . Both groups showed similar functional improvement at 2 years , although DCB patients achieved this level of function with 58 % fewer re interventions . CONCLUSIONS The 24-month outcomes from the trial demonstrate a durable and superior treatment effect of DCB versus PTA with significantly higher primary patency , lower CD-TLR , and similar functional status improvement with fewer repeat interventions . ( R and omized Trial of IN.PACT Admiral Drug Eluting Balloon vs St and ard PTA for the Treatment of SFA and Proximal Popliteal Arterial Disease [ INPACT SFA I ] ; NCT01175850 ; and IN.PACT Admiral Drug-Coated Balloon vs. St and ard Balloon Angioplasty for the Treatment of Superficial Femoral Artery [ SFA ] and Proximal Popliteal Artery [ PPA ] [ INPACT SFA II ] ; NCT01566461 ) Patients with intermittent claudication carry a high risk for cardiovascular complications . The TransAtlantic Inter-Society Consensus ( TASC ) Group estimated a five-year overall mortality of 30 % for these patients , the majority dying from cardiovascular causes . We investigated whether this evaluation is still applicable in nowadays patients . We therefore prospect ively followed 255 male patients with intermittent claudication from the CAVASIC Study during 7 years for overall mortality , vascular morbidity and mortality and local PAD outcomes . Overall mortality reached 16.1 % ( n = 41 ) . Most patients died from cancer ( n = 20 ) . Half of patients ( n = 22 ; 8.6 % ) died within the first five years . Incident cardiovascular events were observed among 70 patients ( 27.5 % ) , 54 ( 21.2 % ) during the first five years . Vascular mortality was low with 5.1 % ( n = 13 ) for the entire and 3.1 % for the first five years of follow-up . Prevalent coronary artery disease did not increase the risk to die from all or vascular causes . PAD symptoms remained stable or improved in the majority of patients ( 67 % ) . In summary , compared to TASC , the proportion of cardiovascular events did not markedly decrease over the last two decades . Vascular mortality , however , was low among our population . This indicates that nowadays patients more often survive cardiovascular events and a major number dies from cancer BACKGROUND The treatment of peripheral artery disease with percutaneous transluminal angioplasty is limited by the occurrence of vessel recoil and restenosis . Drug-coated angioplasty balloons deliver antiproliferative agents directly to the artery , potentially improving vessel patency by reducing restenosis . METHODS In this single-blind , r and omized trial conducted at 54 sites , we assigned , in a 2:1 ratio , 476 patients with symptomatic intermittent claudication or ischemic pain while at rest and angiographically significant atherosclerotic lesions to angioplasty with a paclitaxel-coated balloon or to st and ard angioplasty . The primary efficacy end point was primary patency of the target lesion at 12 months ( defined as freedom from binary restenosis or from the need for target-lesion revascularization ) . The primary safety end point was a composite of freedom from perioperative death from any cause and freedom at 12 months from limb-related death ( i.e. , death from a medical complication related to a limb ) , amputation , and reintervention . RESULTS The two groups were well matched at baseline ; 42.9 % of the patients had diabetes , and 34.7 % were current smokers . At 12 months , the rate of primary patency among patients who had undergone angioplasty with the drug-coated balloon was superior to that among patients who had undergone conventional angioplasty ( 65.2 % vs. 52.6 % , P=0.02 ) . The proportion of patients free from primary safety events was 83.9 % with the drug-coated balloon and 79.0 % with st and ard angioplasty ( P=0.005 for noninferiority ) . There were no significant between-group differences in functional outcomes or in the rates of death , amputation , thrombosis , or reintervention . CONCLUSIONS Among patients with symptomatic femoropopliteal peripheral artery disease , percutaneous transluminal angioplasty with a paclitaxel-coated balloon result ed in a rate of primary patency at 12 months that was higher than the rate with angioplasty with a st and ard balloon . The drug-coated balloon was noninferior to the st and ard balloon with respect to safety . ( Funded by Lutonix-Bard ; LEVANT 2 Clinical Trials.gov number , NCT01412541 . ) BACKGROUND There are no data available on specific causes of death from r and omized trials that have compared coronary artery bypass grafting ( CABG ) with percutaneous coronary intervention ( PCI ) . OBJECTIVES The purpose of this study was to investigate specific causes of death , and its predictors , after revascularization for complex coronary disease in patients . METHODS An independent Clinical Events Committee consisting of expert physicians who were blinded to the study treatment subclassified causes of death as cardiovascular ( cardiac and vascular ) , noncardiovascular , or undetermined according to the trial protocol . Cardiac deaths were classified as sudden cardiac , related to myocardial infa rct ion ( MI ) , and other cardiac deaths . RESULTS In the r and omized cohort , there were 97 deaths after CABG and 123 deaths after PCI during a 5-year follow-up . After CABG , 49.4 % of deaths were cardiovascular , with the greatest cause being heart failure , arrhythmia , or other causes ( 24.6 % ) , whereas after PCI , the majority of deaths were cardiovascular ( 67.5 % ) and as a result of MI ( 29.3 % ) . The cumulative incidence rates of all-cause death were not significantly different between CABG and PCI ( 11.4 % vs. 13.9 % , respectively ; p = 0.10 ) , whereas there were significant differences in terms of cardiovascular ( 5.8 % vs. 9.6 % , respectively ; p = 0.008 ) and cardiac death ( 5.3 % vs. 9.0 % , respectively ; p = 0.003 ) , which were caused primarily by a reduction in MI-related death with CABG compared with PCI ( 0.4 % vs. 4.1 % , respectively ; p < 0.0001 ) . Treatment with PCI versus CABG was an independent predictor of cardiac death ( hazard ratio : 1.55 ; 95 % confidence interval : 1.09 to 2.33 ; p = 0.045 ) . The difference in MI-related death was seen largely in patients with diabetes , 3-vessel disease , or high SYNTAX ( TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries ) trial scores . CONCLUSIONS During a 5-year follow-up , CABG in comparison with PCI was associated with a significantly reduced rate of MI-related death , which was the leading cause of death after PCI . Treatments following PCI should target reducing post-revascularization spontaneous MI . Furthermore , secondary preventive medication remains essential in reducing events post-revascularization . ( TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries [ SYNTAX ] ; NCT00114972 ) BACKGROUND Drug-eluting stents reduce restenosis in coronary arteries , but clinical trials have failed to prove their efficacy in peripheral arteries . We investigated the use of paclitaxel-coated angioplasty balloons and paclitaxel dissolved in the angiographic contrast medium during angioplasty of the leg . METHODS In a small , multicenter trial , we r and omly assigned 154 patients with stenosis or occlusion of a femoropopliteal artery to treatment with st and ard balloon catheters coated with paclitaxel , uncoated balloons with paclitaxel dissolved in the contrast medium , or uncoated balloons without paclitaxel ( control ) . The primary end point was late lumen loss at 6 months . RESULTS The mean ( + /-SD ) age of the patients was 68+/-8 years , 24 % were smokers , and 49 % had diabetes . Twenty-seven percent of the lesions were total occlusions , and 36 % were restenotic lesions . The mean lesion length was 7.4+/-6.5 cm . There were no significant differences in baseline characteristics between the groups . There were no adverse events attributable to the paclitaxel-coated balloons . At 6 months , the mean late lumen loss was 1.7+/-1.8 mm in the control group , as compared with 0.4+/-1.2 mm ( P<0.001 ) in the group treated with paclitaxel-coated balloons and 2.2+/-1.6 mm ( P=0.11 ) in the group treated with paclitaxel in the contrast medium . The rate of revascularization of target lesions at 6 months was 20 of 54 ( 37 % ) in the control group , 2 of 48 ( 4 % ) in the group treated with paclitaxel-coated balloons ( P<0.001 vs. control ) , and 15 of 52 ( 29 % ) in the group treated with paclitaxel in the contrast medium ( P=0.41 vs. control ) ; at 24 months , the rates increased to 28 of 54 ( 52 % ) , 7 of 48 ( 15 % ) , and 21 of 52 ( 40 % ) , respectively . CONCLUSIONS Use of paclitaxel-coated angioplasty balloons during percutaneous treatment of femoropopliteal disease is associated with significant reductions in late lumen loss and target-lesion revascularization . No significant benefit is seen with the use of a paclitaxel-containing contrast medium . ( Clinical Trials.gov number , NCT00156624 [ Clinical Trials.gov ] . ) IMPORTANCE Supervised exercise is recommended as a first-line treatment for intermittent claudication . Combination therapy of endovascular revascularization plus supervised exercise may be more promising but few data comparing the 2 therapies are available . OBJECTIVE To assess the effectiveness of endovascular revascularization plus supervised exercise for intermittent claudication compared with supervised exercise only . DESIGN , SETTING , AND PARTICIPANTS R and omized clinical trial of 212 patients allocated to either endovascular revascularization plus supervised exercise or supervised exercise only . Data were collected between May 17 , 2010 , and February 16 , 2013 , in the Netherl and s at 10 sites . Patients were followed up for 12 months and the data were analyzed according to the intention-to-treat principle . INTERVENTIONS A combination of endovascular revascularization ( selective stenting ) plus supervised exercise ( n = 106 ) or supervised exercise only ( n = 106 ) . MAIN OUTCOMES AND MEASURES The primary end point was the difference in maximum treadmill walking distance at 12 months between the groups . Secondary end points included treadmill pain-free walking distance , vascular quality of life ( VascuQol ) score ( 1 [ worst outcome ] to 7 [ best outcome ] ) , and 36-item Short-Form Health Survey ( SF-36 ) domain scores for physical functioning , physical role functioning , bodily pain , and general health perceptions ( 0 [ severe limitation ] to 100 [ no limitation ] ) . RESULTS Endovascular revascularization plus supervised exercise ( combination therapy ) was associated with significantly greater improvement in maximum walking distance ( from 264 m to 1501 m for an improvement of 1237 m ) compared with the supervised exercise only group ( from 285 m to 1240 m for improvement of 955 m ) ( mean difference between groups , 282 m ; 99 % CI , 60 - 505 m ) and in pain-free walking distance ( from 117 m to 1237 m for an improvement of 1120 m vs from 135 m to 847 m for improvement of 712 m , respectively ) ( mean difference , 408 m ; 99 % CI , 195 - 622 m ) . Similarly , the combination therapy group demonstrated significantly greater improvement in the disease-specific VascuQol score ( 1.34 [ 99 % CI , 1.04 - 1.64 ] in the combination therapy group vs 0.73 [ 99 % CI , 0.43 - 1.03 ] in the exercise group ; mean difference , 0.62 [ 99 % CI , 0.20 - 1.03 ] ) and in the score for the SF-36 physical functioning ( 22.4 [ 99 % CI , 16.3 - 28.5 ] vs 12.6 [ 99 % CI , 6.3 - 18.9 ] , respectively ; mean difference , 9.8 [ 99 % CI , 1.4 - 18.2 ] ) . No significant differences were found for the SF-36 domains of physical role functioning , bodily pain , and general health perceptions . CONCLUSIONS AND RELEVANCE Among patients with intermittent claudication after 1 year of follow-up , a combination therapy of endovascular revascularization followed by supervised exercise result ed in significantly greater improvement in walking distances and health-related quality -of-life scores compared with supervised exercise only . TRIAL REGISTRATION Netherl and s Trial Registry Identifier : NTR2249 Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Purpose : To assess the safety and effectiveness of the MDT-2113 ( IN.PACT Admiral ) drug-coated balloon ( DCB ) for the treatment of de novo and native artery restenotic lesions in the superficial femoral and proximal popliteal arteries vs percutaneous transluminal angioplasty ( PTA ) with an uncoated balloon in a Japanese cohort . Methods : MDT-2113 SFA Japan ( Clinical Trials.gov identifier NCT01947478 ) is an independently adjudicated , prospect i ve , r and omized , single-blinded trial that r and omized ( 2:1 ) 100 patients ( mean age 73.6±7.0 years ; 76 men ) from 11 Japanese centers to treatment with DCB ( n=68 ) or PTA ( n=32 ) . Baseline characteristics were similar between the groups , including mean lesion length ( 9.15±5.85 and 8.89±6.01 cm for the DCB and PTA groups , respectively ) . The primary effectiveness outcome was primary patency at 12 months , defined as freedom from clinical ly-driven target lesion revascularization ( CD-TLR ) and freedom from restenosis as determined by duplex ultrasonography . The safety endpoint was a composite of 30-day device- and procedure-related death and target limb major amputation and clinical ly-driven target vessel revascularization within 12 months . Results : Patients treated with DCBs exhibited superior 12-month primary patency ( 89 % ) compared to patients treated with PTA ( 48 % , p<0.001 ) . The 12-month CD-TLR rate was 3 % for DCB vs 19 % for PTA ( p=0.012 ) . There were no device- or procedure-related deaths , major amputations , or thromboses in either group . Quality -of-life measures showed sustained improvement from baseline to 12 months in both groups . Conclusion : Results from the MDT-2113 SFA Japan trial showed superior treatment effect for DCB vs PTA , with excellent patency and low CD-TLR rates . These results are consistent with other IN.PACT SFA DCB trials and demonstrate the safety and effectiveness of this DCB for the treatment of femoropopliteal lesions in this Japanese cohort Background Paclitaxel‐eluting balloon ( PEB ) angioplasty has superior efficacy compared with conventional balloon angioplasty ( BA ) for de novo lesions of superficial femoral artery ( SFA ) . Studies investigating the angiographic and clinical performance of PEB angioplasty versus BA for in‐stent restenosis of SFA are limited . We performed a r and omized trial to investigate angiographic and clinical performance of PEB versus BA for in‐stent restenosis of SFA . Methods and Results Patients with symptomatic in‐stent restenosis of SFA were r and omly assigned to either PEB or BA at 2 centers in Munich , Germany . The primary end point was the percentage diameter stenosis at 6‐ to 8‐month follow‐up angiography . Secondary end points were the rate of binary restenosis at follow‐up angiography and target lesion revascularization , target vessel thrombosis , ipsilateral amputation , bypass surgery of the affected limb , and all‐cause mortality at 24‐month follow‐up . Seventy patients were assigned to PEB ( n=36 ) or BA ( n=34 ) . Mean lesion length was 139±67 mm , and roughly one third of lesions were completely occluded at the time of the index procedure . At control angiography , the percentage diameter stenosis ( 44±33 % versus 65±33 % , P=0.01 ) and binary restenosis were significantly reduced with PEB versus BA ( 30 % versus 59 % , P=0.03 ) . At 24‐month follow‐up , PEB was associated with a significant reduction of target lesion revascularization in comparison to BA ( 19 % versus 50 % , P=0.007 ) . There was no difference with respect to other outcomes of interest . Conclusions In patients with in‐stent restenosis of SFA , a percutaneous therapy with PEB compared with BA has superior angiographic performance at 6 to 8 months and improved clinical efficacy up to 24‐month follow‐up . Clinical Trial Registration URL : http://www . clinical trials.gov . Unique identifier : NCT01083394 OBJECTIVES This study sought to compare paclitaxel-eluting balloon ( PEB ) with conventional percutaneous transluminal angioplasty ( PTA ) , followed by systematic implantation of a self-exp and ing nitinol bare-metal stent ( BMS ) in patients at risk for restenosis . BACKGROUND PTA is an effective strategy for treating atherosclerosis of the femoropopliteal axis ( FPA ) . Whereas PEB have shown advantage over uncoated balloons in the treatment of simple lesions , it is unknown whether these results are applicable to complex degrees of FPA atheroma . METHODS A total of 104 patients ( 110 FPA lesions in 110 limbs ) were r and omly assigned to either PEB + BMS or PTA + BMS . The primary endpoint was 12-month binary restenosis . Secondary endpoints were freedom from target lesion revascularization and major amputation . Post hoc subanalyses were performed for the comparison of long ( ≥100 mm ) versus short lesions and true lumen versus subintimal approach . RESULTS Mean lesion length was 94 ± 60 versus 96 ± 69 mm in the PEB + BMS and PTA + BMS groups ( p = 0.8 ) , respectively . The primary endpoint occurred in 9 ( 17 % ) versus 26 ( 47.3 % ) of lesions in the PEB + BMS and PTA + BMS groups ( p = 0.008 ) , respectively . A near-significant ( p = 0.07 ) 1-year freedom from target lesion revascularization advantage was observed in the PEB + BMS group . No major amputation occurred . No significant difference was observed according to lesion characteristics or technical approach . CONCLUSIONS Pre-dilation with PEB angioplasty prior to BMS implantation , as compared to PTA + BMS in complex FPA lesions , reduces restenosis and target lesion revascularization at 12-month follow-up . Restenosis reduction is maintained irrespective of lesion length and recanalization technique . ( Drug Eluting Balloon in Peripheral Intervention for the Superficial Femoral Artery [ DEBATE-SFA ] ; NCT01556542 ) Background — Drug-coated balloon angioplasty ( DCBA ) was shown to be superior to st and ard balloon angioplasty ( POBA ) in terms of restenosis prevention for de novo superficial femoral artery disease . For in-stent restenosis , the benefit of DCBA over POBA remains uncertain . Methods and Results — One hundred nineteen patients with superficial femoral artery in-stent restenosis and chronic limb ischemia were recruited over 34 months at 5 German clinical sites and prospect ively r and omized to either DCBA ( n=62 ) or POBA ( n=57 ) . Mean lesion length was 82.2±68.4 mm . Thirty-four ( 28.6 % ) lesions were totally occluded ; 30 ( 25.2 % ) were moderately or heavily calcified . Clinical and duplex ultrasound follow-up was conducted at 6 and 12 months . The primary end point of recurrent in-stent restenosis assessed by ultrasound at 6 months was 15.4 % ( 8 of 52 ) in the DCBA and 44.7 % ( 21 of 47 ) in the POBA group ( P=0.002 ) . Freedom from target lesion revascularization was 96.4 % versus 81.0 % ( P=0.0117 ) at 6 months and 90.8 % versus 52.6 % ( P<0.0001 ) at 12 months , respectively . At 12 months , clinical improvement by ≥1 Rutherford category without the need for target lesion revascularization was observed in 35 of 45 DCBA patients ( 77.8 % ) and 23 of 44 POBA patients ( 52.3 % ; P=0.015 ) . No major amputation was needed . Two patients in the DCBA and 3 patients in the POBA group died . No death was procedure related . Conclusions — DCBA for superficial femoral artery in-stent restenosis is associated with less recurrent restenosis and a better clinical outcome than POBA without an apparent difference in safety . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01305070 Background — The success of percutaneous intervention in peripheral arterial disease is limited by restenosis . The aim of the present pilot study was to evaluate a novel method of local drug delivery . Methods and Results — This r and omized multicenter study with blinded reading enrolled 87 patients in Rutherford class 1 to 4 with occlusion or hemodynamically relevant stenosis , restenosis , or in-stent restenosis of femoropopliteal arteries . Treatment was performed by either conventional uncoated or paclitaxel-coated balloon catheters . The primary end point was late lumen loss at 6 months . Secondary end points included restenosis rate , ankle brachial index , Rutherford class , target lesion revascularization , and tolerance up to > 18 months . Before intervention , there were no significant differences in lesion characteristics such as reference diameter ( 5.3±1.1 versus 5.2±1.0 mm ) , degree of stenosis ( 84±11 % versus 84±16 % ) , proportion of restenotic lesions ( 36 % versus 33 % ) , and mean lesion length ( 5.7 cm [ 0.8 to 22.6 cm ] versus 6.1 cm [ 0.9 to 19.3 cm ] ) between treatment groups . The 6-month follow-up angiography performed in 31 of 45 and 34 of 42 patients showed less late lumen loss in the coated balloon group ( 0.5±1.1 versus 1.0±1.1 mm ; P=0.031 ) . The number of target lesion revascularizations was lower in the paclitaxel-coated balloon group than in control subjects ( 3 of 45 versus 14 of 42 patients ; P=0.002 ) . Improvement in Rutherford class was greater in the coated balloon group ( P=0.045 ) , whereas the improvement in ankle brachial index was not different . The difference in target lesion revascularizations between treatment groups was maintained up to > 18 months . No adverse events were assessed as related to balloon coating . Conclusions — In this pilot trial , paclitaxel balloon coating caused no obvious adverse events and reduced restenosis in patients undergoing angioplasty of femoropopliteal arteries Abstract Objectives Based on a novel paclitaxel – resveratrol drug matrix , the safety and efficacy to inhibit intimal hyperplasia were studied in symptomatic claudicants with morphologically challenging lesions . Background The treatment of peripheral artery occlusive disease ( PAOD ) with percutaneous transluminal angioplasty is limited by occurrence of vessel recoil and neointimal hyperplasia . Drug-coated balloons ( DCB ) deliver drugs to the arterial wall to potentially reduce the restenosis rate . A number of paclitaxel-coated balloon technologies are available to treat peripheral lesions . Methods In this r and omized controlled trial , a total of 153 patients with symptomatic PAOD in femoro-popliteal lesions were r and omized either to DCB or plain old balloon angioplasty ( POBA ) . Results The mean lesion length was 13.2 ± 10.4 cm with target lesion total occlusions in 26.1 % of all patients ( 40/153 ) . The primary endpoint of in-lesion late lumen loss ( LLL ) at 6 months was significantly reduced in the DCB group as compared to the POBA group ( 0.35 mm CI [ 0.19 ; 0.79 mm ] vs. 0.72 mm CI [ 0.68 ; 1.22 mm ] , p = 0.006 ) . At 12 months , the TLR rate in the DCB group was significantly lower as compared to the POBA group ( 17.8 vs. 37.7 % p = 0.008 ) . The censored walking distance increase suggests a benefit for patients who underwent DCB angioplasty as compared to the st and ard POBA treatment ( 12 months 165 ± 105 vs. 94 ± 136 m , p = 0.012 ) . Conclusion The use of paclitaxel – resveratrol-matrix-coated peripheral balloon angioplasty as compared to POBA was associated with significantly reduced in-lesion LLL and reduced TLR rates . Clinical Trials.gov identifier NCT01970579 AIM The aim of the present paper was to make a report of the 12-month clinical outcomes of the DEBELLUM ( Drug-Eluting-Balloon-Evaluation-for-Lower-Limb- mUltilevel-treatMent ) r and omized trial . METHODS From September 2010 to March 2011 , 50 patients were r and omized between drug eluting balloon ( DEB , N.=25 ) and conventional angioplasty balloon ( PTA , N.=25 ) . Patients were symptomatic for claudication and critical limb ischemia , with de novo stenosis or occlusion in the femoropopliteal ( SFA ) and infrapopliteal ( BTK ) region . Only in the SFA primary stenting was allowed and postdilatation performed with DEB or PTA depending on the assigned group . RESULTS One hundred and twenty-two lesions were treated : 92 ( 75.4 % ) SFA , 30 ( 24.6 % ) BTK . Twenty ( 40 % ) patients presented multilevel concomitant femoropopliteal and infra-popliteal lesions . Late lumen loss ( LLL ) was 0.64±0.9 mm in DEB group vs. 1.81±0.1 mm in the control group ( P=0.01 ) . In non-stented segment LLL was 0.63±0.9 mm ( DEB ) vs. 1.70±0.6 mm ( PTA ) , P<0.01 . In the stent subgroup was LLL 0.65±0.2 mm ( DEB ) vs. 1.91±0.3 mm ( PTA ) , P<0.01 . In the femoropopliteal region the overall LLL was 0.61±0.8 mm for DEB vs. 1.84±0.3 mm for PTA ( P=0.02 ) . BTK the overall LLL was 0.66±0.9 mm ( DEB ) vs. 1.69±0.5 mm ( PTA ) ( P=0.03 ) . The overall TLR was 12.2 % for DEB and 35.3 % for PTA ( P<0.05 ) . Amputation rate was 4 % ( DEB ) vs. 12 % ( PTA ) , P=0.36 . Thrombosis was 4 % ( DEB ) vs. 8 % ( PTA ) , P≥0.05 . Major adverse events 24 % ( DEB ) vs. 60 % ( PTA ) , P<0.05 . ABI improved more in the DEB group : 0.81±0.3 vs. 0.68±0.13 ( P=0.02 ) . Fontaine stage increased ( from II b to I ) 80 % DEB vs. 56 % PTA ( P<0.05 ) . CONCLUSION Results confirm and reinforce initial 6-month outcomes . In . Pact DEB balloons can be considered efficient to reduce restenosis rate OBJECTIVES This study sought to compare the effect of paclitaxel-coated balloon ( PCB ) concentration on tissue levels and vascular healing using 3 different PCB technologies ( In . Pact Pacific = 3 μg/mm(2 ) , Lutonix = 2 μg/mm(2 ) and Ranger = 2 μg/mm(2 ) ) in the experimental setting . BACKGROUND The optimal therapeutic dose for PCB use has not been determined yet . METHODS Paclitaxel tissue levels were measured up to 60 days following PCB inflation ( Ranger and In . Pact Pacific ) in the superficial femoral artery of healthy swine ( 18 swine , 36 vessels ) . The familial hypercholesterolemic swine model of superficial femoral artery in-stent restenosis ( 6 swine , 24 vessels ) was used in the efficacy study . Two weeks following bare-metal stent implantation , each in-stent restenosis site was r and omly treated with a PCB or an uncoated control balloon ( Sterling ) . Quantitative vascular analysis and histology evaluation was performed 28 days following PCB treatment . RESULTS All PCB technologies displayed comparable paclitaxel tissue levels 4 h following balloon inflation . At 28 days , all PCB had achieved therapeutic tissue levels ; however , the In . Pact PCB result ed in higher tissue concentrations than did the other PCB groups at all time points . Neointimal inhibition by histology was decreased in all PCB groups compared with the control group , with a greater decrease in the In . Pact group . However , the neointima was more mature and contained less peri-strut fibrin deposits in both 2-μg/mm(2 ) PCB groups . CONCLUSIONS Compared with the clinical ly established PCB dose , lower-dose PCB technologies achieve lower long-term tissue levels but comparable degrees of neointimal inhibition and fewer fibrin deposits . The impact of these findings in restenosis reduction and clinical outcomes needs to be further investigated OBJECTIVES This study sought to evaluate the safety and efficacy of the Lutonix drug-coated balloon ( DCB ) coated with 2 μg/mm(2)paclitaxel and a polysorbate/sorbitol carrier for treatment of femoropopliteal lesions . BACKGROUND Percutaneous treatment of peripheral vascular disease is associated with a high recurrence . Paclitaxel-coated balloons at 3 μg/mm(2 ) formulated differently have shown promising results with reduced restenosis . Methods Subjects at 9 centers with Rutherford class 2 to 5 femoropopliteal lesions were r and omized between June 2009 and December 2009 to treatment with Lutonix DCB ( n = 49 ) versus uncoated balloons ( control group [ n = 52 ] ) , stratified by whether balloon-only treatment ( n = 75 ) or stenting ( n = 26 ) was intended . The primary endpoint was angiographic late lumen loss at 6 months . Secondary outcomes included adjudicated major adverse events ( death , amputation , target lesion thrombosis , reintervention ) , functional outcomes , and pharmacokinetics . RESULTS Demographic , peripheral vascular disease , and lesion characteristics were matched , with mean lesion length of 8.1 3.8 cm and 42 % total occlusions . At 6 months , late lumen loss was 58 % lower for the Lutonix DCB group ( 0.46 1.13 mm ) than for the control group ( 1.09 1.07 mm ; p = 0.016 ) . Composite 24-month major adverse events were 39 % for the DCB group , including 15 target lesion revascularizations , 1 amputation , and 4 deaths versus 46 % for uncoated balloon group , with 20 target lesion revascularizations , 1 thrombosis , and 5 deaths . Pharmacokinetics showed biexponential decay with peak concentration ( Cmax ) of 59 ng/ml and total observed exposure ( AUC(all ) ) of 73 ng h/ml . For successful DCB deployment excluding 8 malfunctions , 6-month late lumen loss was 0.39 mm and the 24-month target lesion revascularization rate was 24 % . CONCLUSIONS Treatment of femoropopliteal lesions with the low-dose Lutonix DCB reduced late lumen loss with safety comparable to that of control angioplasty . ( LEVANT I , The Lutonix Paclitaxel-Coated Balloon for the Prevention of Femoropopliteal Restenosis ; NCT00930813 OBJECTIVES These studies sought to evaluate the clinical outcomes of the slow-release Taxus paclitaxel-eluting stent ( PES ) versus an otherwise identical bare-metal stent ( BMS ) . BACKGROUND Prior studies were not individually powered to generate reliable estimates of low-frequency safety endpoints or to characterize the long-term safety and efficacy profile of PES . METHODS The completed 5-year data bases from the prospect i ve , r and omized , double-blind TAXUS I , II , IV , and V trials were pooled for a patient-level analysis . RESULTS The study population comprised 2,797 r and omized patients ( 1,400 PES and 1,397 BMS ) . At the end of the 5-year study period , PES compared with BMS significantly reduced the rate of ischemia-driven target lesion revascularization ( 12.3 % vs. 21.0 % , p < 0.0001 ) , with consistent reductions across high-risk subgroups and in patients with and without routine angiographic follow-up . There were no significant differences between the stent types in the 1-year or cumulative 5-year rates of death or myocardial infa rct ion ( MI ) . However , cardiac death or MI between 1 and 5 years was increased with PES ( 6.7 % vs. 4.5 % , p = 0.01 ) , as was stent thrombosis ( protocol definition : 0.9 % vs. 0.2 % , p = 0.007 ; ARC definition : 1.4 % vs. 0.9 % , p = 0.18 ) . CONCLUSIONS In this pooled patient-level analysis from the prospect i ve , r and omized , double-blind TAXUS trials , PES compared with BMS result ed in a durable 47 % reduction in the 5-year rate of ischemia-driven target lesion revascularization in simple and complex lesions , with nonsignificant differences in the cumulative 5-year rates of death or MI . Between 1 and 5 years , however , the rates of cardiac death or MI and protocol -defined stent thrombosis were increased with PES Purpose : To evaluate the performance of the Ranger paclitaxel-coated balloon vs uncoated balloon angioplasty for femoropopliteal lesions . Methods : Between January 2014 and October 2015 , the prospect i ve , r and omized RANGER SFA study ( Clinical Trials.gov identifier NCT02013193 ) enrolled 105 patients with symptomatic lower limb ischemia ( Rutherford category 2–4 ) and stenotic lesions in the nonstented femoropopliteal segment at 10 European centers . Seventy-one patients ( mean age 68±8 years ; 53 men ) were enrolled in the Ranger drug-coated balloon ( DCB ) arm and 34 patients ( mean age 67±9 years ; 23 men ) were assigned to the control group . Six-month analysis included angiographic late lumen loss and safety and clinical outcomes assessment s. Results : Baseline characteristics of the DCB and control groups were similar , as were lesion lengths ( 68±46 vs 60±48 mm ; p=0.731 ) , severity of calcification ( p=0.236 ) , and the prevalence of occlusions ( 34 % vs 34 % ; p>0.999 ) . At 6 months , late lumen loss was significantly less for the DCB group vs controls ( –0.16±0.99 vs 0.76±1.4 ; p=0.002 ) . The DCB group had significantly greater freedom from binary restenosis ( 92 % vs 64 % ; p=0.005 ) and primary patency rates ( 87 % vs 60 % ; p=0.014 ) . Target lesion revascularization rates were 5.6 % in the DCB group and 12 % in the control group ( p=0.475 ) . No target limb amputations or device-related deaths occurred in either group . Conclusion : Six-month results suggest that Ranger DCB treatment effectively inhibited restenosis in symptomatic femoropopliteal disease , result ing in improved vessel patency and a low revascularization rate in the short term compared with uncoated balloon angioplasty OBJECTIVES The Global SFA Registry sought to assess safety , clinical benefit , and outcomes of the Lutonix 035 drug-coated balloon ( DCB ) in a heterogeneous , real-world patient population at 12 and 24 months . BACKGROUND Numerous clinical studies have evaluated the use of angioplasty for revascularization of femoropopliteal arteries in peripheral arterial disease with restenosis rates of 40 % to 60 % at 6 to 12 months . Data from recent studies document decreased restenosis rates and improvement in patency in patients receiving angioplasty of femoropopliteal arteries with DCBs . METHODS The multicenter , prospect i ve study enrolled 691 patients in 38 centers from 10 countries treated with the Lutonix 035 DCB in femoropopliteal lesions . The primary safety endpoint was freedom from a composite of target vessel restenosis , major index limb amputation , and device- or procedure-related death at 30 days . The primary effectiveness endpoint was freedom from target lesion restenosis at 12 months . Secondary endpoints were acute device and procedural success and clinical ly assessed primary patency . RESULTS Freedom at 30 days from the composite safety endpoint was 99.4 % . Freedom from target lesion restenosis was 93.4%/89.3 % for the overall population , 93.2%/88.2 % for long lesions up to 500 mm , and 90.7%/84.6 % for in-stent restenosis at 12/24 months . Clinical ly assessed primary patency by Kaplan-Meier estimates was 85.4%/75.6 % at 12/24 months . More than 76 % of patients showed improvement of at least 1 Rutherford category . CONCLUSIONS The Global SFA Registry 24-month outcomes confirm the Lutonix 035 DCB is a safe and effective long-term treatment option in real-world patients with peripheral arterial disease with superficial femoral artery lesions , also in long lesions and in-stent restenosis . ( Lutonix Global SFA Registry ; NCT01864278 ) OBJECTIVES The hypothesis that paclitaxel-eluting balloon angioplasty provides higher 1-year patency rates in femoropopliteal artery in-stent restenosis compared with st and ard percutaneous transluminal angioplasty ( PTA ) was tested . BACKGROUND Several trials have demonstrated that paclitaxel-eluting balloon angioplasty reduces late luminal loss in comparison with PTA . METHOD In a prospect i ve , r and omized , single-blind , dual-center study , 74 patients with symptomatic peripheral artery disease due to in-stent restenosis were treated with either paclitaxel-based drug-eluting balloon ( DEB ) angioplasty ( n = 35 ) or st and ard PTA ( n = 39 ) . Clinical outcomes and patency rates were assessed at 1 , 6 , and 12 months . RESULTS The mean lesion length was 17.3 ± 11.3 cm in the DEB group and 18.4 ± 8.8 cm in the PTA group . A single major complication ( bleeding ) was observed once ( 1.4 % ) . The mean ankle-brachial index before endovascular treatment was 0.65 ± 0.16 in both groups and 0.79 ± 0.2 versus 0.84 ± 0.3 ( p = 0.70 , Student t test ) in the DEB versus PTA group at 12 months . The 12-month primary patency rates were 40.7 % ( 95 % confidence interval [ CI ] : 0.26 to 0.64 ) versus 13.4 % ( 95 % CI : 0.05 to 0.36 ) ( log-rank p = 0.02 ) in the DEB versus PTA group . The odds ratio for PTA over DEB angioplasty for experiencing an event was estimated at 2.8 ( 95 % CI : 1.2 to 6.6 ) . Freedom from clinical ly driven target lesion revascularization was 49.0 % ( 95 % CI : 0.32 to 0.75 ) versus 22.1 % ( 95 % CI : 0.10 to 0.48 ) ( log-rank p = 0.11 ) in the DEB versus PTA group . Clinical improvement by ≥1 Rutherford-Becker category was 68.8 % versus 54.5 % ( p = 0.87 ) in the DEB versus PTA group at 12 months . CONCLUSIONS When treating peripheral artery disease in patients with in-stent restenosis in the femoropopliteal artery , paclitaxel-eluting balloon angioplasty provides significantly higher patency rates than st and ard PTA . ( Paclitaxel Balloon Versus St and ard Balloon in In-Stent Restenoses of the Superficial Femoral Artery [ PACUBA I Trial ] [ PACUBA 1 ] ; NCT01247402 ) Purpose : To report a r and omized trial comparing the Legflow paclitaxel-eluting balloon ( PEB ) + Supera stenting to Supera stenting alone in patients with intermediate to long superficial femoral artery ( SFA ) lesions . Methods : The multicenter RAPID trial ( controlled-trials.com ; identifier IS RCT N47846578 ) r and omized ( 1:1 ) 160 patients ( mean age 67 years ; 102 men ) with Rutherford category 2–6 ischemia to treatment with Legflow PEB + Supera stent or Supera stent alone in intermediate to long SFA lesions ( mean lesion length 15.8±7.4 vs 15.8±7.6 cm , respectively ) . The efficacy outcome was primary patency , defined as freedom from restenosis on duplex ultrasound or angiography . Results : Baseline characteristics including the percentage of occlusions were similar between groups . In the intention-to-treat analysis , the estimated primary patency at 1 year was 68.3 % ( 95 % CI 56.7 % to 79.9 % ) in the PEB + Supera group vs 62.0 % ( 95 % CI 49.1 % to 74.9 % ) in the Supera group ( p=0.900 ) . Per- protocol analysis showed a 12-month primary patency estimate of 74.7 % ( 95 % CI 63.1 % to 86.3 % ) in the PEB + Supera group vs 62.0 % ( 95 % CI 49.1 % to 74.9 % ) in the control group ( p=0.273 ) . Secondary patency estimates at 12 months ( per- protocol analysis ) were 89.0 % ( 95 % CI 80.6 % to 97.4 % ) vs 98.0 % ( 95 % CI 94.1 % to 100 % ; p=0.484 ) ; the estimates for freedom from clinical ly driven target lesion revascularization ( CD-TLR ) were 83.0 % ( 95 % CI 72.8 % to 93.2 % ) and 77.8 % ( 95 % CI 66.6 % to 89.0 % ; p=0.277 ) , respectively . Conclusion : The short-term results from the multicenter RAPID r and omized controlled trial indicate that the Legflow PEB is safe and feasible for the treatment of intermediate to long SFA lesions . In this trial , at least 70 % of the patients suffered an occlusion . The PEB group had higher rates of primary patency and freedom from CD-TLR , although there were no statistically significant differences vs controls OBJECTIVES The aim of this study was to investigate the efficacy and safety of a new paclitaxel-coated balloon catheter in the treatment of stenotic or occluded femoropopliteal arteries . BACKGROUND The incidence of restenosis can be reduced by the use of drug-coated balloons . However , dose , coating composition , and technology are decisive for efficacy . METHODS Two hundred Chinese patients with peripheral arterial occlusive disease were prospect ively r and omized to treatment with new paclitaxel-coated or st and ard uncoated balloon catheters . The primary endpoint was angiographic late lumen loss at 6 months , measured by a blinded core laboratory . Secondary angiographic endpoints ( 6 months ) and specific clinical endpoints ( 1 year ) were binary restenosis , ankle-brachial index , Rutherford stage , clinical ly driven target lesion revascularization , and amputation . RESULTS Patients ' mean age was 66 years , 74 % were men , 31 % were smokers , and 55 % had diabetes . Patients were in Rutherford stages 2 through 5 , with a mean lesion length of 150 mm ; 25 % had in-stent restenosis , 55 % had occlusion or partial occlusion , and 20 % underwent provisional stenting . Late lumen loss at 6 months was available for 89 % , and clinical follow-up was available for > 95 % per group . Mean late lumen loss was 0.05 ± 0.73 mm with coated balloons and 1.15 ± 0.89 mm with uncoated balloons ( p < 0.001 ) . Correspondingly , the rates of restenosis were 22.5 % and 70.8 % ( p < 0.001 ) . After 1 year , the rates of target lesion revascularization were 7.2 % and 39.6 % ( p < 0.001 ) , and Rutherford class and ankle-brachial index improved more markedly in the coated group ( p < 0.046 and p = 0.023 , respectively ) . One major amputation was recorded in the control group . No coating-related adverse events were observed for doses of up to 43 mg paclitaxel per patient . CONCLUSIONS In this medium-sized trial with long superficial femoral artery lesions , the use of paclitaxel-coated balloon catheters markedly improved angiographic and clinical outcomes of interventions despite advanced disease in the majority of patients OBJECTIVES The IN.PACT Global Study is the largest prospect i ve , multicenter , independently adjudicated trial to evaluate a paclitaxel drug-coated balloon in patients with lifestyle-limiting claudication and /or ischemic rest pain due to atherosclerotic disease of the femoropopliteal artery and includes complex lesions beyond what are typically included in r and omized controlled trials . BACKGROUND R and omized controlled trials have demonstrated the safety and efficacy of drug-coated balloons for the treatment of Trans-Atlantic Inter-Society Consensus Document II A and B lesions , but there is a need for large-scale prospect i ve studies to evaluate a broader range of lesions . METHODS The IN.PACT Global Study enrolled 1,535 subjects , and 1,406 ( 1,773 lesions ) were included in the pre-defined clinical cohort analysis . Freedom from clinical ly driven target lesion revascularization was evaluated at 24 months . The safety composite endpoint was freedom from device- and procedure-related death through 30 days and freedom from target limb major amputation and clinical ly driven target vessel revascularization within 24 months . RESULTS Mean lesion length was 12.1 cm , 35.5 % were total occlusions , and 18.0 % had in-stent restenosis . Freedom from clinical ly driven target lesion revascularization at 24 months was 83.3 % , the composite safety endpoint was met in 81.7 % , the 2-year all-cause mortality rate was 7.0 % , and the major target limb amputation rate was 0.7 % . Increased lesion length and the presence of de novo in-stent restenosis or coronary artery disease were associated with increased risk for clinical ly driven target lesion revascularization by 24 months . CONCLUSIONS This real-world study of femoropopliteal artery disease treatment with drug-coated balloons confirmed positive findings reported from more strictly design ed r and omized controlled trials and showed that outcomes are durable in this population up to 2 years after treatment . ( IN.PACT Global Clinical Study ; NCT01609296 ) BACKGROUND Claudication and critical limb threatening ischemia are significant causes of mortality in the elderly . The gold st and ard of superficial femoral artery ( SFA ) revascularization is thus far considered to be the femoropopliteal bypass . The aim of this study was to compare mid-term patency between drug-eluting stents ( DESs ) and prosthetic bypass grafts ( BSX ) . Studies have reported comparable results for both the methods . METHODS Forty-six patients with claudication or rest pain due to a 5 - 25 cm SFA occlusion were r and omized between DES and BSX groups . The follow-up period was 24 months , and the primary outcome measure was overall patency . Secondary outcome measures were primary and primary assisted patency , change in ankle-brachial index ( ABI ) , and amputation-free survival . RESULTS Forty-one patients were eventually analyzed . Six-month secondary patency was 91 % ( DES ) versus 83 % ( BSX ) ( P = 0.450 ) . The corresponding numbers at 12 months in the DES and BSX groups were 74 % and 80 % ( P = 0.750 ) , respectively . At 24 months , the respective numbers were 56 % and 71 % ( P = 0.830 ) . There were no statistically significant differences in primary or assisted primary patency at 1 , 6 , or 12 months . CONCLUSION There were no demonstrable differences in patency rates or clinical outcomes such as ABI or major amputations between DES and BSX . Although underpowered , the results suggest noninferiority of the DES compared with prosthetic bypass surgery . TRIAL REGISTRATION The trial was preregistered at Clinical Trials.org ( NCT01450722 ) BACKGROUND Stenosis is a known complication in bypass vein grafts for peripheral arterial disease . The aim of this study was to evaluate the effect of drug-coated balloons ( DCBs ) in the treatment of vein graft stenoses . DCBs may prevent restenosis in arterial lesions . One small prospect i ve and larger retrospective and registry studies have failed to show benefit from DCBs in vein grafts . Prospect i ve data are scarce . METHODS Sixty patients treated for primary or recurrent stenosis in venous bypass grafts were r and omized to DCB ( n = 30 ) or st and ard balloon angioplasty ( BA ) ( n = 30 ) . Follow-up was 1 year . The primary outcome measure was target lesion revascularization ( TLR ) . Secondary outcome measures were assisted primary patency and secondary patency and graft occlusion . RESULTS Fifty-seven patients were analyzed . Three patients were excluded due to primary technical failure ( 2 DCB , 1 BA ) . Overall TLR rate was 34.5 % and 46.4 % in the DCB and BA groups , respectively ( P = 0.33 ) . Five ( 8.8 % ) grafts occluded during follow-up ( 1 DCB , 4 BA ) . Assisted primary patency was 93.1 % ( DCB ) versus 85.7 % ( BA ) ( P = 0.362 ) and secondary patency was 100 % ( DCB ) versus 89.3 % ( BA ) ( P = 0.076 ) . Subgroup analysis showed a significant benefit from DCB in the treatment of primary stenosis ( TLR rate 15.0 % vs. 18.9 % , P = 0.03 ) . CONCLUSION There was no significant benefit from DCBs for treatment of vein graft stenosis compared to BA , although a trend in favor of DCBs could be seen . TRIAL REGISTRATION Clinical Trials.govNCT03023098 OBJECTIVES A prospect i ve , multinational r and omized controlled trial ( RCT ) and a complementary single-arm study evaluated the 2-year safety and effectiveness of a paclitaxel-coated drug-eluting stent ( DES ) in patients with superficial femoral artery lesions . The RCT compared the DES with percutaneous transluminal angioplasty ( PTA ) and provisional bare-metal stent ( BMS ) placement . BACKGROUND Local drug delivery for superficial femoral artery lesions has been investigated with the intent of limiting restenosis similarly to DES for the coronary arteries . One-year outcomes of DES in the superficial femoral artery are promising , but longer-term benefits have not been established . METHODS In the RCT , patients were r and omly assigned to primary DES implantation ( n = 236 ) or PTA ( n = 238 ) . Acute PTA failure occurred in 120 patients , who underwent secondary r and omization to DES ( n = 61 ) or BMS ( n = 59 ) placement . The single-arm study enrolled 787 patients with DES treatment . RESULTS Compared with the control group , the primary DES group demonstrated significantly superior 2-year event-free survival ( 86.6 % vs. 77.9 % , p = 0.02 ) and primary patency ( 74.8 % vs. 26.5 % , p < 0.01 ) . In addition , the provisional DES group exhibited superior 2-year primary patency compared with the provisional BMS group ( 83.4 % vs. 64.1 % , p < 0.01 ) and achieved higher sustained clinical benefit ( 83.9 % vs. 68.4 % , p = 0.05 ) . Two-year freedom from target lesion revascularization with primary DES placement was 80.5 % in the single-arm study and 86.6 % in the RCT . CONCLUSIONS Two-year outcomes with the paclitaxel-eluting stent support its sustained safety and effectiveness in patients with femoropopliteal artery disease , including the long-term superiority of the DES to PTA and to provisional BMS placement . ( Evaluation of the Zilver PTX Drug-Eluting Stent in the Above-the-Knee Femoropopliteal Artery ; NCT00120406 ; Zilver ( ® ) PTX ™ Global Registry ; NCT01094678 ) Purpose To report 6-month results of the DEBELLUM ( Drug-Eluting Balloon Evaluation for Lower Limb MUltilevel TreatMent ) r and omized trial to evaluate the efficacy of a drug-eluting balloon ( DEB ) to reduce restenosis after treatment of multilevel lower limb occlusive disease vs. a conventional angioplasty balloon ( AB ) . Methods Between September 2010 and March 2011 , 50 consecutive patients ( 37 men ; mean age 66 ± 4 years ) with 122 lesions ( 96 stenoses and 26 occlusions ) of the femoropopliteal ( 92 , 75.4 % ) or below-the-knee ( BTK ) arteries ( 30 , 24.6 % ) were enrolled and r and omly assigned to the DEB ( 25 patients with 57 lesions ) or AB ( 25 patients with 65 lesions ) group . Twenty patients presented multilevel lesions . Mean lesion length was 7.5 ± 3.5 cm . Thirty-one ( 62 % ) of the patients were Fontaine stage IIb , while 19 ( 38 % ) were stage III or IV . DEBs or ABs were used for dilation of de novo lesions or for postdilation after primary stenting ( superficial femoral artery only ) . Patients requiring provisional stenting after angioplasty secondary to flow-limiting dissection or residual stenosis > 50 % were ineligible . Primary endpoint was late lumen loss at 6 months . Secondary endpoints were target lesion revascularization ( TLR ) , amputation , and thrombosis . Results Late lumen loss was lower in the DEB group ( 0.5 ± 1.4 vs. 1.6 ± 1.7 mm , p<0.01 ) . TLR was necessary in 6.1 % of the DEB group vs. 23.6 % of the AB group ( p=0.02 ) . Comparing the DEB to AB groups , the thrombosis rates were 3.0 % vs. 5.2 % ( p=0.6 ) , and the amputation rates were 3.0 % vs. 7.9 % ( p=0.36 ) . The binary restenosis rates were 9.1 % ( 3/33 limbs ) in the DEB group vs. 28.9 % ( 11/38 limbs ) in the control group ( p=0.03 ) . The anklebrachial index improved to a greater degree in the DEB group : 0.87 ± 0.22 vs. 0.70 ± 0.13 ( p<0.05 ) . The Fontaine stage improved in both groups but more so in patients treated with DEBs ( p=0.04 ) . Conclusion The DEBELLUM trial confirmed the ability of paclitaxel-eluting balloons to reduce restenosis vs. conventional balloons at 6 months after treatment of multilevel ( femoropopliteal and BTK ) arterial disease in patients affected by claudication and CLI . A lower TLR rate and better clinical outcomes appear to be associated with the use of DEBs regardless of stent placement Background : Drug-coated balloons ( DCBs ) are a predominant revascularization therapy for symptomatic femoropopliteal artery disease . Because of the differences in excipients , paclitaxel dose , and coating morphologies , varying clinical outcomes have been observed with different DCBs . We report the results of 2 studies investigating the pharmacokinetic and clinical outcomes of a new DCB to treat femoropopliteal disease . Methods : In the ILLUMENATE Pivotal Study ( Prospect i ve , R and omized , Single-Blind , U.S. Multi-Center Study to Evaluate Treatment of Obstructive Superficial Femoral Artery or Popliteal Lesions With A Novel Paclitaxel-Coated Percutaneous Angioplasty Balloon ) , 300 symptomatic patients ( Rutherford class 2–4 ) were r and omly assigned to DCB ( n=200 ) or st and ard angioplasty ( percutaneous transluminal angioplasty [ PTA ] ) ( n=100 ) . The primary safety end point was freedom from device- and procedure-related death through 30 days , and freedom from target limb major amputation and clinical ly driven target lesion revascularization through 12 months . The primary effectiveness end point was primary patency through 12 months . In the ILLUMENATE PK study ( Pharmacokinetic Study of the Stellarex Drug-Coated Angioplasty Balloon ) , paclitaxel plasma concentrations were measured after last DCB deployment and at prespecified times ( at 1 , 4 , 24 hours and at 7 and 14 days postprocedure ) until no longer detectable . Results : In the ILLUMENATE Pivotal Study , baseline characteristics were similar between groups : 50 % had diabetes mellitus , 41 % were women , mean lesion length was 8.3 cm , and 44 % were severely calcified . The primary safety end point was met ( 92.1 % for DCB versus 83.2 % for PTA , P=0.025 for superiority ) and the primary patency rate was significantly higher with DCB ( 76.3 % for DCB versus 57.6 % for PTA , P=0.003 ) . Primary patency per Kaplan-Meier estimates at day 365 was 82.3 % for DCB versus 70.9 % for PTA ( P=0.002 ) . The rate of clinical ly driven target lesion revascularization was significantly lower in the DCB cohort ( 7.9 % versus 16.8 % , P=0.023 ) . Improvements in ankle-brachial index , Rutherford class , and quality of life were comparable , but the PTA cohort required twice as many revascularizations . Pharmacokinetic outcomes showed that all patients had detectable paclitaxel levels after DCB deployment that declined within the first hour ( 54.4±116.9 ng/mL to 1.4±1.0 ng/mL ) . Conclusions : The data demonstrate superior safety and effectiveness of the Stellarex DCB in comparison with PTA , and plasma levels of paclitaxel fall to low levels within 1 hour . Clinical Trial Registration : URL : http:// clinical trials.gov . Unique identifiers : NCT01858428 and NCT01912937 Background : Numerous studies have reported favorable outcomes using drug-coated balloons ( DCBs ) for treatment of symptomatic peripheral artery disease of the superficial femoral and popliteal arteries . However , the treatment effect compared with an uncoated balloon has differed greatly among the r and omized trials , with better outcomes observed with higher-dose DCBs . This European trial was design ed to assess the safety and effectiveness of a next-generation low-dose ( 2-µg/mm2 surface dose of paclitaxel ) DCB . Methods : This was a prospect i ve , r and omized , multicenter , single-blinded trial . Patients were r and omized ( 3:1 ) to treatment with a low-dose DCB or an uncoated percutaneous transluminal angioplasty ( PTA ) balloon . The primary safety end point was a composite of freedom from device- and procedure-related death through 30 days after the procedure and freedom from target limb major amputation and clinical ly driven target lesion revascularization through 12 months after the procedure . The primary effectiveness end point was primary patency at 12 months . Results : Patients were r and omized to treatment with a DCB ( 222 patients , 254 lesions ) or uncoated PTA balloon ( 72 patients , 79 lesions ) after successful predilatation . Mean lesion length was 7.2 and 7.1 cm , and 19.2 % and 19.0 % of lesions represented total occlusions , respectively . The primary safety end point was met , and superiority was demonstrated ; freedom from a primary safety event was 94.1 % ( 193 of 205 ) with DCB and 83.3 % ( 50 of 60 ) with PTA , for a difference of 10.8 % ( 95 % confidence interval , 0.9%–23.0 % ) . The primary effectiveness end point was met , and superiority of DCB over PTA was achieved ( 83.9 % [ 188 of 224 ] versus 60.6 % [ 40 of 66 ] ; P<0.001 ) . Outcomes with DCB were also superior to PTA per the Kaplan-Meier estimate for primary patency ( 89.0 % versus 65.0 % at 365 days ; log-rank P<0.001 ) and for rates of clinical ly driven target lesion revascularization ( 5.9 % versus 16.7 % ; P=0.014 ) . Conclusions : Superiority with a low-dose DCB for femoropopliteal interventions was demonstrated over PTA for both the safety and effectiveness end points . Clinical Trial Registration : URL : http://www . clinical trials.gov . Unique identifier : NCT01858363 Background : Atherosclerosis in the superficial femoral artery is common in patients suffering from peripheral artery disease . Paclitaxel-eluting balloon ( PEB ) angioplasty , stenting , and directional atherectomy ( DA ) have provided new options for the treatment of superficial femoral artery disease ; however , the comparative efficacy of these interventional strategies remains uncertain . Methods : One hundred and fifty-five patients with symptomatic peripheral artery disease due to de novo superficial femoral artery stenotic or occlusive lesions were r and omized to treatment with plain balloon angioplasty ( BA ) followed by PEB angioplasty and stenting ( n=48 ) , BA and stenting ( n=52 ) , or DA with distal protection and bailout stenting ( n=55 ) . The primary end point of the study was percentage diameter stenosis after 6 months measured by angiography . Other end points included target lesion revascularization , thrombosis , ipsilateral amputation , binary restenosis , and all-cause mortality at 6 and 24 months . Results : Baseline and lesion characteristics were comparable in all groups with a mean lesion length of 65.9±46.8 mm and 56 % total occlusions . At 6 months angiography , the percent diameter stenosis was significantly lower in patients treated by PEB angioplasty and stenting ( 34±31 % ) as compared with BA angioplasty and stenting ( 56±29 % , P=0.009 ) or DA ( 55±29 % , P=0.007 ) . Similarly , binary restenosis was significantly lower after treatment with PEB and stenting as compared with BA and stenting or DA . Clinical follow-up at 24 months revealed a lower risk for target lesion revascularization after PEB angioplasty and stenting as compared with BA and stenting or DA . We found no difference in terms of target lesion thrombosis and mortality among groups , and no patient underwent amputation . Conclusions : Treatment of de novo superficial femoral artery lesions with PEB angioplasty and stenting is superior to BA angioplasty and stenting or DA in terms of angiographic diameter stenosis at 6 months and target lesion revascularization at 24 months . Clinical Trial Registration : URL : http://www . clinical trials.gov . Unique identifier : NCT00986752 |
877 | 25,266,070 | Subgroup analyses showed a benefit for clinical cure rates associated with linezolid and increased mortality associated with tigecycline .
In meta-regression , clinical cure rates remained higher in patients treated with linezolid ( P=0.01 ) ; tigecycline displayed a close to significant association with increased mortality ( P=0.05 ) if compared with other bacteriostatic agents .
The categorization of antibiotics into bacteriostatic and bactericidal is unlikely to be relevant in clinical practice if used for abdominal infections , skin and soft tissue infections and pneumonia . | OBJECTIVES Antibiotics are commonly classified into bactericidal and bacteriostatic agents based on their antimicrobial action .
We aim ed to assess whether this distinction is clinical ly relevant . | Background Tigecycline , an exp and ed broad-spectrum glycylcycline , exhibits in vitro activity against many common pathogens associated with community-acquired pneumonia ( CAP ) , as well as penetration into lung tissues that suggests effectiveness in hospitalized CAP patients . The aim of the present study was to compare the efficacy and safety of intravenous ( IV ) tigecycline with IV levofloxacin in hospitalized adults with CAP . Methods In this prospect i ve , double-blind , non-inferiority phase 3 trial , eligible patients with a clinical diagnosis of CAP supported by radiographic evidence were stratified by Fine Pneumonia Severity Index and r and omized to tigecycline or levofloxacin for 7 - 14 days of therapy . Co- primary efficacy endpoints were clinical response in the clinical ly evaluable ( CE ) and clinical modified intent-to-treat ( c-mITT ) population s at test-of-cure ( Day 10 - 21 post-therapy ) . Results Of the 428 patients who received at least one dose of study drug , 79 % had CAP of mild-moderate severity according to their Fine score . Clinical cure rates for the CE population were 88.9 % for tigecycline and 85.3 % for levofloxacin . Corresponding c-mITT population rates were 83.7 % and 81.5 % , respectively . Eradication rates for Streptococcus pneumoniae were 92 % for tigecycline and 89 % for levofloxacin . Nausea , vomiting , and diarrhoea were the most frequently reported adverse events . Rates of premature discontinuation of study drug or study withdrawal because of any adverse event were similar for both study drugs . Conclusion These findings suggest that IV tigecycline is non-inferior to IV levofloxacin and is generally well-tolerated in the treatment of hospitalized adults with CAP.Trial registration Tigecycline ( TGC ) has demonstrated clinical efficacy and safety , in comparison with imipenem/cilastatin in phase 3 clinical trials , for complicated intra-abdominal infection ( cIAI ) . The present study comprised a multicentre , open-label , r and omized study of TGC vs. ceftriaxone plus metronidazole ( CTX/MET ) for the treatment of patients with cIAI . Eligible subjects were r and omized ( 1:1 ) to receive either an initial dose of TGC ( 100 mg ) followed by 50 mg every 12 h or CTX ( 2 g once daily ) plus MET ( 1 - 2 g daily ) , for 4 - 14 days . The primary endpoint was the clinical response in the clinical ly evaluable ( CE ) population at the test of cure ( TOC ) assessment . Of 473 r and omized subjects , 376 were CE . Among these , clinical cure rates were 70.4 % ( 133/189 ) with TGC vs. 74.3 % ( 139/187 ) with CTX/MET ( 95 % CI -13.1 to 5.1 ; p 0.009 for non-inferiority ) . Clinical cure rates for subjects with Acute Physiological and Chronic Health Evaluation II scores > or = 10 were 56.8 % ( 21/37 ) with TGC vs. 58.3 % ( 21/36 ) with CTX/MET . The microbiologic response was similar between the two treatment arms , with microbiological eradication at TOC achieved in 68.1 % ( 94/138 ) of TGC-treated subjects and 71.5 % ( 98/137 ) of CTX/MET-treated subjects . ( The most frequently reported adverse events ( AEs ) for both treatment arms were nausea ( TGC , 38.6 % vs CTX/MET , 27.7 % ) and vomiting ( TGC , 23.3 % vs CTX/MET , 17.7 % ) . Overall discontinuation rates as a result of an AE were 8.9 % and 4.8 % in TGC- and comparator-treated subjects , respectively . The results obtained in the present study demonstrate that TGC monotherapy is non-inferior to a combination regimen of CTX/MET with respect to treating subjects with cIAI OBJECTIVES To compare the efficacy and safety of linezolid and vancomycin for the treatment of methicillin-resistant Staphylococcus aureus ( MRSA ) infections in Japan . METHODS Patients with nosocomial pneumonia , complicated skin and soft-tissue infections or sepsis caused by MRSA were r and omized to receive linezolid ( 600 mg every 12 h ) or vancomycin ( 1 g every 12 h ) . RESULTS One hundred patients received linezolid and 51 received vancomycin with outcomes evaluated at the end of therapy ( EOT ) and at the follow-up ( FU ) , 7 - 14 days later . At EOT , clinical success rates in the MRSA microbiologically evaluable population were 62.9 % and 50.0 % for the linezolid and vancomycin groups , respectively ; and microbiological eradication rates were 79.0 % and 30.0 % in the two groups , respectively ( P < 0.0001 ) . At FU , the clinical success rates were 36.7 % for both groups and the microbiological eradication rates were 46.8 % and 36.7 % , respectively . Reversible anaemia ( 13 % ) and thrombocytopenia ( 19 % ) were reported more frequently in linezolid patients ; laboratory analysis showed mild decrease in platelet counts with full recovery by FU . The mean platelet count in linezolid patients with thrombocytopenia was 101,000/mm(3 ) . Significantly low platelet counts ( < 50,000/mm(3 ) ) were observed more frequently in patients receiving vancomycin than in linezolid patients ( 6 % versus 3 % ) . Mean changes in haemoglobin levels between the two groups were not different . CONCLUSIONS Linezolid is as effective as vancomycin for the treatment of MRSA infections and may be more effective than vancomycin in achieving microbiological eradication . Haematological adverse events were reported more frequently in linezolid-treated patients ; analysis of laboratory data showed a mild reversible trend towards lower platelet counts Tigecycline ( TGC ) , a glycylcycline , has exp and ed activity against Gram-positive and Gram-negative , anaerobic , and atypical bacteria . Two phase 3 studies were conducted . Hospitalized patients with community-acquired pneumonia ( CAP ) were r and omized to intravenous ( IV ) TGC ( 100 mg followed by 50 mg bid ) or IV levofloxacin ( LEV ) ( 500 mg bid ) . In 1 study , patients could be switched to oral LEV after at least 3 days intravenously . The co primary efficacy end points were as follows : clinical response in clinical ly evaluable ( CE ) and clinical modified intent-to-treat ( c-mITT ) population s at test-of-cure ( TOC ) . The secondary end points were as follows : microbiologic efficacy and susceptibility to TGC for CAP bacteria . Safety evaluations were included . Eight hundred ninety-one were patients screened : 846 mITT ( TGC 424 , LEV 422 ) , 574 CE ( TGC 282 , LEV 292 ) . Most patients had Fine Pneumonia Severity Index II to IV ( 80.7 % TGC , 74.4 % LEV , mITT ) . At TOC ( CE ) , TGC cured 253/282 patients ( 89.7 % ) and LEV cured 252/292 patients ( 86.3 % ) ; the absolute difference of TGC-LEV was 3.4 % ( 95 % confidence interval [ CI ] , -2.2 to 9.1 , noninferior [ P < 0.001 ] ) . In c-mITT , TGC cured 319/394 patients ( 81.0 % ) and LEV cured 321/403 patients ( 79.7 % ) ; the absolute difference of TGC-LEV was 1.3 % ( 95 % CI -4.5 to 7.1 , noninferior [ P < 0.001 ] ) . The drug-related adverse events ( AEs ) of nausea ( 20.8 % TGC versus 6.6 % LEV ) and vomiting ( 13.2 % TGC versus 3.3 % LEV ) were significantly higher in TGC ; elevated alanine aminotransferase ( 2.8 % TGC versus 7.3 % LEV ) and aspartate aminotransferase ( 2.6 % TGC versus 6.9 % LEV ) were significantly higher in LEV . Discontinuations for AEs were low ( TGC , 26 patients [ 6.1 % ] ; LEV , 34 patients [ 8.1 % ] ) . TGC appeared safe and achieved cure rates similar to LEV in hospitalized patients with CAP Background Complicated intra-abdominal infections ( cIAI ) remain challenging to treat because of their polymicrobial etiology including multi-drug resistant bacteria . The efficacy and safety of tigecycline , an exp and ed broad-spectrum glycylcycline antibiotic , was compared with imipenem/cilastatin ( IMI/CIS ) in patients with cIAI . Methods A prospect i ve , double-blind , multinational trial was conducted in which patients with cIAI r and omly received intravenous ( IV ) tigecycline ( 100 mg initial dose , then 50 mg every 12 hours [ q12h ] ) or IV IMI/CIS ( 500/500 mg q6h or adjusted for renal dysfunction ) for 5 to14 days . Clinical response at the test-of-cure ( TOC ) visit ( 14–35 days after therapy ) for microbiologically evaluable ( ME ) and microbiological modified intent-to-treat ( m-mITT ) population s were the co- primary efficacy endpoint population s. Results A total of 825 patients received ≥ 1 dose of study drug . The primary diagnoses for the ME group were complicated appendicitis ( 59 % ) , and intestinal ( 8.8 % ) and gastric/duodenal perforations ( 4.6 % ) . For the ME group , clinical cure rates at TOC were 80.6 % ( 199/247 ) for tigecycline versus 82.4 % ( 210/255 ) for IMI/CIS ( 95 % CI -8.4 , 5.1 for non-inferiority tigecycline versus IMI/CIS ) . Corresponding clinical cure rates within the m-mITT population were 73.5 % ( 227/309 ) for tigecycline versus 78.2 % ( 244/312 ) for IMI/CIS ( 95 % CI -11.0 , 2.5 ) . Nausea ( 31.0 % tigecycline , 24.8 % IMI/CIS [ P = 0.052 ] ) , vomiting ( 25.7 % tigecycline , 19.4 % IMI/CIS [ P = 0.037 ] ) , and diarrhea ( 21.3 % tigecycline , 18.9 % IMI/CIS [ P = 0.435 ] ) were the most frequently reported adverse events . Conclusion This study demonstrates that tigecycline is as efficacious as imipenem/cilastatin in the treatment of patients with cIAI A total of 108 children aged 4 - 17 years were r and omized to receive 7 days of azithromycin ( 10 mg/kg/day ; maximum , 500 mg/day ) or ceftriaxone ( 75 mg/kg/day ; maximum , 2.5 g/day ) , to assess the efficacy of the agents for the treatment of uncomplicated typhoid fever . Salmonella typhi was isolated from the initial cultures of blood sample s from 64 patients . A total of 31 ( 91 % ) of the 34 patients treated with azithromycin and 29 ( 97 % ) of the 30 patients treated with ceftriaxone were cured ( P>.05 ) . All 64 isolates were susceptible to azithromycin and ceftriaxone . Of the patients treated with ceftriaxone , 4 subsequently had relapse of their infection . No serious side effects occurred in any study subject . Oral azithromycin administered once daily appears to be effective for the treatment of uncomplicated typhoid fever in children . If these results are confirmed , the agent could be a convenient alternative for the treatment of typhoid fever , especially in individuals in developing countries where medical re sources are scarce Background Tigecycline , a first-in-class broad-spectrum glycylcycline antibiotic , has broad-spectrum in vitro activity against bacteria commonly encountered in complicated intra-abdominal infections ( cIAIs ) , including aerobic and facultative Gram-positive and Gram-negative bacteria and anaerobic bacteria . In the current trial , tigecycline was evaluated for safety and efficacy vs. imipenem/cilastatin in hospitalized Chinese patients with cIAIs . Methods In this phase 3 , multicenter , open-label study , patients were r and omly assigned to receive IV tigecycline or imipenem/cilastatin for ≤2 weeks . The primary efficacy endpoints were clinical response at the test-of-cure visit ( 12 - 37 days after therapy ) for the microbiologic modified intent-to-treat and microbiologically evaluable population s. Because the study was not powered to demonstrate non-inferiority between tigecycline and imipenem/cilastatin , no formal statistical analysis was performed . Two-sided 95 % confidence intervals ( CIs ) were calculated for the response rates in each treatment group and for differences between treatment groups for descriptive purpose s. Results One hundred ninety-nine patients received ≥1 dose of study drug and comprised the modified intent-to-treat population . In the microbiologically evaluable population , 86.5 % ( 45 of 52 ) of tigecycline- and 97.9 % ( 47 of 48 ) of imipenem/cilastatin-treated patients were cured at the test-of-cure assessment ( 12 - 37 days after therapy ) ; in the microbiologic modified intent-to-treat population , cure rates were 81.7 % ( 49 of 60 ) and 90.9 % ( 50 of 55 ) , respectively . The overall incidence of treatment-emergent adverse events was 80.4 % for tigecycline vs. 53.9 % after imipenem/cilastatin therapy ( P < 0.001 ) , primarily due to gastrointestinal-related events , especially nausea ( 21.6 % vs. 3.9 % ; P < 0.001 ) and vomiting ( 12.4 % vs. 2.0 % ; P = 0.005 ) . Conclusions Clinical cure rates for tigecycline were consistent with those found in global cIAI studies . The overall safety profile was also consistent with that observed in global studies of tigecycline for treatment of cIAI , as well as that observed in analyses of Chinese patients in those studies ; no novel trends were observed . Trial Registration Clinical Trials.gov OBJECTIVES To compare the effect of tigecycline monotherapy , a first-in-class , exp and ed broad spectrum glycylcycline , with the combination of vancomycin and aztreonam ( V + A ) in the treatment of complicated skin and skin structure infections ( cSSSI ) . METHODS A phase 3 , double-blind study conducted in 8 countries enrolled adults with cSSSI who required intravenous ( IV ) antibiotic therapy for > or = 5 days . Patients were r and omly assigned ( 1:1 ) to receive either tigecycline or V + A for up to 14 days . Primary endpoint was the clinical cure rate at the test-of-cure visit . Secondary endpoints included microbiologic efficacy and in vitro susceptibility to tigecycline of bacteria that cause cSSSI . Safety was assessed by physical examination , laboratory analyses , and adverse event reporting . RESULTS A total of 596 patients were screened for enrollment , 573 were analyzed for safety , 537 were included in the clinical modified intent-to-treat ( c-mITT ) population , 397 were clinical ly evaluable ( CE ) , and 228 were microbiologically evaluable ( ME ) . At test-of-cure , cure rates were similar between tigecycline and V + A groups in the CE population ( 82.9 % versus 82.3 % , respectively ) and in the c-mITT population ( 75.5 % versus 76.9 % , respectively ) . Microbiologic eradication rates ( subject level ) at test-of-cure in the ME population were also similar between tigecycline and V + A. Frequency of adverse events was similar between groups , although patients receiving tigecycline had higher incidence of nausea , vomiting , dyspepsia , and anorexia , while increased ALT/SGPT , pruritus , and rash occurred significantly more often in V + A-treated patients . CONCLUSIONS This study demonstrates that the efficacy of tigecycline monotherapy for the treatment of patients with cSSSI is statistically noninferior to the combination of V + BACKGROUND Dalbavancin , a novel lipoglycopeptide with a pharmacokinetic profile that allows weekly dosing , is active against gram-positive bacteria , including methicillin-resistant Staphylococcus aureus ( MRSA ) . The efficacy of dalbavancin for treatment of skin and skin structure infections ( SSSIs ) was demonstrated in a phase 2 study . METHODS In a phase 3 noninferiority study , patients with complicated SSSIs , including infections known or suspected to involve MRSA , were r and omized ( ratio , 2 : 1 ) in a double-blind manner to receive dalbavancin ( 1000 mg given intravenously on day 1 and 500 mg given intravenously on day 8) or linezolid ( 600 mg given intravenously or intravenously/orally every 12 h for 14 days ) . Efficacy was assessed by determining clinical and microbiological responses at the end of therapy and at the test-of-cure visit . Relapses were identified by additional follow-up approximately 1 month later . RESULTS MRSA was identified in 51 % of patients from whom a pathogen was isolated at baseline . Dalbavancin and linezolid demonstrated comparable clinical efficacy in the clinical ly evaluable population at the test-of-cure visit ( 88.9 % and 91.2 % success , respectively ) . The rate of clinical success at the end of therapy was > 90 % in both arms . Less than 1.0 % of patients in either treatment arm experienced relapse after the test-of-cure visit . Both treatments yielded successful microbiological response in excess of 85 % among microbiologically evaluable patients at end of therapy and at the test-of-cure visit for all pathogens combined , for all S. aureus strains , and for MRSA . Gastrointestinal symptoms were among the most common adverse events in both arms . A higher proportion of patients in the linezolid arm reported adverse events that were judged by the investigator to be probably/possibly related to treatment ( dalbavancin arm , 25.4 % of subjects ; linezolid arm , 32.2 % of subjects ) . CONCLUSIONS Two doses of dalbavancin ( 1000 mg given on day 1 followed by 500 mg given on day 8) were as well tolerated and as effective as linezolid given twice daily for 14 days for the treatment of patients with complicated SSSI , including those infected with MRSA BACKGROUND Post hoc analyses of clinical trial data suggested that linezolid may be more effective than vancomycin for treatment of methicillin-resistant Staphylococcus aureus ( MRSA ) nosocomial pneumonia . This study prospect ively assessed efficacy and safety of linezolid , compared with a dose-optimized vancomycin regimen , for treatment of MRSA nosocomial pneumonia . METHODS This was a prospect i ve , double-blind , controlled , multicenter trial involving hospitalized adult patients with hospital-acquired or healthcare-associated MRSA pneumonia . Patients were r and omized to receive intravenous linezolid ( 600 mg every 12 hours ) or vancomycin ( 15 mg/kg every 12 hours ) for 7 - 14 days . Vancomycin dose was adjusted on the basis of trough levels . The primary end point was clinical outcome at end of study ( EOS ) in evaluable per- protocol ( PP ) patients . Prespecified secondary end points included response in the modified intent-to-treat ( mITT ) population at end of treatment ( EOT ) and EOS and microbiologic response in the PP and mITT population s at EOT and EOS . Survival and safety were also evaluated . RESULTS Of 1184 patients treated , 448 ( linezolid , n = 224 ; vancomycin , n = 224 ) were included in the mITT and 348 ( linezolid , n = 172 ; vancomycin , n = 176 ) in the PP population . In the PP population , 95 ( 57.6 % ) of 165 linezolid-treated patients and 81 ( 46.6 % ) of 174 vancomycin-treated patients achieved clinical success at EOS ( 95 % confidence interval for difference , 0.5%-21.6 % ; P = .042 ) . All-cause 60-day mortality was similar ( linezolid , 15.7 % ; vancomycin , 17.0 % ) , as was incidence of adverse events . Nephrotoxicity occurred more frequently with vancomycin ( 18.2 % ; linezolid , 8.4 % ) . CONCLUSIONS For the treatment of MRSA nosocomial pneumonia , clinical response at EOS in the PP population was significantly higher with linezolid than with vancomycin , although 60-day mortality was similar Summary A prospect i ve , r and omized , multicentre trial was conducted to evaluate the efficacy and safety of roxithromycin ( 150 mg b.i.d . orally ) and penicillin ( 2.5 MU × 8 daily intravenously , then 6 MU daily orally ) in the treatment of hospitalized adult patients with erysipelas . Seventy‐two patients entered the study . Thirty‐one patients in the roxithromycin group and 38 patients in the penicillin group completed the trial . The overall efficacy rates ( cure without additional antibiotics ) were 84 % ( 26/31 ) in the roxithromycin group and 76 % ( 29/38 ) in the penicillin group ( P= 0.43 ) . No side‐effects were observed in the roxithromycin‐treated patients whereas rashes occurred in two cases in the penicillin group , leading to exclusion from the study . Oral roxithromycin can thus be considered an effective and well‐tolerated treatment for erysipelas in adult hospitalized patients ABSTRACT This r and omized , double-blind , multicenter trial compared the efficacy and safety of linezolid , an oxazolidinone , with those of oxacillin-dicloxacillin in patients with complicated skin and soft tissue infections . A total of 826 hospitalized adult patients were r and omized to receive linezolid ( 600 mg intravenously [ i.v . ] ) every 12 h or oxacillin ( 2 g i.v . ) every 6 h ; following sufficient clinical improvement , patients were switched to the respective oral agents ( linezolid [ 600 mg orally ] every 12 h or dicloxacillin [ 500 mg orally ] every 6 hours ) . Primary efficacy variables were clinical cure rates in both the intent-to-treat ( ITT ) population and clinical ly evaluable ( CE ) patients and microbiological success rate in microbiologically evaluable ( ME ) patients . Safety and tolerability were evaluated in the ITT population . Demographics and baseline characteristics were similar across treatment groups in the 819 ITT patients . In the ITT population , the clinical cure rates were 69.8 and 64.9 % in the linezolid and oxacillin-dicloxacillin groups , respectively ( P = 0.141 ; 95 % confidence interval −1.58 to 11.25 ) . In 298 CE linezolid-treated patients , the clinical cure rate was 88.6 % , compared with a cure rate of 85.8 % in 302 CE patients who received oxacillin-dicloxacillin . In 143 ME linezolid-treated patients , the microbiological success rate was 88.1 % , compared with a success rate of 86.1 % in 151 ME patients who received oxacillin-dicloxacillin . Both agents were well tolerated ; most adverse events were of mild-to-moderate intensity . No serious drug-related adverse events were reported in the linezolid group . These data support the use of linezolid for the treatment of adults with complicated skin and soft tissue infections Two phase 3 , double-blind studies in hospitalized adults with complicated skin and skin-structure infections ( cSSSI ) determined the safety and efficacy of tigecycline versus that of vancomycin-aztreonam . Patients received tigecycline ( 100 mg , followed by 50 mg intravenously twice daily ) or vancomycin ( 1 g intravenously twice daily ) plus aztreonam ( 2 g intravenously twice daily ) for up to 14 days . Population s were as follows : 1116 patients ( 566 treated with tigecycline , and 550 treated with vancomycin-aztreonam ) constituted the modified intent-to-treat ( mITT ) population , 1057 patients ( 538 treated with tigecycline , and 519 treated with vancomycin-aztreonam ) constituted the clinical mITT ( c-mITT ) population , and 833 patients ( 422 treated with tigecycline , and 411 treated with vancomycin-aztreonam ) constituted the clinical ly evaluable population . Clinical responses to tigecycline and vancomycin-aztreonam at test-of-cure were similar : c-mITT , 79.7 % ( 95 % confidence interval [ CI ] , 76.1%-83.1 % ) versus 81.9 % ( 95 % CI , 78.3%-85.1 % ) ( P = .4183 ) ; and clinical ly evaluable , 86.5 % ( 95 % CI , 82.9%-89.6 % ) versus 88.6 % ( 95 % CI , 85.1%-91.5 % ) ( P = .4233 ) . Adverse events were similar , with increased nausea and vomiting in the tigecycline group and increased rash and elevated hepatic aminotransferase levels in the vancomycin-aztreonam group . Tigecycline monotherapy is as safe and efficacious as the vancomycin-aztreonam combination in treating patients with cSSSI Abstract Two different doses of quinupristin/dalfopristin were compared with intravenous vancomycin with regard to the efficacy and safety in the treatment of catheter-related staphylococcal bacteremia . A total of 39 patients were enrolled from 13 centers . For all treated patients with a baseline pathogen , outcome was comparable for all antibiotic study regimens . Discontinuation of the antibiotic for an adverse clinical event occurred in 12 % of patients receiving quinupristin/dalfopristin and in 15 % of those receiving vancomycin . Quinupristin/dalfopristin may have the potential to serve as an alternative agent in the treatment of catheter-related staphylococcal bacteremia . However , larger prospect i ve r and omized trials are required Abstract An international , r and omized , open-label , comparative study was undertaken in order to assess the efficacy and safety of azithromycin and cefuroxime , short sequential vs st and ard sequential therapy , respectively , in the treatment of patients with community-acquired pneumonia ( CAP ) . 180 adult patients were included in the study . 89 patients received azithromycin 500 mg intravenously ( i.v . ) once daily for 1 - 4 days followed by azithromycin 500 mg orally once daily for 3 days . 91 patients received cefuroxime 1.5 g i.v . three times daily for 1 - 4 days followed by cefuroxime axetil 500 mg orally twice daily for 7 days . Clinical efficacy was achieved in 67/82 ( 81.7 % ) patients treated with azithromycin , and in 73/89 ( 82.0 % ) patients treated with cefuroxime . The mean duration of total ( i.v . and oral ) therapy was significantly shorter for the azithromycin group than for the cefuroxime group ( 6.2 days vs 10.1 days ) . Adverse events were recorded in 38.2 % of patients treated with azithromycin , and in 29.7 % of patients treated with cefuroxime ( p = 0.20 ) . Shorter sequential i.v.-to-oral azithromycin therapy of patients with CAP was as effective as st and ard sequential i.v.-to-oral cefuroxime therapy In this r and omised , double-blind , comparator-controlled , multicentre study conducted in China , 142 hospitalised patients aged 18 - 75 years with pneumonia ( n=80 ) or complicated skin and soft-tissue infection ( cSSTI ) ( n=62 ) due to suspected or known Gram-positive pathogens were r and omised ( 1:1 ) to receive either linezolid 600 mg ( n=71 ) or vancomycin 1 g in patients aged < or = 60 years or 0.75 g in patients aged > 60 years ( n=71 ) intravenously every 12h . The duration of treatment was 10 - 21 days for patients with pneumonia and 7 - 21 days for patients with cSSTI . Clinical outcomes were assessed at end-of-treatment ( EOT ) visit and follow-up ( FU ) visit 7 - 28 days post therapy . Staphylococcus aureus was the most common pathogen at baseline and most of these isolates were resistant to meticillin . All isolates were susceptible to linezolid and vancomycin . For the evaluable patients , the effective treatment rate for linezolid was higher than that for vancomycin at EOT ( 86.9 % ( 53/61 ) vs. 61.7 % ( 37/60 ) ) and at FU ( 83.1 % ( 49/59 ) vs. 64.9 % ( 37/57 ) ) . Pathogen eradication rates for the microbiologically evaluable patients at FU were 79.2 % ( 42/53 ) for linezolid and 61.5 % ( 32/52 ) for vancomycin . The incidence of drug-related adverse events ( AEs ) was 25.4 % ( 18/71 ) for linezolid and 16.9 % ( 12/71 ) for vancomycin . Four ( 5.6 % ) linezolid-treated and eight ( 11.3 % ) vancomycin-treated patients discontinued the study drug because of an AE . Linezolid was well tolerated and effective for the treatment of infections caused by Gram-positive pathogens , including meticillin-resistant S. aureus OBJECTIVE To compare trimethoprim-sulfamethoxazole ( TMP-SMZ ) and vancomycin regarding efficacy and safety in the therapy of serious Staphylococcus aureus infections . DESIGN R and omized , double-blind comparative trial . SETTING A tertiary-care hospital . PATIENTS One hundred and one intravenous drug users hospitalized with S. aureus infection . MEASUREMENTS Cure and failure rates ; blood and wound cultures ; minimum inhibitory and bactericidal concentrations ; serum inhibitory and bactericidal titers ; temperature ; leukocyte count ; duration s of treatment and hospitalization ; and toxicity . RESULTS Of 228 intravenous drug users , 101 had S. aureus infection and were included in the efficacy analysis ( 43 received TMP-SMZ and 58 received vancomycin ) . Methicillin-resistant S. aureus ( MRSA ) accounted for 47 % of S. aureus isolates , and 65 % of patients were bacteremic . Infections were cured in 57 of 58 vancomycin recipients and in 37 of 43 TMP-SMZ recipients ( P less than 0.02 ) . Failure occurred mostly in patients with tricuspid valve endocarditis and only in those with infection caused by methicillin-sensitive S. aureus ( MSSA ) . The mean duration of bacteremia was 6.7 days in TMP-SMZ recipients and 4.3 days in vancomycin recipients . Among 222 subjects hospitalized for at least 24 hours , toxicity rates were similar for TMP-SMZ ( 23 % ) and vancomycin ( 20 % ) recipients ; nausea and vomiting were associated with TMP-SMZ and inflammation at the intravenous site was associated with vancomycin . Forty-four percent of TMP-SMZ recipients and 29 % of vancomycin recipients experienced side effects in the efficacy cohort ( P greater than 0.05 ) . CONCLUSIONS Vancomycin is superior to TMP-SMZ in efficacy and safety when treating intravenous drug users who have staphylococcal infections . However , all treatment failures occurred in patients with MSSA infection at any site . Therefore , TMP-SMZ may be considered as an alternative to vancomycin in selected cases of MRSA infection BACKGROUND Community-acquired pneumonia ( CAP ) affects 5 - 10 million adults annually in the United States with approximately 1.1 million hospitalizations . Current guidelines recommend fluoroquinolones as monotherapy for treatment of CAP in general medical wards and doxycycline monotherapy for outpatient therapy only . Fluoroquinolones are expensive and development of bacterial resistance to them has become a concern . Therefore , we studied whether doxycycline is as efficacious as levofloxacin in treatment of CAP in general medical wards . METHODS In this prospect i ve double-blinded trial , non-pregnant adults with clinical and radiological evidence of pneumonia requiring hospitalization were enrolled . Patients who were septic , hypoxic requiring intubations , nursing home residents , diagnosed with severe hepatic or renal dysfunction , recently hospitalized or immunocompromised were excluded from the study . Subjects were r and omly assigned to either i.v . levofloxacin 500 mg daily or doxycycline 100 mg twice daily . After discharge , patients were followed for 2 months . RESULTS There were 30 patients in the levofloxacin group and 35 patients in the doxycycline group . Groups were comparable in both clinical and laboratory profiles . Additionally , efficacy of treatment was not significantly different between the two groups ( P = 0.844 ) . Length of stay was 5.7 + /- 2.05 days in the levofloxacin group and 4.0 + /- 1.82 days in the doxycycline group ( P < 0.0012 ) . Failure rate was similar in both groups ( P = 0.893 ) . Total antibiotic cost was $ 122.07 + /- 15.84 for levofloxacin and $ 64.98 + /- 24.4 for doxycycline ( P < 0.0001 ) . CONCLUSIONS Our study supports doxycycline as an effective and economical alternative therapy for levofloxacin in the empirical treatment of CAP in general medical wards Azithromycin , a recently introduced antibiotic , offers the potential advantages of short-course administration and lower toxicity compared to other macrolides . Approved for the treatment of mild pneumonia , this drug was investigated in a study of patients hospitalized for community-acquired pneumonia . In an open-labelled r and omized study , oral azithromycin was compared with intravenous benzylpenicillin in patients suspected to have pneumonococcal pneumonia . Azithromycin was also compared with erythromycin , both administered orally , in all other patients . Three hundred thirty-four patients with community-acquired pneumonia were hospitalized , 108 of whom were r and omized ; 104 could be evaluated . A need for intravenous therapy was the most common reason for exclusion . In the pneumococcal group , 35 patients received azithromycin and 29 benzylpenicillin . The clinical and radiological success rate achieved with azithromycin ( 83 % ) was considerably higher than that achieved with benzylpenicillin ( 66 % ) , though the difference was not significant . In the non-pneumococcal group , 19 patients received azithromycin and 21 erythromycin ; no differences in the success rate were found ( 79 % and 76 % , respectively ) . Eight patients on azithromycin had a blood culture positive forStreptococcus pneumoniae ; in three of these patients therapy was changed . None of the five patients with pneumococcal bacteraemia who received benzylpenicillin required a change in therapy . It is concluded that oral azithromycin , administered as short-course therapy , is an appropriate antibiotic for treating patients with community-acquired pneumonia . However , it is not yet certain that azithromycin is a good choice for patients with pneumococcal bacteraemia BACKGROUND Over the past 50 years , antibiotics of choice for treatment of plague , including streptomycin , chloramphenicol , and tetracycline , have mostly become out date d or unavailable . To test gentamicin in the treatment of naturally occurring plague and the implication s of its use in the treatment of bioterrorist plague , a r and omized , comparative , open-label , clinical trial comparing monotherapy with gentamicin or doxycycline was conducted in Tanzania . METHODS Sixty-five adults and children with symptoms of bubonic , septicemic , or pneumonic plague of < or =3 days duration were enrolled in the study . Bubo aspirates and blood were cultured for Yersinia pestis . Acute-phase and convalescent-phase serum sample s were tested for antibody against fraction 1 antigen of Y. pestis . Thirty-five patients were r and omized to receive gentamicin ( 2.5 mg/kg intramuscularly every 12 h for 7 days ) , and 30 patients were r and omized to receive doxycycline ( 100 mg [ adults ] and 2.2 mg/kg [ children ] orally every 12 h for 7 days ) . Serum creatinine concentrations were measured before and after treatment , and peak and trough concentrations of antibiotics were measured . RESULTS Three patients , 2 of whom were treated with gentamicin and 1 of whom was treated with doxycycline , died on the first or second day of treatment , and these deaths were attributed to advanced disease and complications including pneumonia , septicemia , hemorrhage , and renal failure at the start of therapy . All other patients experienced cure or an improved condition after receiving therapy , result ing in favorable response rates of 94 % for gentamicin ( 95 % CI , 81.1%-99.0 % ) and 97 % for doxycycline ( 95 % CI , 83.4%-99.8 % ) . Y. pestis isolates obtained from 30 patients belonged to biotype antigua and were susceptible to gentamicin and doxycycline , which had MICs of 0.13 mg/L and 0.25 - 0.5 mg/L , respectively . Serum concentrations of antibiotics were within therapeutic ranges , and adverse events were infrequent . Patients treated with gentamicin demonstrated a modest increase in the mean serum creatinine concentration after treatment ( P<.05 , by paired t test ) . CONCLUSIONS Both gentamicin and doxycycline were effective therapies for adult and pediatric plague , with high rates of favorable responses and low rates of adverse events BACKGROUND This open-label study compared oral or intravenous linezolid with intravenous vancomycin for treatment of complicated skin and soft-tissue infections ( cSSTIs ) caused by methicillin-resistant Staphylococcus aureus ( MRSA ) . METHODS Patients with proven MRSA cSSTI were r and omized to receive linezolid or vancomycin . Clinical and microbiologic outcomes , duration of antimicrobial therapy , length of hospital stay , and safety were assessed . RESULTS In the per- protocol population , the rate of clinical success was similar in linezolid- and vancomycin-treated patients ( P = .249 ) . The rate of success was significantly higher in linezolid-treated patients in the modified intent-to-treat population ( P = .048 ) . The microbiologic success rate was higher for linezolid at the end of treatment ( P < .001 ) and was similar at the end of the study ( P = .127 ) . Patients receiving linezolid had a significantly shorter length of stay and duration of intravenous therapy than patients receiving vancomycin . Both agents were well tolerated . Adverse events were similar to each drug 's established safety profile . CONCLUSIONS Linezolid is an effective alternative to vancomycin for the treatment of cSSTI caused by MRSA BACKGROUND This r and omized , open-label , multi-center trial compared tigecycline ( TGC ) , a broad-spectrum glycylcycline , with ceftriaxone-metronidazole ( CTX/MET ) for the treatment of complicated intra-abdominal infections ( cIAI ) . METHODS Eligible subjects were r and omized to receive TGC 100 mg followed by 50 mg q 12 h or CTX 2 g qd plus MET 1 - 2 g daily for 4 - 14 days . Subjects were stratified by Acute Physiology and Chronic Health Evaluation ( APACHE ) II score ≤10 or > 10 and could not receive oral therapy . The primary endpoint was clinical response in the clinical ly evaluable ( CE ) population at the test of cure ( TOC ) assessment 8 - 44 days after the last drug dose . RESULTS Clinical responses in the CE population were 81.8 % ( 162/198 ) vs. 79.4 % ( 150/189 ) for TGC and CTX/MET , respectively ; a weighted estimate of the difference of 1.6 ( 95 % confidence interval [ CI ] -6.4 , 9.6 ) . In the microbiologically evaluable ( ME ) population , microbiological eradication rates were 82.4 % ( 98/119 ) for TGC vs. 79.6 % ( 86/108 ) for CTX/MET : a difference of 2.7 ( 95 % CI -7.9 , 13.3 ) . Common adverse events were nausea ( 21.6 % TGC vs. 21.3 % CTX/MET ) and vomiting ( 17.7 % TGC vs. 13.2 % CTX/MET ) . Discontinuation rates because of adverse events were 7.8 % for TGC and 6.4 % for CTX/MET . CONCLUSIONS Tigecycline was effective in the treatment of cIAI and was non-inferior to CTX/MET for the treatment of cIAI in hospitalized adults . Clinical Trials Identifier : NCT00230971 Intravenous ( i.v . ) to oral linezolid ( 600 mg twice daily for both , with optional aztreonam ) and a cephalosporin regimen ( i.v . ceftriaxone 1 g twice daily followed by oral cefpodoxime 200 mg twice daily ) were compared for the treatment of community-acquired pneumonia ( CAP ) , with emphasis on patients with Streptococcus pneumoniae . This multicenter , r and omized , open-label trial was conducted in 27 countries in 6 continents . Efficacy was assessed 12 - 28 d following treatment . Clinical and laboratory safety assessment s were evaluated ; isolates for microbiologic assessment s were identified primarily by sputum or blood culture . In all treated patients ( linezolid , n = 381 ; ceftriaxone/cefpodoxime , n = 366 ) , linezolid had a higher clinical cure rate than ceftriaxone/cefpodoxime ( 83.0 % vs. 76.4 % , respectively ; p = 0.040 ) . S. pneumoniae was isolated in 73.2 % ( 186/254 ) of patients at baseline , with similar eradication rates in the linezolid and ceftriaxone/cefpodoxime groups ( 88.7 % vs. 89.9 % , respectively ; p = 0.830 ) . Linezolid had a superior clinical cure rate ( 93.1 % vs. 68.2 % ; p = 0.021 ) in patients with S. pneumoniae bacteremia . Logistic regression analyses revealed that linezolid-treated patients with bacteremia , pleural effusion , cardiac comorbidities , diabetes or abnormal white blood cell counts had significantly better outcomes than cephalosporin-treated patients . Both regimens were well tolerated , although the incidence of drug-related adverse events was higher in the linezolid group than in the ceftriaxone/cefpodoxime group ( 21.3 % vs. 11.2 % , respectively ; p = 0.0002 ) . In summary , empiric i.v./oral linezolid was more effective than ceftriaxone/cefpodoxime in patients hospitalized with CAP , with comparable cure rates in S. pneumoniae pneumonia and higher cure rates in pneumonia complicated by bacteremia BACKGROUND Gram-positive pathogens can cause serious infections in neutropenic patients with cancer , and vancomycin therapy is often initiated empirically . Linezolid may offer an option for these patients . METHODS To compare the safety and efficacy of linezolid and vancomycin in febrile , neutropenic patients with cancer , we conducted a double-blind , multicenter equivalence study . Eligible patients with proven or suspected infection due to a gram-positive pathogen were r and omized to receive linezolid or vancomycin . RESULTS Clinical success rates 7 days after completion of therapy ( primary end point ) were equivalent between groups in the intent-to-treat ( ITT ) analysis ( linezolid , 219 [ 87.3 % ] of 251 patients ; vancomycin , 202 [ 85.2 % ] of 237 patients ; 95 % CI , -4.1 to 8.1 ; P=.52 ) , modified ITT analysis , clinical ly evaluable analysis , and microbiologically evaluable analysis , as well as between subsets analyzed by malignancy and infection type . Mean time to defervescence was shorter for linezolid than vancomycin in the modified ITT ( 6.6 vs. 8.5 days ; P=.04 ) and microbiologically evaluable subsets ( 5.9 vs. 9.1 days ; P=.01 ) , although post hoc analyses revealed delayed recovery of absolute neutrophil counts for linezolid in these subsets ( P<.05 ) . There were no between-group differences in microbiologic success rates in the modified ITT subset ( 41 [ 57.7 % ] of 71 patients vs. 29 [ 50.0 % ] of 58 patients ; P=.38 ) and microbiologically evaluable subsets , as well as in mortality rates in the ITT subset ( 17 [ 5.6 % ] of 304 patients vs. 23 [ 7.6 % ] of 301 patients ; P=.31 ) and all subsets . Distribution of adverse events , including reported hematologic events , was similar between groups , except that linezolid was associated with fewer drug-related adverse events ( 52 [ 17.2 % ] of 303 patients vs. 72 [ 24.0 % ] of 300 patients ; P=.04 ) and fewer cases of drug-related renal failure ( 1 [ 0.3 % ] of 303 patients vs. 7 [ 2.3 % ] of patients ; P=.04 ) . CONCLUSIONS Linezolid demonstrated efficacy and similar safety outcomes equivalent to those for vancomycin in febrile neutropenic patients with cancer Abstract Tigecycline ( TGC ) , a first-in-class glycylcycline that has been approved for treating complicated skin and skin structure infections and complicated intra-abdominal infections , has an exp and ed spectrum of activity against Gram-positive , Gram-negative , anaerobic , and atypical bacteria , including resistant strains . The purpose of this study was to compare the efficacy and safety of TGC with levofloxacin ( LEV ) in adult hospitalized patients with community-acquired pneumonia ( CAP ) in a r and omised , doubleblind , phase 3 multinational trial . This analysis evaluated TGC efficacy and safety in the European region . Hospitalised patients from 53 centres in 18 countries received 7 - 14 days of i.v . TGC ( 100-mg loading dose followed by 50 mg every 12 hours ) or i.v . LEV ( 500 mg once or twice daily ) . Co- primary efficacy endpoints were clinical response in clinical ly evaluable ( CE ) and clinical modified intent-to-treat ( c-mITT ) population s at test-of-cure ( TOC ) . Results indicated that 358 patients received at least 1 dose of study medication ( mITT : TGC 177 , LEV 181 ) , 245 were CE ( TGC 125 , LEV 120 ) . Demographics were similar in both groups and the majority of patients had a Fine Pneumonia Severity Index of II to IV ( 84.4 % TGC , 78.2 % LEV , mITT ) . At TOC ( CE ) , TGC cured 112/125 patients ( 89.6 % ; 95 % CI 82.9 , 94.3 ) and LEV cured 103/120 patients ( 85.8 % ; 95 % CI 78.3 , 91.5 ) , absolute difference of TGC-LEV 3.8 % ( 95 % CI -5.3 , 12.8 ; test for noninferiority p<0.001 ) . For those CE patients with a Fine score of < III or III/IV , TGC cured 90.0 % and 88.9 % , and LEV cured 88.5 % and 83.6 % , respectively . In c-mITT , TGC cured 146/173 patients ( 84.4 % ; 95 % CI 78.1 , 89.5 ) and LEV cured 142/173 patients ( 82.1 % ; 95 % CI 75.5 , 87.5 ) , absolute difference of TGC-LEV 2.3 % ( 95 % CI 6.1 , 10.8 ; test for noninferiority p<0.001 ) . In c-mITT patients with a Fine score of < III or III/IV , TGC cured 86.3 % and 81.9 % , and LEV cured 80.7 % and 83.1 % , respectively . Both regimens were generally well tolerated with only a few patients being withdrawn from the study because of any adverse event ( 3 ; 1.6 % TGC versus 2 , 1.1 % LEV ) . The authors concluded that TGC was safe and efficacious in patients hospitalised with CAP , achieving similar efficacy to that of the comparator BACKGROUND To compare the monotherapy of tigecycline with vancomycin-aztreonam in hospitalized patients from India and Taiwan with complicated skin and skin structure infections ( cSSSIs ) . METHODS Safety and efficacy data were analyzed for Indian ( n = 86 ) and Taiwanese ( n = 41 ) patients hospitalized with cSSSIs who participated in two international Phase 3 , r and omized , double-blind studies . RESULTS Patients were treated for 5 - 14 days . Cure rates at the test-of-cure assessment ( 12 - 92 days post-therapy ) were generally similar between tigecycline and vancomycin-aztreonam in the clinical ly evaluable population s ( India , 83.3 % vs. 75.8 % ; Taiwan , 78.6 % vs. 90 % ) and in the clinical modified intent-to-treat population s ( India , 78.6 % vs. 66.7 % ; Taiwan , 73.3 % vs. 75.0 % ) . Nausea and vomiting occurred more frequently with tigecycline , but overall safety and tolerability were comparable between the two treatments . CONCLUSIONS Tigecycline monotherapy is a safe and effective therapy for cSSSIs in geographically distinct population s in Asia In an open , prospect i ve , r and omised study , the clinical and bacteriological efficacy of intravenously administered clarithromycin was compared with that of amoxicillin-clavulanic acid in 112 patients with community-acquired pneumonia requiring hospitalisation . Clinical cure or improvement occurred in 86 % ( 48/56 ) of the clarithromycin-treated patients and 84 % ( 47/56 ) of the amoxicillin-clavulanic acid-treated patients . The rate of bacteriologie eradication was similar for the two drugs as were the rapidity of a clinical response and the rate of improvement of radiological signs . Clarithromycin had a slightly higher rate of side-effects mainly due to phlebitis caused by the intravenous treatment , but treatment could be continued in all cases . Clarithromycin should be used with caution in patients being treated with digoxin because of a significant risk of bradycardia result ing from drug interaction ABSTRACT In a previous phase 3 study , the cure rates that occurred in patients with hospital-acquired pneumonia treated with tigecycline at the approved dose were lower than those seen with patients treated with imipenem and cilastatin ( imipenem/cilastatin ) . We hypothesized that a higher dose of tigecycline is necessary in patients with hospital-acquired pneumonia . This phase 2 study compared the safety and efficacy of two higher doses of tigecycline with imipenem/cilastatin in subjects with hospital-acquired pneumonia . Subjects with hospital-acquired pneumonia were r and omized to receive one of two doses of tigecycline ( 150 mg followed by 75 mg every 12 h or 200 mg followed by 100 mg every 12 h ) or 1 g of imipenem/cilastatin every 8 h. Empirical adjunctive therapy was administered for initial coverage of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa infection , depending on the r and omization regimen . Clinical response , defined as cure , failure of treatment , or indeterminate outcome , was assessed 10 to 21 days after the last day of therapy . In the clinical ly evaluable population , clinical cure with tigecycline 100 mg ( 17/20 , 85.0 % ) was numerically higher than with tigecycline 75 mg ( 16/23 , 69.6 % ) and imipenem/cilastatin ( 18/24 , 75.0 % ) . No new safety signals with the high-dose tigecycline were identified . A numerically higher clinical response was observed with the 100-mg dose of tigecycline . This supports our hypothesis that a higher area under the concentration-time curve over 24 h in the steady state divided by the MIC ( AUC/MIC ratio ) may be necessary to achieve clinical cure in patients with hospital-acquired pneumonia . Further studies are necessary . ( The Clinical Trials.gov identifier for this clinical trial is NCT00707239 . Tigecycline exhibits potent in vitro activity against many community-acquired pneumonia ( CAP ) pathogens , including antibiotic-resistant ones . Its spectrum of activity and ability to penetrate lung tissue suggest it may be effective for hospitalized CAP patients . Hospitalized CAP patients ( n=418 ) were r and omized to receive intravenous ( i.v . ) tigecycline or levofloxacin . Patients could be switched to oral levofloxacin after receiving 6 or more doses of i.v . study medication . Therapy duration was 7 to 14 days . Co primary efficacy end points were clinical responses in the clinical ly evaluable ( CE : tigecycline , n=138 ; levofloxacin , n=156 ) and clinical modified intent-to-treat ( c-mITT : tigecycline , n=191 ; levofloxacin , n=203 ) population s at test-of-cure ( TOC ) . Safety was assessed in the mITT population ( tigecycline , n=208 ; levofloxacin , n=210 ) . Cure rates in tigecycline and levofloxacin groups were comparable in CE ( 90.6 % versus 87.2 % , respectively ) and c-mITT ( 78 % versus 77.8 % , respectively ) population s at TOC . Nausea and vomiting occurred in significantly more tigecycline-treated patients ; elevated alanine aminotransferase and aspartate aminotransferase levels were reported in significantly more levofloxacin-treated patients . There were no significant differences in hospital length of stay , median duration of i.v . or oral antibiotic treatments , hospital readmissions , or number of patients switched to oral levofloxacin . Tigecycline was safe , effective , and noninferior to levofloxacin in hospitalized patients with CAP ABSTRACT The purpose of this study was to evaluate intravenous ( i.v . ) azithromycin followed by oral azithromycin as a monotherapeutic regimen for community-acquired pneumonia ( CAP ) . Two trials of i.v . azithromycin used as initial monotherapy in hospitalized CAP patients are summarized . Clinical efficacy is reported from an open-label r and omized trial of azithromycin compared to cefuroxime with or without erythromycin . Bacteriologic and clinical efficacy results are also presented from a noncomparative trial of i.v . azithromycin that was design ed to give additional clinical experience with a larger number of pathogens . Azithromycin was administered to 414 patients : 202 and 212 in the comparative and noncomparative trials , respectively . The comparator regimen was used as treatment for 201 patients ; 105 were treated with cefuroxime alone and 96 were given cefuroxime plus erythromycin . In the comparative trial , clinical outcome data were available for 268 evaluable patients with confirmed CAP at the 10- to 14-day visit , with 106 ( 77 % ) of the azithromycin patients cured or improved and 97 ( 74 % ) of the comparator patients cured or improved . Mean i.v . treatment duration and mean total treatment duration ( i.v . and oral ) for the clinical ly evaluable patients were significantly ( P < 0.05 ) shorter for the azithromycin group ( 3.6 days for the i.v . group and 8.6 days for the i.v . and oral group ) than for the evaluable patients given cefuroxime plus erythromycin ( 4.0 days for the i.v . group and 10.3 days for the i.v . and oral group ) . The present comparative study demonstrates that initial therapy with i.v . azithromycin for hospitalized patients with CAP is associated with fewer side effects and is equal in efficacy to a 1993 American Thoracic Society-suggested regimen of cefuroxime plus erythromycin when the erythromycin is deemed necessary by clinicians ABSTRACT In a r and omized , double-blind , controlled trial , 546 patients with complicated skin and skin structure infections received tigecycline 100 mg/day ( a 100-mg initial dose and then 50 mg intravenously twice daily ) or the combination of vancomycin 2 g/day ( 1 g intravenously twice daily ) and aztreonam 4 g/day ( 2 g intravenously twice daily ) for up to 14 days . The primary end point was the clinical response in the clinical modified intent-to-treat ( c-mITT ) and clinical ly evaluable ( CE ) population s at the test-of-cure visit 12 to 92 days after the last dose . The microbiologic response at the test-of-cure visit was also assessed . Safety was assessed by physical examination , laboratory results , and adverse event reporting . Five hundred twenty patients were included in the c-mITT population ( tigecycline group , n = 261 ; combination group , n = 259 ) , and 436 were clinical ly evaluable ( tigecycline group , n = 223 ; combination group , n = 213 ) . The clinical responses in the tigecycline and the combination vancomycin and aztreonam groups were similar in the c-mITT population ( 84.3 % versus 86.9 % ; difference , −2.6 % [ 95 % confidence interval , −9.0 , 3.8 ] ; P = 0.4755 ) and the CE population ( 89.7 % versus 94.4 % ; difference , −4.7 % [ 95 % confidence interval , −10.2 , 0.8 ] ; P = 0.1015 ) . Microbiologic eradication ( documented or presumed ) occurred in 84.8 % of the patients receiving tigecycline and 93.2 % of the patients receiving vancomycin and aztreonam ( difference , −8.5 [ 95 % confidence interval , −16.0 , −1.0 ] ; P = 0.0243 ) . The numbers of patients reporting adverse events were similar in the two groups , with increased nausea and vomiting rates in the tigecycline group and an increased incidence of rash and increases in alanine aminotransferase and aspartate aminotransferase levels in the combination vancomycin and aztreonam group . Tigecycline was shown to be safe and effective for the treatment of complicated skin and skin structure infections |
878 | 23,076,903 | Compared to women who had GA , women who had either epidural anaesthesia or spinal anaesthesia were found to have a significantly lower difference between pre and postoperative haematocrit .
There is no evidence from this review to show that RA is superior to GA in terms of major maternal or neonatal outcomes . | BACKGROUND Regional anaesthesia ( RA ) and general anaesthesia ( GA ) are commonly used for caesarean section ( CS ) and both have advantages and disadvantages .
It is important to clarify what type of anaesthesia is more efficacious .
OBJECTIVES To compare the effects of RA with those of GA on the outcomes of CS . | UNLABELLED Anesthetic methods used during cesarean section have advantages and disadvantages to both mothers and infants and may result in short and long term neonatal effects . OBJECTIVE To determine the effects of general and regional anesthesia on the infants , a prospect i ve , r and omized trial was performed in Siriraj Hospital , Mahidol University . MATERIAL AND METHOD 341 uncomplicated pregnant women who were to be delivered at term by Cesarean section were recruited and r and omized to receive general anesthesia , GA ( 103 ) ; epidural anesthesia , EA ( 120 ) and spinal anesthesia , SA ( 118 ) . The immediate fetal and neonatal effects were assessed by cord blood gas analysis and the infant 's Apgar scores . The Neurologic and Adaptive Capacity Scores ( NACS ) was performed within 4 hours after birth by two pediatricians who were blind to the anesthetic method . RESULT Maternal age , weight , height , duration of the operation and infants ' birth weight were not different among the study groups . In the EA and SA group , maternal systolic blood pressure decreased more than 20 per cent from the baseline in more than half . The infants ' Apgar scores at 1 and 5 minutes were 8.3 + /- 1.9 ; 8.2 + /- 1.6 ; 6.7 + /- 2.8 , and 9.7 + /- 0.9 ; 9.8 + /- 0.7 ; 9.2 + /- 1.6 in EA , SA and GA group respectively . The adaptive capacity , active tone , passive tone , general assessment and primary reflexes of the NACS were not statistically different . CONCLUSION Apgar scores of the infants whose mothers received general anesthesia were lower than infants whose mothers received regional anesthesia but the NACS were not statistically different among the three study groups Ninety healthy parturients undergoing elective caesarean section were r and omly allocated to receive either general ( n = 30 ) , epidural ( n = 30 ) or spinal ( n = 30 ) anaesthesia . Acid-base status , Apgar score and neurobehavioural status , using the neurologic and adaptive capacity scoring ( NACS ) system , were studied in the newborn . Apgar scores and acid-base parameters were similar in all the three groups . NACS testing revealed significantly more vigorous babies in the spinal anaesthesia group than in the other two groups at 15 min and 2 h interval after delivery , despite a higher incidence of maternal hypotension . We conclude that newborns tend to have a better neurobehavioural status in the early post-delivery period if their mothers receive spinal anaesthesia rather than general or epidural anaesthesia for caesarean section Objective : To compare general , epidural and combined spinal-epidural anesthesia with respect to short-term outcome of newborns delivered by elective Cesarean section of healthy parturients with normal pregnancies . Study design : A total of 238 eight pregnant women admitted to our institution between January 1998 and July 2002 , for whom elective Cesarean section was planned after 38 weeks ' gestation , were grouped according to the kind of anesthesia used for the procedure . Maternal characteristics , birth weight , Apgar scores , and maternal and umbilical artery ( UA ) acid-base parameters were analyzed . Results : Maternal pH was significantly lower and pCO2 and pO2 were significantly higher in the general anesthetic group , compared to the other two groups ( 7.38 ± 0.03 vs. 7.43 ± 0.02 and 7.43 ± 0.05 , respectively ; 35.03 ± 3.88 mmHg vs. 29.25 ± 5.05 mmHg and 29.64 ± 4.16 mmHg , respectively ; and 224.56 ± 86.77 mmHg vs. 151.28 ± 38 mmHg and 157.36 ± 53.51 mmHg , respectively , p < 0.05 ) . The pH of the UA was higher in the general anesthetic group , compared to the spinal-epidural group ( 7.29 ± 0.02 vs. 7.26 ± 0.06 , p < 0.05 ) . The pO2 as well as O2 saturation of the UA were higher when general anesthetic was administered , compared to the two regional modalities ( 15.60 ± 5.48 mmHg vs. 9.29 ± 4.41 mmHg and 9.20 ± 4.06 mmHg , respectively ; and 17.37 ± 9.79 % vs. 7.87 ± 4.98 % and 6.90 ± 5.22 % , respectively , p < 0.05 ) . UA O2 saturation fell to zero in some cases in the combined spinal-epidural group , without an evident effect on fetal well-being . No fetal acidemia was noted in any group . Neonatal outcomes were similar in the three groups studied . Conclusions : Type of anesthesia does not influence short-term outcomes in infants born via elective Cesarean section , although differences in acid-base status of both the mother and especially the newborn recommend careful use of spinal anesthesia Both epidural and general anesthesia can impair thermoregulatory mechanisms during surgery . However , there is lack of information about the effects of different methods of anesthesia on newborn temperature . The purpose of this study was to determine whether there are differences in newborn rectal temperature related to type of anesthesia . Sixty-three pregnant women were r and omly assigned to receive general or epidural anesthesia . Maternal core temperature was measured three times with a rectal probe just before anesthesia , at the beginning of surgery and at delivery . In addition , umbilical vein blood was sample d for pH. The rectal temperatures of the babies were recorded immediately after delivery , and Apgar scores were determined 1 , 5 , and 10 min after birth . The duration of anesthesia and the volume of intravenous fluid given during the procedure ( 833 + /- 144 vs 420 + /- 215 mL ) were significantly higher in the epidural group than in the general anesthesia group ( P < 0.0001 ) . Maternal rectal temperatures were not different in both groups at all measurements . In contrast , newborn rectal temperatures were lower in the epidural anesthesia group than in the general anesthesia group ( 37.4 + /- 0.3 vs 37.6 + /- 0.3 degrees C ; P < 0.05 ) immediately after birth . Furthermore , the umbilical vein pH value ( 7.31 + /- 0.05 vs 7.33 + /- 0.01 ; P < 0.05 ) and Apgar scores at the 1st-min measurement ( 8.0 + /- 0.9 vs 8.5 + /- 0.7 ; P < 0.05 ) were lower in the epidural anesthesia group than in the general anesthesia group . Since epidural anesthesia requires more iv fluid infusion and a longer time for cesarean section , it involves a risk of a mild temperature reduction for the baby which , however , did not reach the limits of hypothermia OBJECTIVE To compare general and spinal anesthesia with respect to the short-term outcome of newborns born by elective cesarean deliveries . METHODS Pregnant women admitted to our hospital from January 1999 to July 2000 , for whom elective repeat cesareans were planned after 37 weeks gestation , were allocated r and omly after their informed consent to spinal anesthesia or general anesthesia . Maternal age , gestational age , birth weight , Apgar 's score , hospital stay duration , and duration of cesarean section time were all noted . The rate of the neonatal respiratory depression , perinatal asphyxia , and admittance to the neonatal intensive care unit of the infants were documented . We also studied arterial sample s withdrawn from the cord for the pH , bicarbonate , PaO(2 ) ( oxygen pressure , arterial ) , and PaCO(2 ) ( carbon dioxide pressure , arterial ) . The serum levels of creatine kinase with myocardial-specific isoform , aspartate aminotransferase , alanine aminotransferase , and total cortisol levels of the newborns were measured and served in ruling out perinatal stress and in confirming the diagnosis of perinatal asphyxia ( and of myocardial damage ) . Statistical analyses was performed with the use of an unpaired Student 's t-test , Chi-square test , and a power calculation was done . RESULTS From the r and omly selected patients , we had 38 ( 45.2 % ) infants for general anesthesia and 46 ( 54.8 % ) for spinal anesthesia . None of our primary endpoints favored any of the study groups , and the clinical short-term outcome of the infants was similar in the neonates born both by spinal and general anesthesia ( P>0.05 ) . The biochemical assays did not rule out or confirm any differences in the occurrence of perinatal stress ( P>0.05 ) . CONCLUSION Anesthesia type does not seem to influence the short-term outcome of the newborn infants for the elective cesarean deliveries . We believe that both spinal and general anesthesia could be performed in elective term cesarean deliveries without any risk to the newborn infants OBJECTIVE To evaluate the suitability of spinal and general anaesthesia for cesarean section . METHODS The prospect i ve , double-blinded study , done between March and December 2009 , at Central Education and Research Hospital , Erzurum , Turkey , involved 60 patients undergoing elective cesarean surgery . They were grouped according to the kind of anaesthesia , with each group having 30 patients each . Postoperative pain scores , opioid requirement , side effects and patient satisfaction were compared through statistical analysis using SPSS version 10 . RESULTS Patient demographics were similar in both groups . Patients in the general anaesthesia group consumed 638.4 + /- 179.10 microg fentanyl , while patients in the spinal anaesthesia group consumed 356.3 + /- 87.1 microg . The number of patients requiring opioid via Patient Controlled Analgesia in the first 24 hours was significantly higher in the general anaesthesia group . Patient satisfaction was significantly higher in the spinal anaesthesia group . CONCLUSION Type of anaesthesia for elective cesarean section is important to provide sufficient post-operative analgesia and patient satisfaction Forty-seven healthy parturients undergoing elective Caesarean section were r and omly allocated to either general anaesthesia ( n = 24 ) or epidural anaesthesia ( n = 23 ) under st and ardized anaesthetic and surgical conditions . Seven women of the epidural group required additional systemic analgesia or sedation following delivery of the neonate . Nine of 24 newborns obtained 1-min Apgar scores below 7 after general anaesthesia compared to only 3/23 after epidural anaesthesia . The time period to establish normal colour in the babies was 2.2 min after epidural and 4.9 min after general anaesthesia . Three of the 24 general-anaesthesia newborns demonstrated a tendency to hypotonia compared to only one in the epidural group . Twenty-four hours and 7 days after delivery all infants of both groups were completely normal . At the time of delivery maternal PO2 was higher in the general anaesthesia compared to the epidural group , due to higher inspired oxygen concentrations . Comparable results were obtained in umbilical PO2 venous values ; lower pH values , however , were observed in the umbilical artery after general anaesthesia . There were no significant differences in the glucose levels between the groups . A significant correlation was established between uterine incision-delivery interval and 1-min neonatal Apgar scores in the general-anaesthesia group , but not in the epidural group . Our investigation did not show either the incision-delivery interval or the start of operation-delivery interval to play a role in neonatal outcome . Epidural anaesthesia is superior to general anaesthesia in Caesarean section under normal conditions with regard to neonatal outcome . Whether this is also true for critical conditions can not be concluded from this study Background There are no r and omized studies on neonatal outcome after spinal versus general anesthesia for cesarean delivery in preeclamptic patients with a nonreassuring fetal heart trace . This study examined both markers of neonatal hypoxia and maternal hemodynamics . Methods Seventy patients were r and omized to general ( n = 35 ) or spinal anesthesia ( n = 35 ) . The general anesthesia group received thiopentone , magnesium sulfate , and suxamethonium intravenously before intubation , followed by 50 % nitrous oxide in oxygen , 0.75–1.5 % isoflurane , and morphine after delivery . The target end-tidal partial pressure of carbon dioxide ( Pco2 ) was 30–34 mmHg . The spinal anesthesia group received 1.8 ml hyperbaric bupivacaine plus 10 & mgr;g fentanyl at the L3–L4 interspace . Heart rate and blood pressure were measured at specific time points . Hypotension was treated with ephedrine . Maternal arterial and neonatal umbilical arterial blood gas sample s were taken at delivery . Resuscitation requirements were recorded . Results In both groups , hemodynamic measures remained within acceptable limits . Spinal anesthesia patients required more ephedrine ( 13.7 vs. 2.7 mg ) . Maternal Paco2 was lower in the spinal group ( 28.9 vs. 32.4 mmHg ) . One-minute Apgar scores were lower after general anesthesia . Base deficit was greater ( 7.13 vs. 4.68 mEq/l ) and neonatal umbilical arterial pH was lower ( 7.20 vs. 7.23 ) after spinal anesthesia . Post hoc analysis showed that if maternal diastolic blood pressure on admission was greater than 110 mmHg , neonatal umbilical arterial base deficit was greater after spinal anesthesia . There was no difference in the number of patients with Apgar scores less than 7 at 1 or 5 min or umbilical arterial pH less than 7.2 or in the requirements for resuscitation . Conclusions In preeclamptic patients with a nonreassuring fetal heart trace , spinal anesthesia for cesarean delivery was associated with a greater mean neonatal umbilical arterial base deficit and a lower median umbilical arterial pH. The clinical significance remains to be established . Maternal hemodynamics were similar and acceptable with either anesthetic technique In this r and omized , multicenter study we compared the hemodynamic effects of spinal and epidural anesthesia for cesarean delivery in severely preeclamptic patients . The epidural group ( n = 47 ) received 2 % lidocaine with epinephrine 1:400,000 , 18 - 23 mL , followed by 3 mg of morphine after delivery . The spinal group ( n = 53 ) received 2.2 mL of 0.5 % hyperbaric bupivacaine plus 0.2 mg morphine . We hypothesized that the lowest MAP ( mean arterial blood pressure , the primary outcome ) during the delivery period would have to be at least 10 mm Hg less in the spinal group to be of clinical importance . We found that there was a statistically significant difference in MAP , with more patients in the spinal group exhibiting hypotension ( P < 0.001 ) . Although the incidence of hypotension ( systolic arterial blood pressure , SAP < or = 100 mm Hg ) was more frequent in the spinal group than in the epidural group ( 51 % versus 23 % ) , the duration of significant hypotension ( SAP < or = 100 mm Hg ) was short ( < or = 1 min ) in both groups . There was more use of ephedrine in the spinal group than in the epidural group ( median , 6 versus 0 mg ) but hypotension was easily treated in all patients . Neonatal outcomes assessed by Apgar scores and the umbilical arterial blood gas analysis were similar in both groups . Adverse neonatal outcomes ( 5-min Apgar score < 7 and umbilical arterial blood pH < 7.20 ) were found in only 2 premature newborns ( weight < 1500 g ) who were born without maternal hypotension after regional anesthesia . We conclude that the results of this large prospect i ve study support the use of spinal anesthesia for cesarean delivery in severely preeclamptic patients OBJECTIVE To study the efficacy and safety of spinal anesthesia for elective cesarean section as compared with general anesthesia . PATIENTS AND METHODS 175 women undergoing elective cesarean section were studied prospect ively . They were allocated into two groups ; the first group ( n=60 ) received spinal anesthesia , and the second one ( n=115 ) received general anesthesia for elective cesarean section . Preoperative and intraoperative BP and IV fluids were recorded . Chi-Square and Fisher 's exact tests were used to compare differences between the two groups ; p < 0.05 was considered significant . RESULTS There were no differences between the two groups in terms of demographics , indication for elective cesarean section , operative time , gestational age , 1 and 5-min Apgar scores , and the means of preoperative and postoperative systolic and diastolic BP . A statistically significant increase was observed in terms of hypotension , postoperative analgesia , pre-induction and intraoperative IV fluids in the spinal group as compared to the general anesthesia group ( p < 0.001 , p < 0.01 , and p < 0.01 , respectively ) . CONCLUSION Spinal anesthesia is as effective as a general anesthesia . Maternal and fetal outcome are favorable . Maternal hypotension can be managed successfully with modest doses of ephedrine and IV fluid infusions . It provides sufficient postoperative analgesia allowing the mother to have more vitality and comfort than those who receive general anesthesia Purpose Neonatal jaundice , a frequent problem in neonatology , can be influenced by many factors . Here , we sought to clarify the role of anesthesia and to compare the effects of various anesthesiological strategies on neonatal bilirubin levels during cesarean section . Methods We prospect ively enrolled 167 ASA I – II status uncomplicated pregnant women who delivered by cesarean section as the study group . The patients were r and omized based on anesthesiological strategy : inhalation ( IA ) , spinal ( SA ) , total intravenous ( TIVA ) , and epidural anesthesia ( EA ) groups . Neonatal total ( TB ) and direct bilirubin ( DB ) levels at the 24th hour and 5th day of life and the need for phototherapy were compared between the groups . Results Direct bilirubin levels at 24th hour of SA group and EA group were higher compared to IA group ( p = 0.008 ) . When DB levels at fifth day were compared , levels in group TIVA were significantly higher than group SA ( p = 0.019 ) . TB levels at fifth day in group TIVA were higher than SA and EA groups ( p = 0.05 ) . The percentage of newborns needing phototherapy did not differ significantly among groups , but was highest in the TIVA group ( 25 % ) , followed by the IA ( 15 % ) , EA ( 10 % ) and SA ( 7 % ) groups ( p = 0.08 ) . Conclusions EA and SA at cesarean section seem to be better among the four anesthesia techniques considering neonatal hyperbilirubinemia . Our findings are consistent with the idea that anesthesia may be a risk factor for hyperbilirubinemia . Although anesthesia may not significantly increase the need for interventions such as phototherapy , it may increase the burden of time , labor and cost This r and omized study compared sevoflurane 1 % and isoflurane 0.5 % in terms of maternal and neonatal outcomes . In addition , neonatal outcome in both groups was compared with a cohort of patients delivered by cesarean birth using spinal anesthesia . Fifty-five patients presenting for elective cesarean birth under general anesthesia were r and omly assigned to receive either sevoflurane 1 % or isoflurane 0.5 % in a 50 % nitrous oxide and oxygen mixture for maintenance . Twenty patients requesting regional anesthesia received a subarachnoid block using 1.5 mL bupivacaine 0.75 % in 8.25 % dextrose with fentanyl 10 micro gram . Intraoperative hemodynamic variables and perioperative adverse events were recorded . Neonatal data included Apgar scores at 1 and 5 min , umbilical artery gas analysis , neurologic adaptive capacity scores ( NACS ) at 2 and 24 h , and a modified neonatal behavioral assessment scale ( NBAS ) at 24 h. Sevoflurane and isoflurane at equianesthetic concentrations ( 0.46 MAC-h [ minimum alveolar anesthetic concentration hours ] ) were associated with similar blood pressure and heart rate changes during the operation . Blood loss , uterine tone , and perioperative complications were not problematic and were similar with the two drugs . No differences were seen in emergence times or in the time to being judged fit for discharge from the recovery room . Similarly , the level of postoperative comfort was the same in both groups . Comparing the general and the spinal anesthetic groups , no differences could be detected in neonatal outcome . Fluoride concentrations were modestly increased above preoperative levels in maternal and umbilical blood sample s after sevoflurane administration . We conclude that there are no significant differences between sevoflurane 1 % and isoflurane 0.5 % for maintenance of general anesthesia during cesarean birth . ( Anesth Analg 1995;81:90 - 5 Objective To evaluate the maternal and fetal effects of three anesthetic methods used r and omly in women with severe preeclampsia who required cesarean delivery . Methods Eighty women with severe preeclampsia , who were to be delivered by cesarean , were r and omized to general ( 26 women ) , epidural ( 27 ) , or combined spinalepidural ( 27 ) anesthesia . The mean preoperative blood pressure ( BP ) was approximately 170/110 mmHg , and all women had proteinuria . Anesthetic and obstetric management included antihypertensive drug therapy and limited intravenous ( IV ) fluid and drug therapy . Results The mean gestational age at delivery was 34.8 weeks . All infants were born in good condition as assessed by Apgar scores and umbilical arterial blood gas determinations . Maternal hypotension result ing from regional anesthesia was managed without excessive IV fluid administration . Similarly , maternal BP was managed without severe hypertensive effects in women undergoing general anesthesia . There were no serious maternal or fetal complications attributable to any of the three anesthetic methods . Conclusion General as well as regional anesthetic methods are equally acceptable for cesarean delivery in pregnancies complicated by severe preeclampsia if steps are taken to ensure a careful approach to either method Background : In 1981 , with support from the American Society of Anesthesiologists and the American College of Obstetricians and Gynecologists , anesthesia and obstetric providers were surveyed to identify the personnel and methods used to provide obstetric anesthesia in the United States . The survey was exp and ed and repeated in 1992 with support from the same organizations . Methods : Comments and questions from the American Society of Anesthesiologists Committee on Obstetrical Anesthesia and the American College of Obstetricians and Gynecologists Committee on Obstetric Practice were added to the original survey instrument to include newer issues while allowing comparison with data from 1981 . Using the American Hospital Association registry of hospitals , hospitals were differentiated by number of births per year ( stratum I , > or= to 1,500 births ; stratum II , 500–1,499 births ; stratum III , < 500 births ) and by U.S. census region . A stratified r and om sample of hospitals was selected . Two copies of the survey were sent to the administrator of each hospital , one for the chief of obstetrics and one for the chief of anesthesiology . Results : Compared with 1981 data , there was an overall reduction in the number of hospitals providing obstetric care ( from 4,163 to 3,545 ) , with the decrease occurring in the smallest units ( 56 % of stratum III hospitals in 1981 compared with 45 % in 1992 ) . More women received some type of labor analgesia , and there was a 100 % increase in the use of epidural analgesia . However , regional analgesia was unavailable in 20 % of the smallest hospitals . Spinal analgesia for labor was used in 4 % of parturients . In 1981 , obstetricians provided 30 % of epidural analgesia for labor ; they provided only 2 % in 1992 . Regional anesthesia was used for 78–85 % ( depending on strata ) of patients undergoing cesarean section , result ing in a marked decrease in the use of general anesthesia . Anesthesia for cesarean section was provided by nurse anesthetists without the medical direction of an anesthesiologist in only 4 % of stratum I hospitals but in 59 % of stratum III hospitals . Anesthesia personnel provided neonatal resuscitation in 10 % of cesarean deliveries compared with 23 % in 1981 . Conclusions : Compared with 1981 , analgesia is more often used by parturients during labor , and general anesthesia is used less often in patients having cesarean section deliveries . In the smallest hospitals , regional analgesia for labor is still unavailable to many parturients , and more than one half of anesthetics for cesarean section are provided by nurse anesthetists without medical direction by an anesthesiologist . Obstetricians are less likely to personally provide epidural analgesia for their patients . Anesthesia personnel are less involved in newborn resuscitation Objective . To compare neonatal short-term outcome in patients who underwent spinal , general anaesthesia and conversion from spinal to general anaesthesia . Methods . One hundred seventy-nine pregnant women undergoing elective caesarean section were allocated r and omly to general ( n = 89 ) or spinal anaesthesia ( n = 90 ) and compared with 63 patients who required conversion to general anaesthesia . Umbilical cord artery pH , Apgar score as well as its individual parameter and need for assisted ventilation were evaluated . Results . No differences were found in pH values ( p = 0.35 ) , while the need for assisted ventilation differed significantly ( p = 0.001 ) . The rate of depressed newborns was 1.1 % in the spinal group , 25.9 % in the general group and 12.7 % in the conversion group with a significant difference for all comparisons . At 5-min , all newborns were vigorous . At 1 min , a higher score for each parameter was found in spinal group with respect to general group , while ‘ activity ’ , ‘ grimace ’ and ‘ respiration ’ showed a higher score in conversion group than in general group . At 5 min , a difference was found only for ‘ activity ’ . Conclusions . All kinds of anaesthesia seem to be safe , but loco-regional blockade shows more advantages on the neonatal outcome also when a conversion is necessary Umbilical arterial blood gas analysis is the most objective method to assess fetal well being at birth , is the gold st and ard assessment of uteroplacental function and fetal oxygenation/acid-base status at birth , and it excludes the diagnosis of birth asphyxia in approximately 80 % of depressed newborns at term . This study was design ed to determine the effect of the type of delivery on umbilical cord blood gases and on free radical activity together with antioxidation in the fetus . Ninety-six pregnant women between 37 and 42 weeks of gestation were included to the study and r and omly assigned to the one of three groups : Group 1 ( n = 40 ) were vaginally delivered , Group 2 ( n = 26 ) had cesarean section with epidural anaesthesia , and Group 3 ( n = 30 ) had cesarean section under general anaesthesia . Umbilical artery blood gas analysis was performed just after the delivery of the fetus together with melondealdehyde and glutathione . The umbilical arterial PO2 was found to be higher in Group 3 , and malondealdehyde and glutathione levels were lower in newborns of Group 2 . It can be concluded that cesarean section with epidural anaesthesia is safer when lipid peroxides are concerned There are few consistent guidelines in choosing anesthesia for cesarean section for a parturient with placenta previa . This prospect i ve r and omized trial was organized to compare the maternal hemodynamics , blood loss and neonatal outcome of general versus epidural anesthesia for cesarean section with the diagnosis of grade 4 placenta previa . After giving informed consent , 12 patients received general anesthesia and 13 received epidural . Intraoperative blood pressures demonstrated a more stable course in the epidural group than in the general group . Blood loss did not differ significantly between the groups ( 1622 + /- 775 mL vs. 1418 + /- 996 mL ) . General anesthesia result ed in lower immediate postoperative hematocrit level ( 28.1 + /- 3.5 % vs. 32.5 + /- 5.0 % , P < 0.05 ) . The patients in the general group received a significantly larger transfusion than the epidural group ( 1.08 + /- 1.6 vs. 0.38 + /- 0.9 units , P < 0.05 ) . The Apgar scores at 1 and 5 min were similar in the two groups ( 8 [ 4 - 9 ] vs. 8 [ 7 - 9 ] and 10 [ 6 - 10 ] vs. 9 [ 9 - 10 ] , respectively ) . We concluded that epidural anesthesia is superior to general anesthesia in elective cesarean section for grade 4 placenta previa with regard to maternal hemodynamics and blood loss . There was no difference in neonatal outcome BACKGROUND Eclamptic patients undergoing caesarean delivery present extreme management problems for both obstetricians and anaesthetists . These problems reflect a poor maternal and perinatal outcome . OBJECTIVE To determine outcomes following the use of infiltrative anaesthesia ( gLA ) compared with general anaesthesia ( gGA ) in eclamptic patients undergoing caesarean section . METHODS Eclamptic patients scheduled for emergency caesarean section were prospect ively studied . They were r and omised into two groups to receive either infiltration with local anaesthetic or general anaesthesia for caesarean section . The protocol used for this study included clinical and sociodemographic data , chest examination prior to administration of anaesthesia , maternal and perinatal outcome , duration of maternal hospital stay and intraoperative blood pressure measurement . RESULTS There were a total of 76 eclamptic patients in the study . There were no significant differences between the infiltration and general anaesthesia groups with regard to clinical and bio-socio-demographic parameters . Fourteen ( 40.0 % ) newborns in the gLA had lowerApgar scores in the first minute than 27 ( 73.0 % ) in the gGA group . Five ( 14.3 % ) newborns were stillbirths in gLA while 2 ( 5.4 % ) were found in the gGA . Twenty-one ( 60.0 % ) in gLA had Apgar scores e"8 compared to 10 ( 27.0 % ) in the gGA . The duration of hospital stay was longer in the gGA ( 17.1+/-4.1 days ) than the gLA ( 13.0+/-1.6 days ) with a statistically significant difference ( p<0.0001 ) . There were five ( 12.5 % ) maternal deaths in the gGA and two ( 5.0 % ) in the gLA . Intraoperatively , the mean arterial pressure and mean systolic pressure at skin incision were consistently and significantly higher in the gGA group than in gLA group . CONCLUSION Local infiltrative anaesthesia appears to have a better maternal and perinatal outcome than general anaesthesia for eclamptic patients undergoing caesarean section We assessed the influence of anesthetic technique for cesarean section on neonatal outcome . Thirty parturient women ( ASA I/II ) were r and omly allocated into two groups . In Group GA general anesthesia was induced with 4 mg·kg–1 thiopental and 1.5 mg·kg–1 succinylcholine . In group EA epidural anesthesia was performed with 20 ml 0.375 % bupivacaine through L3–4 inter-space . 1-min Apgar scores were significantly higher in group EA ( p < 0.001 ) . Neurologic and Adaptive Capacity scores at 2 and 24 h were higher in group EA ( p < 0.001 ) . In terms of blood gas values , umbilical arterial pH and pO2 values were higher in group EA ( p < 0.05 and p < 0.001 , respectively ) . The first breast-feeding intervals were found to be shorter in group EA ( p < 0.001 ) . We conclude that in terms of better Apgar and NAC scores , acid-base status and earlier initiation of breast-feeding , the epidural anesthesia may be preferred to general anesthesia in cesarean section BACKGROUND Cytokines are significant mediators of the immune response to surgery and also play a role in parturition . The aim of the study was to investigate the impact of the anesthetic technique for cesarean section on plasma levels of cytokines IL-6 and TNF-alpha . METHODS Thirty-five parturients scheduled for elective cesarean section were r and omly assigned to general ( n=18 ) or neuraxial ( n=17 ) anesthesia . The general anesthesia group received thiopental 4 mg/kg , succinylcholine 1 - 1.5 mg/kg and 1 % end-tidal concentration of sevoflurane in nitrous oxide and 50 % oxygen . The neuraxial anesthesia group received intrathecal 0.5 % levobupivacaine 1.8 - 2.2 mL and epidural fentanyl 1 microg/kg . Blood sample s were taken for IL-6 and TNF-alpha immediately after positioning the parturient on the operating table , after uterine incision and before the umbilical cord clamping and 24h after surgery ( T(1 ) , T(2 ) and T(3 ) respectively ) . RESULTS The two groups did not differ in IL-6 ( P=0.15 ) or TNF-alpha ( P=0.73 ) serum concentrations at any time point . In the general and neuraxial anesthesia groups , IL-6 serum concentrations were significantly higher in the third blood sample , T(3 ) ( 12.2+/-5.0 and 15.2+/-4.3 pg/mL ) , than in T(1 ) ( 0.41+/-0.38 and 0.29+/-0.10 pg/mL ) and T(2 ) ( 0.37+/-0.47 and 0.24+/-0.05 ) respectively ( P<0.001 ) . Within each group , serum TNF-alpha concentrations did not differ significantly over time ( P=0.44 ) . CONCLUSIONS Under the present study design anesthetic technique did not affect IL-6 or TNF-alpha concentrations in parturients undergoing elective cesarean section . Serum IL-6 levels increased 24 h postoperatively independently of anesthetic technique Ideal method of anaesthesia during caesarean section in women with severe pre-eclampsia is difficult to decide . The aim and objective of the study were to compare neonatal outcome in women with severe pre-eclampsia , undergoing caesarean section in intrapartum period , either under general or spinal anaesthesia . Women with severe pre-eclampsia , undergoing caesarean section in intrapartum period , were included in the study . Diastolic blood pressure was kept below 100 mm Hg by giving parenteral labetalol pre-operatively . All women received prophylactic magnesium sulphate ( 5 g IV and 10 g IM ) . Maternal blood- gas parameters were measured . Scalp blood pH estimation was done in all cases . Women undergoing caesarean section were r and omised into two groups and received either spinal or general anaesthesia . Umbilical arterial catheterisation was done for collecting blood for estimating neonatal blood- gas parameters . Complete data was available in 82 women . Both the groups were comparable in terms of general demographic data , except that percentage of women having an induced labour was significantly more in the general anaesthesia group . Induction of anaesthesia and delivery interval was prolonged for the spinal group . Mean dose of phenylephrine was significantly higher for the spinal anaesthesia group . Preoperative maternal blood-gas parameters and foetal scalp blood pH were comparable in between groups . Difference in neonatal umbilical artery base deficit in between groups was not statistically significant ( p = 0.99 ) . Correlation coefficient between maternal base deficit and foetal base deficit was 0.414 ( p = 0.01 ) and 0.06 ( p > 0.1 ) respectively for general and spinal anaesthesia . Subgroup analysis in the population with pre-operative scalp blood pH < 7.2 , neonatal umbilical artery base deficit was significantly higher in general anaesthesia group . Five minutes APGAR score was comparable but resuscitation at birth was more common in the general anaesthesia group . Correlation coefficient between maternal base deficit and foetal base deficit in this subgroup was 0.42 ( p = 0.05 ) and -0.57 ( p < 0.05 ) respectively for general and spinal anaesthesia OBJECTIVE A prospect i ve r and omized trial was organized to compare the effectiveness of general and regional anesthesia for cesarean section ( C/S ) . METHOD Three hundred and forty-one patients were r and omized into the general anesthesia group ( GA ) , epidural anesthesia group ( EA ) and spinal anesthesia group ( SA ) . The effectiveness of interest was success rate , blood loss and patient satisfaction . RESULT We found that the success rates of EA and SA were lower than GA . Success in EA should be improved by using an epidural catheter to add more local anesthetic drug instead of a single shot ; and the surgeon should allow more time for the block to work adequately . Success in SA should be improved by using bupivacaine instead of lidocaine . GA result ed in significantly more blood loss , lower postoperative hematocrit , and higher proportion of patients who had postoperative hematocrit < 30 per cent than EA and SA . The patients ' satisfaction scores were not different among the 3 techniques . This meant that , given adequate explanation and perioperative care , Thai women were satisfied with regional anesthesia . CONCLUSION Regional anesthesia is a better choice of anesthesia for C/S than general anesthesia . However , the availability of different techniques and ability to change the technique when needed were very useful and important . If GA is chosen , all safety procedures must be followed . Oxygen supplement and endotracheal intubation facilities must be available in all techniques . Guidelines of anesthesia for C/S at a national level should be agreed upon , including the type of personnel , monitoring equipment and postoperative care OBJECTIVE The purpose of this study was to examine neonatal outcomes among women with a planned cesarean and a planned vaginal delivery at term . STUDY DESIGN This prospect i ve survey was conducted on 18,653 singleton deliveries that represent 24 maternity units during a 6-month period . The data were retrieved from the Medical Birth Registry of Norway and analyzed according to intended mode of delivery . RESULTS Compared with planned vaginal deliveries , planned cesarean delivery increased transfer rates to the neonatal intensive care unit from 5.2 % to 9.8 % ( P < .001 ) . The risk for pulmonary disorders ( transient tachypnea of the newborn infant and respiratory distress syndrome ) rose from 0.8 % to 1.6 % ( P = .01 ) . There were no significant differences in the risks for low Apgar score and neurologic symptoms . CONCLUSION A planned cesarean delivery doubled both the rate of transfer to the neonatal intensive care unit and the risk for pulmonary disorders , compared with a planned vaginal delivery Objective . To determine the impact of the method of delivery and type of obstetric anesthesia on oxidative stress in neonates . Methods . The trial included 164 women in two groups of elective cesarean delivery ( CD ) and uncomplicated vaginal delivery ( VD ) at term . The CD group was r and omized to either a spinal or general anesthesia and the VD group was r and omized to either a local or a spinal saddle block . The main outcome measures were the umbilical venous blood glutathione and malondialdhyde ( MDA ) . Results . Neonates of CD had significantly higher levels of MDA and pO2 and lower glutathione levels than VD . However , in regression analysis , the mode of delivery and type of anesthesia were independent factors that determine the level of MDA but not the level of glutathione . Gestational age was a significant predictor of the glutathione level while birth weight was a significant predictor of the MDA level . Conclusion . The oxidative status of the newborn is not simply a reflection of the mode of delivery and type of anesthesia . The impact of gestational age and birth weight appears to be crucial . This must be considered when planning elective delivery Umbilical cord blood was collected immediately after parturition in full term neonates during Caesarean section under either general or epidural anaesthesia . Using a radioimmunoassay technique , beta-endorphin concentrations were measured in the plasma of neonates and Apgar scores were evaluated . The mean value of beta-endorphin was 56.80 + /- 14.35 ( pg mL-1 ) in the general anaesthesia group , and 53.17 + /- 10.58 ( pg mL-1 ) in the epidural anaesthesia group ( N.S. ) STUDY OBJECTIVE To determine the frequency of electrocardiographic ( ECG ) changes and to assess the occurrence of myocardial ischemia during elective cesarean delivery with either regional or general anesthesia . DESIGN R and omized , prospect i ve , single-blinded clinical trial . SETTING Large referral hospital . PATIENTS 40 ASA physical status I and II term parturients . INTERVENTIONS Patients were divided r and omly into two groups as follows : the regional anesthesia group ( group 1 , n = 20 ) and the general anesthesia group ( group 2 , n = 20 ) . MEASUREMENTS In each case , continuous ECG was done using a 7-lead Holter monitor in the operating room , continuing for 24 hours after surgery . All Holter traces were analyzed by a study -blinded cardiologist . Blood sample s were collected preoperatively ( baseline ) and at one , 5 , and 24 hours postoperatively . Serum troponin T , creatinine kinase-MB , and myoglobin levels were measured . MAIN RESULTS Two patients in group 1 ( 10 % ) and one patient in group 2 ( 5 % ) showed one mm ST-segment depression for two to 5 minutes . In all 40 cases , troponin T levels were in the normal range at all time points studied . In both groups , mean serum creatinine kinase-MB and myoglobin levels at one and 5 hours postoperatively were significantly higher than at baseline ( P < 0.05 ) . These high CK-MB and myoglobin levels were returned to normal ranges at the end of the study period ; none of these women showed ST-segment changes . CONCLUSION The ST-segment changes are not frequent in healthy women undergoing elective cesarean delivery during either regional or general anesthesia , and we found no evidence of myocardial injury |
879 | 31,785,111 | Our review revealed that HCV infection significantly alters serum levels of markers of inflammation , endothelial function , and cardiac dysfunction prior to HCV treatment , and some of which may change in response to HCV therapy .
Current risk stratification tools for development of CVD in the general population may not account for the increased inflammatory markers that appear to be elevated among HCV‐infected patients contributing to increased CVD risk | Abstract Hepatitis C virus ( HCV ) infects 180 million people worldwide and over 4 million people in the United States .
HCV infection is a major cause of chronic liver disease and is recognized as a risk factor for clinical cardiovascular disease ( CVD ) .
Many studies have shown increased prevalence of cardiac and inflammatory biomarkers in patients with chronic HCV infection ( CHC ) , and though these markers may be used to risk stratify people for cardiac disease in the general population their role in the HCV population is unknown .
Patients with CHC have elevated cardiac and inflammatory biomarkers compared to noninfected controls which may play a role in CVD risk stratification .
We undertook a systematic review of inflammatory and cardiac biomarkers in people with HCV infection with a focus on the effect of CHC on serum levels of these markers and their utility as predictors of CVD in this population . | Background —Vascular cell adhesion molecule (VCAM)-1 , intercellular adhesion molecule (ICAM)-1 , and E-selectin mediate adhesion and transmigration of leukocytes to the vascular endothelial wall and may promote plaque growth and instability . In a prospect i ve study , we evaluated the effect of soluble adhesion molecules on the risk of future cardiovascular events among patients with angiographically documented coronary artery disease ( CAD ) . Methods and Results —We obtained baseline sample s from a prospect i ve cohort of 1246 patients with CAD . Besides various markers of inflammation , soluble VCAM-1 ( sVCAM-1 ) , sICAM-1 , and sE-selectin were determined . Follow-up information on cardiovascular events was obtained ( mean , 2.7 ; maximum , 4.1 years ) . Independently higher levels of sVCAM-1 ( 1932 versus 1128 ng/mL;P < 0.0001 ) , sICAM-1 ( 353 versus 287 ng/mL;P = 0.015 ) , and sE-selectin ( 81 versus 63 ng/mL;P = 0.003 ) were observed in patients with future death from cardiovascular causes . In a multivariate model , fatal risk was 2.1-fold ( 1.1 to 4.0 ) higher in patients within the top quartile of baseline sVCAM-1 concentrations compared with lower quartiles . This association was present independent of general inflammatory response as reflected by low or high C-reactive protein ( hs-CRP ) levels . In a model that simultaneously controlled for all inflammatory and soluble adhesion markers determined , only sVCAM-1 remained independently significant for future fatal cardiovascular events , with a 2.8-fold increase in risk ( P = 0.003 ) . Conclusions —Soluble adhesion molecules sVCAM-1 , sICAM-1 , and sE-selectin were significantly related to future death from cardiovascular causes among patients with documented CAD . Especially sVCAM-1 added to the predictive value of classic risk factors and hs-CRP in determining the risk of future cardiovascular death BACKGROUND Interleukin-6 ( IL-6 ) plays a central role in inflammation and tissue injury . However , epidemiological data evaluating the role of IL-6 in atherogenesis are sparse . METHODS AND RESULTS In a prospect i ve study involving 14 916 apparently healthy men , we measured baseline plasma concentration of IL-6 in 202 participants who subsequently developed myocardial infa rct ion ( MI ) and in 202 study participants matched for age and smoking status who did not report vascular disease during a 6-year follow-up . Median concentrations of IL-6 at baseline were higher among men who subsequently had an MI than among those who did not ( 1.81 versus 1 . 46 pg/mL ; P=0.002 ) . The risk of future MI increased with increasing quartiles of baseline IL-6 concentration ( P for trend < 0.001 ) such that men in the highest quartile at entry had a relative risk 2.3 times higher than those in the lowest quartile ( 95 % CI 1.3 to 4.3 , P=0.005 ) ; for each quartile increase in IL-6 , there was a 38 % increase in risk (P=0.001).This relationship remained significant after adjustment for other cardiovascular risk factors , was stable over long periods of follow-up , and was present in all low-risk subgroups , including nonsmokers . Although the strongest correlate of IL-6 in these data was C-reactive protein ( r=0.43 , P<0.001 ) , the relationship of IL-6 with subsequent risk remained after control for this factor ( P<0.001 ) . CONCLUSIONS In apparently healthy men , elevated levels of IL-6 are associated with increased risk of future MI . These data thus support a role for cytokine-mediated inflammation in the early stages of atherogenesis BACKGROUND Increased levels of the inflammatory biomarker high-sensitivity C-reactive protein predict cardiovascular events . Since statins lower levels of high-sensitivity C-reactive protein as well as cholesterol , we hypothesized that people with elevated high-sensitivity C-reactive protein levels but without hyperlipidemia might benefit from statin treatment . METHODS We r and omly assigned 17,802 apparently healthy men and women with low-density lipoprotein ( LDL ) cholesterol levels of less than 130 mg per deciliter ( 3.4 mmol per liter ) and high-sensitivity C-reactive protein levels of 2.0 mg per liter or higher to rosuvastatin , 20 mg daily , or placebo and followed them for the occurrence of the combined primary end point of myocardial infa rct ion , stroke , arterial revascularization , hospitalization for unstable angina , or death from cardiovascular causes . RESULTS The trial was stopped after a median follow-up of 1.9 years ( maximum , 5.0 ) . Rosuvastatin reduced LDL cholesterol levels by 50 % and high-sensitivity C-reactive protein levels by 37 % . The rates of the primary end point were 0.77 and 1.36 per 100 person-years of follow-up in the rosuvastatin and placebo groups , respectively ( hazard ratio for rosuvastatin , 0.56 ; 95 % confidence interval [ CI ] , 0.46 to 0.69 ; P<0.00001 ) , with corresponding rates of 0.17 and 0.37 for myocardial infa rct ion ( hazard ratio , 0.46 ; 95 % CI , 0.30 to 0.70 ; P=0.0002 ) , 0.18 and 0.34 for stroke ( hazard ratio , 0.52 ; 95 % CI , 0.34 to 0.79 ; P=0.002 ) , 0.41 and 0.77 for revascularization or unstable angina ( hazard ratio , 0.53 ; 95 % CI , 0.40 to 0.70 ; P<0.00001 ) , 0.45 and 0.85 for the combined end point of myocardial infa rct ion , stroke , or death from cardiovascular causes ( hazard ratio , 0.53 ; 95 % CI , 0.40 to 0.69 ; P<0.00001 ) , and 1.00 and 1.25 for death from any cause ( hazard ratio , 0.80 ; 95 % CI , 0.67 to 0.97 ; P=0.02 ) . Consistent effects were observed in all subgroups evaluated . The rosuvastatin group did not have a significant increase in myopathy or cancer but did have a higher incidence of physician-reported diabetes . CONCLUSIONS In this trial of apparently healthy persons without hyperlipidemia but with elevated high-sensitivity C-reactive protein levels , rosuvastatin significantly reduced the incidence of major cardiovascular events . ( Clinical Trials.gov number , NCT00239681 . Background Patients with chronic HCV infection have increased liver iron . Recently identified protein hepcidin synthesized in the liver , is thought to be a key regulator for iron homeostasis and is induced by infection and inflammation . Lower erythropoietin and iron supplementation requirements were previously reported in HD patients with HCV infection . We investigated the association of prohepcidin with inflammation and iron parameters in HD patients with and without chronic HCV infection . Methods Sixty patients ( 27 male , 33 female , mean age 50 ±15 years ) on chronic HD were included . Parameters related to iron metabolism ( ferritin , serum iron and total iron binding capacity ( TIBC ) ) , inflammation ( hs-CRP , TNF-α and IL-6 ) and prohepcidin levels were measured . The response to treatment ( erythropoiesis-stimulating agent ( ESA ) resistance index ) was assessed from the ratio of the weekly erythropoietin ( rhuEPO ) dose to hemoglobin ( Hb ) per unit weight . Results Serum prohepcidin levels of HCV positive patients ( 135 ± 25 ng/mL ) were significantly lower than HCV negative patients [ 148 ± 18 ng/mL , ( p = 0.025 ) ] . Serum IL-6 levels of HCV positive patients were also significantly lower than HCV negative patients ( p = 0.016 ) . Serum prohepcidin levels were positively correlated with ferritin ( r = 0.405 , p = 0.001 ) and IL-6 ( r = 0.271 , p = 0.050 ) levels in HD patients . In the HCV positive group , serum prohepcidin levels significantly correlated with ferritin levels ( r = 0.514 p = 0.004 ) . In the HCV negative group , serum prohepcidin levels significantly correlated with serum IL-6 levels ( r = 0.418 , p = 0.027 ) . In multiple regression analysis performed to predict prohepcidin in HCV positive patients , serum ferritin was found to be an independent variable ( r = 0.28 , p = 0.008 ) . Conclusions HCV positive HD patients have low levels of serum prohepcidin and IL-6 which might account for iron accumulation together with lower iron and rhuEPO requirements in these patients BACKGROUND Since inflammation is believed to have a role in the pathogenesis of cardiovascular events , measurement of markers of inflammation has been proposed as a method to improve the prediction of the risk of these events . METHODS We conducted a prospect i ve , nested case-control study among 28,263 apparently healthy postmenopausal women over a mean follow-up period of three years to assess the risk of cardiovascular events associated with base-line levels of markers of inflammation . The markers included high-sensitivity C-reactive protein ( hs-CRP ) , serum amyloid A , interleukin-6 , and soluble intercellular adhesion molecule type 1 ( sICAM-1 ) . We also studied homocysteine and a variety of lipid and lipoprotein measurements . Cardiovascular events were defined as death from coronary heart disease , nonfatal myocardial infa rct ion or stroke , or the need for coronary-revascularization procedures . RESULTS Of the 12 markers measured , hs-CRP was the strongest univariate predictor of the risk of cardiovascular events ; the relative risk of events for women in the highest as compared with the lowest quartile for this marker was 4.4 ( 95 percent confidence interval , 2.2 to 8.9 ) . Other markers significantly associated with the risk of cardiovascular events were serum amyloid A ( relative risk for the highest as compared with the lowest quartile , 3.0 ) , sICAM-1 ( 2.6 ) , interleukin-6 ( 2.2 ) , homocysteine ( 2.0 ) , total cholesterol ( 2.4 ) , LDL cholesterol ( 2.4 ) , apolipoprotein B-100 ( 3.4 ) , HDL cholesterol ( 0.3 ) , and the ratio of total cholesterol to HDL cholesterol ( 3.4 ) . Prediction models that incorporated markers of inflammation in addition to lipids were significantly better at predicting risk than models based on lipid levels alone ( P<0.001 ) . The levels of hs-CRP and serum amyloid A were significant predictors of risk even in the subgroup of women with LDL cholesterol levels below 130 mg per deciliter ( 3.4 mmol per liter ) , the target for primary prevention established by the National Cholesterol Education Program . In multivariate analyses , the only plasma markers that independently predicted risk were hs-CRP ( relative risk for the highest as compared with the lowest quartile , 1.5 ; 95 percent confidence interval , 1.1 to 2.1 ) and the ratio of total cholesterol to HDL cholesterol ( relative risk , 1.4 ; 95 percent confidence interval , 1.1 to 1.9 ) . CONCLUSIONS The addition of the measurement of C-reactive protein to screening based on lipid levels may provide an improved method of identifying persons at risk for cardiovascular events Tumor necrosis factor-alpha ( TNF-alpha ) plays a central role in the host 's immunomodulatory response to infective agents . To evaluate the TNF-alpha system in patients with chronic hepatitis C virus ( HCV ) infection , plasma , serum , and peripheral blood mononuclear cells ( P BMC ) were prospect ively collected from 53 patients and 33 healthy control subjects . Circulating TNF-alpha and TNF receptors were assayed by their respective enzyme immunoassays . In addition , TNF-alpha mRNA was quantitated in P BMC using a branched DNA assay , and production of TNF-alpha by P BMC with and without lipopolysaccharide was also assessed . Patients with chronic HCV infection had a higher level of circulating TNF-alpha compared to healthy control subjects ( 9.62 + /- 6.01 vs 3.66 + /- 1.23 pg/ml , P < 0.001 ) . They also had higher circulating levels of TNF receptors compared to control ( CD120a : 3323 + /- 1267 , pg/ml , N = 49 vs 1855 + /- 422 pg/ml , N = 33 , P < 0.001 ; CD120b : 1290 + /- 650 pg/ml , N = 51 , vs 863 + /- 207 pg/ml , N = 33 , P < 0.001 ) . Plasma TNF-alpha level correlated with circulating CD120a ( r = 0.52 , N = 49 , P < 0.001 ) and weakly with CD120b ( r = 0.32 , N = 51 , P = 0.02 ) . Plasma TNF-alpha also correlated with markers of hepatocellular injury , including ALT ( r = 0.34 , N = 53 , P = 0.01 ) and alpha-GST ( r = 0.31 , N = 43 , P = 0.042 ) , but not with serum HCV RNA levels . There was no difference in the TNF-alpha mRNA levels in P BMC between patients with chronic HCV infection ( 1.4 + /- 1.9 units/10[6 ] cells , N = 8) and healthy control subjects ( 2.1 + /- 1.4 units/10[6 ] cells , N = 8 , P = NS ) . There was also no difference in the spontaneous production of TNF-alpha by P BMC ( 1 x 10[6 ] cells/ml ) between patients with chronic HCV infection ( 14.2 + /- 36.5 pg/ml , N = 11 ) and healthy subjects ( 11.9 + /- 14.0 pg/ml , N = 14 , P = NS ) . However , patients with chronic HCV infection produced more TNF-alpha upon stimulation with lipopolysaccharide compared to healthy control subjects ( 1278 + /- 693 pg/ml , N = 11 , vs 629 + /- 689 pg/ml , N = 14 , P < 0.05 ) . These data indicate that the TNF-alpha system is activated in patients with chronic HCV infection Many patients with hepatitis C chronic infection ( HCV+ patients ) experience symptoms ( fatigue , dyspnea ) not proportional to the liver involvement and resemble symptoms of heart failure ( HF ) . To our knowledge , no study evaluated at the same time serum levels of N-terminal pro-brain natriuretic peptide ( NT-proBNP ) and tumor necrosis factor alpha ( TNF-alpha ) in HCV+ patients . Circulating NT-proBNP and TNF-alpha were assayed in 60 HCV+ patients , and in 60 sex- and age-matched controls . HCV+ patients showed significantly higher mean NT-proBNP and TNF-alpha levels than controls ( P < 0.003 ) . By defining high NT-proBNP level as a value higher than 125 pg/mL ( the single cutoff point for out patients under 75 years of age ) , 28 % of HCV+ and 7 % controls had high NT-proBNP ( chi-square ; P < 0.002 ) . With a cutoff point of 900 pg/mL ( that should be used for ruling in HF in patients age 50 - 75 ; such as the patients in our study ) , 3 % HCV+ and 0 controls had high NT-proBNP . In conclusion , the study demonstrates high levels of circulating NT-proBNP and TNF-alpha in HCV+ patients . The increase of NT-proBNP may indicate the presence of a sub clinical cardiac dysfunction . Further prospect i ve studies quantifying symptoms and correlating these with echocardiographic parameters are needed to confirm this association BACKGROUND The relationships between soluble CD14 ( sCD14 ) , endotoxin ( lipopolysaccharide [ LPS ] ) , and progression of atherosclerosis have not been defined in human immunodeficiency virus ( HIV ) infection . METHODS We retrospectively assessed serum sCD14 and LPS levels of 91 subjects in a prospect i ve 3-year study of carotid artery intima-media thickness ( CIMT ) ( AIDS Clinical Trials Group [ ACTG ] 5078 ) , where subjects were enrolled as risk factor-controlled triads of HIV-uninfected ( n = 36 ) and HIV-infected individuals with ( n = 29 ) or without ( n = 26 ) protease inhibitor (PI)-based therapy for ≥2 years . The primary end point was the yearly rate of change of CIMT ( ΔCIMT ) . RESULTS In multivariate analysis of the HIV-infected subjects , each 1 µg/mL above the mean of baseline serum sCD14 corresponded to an additional 1.52 µm/y ( 95 % confidence interval , .07 - 2.98 ; P = .04 ) in the ΔCIMT . Every 100 pg/mL above the mean of baseline serum LPS corresponded to an additional 0.49 µm/y ( 95 % confidence interval , .18-.81 ; P = .003 ) in the ΔCIMT . However , in univariate analysis in the HIV-uninfected group sCD14 ( P = .33 ) and LPS ( P = .27 ) levels were not associated with higher ΔCIMT . HIV infection and PI therapy were not associated with baseline serum LPS and sCD14 levels ( P > .1 ) . CONCLUSIONS Our data are among the first to suggest that serum biomarkers of microbial translocation ( LPS ) and macrophage activation ( sCD14 ) predict sub clinical atherosclerosis progression in HIV-infected persons BACKGROUND Pro-inflammatory monocytes/macrophages may contribute to increased atherosclerosis in human immunodeficiency virus (HIV)-infected patients . We investigate -- to our knowledge , for the first time -- sCD163 and other markers of monocyte activation in relationship to atherosclerotic plaque in HIV-infected patients . METHODS One hundred two HIV-infected and 41 HIV-seronegative men with equivalent cardiovascular risk factors and without history of coronary artery disease were prospect ively recruited and underwent computed tomography coronary angiography . RESULTS sCD163 levels and presence of plaque were significantly higher among antiretroviral-treated subjects with undetectable HIV RNA levels , compared with seronegative controls ( 1172 ± 646 vs. 883 ± 561 ng/mL [ P = .02 ] for sCD163 and 61 % vs. 39 % [ P = .03 ] for presence of plaque ) . After adjusting for age , race , lipids , blood pressure , glucose , smoking , sCD14 , and HIV infection , sCD163 remained independently associated with noncalcified plaque ( P = .008 ) . Among HIV-infected patients , sCD163 was associated with coronary segments with noncalcified plaque ( r = 0.21 ; P = .04 ) , but not with calcium score . In contrast , markers of generalized inflammation , including C-reactive protein level , and D-dimer were not associated with sCD163 or plaque among HIV-infected patients . CONCLUSIONS sCD163 , a monocyte/macrophage activation marker , is increased in association with noncalcified coronary plaque in men with chronic HIV infection and low or undetectable viremia . These data suggest a potentially important role of chronic monocyte/macrophage activation in the development of noncalcified vulnerable plaque . CLINICAL TRIAL REGISTRATION NCT00455793 Background —Neurohormones are considered markers of heart failure progression . We examined whether changes in brain natriuretic peptide ( BNP ) and norepinephrine ( NE ) over time are associated with corresponding changes in mortality and morbidity in the Valsartan Heart Failure Trial . Methods and Results —Plasma BNP and NE were measured before r and omization and during follow-up in ≈4300 patients in the Valsartan Heart Failure Trial . The relation between baseline BNP and NE and all-cause mortality and first morbid event ( M&M ) was analyzed in subgroups , with values above and below the median , and by quartiles . The change and percent change from baseline to 4 and 12 months in BNP and NE were also analyzed by quartiles for subsequent M&M. Risk ratios for M&M were calculated using a Cox proportional hazard model . Risk ratio of M&M for patients with baseline BNP or NE above the median was significantly higher than that for patients with values below the median . Baseline BNP and NE in quartiles also showed a quartile-dependent increase in M&M. BNP had a stronger association with M&M than NE . Patients with the greatest percent decrease in BNP and NE from baseline to 4 and 12 months had the lowest whereas patients with greatest percent increase in BNP and NE had the highest M&M. Conclusions —Not only are plasma BNP and NE important predictors of heart failure M&M , but changes in these neurohormones over time are associated with corresponding changes in M&M. These data further reinforce their role as significant surrogate markers in HF and underscore the importance of including their measurement in HF trials AIMS The objective of this study was to determine the integrative utility of measuring plasma NT-proBNP levels with echocardiography in the evaluation of dyspnoeic patients . METHODS AND RESULTS Of 599 emergency department patients enrolled in a clinical study of NT-proBNP at a tertiary-care hospital , 134 ( 22 % ) had echocardiographic results available for analysis . Echocardiographic parameters correlating with NT-proBNP levels were determined using multivariable linear-regression analysis . Independent predictors of 1-year mortality were determined using Cox-proportional hazard analysis . Independent relationships were found between NT-proBNP levels and ejection fraction ( P = 0.012 ) , tissue Doppler early and late mitral annular diastolic velocities ( P = 0.007 and 0.018 ) , right ventricular ( RV ) hypokinesis ( P = 0.006 ) , and tricuspid regurgitation severity ( P < 0.001 ) and velocity ( P = 0.007 ) . An NT-proBNP level < 300 pg/mL had a negative predictive value of 91 % for significant left ventricular systolic and diastolic dysfunction . Overall 1-year mortality was 20.1 % and was independently predicted by NT-proBNP level [ HR 8.65 , 95 % confidence interval ( CI ) 2.7 - 27.8 , P = 0.0003 ] , ejection fraction ( HR 0.95 , 95 % CI 0.91 - 0.99 , P = 0.009 ) , RV dilation ( HR 2.98 , 95 % CI 1.05 - 12.8 , P = 0.04 ) , and systolic blood pressure ( HR 0.97 , 95 % CI 0.96 - 0.99 , P = 0.01 ) . CONCLUSION NT-proBNP levels correlate with , and provide important prognostic information beyond , echocardiographic parameters of cardiac structure and function . Routine NT-proBNP testing may thus be useful to triage patients to more timely or deferred echocardiographic evaluation Cytokine production has been implicated in the antiviral response to interferon-alpha ( IFN-alpha ) in hepatitis C and in the development of IFN-alpha-related side effects . We characterized acute changes in serum cytokine levels following administration of a single dose of consensus IFN ( IFN-con1 ) and during continuous treatment of chronic hepatitis C patients . Serum sample s were collected at baseline , at multiple times early after IFN administration , and weekly thereafter . Viral RNA titers were assessed by RT-PCR , and viral kinetics were followed . ELISA assays were used to measure IFN-gamma , tumor necrosis factor-alpha ( TNF-alpha ) , interleukin-2 ( IL-2 ) , IL-4 , IL-6 , and IL-16 . Serum cytokine levels were low at baseline . IL-6 was detected in patients with hepatitis C but not in healthy control subjects by either ELISA or RT-PCR , indicating that low levels of circulating IL-6 were associated with hepatitis C infection . None of the cytokines measured increased significantly after IFN administration except for IL-6 . IL-6 levels rose rapidly , peaked at 6 - 15 h in a dose-dependent manner , and returned to baseline by 48 h in both patients receiving a single dose of IFN and those receiving continuous treatment . This was confirmed by RT-PCR . Pretreatment IL-6 levels were directly correlated with area under the curve ( AUC ) for IL-6 during the 24 h after IFN dosing ( r = 0.611 , p = 0.007 ) . Viral titers decreased within 24 - 48 h after a single dose of IFN-con1 . Changes in hepatitis C RNA titers were not significantly associated with pretreatment IL-6 levels or with changes in IL-6 levels . In conclusion , ( 1 ) baseline serum cytokine levels , except for IL-6 , were low or within the normal range in patients with hepatitis C , ( 2 ) IL-6 levels were detected in some patients with hepatitis C before treatment but not in healthy controls , ( 3 ) IL-6 levels increased acutely after a single dose of IFN-alpha , and IL-6 induction was related to baseline IL-6 level , and ( 4 ) changes in IL-6 levels did not correlate with the early virologic response to IFN OBJECTIVES : Noninvasive markers of liver fibrosis correlate with the stage of liver fibrosis , but have not been widely applied to predict liver-related mortality . METHODS : We assessed the ability of two indices of liver fibrosis , aspartate aminotransferase (AST)-to-platelet ratio index ( APRI ) and Fib-4 , and two markers of extracellular matrix metabolism , hyaluronic acid ( HA ) and YKL40 , to predict liver mortality in a prospect i ve cohort of hepatitis C virus (HCV)-infected individuals with and without HIV coinfection . These were compared with two established prognostic scores , the Child – Pugh – Turcotte ( CPT ) and model of end-stage liver disease ( MELD ) scores . RESULTS : A total of 303 subjects , of whom 207 were HIV positive at study entry , were followed up for a mean period of 3.1 years . There were 33 deaths due to liver disease . The ability of each test and score to predict 3-year liver mortality was expressed as the area under the receiver operator curve . The area under the receiver operator curve 95 % confidence intervals were : HA 0.92 ( 0.86–0.96 ) , CPT 0.91 ( 0.79–0.96 ) , APRI 0.88 ( 0.80–0.93 ) , Fib-4 0.87 ( 0.77–0.92 ) , MELD 0.84 ( 71–0.91 ) . In multivariate analyses HA , APRI , and fib-4 were independent predictors of mortality when included in models with MELD or CPT . CONCLUSION : Noninvasive markers of liver fibrosis are highly predictive of liver outcome in HCV-infected individuals with and without HIV coinfection . These markers seem to have a prognostic value independent of CPT and MELD BACKGROUND In chronic viral hepatitis C , hepatocytes inflammation , necrosis and apoptosis occur . To evaluate hepatocyte apoptotic rate , a serum concentration of proapoptotic FaS protein and its lig and ( FaS/FaSL ) as well tumor necrosis factor-alpha ( TNF-alpha ) and antiapoptotic hepatocyte growth factor ( HGF ) may be used . The aim of the study was to evaluate the hepatic apoptosis rate in patients with hepatitis virus C infection and its correlations with the degree of liver inflammation and staging , biochemical tests , viral load and the duration of the infection . PATIENTS AND METHODS 60 adults ( 30 chronic hepatitis C patients and 30 controls ) were included into the study . Serum levels of FaS/FaSL , TNFalpha and HGF were evaluated using the ELISA method . The results were correlated with viral load , biochemical tests , as well ultrasonographic and histopathological ( grading , staging ) examinations . RESULTS TNF-alpha level in HCV-infected patients was significantly higher than in the controls ( 11.0 + /- 19.3 pg/ml vs. 3.3 + /- 2.8 pg/ml , p = 0.04 ) . FaS/ FaSL and HGF did not differ significantly in both groups . TNF-alpha level was higher in patients with low staging ( fibrosis F-0 ) than in those with higher staging ( F-1 , F-2 , F-3)--according to the Batts-Ludwig scale . Other markers ( FaS/FaSL and HGF ) did not differ in groups with variant staging . No significant differences were observed in relation to grading . CONCLUSIONS The measurement of FaSIFaSL , TNF-alpha and HGF does not allow for the assessment about apoptotic rate in patients with chronic hepatitis C. Explanation of this problem need follow-up studies on larger groups with the use of more complex methods BACKGROUND The diagnostic utility of N-terminal pro-B-type natriuretic peptide ( NT-proBNP ) in heart failure has been documented . However , most of the data were derived from countries with high healthcare re source use , and r and omized evidence for utility of NT-proBNP was lacking . METHODS AND RESULTS We tested the hypothesis that NT-proBNP testing improves the management of patients presenting with dyspnea to emergency departments in Canada by prospect ively comparing the clinical and economic impact of a r and omized management strategy either guided by NT-proBNP results or without knowledge of NT-proBNP concentrations . Five hundred patients presenting with dyspnea to 7 emergency departments were studied . The median NT-proBNP level among the 230 subjects with a final diagnosis of heart failure was 3697 compared with 212 pg/mL in those without heart failure ( P<0.00001 ) . Knowledge of NT-proBNP results reduced the duration of ED visit by 21 % ( 6.3 to 5.6 hours ; P=0.031 ) , the number of patients rehospitalized over 60 days by 35 % ( 51 to 33 ; P=0.046 ) , and direct medical costs of all ED visits , hospitalizations , and subsequent outpatient services ( US $ 6129 to US $ 5180 per patient ; P=0.023 ) over 60 days from enrollment . Adding NT-proBNP to clinical judgment enhanced the accuracy of a diagnosis ; the area under the receiver-operating characteristic curve increased from 0.83 to 0.90 ( P<0.00001 ) . CONCLUSIONS In a universal health coverage system m and ating judicious use of healthcare re sources , inclusion of NT-proBNP testing improves the management of patients presenting to emergency departments with dyspnea through improved diagnosis , cost savings , and improvement in selected outcomes BACKGROUND Studies have shown disparate results in relation to the role of plasma concentrations of cell adhesion molecules in atherosclerosis . Moreover , the differentiation of primary vs secondary alterations of these markers , in response to myocardial injury , has not been clear . We measured specific soluble cell adhesion molecules and inflammatory markers in men admitted acutely with chest pain and compared them to healthy controls . METHODS AND RESULTS We prospect ively studied men ( total n=241 ) , admitted acutely with chest pain ( 7.4+/-9.4 h , 71 % within 10 h ) , unstable angina ( n=67 ) , acute myocardial infa rct ion ( n=47 ) and chest pain without ischaemic heart disease ( n=45 ) and compared them with a stratified sample of r and omly selected healthy controls ( n=82 ) . Soluble intercellular adhesion molecule ( sICAM-1 ) , endothelial selectin , vascular cell adhesion molecule , interleukin-6 and C-reactive protein were measured by ELISA and P-selectin expression by flow cytometry . Multiple regression analysis was used to control for the impact of classical risk factors . At baseline ICAM-1 , interleukin-6 and C-reactive protein were significantly elevated in patient groups whereas no difference in vascular cell adhesion molecule or endothelial selectin was found . At 3 month follow-up , ICAM-1 level was unchanged in ischaemic heart disease patients . In all groups C-reactive protein and interleukin-6 levels were lower at review . ICAM-1 levels at follow-up were higher in ischaemic heart disease groups ( but not in chest pain without ischaemic heart disease ) relative to controls and remained so only in the unstable angina group following regression . sICAM-1 , interleukin-6 and C-reactive protein strongly correlated with smoking . In the acute phase , ICAM-1 was confounded by smoking following regression and C-reactive protein and interleukin-6 remained significant in both ischaemic heart disease groups after multiple regression . There was no relationship to events which occurred in 23 % of ischaemic heart disease patients ( further acute myocardial infa rct ion 5.3 % , sudden cardiac death 0.9 % or recurrent angina 16.7 % ) . CONCLUSION We found an inflammatory response with higher sICAM-1 , interleukin-6 and C-reactive protein in patients presenting soon after developing an acute coronary syndrome . As sICAM-1 was not affected by the acute event this plasma marker may be an important risk factor for the development of the acute coronary syndrome , particularly unstable angina This prospect i ve study analyzed the relationship between several biological markers related to liver fibrosis at 3 months and 1 year post liver transplantation in 37 patients ( 19 with hepatitis C virus [ HCV ] , 18 with alcoholic liver disease ) . Severe HCV recurrence ( HCV-SR ) was defined as fibrosis stage > or = F1 ( METAVIR score ) at 1 year and /or a value of hepatic venous pressure gradient > or=6 mmHg . We found HCV-SR patients had higher values of monocyte chemotactic protein-1 ( MCP-1 ) , soluble vascular cell adhesion molecule-1 ( sVCAM-1 ) , and hyaluronic acid ( HA ) than non-severe HCV recurrence patients ( P<0.05 ) . Moreover , receiver operating characteristic curve analysis showed that interferon-inducible protein 10 ( IP-10 ) ( area under the curve [ AUC ] : 0.74 ; confidence interval [ CI ] 95 % : 0.49 - 0.91 ; P=0.043 ) , MCP-1 ( AUC : 0.78 ; CI 95 % : 0.54 - 0.94 ; P=0.007 ) , sVCAM-1 ( AUC : 0.89 ; CI 95 % : 0.67 - 0.98 ; P=0.005 ) , and HA ( AUC : 0.80 ; CI 95 % : 0.55 - 0.94 ; P=0.035 ) have good predictive capacity for identifying severe HCV infection . The evaluation of these biomarkers may be useful in the early identification of patients in whom a more aggressive therapeutic approach could be necessary Importance Persons with human immunodeficiency virus ( HIV ) that is treated with antiretroviral therapy have improved longevity but face an elevated risk of myocardial infa rct ion ( MI ) due to common MI risk factors and HIV-specific factors . Despite these elevated MI rates , optimal methods to predict MI risks for HIV-infected persons remain unclear . Objective To determine the extent to which existing and de novo estimation tools predict MI in a multicenter HIV cohort with rigorous MI adjudication . Design , Setting , and Participants We evaluated the performance of st and ard of care and 2 new data -derived MI risk estimation models in 5 Centers for AIDS Research Network of Integrated Clinical Systems sites across the United States where a multicenter clinical prospect i ve cohort of 19 829 HIV-infected adults received care in inpatient and outpatient setting s since 1995 . The new risk estimation models were vali date d in a separate cohort from the derivation cohort . Exposures Traditional cardiovascular risk factors , HIV viral load , CD4 lymphocyte count , statin use , antihypertensive use , and antiretroviral medication use were used to calculate predicted event rates . Main Outcomes and Measures We observed MI rates over the course of follow-up that were scaled to 10 years using the Greenwood-Nam-D’Agostino Kaplan-Meier approach to account for dropout and loss to follow-up before 10 years . Results Of the 11 288 patients with complete baseline data , 6904 were white and 9250 were men . Myocardial infa rct ion rates were higher among black men ( 6.9 per 1000 person-years ) and black women ( 7.2 per 1000 person-years ) than white men ( 4.4 per 1000 person-years ) and white women ( 3.3 per 1000 person-years ) , older participants ( 7.5 vs 2.2 MI per 1000 person-years for adults 40 years and older vs < 40 years old at study entry , respectively ) , and participants who were not virally suppressed ( 6.3 vs 4.7 per 1000 person-years for participants with and without detectable viral load , respectively ) . The 2013 Pooled Cohort Equations , which predict composite rates of MI and stroke , adequately discriminated MI risk ( Harrell C statistic = 0.75 ; 95 % CI , 0.71 - 0.78 ) . Two data -derived models incorporating HIV-specific covariates exhibited weak calibration in a validation sample and did not discriminate risk any better ( Harrell C statistic = 0.72 ; 95 % CI , 0.67 - 0.78 and 0.73 ; 95 % CI , 0.68 - 0.79 ) than the Pooled Cohort Equations . The Pooled Cohort Equations were moderately calibrated in the Centers for AIDS Research Network of Clinical Systems but predicted consistently lower MI rates . Conclusions and Relevance The Pooled Cohort Equations discriminated MI risk and were moderately calibrated in this multicenter HIV cohort . Adding HIV-specific factors did not improve model performance . As HIV-infected cohorts capture and assess MI and stroke outcomes , research ers should revisit the performance of risk estimation tools The changes in balance of cytokine profile may result in either recovery or persistence of hepatitis B virus ( HBV ) and hepatitis C virus ( HCV ) infections . This study aims to reveal a possible correlation between cytokine levels , ie , tumor necrosis factor (TNF)-α ; interferon-gamma ( IFN-γ ) ; interleukin (IL)-10 , IL-18 , and transforming growth factor-beta ( TGF-β ) ; and Ishak score or fibrosis in patients with chronic hepatitis B ( CHB ) or chronic hepatitis C ( CHC ) . Fifty patients with CHB ( n=25 ) , CHC ( n=25 ) , and the control group of subjects with negative hepatitis B and C serology ( n=30 ) were included in the study . Patients who did not agree to participate in the study were excluded . Serum cytokine levels were measured by ELISA . Liver biopsies from the patients were also taken for pathological analyses by the same pathologist . The serum levels of TNF-α , IL-10 , and IL-18 in the hepatitis C group were significantly high compared with those of the control group ( P=0.017 , P=0.001 , and P=0.004 respectively ) , but , only IL-10 levels in the hepatitis B group were significantly high ( P=0.001 ) . These groups did not show any significant difference with respect to IFN-γ or TGF-β levels . In patients with CHB or CHC , there was a significant correlation ( P=0.000 ) between TNF-α and Ishak score or fibrosis ; but no such correlation was found with IFN-γ , IL-10 , IL-18 , or TGF-β . Result of the current study indicated that cytokine activities were important indicators of clinical severity and progression of HBV- and HCV infections . Further investigations on possible effects of cytokines on hepatocellular damage and fibrosis should be done to arrange new immunopathological approaches to viral hepatitis Chemokines and cytokines play a vital role in directing and regulating immune responses to viral infections . Persistent hepatitis C virus ( HCV ) infection is characterized by the loss of anti-HCV cellular immune responses , while control of HCV infection is associated with maintenance of anti-HCV cellular immune responses . To determine whether plasma concentrations of 19 chemokines and cytokines controlling T-cell trafficking and function differed based on infection outcome , we compared them in at-risk subjects followed prospect ively for HCV infection . Levels were compared over time in subjects who controlled HCV infection ( Clearance ) and subjects who developed persistent HCV infection ( Persistence ) at two time points during acute infection : ( i ) first viraemic sample ( initial viraemia ) and ( ii ) last viraemic sample in Clearance subjects and time-matched sample s in Persistence subjects . At initial viraemia , increased pro-inflammatory tumour necrosis factor α ( TNFα ) plasma concentrations were observed in the Clearance group , while the plasma levels of anti-inflammatory interleukin (IL)-2 , IL-10 and IL-13 were higher in the Persistence group . IL-13 was positively correlated with IL-2 and IL-10 at initial viraemia in the Persistence group . At the time of last viraemia , plasma levels of eotaxin , macrophage chemoattractant protein-4 ( MCP-4 ) , IL-5 and IL-10 were higher in the Persistence group and IL-10 and IL-5 levels were positively correlated . Collectively , these results suggest that the development of persistent infection is associated with an anti-inflammatory and pro-fibrogenic chemokine and cytokine profile that is evident at the onset of infection and maintained throughout acute infection BACKGROUND The intercellular adhesion molecule ICAM-1 mediates adhesion and transmigration of leucocytes to the vascular endothelial wall , a step proposed to be critical in the initiation and progression of atherosclerosis . Whether concentrations of soluble ICAM-1 ( sICAM-1 ) are raised in apparently healthy individuals who later suffer acute myocardial infa rct ion is unknown . METHODS We obtained baseline plasma sample s from a prospect i ve cohort of 14,916 healthy men enrolled in the Physicians ' Health Study . With a nested case-control design , we measured sICAM-1 concentrations for 474 participants who developed a first myocardial infa rct ion , and 474 controls ( participants who remained healthy throughout the 9-year follow-up ) . Cases were matched to controls according to age and smoking status at the time of myocardial infa rct ion . FINDINGS We found a significant association between increasing concentration of sICAM-1 and risk of future myocardial infa rct ion ( p = 0.003 ) , especially among participants with baseline sICAM-1 concentrations in the highest quartile ( > 260 ng/mL ; relative risk 1.6 [ 95 % Cl 1.1 - 2.4 ] , p = 0.02 ) . This association was present overall as well as among non-smokers , and persisted after control for lipid and non-lipid risk factors . In multivariate analyses , the risk of future myocardial infa rct ion was 80 % higher for participants with baseline sICAM-1 concentrations in the highest quartile ( relative risk 1.8 [ 1.1 - 2.8 ] , p = 0.02 ) . Similar risk estimates were seen among non-smokers . We found slight but significant correlations between sICAM-1 and fibrinogen , high-density-lipoprotein cholesterol , homocysteine , triglycerides , tissue-type plasminogen-activator antigen , and C-relative protein , but adjustment for these altered the risk little . The risk of myocardial infa rct ion associated with raised concentrations of sICAM-1 seemed to increase with length of follow-up . INTERPRETATION Our data support the hypothesis that cellular mediators of inflammation have a role in atherogenesis and provide a clinical basis to consider antiadhesion therapies as a novel means of cardiovascular disease prevention BACKGROUND The prognostic influences of fibrinogen and C-reactive protein levels and their relations to myocardial damage in unstable coronary artery syndromes have not been well described . METHODS AND RESULTS Fibrinogen and C-reactive protein were determined at inclusion and related to outcome after 5 months in 965 patients with unstable angina or non-Q-wave myocardial infa rct ion r and omized to 5 weeks with low-molecular-weight heparin or placebo . The probabilities of death were 1.6 % , 4.6 % , and 6.9 % ( P=.005 ) and the probabilities of death and /or myocardial infa rct ion were 9.3 % , 14.2 % , and 19.1 % ( P=.002 ) , respectively , in patients stratified by tertiles of fibrinogen ( < 3.38 , 3.38 to 3.99 , and > or = 4.0 g/L ) . The probabilities of death were 2.2 % , 3.6 % , and 7.5 % ( P=.003 ) after stratification of patient data by tertiles of C-reactive protein level ( < 2 , 2 to 10 , and > 10 mg/L ) . In logistic multiple regression analysis , increased fibrinogen levels were independently associated with the incidence of death and /or myocardial infa rct ion ( P=.013 ) , and elevated C-reactive protein level was associated with the incidence of death ( P=.012 ) . The increased relative risk of subsequent death or myocardial infa rct ion in individuals with an elevated fibrinogen level was consistent in most subgroups evaluated ; although significantly so only in patients with signs of myocardial damage . CONCLUSIONS Increased levels of both fibrinogen and C-reactive protein are associated with a worse outcome in patients with unstable coronary artery disease . The increased risk associated with elevated fibrinogen levels is independent of , and additive to , the prognostic influence of myocardial damage BACKGROUND Chronic inflammation , as defined by persistent immune activation , is associated with adverse clinical outcomes . People who inject drugs ( PWID ) have evidence of persistent immune activation . Here , in a cohort of PWID with or without hepatitis C virus ( HCV ) infection , we sought to dissect out the contribution of chronic HCV infection ( common in PWID ) from the effects of injection drug use itself . METHODS Four groups of study volunteers were recruited : group 1 comprised active PWID ; group 2 , individuals who ceased injecting drugs 1 - 2 months before recruitment ; group 3 , individuals who ceased injecting drugs 3 - 4 months before recruitment ; and group 4 , healthy volunteers . Soluble and cell-associated markers of immune activation were quantified . RESULTS HCV-viremic PWID have elevated levels of immune activation when compared to healthy volunteers . Cessation of injection drug use results in a decline in immune activation in the absence of HCV viremia , while HCV-viremic individuals who previously were PWID continue to harbor elevated levels of immune activation , as defined by increased levels of soluble CD14 and tumor necrosis factor α and by the presence of CD38+HLA-DR+ CD4 + and CD8 + T cells . CONCLUSIONS Immune activation , a well-defined surrogate of poor clinical outcome that is elevated in PWID , can regress to normal levels in former injection drug users who are HCV aviremic . Therefore , enhanced harm-reduction efforts should incorporate aggressive treatment of HCV infection . CLINICAL TRIALS REGISTRATION NCT01831284 BACKGROUND Previous results from the SMART study showed that HIV/viral hepatitis co-infected persons with impaired liver function are at increased risk of death following interruption of antiretroviral therapy ( ART ) . OBJECTIVES To investigate the influence of fibrosis and ART interruption on levels of biomarkers of inflammation , coagulation and microbial translocation in HIV/HCV co-infected persons in the SMART study . STUDY DESIGN All HIV/HCV co-infected persons with stored plasma at study entry and at six months of follow-up were included ( N=362 ) . D-dimer , IL-6 , sCD14 and hepatic synthesized coagulation markers were measured and compared according to the liver fibrosis marker hyaluronic acid ( HA ) at study entry . Percent difference in changes in biomarker levels from study entry to month 6 was compared between r and omization groups and according to study entry HA levels . RESULTS At study entry , persons with elevated HA ( > 75ng/mL vs. ≤75ng/mL ) had higher median ( IQR ) levels of IL-6 [ 4.14pg/mL ( 2.60 - 6.32 ) vs. 2.74pg/mL ( 1.88 - 3.97 ) ] and soluble CD14 [ 2163ng/mL ( 1952 - 2916 ) vs. 1979ng/mL ( 1742 - 2310 ) ] ( p<0.001 ) . Elevated HA was also associated with alterations of both pro- and anti-coagulation markers but the overall coagulation profile was not affected . Interruption of ART lead to a particularly pronounced increase in IL-6 levels in persons with elevated HA levels ( p=0.01 for interaction between r and omization group and continuous HA level ) . CONCLUSIONS HIV/HCV co-infected persons with impaired liver function are in an enhanced pro-inflammatory state which is further exacerbated upon interruption of ART Insulin resistance is associated with highly active antiretroviral therapy in HIV-infected patients , and the risk of developing insulin resistance is increased in hepatitis C virus (HCV)-infected patients . The aim of the present study was to determine whether hepatitis C virus infection constitutes an additional risk factor for insulin resistance or other prothrombotic conditions in HIV – HCV coinfected patients under highly active antiretroviral therapy . One hundred eighteen HIV-infected patients were studied : 50 who had no history of anti-HIV treatment and 68 who were receiving therapy with highly active antiretroviral treatment . The treatment-naive group consisted of 35 HCV-negative subjects and 15 HCV-positive ones . Within the treated group , 50 patients were HCV negative and 18 were HCV positive . For each patient , the lipid profile was determined and the following values measured : glucose , soluble P-selectin ( as a marker of platelet activation ) , soluble thrombomodulin , von Willebr and factor and soluble vascular cell adhesion molecule-1 ( as endothelial markers ) , and insulin resistance . No significant difference ( p>0.05 ) for any variable was found among subjects with or without HCV coinfection in the treatment-naïve group . Among patients under highly active antiretroviral therapy , however , those with HCV coinfection showed higher values ( p<0.05 ) for insulin resistance ( homeostasis model assessment value : 2.65 vs. 1.79 ) , glucose ( 93 vs. 86 mg/dl ) , endothelial markers ( von Willebr and factor , 204 vs. 123 % ; soluble vascular cell adhesion molecule-1 , 650 vs. 482 ng/ml ) , and platelet activation marker ( soluble P-selectin , 78 vs. 51 ng/ml ) in parallel with lower CD4 + cells counts ( 289 vs. 402 cells/mm3 ) and higher HIV-1 viral loads ( 305 vs. 50 copies/ml ) compared to patients without HCV coinfection . Glucose , soluble P-selectin , and von Willebr and factor were independently related to HCV infection . The presence of HCV coinfection during HIV treatment was closely related to higher values of insulin resistance , to activated platelets , and to endothelial perturbation in parallel with lower CD4 + cell counts and higher HIV-1 viral loads compared to patients without HCV coinfection . On the basis of these results , it may be preferable to treat HCV infection prior to initiating treatment for HIV infection in HIV – HCV – coinfected patients Many patients chronically infected by hepatitis C virus ( HCV ) experience symptoms like fatigue , dyspnea and reduced physical activity . However , in many patients , these symptoms are not proportional to the liver involvement and could resemble symptoms of chronic heart failure . To our knowledge , no study evaluated serum levels of N-terminal pro-brain natriuretic peptide ( NT-proBNP ) in a large series of patients with HCV chronic infection ( HCV+ ) . Serum NT-proBNP was assayed in 50 patients HCV+ and in 50 sex- and age-matched controls . HCV+ patients showed significantly higher mean NT-proBNP level than controls ( P = 0.001 ) . By defining high NT-proBNP level as a value higher than 125 pg/mL ( the single cut-off point for patient under 75 years of age ) , 34 % HCV+ and 6 % controls had high NT-proBNP ( Fisher exact test ; P < 0.001 ) . With a cut-off point of 300 pg/mL ( used to rule out chronic heart failure in patients under 75 years of age ) 10 % HCV+ and 0 controls had high NT-proBNP ( Fisher exact test ; P = 0.056 ) . With a cut-off point of 900 pg/mL ( used for ruling in chronic heart failure in patients with age 50 - 75 ) 8 % HCV+ patients and 0 controls had high NT-proBNP ( Fisher exact test ; P = 0.12 ) . The study demonstrates high levels of circulating NT-proBNP in HCV+ patients compared to healthy controls . The increase of NT-proBNP may indicate the presence of a sub- clinical cardiac dysfunction . Further prospect i ve studies quantifying these symptoms in correlation with echocardiography are needed to confirm this association |
880 | 32,222,816 | Conclusion : Facilitated tucking position may improve the pain during painful procedures .
What is Known : • Exposure of premature babies to painful procedures is associated with changes in brain development , regardless of other factors . •
Facilitated tucking reduces the expression of pain in premature infants .
What is New : • Facilitated tucking position was efficient in pain management of preterm infants when compared to routine care .
• Facilitated tucking compared to opioid or oral glucose did not achieve a significant reduction in pain intensity .
What is Known : • Exposure of premature babies to painful procedures is associated with changes in brain development , regardless of other factors . •
Facilitated tucking reduces the expression of pain in premature infants .
What is New : • Facilitated tucking position was efficient in pain management of preterm infants when compared to routine care .
• Facilitated tucking compared to opioid or oral glucose did not achieve a significant reduction in pain intensity | We performed a systematic review and meta- analysis to investigate the effects of facilitated tucking position during painful procedure in pain management of preterm infants . | Abstract Background : According to research findings , pain experience in neonatal period leads to short- and long-term complications that could be prevented by means of neonatal pain relief . Therefore , this study aim ed to investigate the effect of facilitated tucking position on neonatal pain during heel prick blood sampling . Methods : This is a cross over clinical trial was done on 40 premature neonates . During blood sampling , neonates were put in either facilitated tucking or routine positions r and omly and Premature Infant Pain Profile ( PIPP ) was completed for each neonate . In the next sampling time , positions were changed and the process repeated . Data were analyzed using descriptive statistics , repeated measure ANOVA , and independent t-test . Results : Results showed that the mean pain intensity in each position was increased during sampling ( p = .0001 ) and after that was decreased significantly ( p = .001 ) , but before , during , and after sampling there was no significant difference between the two positions ( p > .05 ) . Conclusions : Overall findings showed that comparing neonates in the two positions ; there was no significant difference in their pain intensity . These results are almost in contrast with many research es findings in this area . It seems there is a need to further investigation regarding this subject OBJECTIVES : To test the comparative effectiveness of 2 nonpharmacologic pain-relieving interventions administered alone or in combination across time for repeated heel sticks in preterm infants . METHODS : A multicenter r and omized controlled trial in 3 NICUs in Switzerl and compared the effectiveness of oral sucrose , facilitated tucking ( FT ) , and a combination of both interventions in preterm infants between 24 and 32 weeks of gestation . Data were collected during the first 14 days of their NICU stay . Three phases ( baseline , heel stick , recovery ) of 5 heel stick procedures were videotaped for each infant . Four independent experienced nurses blinded to the heel stick phase rated 1055 video sequences presented in r and om order by using the Bernese Pain Scale for Neonates , a vali date d pain tool . RESULTS : Seventy-one infants were included in the study . Interrater reliability was high for the total Bernese Pain Scale for Neonates score ( Cronbach ’s α : 0.90–0.95 ) . FT alone was significantly less effective in relieving repeated procedural pain ( P < .002 ) than sucrose ( 0.2 mL/kg ) . FT in combination with sucrose seemed to have added value in the recovery phase with lower pain scores ( P = .003 ) compared with both the single-treatment groups . There were no significant differences in pain responses across gestational ages . CONCLUSIONS : Sucrose with and without FT had pain-relieving effects even in preterm infants of < 32 weeks of gestation having repeated pain exposures . These interventions remained effective during repeated heel sticks across time . FT was not as effective and can not be recommended as a nonpharmacologic pain relief intervention for repeated pain exposure BACKGROUND Preterm infants manifest pain and stress by behavioural agitation and state change . Few studies have explored the effects of combining nonpharmacological interventions , i.e. non-nutritive sucking , oral sucrose , and facilitated tucking , on infants ' behaviours across painful procedures . OBJECTIVES To explore the effects of combined use of three nonpharmacological interventions ( non-nutritive sucking , oral sucrose , and facilitated tucking ) on infants ' pain- and stress-related behaviours during four assessment phases : baseline , intervention , heel stick , and recovery . DESIGN Prospect i ve , r and omised controlled trial . SETTING Level III neonatal intensive care unit in Taipei . METHOD A convenience sample of 110 infants ( gestational age 27 - 37 weeks ) needing heel sticks was r and omly assigned to five combinations of nonpharmacological treatments : ( 1 ) routine care , ( 2 ) non-nutritive sucking+facilitated tucking , ( 3 ) oral sucrose+facilitated tucking , ( 4 ) non-nutritive sucking+oral sucrose , and ( 5 ) non-nutritive sucking+oral sucrose+facilitated tucking . Outcomes were infants ' withdrawal or stress ( grimace , limb and trunk extension or squirming ) and approach or self-soothing ( sucking , sucking search , or mouthing ; h and holding or grasping ; and h and to mouth , face ) behaviours . RESULTS The frequency of infants ' withdrawal behaviours decreased significantly when they received combinations of nonpharmacological interventions before heel stick . Specifically , grimace frequency decreased by 32.2 % , 30.6 % , 19.7 % , and 13.8 % in infants receiving oral sucrose+non-nutritive sucking+facilitated tucking , non-nutritive sucking+oral sucrose , oral sucrose+facilitated tucking , and non-nutritive sucking+facilitated tucking , respectively , compared to those receiving routine care across assessment phases . Furthermore , infants ' frequency of limb and trunk extension or squirming decreased by 24.0 % when they received non-nutritive sucking+oral sucrose+facilitated tucking compared to those receiving routine care . Infants ' frequency of approach behaviours did not change significantly across all phases when they received non-nutritive sucking+oral sucrose+facilitated tucking , non-nutritive sucking+oral sucrose , and oral sucrose+facilitated tucking compared to those receiving routine care . CONCLUSIONS The combined use of nonpharmacological interventions ( non-nutritive sucking+oral sucrose+facilitated tucking ) effectively reduced the frequencies of infants ' withdrawal behaviours , i.e. grimace and limb and trunk extension or squirming . Our results provide evidence supporting clinicians ' incorporation of the combined use of facilitated tucking , oral sucrose , and non-nutritive sucking into clinical practice during painful procedures . Heel-stick procedures can be atraumatic when conducted while infants are stable and quiet , appropriately positioned , and stabilised and by offering facilitated tucking , oral sucrose , and non-nutritive sucking before gently sticking the heel and squeezing blood Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more PURPOSE To determine the effect of facilitated tucking ( FT ) on pain in preterm newborns during heel stick procedure done as a part of neonatal intensive care . METHODS This r and omized controlled cross-over pilot study included 20 preterm newborns of both sexes between gestational ages ( GA ) of 28 and 36 weeks based upon the eligibility criteria . Pain was measured using Premature Infant Pain Profile ( PIPP ) following both heel stick with FT and without FT . RESULTS The newborns had a lower PIPP score at 30 seconds ( Mean , SD : 8.80 , 3.82 ) , 60 seconds ( Mean , SD : 7.55 , 3.28 ) , 90 seconds ( Mean , SD : 7.25 , 3.06 ) and 120 seconds ( Mean , SD : 6.65 , 3.05 ) when heel stick was done with FT compared to the same procedure done without FT at 30 seconds ( Mean , SD : 11.20 , 3.44 ) , 60 seconds ( Mean , SD : 10.75 , 3.24 ) , 90 seconds ( Mean , SD : 10.60 , 3.22 ) and 120 seconds ( Mean , SD : 10.50 , 3.15 ) . A ( 2 X 4 ) factorial ANOVA showed a statistically significant difference between these two procedures in all the time periods viz . , 30 seconds ( p=0.044 ) , 60 seconds ( p=0.004 ) , 90 seconds ( p=0.002 ) and 120 seconds ( p < 0.0001 ) at 0.05 level in PIPP score and favoring FT . CONCLUSION FT is an effective non-pharmacological pain management in preterm newborns during routine neonatal intensive care BACKGROUND Preterm infants ' repeated exposure to painful procedures may contribute to negative consequences . Thus , improving preterm infants ' neurodevelopmental outcomes requires prioritising their pain management . OBJECTIVES To compare the effectiveness of two non-pharmacological pain-relief strategies ( non-nutritive sucking and facilitated tucking ) with routine care on preterm infants ' pain , behavioural , and physiological responses before , during , and after heel-stick procedures . DESIGN Prospect i ve , r and omised controlled crossover trial . SETTING Level III Neonatal Intensive Care Unit in Taipei . METHOD Thirty-four preterm infants ( gestational age 29 - 37 weeks ) needing three procedural heel sticks were recruited by convenience sampling and r and omly assigned to a sequence of three treatments ( two pain-relief interventions and the control condition ) : ( 1 ) routine care , non-nutritive sucking , facilitated tucking , ( 2 ) non-nutritive sucking , facilitated tucking , routine care , and ( 3 ) facilitated tucking , routine care , non-nutritive sucking . Each treatment condition was performed on a different day to avoid any carry-over effect . Pain was measured by the Premature Infant Pain Profile ( PIPP ) , infant behaviour by a behavioural coding scheme , and physiological signals by electrocardiogram monitors . All data were collected 3 min without stimuli ( baseline ) , during heel-stick procedures , and recovery . RESULTS Infants receiving non-nutritive sucking and facilitated tucking had significantly lower mean ( st and ard deviation ) pain scores during heel-stick procedures ( 6.39 [ 3.35 ] and 7.15 [ 3.88 ] , respectively ) than those receiving routine care ( 9.52 [ 4.95 ] ) . Infants receiving non-nutritive sucking and facilitated tucking had significantly lower odds ratios ( 0.39 , p=0.011 and 0.34 , p=0.005 , respectively ) for pain ( PIPP score≥6 ) than infants receiving routine care after adjusting for time , baseline pain scores , and infants ' characteristics . Similarly , infants receiving non-nutritive sucking and facilitated tucking had significantly lower odds ratios ( 0.23 , p<0.001 and 0.28 , p=0.03 , respectively ) for moderate-to-severe pain ( PIPP score≥12 ) than infants receiving routine care . Infants receiving facilitated tucking had lower frequency ratios for stress-related behaviours , abnormal heart rates , and decreased oxygen saturation than infants receiving routine care . CONCLUSIONS Both non-nutritive sucking and facilitated tucking effectively reduced pain scores more than routine care during heel-stick procedures . Non-nutritive sucking reduced PIPP pain scores more effectively than facilitated tucking . However , facilitated tucking showed broader effects not only on relieving pain , but also on enhancing infants ' physiological and behavioural stability during heel-stick procedures Background This study was conducted to evaluate the pain perceptions of newborns during the hepatitis B ( HBV ) vaccinations performed in the facilitated tucking position and the classical holding position , respectively . Methods The r and omized controlled experimental study was conducted between 1 September 2014 and 30 December 2014 at the neonatal intensive care unit of a Turkish university hospital . One group of infants was held in the facilitated tucking position ( the treatment group ; n = 30 ) during HBV vaccination ; infants in the other group were held in the classical holding position ( the control group ; n = 30 ) during HBV vaccination . The Neonatal Infant Pain Scale ( NIPS ) scores of the infants in the treatment and control groups were compared during procedure . Also , the infants ’ physiological parameters were compared before , during , and after the procedure . Descriptive statistics , a chi-square test , and an independent sample s t-test were used to assess the data . Results The mean pain scores of infants vaccinated in the facilitated tucking position ( 2.83 ± 1.18 ) were significantly statistically lower than the scores of infants vaccinated in the classical holding position ( 6.47 ± 1.07 ) ( p < 0.05 ) . Conclusions The pain perceptions of newborns held in the facilitated tucking position during HBV vaccination were lower . The facilitated tucking position , a non-pharmacological method , is recommended as an effective and useful method for reducing pain during the procedure Background : Premature infants not only feel and underst and the pain , but also respond more intensively compared with term infants . Non-pharmacological methods of pain control are suitable to relieve pain in painful procedures . The facilitated tucking position is considered as a non-pharmacological method of pain control in infants ; however , its impact on frequent and repeated procedural pain such as endotracheal suctioning remains to be studied . Objectives : This paper is the report of a study that examined the impact of facilitated tucking position on behavioral pain during suctioning in premature neonates . Design : This was a clinical trial study with a crossover design . Setting s : The study was conducted in a level II Neonatal Intensive Care Unit , located in a teaching hospital , affiliated to Tehran University of Medical Sciences , Tehran , Iran . Participants : Thirty four infants were enrolled in this study based on the following inclusion criteria : age between 29 to 37 weeks of gestational age , birth weight 1200 grams or more , having an endotracheal tube , no congenital anomalies , no seizures diagnosis , no chest tubes , no intracranial hemorrhage higher than degree II , not receiving opiates and sedatives four hours before intervention and not receiving any painful procedure at least half an hour before the intervention . Methods : The sample s were r and omly received a sequence of suctioning with/without or suctioning without/with facilitated tucking . Preterm Infant Pain Profile ( PIPP ) was used to collect the data . SPSS version 16.0 for Windows ( SPSS Inc. , Chicago , IL , USA ) was used for statistical analysis . Results : While 38.2 % of infants experienced severe pain during suctioning without intervention , only 8.8 % of them experienced severe pain during suctioning with intervention . The results of the paired t-test show that there is a statistically significant difference in the mean scores of pain between non-intervention and intervention cases ( p<0.001 ) , and the mean pain score substantially reduced in cases with intervention . Conclusions : Given the multiplicity of endotracheal suctioning frequency and the impossibility of frequent use of pharmacological methods of pain relief , the facilitated tucking position can be used as a safe non-pharmacological method for procedural pain management ABSTRACT Procedural pain in the neonatal intensive care unit triggers a cascade of physiological , behavioral and hormonal disruptions which may contribute to altered neurodevelopment in infants born very preterm , who undergo prolonged hospitalization at a time of physiological immaturity and rapid brain development . The aim of this study was to examine relationships between cumulative procedural pain ( number of skin‐breaking procedures from birth to term , adjusted for early illness severity and overall intravenous morphine exposure ) , and later cognitive , motor abilities and behavior in very preterm infants at 8 and 18 months corrected chronological age ( CCA ) , and further , to evaluate the extent to which parenting factors modulate these relationships over time . Participants were N = 211 infants ( n = 137 born preterm ⩽32 weeks gestational age [ GA ] and n = 74 full‐term controls ) followed prospect ively since birth . Infants with significant neonatal brain injury ( periventricular leucomalacia , grade 3 or 4 intraventricular hemorrhage ) and /or major sensori‐neural impairments , were excluded . Poorer cognition and motor function were associated with higher number of skin‐breaking procedures , independent of early illness severity , overall intravenous morphine , and exposure to postnatal steroids . The number of skin‐breaking procedures as a marker of neonatal pain was closely related to days on mechanical ventilation . In general , greater overall exposure to intravenous morphine was associated with poorer motor development at 8 months , but not at 18 months CCA , however , specific protocol s for morphine administration were not evaluated . Lower parenting stress modulated effects of neonatal pain , only on cognitive outcome at 18 months BACKGROUND There is a need for a safe and effective non-pharmacological pain management method for preterm infants . The parents could be given an active role in the pain management which may help the parents to cope with the stress related to painful situations of the infant . AIMS To examine the effectiveness of a method called ' facilitated tucking by parents ' ( a parent holds the infant in a flexed position ) in pain management during endotracheal/pharyngeal suctioning of preterm infants . In addition , the parental perception of the method was studied . STUDY DESIGN A r and omized crossover trial . SUBJECTS Twenty preterm infants with one of their parents participated in the study . Infants ' gestational age ranged from 24 to 33 ( median 28 ) weeks and postnatal age from 6 to 37 days ( median 15 days ) . OUTCOME MEASURES The primary outcome was the Neonatal Infant Pain Scale ( NIPS ) score . Heart rate and oxygen saturation were recorded . Parents completed a question naire about their perception of the procedure . RESULTS The highest NIPS score was median 3 ( range from 2 to 6 ) using ' facilitated tucking by parents ' and median 5 ( range from 2 to 7 ) without tucking during suctioning ( p < 0.001 ) . The infants calmed down more quickly after ' facilitated tucking by parents ' ( 5 s vs. 17 s , p = 0.024 ) . Nineteen out of twenty parents preferred facilitated tucking during suctioning compared to control care . CONCLUSIONS Facilitated tucking by parents is an effective and safe pain management method during suctioning of preterm infants . This study shows that parents can be given an active role in the pain care of their preterm infants Purpose : This study compared the efficacy of a behavioral pain reducing intervention ( facilitated tucking ) with st and ard neonatal intensive care unit ( NICU ) care for decreasing procedural pain ( endotracheal suctioning ) in very low birthweight ( VLBW ) infants . Study Design and Methods : A prospect i ve r and omized crossover design with infants as their own controls were used . The sample consisted of 40 VLBW infants , 23–32 weeks gestation , and weighing 560–1498 g with tracheal intubation . The infants were observed twice during each endotracheal suctioning experience ; one suctioning was done according to normal nursery routine ; another was done using facilitated tucking ( the caregiver “ h and -swaddling ” the infant by placing a h and on the infant ’s head and feet while providing flexion and containment ) . The Premature Infant Pain Profile ( PIPP ) measured the infant ’s pain response , and severity of illness of each infant was measured by the Score for Neonatal Acute Physiology ( SNAP ) and the NTISS ( Neonatal Therapeutic Intervention Scoring System ) . Repeated measures analysis of variance ( RMANOVA ) determined the efficacy of facilitated tucking for reducing procedural pain ( PIPP ) and the effects of order of intervention vs. control . Regression analyses examined the relationship of gestational age , severity of illness , and number of painful procedures to the pain response . Results : There was a significant difference between the PIPP scores for tucking and nontucking positions ( p = 0.001 ) and a nonsignificant interaction with order ( p = 0.64 ) as well as a nonsignificant main effect for order ( p = 0.46 ) . In the regression analyses , all predictors taken together did not significantly predict PIPP scores in the tucked position ( p = 0.11 ) or nontucked position ( p = 0.57 ) . Clinical Implication s : Facilitated tucking is a developmentally sensitive , nonpharmacological comfort measure that can relieve procedural pain in VLBW infants . Nurses need to be increasingly aware of infant pain during daily care taking , and to use vali date d pain assessment instruments . Further clinical research on individual pain assessment is needed for better underst and ing of the quality and significance of pain for each infant , and the factors that affect pain expression OBJECTIVE To identify the effectiveness of " facilitated tucking , " a nonpharmacologic nursing intervention , as a comfort measure in modulating preterm neonates ' physiologic and behavioral responses to minor pain . DESIGN Prospect i ve , repeated measure , r and om sequencing , and experimental . SETTING Level III neonatal intensive-care unit of a tertiary care university pediatric hospital . PARTICIPANTS Thirty preterm neonates , 25 - 35 weeks gestation . INTERVENTIONS Heart rate , oxygen saturation , and sleep state were recorded 12 minutes before , during , and 15 minutes after two heelsticks , one with and one without facilitated tucking . HYPOTHESIS Premature neonates will have less variation in heart rate and hemoglobin oxygen saturation , shorter crying and sleep disruption times , and less fluctuation in sleep states in response to the painful stimulus of a heelstick with facilitated tucking than without . RESULTS Neonates demonstrated a lower mean heart rate 6 - 10 minutes post-stick ( p < 0.04 ) , shorter mean crying time ( p < 0.001 ) , shorter mean sleep disruption time ( p < 0.001 ) , and fewer sleep-state changes ( p = 0.003 ) after heelstick with facilitated tucking than without . CONCLUSION Facilitated tucking is an effective comfort measure in attenuating premature neonates ' psychologic and behavioral responses to minor pain AIMS AND OBJECTIVES To determine the effectiveness of facilitated tucking in reducing pain when venepuncture is being performed on preterm infants . BACKGROUND Preterm neonates are exposed to a myriad of invasive , often painful , procedures throughout their stay in the neonatal intensive care unit . A growing volume of evidence shows that pain in preterm infants has both short- and long-term deleterious effects . It is within the power and ethical responsibility of neonatal nurses to help premature babies cope with procedural pain . DESIGN A quasi-experimental study with two groups : control and treatment group . METHODS A study was conducted on a cohort of preterm infants ( n = 42 ) , divided into control ( n = 21 ) and treatment ( n = 21 ) groups , to determine the effect of facilitated tucking on pain relief during venepuncture on preterm infants in the neonatal intensive care unit . The severity of pain was measured using the Premature Infant Pain Profile score . The primary outcome measure was reduction in the Premature Infant Pain Profile scores . RESULTS The Premature Infant Pain Profile score for the treatment group was significantly lower ( M = 6·62 , SD 2·598 ) than for the control group ( 6·62 ± 2·60 vs. 8·52 ± 2·99 , respectively , t = -2·202 , p < 0·05 ) . CONCLUSIONS Facilitated tucking reduced the Premature Infant Pain Profile scores in preterm infants . RELEVANCE TO CLINICAL PRACTICE The findings of this study suggest that facilitated tucking is able to alleviate pain ; therefore , nurses must be able to carry out facilitated tucking when necessary BACKGROUND Preterm infant pain can be relieved by combining non-nutritive sucking ( sucking ) , oral sucrose , and facilitated tucking ( tucking ) , but the pain-relief effects of oral expressed breast milk ( breast milk ) are ambiguous . AIMS We compared the effects of combined sucking+ breast milk , sucking+breast milk+tucking , and routine care on preterm infant pain during and after heel-stick procedures . DESIGN A prospect i ve , r and omized controlled trial . SETTING S Level III neonatal intensive care unit and a neonatal unit at a medical center in Taipei . PARTICIPANTS /SUBJECTS Preterm infants ( N=109 , gestational age 29 - 37 weeks , stable disease condition ) needing procedural heel sticks were recruited by convenience sampling and r and omly assigned to three treatment conditions : routine care , sucking+ breast milk , and sucking+breast milk+ tucking . METHODS Pain was measured by watching video recordings of infants undergoing heel-stick procedures and scoring pain at 1-min intervals with the Premature Infant Pain Profile . Data were collected over eight phases : baseline ( phase 1 , 10min without stimuli before heel stick ) , during heel stick ( phases 2 and 3 ) , and a 10-min recovery ( phases 4 - 8 ) . RESULTS For infants receiving sucking+ breast milk , pain-score changes from baseline across phases 2 - 8 were 2.634 , 4.303 , 2.812 , 2.271 , 1.465 , 0.704 , and 1.452 units lower than corresponding pain-score changes of infants receiving routine care ( all p-values < 0.05 except for phases 6 and 7 ) . Similarly , for infants receiving sucking + breast milk+ tucking , pain-score changes from baseline were 2.652 , 3.644 , 1.686 , 1.770 , 1.409 , 1.165 , and 2.210 units lower than corresponding pain-score changes in infants receiving routine care across phases 2 - 8 ( all p-values < 0.05 except for phase 4 ) . After receiving sucking + breast milk + tucking and sucking + breast milk , infants ' risk of mild pain ( pain score ≥6 ) significantly decreased 67.0 % and 70.1 % , respectively , compared to infants receiving routine care . After receiving sucking + breast milk + tucking and sucking + breast milk , infants ' risk of moderate-to-severe pain ( pain score ≥12 ) decreased 87.4 % and 95.7 % , respectively , compared to infants receiving routine care . CONCLUSION The combined use of sucking+breast milk + tucking and sucking+breast milk effectively reduced preterm infants ' mild pain and moderate-to-severe pain during heel-stick procedures . Adding facilitated tucking helped infants recover from pain across eight phases of heel-stick procedures . Our findings advance knowledge on the effects of combining expressed breast milk , sucking , and tucking on preterm infants ' procedural pain BACKGROUND Pain and stress agitate preterm infants , interrupting their sleep . Frequent high arousal states may affect infants ' brain development and illness recovery . Preserving infants ' sleep and relieving their pain during painful procedures are both important for their health . OBJECTIVES To compare the effectiveness of different combinations of non-nutritive sucking ( sucking ) , oral sucrose , and facilitated tucking ( tucking ) with routine care on infants ' sleep-wake states before , during , and after heel-stick procedures . DESIGN Prospect i ve , r and omised controlled trial . SETTING Level III Neonatal Intensive Care Unit in Taipei . METHOD A convenience sample of 110 infants ( gestational age 26.4 - 37 weeks ) needing heel sticks were r and omly assigned to five combinations of non-pharmacological treatments : sucking-oral sucrose-tucking ; sucking-oral sucrose ; oral sucrose-tucking ; sucking-tucking ; and routine care . Infant states , measured by a state-coding scheme , included quiet sleep , active sleep , transition , quiet awake , active awake , and fussing or crying . All states were recorded at 1-min intervals during four phases : baseline , intervention , heel-stick procedures , and recovery . RESULTS Infants receiving sucking-oral sucrose-tucking or sucking-oral sucrose experienced 52.8 % ( p=0.023 ) and 42.6 % ( p=0.063 ) more quiet-sleep occurrences than those receiving routine care after adjusting for phase , baseline states , non-treatment sucking during baseline and recovery , positioning , and infants ' characteristics . Infants receiving oral sucrose-tucking , sucking-oral sucrose , sucking-oral sucrose-tucking , and sucking-tucking experienced 77.3 % ( p<0.001 ) , 72.1 % ( p=0.008 ) , 51.5 % ( p=0.017 ) , and 33.0 % ( p=0.105 ) fewer occurrences of fussing or crying , respectively , than those receiving routine care after adjusting for related factors . CONCLUSIONS The four treatment combinations differentially reduced infants ' high arousal across heel-stick procedures . The combined use of oral sucrose-tucking , sucking-oral sucrose , and sucking-oral sucrose-tucking more effectively reduced occurrences of infant fussing or crying than routine care . Treatment combinations of sucking-oral sucrose-tucking and sucking-oral sucrose also better facilitated infants ' sleep than routine care . To preserve infants ' sleep , clinicians should use combinations of non-nutritive sucking , oral sucrose , and facilitated tucking to reduce agitation during painful procedures BACKGROUND Reducing acute pain in premature infants during neonatal care improves their neurophysiological development . The use of pharmacological and non-pharmacological analgesia , such as sucrose , is limited per day , particularly for very preterm infants . Thus , the usual practice of non-nutritive sucking is often used alone . Facilitated tucking could be an additional strategy to non-nutritive sucking for reducing pain . To the best of our knowledge , no r and omized trial has compared the combination of facilitated tucking and non-nutritive sucking to non-nutritive sucking alone . OBJECTIVES To compare the efficacy of facilitated tucking in combination with non-nutritive sucking ( intervention group ) to non-nutritive sucking alone ( control group ) in reducing pain during the heel-stick procedure in very preterm infants . DESIGN Prospect i ve , r and omized controlled trial . SETTING S Level III and II neonatal care units , including the neurosensory care management program . METHODS Very preterm infants ( gestational age between 28 and 32 weeks ) were r and omly assigned by a computer programme to the intervention or control group during a heel-stick procedure within the first 48 h of life . In both groups , infants were placed in an asymmetric position on a cushion ; noise and light were limited following routine care . A heel-stick was performed first in the care sequence . In the intervention group , facilitated tucking was performed by a nurse or nursing assistant . The procedure was video recorded from 15 s ( T-15 s ) before the procedure until three minutes ( T + 3 min ) after the end of the procedure . Pain was blindly assessed by two independent specialist nurses . The primary outcome was the pain score evaluated 15 s before the procedure and 30 s immediately after by the premature infant pain profile ( PIPP ) scale . The secondary outcome was the pain score evaluated between T-15 s and T + 3 min by the DAN scale ( a French acronym for the acute pain of a newborn ) . RESULTS Sixty infants were included ( 30 in each group ) . The PIPP pain scores did not differ between the intervention group ( median : 8.0 ; interquartile range ( IQR ) : 6.0 - 12.0 ) and the control group ( median : 9.5 ; IQR : 7.0 - 13.0 , p = 0.32 ) . Pain assessed by the DAN scale at T + 3 min was lower in the intervention group than in the control group ( median : 0.3 ; IQR : 0.0 - 1.0 and 2.0 ; IQR : 0.5 - 3.0 , respectively , p = 0.001 ) . CONCLUSIONS The combined use of facilitated tucking and non-nutritive sucking did not significantly alleviate pain during the heel-stick procedure . However , the addition of facilitated tucking facilitated faster pain recovery following the heel-stick procedure Problem Current research suggests behavioral and environmental interventions to prevent neonatal pain prior to an invasive procedure are rarely administered and seldom documented . The aim of this study was to systematic ally review findings from published r and omized controlled trials that tested the effects of behavioral and environmental procedural pain management interventions on behavioral pain response in preterm infants . Eligibility Criteria R and omized controlled trials examining the effects of behavioral and environmental pain management interventions on behavioral pain response in preterm infants were identified . Articles accepted for inclusion met the following criteria : English language , original , peer refereed , r and omized controlled clinical trials published within the past 5 years , study sample : preterm infants , setting : neonatal intensive care units , study intervention behavioral and environmental , outcome pain measurement score from valid and reliable pain scale . Sample Fourteen r and omized controlled trials from a literature search of PubMed and Medline data bases were included in this review . Results Across all age groups , facilitated tucking , oral sucrose , and kangaroo care decreased behavioral and physiologic pain response alone and in combination with other behavioral and environmental interventions . Conclusion Among preterm infants , facilitated tucking , oral sucrose , and kangaroo care significantly mitigates biobehavioral pain response associated with acutely painful procedures . Implication s Evidence suggests that behavioral and environmental interventions can decrease biobehavioral pain response associated with acutely painful procedures in preterm infants . This review highlights the need for rigorous studies to help healthcare providers to build a tailored pain treatment plan for preterm infants Preterm neonates hospitalized in the neonatal intensive care unit undergo frequent painful procedures daily , often without pain treatment , with associated long-term adverse effects . Maternal-infant skin-to-skin contact , or kangaroo care ( KC ) , and sweet-tasting solutions such as sucrose are effective strategies to reduce pain during a single procedure ; however , evidence of sustained efficacy over repeated procedures is limited . We aim ed to determine the relative sustained efficacy of maternal KC , administered alone or in combination with 24 % sucrose , to reduce behavioral pain intensity associated with routine neonatal procedures , compared with 24 % sucrose alone . Stable preterm infants ( n = 242 ) were r and omized to receive KC and water , KC and 24 % sucrose , or 24 % sucrose before all routine painful procedures throughout their neonatal intensive care unit stay . Pain intensity , determined using the Premature Infant Pain Profile , was measured during 3 medically indicated heel lances distributed across hospitalization . Maternal and neonatal baseline characteristics , Premature Infant Pain Profile scores at 30 , 60 , or 90 seconds after heel lance , the distribution of infants with pain scores suggesting mild , moderate , or severe pain , Neurobehavioral Assessment of the Preterm Infant scores , and incidence of adverse outcomes were not statistically significantly different between groups . Maternal KC , as a pain-relieving intervention , remained efficacious over time and repeated painful procedures without evidence of any harm or neurological impact . It seemed to be equally effective as 24 % oral sucrose , and the combination of maternal KC and sucrose did not seem to provide additional benefit , challenging the existing recommendation of using sucrose as the primary st and ard of care Objectives The purpose of this study was to compare the effectiveness of “ facilitated tucking by parents ” ( FTP ) in which a parent holds by her h and s the infant in a side-lying flexed position offering support and skin contact , oral glucose , opioid ( oxycodone ) , and placebo ( oral water ) in the context of heel stick and pharyngeal suctioning in very preterm infants . We hypothesized that nonpharmacologic methods equal the pharmacologic method and are superior to placebo in pain management . Methods A prospect i ve r and omized placebo-controlled crossover trial . The study patients ( n=20 ) were born at a mean gestational age of 28 + 1 weeks and were studied at postconceptional age of 28 to 32 weeks . Pain measurements with Premature Infant Pain Profile and Neonatal Infant Pain Scale covered the first 30 seconds after the beginning of the painful stimulus . Results Premature Infant Pain Profile scores were significantly lower with oral glucose ( mean : 4.85±1.73 , P≤0.001 ) and FTP ( mean : 5.20±1.70 , P=0.004 ) when compared with placebo ( mean : 7.05±2.16 ) after heel stick . During pharyngeal suctioning , the scores were lowest with oral glucose ( mean : 11.05±2.31 , P=0.014 ) and FTP ( mean : 11.25±2.47 , P=0.034 ) compared with placebo ( mean : 12.40±2.06 ) . Opioid equaled placebo in both procedures . Neonatal Infant Pain Scale scores were significantly lower with FTP ( P≤0.001 ) and opioid ( P=0.018 ) after heel stick , and during pharyngeal suctioning with FTP ( P=0.001 ) compared with placebo . We found significantly more short-term adverse effects per administration with oral glucose ( 21.25 % ) and oral water ( 12.5 % ) compared with opioid ( 5 % ) or FTP ( 5 % ) . Discussion Our study demonstrated that FTP is not just equal , but preferable to other pain management methods when both efficacy and safety are considered Abstract Objective : Premature infants respond more intensively to pain compared with term infants . Facilitated tucking position as a non-pharmacological method of pain in infants has been suggested ; however , its effect on acute procedural pain such as endotracheal suctioning remains to be studied . This study examined the effect of facilitated tucking position during suctioning on physiological responses and coping with stress in premature infants . Methods : This was a r and omized controlled crossover study . Thirty-four premature infants received an order of either suctioning with intervention – suctioning without intervention , or suctioning without intervention – suctioning with intervention . Neonatal Infant Pain Scale ( NIPS ) was used to collect the data . Results : No statistical significant difference was seen between intervention and non-intervention cases in terms of the average time duration to reach the pain score to one or zero , and also , in the average of changes in oxygen saturation . However , changes in heart rate were less in intervention cases . Conclusion : The effect of facilitated tucking position on coping with stress was not found in this study . This non-pharmacological strategy can be suggested because of its effect on reducing changes in heart rate during painful procedure . It is suggested to replicate the study with larger number of sample |
881 | 25,921,230 | RESULTS We found the Raymond scale to be predictive of retreatment , with statistically higher rates of retreatment with higher initial Raymond grade .
Furthermore , we found a higher probability of rebleeding for initial grade s 2 or 3 versus grade 1 , which approached significance .
The rebleed rates were probably affected by monitoring and treatment of recurrence .
However , although there was a trend towards higher recurrence rates with initial grade , this was not statistically significant .
The modified Raymond-Roy scale appears to provide reasonable predictive value for treated aneurysm , especially for the clinical ly more important aspects of retreatment and rebleed rates | BACKGROUND AND PURPOSE The Raymond-Roy grading scale is used for aneurysm coiling with only limited data on its validity .
The scale was developed based on the extent of initial aneurysm occlusion from 1 to 3 .
However , the model usefulness in evaluating recurrence , retreatment , and rebleeding is unknown .
Our goal was to perform a meta- analysis to evaluate the predictiveness of the Raymond scale . | Introduction Endovascular treatment of cerebral aneurysms includes follow-up imaging to identify aneurysms that may need retreatment . The aim of this study was to determine predictors of incomplete aneurysm occlusion at 1 year after endovascular coiling for ruptured cerebral aneurysms . Methods In 129 patients of the Prospect i ve Registry of Subarachnoid Aneurysms Treatment cohort , ruptured aneurysms were coiled within 14 days of onset and both initial post-coiling and 1-year follow-up digital subtraction angiography or magnetic resonance angiography were obtained . Factors predicting 1-year incomplete aneurysm occlusion ( retreatment within 1-year or residual aneurysms at 1 year ) were determined using multivariate logistic regression analyses . Results One-year incomplete aneurysm occlusion was identified in 59 patients , including ten patients who were retreated within 1-year post-coiling . Dome size ≥7.5 mm ( P = 0.007 , odds ratio ( OR ) = 5.00 , 95 % confidence interval ( CI ) = 1.55–16.15 ) , pre-treatment aneurysm re-rupture ( P = 0.023 , OR = 3.50 , 95 % CI = 1.19–10.31 ) , non-small size/small neck aneurysm ( dome size , ≥10 mm or neck size , ≥4 mm ; P = 0.022 , OR = 3.26 , 95 % CI = 1.19–8.96 ) , and residual aneurysms on immediate post-coiling angiograms ( P = 0.017 , OR = 1.43 , 95 % CI = 1.07–1.93 ) significantly predicted incomplete aneurysm occlusion at 1-year post-coiling . Conclusions In addition to the characteristics of aneurysm and initially incomplete aneurysm occlusion , this study showed pre-treatment aneurysm re-rupture to be a predictor that favors closer imaging follow-ups for coiled aneurysms Background and Purpose — We sought to better define the morbidity of endovascular Guglielmi detachable coil ( GDC ) treatment of unruptured cerebral aneurysms and to discuss its role in the prevention of subarachnoid hemorrhage . Methods — We conducted an observational study from August 1992 to June 1999 of 125 unruptured aneurysms treated with GDC in 116 patients : 91 women ( 78.4 % ) and 25 men ( 21.6 % ) , aged 30 to 78 years ( mean age , 50.6 years ) . Immediate and late clinical results were recorded for any neurological event or hemorrhage related to the treated unruptured aneurysm . Angiographic results are reported as immediate , early ( 2 to 12 months ) , intermediate ( 12 to 30 months ) , and late follow-up ( > 30 months ) . Results — Immediate angiographic results showed complete obliteration ( class 1 ) in 59 ( 47.2 % ) or residual neck ( class 2 ) in 53 aneurysms ( 42.4 % ) , leaving 6 residual aneurysms ( 4.8 % ) and 7 failures ( 5.6 % ) . Early follow-up angiograms , available in 100 treated aneurysms ( 84 % ) , revealed class 1 in 52 % and class 2 in 41 % . Intermediate angiograms , available in 53 aneurysms ( 44.5 % ) , showed class 1 in 47.2 % and class 2 in 43.4 % , while late results , available in 37 lesions ( 31.1 % ) , had class 1 and 2 in 48.6 % and 37.8 % , respectively . Six patients suffered a permanent neurological deficit at last follow-up ( 5.2 % ) , with a good outcome in 5 patients and fair outcome in 1 patient . There was no mortality . There was no aneurysmal rupture during a mean clinical follow-up of 32.1 months . Conclusions — Endovascular treatment with GDC for unruptured aneurysms is relatively safe . Its role in the prevention of aneurysmal rupture remains to be determined , preferably by a r and omized study Background Coil embolization has gained importance in the management of intracranial aneurysms over the past decade . However , the recurrence risk after embolization m and ates closer follow-up than surgical clip ligation . Currently , there is no reliable system for predicting aneurysm sac thrombosis . An aneurysm embolization grade ( AEG ) reported previously by the senior author ( EMD ) has been proposed as a tool for predicting the durability of aneurysm occlusion based on hemodynamic characteristics . Here , we present our internal validity results . Methods AEG and Raymond – Roy Occlusion Classification ( RROC ) scores were prospect ively assigned to all aneurysms coiled from June 2008 to June 2011 . The prospect ively assigned AEG and RROC scores from the cerebral angiograms were collected for data analysis and validity assessment of the AEG system . 110 consecutive patients who had aneurysm coil embolization were included in this study . Results The post-coiling AEG significantly predicted follow-up angiographic filling characteristics . Pairwise comparisons revealed that the follow-up AEG for those initially scored ‘ A ’ ( complete obliteration ) was significantly better than the contrast-flow groups . Significant differences were also noted between contrast-stasis and contrast-flow groups . A pairwise comparison between RROC scores demonstrated that only the RROC Type 1 could be used to predict follow-up occlusion durability . Stent placement in wide-neck aneurysms had no effect on initial AEG , RROC , or long-term occlusion durability . Packing density significantly predicted initial AEG and RROC , but had no effect on long-term occlusion . Conclusions The AEG system is uniquely based on angiographic filling characteristics of the aneurysm , and this study demonstrated its high predictive value for determining aneurysm sac thrombosis . Assigning an AEG to the aneurysm can guide the neurointerventionalist in discussion s with the patient regarding the probability of aneurysm recurrence and potential need for retreatment Background and Purpose — Our aim in this study was to assess the incidence and determining factors of angiographic recurrences after endovascular treatment of aneurysms . Methods — A retrospective analysis of all patients with selective endosaccular coil occlusion of intracranial aneurysms prospect ively collected from 1992 to 2002 was performed . There were 501 aneurysms in 466 patients ( mean±SD age , 54.20±12.54 years ; 74 % female ) . Aneurysms were acutely ruptured ( 54.1 % ) or unruptured ( 45.9 % ) . Mean±SD aneurysm size was 9.67±5.91 mm with a 4.31±1.97-mm neck . The most frequent sites were basilar bifurcation ( 27.7 % ) and carotid ophthalmic ( 18.0 % ) aneurysms . Recurrences were subjectively divided into minor and major ( ideally necessitating re-treatment ) . The most significant predictors of angiographic recurrence were determined by logistic regression . These results were confirmed by & khgr;2 , t tests , or ANOVAs followed , when appropriate , by Tukey ’s contrasts . Results — Short-term ( ≤1 year ) follow-up angiograms were available in 353 aneurysms ( 70.5 % ) and long-term ( > 1 year ) follow-up angiograms , in 277 ( 55 % ) , for a total of 383 ( 76.5 % ) followed up . Recurrences were found in 33.6 % of treated aneurysms that were followed up and that appeared at a mean±SD time of 12.31±11.33 months after treatment . Major recurrences presented in 20.7 % and appeared at a mean of 16.49±15.93 months . Three patients ( 0.8 % ) bled during a mean clinical follow-up period of 31.32±24.96 months . Variables determined to be significant predictors ( P < 0.05 ) of a recurrence included aneurysm size ≥10 mm , treatment during the acute phase of rupture , incomplete initial occlusions , and duration of follow-up . Conclusions — Long-term monitoring of patients treated by endosaccular coiling is m and atory BACKGROUND AND PURPOSE : The purpose of this study was to analyze angiographic and clinical results before and after additional endovascular therapy in patients with previously coiled but reopened cerebral aneurysms and to identify possible risk factors for retreatment of an aneurysm . MATERIAL S AND METHODS : Follow-up with selective digital subtraction angiography was performed in 323/596 ( 54.2 % ) patients harboring 342 aneurysms with a mean follow-up time of 28.6 months . The patients were divided into 3 groups : group A , who remained stable after initial treatment ; group B , who showed minor morphologic changes ; and group C , who underwent repeat treatment . Univariate and multivariate regression analyses were performed to determine possible risk factors for aneurysmal retreatment . RESULTS : Single or multiple retreatment was performed in 33 of 323 ( 10.2 % ) patients . Retreatment of small aneurysms ( ≤10 mm ) with small necks ( ≤4 mm ) was performed in 6 of 214 aneurysms . When summarizing all other aneurysms as a “ risk group ” ( n = 128 ) , the odds ratio ( OR ) for retreatment in the “ risk group ” was 3.11 ( 95 % CI : 1.43–6.75 ; P = .004 ) . In patients with residual aneurysm after the first treatment , OR for retreatment was 3.96 ( 95 % CI : 1.48–10.65 ; P = .006 ) , whereas a neck remnant , clinical presentation , and aneurysmal localization were not predictive . We observed no result ing morbidity and mortality from the 33 retreatment procedures . CONCLUSION : In our series , the retreatment of aneurysmal recurrences was a safe procedure . The best single predictors of aneurysmal recurrence were aneurysmal anatomy ( neck width > 4 mm and diameter > 10 mm ) and the presence of a residual aneurysm after initial treatment . A limitation in our study was the significant number of patients lost to follow-up ( 22.7 % ) |
882 | 23,246,209 | Secondary outcomes included lower levels of depression and cortisol .
This review provides evidence that cognitive , behavioral , and mindfulness interventions are effective in reducing stress in university students . | BACKGROUND Recent research has revealed concerning rates of anxiety and depression among university students .
Nevertheless , only a small percentage of these students receive treatment from university health services .
Universities are thus challenged with instituting preventative programs that address student stress and reduce result ant anxiety and depression . | BACKGROUND This study examined the effects of an 8-week stress reduction program based on training in mindfulness meditation . Previous research efforts suggesting this program may be beneficial in terms of reducing stress-related symptomatology and helping patients cope with chronic pain have been limited by a lack of adequate comparison control group . METHODS Twenty-eight individuals who volunteered to participate in the present study were r and omized into either an experimental group or a nonintervention control group . RESULTS Following participation , experimental subjects , when compared with controls , evidence d significantly greater changes in terms of : ( 1 ) reductions in overall psychological symptomatology ; ( 2 ) increase in overall domain-specific sense of control and utilization of an accepting or yielding mode of control in their lives , and ( 3 ) higher scores on a measure of spiritual experiences . CONCLUSIONS The techniques of mindfulness meditation , with their emphasis on developing detached observation and awareness of the contents of consciousness , may represent a powerful cognitive behavioral coping strategy for transforming the ways in which we respond to life events . They may also have potential for relapse prevention in affective disorders Background : Although mindfulness meditation interventions have recently shown benefits for reducing stress in various population s , little is known about their relative efficacy compared with relaxation interventions . Purpose : This r and omized controlled trial examines the effects of a 1-month mindfulness meditation versus somatic relaxation training as compared to a control group in 83 students ( M age=25 ; 16 men and 67 women ) reporting distress . Method : Psychological distress , positive states of mind , distractive and ruminative thoughts and behaviors , and spiritual experience were measured , while controlling for social desirability . Results : Hierarchical linear modeling reveals that both meditation and relaxation groups experienced significant decreases in distress as well as increases in positive mood states over time , compared with the control group ( p<.05 in all cases ) . There were no significant differences between meditation and relaxation on distress and positive mood states over time . Effect sizes for distress were large for both meditation and relaxation ( Cohen ’s d=1.36 and .91 , respectively ) , whereas the meditation group showed a larger effect size for positive states of mind than relaxation ( Cohen ’s d=.71 and .25 , respectively ) . The meditation group also demonstrated significant pre-post decreases in both distractive and ruminative thoughts/behaviors compared with the control group ( p<.04 in all cases ; Cohen ’s d=.57 for rumination and .25 for distraction for the meditation group ) , with mediation models suggesting that mindfulness meditation ’s effects on reducing distress were partially mediated by reducing rumination . No significant effects were found for spiritual experience . Conclusions : The data suggest that compared with a no-treatment control , brief training in mindfulness meditation or somatic relaxation reduces distress and improves positive mood states . However , mindfulness meditation may be specific in its ability to reduce distractive and ruminative thoughts and behaviors , and this ability may provide a unique mechanism by which mindfulness meditation reduces distress Psychosocial stress is a potent activator of the hypothalamus-pituitary-adrenal ( HPA ) axis . While neuroendocrine stress responses are essential for the maintenance of homeostasis , evidence suggests that excessive activation of the HPA axis constitutes a risk for disease and psychopathology . The purpose of the present study was to assess the effect of cognitive-behavioral stress management training on endocrine stress responses and cognitive appraisal under acute psychosocial stress among healthy young subjects . Forty-eight healthy , non-smoking male students without acute or chronic medical or psychiatric disorder on self report were r and omly assigned to receive group-based cognitive-behavioral stress management training either before or after a st and ardized psychosocial stress test ( Trier Social Stress Test , TSST ) . Endocrine and psychological stress responses were assessed with salivary free cortisol response and cognitive appraisal processes to the TSST . In comparison with the control group , subjects in the treatment group showed an attenuated endocrine response ( F ( 2.55/117.41 ) = 3.81 ; P = 0.02 ; effect size f(2 ) = 0.35 ) to the TSST . In addition , subjects in the SIT group had lower stress appraisal and higher control expectancies ( F ( 2/45 ) = 6.56 ; P = 0.003 , effect size f(2 ) = 0.29 ) compared to controls . Short group-based cognitive-behavioral stress management training reduces the neuroendocrine stress response to an acute stressor in healthy subjects . Therefore , stress management training may prove useful in preventing detrimental effects of stress-induced neuroendocrine The inability to cope successfully with the enormous stress of medical education may lead to a cascade of consequences at both a personal and professional level . The present study examined the short-term effects of an 8-week meditation-based stress reduction intervention on premedical and medical students using a well-controlled statistical design . Findings indicate that participation in the intervention can effectively ( 1 ) reduce self-reported state and trait anxiety , ( 2 ) reduce reports of overall psychological distress including depression , ( 3 ) increase scores on overall empathy levels , and ( 4 ) increase scores on a measure of spiritual experiences assessed at termination of intervention . These results ( 5 ) replicated in the wait-list control group , ( 6 ) held across different experiments , and ( 7 ) were observed during the exam period . Future research should address potential long-term effects of mindfulness training for medical and premedical students The challenges of providing exemplary undergraduate nursing education can not be underestimated in an era when burnout and negative mood states predictably lead to alarming rates of academic as well as career attrition . While the multi-dimensional nature of this complex issue has been extensively eluci date d , few rational strategies exist to reverse a disheartening trend recognizable early in the educational process that subsequently threatens to undermine the future viability of quality healthcare . This controlled prospect i ve crossover study examined the impact of a 6-session Recreational Music-making ( RMM ) protocol on burnout and mood dimensions as well as Total Mood Disturbance ( TMD ) in first year associate level nursing students . A total of 75 first year associate degree nursing students from Allegany College of Maryl and ( ACM ) participated in a 6-session RMM protocol focusing on group support and stress reduction utilizing a specific group drumming protocol . Burnout and mood dimensions were assessed with the Maslach Burnout Inventory and the Profile of Mood States respectively . Statistically significant reductions of multiple burnout and mood dimensions as well as TMD scores were noted . Potential annual cost savings for the typical associate degree nursing program ( $ 16,800 ) and acute care hospital ( $ 322,000 ) were projected by an independent economic analysis firm . A cost-effective 6-session RMM protocol reduces burnout and mood dimensions as well as TMD in associate degree nursing students Mindfulness-based stress reduction ( MBSR ) has shown effectiveness for a variety of mental health conditions . However , it is not known for whom the intervention is most effective . In a r and omized controlled trial ( N = 30 ) , we explored whether individuals with higher levels of pretreatment trait mindfulness would benefit more from MBSR intervention . Results demonstrated that relative to a control condition ( n = 15 ) , MBSR treatment ( n = 15 ) had significant effects on several outcomes , including increased trait mindfulness , subjective well-being , and empathy measured at 2 and 12 months after treatment . However , relative to controls , MBSR participants with higher levels of pretreatment mindfulness showed a larger increase in mindfulness , subjective well-being , empathy , and hope , and larger declines in perceived stress up to 1 year after treatment Psychosocial stress leads to a release of cortisol . While this psychoneuroendocrine response helps to maintain physiological as well as psychological equilibrium under stress , exaggerated secretion of cortisol has been shown to have negative effects on somatic health and cognitive functioning . The study set out to examine the long-term effects of cognitive-behavioral stress management training on cortisol stress responses in healthy men and women . Eighty-three healthy subjects were r and omly assigned to cognitive-behavioral stress management ( CBSM ) training or a control condition . Four months after the CBSM , 76 subjects underwent a st and ardized psychosocial stress test . Salivary cortisol responses were assessed repeatedly before and after the stress test . Subjects in the CBSM group showed significantly reduced cortisol stress responses . With regard to gender , this effect was observed in both men and women . However , the magnitude of the CBSM effect on cortisol responses was smaller in women than in men . Use of oral contraceptives in women influenced the cortisol response , but did not have an impact on the CBSM effect on cortisol . The results show that the previously reported attenuation of cortisol stress responses through CBSM persists and are observable in both men and women . Since stress-induced alterations of hypothalamus pituitary adrenal axis functioning are discussed to be involved in the onset and maintenance of both somatic and psychiatric conditions , similar interventions could be used for prevention and therapy of these detrimental stress effects Abstract The authors examined the effect of a 6-week mind/body intervention on college students ' psychological distress , anxiety , and perception of stress . One hundred twenty-eight students were r and omly assigned to an experimental group ( n = 63 ) or a waitlist control group ( n = 65 ) . The experimental group received 6 90-minute group-training sessions in the relaxation response and cognitive behavioral skills . The Symptom Checklist-90-Revised , Spielberger State-Trait Anxiety Inventory , and the Perceived Stress Scale were used to assess the students ' psychological state before and after the intervention . Ninety students ( 70 % of the initial sample ) completed the post assessment measure . Significantly greater reductions in psychological distress , state anxiety , and perceived stress were found in the experimental group . This brief mind/body training may be useful as a preventive intervention for college students , according to the authors , who called for further research to determine whether the observed treatment effect can be sustained over a longer period of time The purpose of this study was to compare the effects of Benson 's relaxation technique ( BRT ) with Benson 's technique augmented with GSR biofeedback ( i.e. , biofeedback-aided relaxation , BAR ) on the psychological stress symptoms of well college students . Seventy-eight normotensive college students were r and omly assigned to one of three groups : the BRT group , the BAR group , and a control group . The BRT and BAR students were asked to practice their respective relaxation technique daily for an eight-week period . Pre- and postintervention , all subjects were administered a state-anxiety inventory and a profile-of-mood state ( POMS ) test . Posttest analysis indicated that the BAR group had significantly lower state anxiety and POMS than the BRT and control groups ( p less than 0.05 ) . It was evident from the results that BAR did augment BRT in lowering psychological stress symptoms . Part of the effectiveness was due to the expectation of relief on the part of the BAR group . It was recommended that nurses study the effects of BAR in clinical setting This study examined the effectiveness of audiotaped imagery in reducing anxiety and improving test performance among first-year nursing students . Volunteer subjects were r and omly assigned to three groups , imagery-only , imagery/relaxation , and a no-treatment control group . Pottest state anxiety scores in these groups were significantly lower ( p = .001 ) than in the no-treatment control group . Test performance did not differ significantly ( p = .067 ) . Subjects using the audiotaped imagery reported an increased sense of well-being , improved ability to sleep , greater energy , and improved self-confidence OBJECTIVE This study aim ed to determine whether the practice of mindfulness reduces the level of stress experienced by senior medical students . METHODS We carried out a multicentre , single-blinded , r and omised controlled trial with intention-to-treat analysis in three clinical schools attached to the University of Tasmania , Hobart , Tasmania . Participants included 66 medical students in their final 2 years of study in 2009 . Participants were block-r and omised to either an intervention or a usual care control group . The intervention used an audio CD of guided mindfulness practice design ed and produced for this trial . Participants were advised to use the intervention daily over the 8 weeks of the trial . All participants completed two self-report question naires , at baseline and at 8 weeks , respectively . The intervention group also completed a question naire at 16 weeks to provide follow-up data . The primary outcome measure was the difference over time in scores on the Perceived Stress Scale ( PSS ) . The secondary outcome measure referred to differences over time in scores on the subscales of the Depression , Anxiety and Stress Scale ( DASS ) . RESULTS Mean baseline scores on the PSS and the stress component of the DASS were 15.7 ( maximal score of 40 ) and 13.2 ( maximal score of 42 ) , respectively , both of which exceed scores in age-matched normative control data . Using multivariable analysis , participants in the intervention group demonstrated significant reductions in scores on the PSS ( - 3.44 , 95 % confidence interval [ CI ] - 6.20 to - 0.68 ; p < 0.05 ) and the anxiety component of the DASS ( - 2.82 , 95 % CI - 4.99 to - 0.64 ; p < 0.05 ) . A borderline significant effect was demonstrated on the stress component of the DASS ( - 3.69 , 95 % CI - 7.38 to 0.01 ; p = 0.05 ) . Follow-up at 8 weeks post-trial revealed that the effect was maintained . CONCLUSIONS Mindfulness practice reduced stress and anxiety in senior medical students . Stress is prevalent in medical students and can have adverse effects on both student health and patients . A simple , self-administered , evidence -based intervention now exists to manage stress in this at-risk population and should be widely utilised It is assumed that chronic or extensive release of cortisol due to stress has deleterious effects on somatic and psychological health , making interventions aim ing to reduce and /or normalize cortisol secretion to stress of interest . Cognitive-behavioral stress management ( CBSM ) has repeatedly been shown to effectively reduce cortisol responses to acute psychosocial stress . However , the effects of CBSM on psychoneuroendocrine responses during " real-life " stress have yet not been examined in healthy subjects . Eight weeks before all subjects took an important academic exam , 28 healthy economics students were r and omly assigned to four weekly sessions of cognitive behavioral stress management ( CBSM ) training or a waiting control condition . Psychological and somatic symptoms were repeatedly assessed throughout the preparation period . Salivary cortisol ( cortisol awakening response and short circadian cortisol profile ) was repeatedly measured at baseline and on the day of the exam . In addition , cognitive appraisal was assessed on the day of the exam . Subjects in the CBSM group showed significantly lower anxiety and somatic symptom levels throughout the period prior to the exam . On the day of the exam , groups differed in their cortisol awakening stress responses , with significantly attenuated cortisol levels in controls . Short circadian cortisol levels did not differ between groups . Interestingly , groups differed in their associations between cortisol responses before the exam and cognitive stress appraisal , with dissociation in controls but not in the CBSM group . The results show that CBSM reduces psychological and somatic symptoms and influences the ability to show a cortisol response corresponding to subjectively perceived stress . In line with current psychoneuroendocrine models , the inability to mount a cortisol response corresponding to the cognitive appraisal in controls could be a result of a dysregulated HPA axis , probably as a consequence of longlasting stress The study examined the effectiveness of cognitive behavioral therapy ( CBT ) with university students suffering from moderate to severe depressive symptoms in Jordan . Eighty-four university students were recruited and assigned r and omly to control and intervention groups . Intervention impact was assessed on measures of depressive symptoms , perceived stress , and coping strategies at three time points ; baseline , postintervention , and 3-months postintervention . The interventional model used was the Modified Teaching Kids to Cope ( MTKC ) , and the control group received no treatment . Overall , using CBT showed a significant improvement in the outcome measures . At postintervention , students had lower scores on perceived stress , lower depressive symptoms , less use of avoidance coping strategies , and more use of approach coping strategies . The findings are discussed in terms of treatment implication s and recommendations for use at academic and health care setting The purpose of this study was to investigate the effects of a 5-week stress management program for 40 junior baccalaureate nursing students . A quasi-experimental pretest-posttest control group design was used . The stress management group included training sessions using cognitive modification techniques and Stroebel 's Quieting Response ( QR ) augmented with biofeedback techniques for self-relaxation . A significant reduction of state anxiety ( P < .001 ) was reported on the State-Trait Anxiety Inventory ( STAI ) by the experimental groups , while the state anxiety of the control groups remained relatively unchanged . There were no significant changes in trait anxiety scores . Urinary potassium excretion was measured as an index of the adrenal stress response . Findings revealed no statistically significant correlation between potassium excretion and scores on the STAI . These results support the benefits of integrating a stress management program into curricula for nursing students Abstract Objectives : Many suicidal college students do not receive mental health treatment , and the reasons for this are not fully understood . This study examines how attitudes , beliefs , and social network factors relate to help seeking among suicidal students . Participants : A r and om sample of 8,487 undergraduate and graduate students from 15 US universities participated . Methods : A Web-based survey administered in spring 2009 examined correlates of mental health service utilization among students reporting serious thoughts of suicide in the previous year ( n = 543 ) . Results : Correlates of treatment use included perceived need , beliefs that treatment is effective , contact with service users , lower personal stigma , higher perceived stigma , fewer positive relationships , and sexual minority or Caucasian identity . Conclusions : Help seeking among suicidal students is associated with a range of personal and social network factors . Campus strategies to enhance help seeking should be tailored to address identified facilitators and barriers to treatment use among target population Objective and Participants : The authors evaluated the effects on stress , rumination , forgiveness , and hope of two 8-week , 90-min/wk training programs for college undergraduates in meditation-based stress-management tools . Methods : After a pretest , the authors r and omly allocated college undergraduates to training in mindfulness-based stress reduction ( MBSR ; n = 15 ) , Easwaran 's Eight-Point Program ( EPP ; n = 14 ) , or wait-list control ( n = 15 ) . The authors gathered pretest , posttest , and 8-week follow-up data on self-report outcome measures . Results : The authors observed no post-treatment differences between MBSR and EPP or between posttest and 8-week follow-up ( p > .10 ) . Compared with controls , treated participants ( n = 29 ) demonstrated significant benefits for stress ( p < .05 , Cohen 's d = -.45 ) and forgiveness ( p < .05 , d = .34 ) and marginal benefits for rumination ( p < .10 , d = -.34 ) . Conclusions : Evidence suggests that meditation-based stress-management practice s reduce stress and enhance forgiveness among college undergraduates . Such programs merit further study as potential health-promotion tools for college population |
883 | 18,518,933 | Similar to previously reported meta-analyses , we did not find a significant effect of CRRT on the OR of survival .
The progressive reduction in the OR of survival with CRRT relative to IHD might reflect progressive improvements in IHD .
The OR of DD was not affected by mode of RRT .
In conclusion , compared with IHD , CRRT does not offer an advantage with regards to survival or DD in ARF . | BACKGROUND Acute renal failure ( ARF ) still bears a poor prognosis with mortality rates up to 70 % and the ideal form of renal replacement therapy ( RRT ) remains controversial .
The purpose of this study was to conduct a systematic review and meta- analysis of all r and omized controlled trials ( RCT ) to examine the effect of dialysis modality ( IHD : Intermittent haemodialysis ; CRRT : continuous renal replacement therapy ) on survival of patients with ARF and to also study the effect of each modality on dialysis dependence ( DD ) . | BACKGROUND Despite the widespread use of continuous renal replacement therapy in critically ill patients with acute renal failure ( ARF ) , there are few data supporting its benefits over conventional intermittent hemodialysis ( IHD ) . We sought to analyze differences in survival between modalities in a study that compared continuous venovenous hemodialysis ( CVVHD ) with IHD . METHODS Eighty critically ill patients with ARF requiring dialysis were r and omized after stratification by severity of illness to treatment with CVVHD or IHD . RESULTS There were no differences in survival or renal recovery between groups . In patients who died , mean survival time was 10.7 + /- 11.2 days for the IHD group versus 14.3 + /- 16.1 days for the CVVHD group ( P = not significant ) . There was greater net volume removal in the CVVHD group during 72 hours . Declines in urine output during 72 hours were similar between groups . Mean arterial pressure off and on dialysis therapy was analyzed retrospectively . There was a significant decrease in mean arterial pressure for patients on IHD therapy not seen in those on CVVHD therapy , but this did not lead to a survival advantage . CONCLUSION Despite greater volume control , CVVHD did not lead to an improvement in survival , preservation of urine output , or renal recovery compared with IHD in patients with ARF Among critically ill patients , acute kidney injury ( AKI ) requiring dialysis is associated with mortality rates generally in excess of 50 % . Continuous renal replacement therapies ( CRRT ) often are recommended and widely used , although data to support its superiority over intermittent hemodialysis ( IHD ) are lacking . Data from the Program to Improve Care in Acute Renal Disease ( PICARD ) , a multicenter observational study of AKI , were analyzed . Among 398 patients who required dialysis , the risk for death within 60 d was examined by assigned initial dialysis modality ( CRRT [ n = 206 ] versus IHD [ n = 192 ] ) using st and ard Kaplan-Meier product limit estimates , proportional hazards ( " Cox " ) regression methods , and a propensity score approach to account for selection effects . Crude survival rates were lower for patients who were treated with CRRT than IHD ( survival at 30 d 45 versus 58 % ; P = 0.006 ) . Adjusted for age , hepatic failure , sepsis , thrombocytopenia , blood urea nitrogen , and serum creatinine and stratified by site , the relative risk for death associated with CRRT was 1.82 ( 95 % confidence interval 1.26 to 2.62 ) . Further adjustment for the propensity score did not material ly alter the association ( relative risk 1.92 ; 95 % confidence interval 1.28 to 2.89 ) . Among critically ill patients with AKI , CRRT was associated with increased mortality . Although the results could reflect residual confounding by severity of illness , these data provide no evidence for a survival benefit afforded by CRRT . Larger , prospect i ve , r and omized clinical trials to compare CRRT and IHD in severe AKI are needed The syndrome of sepsis-associated severe acute renal failure is a frequent component of sepsis-induced multiorgan failure . Continuous hemofiltration techniques are often used in its dialytic management but little is known about their impact . The aim of this study is to define the biochemical and clinical impact of continuous hemodiafiltration ( CHD ) in the management of this syndrome and to retrospectively compare it to that of conventional dialysis . A prospect i ve , cohort study and retrospective comparison with historical controls was conducted at an intensive care unit ( ICU ) of a tertiary institution . Eighty-seven consecutive septic patients with acute renal failure were treated by continuous hemodiafiltration and 40 consecutive similar patients by conventional dialysis . All new cases of severe acute renal failure with sepsis were treated by means of continuous hemodiafiltration . Historical controls were treated by means of conventional dialysis . Illness and sepsis severity were assessed on admission and prior to initiation of treatment . Biochemical variables were assessed daily . Outcome was measured as discharge from the ICU , duration of oliguria and discharge from hospital . Of the 87 patients treated by hemodiafiltration , 86 had multiorgan failure , 71 ( 81.6 % ) septic shock and 52 ( 59.8 % ) bacteremia/fungemia . Their APACHE II score on admission was 29.9 and their mean organ failure score prior to treatment was 4.3 . Hemodiafiltration result ed in a significant fall in mean urea and creatinine levels within 24 h and in the correction of acidosis . The mean alveolar-arterial gradient fell from 276 to 211 mm Hg ( p < 0.02 ) within 24 h of therapy . Complications were few and mostly related to vascular access . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Acute renal failure ( ARF ) requiring dialysis in critically ill patients is associated with an in-hospital mortality rate of 50 to 80 % . The worldwide st and ard for renal replacement therapy is intermittent hemodialysis ( IHD ) . Continuous hemodialysis and hemofiltration techniques have recently emerged as alternative modalities . These two therapies have not been directly compared . METHODS A multicenter , r and omized , controlled trial was conducted comparing two dialysis modalities ( IHD vs. continuous hemodiafiltration ) for the treatment of ARF in the intensive care unit ( ICU ) . One hundred sixty-six patients were r and omized . Principal outcome measures were ICU and hospital mortality , length of stay , and recovery of renal function . RESULTS Using intention-to-treat analysis , the overall ICU and in-hospital mortalities were 50.6 and 56.6 % , respectively . Continuous therapy was associated with an increase in ICU ( 59.5 vs. 41.5 % , P < 0.02 ) and in-hospital ( 65.5 vs. 47.6 % , P < 0.02 ) mortality relative to intermittent dialysis . Median ICU length of stay from the time of nephrology consultation was 16.5 days , and complete recovery of renal function was observed in 34.9 % of patients , with no significant group differences . Despite r and omization , there were significant differences between the groups in several covariates independently associated with mortality , including gender , hepatic failure , APACHE II and III scores , and the number of failed organ systems , in each instance biased in favor of the intermittent dialysis group . Using logistic regression to adjust for the imbalances in group assignment , the odds of death associated with continuous therapy was 1.3 ( 95 % CI , 0.6 to 2.7 , P = NS ) . A detailed investigation of the r and omization process failed to explain the marked differences in patient assignment . CONCLUSIONS A r and omized controlled trial of alternative dialysis modalities in ARF is feasible . Despite the potential advantages of continuous techniques , this study provides no evidence of a survival benefit of continuous hemodiafiltration compared with IHD . This study did not control for other major clinical decisions or other supportive management strategies that are widely variable ( for example , nutrition support , hemodynamic support , timing of initiation , and dose of dialysis ) and might material ly influence outcomes in ARF . St and ardization of several aspects of care or extremely large sample sizes will be required to answer optimally the questions originally posed by this investigation BACKGROUND Acute renal failure ( ARF ) is associated with a persistent high mortality in critically ill patients in intensive care units ( ICUs ) . Most studies to date have focused on patients with established , intrinsic ARF or relatively severe ARF due to multiple factors . None have examined outcomes of dialysis-dependent chronic renal failure [ end-stage renal disease ( ESRD ) ] patients in the ICU . We examined the incidence and outcomes of ARF in the ICU using a st and ard definition and compared these to outcomes of ICU patients with either ESRD or no renal failure . We sought to determine the impact of renal dysfunction and /or loss of organ function on outcome . METHODS We prospect ively scored 1530 admissions to eight ICUs over a 10-month period for illness severity at ICU admission using the Acute Physiological and Chronic Health Evaluation ( APACHE III ) evaluation tool . Patients were defined as having ARF based on the definition of Hou et al ( Am J Med 74:243 - 248,1983 ) design ed to detect significant measurable declines in renal function based on serum creatinine . ESRD patients were identified as being chronically dialysis-dependent prior to ICU admission and the remainder had no renal failure . Clinical characteristics at ICU admission and ICU and hospital outcomes were compared between the three groups . RESULTS We identified 254 cases of ARF , 57 cases of ESRD and 1219 cases of no renal failure for an incidence of ARF of 17 % . Roughly half the ARF patients had ARF at ICU admission and the remainder developed ARF during their ICU stay . Only 11 % of ARF patients required dialysis support . ARF patients had significantly higher acute illness severity scores than those with no renal failure , whereas patients with ESRD had intermediate severity scores . ICU mortality was 23 % for patients with ARF , 11 % for those with ESRD , and 5 % for those with no renal failure . There was no difference in outcome between patients who had ARF at ICU admission and those who developed ARF in the ICU . Patients with ARF severe enough to require dialysis had a mortality of 57 % . APACHE III predicted outcome very well in patients with no renal failure and patients with ARF at the time of scoring but underpredicted mortality in those who developed ARF after ICU admission and overestimated mortality in patients with ESRD . CONCLUSIONS ARF is common in ICU patients and has a persistent negative impact on outcomes , although the majority of ARF is not severe enough to require dialysis support . The mortality of patients with ARF from all causes is almost exactly similar to that noted using the same criteria two decades ago . More profound ARF requiring dialysis continues to have an even greater mortality . Nevertheless , acute declines in renal function are associated with a mortality that is not well explained simply by loss of organ function . The majority of ARF patients who did not require dialysis still had a considerably higher mortality than the ESRD patients , all of whom required dialysis ; while ARF patients who did require dialysis had a much higher morality than ESRD patients . APACHE III performs well and captures the mortality of patients with ARF at the time of scoring . Development of ARF after scoring has a profound effect on st and ardized mortality . We were unable to identify a unique mortality associated with ARF , but the presence of measurable renal insufficiency continues to be a sensitive marker for poor outcome A potential application of the continuous renal replacement therapies is the extracorporeal removal of inflammatory mediators in septic patients . Cytokine elimination with continuous renal replacement therapies has been demonstrated in several clinical studies , but so far without important effects on their serum concentrations . Improved knowledge of the cytokine removal mechanisms could lead to the development of more efficient treatment strategies . In the present study , 15 patients with septic shock and acute renal failure were observed during the first 24 h of treatment with continuous venovenous hemofiltration ( CVVH ) with an AN69 membrane . After 12 h , the hemofilter was replaced and the blood flow rate ( QB ) was switched from 100 ml/min to 200 ml/min or vice versa . Pre- and postfilter plasma and ultrafiltrate concentrations of selected inflammatory and anti-inflammatory cytokines were measured at several time points allowing the calculation of a mass balance . Cytokine removal was highest 1 h after the start of CVVH and after the change of the membrane ( ranging from 25 to 43 % of the prefilter amount ) , corresponding with a significant fall in the serum concentration of all cytokines . The inhibitors of inflammation were removed to the same extent as the inflammatory cytokines . Adsorption to the AN69 membrane appeared to be the main clearance mechanism , being most pronounced immediately after installation of a new membrane and decreasing steadily thereafter , indicating rapid saturation of the membrane . A QB of 200 ml/min was associated with a 75 % increase of the ultrafiltration rate and a significantly higher convective elimination and membrane adsorption than at a QB of 100 ml/min . The results indicate that optimal cytokine removal with CVVH with an AN69 membrane could be achieved with a combination of a high QB/ultrafiltration rate and frequent membrane changes BACKGROUND Mortality rates of critically ill patients with acute renal failure ( ARF ) requiring renal replacement therapy ( RRT ) are high . Intermittent and continuous RRT are available for these patients on the intensive care units ( ICUs ) . It is unknown which technique is superior with respect to patient outcome . METHODS We r and omized 125 patients to treatment with either continuous venovenous haemodiafiltration ( CVVHDF ) or intermittent haemodialysis ( IHD ) from a total of 191 patients with ARF in a tertiary-care university hospital ICU . The primary end-point was ICU and in-hospital mortality , while recovery of renal function and hospital length of stay were secondary end-points . RESULTS During 30 months , no patient escaped r and omization for medical reasons . Sixty-six patients were not r and omized for non-medical reasons . Of the 125 r and omized patients , 70 were treated with CVVHDF and 55 with IHD . The two groups were comparable at the start of RRT with respect to age ( 62+/-15 vs 62+/-15 years , CVVHDF vs IHD ) , gender ( 66 vs 73 % male sex ) , number of failed organ systems ( 2.4+/-1.5 vs 2.5+/-1.6 ) , Simplified Acute Physiology Scores ( 57+/-17 vs 58+/-23 ) , septicaemia ( 43 vs 51 % ) , shock ( 59 vs 58 % ) or previous surgery ( 53 vs 45 % ) . Mortality rates in the hospital ( 47 vs 51 % , CVVHDF vs IHD , P = 0.72 ) or in the ICU ( 34 vs 38 % , P = 0.71 ) were independent of the technique of RRT applied . Hospital length of stay in the survivors was comparable in patients on CVVHDF [ median ( range ) 20 ( 6 - 71 ) days , n = 36 ] and in those on IHD [ 30 ( 2 - 89 ) days , n = 27 , P = 0.25 ] . The duration of RRT required was the same in both groups . CONCLUSION The present investigation provides no evidence for a survival benefit of continuous vs intermittent RRT in ICU patients with ARF Abstract Objectives . To describe the current practice of hemodialysis in acute renal failure ( ARF ) and to estimate the impact of hemodialysis modality on patient outcome . Design . Prospect i ve multicenter observational study conducted from March 1996 to May 1997 . Setting . The 28 multidisciplinary ICUs in the Rhône-Alpes region in France . Patients . The 587 patients who required hemodialysis . Measurements and results . Patients were followed until hospital discharge . Among the 587 patients 354 received continuous ( CRRT ) and 233 intermittent ( IRRT ) renal replacement therapy as first choice . CRRT patients had a higher number of organ dysfunctions on admission and at the time of ARF and higher SAPS II at time of ARF . Mortality was 79 % in the CRRT group and 59 % in the IRRT group . Logistic regression analysis showed decreased patient survival to be associated with SAPS II on admission , oliguria , admission from hospital or emergency room , number of days between admission and ARF , cardiac dysfunction at time of ARF , and ischemic ARF . No underlying disease or nonfatal disease , and absence of hepatic dysfunction were associated with an increase in patient survival . The type of renal replacement therapy was not significantly associated with outcome . Conclusions . Renal replacement therapy mode was not found to have any prognostic value . R and omized controlled trials should be undertaken to assess this important question BACKGROUND Despite the widespread availability of dialytic and intensive care unit technology , the probability of early mortality in critically ill persons with acute renal failure is distressingly high . Previous efforts to predict outcome in this population have been limited by small sample size and the absence of uniform exclusion criteria . Additionally , data obtained decades ago may not apply today owing to changes in case mix . METHODS The medical records of 132 consecutive patients in the intensive care unit with acute renal failure who required dialysis from 1991 through 1993 were evaluated by a blinded review er . RESULTS The overall in-hospital mortality rate was 70 % . Twelve readily available historical , clinical , and laboratory variables were significantly associated with in-hospital mortality . Multivariate logistic regression analysis showed that mechanical ventilation , malignancy , and nonrespiratory organ system failure were independently associated with in-hospital mortality . Using a 95 % positivity criterion , this model identified 24 % of high-risk patients who died , without misclassification of any survivors . Of those who survived to hospital discharge , 33 % were dialysis dependent and 28 % were institutionalized long-term . CONCLUSIONS Among critically ill patients , acute renal failure requiring dialysis is an ominous condition with a high risk of in-hospital mortality . This risk appears to depend largely on comorbid conditions , such as the need for mechanical ventilation and underlying malignancy . While this prognostic model requires prospect i ve validation , it appears to identify a substantial fraction of patients for whom dialysis may be of limited or no benefit BACKGROUND Whether continuous renal replacement therapy is better than intermittent haemodialysis for the treatment of acute renal failure in critically ill patients is controversial . In this study , we compare the effect of intermittent haemodialysis and continuous venovenous haemodiafiltration on survival rates in critically ill patients with acute renal failure as part of multiple-organ dysfunction syndrome . METHODS Our prospect i ve , r and omised , multicentre study took place between Oct 1 , 1999 , and March 3 , 2003 , in 21 medical or multidisciplinary intensive-care units from university or community hospitals in France . Guidelines were provided to achieve optimum haemodynamic tolerance and effectiveness of solute removal in both groups . The two groups were treated with the same polymer membrane and bicarbonate-based buffer . 360 patients were r and omised , and the primary endpoint was 60-day survival based on an intention-to-treat analysis . FINDINGS Rate of survival at 60-days did not differ between the groups ( 32 % in the intermittent haemodialysis group versus 33 % in the continuous renal replacement therapy group [ 95 % CI -8.8 to 11.1 , ] ) , or at any other time . INTERPRETATION These data suggest that , provided strict guidelines to improve tolerance and metabolic control are used , almost all patients with acute renal failure as part of multiple-organ dysfunction syndrome can be treated with intermittent haemodialysis BACKGROUND Mortality in severe acute renal failure ( ARF ) requiring renal replacement therapy ( RRT ) approximates 50 % and varies with clinical severity . Continuous RRT ( CRRT ) has theoretical advantages over intermittent hemodialysis ( IHD ) for critical patients , but a survival advantage with CRRT is yet to be clearly demonstrated . To date , no prospect i ve controlled trial has sufficiently answered this question , and the present prospect i ve outcome study attempts to compare survival with CRRT versus that with IHD . METHODS Multivariable Cox-proportional hazards regression was used to analyze the impact of RRT modality choice ( CRRT vs. IHD ) on in-hospital and 100-day mortality among ARF patients receiving RRT during 2000 and 2001 at University of Michigan , using an " intent-to-treat " analysis adjusted for multiple comorbidity and severity factors . RESULTS Overall in-hospital mortality before adjustment was 52 % . Triage to CRRT ( vs IHD ) was associated with higher severity and unadjusted relative rate ( RR ) of in-hospital death ( RR = 1.62 , p = 0.001 , n = 383 ) . Adjustment for comorbidity and severity of illness reduced the RR of death for patients triaged to CRRT and suggested a possible survival advantage ( RR = 0.81 , p = 0.32 ) . Analysis restricted to patients in intensive care for more than five days who received at least 48 hours of total RRT , showed the RR of in-hospital mortality with CRRT to be nearly 45 % lower than IHD ( RR = 0.56 , n = 222 ) , a difference in RR that indicates a strong trend for in-hospital mortality with borderline statistical significance ( p = 0.069 ) . Analysis of 100-day mortality also suggested a potential survival advantage for CRRT in all cohorts , particularly among patients in intensive care for more than five days who received at least 48 h of RRT ( RR = 0.60 , p = 0.062 , n = 222 ) . CONCLUSION Applying the present methodology to outcomes at a single tertiary medical center , CRRT may appear to afford a survival advantage for patients with severe ARF treated in the ICU . Unless and until a prospect i ve controlled trial is realized , the present data suggest potential survival advantages of CRRT and support broader application of CRRT among such critically ill patients BACKGROUND Parameters of splanchnic regional perfusion , like intramucosal pH ( pHi ) and pCO(2 ) ( pCO(2)i ) , may predict outcome in septic shock patients . Continuous venovenous haemofiltration ( CVVH ) has been considered beneficial in haemodynamically unstable septic shock patients . In a prospect i ve , r and omized , clinical study , we investigated whether CVVH , in comparison to intermittent haemodialysis ( IHD ) , is able to improve splanchnic regional perfusion in critically ill patients . METHODS Thirty septic shock patients with acute renal failure were r and omized to either CVVH ( n=20 ) or IHD ( n=10 ) groups for renal replacement therapy . Patient characteristics at baseline were not different in terms of severity of illness ( APACHE II scores ) , haemodynamics , and pHi/pCO(2)i values . Systemic haemodynamics , oxygen transport variables , and splanchnic regional perfusion parameters were measured at 0.5 , 2 , 4 and 24 h after initiation of renal replacement therapy . There were no major changes in vasopressor support throughout the 24-h study period . RESULTS In contrast to IHD , CVVH caused a decrease in heart rate ( -3+/-11 vs + 9+/-8/min , P<0.01 ) and an increase in systolic blood pressure ( + 12+/-1 vs -5+/-17 mmHg , P<0.05 ) after 2 h. After 24 h , increased systemic vascular resistance was found in the CVVH group in comparison with the IHD group ( + 312+/-755 vs -29+/-89 dyne/cm(5 ) , P<0.05 ) and was accompanied by a decrease in cardiac output ( -1.54+/-1.4 vs -0.25+/-0.9 l/min , P<0.01 ) . However pHi values remained constant throughout the 24-h study period in both groups and were not different between the groups ( CVVH 7.19+/-0.1 vs IHD 7.19+/-0.1 , n.s . ) as did the pCO(2)i values ( CVVH + 7+/-17 vs IHD 0+/-15 mmHg , n.s . ) and pCO(2 ) gap values ( CVVH + 6+/-15 vs IHD + 5+/-12 mmHg , n.s . ) . CONCLUSIONS Despite different changes of systemic haemodynamics between CVVH and IHD , CVVH did not improve parameters of splanchnic regional perfusion like pHi , pCO(2)i or pCO(2 ) gap in septic shock patients BACKGROUND Extended dialysis is an increasingly used modality of renal replacement therapy that theoretically offers advantages of both intermittent and continuous therapies in the intensive care unit ( ICU ) . METHODS We r and omly treated 39 ventilated critically ill patients with oliguric acute renal failure with either continuous venovenous hemofiltration ( CVVH ; n = 19 ; age , 50.1 + /- 3.2 years ; Acute Physiology and Chronic Health Assessment II [ APACHE II ] score , 32.3 + /- 1.2 ; 79 % sepsis ) and a substitution fluid rate of at least 30 mL/kg/h for 24 hours or with extended dialysis for 12 hours ( n = 20 ; age , 50.8 + /- 3.6 years ; APACHE II score , 33.6 + /- 1.0 ; 85 % sepsis ) . The latter was performed using an easy-to-h and le , single-pass , batch dialysis system . All hemodynamic parameters were monitored invasively by means of an indwelling arterial catheter . RESULTS Average mean arterial blood pressure , heart rate , cardiac output , systemic vascular resistance , and catecholamine dose were not significantly different in both therapies . Urea reduction rate was similar with extended dialysis compared with CVVH therapy ( 53 % + /- 2 % versus 52 % + /- 3 % ; P = not significant ) despite an average rate of substitution fluid with the latter of 3.2 + /- 0.1 L/h . This was corroborated by the finding of similar amounts of urea eliminated in the collected spent total hemofiltration and dialysis fluid . Correction of acidosis was accomplished faster with extended dialysis than CVVH , and the amount of heparin used was significantly lower with extended dialysis ( P < 0.01 ) . CONCLUSION Extended dialysis combines excellent detoxification with cardiovascular tolerability , even in severely ill patients in the ICU . The technically simple dialysis system used offers flexibility of treatment time The morbidity and mortality benefits of new forms of continuous renal replacement therapy remain controversial . The authors have compared a cohort of consecutive prospect ively studied critically ill patients with acute renal failure treated with continuous venovenous hemodiafiltration ( CVVHD ) ( n = 76 ) to a previously described antecedent group of patients treated in intensive care with intermittent hemodialysis or peritoneal dialysis ( conventional dialysis [ CD ] ) ( n = 84 ) . Patients were comparable for mean age , gender distribution , and mean number of failing organs ( CVVHD : 4 ; CD : 3.9 ) . CVVHD patients were more severely ill as measured by APACHE II score ( CVVHD : score of 29 ; CD : score of 25.8 ) . Despite their greater illness severity , CVVHD patients more often survived to hospital discharge ( CVVHD : 40.8 % ) than did CD patients ( CD : 29.8 % ; NS ) . After adjustment for illness severity , in patients with two , three , or four failing organs , survival was 54.3 % for CVVHD versus 29.3 % for CD ( p < 0.01 ) . Survival was 48 % for CVVHD patients with an intermediate APACHE II score ( 24 to 29 ) , compared with 12.5 % for comparable CD patients ( p < 0.01 ) . No statistically significant differences were seen at either extreme of illness severity . Complications were significantly fewer during CVVHD ( 1 vs. 18 ) . These data support the view that CVVHD reduces morbidity and mortality in critically ill patients with acute renal failure The mortality of patients with acute renal failure ( ARF ) remains high , and in several large studies approaches 60 % . This mortality is particularly high in patients with ARF who require dialysis and has not changed substantially over several years , despite the introduction of major advances in monitoring and treatment . Increasing prevalence of comorbidities has been suggested as the major factor in this persistently high mortality . This study investigates the potential role of the dialysis membrane on patient outcome in a prospect i ve multicenter study of 153 patients with ARF requiring dialysis . The membrane assignment was made in alternating order and was limited to membranes with low complement activation ( Biocompatible [ BCM ] ) and cellulosic , high complement activation ( Bioincompatible [ BICM ] ) . Both types of membranes were low-flux membranes . Patients were dialyzed with the assigned membrane until recovery , discharge from hospital , or death . The severity of illness of each patient was assessed using the APACHE II score at the time of initiation of dialysis . A logistic regression analysis was used to adjust for the APACHE II score . The results of the study showed a statistically significant difference in survival ( 57 % in patients on BCM , 46 % in patients on BICM ; P = 0.03 ) and in recovery of renal function ( 64 % in patients on BICM and 43 % in patients on BICM ; P = 0.001 ) . These differences were particularly marked in the patients who were nonoliguric ( > 400 ml/d of urine output ) at initiation of the study . In the subset of patients who were nonoliguric at the start of dialysis , a larger fraction ( 70 % ) became oliguric after initiating dialysis on a BICM membrane , in contrast to 44 % who were initiated on a BCM membrane ( P = 0.03 ) . It is concluded that the biocompatibility of the dialysis membrane plays a role in the outcome of patients with ARF , particularly those who are nonoliguric at the time of initiation of dialysis Continuous venovenous hemofiltration ( CVVH ) or CVVH with additional diffusive dialysis ( CVVH-D ) has theoretical advantages in treating severe acute renal failure ( ARF ) , but no prospect i ve clinical trials or restrospective comparison studies have clearly shown its superiority over intermittent hemodialysis ( HD ) . To evaluate this question , all 349 adult patients with ARF receiving renal replacement therapy ( RRT ) at our medical center during 1995 and 1996 were analyzed using multivariate Cox proportional hazards methods . Initial univariate analysis showed the odds of death when receiving initial CVVH to be more than twice those when receiving initial HD ( risk for death , 2.03 ; P < 0.01 ) . Progressive exclusion of patients in whom the RRT modality might not be open to choice and the risk for death was very high ( systolic blood pressure < 90 mm Hg ; total bilirubin level > 15 mg/dL ; or total RRT < 48 hours ) for total RRT left 227 patients in whom the risk for death was 1.09 ( 95 % confidence interval [ CI ] , 0.67 to 1.80 ; P = 0.72 ) for initial CVVH , virtually equivalent to the risk for initial HD . Comorbid indicators significantly associated with death or failure to recover renal function included : older age ; medical rather than surgical diagnosis ; preexisting infection or trauma and liver disease as primary diagnoses ; and abnormal bilirubin level or vital signs at initiation of RRT . These results show that the high crude mortality rate of patients undergoing CVVH was related to severity of illness and not the treatment choice itself . With the addition of more inclusive comorbidity data and a broader spectrum of interim outcomes , this type of analysis is a practical alternative to what would almost assuredly be a cumbersome and costly prospect i ve , controlled trial comparing traditional HD with CVVH BACKGROUND Sepsis is a major cause of acute renal failure in hospital patients , but its incidence and the associated prognostic factors have rarely been assessed prospect ively by multivariate analysis . METHODS We conducted a prospect i ve 6-month study in 20 multidisciplinary intensive care units to assess the prognosis of patients hospitalized with acute renal failure due to sepsis . Sepsis syndrome and septic shock were defined according to the criteria of the Society of Critical Care Medicine Consensus Conference . Severity scoring indexes ( SAPS , APACHE II , and organ system failure ( OSF ) ) were measured on ICU admission and on inclusion . The end-point was hospital mortality . RESULTS Acute renal failure had a septic origin in 157 patients ( Group 1 ) , comprising 68 with septic shock and 89 with sepsis syndrome , and did not result from infection in 188 patients ( Group 2 ) . Patients with septic acute renal failure were older ( mean age : 62.2 versus 57.9 years , P<0.02 ) and had on inclusion a higher SAPS ( 19.3 versus 16.1 , P<0.001 ) , APACHE II ( 29.6 versus 24.3 , P<0.001 ) , and OSF ( 2.07 versus 1.52 , P<0.001 ) than patients with non-septic acute renal failure . They had a higher need for mechanical ventilation ( 69.1 % versus 47.3 % , P<0.001 ) , and acute renal failure was more often delayed during the ICU stay than was present on admission ( 47.7 % versus 32.4 % respectively , P<0.005 ) . Hospital mortality was higher in patients with septic acute renal failure ( 74.5 % ) than in those whose renal failure did not result from sepsis ( 45.2 % , P<0.001 ) . Mortality was influenced by the presence of a septic shock ( 79.4 % ) or of a sepsis syndrome on inclusion ( 70.8 % ) . Using a stepwise logistic regression model , sepsis was an independent predictor of hospital mortality ( OR , 2.51 ; 95 % CI , 1.44 - 4.39 ) as well as a delayed occurrence of acute renal failure , oliguria , an altered previous health status hospitalization prior to ICU , need for mechanical ventilation , age and severity scoring indexes on inclusion . In total patients , mortality was higher in dialyzed than in non-dialyzed patients ( P<0.001 ) , and in those treated by continuous compared to intermittent techniques ( P<0.01 ) . Patients dialyzed with biocompatible membranes had a lower mortality than those treated with cellulose membranes ( P<0.005 ) . CONCLUSIONS Patients with acute renal failure due to sepsis have a worse prognosis than those with non-septic acute renal failure . Sepsis and the above-defined predictive factors are to be considered in studies on prognosis of ARF patients . Our results suggest that the use of biocompatible membranes may reduce significantly mortality in these patients Background Continuous renal replacement therapy is increasingly used in the management of acute renal failure in critically ill patients . The advantages of continuous renal replacement therapy ( CRRT ) over intermittent hemodialysis ( IHD ) , however , are not yet fully documented . In particular , it is unknown whether continuous veno-venuous hemodiafiltration ( CVVHDF ) provides better control of azotemia than IHD . Objectives To study the effect on azotemic control of changing acute renal failure treatment from IHD to CVVHDF . Setting s Tertiary intensive care unit . Patients Forty seven consecutive critically ill patients with multiorgan failure and acute renal failure treated with IHD and 47 similar patients treated with CVVHDF . Methods Analysis of daily morning urea and creatinine concentrations over the period of renal replacement therapy in the ICU . Statistical comparison of data . Results The two groups of patients were comparable for mean age ( 55 years for IHD vs. 60 years for CVVHDF ; NS ) and number of failing organs prior to therapy ( mean of 4.2 for IHD vs. 3.7 for CVVHDF ; NS ) . Severity of illness at admission as assessed by APACHE II score , however , was greater for patients receiving CVVHDF ( 29.4 vs 25.7 ; p<0.003 ) . CVVHDF was associated with a significantly lower plasma urea ( p < 0.0001 ) and serum creatinine ( p<0.01 ) level at 24 hours of treatment despite similar levels at the start of therapy . Throughout the duration of therapy , mean urea levels ( 35.0 mmol/L for IHD vs 23.4 mmol/L for CVVHDF ) and mean serum creatinine levels ( 513 micromoles/L for IHD and 263 micromoles/L for CVVHDF ) showed significantly ( p < 0.0001 ) better control of uremia with CRRT . Conclusions Changing the form of renal replacement therapy from intermittent hemodialysis to continuous hemofiltration is associated with improved control of azotemia . The superior adequacy of small solute clearance achieved during CVVHDF provides additional support for its preferential use in the management of acute renal failure in the ICU |
884 | 18,675,569 | CONCLUSIONS The fairly high placebo effect observed is very similar to data obtained from patients affected by atypical facial pain . | BACKGROUND A systematic review from the Cochrane Collaboration stated that alpha-lipoic acid ( ALA ) may help in the management of burning mouth syndrome ( BMS ) .
Because all of the data on ALA came from a single group , it has been stressed that its effectiveness should be reproduced in other population s. AIM A double-blind , r and omized , placebo-controlled study , including two test groups ( Group A and Group B ) and one control group ( Group C ) , was carried out to evaluate the efficacy of systemic ALA ( 400 mg ) and ALA ( 400 mg ) plus vitamins in the treatment of BMS . | INTRODUCTION Although a significant amount of evidence indicates the efficacy of some antidepressants in treating psychogenic pain and somatoform disorder , very few studies have investigated their possible therapeutic action in burning mouth syndrome ( BMS ) . The purpose of this 8-week , single-blind study was to provide preliminary data on the efficacy and tolerability of amisulpride and the selective serotonin reuptake inhibitors ( SSRIs ) paroxetine and sertraline for patients with BMS . METHOD Seventy-six patients with BMS ( diagnosed according to the criteria in the literature and integrating the Diagnostic Interview Schedule-Revised for a complete psychiatric assessment ) , with no possible local or systemic causes and without concurrent major depression , were r and omly assigned to receive amisulpride ( 50 mg/day ) , paroxetine ( 20 mg/day ) , or sertraline ( 50 mg/day ) . Efficacy assessment s included a visual analogue scale ( VAS ) for pain intensity , the Hamilton Rating Scale for Depression ( HAM-D ) , the Hamilton Rating Scale for Anxiety ( HAM-A ) , and the Clinical Global Impressions scale ( CGI ) . RESULTS All 3 treatment regimens result ed in a significant improvement from baseline in burning mouth symptoms at week 8 as demonstrated by the quantitative ( mean reduction in VAS , HAM-D , and HAM-A scores ) and qualitative ( percentage of responders ) analyses . Amisulpride showed a shorter response latency than the SSRIs . No serious adverse events were reported , and the incidence of side effects did not differ among the 3 groups . None of the patients who received amisulpride withdrew from the trial , whereas withdrawal from the trial occurred within the first week of treatment in 11.5 % of patients ( N = 3 ) treated with paroxetine and in 21.7 % of patients ( N = 5 ) treated with sertraline . CONCLUSION The data suggest that amisulpride and SSRIs may be effective treatments for BMS ; they are equally effective and equally well tolerated in the short-term treatment of BMS . Amisulpride is associated with better compliance within the first week of treatment and with a shorter response latency in comparison with SSRIs . This finding may indicate that amisulpride is especially useful at the beginning of drug therapy of BMS . Double-blind , placebo-controlled trials are needed to further document the efficacy of amisulpride and SSRIs in the treatment of BMS OBJECTIVE The purpose of this study was to evaluate the efficacy of the topical use of benzydamine hydrochloride 0.15 % oral mouthwashes in the control of burning mouth syndrome symptoms . STUDY DESIGN In this double-blind , r and omized , longitudinal investigation , each of 30 patients with burning mouth syndrome was assigned to one of 3 management modalities . Those in group A received an oral rinse solution of benzydamine hydrochloride 0.15 % 3 times a day for 4 weeks , those in group B received a placebo 3 times a day for 4 weeks , and those in group C did not receive any kind of treatment . A visual analog scale was used for evaluation of the symptoms ; a Kruskal-Wallis analysis of variance exact test was performed on the result ing data . RESULTS The findings of this investigation failed to reveal significant differences among the groups . CONCLUSIONS The clinical application of benzydamine hydrochloride oral rinses in the treatment of patients with burning mouth syndrome did not demonstrate significative efficacy in comparison with use of a placebo solution AIMS An 8-week parallel , placebo-controlled , double-blind trial evaluated the efficacy of the antidepressant trazodone in the treatment of chronic burning mouth pain . METHODS Thirty-seven carefully selected women aged 39 to 71 ( mean 58.6 years ) were r and omized to receive either 200 mg of trazodone or a placebo in a similar manner . Pain and pain-related symptoms were evaluated on a visual analogue scale and other measures at 0 , 2 , 4 , and 8 weeks . RESULTS There were no significant differences between the groups in treatment effects for pain or pain-related symptoms . Seven patients in the trazodone group and 2 in the placebo group failed to complete the trial because of side effects . The most common side effects were dizziness and drowsiness . CONCLUSION In this controlled trial , trazodone failed to relieve burning mouth pain The effects of local application of estrone and progesterone on the oral mucosa was studied in sixty-one patients . These included forty-one postmenopausal women with various subjective oral complaints , ten postmenopausal women with no oral complaints , and ten normally menstruating women . Subjective complaints ( dryness , bad taste , burning sensation , and viscous saliva ) , quantity of saliva , and histologic changes in buccal mucosa were evaluated before and after treatment . Treatment comprised three modalities : an ointment containing estrone alone ; another ointment of estrone and progesterone ; and a third with a placebo base . These were massaged three times daily over the gingivae and oral mucosa for 30 days . A significant increase in secretion of saliva was observed with all three treatment modalities . Biopsies showed marked proliferative changes with all three types of ointment . A moderate improvement in subjective complaints followed all types of medication . These results indicate no specific effect of female sex hormones on the factors considered in this study . It appears that simple , repeated massage with any suitable ointment base is an effective method of inducing proliferative changes in atrophic buccal mucosa , increasing salivary secretion , and alleviating some of the subjective oral complaints of postmenopausal women & NA ; Stomatodynia is characterised by a spontaneous burning pain in the oral mucosa without known cause or recognised treatment . The purpose of this double‐blind , r and omised , multicentre parallel group study was to evaluate the efficacy of the topical use of clonazepam . Forty‐eight patients ( 4 men and 44 women , aged 65±2.1 years ) were included , of whom 41 completed the study . The patients were instructed to suck a tablet of 1 mg of either clonazepam or placebo and hold their saliva near the pain sites in the mouth without swallowing for 3 min and then to spit . This protocol was repeated three times a day for 14 days . The intensity was evaluated by a 11‐point numerical scale before the first administration and then after 14 days . Two weeks after the beginning of treatment , the decrease in pain scores was 2.4±0.6 and 0.6±0.4 in the clonazepam and placebo group , respectively ( P=0.014 ) . Similar effects were obtained in an intent‐to‐treat analysis ( P=0.027 ) . The blood concentration of clonazepam was similar whether it was measured 14 days after sucking a tablet three times a day or during the 5 h that followed sucking a single tablet ( n=5 ) . It is hypothesised that clonazepam acts locally to disrupt the mechanism(s ) underlying stomatodynia BACKGROUND Alpha-lipoic acid ( ALA ) is a potent antioxidant mitochondrial coenzyme , trometamol salt of thioctic acid , shown in clinical studies to be neuroprotective and in a preliminary study to have an effect on the symptomatology of Burning Mouth Syndrome ( BMS ) . METHODS We were interested in extending our studies as to whether alpha-lipoic acid might improve the symptomatology in BMS and therefore carried out a larger open controlled clinical study on the effects of alpha-lipoic acid on BMS symptomatology . RESULTS We have examined the effects on 4 groups of 20 patients with BMS of ALA , compared with bethanecol , Biotene and placebo , and found ALA of remarkable benefit with minimal adverse effects . CONCLUSIONS These results suggest that double-blind r and omized controlled multicenter studies of ALA are indicated The effect of cognitive therapy ( CT ) on resistant burning mouth syndrome ( BMS ) was studied . Thirty patients with resistant BMS after odontological and medical treatment were r and omly divided into two equal groups ; a therapy group ( TG ) was treated with CT and an attention/placebo group ( APG ) served as a control group . The intensity of BMS , which was estimated by the use of a visual analogue scale , was significantly reduced in the TG directly after CT was completed and was further reduced in a 6-month follow-up . The APG did not show any decrease in intensity of BMS . The results of this study indicate that , in some cases , resistant BMS probably is of psychological origin BACKGROUND Alpha-lipoic acid ( ALA ) , is a potent antioxidant mitochondrial coenzyme , the trometamol salt of thioctic acid that has been shown in clinical studies to be neuroprotective . This study examined the effect of ALA on the symptomatology of Burning mouth syndrome ( BMS ) . SUBJECTS AND METHODS Forty-two patients with BMS and no clinical or laboratory evidence of organic oral disease were divided into two groups ( Test and Control ) each of 21 subjects , matched for age and sex . The Test group were given ALA ( thioctic acid ; Tiobec ) for 30 days , as 600 mg per day orally for 20 days followed by 200 mg per day for 10 days . The Control group were given cellulose starch 100 mg per day as placebo for 30 days . All BMS patients were review ed at 10-day intervals and scored for changes in symptomatology . RESULTS Significant improvements were shown in the symptomatology of BMS in up to two-thirds of patients with BMS receiving alpha-lipoic acid , in about 15 % of those using placebo and also in up to two-thirds of those who , having tried placebo , were switched to ALA It has been suggested that placebo analgesia involves both higher order cognitive networks and endogenous opioid systems . The rostral anterior cingulate cortex ( rACC ) and the brainstem are implicated in opioid analgesia , suggesting a similar role for these structures in placebo analgesia . Using positron emission tomography , we confirmed that both opioid and placebo analgesia are associated with increased activity in the rACC . We also observed a covariation between the activity in the rACC and the brainstem during both opioid and placebo analgesia , but not during the pain-only condition . These findings indicate a related neural mechanism in placebo and opioid analgesia BACKGROUND Burning mouth syndrome ( BMS ) has features of a neuropathy and could be related to the production of the toxic free radicals that are released in stress situations . Alpha-lipoic acid is an antioxidant able to increase the levels of intracellular glutathione and eliminate free radicals . This study aim ed to examine the effectiveness of alpha-lipoic acid in the therapy of BMS . METHOD This was a double blind , controlled study conducted for two months on 60 patients with constant BMS . Comparing alpha-lipoic acid ( test ) with cellulose starch ( placebo ) , there was no laboratory evidence of deficiencies in iron , vitamins or thyroid function and no hyperglycaemia . RESULTS AND CONCLUSION Following treatment with alpha-lipoic acid , there was a significant symptomatic improvement , compared with placebo , with the majority showing at least some improvement after 2 months , thus supporting the hypothesis that burning mouth syndrome is a neuropathy . This improvement was maintained in over 70 % of patients at the 1 year follow-up |
885 | 21,396,877 | For calcific RC-tendinosis , strong evidence was found for effectiveness in favour of high-ESWT versus low-ESWT in short-term .
Moderate evidence was found in favour of high-ESWT versus placebo in short- , mid- and long-term and versus low-ESWT in mid- and long-term .
Moreover , high-ESWT was more effective ( moderate evidence ) with focus on calcific deposit versus focus on tuberculum major in short- and long-term .
RSWT was more effective ( moderate evidence ) than placebo in mid-term .
For non-calcific RC-tendinosis , no strong or moderate evidence was found in favour of low- , mid- or high-ESWT versus placebo , each other , or other treatments .
This review shows that only high-ESWT is effective for treating calcific RC-tendinosis .
No evidence was found for the effectiveness of ESWT to treat non-calcific RC-tendinosis | Extracorporeal shock-wave therapy ( ESWT ) is suggested as a treatment alternative for calcific and non-calcific rotator cuff tendinosis ( RC-tendinosis ) , which may decrease the need for surgery .
In this study we assessed the evidence for effectiveness of ESWT for these disorders . | We carried out a prospect i ve , r and omised controlled trial on two groups of 40 patients with painful calcific tendonitis and a mean age of 48.4 years ( 32.5 to 67.3 ) . All were to undergo arthroscopic removal of the calcific deposit within six months after r and omisation . The 40 patients in group I received ultrasound-guided needling followed by high-energy shock-wave therapy and the 40 in group II had shock-wave therapy alone . In both groups one treatment consisting of 2500 impulses of shock waves with an energy flux density of 0.36 mJ/mm(2 ) was applied . The clinical and radiological outcome was assessed using the 100-point Constant shoulder scoring system and st and ardised radiographs . The mean follow-up was 4.1 months and no patient was lost to follow-up . Both groups had significant improvement in their Constant shoulder score . Radiographs showed disappearance of the calcific deposit in 60.0 % of the shoulders in group I and in 32.5 % of group II ( p < 0.05 ) . Significantly better clinical and radiological results were obtained in group I than in group II . Arthroscopic removal of the deposit was avoided in 32 patients of group I and in 22 of group II . No severe side-effects were recorded . Ultrasound-guided needling in combination with high-energy shock-wave therapy is more effective than shock-wave therapy alone in patients with symptomatic calcific tendonitis , giving significantly higher rates of elimination of the calcium deposits , better clinical results and reduction in the need for surgery OBJECTIVES To evaluate the therapeutic effect of extracorporeal shock wave therapy ( ESWT ) in shoulders with chronic calcific tendinitis , to compare the functional outcomes of ESWT and transcutaneous electric nerve stimulation ( TENS ) therapy , and to investigate which types of calcium deposit effectively respond to ESWT . DESIGN R and omized controlled trial . SETTING Outpatient clinics of the departments of physical medicine and rehabilitation and of orthopedics and traumatology of a veterans hospital in Taiwan . PARTICIPANTS Sixty patients with continuous shoulder pain for 6 months or more and with radiographically and sonographically verified calcific tendinitis . Patients were r and omly allocated to receive ESWT ( 33 shoulders ) or TENS treatment ( 30 shoulders ) . INTERVENTIONS ESWT was performed with 2000 shock waves at 2Hz and energy level between.26 and .32mJ/mm(2 ) per session . Treatment was given in 2 sessions , 14 days apart . TENS therapy was given 3 times a week for 4 weeks . MAIN OUTCOME MEASURES Mean Constant score , visual analog scale ( VAS ) , manual muscle test , and changes of sonographic size and shape of calcium deposits were calculated for 4 time points : at baseline , 2 weeks , 4 weeks , 12 weeks posttherapy . RESULTS In both groups , Constant score and VAS improved significantly at 2- , 4- , and 12-week follow-ups ( P<.05 ) , and the size of calcium deposits decreased significantly at the 4- and 12-week follow-ups . Moreover , the arc-shaped calcific plaques of the rotator cuff were markedly meliorated with ESWT . CONCLUSIONS ESWT is more effective in the treatment of chronic calcific tendinitis of the shoulder than is TENS therapy , especially for arc-type calcific plaque In a prospect i ve r and omised trial of calcifying tendinitis of the rotator cuff , we compared the efficacy of dual treatment sessions delivering 2500 extracorporeal shock waves at either high- or low-energy , via an electromagnetic generator under fluoroscopic guidance . Patients were eligible for the study if they had more than a three-month history of calcifying tendinitis of the rotator cuff , with calcification measuring 10 mm or more in maximum dimension . The primary outcome measure was the change in the Constant and Murley Score . A total of 80 patients were enrolled ( 40 in each group ) , and were re-evaluated at a mean of 110 ( 41 to 255 ) days after treatment when the increase in Constant and Murley score was significantly greater ( t-test , p = 0.026 ) in the high-energy treatment group than in the low-energy group . The improvement from the baseline level was significant in the high-energy group , with a mean gain of 12.5 ( -20.7 to 47.5 ) points ( p < 0.0001 ) . The improvement was not significant in the low-energy group . Total or subtotal resorption of the calcification occurred in six patients ( 15 % ) in the high-energy group and in two patients ( 5 % ) in the low-energy group . High-energy shock-wave therapy significantly improves symptoms in refractory calcifying tendinitis of the shoulder after three months of follow-up , but the calcific deposit remains unchanged in size in the majority of patients Background Low-energy extracorporeal shock wave therapy is an alternative treatment , with limited evidence for effectiveness , for calcific tendinitis of the rotator cuff . Hypothesis Objective localization of the calcium deposit by 3-dimensional , computer-assisted navigation reveals superior clinical and radiographic outcomes compared to localization through patient-to-therapist feedback . Study Design R and omized controlled clinical trial ; Level of evidence , 1 . Methods A prospect i ve , r and omized , single-blind study was carried out on 50 patients . The population was divided into 2 groups of equal numbers ( navigation group and feedback group ) . In all patients , treatment-resistant pain was evident for longer than 6 months . A total of 3 therapy sessions of constant low-energy focused shock wave therapy was administered in weekly intervals in both groups . Local anesthesia was not applied . Radiographs and clinical assessment , including the Constant and Murley shoulder scoring system and the visual analog scale for pain , were performed both before therapy and after 12 weeks . In the navigation group , the calcium deposit was localized using a radiographically guided , 3-dimensional , computer-assisted device . The feedback group was treated after locating the point of maximum tenderness through palpation by the therapist with feedback from the patient . Results Both groups had significant improvements in the Constant and Murley score and the visual analog scale after 12 weeks . The results from the navigation group were statistically significantly superior to those of the feedback group . In the navigation group , 6 calcium deposits disappeared and 9 altered , compared to 1 disappearance and 12 alterations in the feedback group . No severe complications occurred . Conclusion Three-dimensional , computer-assisted navigation reveals significantly better results and is therefore recommended when extracorporeal shock wave therapy is used in the treatment of calcific tendinitis of the rotator cuff Objective : To compare the effectiveness of different energy densities of extracorporeal shock wave therapy ( ESWT ) for managing chronic heel pain . Design : A r and omized clinical trial . Setting : Hospital-based practice . Subjects : Fifty-seven patients with chronic heel pain were recruited ; eight patients withdrew from the study . Interventions : Subjects were r and omized into three groups receiving : ( 1 ) a ‘ fixed ’ energy density , ( 2 ) ‘ maximum tolerable ’ energy density , or ( 3 ) control treatment once a week for three weeks . Outcome measures : Pain on palpation , pain on tension , maximum tolerable walking/st and ing duration and Foot Function Index were assessed before treatment in each treatment session and at the three-week follow-up . Results : By week 3 , the ‘ maximum tolerable ’ energy density group experienced a 66 % cumulative reduction in pain from tension , a 65 % reduction on palpation and a 112 % cumulative increase in maximum tolerable walking/st and ing duration . The ‘ fixed ’ energy density group experienced a 45 % cumulative reduction in pain from tension , a 32 % reduction in pain on palpation , and a 45 % increase in walking/st and ing tolerance . The ‘ maximum tolerable ’ energy density group also showed a significantly greater reduction in Foot Function Index scores than the other two groups . Therapeutic effects were maintained at least up to the three-week follow-up period . The control group had no significant changes in any outcome measures across time periods . Conclusion : The delivery of ESWT with a maximum tolerable energy density is a more effective treatment protocol than a fixed energy density in terms of relieving pain and restoring the functional activity of people suffering from chronic heel pain . The analgesic effects were maintained at least up to the three-week follow-up We have performed a double-blind placebo-controlled trial of moderate doses of extracorporeal shock-wave therapy ( ESWT ) for non-calcific tendonitis of the rotator cuff . Adults ( 74 ) with chronic tendonitis of the rotator cuff were r and omised to receive either active ( 1500 pulses ESWT at 0.12 mJ/mm2 ) or sham treatment , monthly for three months . All were assessed before each treatment , and at one and three months after the completion of treatment . The outcome was measured with regard to pain in the shoulder , including a visual analogue score for night pain , and a disability index . There were no significant differences between the two groups before treatment . The mean duration of symptoms in both groups was 23.3 months . Both showed significant and sustained improvements from two months onwards . There was no significant difference between them with respect to change in the Shoulder Pain and Disability Index ( SPADI ) scores or night pain over the six-month period . A mean ( + /-SD ; range ) change in SPADI of 16.1 + /- 27.2 ( 0 to 82 ) in the treatment group and 24.3 + /- 24.8 ( -11 to 83 ) in the sham group was noted at three months . At six months the mean changes were 28.4 + /- 25.9 ( -24 to 69 ) and 30.4 + /- 31.2 ( -12 to 88 ) , respectively . Similar results were noted for night pain . We conclude that there is a significant and sustained placebo effect after moderate doses of ESWT in patients with non-calcific tendonitis of the rotator cuff , but there is no evidence of added benefit when compared with sham treatment UNLABELLED The aim of a prospect i ve study was to examine the effects of high energetic shock wave treatment on the course of calcareous tendinitis of the shoulder . 20 patients were entered into the study . Shock waves were applied to the calcifications with a Lithotripter MFL 5000 in two sessions of 2000 impulses each . The shock wave producing energy was 18 kV-22 kV. 6 and 12 weeks after treatment subjective and functional condition was checked by means of a 100-points functional score ; all patients underwent x-ray control and MRI imaging . RESULTS After 12 weeks 14 patients showed a marked improvement of symptoms , the average improvement on score measuring 25 points . The x-rays of 7 patients showed a complete resorption of the calcifications , in 5 cases partial disintegration of the calcium deposits was seen . The overall morbidity was low with 14 patients developing transient hematomas ; MRI imaging showed no severe damages of bone and soft tissue Arm , neck and /or shoulder complaints are common in western societies . In the Netherl and s , general practice guidelines are issued on shoulder pain and epicondylitis only . Little is known about actual management of the total range of diagnoses . The objectives of the study are : to determine management in patients consulting the GP with a new episode of non-traumatic arm neck and shoulder complaints up to 6 months after the first consultation . To evaluate differences in management between patients with specific diagnoses versus non-specific diagnoses and between specific diagnostic groups . In a prospect i ve cohort study in general practice . We recruited 682 eligible patients . Data on diagnosis , management , patient- and complaint-characteristics were collected . Co-occurrence of treatment options was presented in scaled rectangles . After 6 months , additional diagnostic tests had been performed in 18 % of the patients , mainly radiographic examination ( 14 % ) . Further , 49 % had been referred for physiotherapy and 12 % to the medical specialist . Patients with specific diagnoses were more frequently referred for specialist treatment , and patients with non-specific diagnoses for physiotherapy . Corticosteroid injections ( 17 % ) were mainly applied specific diagnoses ( e.g. impingement syndrome , frozen shoulder , carpal tunnel and M. Quervain ) . Frequencies of prescribed medication ( 51 % ) did not differ between specific and non-specific diagnoses . In 19 % of the patients no referral , prescribed analgesics or injection was applied . Braces ( 4 % ) were mainly prescribed in epicondylitis . Overall , management most frequently consisted of prescribed analgesics and referral for physiotherapy . Specific and non-specific diagnostic subgroups differed in the frequency corticosteroid injections were applied , and referrals to physiotherapy and to a medical specialist We report a prospect i ve study of the effects of extracorporeal shock-wave therapy in 195 patients with chronic calcifying tendinitis . In part A 80 patients with chronic symptoms were r and omly assigned to a control and three subgroups which had different treatment by low-energy and high-energy shock waves . In part B 115 patients had either one or two high-energy sessions . We recorded subjective , functional and radiological findings at six months after treatment . The results showed energy-dependent success , with relief of pain ranging from 5 % in our control group up to 58 % after two high-energy sessions . The Constant scores and the radiological disintegration of calcification were also dose-dependent . Shockwave therapy should be considered for chronic pain due to calcific tendinitis which is resistant to conservative treatment A prospect i ve , controlled , r and omised trial was performed to compare the effect of high-energy extracorporeal shock wave therapy ( ESWT ) versus low-energy ESWT in treatment of rotator cuff tendinopathy . Forty adult patients were included in the study . Patients in the intervention group received 6000 impulses of high-energy ( ED+ 0.78 mJ/mm2 ) in 3 sessions under local anaesthesia . Patients in the control group received 6000 impulses of a low-energy ESWT ( ED+ 0.33 mJ/mm2 ) under local anaesthesia . Follow-up examinations were performed 12 weeks and one year after treatment by an independent observer . An increase in function and a reduction of pain were found in both groups ( p < 0.001 ) . Although the improvement in Constant score was greater in the high-energy group compared to the low-energy group , statistical analyses showed no significant difference between the groups with respect to all parameters studied ( Constant score/pain/subjective improvement ) after 12 weeks and one year follow-up . No statistically significant differences were found between the results of high-energy and low-energy ESWT of rotator cuff tendinopathy We prospect ively studied extracorporeal shock wave therapy ( ESWT ) for calcific tendinitis of the shoulder in 46 consecutive patients . All patients were r and omly divided into 2 groups : treatment and control . The 33 patients in the treatment group received 2 courses of ESWT at the energy density of 0.55 mJ/mm(2 ) ( 1000 impulses ) . The control group underwent sham treatment with a dummy electrode ( 13 patients ) . Evaluation included the Constant score , pain scale , and radiographs . The ESWT results were good to excellent in 87.9 % of shoulders ( 29/33 ) and fair in 12.1 % ( 4/33 ) , and the control results were fair in 69.2 % ( 9/13 ) and poor in 30.1 % ( 4/13 ) . Among ESWT patients , calcium deposits were completely eliminated in 7 cases ( 21.2 % ) , partially eliminated in 11 ( 36.3 % ) , and unchanged in 15 ( 45.4 % ) . In contrast , elimination was partial in 2 control patients ( 15.3 % ) and unchanged in 11 ( 84.7 % ) . There was no significant difference between Gärtner type I and type II groups in the Constant score ( P > .05 ) . ESWT shows promise for pain relief and functional restoration of calcific tendinitis with negligible complications CONTEXT Extracorporeal shock wave therapy ( ESWT ) has been used to treat calcific tendonitis of the shoulder , but trials of ESWT for this purpose have had method ological deficiencies and thus there is limited evidence for its effectiveness . OBJECTIVE To determine whether fluoroscopy-guided ESWT improves function , reduces pain , and diminishes the size of calcific deposits in patients with chronic calcific tendonitis of the shoulder . DESIGN , SETTING , AND PARTICIPANTS Double-blind , r and omized , placebo-controlled trial conducted between February 1997 and March 2001 among 144 patients ( of 164 screened ) recruited from referring primary care physicians , orthopedic surgeons , and sports physicians in 7 orthopedic departments in Germany and Austria . INTERVENTIONS Either high-energy ESWT , low-energy ESWT , or placebo ( sham treatment ) . The 2 ESWT groups received the same cumulative energy dose . Patients in all 3 groups received 2 treatment sessions approximately 2 weeks apart , followed by physical therapy . MAIN OUTCOME MEASURES The primary end point was the change in the mean Constant and Murley Scale ( CMS ) score from baseline to 6 months after the intervention . Secondary end points were changes in the mean CMS scores at 3 and 12 months , as well as changes in self-rated pain and radiographic change in size of calcific deposits at 3 , 6 , and 12 months . RESULTS Of 144 patients enrolled , all completed treatment as r and omized and 134 completed the 6-month follow-up . Both high-energy and low-energy ESWT result ed in significant improvement in the 6-month mean ( 95 % confidence interval [ CI ] ) CMS score compared with sham treatment ( high-energy ESWT : 31.0 [ 26.7 - 35.3 ] points ; low-energy ESWT : 15.0 [ 10.2 - 19.8 ] points ; sham treatment : 6.6 [ 1.4 - 11.8 ] points ; P<.001 for both comparisons ) . Patients who received high-energy ESWT also had significant 6-month CMS improvements compared with those who received low-energy ESWT ( P<.001 ) . We found similar results for both the 3-month and 12-month CMS comparisons , as well as for self-rated pain and radiographic changes at 3 , 6 , and 12 months . CONCLUSIONS Both high-energy and low-energy ESWT appeared to provide a beneficial effect on shoulder function , as well as on self-rated pain and diminished size of calcifications , compared with placebo . Furthermore , high-energy ESWT appeared to be superior to low-energy ESWT BACKGROUND AND PURPOSE Radial shock-wave therapy ( RSWT ) is a pneumatically generated , low- to medium-energy type of shock-wave therapy . This single-blind , r and omized , " less active similar therapy"-controlled study was performed to evaluate the effectiveness of RSWT for the management of calcific tendinitis of the shoulder . SUBJECTS Ninety patients with radiographically verified calcific tendinitis of the shoulder were tested . METHODS Subjects were r and omly assigned to either a treatment group ( n=45 ) or a control group ( n=45 ) . Pain and functional level were evaluated before and after treatment and at a 6-month follow-up . Radiographic modifications in calcifications were evaluated before and after treatment . RESULTS The treatment group displayed improvement in all of the parameters analyzed after treatment and at the 6-month follow-up . Calcifications disappeared completely in 86.6 % of the subjects in the treatment group and partially in 13.4 % of subjects ; only 8.8 % of the subjects in the control group displayed partially reduced calcifications , and none displayed a total disappearance . DISCUSSION AND CONCLUSION The results suggest that the use of RSWT for the management of calcific tendinitis of the shoulder is safe and effective , leading to a significant reduction in pain and improvement of shoulder function after 4 weeks , without adverse effects The effects of various extracorporal shock wave energy levels and impulse rates were investigated using an in vitro model . In addition , we performed a controlled , r and omized study to examine the clinical outcome after treatment for calcific tendinitis of the shoulder . Two groups of 40 patients each received 2000 impulses twice with an energy flux density of 0.23 mJ/mm2 and then 0.42 mJ/mm2 . The results were evaluated by the Constant and Murley score . Disintegration of the implanted deposits requires an energy of at least 0.42 mJ/mm2 and 2000 impulses . The clinical trial showed resorption of calcific deposits in 37.5 % ( 0.23 mJ/mm2 ) and 55.0 % ( 0.42 mJ/mm2 ) . After 1 year the Constant and Murley score increased from 46 to 68 at 0.23 mJ/mm2 and from 48 to 73 points at 0.42 mJ/mm2 . Based on our experimental and clinical results it is evident that disintegration of calcific deposits is dose-dependent . Because of the time that elapses until changes became evident on the radiographs , an instant and sole mechanical effect on the calcific deposits is unlikely . Therefore , a combined mechanical and cellular mechanism for absorption of the calcific deposits must be presumed We have performed a controlled , r and omised study to analyse the effects of low-energy shock-wave therapy ( ESWT ) on function and pain in tendinitis of the supraspinatus without calcification . There were 20 patients in the treatment group and 20 in the control group . The former group received 6,000 impulses ( energy flux density , 0.11 mJ/mm2 ) in three sessions after local anaesthesia . The control group had 6000 impulses of sham ESWT after local anaesthesia . The patients were examined at six and 12 weeks after treatment by an independent observer who evaluated the Constant score and level of pain . We found an increase in function and a reduction of pain in both groups ( p < or = 0.001 ) . Statistical analysis showed no difference between the groups for the Constant score and for pain . We therefore do not recommend ESWT for the treatment of tendinitis of supraspinatus A controlled prospect i ve r and omized study was design ed to analyze the effect of extracorporeal shock wave therapy on calcifying tendinopathy of the shoulder focused on the calcified area or the origin of the supraspinatus tendon . Fifty patients were included in the study and were treated with a Storz Minilith Sl-1 shock wave generator . The first group of patients received 4000 impulses ( positive energy flux density , 0.78 mJ/mm2 ) in two treatment sessions after receiving local anesthesia at the origin of the supraspinatus tendon . Patients in the second group received extracorporeal shock wave therapy at the calcified area . Followups were done 12 weeks and 1 year after treatment by an independent observer . An increase of function and a reduction of pain occurred in both groups . Statistical analyses showed a significant superiority of extracorporeal shock wave application at the calcified area in the primary end point ( Constant and Murley score ) . Therefore , exact fluoroscopic focusing of extracorporeal shock wave therapy at the calcific deposit for treatment of calcifying tendinopathy of the supraspinatus muscle is recommended . Based on these results , extracorporeal shock wave application should be focused fluoroscopically with appropriate shock wave generators BACKGROUND AND AIM Supraspinatus tendinitis is usually treated by antiinflammatoric drugs , local injections , physiotherapy or low-dose irradiation . A novel approach is the use of Extracorporeal Shock Wave Therapy ( ESWT ) if conservative therapies have failed . So far there has been no controlled study comparing the effectiveness of ESWT with an established conservative method of therapy such as X-ray stimulation radiotherapy . PATIENTS AND METHOD 30 patients with chronic supraspinatus tendinitis were admitted into the prospect i ve r and omized study . After r and omization the patients were treated either with X-ray stimulation radiotherapy with 6 x 0.5 Gy on the ICRU reference point ( 1 fraction/day ) with cobalt 60 gamma rays or three times with 2000 pulses ( energy flux density ED+ 0.1 mJ/mm2 ) in 1 week intervals using a Storz Minilith SL1 . Primary endpoint was the age-corrected constant score 3 months after intervention . RESULTS Acute side effects caused by the irradiation were not observed , as expected . One patient described pain and one patient showed a moderate skin irritation after ESWT . In the radiotherapy group average the age-corrected constant score improved from 47.6 through 79.5 points to 87.4 points . In the ESWT group it rose from 50.1 points before ESWT to 91.4 points after 12 weeks and 97.8 after 52 weeks . CONCLUSION No statistically significant differences were proven between ESWT and radiotherapy . ESWT appears to be equivalent but not superior to radiotherapy in treating chronic supraspinatus tendinitis syndrome . A comprehensive r and omized study is , however , necessary to ensure the equivalence of ESWT |
886 | 28,541,262 | Conclusions : The primary goal of clinical investigation is to identify the cause of upper gastrointestinal symptoms rather than H pylori infection . | Background : Because of the changing epidemiology of Helicobacter pylori infection and low efficacy of currently recommended therapies , an up date of the European Society for Paediatric Gastroenterology Hepatology and Nutrition/North American Society for Pediatric Gastroenterology , Hepatology and Nutrition recommendations for the diagnosis and management of H pylori infection in children and adolescents is required . | Background / Objectives : Helicobacter pylori infection and iron and vitamin B12 deficiencies are widespread in economically disadvantaged population s. There is emerging evidence that H. pylori infection has a negative effect on the absorption of these micronutrients . The aim of this study was to evaluate the effect of H. pylori infection on the efficacy of micronutrient ( including iron and vitamin B12)-fortified foods supplied for 1 year in marginally nourished children . Subjects/ Methods : In all , 543 Indian children , aged 6–10 years , participated in a double-blind , r and omized controlled intervention trial , receiving foods fortified with either high ( 100 % Recommended Dietary Allowances ( RDA ) ) or low ( 15 % RDA ) amounts of iron , vitamin B12 and other micronutrients . The presence of H. pylori infection was diagnosed by the 13C-labeled urea breath test at 11 months after the start of the intervention . Blood hemoglobin , serum ferritin ( SF ) , total body iron and plasma vitamin B12 were estimated at baseline and 12 months , and differences between these time points were assessed using an independent t-test . Results : Overall , the prevalence of H. pylori infection in this group of children was 79 % . Baseline hemoglobin , SF , body iron and vitamin B12 concentrations were not associated with H. pylori infection . The response to the intervention ( either high or low amounts of iron and vitamin B12 fortification ) in terms of change in iron markers and vitamin B12 status did not differ between children with and without H. pylori infection . Conclusions : This study shows that the presence of H. pylori infection did not affect the efficacy of long-term iron and vitamin B12 fortification in these marginally nourished children Purpose The aim of this study was to assess and compare the efficacies of proton pump inhibitor-based triple therapy and bismuth-based quadruple therapy as first-line treatments for Helicobacter pylori eradication in Korean children . Methods We retrospectively review ed the data of children who had been diagnosed with H. pylori infection at the Seoul National University Bundang Hospital from March 2004 to August 2012 . The patients were r and omly assigned to receive either triple therapy consisting of omeprazole , amoxicillin , and clarithromycin for 2 weeks ( OAC group ) or quadruple therapy comprising omeprazole , amoxicillin , metronidazole , and bismuth salts for 1 week ( OAMB group ) . The patients were evaluated for eradication of H. pylori infection at 4 weeks after the completion of the treatment . Results Of the 129 children enrolled in this study , 118 ( 91.5 % ) were included in the final analysis . The eradication rates in OAC and OAMB groups were 67.7 % ( 42/62 ) and 83.9 % ( 47/56 ) , respectively , which were significantly different between the 2 treatment groups ( p=0.041 ) . The eradication rates in the OAMB group during the periods 2004 - 2006 , 2007 - 2009 , and 2010 - 2012 were superior to those in the OAC group . Conclusion This study indicated that the 1-week bismuth-based quadruple therapy , compared with the st and ard 2-week triple therapy , was significantly more successful in eradicating H. pylori infection in Korean children AIM To assess whether antibiotic resistance varies between the antrum and corpus of the stomach of patients that are either Helicobacter pylori ( H. pylori ) therapy-naive or pre-treated . METHODS H. pylori strains were isolated from antrum and corpus biopsies from 66 patients that received a diagnostic gastroduodenoscopy for variant clinical indications . Antimicrobial susceptibility to amoxicillin , clarithromycin , tetracycline , metronidazole , levofloxacin and rifabutin was tested with the E-test method on Iso-Sensitest agar with 10 vol% defibrinated horse blood . In patients with a different antibiotic susceptibility pattern between the isolates from the antrum and corpus , DNA fingerprinting via r and om amplified polymorphic DNA analysis was performed to detect differences among DNA patterns of H. pylori isolates . RESULTS Primary , secondary and tertiary resistance to clarithromycin was 6.9 % , 53.8 % and 83.3 % , retrospectively . Metronidazole and levofloxacin resistance also increased according to the number of previous treatments ( 17.2 % , 69.2 % , 83.3 % ; 13.8 % , 23.1 % , 33.3 % ) . Tertiary resistance to rifabutin was detected in 12.5 % of patients . In none of the 66 patients a resistance against amoxicillin or tetracycline was detectable . Discordant antibiotic susceptibility between antrum and corpus isolates for different antibiotics was seen in 15.2 % ( 10/66 ) of the patients . Two out of those ten patients were naive to any H. pylori antibiotic treatment . The remaining eight patients previously received at least one eradication therapy . DNA fingerprinting analysis revealed no substantial differences among DNA patterns between antrum and corpus isolates in the majority of patients suggesting an infection with a single H. pylori strain . CONCLUSION Different antibiotic susceptibility between antrum and corpus biopsies is a common phenomenon and a possible explanation for treatment failure . Resistant H. pylori strains may be missed if just one biopsy from one anatomic site of the stomach is taken for H. pylori susceptibility testing In the present study , we investigated the prevalence of anaemia and Fe deficiency anaemia ( IDA ) and explored the relationship between Helicobacter pylori infection and IDA in adolescent girls . A total of 1037 adolescent girls from Suihua , China were enrolled . Hb , serum ferritin ( SF ) , serum transferrin receptor ( sTfR ) and serum IgG antibodies to H. pylori were measured . Participants with IDA and co-existing H. pylori infection ( n 80 ) who had an intake of > 25 mg/d of Fe were assigned r and omly to the intervention and control groups . Patients in the intervention group were administered a 12-week course of oral EDTA-Na-Fe ( 60 mg Fe/dose , three times a week ) and a 2-week course of colloidal bismuth subcitrate , amoxicillin and metronidazole . Subjects in the control group were administered EDTA-Na-Fe alone . Hb , SF and sTfR were reassessed 3 months after the 12-week regimen ended . Prevalence of anaemia , Fe deficiency ( defined as SF < 12·0 μg/l ) , IDA and H. pylori infection in the population of 1037 was 19.5 , 40.4 , 17.1 and 31.2 % , respectively . The prevalence of H. pylori infection in the IDA group was 46.9 % , while the non-anaemic group had 28.1 % prevalence . A significant increase in Hb and SF and a decrease in sTfR value were found in the intervention group and the H. pylori-negative group . Findings suggest that IDA is still one of the prominent problems in adolescent girls . There is an association between H. pylori infection and IDA . Treatment of H. pylori infection is associated with a more rapid response to oral Fe therapy IMPORTANCE The long-term effectiveness of Helicobacter pylori eradication programs for preventing gastric cancer will depend on recurrence risk and individual and community factors . OBJECTIVE To estimate risk of H. pylori recurrence and assess factors associated with successful eradication 1 year after treatment . DESIGN , SETTING , AND PARTICIPANTS Cohort analysis of 1463 r and omized trial participants aged 21 to 65 years from 7 Latin American communities , who were treated for H. pylori and observed between September 2009 and July 2011 . INTERVENTIONS R and omization to 1 of 3 treatment groups : 14-day lansoprazole , amoxicillin , and clarithromycin ( triple therapy ) ; 5-day lansoprazole and amoxicillin followed by 5-day lansoprazole , clarithromycin , and metronidazole ( sequential ) ; or 5-day lansoprazole , amoxicillin , clarithromycin , and metronidazole ( concomitant ) . Participants with a positive (13)C-urea breath test ( UBT ) 6 to 8 weeks posttreatment were offered voluntary re-treatment with 14-day bismuth-based quadruple therapy . MEASUREMENTS Recurrent infection after a negative posttreatment UBT and factors associated with successful eradication at 1-year follow-up . RESULTS Among participants with UBT-negative results who had a 1-year follow-up UBT ( n=1091 ) , 125 tested UBT positive , a recurrence risk of 11.5 % ( 95 % CI , 9.6%-13.5 % ) . Recurrence was significantly associated with study site ( P = .03 ) , nonadherence to initial therapy ( adjusted odds ratio [ AOR ] , 2.94 ; 95 % CI , 1.31 - 6.13 ; P = .01 ) , and children in the household ( AOR , 1.17 ; 95 % CI , 1.01 - 1.35 per child ; P = .03 ) . Of the 281 with positive posttreatment UBT results , 138 completed re-treatment , of whom 93 tested UBT negative at 1 year . Among the 1340 who had a 1-year UBT , 80.4 % ( 95 % CI , 76.4%-83.9 % ) , 79.8 % ( 95 % CI , 75.8%-83.5 % ) , and 77.8 % ( 95 % CI , 73.6%-81.6 % ) had UBT-negative results in the triple , sequential , and concomitant groups , respectively ( P = .61 ) , with 79.3 % overall effectiveness ( 95 % CI , 77.1%-81.5 % ) . In a single-treatment course analysis that ignored the effects of re-treatment , the percentage of UBT-negative results at 1 year was 72.4 % ( 95 % CI , 69.9%-74.8 % ) and was significantly associated with study site ( P < .001 ) , adherence to initial therapy ( AOR , 0.26 ; 95 % CI , 0.15 - 0.42 ; P < .001 ) , male sex ( AOR , 1.63 ; 95 % CI , 1.25 - 2.13 ; P < .001 ) , and age ( AOR , 1.14 ; 95 % CI , 1.02 - 1.27 per decade ; P = .02 ) . One-year effectiveness among all 1463 enrolled participants , considering all missing UBT results as positive , was 72.7 % ( 95 % CI , 70.3%-74.9 % ) . CONCLUSIONS AND RELEVANCE One year after treatment for H. pylori infection , recurrence occurred in 11.5 % of participants who had negative posttreatment UBT results . Recurrence determinants ( ie , nonadherence and demographics ) may be as important as specific antibiotic regimen in determining the long-term success of H. pylori eradication interventions . Study findings are relevant to the feasibility of programs for the primary prevention of gastric cancer in high-incidence regions of Latin America . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01061437 OBJECTIVES The aim of this study was to prospect ively assess the pattern of evolution of primary resistance to antibiotics in Helicobacter pylori strains isolated from Portuguese children over a 10 year period ( 2000 - 09 ) . METHODS A total of 1115 H. pylori strains were tested for antibiotic susceptibility to clarithromycin , metronidazole , amoxicillin , ciprofloxacin and tetracycline . RESULTS H. pylori strains were isolated from children and adolescents [ ages 4 months-18 years ( mean age 10.17 ± 4.03 years ) ] , comprising 562 ( 50.4 % ) boys and 553 ( 49.6 % ) girls . Overall , the primary resistance rate was 34.7 % to clarithromycin , 13.9 % to metronidazole and 4.6 % to ciprofloxacin , while 6.9 % were resistant to two of these antibiotics simultaneously . Resistance to amoxicillin and to tetracycline was not detected . In general , the resistance rate was not associated with gender or the children 's age . European ethnicity , when compared with an African background , was associated with clarithromycin resistance [ P = 0.002 ; odds ratio ( OR ) = 0.30 ; 95 % confidence interval ( CI ) 0.14 - 0.66 ] , while the inverse situation was observed for metronidazole ( P < 0.001 ; OR = 3.50 ; 95 % CI 1.90 - 6.45 ) . No significant temporal trend was noticed for resistance to clarithromycin and metronidazole , whereas ciprofloxacin and double-resistance rates have significantly increased over time ( P = 0.004 and P = 0.05 , respectively ) . CONCLUSIONS The primary resistance rate of H. pylori strains isolated from Portuguese children to the commonly used anti-H. pylori antibiotics used is high . Additionally , the increasing trend of ciprofloxacin-resistant and double-resistant strains may compromise H. pylori eradication in a high-prevalence population Empiric triple therapy for Helicobacter pylori should be ab and oned when clarithromycin resistance rate is > 15–20 % . Optimisation of triple therapy ( high‐dose acid suppression and 14‐day duration ) can increase eradication rates by 10 % BACKGROUND The eradication of Helicobacter pylori has been associated with remission of immune thrombocytopenia ( ITP ) in approximately half of eradicated patients . Data on children are limited to small case series . PROCEDURE Children from 16 centers in Italy , who were less than 18 years of age and diagnosed with chronic ITP ( cITP ) , were screened for H. pylori infection . Positive patients underwent st and ard triple therapy with amoxicillin , clarithromycin , and omeprazole . The eradication response was defined as follows : complete response , platelet ( PLT ) count ≥ 150 × 10(9 ) /L ; partial response , PLT count of at least 50 × 10(9 ) /L ; no response , PLT count < 50 × 10(9 ) /L. RESULTS Of 244 screened patients , 50 ( 20 % ) had H. pylori infection , 37 of which received eradication therapy and completed follow-up . Eradication was successful in 33/37 patients ( 89 % ) . PLT recovery was demonstrated in 13/33 patients after eradication ( 39 % ) , whereas spontaneous remission was observed in 17/166 ( 10 % ) H. pylori-negative patients ( P < 0.005 ) . Responders more often required second line eradication ( 9/13 ) , whereas a second cycle was required in 3/20 non-responders ( P < 0.005 ) . CONCLUSIONS Among the large cohort of patients , those who underwent successful H. pylori eradication showed a significantly higher PLT response . Therefore , it may be appropriate to look for H. pylori and eventually eradicate it in children with cITP BACKGROUND & AIMS Chronic abdominal pain is the most common indication for esophagogastroduodenoscopy ( EGD ) in children . However , little is known about the accuracy of EGD-based diagnosis or the outcomes of the patients who undergo this procedure . We examined the diagnostic yield of EGD and short-term outcomes of children who underwent this procedure for chronic abdominal pain . METHODS We conducted a prospect i ve study of 290 children ( 4 - 18 years old ; mean age , 11.9 ± 3.5 years ; 93 girls ) who underwent EGD for the primary indication of chronic abdominal pain ( 216 with at least 1 alarm feature ) at a US pediatric gastroenterology referral center . We collected data on demographic features ( age , sex ) , clinical characteristics ( alarm features , Rome III criteria ) , and EGD results for each patient . All subjects with diagnostic lesions were followed for at least 1 year after EGD to determine short-term outcomes . RESULTS Overall , EGD provided an accurate diagnosis for 109 children ( 38 % ) . Diagnoses included esophagitis ( 21.0 % ) , eosinophilic gastroenteritis ( 4.1 % ) , eosinophilic esophagitis ( 3.8 % ) , Helicobacter pylori infection ( 2.0 % ) , celiac disease ( 0.6 % ) , and Crohn 's disease ( 0.4 % ) . Short-term outcomes were available for 81 % of patients with diagnostic findings , and medical therapy was effective in approximately 67 % of these children . CONCLUSIONS EGD is valuable for the diagnosis of children with abdominal pain , with a 38 % diagnostic yield . EGD identified disorders for which medical therapy was effective in 67 % of children during the year after diagnosis Background : To analyze risk factors associated with gastro-duodenal ulcers and erosions in children . Methods : Open , prospect i ve , multicenter , case-control study carried out in 11 European countries in patients with gastric or duodenal ulcers/erosions and 2 age-matched controls each . Possible risk factors were recorded . Logistic regression models were performed with adjustment for centers and age groups . Results : Seven-hundred thirty-two patients ( 244 cases , 153 with erosions only and 91 with ulcers , and 488 controls ) were recruited . Children receiving antimicrobials or acid suppressive drugs before endoscopy were excluded ( 202 cases/390 controls remained for risk factor analysis ) . Helicobacter pylori was detected more frequently in cases than controls but only in 32.0 % versus 20.1 % in controls ( P = 0.001 ) . Independent exposure factors for gastric ulcers were male gender ( P = 0.001 ) , chronic neurologic disease ( P = 0.015 ) , chronic renal disease ( P < 0.001 ) and nonsteroidal anti-inflammatory drug consumption ( P = 0.035 ) . Exposure factors for duodenal ulcers were H. pylori infection ( P < 0.001 ) and steroid consumption ( P = 0.031 ) . Chronic renal disease was the only independent factor associated with gastric erosions ( P = 0.026 ) , those associated with duodenal erosions being H. pylori infection ( P = 0.023 ) , active smoking ( P = 0.006 ) and chronic arthritis ( P = 0.008 ) . No risk factor was identified in 97/202 ( 48.0 % ) cases . Conclusions : H. pylori remains a risk factor for duodenal , but not for gastric lesions in children in countries with low prevalence of infection . No risk factor could be identified in half of the children with gastro-duodenal ulcers/erosions BACKGROUND & AIMS Helicobacter pylori infection in children infrequently causes gastroduodenal mucosal ulceration . Because H pylori induces T-cell dependent gastric inflammation in adults and T regulatory ( Treg ) cells suppress T-cell-dependent pathology , we evaluated gastric histopathology and Treg cell responses in H pylori-infected children and adults . METHODS Gastric tissue from 36 children and 79 adults with abdominal symptoms in Santiago , Chile , was evaluated prospect ively for H pylori bacteria and histopathology using the Sydney classification and Treg responses using immunoassay , immunohistochemistry , and real-time polymerase chain reaction . RESULTS Eighteen ( 50 % ) of the children and 51 ( 65 % ) of the adults were infected with H pylori . Children and adults were colonized with similar levels of H pylori . However , the level of gastritis in the children was reduced substantially compared with that of the adults ( P < .05 ) . Coincident with reduced gastric inflammation , the number of Treg cells and levels of Treg cytokines ( transforming growth factor [TGF]-beta1 and interleukin-10 ) were increased markedly in the gastric mucosa of H pylori-infected children compared with that of infected adults ( P < .03 and < .05 , respectively ) . Also , H pylori infection in the children was associated with markedly increased levels of gastric TGF-beta1 and interleukin-10 messenger RNA . Importantly , gastric TGF-beta1 in H pylori-infected children localized predominantly to mucosal CD25(+ ) and Foxp3(+ ) cells , indicating a Treg source for the TGF-beta1 . CONCLUSIONS Gastric pathology is reduced and local Treg cell responses are increased in H pylori-infected children compared with infected adults , suggesting that gastric Treg cell responses down-regulate the inflammation and ulceration induced by H pylori in children Abstract Objectives . To determine the antibiotic susceptibility of Helicobacter pylori isolates from Israeli children ; assess the role of previous antibiotic use in the development of antibiotic resistance and examine the possibility of simultaneous colonization of strains with different resistance patterns in the same patients . Material and methods . A prospect i ve case-series design was used . The study group included 174 patients aged 1–18 years referred to the Schneider Children 's Medical Center of Israel for gastroscopy over a 2.5-year period . Antibiotic susceptibility to amoxicillin , clarithromycin , metronidazole , tetracycline , and levofloxacin was determined by E-test on gastric biopsies ( 2 per patient ) . Clinical and demographic data were obtained by question naire . Results . Cultures for H. pylori yielded 55 isolates from 53 children . In treatment-naïve children , the prevalence rate of primary resistance to clarithromycin was 25 % and to metronidazole , 19 % . Respective rates in children previously treated for H. pylori infection were 42 % ( p = 0.22 ) and 52 % ( p = 0.016 ) . Simultaneous resistance to both drugs was found in 13 % of isolates ( n = 7 ) , all from children with previous treatment failure . No resistance was found to amoxicillin , tetracycline or levofloxacin . Clarithromycin resistance was associated with macrolide use for any indication during the previous year ( p = 0.033 ) . In 2 patients ( 3.8 % ) , a different H. pylori strain was cultured from each biopsy . Conclusions . H. pylori resistance to clarithromycin and metronidazole is high in Israeli children , particularly in those previously treated for H. pylori infection , in whom culture-based treatment should be considered . The simultaneous colonization of multiple strains in a minority of patients needs to be further characterized Helicobacter pylori infection occurs in children and adults worldwide . St and ard triple therapy of omeprazole , amoxicillin and clarithromycin ( OAC ) may not be optimal UNLABELLED The goal of first-line Helicobacter pylori therapy is to reach an eradication rate of 90 % to avoid further investigations , antibiotic use , and spreading of resistant strains . AIM To evaluate the eradication rate of high-dose sequential therapy in treatment-naïve children and to assess factors associated with failure . METHODS Prospect i ve data assessed in a registry from nine European centers between October 2009 and December 2011 . Children with biopsy-proven Helicobacter pylori infection were prescribed 5 days of esomeprazole and amoxicillin , followed by 5 days of esomeprazole , clarithromycin , and metronidazole according to bodyweight . Eradication was assessed after 8 - 12 weeks . Primary endpoint was the eradication rate in children who received at least one dose and had follow-up data . Multivariate analysis evaluated potential factors for treatment success including sex , age , center , migrant status , antibiotic resistance , and adherence to therapy . RESULTS Follow-up was available in 209 of 232 patients ( age range 3.1 - 17.9 years , 118 females ) . Primary resistance occurred for clarithromycin in 30 of 209 ( 14.4 % ) , for metronidazole in 32 ( 15.3 % ) , for both antibiotics in 7 ( 3.3 % ) , and culture failed in 6 ( 2.9 % ) . Eradication was achieved in 168 of 209 children ( 80.4 % , 95 % CI 75.02 - 85.78 ) , in 85.8 % with no resistance , 72.6 % with single resistance , and 28.6 % with double resistance . Independent factors affecting eradication rate included resistance to clarithromycin ( adjusted ORs 0.27 ( 0.09 - 0.84 ) , p = .024 ) , to metronidazole ( 0.25 ( 0.009 - 0.72 ) , p = .010 ) or to both ( 0.04 ( 0.01 - 0.35 ) , p = .004 ) , and intake of ≤ 90 % of prescribed drugs ( 0.03 ( 0.01 - 0.18 ) , p < .001 ) . CONCLUSION A high-dose 10-day sequential therapy can not be recommended in treatment-naïve children Aims : The aim of the study was to compare sequential versus tailored triple therapy regimens on Helicobacter pylori ( H pylori ) eradication rates in children and to assess the effect of antimicrobial susceptibility . Patients and Methods : Prospect i ve , open-label , multicenter study . Children received r and omly either a 10-day sequential treatment comprising omeprazole ( OME ) with amoxicillin for 5 days and OME , clarithromycin ( CLA ) , and metronidazole ( MET ) for the remaining 5 days , or a 7-day triple therapy comprising OME with amoxicillin and CLA in cases of a CLA-susceptible strain or MET in cases of CLA-resistant strain . H pylori eradication was assessed by 13C-urea breath test . Results : One hundred sixty-five children , 95 girls and 70 boys , of median age 10.4 years , were included . The intention-to-treat ( ITT ) eradication rate was 76.9 % ( sequential 68/83 = 81.9 % , triple therapy 59/82 = 71.9 % , ns ) , and the per- protocol ( PP ) eradication rate was 84.6 % ( sequential 68/77 = 88.3 % , triple therapy 59/73 = 81.8 % , ns ) . Eradication rates tended to be higher using the sequential treatment , but the difference was only statistically significant for ITT analysis in children harboring both CLA- and MET-susceptible strains ( 87.8 % vs 68.5 % , odds ratio [ OR ] 3.3 , P = 0.03 ) . Both ITT and PP eradication rates were significantly lower with sequential treatment in CLA-resistant compared with CLA-susceptible strains ( ITT : 56.2 % vs 72.7 % , OR 5.5 , P = 0.008 ; PP 64.3 % vs 80.0 % , OR 7.9 , P = 0.009 ) . Both treatments were well tolerated . Conclusions : Sequential treatment is greatly effective for eradicating H pylori in children except in CLA-resistant strains . Sequential treatment can be used as a first-line therapy , but only in areas with a low CLA resistance rate Background : The increasing number of pediatric patients infected with multiresistant Helicobacter pylori strains calls for evaluation of treatment regimens . Second-line antibiotics such as tetracycline or quinolones are not licensed for children . Because in vivo resistance to metronidazole may be overcome in vivo by a high dose and prolonged intake , we evaluated the eradication rate and side effects of a high-dose triple therapy in pediatric patients with culture-proven double resistance . Patients and Methods : In this open multicentre trial , 62 children ( < 18 years , body weight > 15 kg ) infected with an H pylori strain resistant to metronidazole and clarithromycin were treated according to body weight classes with amoxicillin ( ∼75 mg/kg/day ) , metronidazole ( ∼25 mg/kg/day ) and esomeprazole ( ∼1.5 mg/kg/day ) for 2 weeks . Adherence and adverse events were assessed by a 2-week diary and telephone interviews at days 7 and 14 of treatment . Primary outcome was a negative 13C-urea breath test after 6 weeks . Results : Of 62 patients , 5 were lost to follow-up , 12 were nonadherent , and 45 treated per protocol . Eradication rates were 66 % ( 41/62 ) [ confidence interval 54–78 ] ( intention to treat ) and 73 % ( 33/45 ) [ confidence interval 60–86 ] ( per protocol ) . Success of treatment was not related to dose per kilogram body weight . Mild to moderate adverse events were reported by 21 patients , including nausea ( 10.8 % ) , diarrhoea ( 8.9 % ) , vomiting ( 7.1 % ) , abdominal pain ( 5.4 % ) , and headache ( 3.6 % ) , and led to discontinuation in 1 child . Conclusion : High-dose amoxicillin , metronidazole , and esomeprazole for 2 weeks is a good treatment option in children infected with a double resistant H pylori strain Objective Resistance to antibiotics is the major cause of treatment failure of Helicobacter pylori infection . A study was conducted to assess prospect ively the antibacterial resistance rates of H pylori in Europe and to study the link between outpatient antibiotic use and resistance levels in different countries . Design Primary antibiotic resistance rates of H pylori were determined from April 2008 to June 2009 in 18 European countries . Data on yearly and cumulative use over several years of systemic antibacterial agents in ambulatory care for the period 2001–8 were expressed in Defined Daily Doses ( DDD ) per 1000 inhabitants per day . The fit of models and the degree of ecological association between antibiotic use and resistance data were assessed using generalised linear mixed models . Results Of 2204 patients included , H pylori resistance rates for adults were 17.5 % for clarithromycin , 14.1 % for levofloxacin and 34.9 % for metronidazole , and were significantly higher for clarithromycin and levofloxacin in Western/ Central and Southern Europe ( > 20 % ) than in Northern European countries ( < 10 % ) . Model fit improved for each additional year of antibiotic use accumulated , but the best fit was obtained for 2005 . A significant association was found between outpatient quinolone use and the proportion of levofloxacin resistance ( p=0.0013 ) and between the use of long-acting macrolides only and clarithromycin resistance ( p=0.036 ) . Conclusion In many countries the high rate of clarithromycin resistance no longer allows its empirical use in st and ard anti-H pylori regimens . The knowledge of outpatient antibiotic consumption may provide a simple tool to predict the susceptibility of H pylori to quinolones and to macrolides and to adapt the treatment strategies BACKGROUND Low Helicobacter pylori eradication rates are common in pediatric trials especially in developing countries . The aim of the study was to investigate the role of antibiotic resistance , drug dosage , and administration frequency on treatment outcome for children in Vietnam . MATERIAL S AND METHODS Antibiotics resistance of H. pylori was analyzed by the Etest in 222 pretreatment isolates from children 3 - 15 years of age who were originally recruited in a r and omized trial with two treatment regiments : lansoprazole with amoxicillin and either clarithromycin ( LAC ) or metronidazole ( LAM ) in two weight groups with once- or twice-daily administration . The study design was an observational study embedded in a r and omized trial . RESULTS The overall resistance to clarithromycin , metronidazole , and amoxicillin was 50.9 % , 65.3 % , and 0.5 % , respectively . In LAC , eradication was linked to the strains being susceptible to clarithromycin ( 78.2 % vs 29.3 % , p = .0001 ) . Twice-daily dosage of proton-pump inhibitor ( PPI ) and clarithromycin was more effective for eradication than once-daily dosage for resistant strains ( 50.0 % vs 14.7 % , p = .004 ) and tended to be so also for sensitive strains ( 87.5 % vs 65.2 % , p = .051 ) . Exact antibiotic dose per body weight result ed in more eradication for resistant strains ( 45.3 % vs 8.0 % , p = .006 ) . These differences were less pronounced for the LAM regimen , with twice-daily PPI versus once daily for resistant strains result ing in 69.2 % and 50.0 % eradication ( p = .096 ) , respectively . CONCLUSIONS Helicobacter pylori clarithromycin resistance was unexpectedly high in young children in Vietnam . Clarithromycin resistance was an important cause for eradication treatment failure . Twice-daily administration and exact antibiotic dosing result ed in more eradicated infections when the strains were antibiotic resistant , which has implication s for the study design in pediatric H. pylori eradication trials OBJECTIVE To report the prevalence rates and correlates for anaemia , iron deficiency ( ID ) and iron-deficiency anaemia ( IDA ) among Inuit preschool-aged children . DESIGN A cross-sectional study assessed iron intake , demographic information , medical history , anthropometrics , Hb , ferritin , C-reactive protein and antibodies to Helicobacter pylori . SETTING Sixteen selected Inuit communities in Nunavut Territory , Canada . SUBJECTS Inuit ( n 388 ) aged 3 - 5 years r and omly recruited from communities . RESULTS Anaemia ( 3 - 4 years : Hb < 110 g/l ; 5 years : Hb < 115 g/l ) was prevalent in 16·8 % of children . The prevalence of ID ( ferritin < 12 μg/l ) was 18·0 % and that of IDA was 5·4 % . When ID was defined as ferritin < 10 μg/l , 10·8 % of children were iron deficient and 3·3 % had IDA . In multiple logistic regression , boys were more likely to be iron deficient ( OR = 2·28 , 95 % CI 1·17 , 8·25 ) , but no other risk factor emerged for ID . Three- to 4-year-olds were less likely than 5-year-olds to have anaemia from causes other than ID ( OR = 0·11 , 95 % CI 0·08 , 0·58 ) . Anaemia from other causes was more common among children residing in crowded homes ( OR = 2·30 , 95 % CI 1·37 , 12·31 ) and those treated for past-year ear infection ( OR = 1·35 , 95 % CI 1·05 , 7·21 ) . CONCLUSIONS The low prevalence of ID and IDA is encouraging , but efforts are still needed to reduce rates as they continue to be higher than general population rates . Household crowding and infections may contribute to anaemia and warrant further research BACKGROUND Helicobacter pylori is one of the most common gastric pathogens , affecting at least half the world 's population , and is strongly associated with gastritis , peptic ulcer , gastric adenocarcinoma , and lymphoma . We aim ed to assess the efficacy , safety , and immunogenicity of a three-dose oral recombinant H pylori vaccine in children in China . METHODS We did this r and omised , double-blind , placebo-controlled , phase 3 trial at one centre in Ganyu County , Jiangsu Province , China . Healthy children aged 6 - 15 years without past or present H pylori infection were r and omly assigned ( 1:1 ) , via computer-generated r and omisation codes in blocks of ten , to receive the H pylori vaccine or placebo . Participants , their guardians , and study investigators were masked to treatment allocation . The primary efficacy endpoint was the occurrence of H pylori infection within 1 year after vaccination . We did analysis in the per- protocol population . This trial is registered with Clinical Trials.gov , number NCT02302170 . FINDINGS Between Dec 2 , 2004 , and March 19 , 2005 , we r and omly assigned 4464 participants to either the vaccine group ( n=2232 ) or the placebo group ( n=2232 ) , of whom 4403 ( 99 % ) participants completed the three-dose vaccination schedule and were included in the per- protocol efficacy analysis . We extended follow-up to 3 years . We recorded 64 events of H pylori infection within the first year ( 14 events in 2074·3 person-years at risk in the vaccine group vs 50 events in 2089·6 person-years at risk in the placebo group ) , result ing in a vaccine efficacy of 71·8 % ( 95 % CI 48·2 - 85·6 ) . 157 ( 7 % ) participants in the vaccine group and 161 ( 7 % ) participants in the placebo group reported at least one adverse reaction . Serious adverse events were reported in five ( < 1 % ) participants in the vaccine group and seven ( < 1 % ) participants in the placebo group , but none was considered to be vaccination related . INTERPRETATION The oral recombinant H pylori vaccine was effective , safe , and immunogenic in H pylori-naive children . This vaccine could substantially reduce the incidence of H pylori infection ; however , follow up over a longer period is needed to confirm the protection of the vaccine against H pylori-associated diseases . FUNDING Chongqing Kangwei Biological Technology |
887 | 18,768,018 | The Vector ultrasonic scaler provided comparable clinical and microbiological periodontal healing results as scaling and root planing and conventional ultrasonic system in moderately deep pockets .
The Vector ultrasonic scaler may be used as a gentle root debridement device for supportive periodontal therapy , as an alternative to other conventional ultrasonic system . | AIM To review the available literature , considering the effect of instrumentation with the Vector ultrasonic scaler on human teeth in vitro and in vivo compared to conventional ultrasonic instruments and /or h and instrumentation .
The assessed effects are calculus removal , time of instrumentation , root surface aspects , cell attachment , patients ' perception , bleeding upon probing , pocket depth , clinical attachment loss and microbiological effects . | BACKGROUND Patient discomfort is one reason for poor compliance with supportive periodontal therapy ( SPT ) . The aim of this study was to compare the levels of discomfort during SPT , using the Vector system and treatment with a conventional ultrasonic scaler . METHODS Forty-six patients with an SPT programme were debrided using both the Vector system and a conventional piezo-electric scaler ( Sirona ) in a split mouth design . A visual analogue scale was used to evaluate of pain scores upon completion of treatment . A verbal response scale(VRS ) was used to assess discomfort , vibration and noise associated with the scaling system , as well as the volume and taste of the coolant used by these systems . RESULTS Patients instrumented with the Vector system experienced approximately half the amount of pain compared with the conventional ultrasonic scaling system . The VRS showed that the Vector system caused less discomfort than the conventional ultrasonic scaling system when assessed for pain , vibration , noise and volume of coolant . These findings were all statistically significant . There was , however , no statistically significant difference between the two systems when assessed for taste . CONCLUSION During SPT the Vector system caused reduced discomforting sensations compared with conventional methods and may be useful in improving compliance with SPT programmes OBJECTIVE A study was conducted to examine the effectiveness of scaling and root planing using a new ultrasonic scaler ( Vector ) . METHODS Eighty extracted teeth affected by periodontal disease were sorted into four groups of 20 , each of which was subjected to one the following procedures : use of the Vector , Vector with polish , Enac and a Gracey scaler . The time spent on cleaning was measured . Half of the sample teeth were examined at r and om for surface roughness , and the surface texture was evaluated by means of the Remaining Calculus Index ( RCI ) and the Roughness and Loss of Tooth Substance Index ( RLTSI ) . The remaining sample s were incubated in dishes with a suspension of fibroblasts . After measuring the number of attached cells , the attachment of fibroblasts was observed by scanning electron microscopy . RESULTS The RLTSI values in the Vector and Vector with polish groups were significantly lower than those in the Enac and Gracey groups , whereas the number of attached cells in the Vector with polish group was larger than in the Enac group . Cell attachment in the Vector and Vector with polish groups proved to be better than in the Enac and Gracey groups . CONCLUSION Since use of the Vector with polish was able to provide scaling and root planing with minimal damage and tight attachment of fibroblasts , it is suggested that this may be a useful instrument for scaling and root planing BACKGROUND A recently introduced piezo-driven ultrasonic device ( Vector ) generates longitudinal oscillations . As a result , the instrument tip moves parallel to the tooth surface . By avoiding vertical oscillations , maintenance treatment with the Vector device should be less painful than treatment with conventional systems . We investigated whether patients perceive treatment with the Vector device as less painful than with a conventional ultrasonic device , and whether the clinical efficacy of the Vector device is comparable with that of the conventional ultrasonic device in maintenance patients . MATERIAL AND METHODS Thirty-eight maintenance patients with moderate to advanced periodontal disease took part in this prospect i ve , r and omized controlled clinical study . Each patients had to have at least two teeth with probing depths of > 4 mm . They were treated either with Dentsply ( n=22 ) at a reduced power setting or with the Vector device ( n=16 ) . The observation period was 6 months . Probing pocket depth , attachment level , and bleeding upon probing were assessed at six sites on each treated tooth by a blinded investigator Patient were asked to report perceived pain during instrumentation with a visual analog scale immediately after treatment , in the evening of the treatment day , and in the evenings 1 and 2 days after treatment . RESULTS Bleeding on probing , probing depth , and attachment level improved in both instrumentation groups from baseline to month 6 ; however , there was no difference between the two instrumentation modalities . The patients perceived treatment with neither instrument as unpleasant , and their perception of pain intensity both during instrumentation and on the following days did not differ . CONCLUSION In maintenance therapy , clinical efficacy of the vector device is comparable with that of conventional ultrasonic device . It makes no difference whether the ultrasonic device at a reduced power setting or the Vector device is used , since patients perceive both instruments as causing very little pain AIM To compare the effectiveness of treatment of peri-implantitis with a novel ultrasonic device , the Vector system , with that of subgingival debridement with carbon fiber curettes . MATERIAL AND METHODS The study , comprising 11 patients with at least two screw type implants with bleeding on probing ( BOP ) , probing pocket depth ( PPD ) > or = 5 mm , and at least 1.5 mm radiographic bone loss and exposed implant threads , was carried out as a single blind r and omized clinical trial . At baseline one r and omly chosen implant in each patient was treated by the Vector system ( test ) while the other implant ( control ) was treated by submucosal debridement with a carbon fiber curette . After 3 months , the same treatments were repeated . Plaque , BOP , and PPD were recorded on all implant surfaces at baseline , and after 3 and 6 months . Bone levels were recorded on radiographs taken prior to the start of the study , and after 6 months . RESULTS Oral hygiene around both test and control implants was improved at 3 and 6 months compared with baseline . At 6 months , four of the Vector-treated sites , and only one site treated with curettes , had stopped to bleed . In neither the test nor the control group , were there any differences between baseline and 6 months regarding PPD and bone levels . CONCLUSION Although there was a greater reduction in the number of sites with BOP following treatment with the Vector system than following instrumentation with carbon fiber curettes , there was no significant difference between the two methods BACKGROUND AND OBJECTIVES The aim of the present study was to investigate the in vivo effects of an Er : YAG laser ( ERL ) , an ultrasonic system and scaling and root planing ( SRP ) on the biocompatibility of periodontally diseased root surfaces in cultures of human periodontal ligament fibroblasts ( PDL ) . STUDY DESIGN / MATERIAL S AND METHODS Forty single rooted teeth , considered for extraction due to severe periodontal destruction , have been r and omly assigned to the following groups : ( 1 ) ERL at 160 mJ/pulse and 10 Hz , or ( 2 ) Vector ultrasonic system ( VUS ) , or ( 3 ) SRP using h and instruments , or ( 4 ) untreated control ( C ) . Immediately after instrumentation , all test and control teeth were extracted and root specimens ( 4 mm2 ) were prepared from all mesial and distal surfaces ( n=80 ) . Following the prescribed treatments , the root specimens were incubated with human PDL fibroblast cultures . Adherent cells were stained with methylene blue and counted using a reflected light microscope and the cell density per mm2 was calculated . Additionally , the cell morphology was investigated using SEM ( n=8 teeth ) . RESULTS Cell counts within each group yielded the following means and st and ard deviations ( cells/mm2 ) : ERL , 111+/-27 ; VUS , 75+/-25 ; SRP , 41+/-17 ; control , 25+/-11 . Analysis of variance ( ANOVA ) revealed significant differences in the number of attached cells between the test and control groups ( P<0.001 , P<0.001 , P<0.01 , respectively ) . ERL and VUS treated specimens showed significantly higher numbers of cells/mm2 than the SRP group ( P<0.001 , respectively ) . The difference between the ERL and VUS group was statistically significant ( P<0.001 ) . CONCLUSIONS The results of the present study indicate that ( i ) ERL , VUS , and SRP promote the attachment of PDL fibroblasts on previously diseased root surfaces , ( ii ) periodontally diseased root surfaces inhibit the adherence of PDL fibroblasts , and ( iii ) the surface structure of ERL and VUS instrumented roots seem to offer better conditions for the adherence of PDL fibroblasts than SRP The aim of this study was to measure subjective intensities of pain during the treatment of periodontal lesions with the Vector-system when compared to pain occurring during the treatment with conventional methods . Twenty patients , each of whom had three teeth with comparable periodontal pocket depths , were treated using three different methods : ( i ) scaling and root planing with h and instruments , ( ii ) cleaning with a conventional ultrasonic instrument ( Siroson S ) and ( iii ) cleaning with the Vector-system . The subjective intensities of pain during the treatment were measured with an intermodal intensity comparison . A visual analog scale was used for the evaluation after the treatment . The results of the intermodal intensity comparison during treatment showed that the use of the Vector-system caused less pain than the cleaning with h and instruments or the conventional ultrasonic system ( P < 0.05 ) . The intermodal intensity comparisons of cleaning with h and instruments and cleaning with the conventional ultrasonic system were not significantly different ( P > 0.05 ) . These results could be confirmed by the visual analog scale . Using the Vector-system for cleaning periodontal lesions it is possible to reduce pain sensations compared to conventional methods . Using cleaning methods that cause less discomfort and pain , it might be possible to increase the patient 's compliance during non-surgical periodontal therapy and recall The goal of this study was to determine whether an ultrasonic scaler with a modified tip is as effective as a curet in providing supportive periodontal treatment for patients , based on clinical parameters of periodontal disease . Nine patients with 10 sites exhibiting probing pocket depth > or = 3 mm were treated at 0 , 90 , and 180 days in a single-blind , split-mouth design for supportive periodontal treatment with either Gracey curets ( GC ) or an ultrasonic scaler with a modified tip ( MU ) . Clinical parameters included plaque index , gingival index , bleeding on probing , darkfield microscopy , and elastase presence . Probing pocket depths and attachment levels were measured using an electronic probe . Measurements of clinical parameters were taken at 0 , 14 , 45 , 90 , 135 , and 180 days . The results showed that treatment with MU was as effective as treatment with GC in all clinical parameters measured . Both treatment modalities were effective in reducing the elastase levels . Instrumentation time was significantly reduced with the MU ( 3.9 minutes vs. 5.9 minutes , P < 0.05 ) . The MU instrument effectively reduced the microbial environment in a significantly shorter time as compared to GC BACKGROUND Surgical periodontal treatment with enamel matrix protein derivative ( EMD ) has been shown to promote periodontal regeneration . However , it is not known whether nonsurgical periodontal therapy with additional subgingival application of EMD may also enhance periodontal regeneration . The purpose of this study was to clinical ly and histologically evaluate healing of human intrabony defects following non-surgical periodontal treatment with and without application of EMD . METHODS Sixteen patients , each of whom displayed one advanced intrabony defect around teeth or roots scheduled for extraction , were included in the study . The defects were treated as follows : 1 ) scaling and root planing with h and instruments and application of EMD ; 2 ) scaling with an ultrasonic instrument and application of EMD ; or 3 ) scaling with an ultrasonic instrument alone . Healing was uneventful in all cases . Six months after surgery , the teeth or roots were extracted together with some of their surrounding soft and hard tissues and processed for histologic evaluation . RESULTS Clinical examination revealed a probing depth reduction and a gain of clinical attachment after all 3 treatment modalities . The histological evaluation , however , revealed that healing in all 3 procedures was predominantly characterized by formation of a long junctional epithelium along the instrumented root surface and no predictable regeneration of attachment apparatus . CONCLUSION Within its limits , the present study failed to show periodontal regeneration in advanced human intrabony defects following non-surgical treatment with subgingival application of EMD OBJECTIVE The aim of this r and omised , split-mouth , controlled clinical trial was to evaluate the effectiveness of a controlled-release chlorhexidine chip ( CHX chip ) as an adjunctive therapy to scaling and root planing ( SRP ) with a newly developed ultrasonic device in supportive periodontal therapy ( SPT ) . MATERIAL S AND METHODS Twenty patients with moderate-to-severe chronic periodontitis , displaying at least four sites with probing depth ( PD ) > or = 5 mm and persistent bleeding on probing ( BOP ) , were recruited for the study . The target sites were r and omly treated with either a newly developed piezo-driven ultrasonic device Vector -- or ultrasonic system ( VUS ) + CHX chip or VUS alone without adjunctive antimicrobial treatment . The clinical parameters , plaque index ( PI ) , gingival index ( GI ) , BOP , PD and clinical attachment level ( CAL ) were recorded at baseline and after 1 , 3 and 6 months . RESULTS At baseline , there were no significant differences between test and control sites for any of the investigated parameters . The average reduction of PD and improvement in CAL was greater in the VUS + CHX chip sites than in sites treated with the VUS alone at 1 , 3 and 6 months ( P < 0.05 ) . The mean reductions on PD and CAL were 0.7 and 0.6 mm for the control sites and 2.2 and 1.9 mm for the test sites , respectively . Also , the mean reduction in BOP scores were higher in the VUS + CHX chip sites compared to VUS alone at 1 , 3 and 6 months ( P < 0.05 ) . PI scores were not significantly different between VUS + CHX chip sites and VUS alone sites at any visit . CONCLUSION These data suggest that CHX chip application following SRP with the tested ultrasonic device is beneficial in improving periodontal parameters in patients on SPT OBJECTIVES The aim of the present study was to evaluate the effects of fluorescence-controlled Er : YAG laser radiation , an ultrasonic device or h and instruments on periodontally diseased root surfaces in vivo . MATERIAL AND METHODS Seventy-two single-rooted teeth ( n=12 patients ) were r and omly treated in vivo by a single course of subgingival instrumentation using ( 1 - 3 ) an Er : YAG laser ( ERL1 : 100 mJ ; ERL2 : 120 mJ ; ERL3 : 140 mJ ; 10 Hz ) , or ( 4 ) the Vector ultrasonic system ( VUS ) or ( 5 ) h and instruments ( SRP ) . Untreated teeth served as control ( UC ) . Areas of residual subgingival calculus ( RSC ) and depth of root surface alterations were assessed histo-/morphometrically . RESULTS Highest values of RSC areas ( % ) were observed in the SRP group ( 12.5+/-6.9 ) . ERL(1 - 3 ) ( 7.8+/-5.8 , 8.6+/-4.5 , 6.2+/-3.9 , respectively ) revealed significantly lower RSC areas than SRP . VUS ( 2.4+/-1.8 ) exhibited significantly lower RSC areas than SRP and ERL(1 , 2 ) . Specimens treated with SRP revealed conspicuous root surface damage , while specimens treated with ERL(1 - 3 ) and VUS exhibited a homogeneous and smooth appearance . CONCLUSION Within the limits of the present study , it may be concluded that ERL and VUS enabled ( i ) a more effective removal of subgingival calculus and ( ii ) a predictable root surface preservation in comparison with SRP OBJECTIVES The Vector ultrasonic system provides root debridement supported by different abrasive irrigation fluids . The aim of this study was to investigate the clinical outcome of initial therapy with subgingival low-abrasive debridement . MATERIAL AND METHODS Twenty patients , who had at least two teeth with pocket depths > 5 mm in each quadrant , took part in this prospect i ve r and omized clinical study . Patients were treated in a split-mouth design as one test quadrant ( 1 ) subgingivally with Vector fluid polish ( VU-H ) and as three control quadrants , ( 2 ) with only supragingival polishing ( PO-H ) , ( 3 ) with h and instruments ( HI-H ) performed by a hygienist and ( 4 ) with h and instruments ( HI-D ) performed by a dentist . At baseline , 3 and 6 months after treatment , pocket depths and attachment levels ( ALs ) were measured and bleeding on probing ( BOP ) was recorded . RESULTS At 6-month evaluation , all groups showed an improvement in clinical parameters . No statistically significant differences in any of the investigated parameters could be observed between the Vector group and the h and scaling groups , or when comparing the results of the two different operators . CONCLUSION This study demonstrates that Vector treatment with polishing fluid was able to reduce pocket depths and the prevalence of BOP and improve clinical AL in a similar way as scaling with curettes The aim of the present study was to investigate the effects of an Er : YAG laser ( ERL ) and the Vector ultrasonic system ( VS ) on the biocompatibility of titanium implants in cultures of human osteoblast-like cells ( SAOS-2 ) . One hundred and sixty-eight titanium discs with four different surfaces ( s and -blasted and acid-etched , titanium plasma-sprayed , machine-polished , and hydroxyapatite-coated ) were used to evaluate cell attachment . The sample s were equally and r and omly assigned to the following groups : ( 1 ) an ERL at an energy level of 100 mJ/pulse and 10 Hz using a special application tip , ( 2 ) the VS using carbon fibre tips , or ( 3 ) untreated control ( C ) . The discs were placed in culture plates , covered with a solution of SAOS-2 cells , and incubated for 7 days . The specimens were then washed with phosphate buffer to remove cells not attached to the surface , and the adherent cells were stained with hematoxilin-eosin . Cells were counted using a reflected light microscope and the cell density per mm2 was calculated . Additionally , cell morphology and surface alterations of the titanium discs after treatment were investigated using scanning electron microscopy ( SEM ) . All titanium discs treated with ERL demonstrated nearly the same cell density per mm2 as the untreated C surfaces . There was a significant decrease in the number of cells that attached to the implant surfaces treated with VS . The SEM examination showed no visible differences between lased and C titanium surfaces . All surfaces treated with VS showed conspicuous surface damage and debris of the used carbon fibres . The results of the present study indicate that ( i ) ERL does not damage titanium surfaces and subsequently does not influence the attachment rate of SAOS-2 cells , and ( ii ) VS , used with this type of carbon fibre tip , does not seem to be suitable for the instrumentation of titanium surfaces AIM The aim of this study was to evaluate in vivo the effectiveness of scaling and root planing of a power-driven mechanism compared with h and instruments and ultrasonic insert alone with a split-mouth design after 3 and 6 months . METHODS Healing events after initial periodontal therapy were investigated in 20 patients with moderate-to-severe adult periodontitis . Plaque index ( PlI ) , bleeding on probing ( PBI ) , probing pocket depth ( PPD ) , probing attachment level ( PAL ) and number of moderate and deep pockets ( NMP , NDP ) were recorded at baseline and 3 and 6 months after treatment . Oral hygiene instruction was provided for each patient . R and omly assigned quadrants per patient were scaled and root planed with h and instrumentation ( curettes , hoes and files ) , with reciprocating power-driven instruments , with ultrasonic scaler alone and with the combined use of ultrasonic scaler and power-driven inserts . The Friedman test was applied to test the significance of difference between the various methods of root instrumentation . Repeated measures of analysis of variance ( manova ) were used to analyse the time effect on the different treatments . RESULTS At the 6-month evaluation , all groups in the scaling and root planing treatment presented with an improvement in the measured clinical parameters , as compared with baseline . No statistical differences ( p>0.05 ) were observed in the assessed periodontal indices among the study sites between the four groups for either treatment . CONCLUSIONS Under our experimental conditions , this clinical study demonstrates that mechanized root planing with power-driven instruments , as effective as the usual procedures ( h and and sonic instruments ) , represents a satisfactory and alternative means of nonsurgical root therapy OBJECTIVES The aim of this prospect i ve , r and omized , controlled clinical study was to compare the effectiveness of a newly developed ultrasonic device to that of scaling and root planing for non-surgical periodontal treatment . MATERIAL AND METHODS Thirty-eight patients with moderate to advanced chronic periodontal disease were treated according to an " one-stage procedure " with either a newly developed ultrasonic device ( VUS ) ( Vector-ultrasonic system ) or scaling and root planing ( SRP ) using h and instruments . Clinical assessment s by plaque index ( PlI ) , gingival index ( GI ) , bleeding on probing ( BOP ) , probing depth ( PD ) , gingival recession ( GR ) , and clinical attachment level ( CAL ) were made prior to and at 6 months after treatment . Differences in clinical parameters were analyzed using the Wilcoxon signed ranks test and Mann and Whitney U-test . RESULTS No differences in any of the investigated parameters were observed at baseline between the two groups . The mean value of BOP decreased in the VUS group from 32 % at baseline to 20 % after 6 months ( p<0.001 ) and in the SRP group from 30 % at baseline to 18 % after 6 months ( p<0.001 ) . The results have shown that at moderately deep sites ( initial PD 4 - 5 mm ) mean CAL changed in the test group from 4.6+/-1.2 to 4.2+/-1.6 mm ( p < 0.001 ) and in the control group from 4.8+/-1.3 to 4.4+/-1.5 mm ( p<0.001 ) . At deep sites ( initial PD>6 mm ) mean CAL changed in the test group from 8.5+/-1.9 to 7.9+/-2.4 mm ( p<0.001 ) and in the control group from 7.9+/-1.6 to 7.2+/-2.2 mm ( p<0.001 ) . No statistically significant differences in any of the investigated parameters were found between the two groups . CONCLUSION Non-surgical periodontal therapy with the tested ultrasonic device may lead to clinical improvements comparable to those obtained with conventional h and instruments |
888 | 17,095,741 | Soft tissue changes that were reported as being statistically significant were of question able clinical significance . | The objective of the present systematic review was to evaluate , through lateral cephalograms , facial soft tissue changes after the use of the Activator and Bionator appliances in Class II division 1 malocclusion subjects . | A prospect i ve clinical study with a r and om allocation of 47 adolescent patients to three different functional appliance groups was established and compared with an untreated control group over a 9-month period . Treatment was undertaken with either a Bionator , Twin Block , or Bass appliance . Pre- and post-treatment cephalograms were used to quantify the skeletal and dentoalveolar changes produced by the appliances and compared with those observed in the control group as a result of growth . Both the Bionator and Twin Block appliances demonstrated a statistically significant increase in m and ibular length ( 3.9 + /- 2.7 mm ; 3.7 + /- 2.1 mm , respectively ) compared with the control group ( P < 0.05 ) , with an anterior movement of pogonion and point B. Highly statistically significant increases ( P < 0.01 ) were seen in lower face heights for all the appliance groups compared with the control group . The Twin Block group showed the least forward movement of point A due to a change in the inclination of the maxillary plane . The Bionator and Twin Block groups showed statistically significant reductions in the inclination of the upper incisors to the maxillary plane ( P < 0.05 ) . The Bass group showed minimal change in the inclination of the lower labial segment to the m and ibular plane . The Bionator group demonstrated the greatest proclination of the lower labial segment ( 4.0 + /- 3.6 degrees ) . Clinical ly important changes were measured in all the appliance groups when compared with the control group . Differences were also identified between the functional appliance groups . The Twin Block appliance and , to a lesser extent , the Bionator appeared the most effective in producing sagittal and vertical changes The purpose of this study was to determine the changes in the soft tissue profile in patients treated in the mixed dentition with a bionator . Two groups of 30 individuals , between 9 and 12 years old and with Class II , Division 1 , malocclusion were matched for age , sex , observation time , and dentofacial characteristics . Patients in the first group were treated with a bionator for an average of 18.7 months , result ing in a Class I molar relationship and reduction of overjet . The second group acted as a control and individuals did not receive any form of orthodontic treatment . Pretreatment and posttreatment cephalograms were analyzed and paired t-tests were used to compare the significance of changes between the two groups . Compared with the control group , the treated group demonstrated 1.97 degrees decrease in ANB , a 3.35 mm increase in anterior facial height , 2.22 degrees decrease in soft tissue profile convexity , and 17.4 degrees increase in mentolabial angle The short- and long-term effects of the Herbst appliance on the facial profile were determined in 69 Class II , division 1 malocclusions treated for 7 months and followed for 5 - 10 years post-treatment . Forty-nine subjects exhibited a stable long-term treatment result , while 20 cases relapsed . Lateral cephalometric radiographs from before treatment , after treatment , 6 months post-treatment , and 5 - 10 years post-treatment were analysed . As a rule Herbst treatment result ed in a reduction of the facial hard and soft tissue profile convexity . In relation to the E-line , the upper lip became retrusive , while the lower lip remained , on average , unchanged . During the post-treatment period of 5 - 10 years the hard tissue profile convexity was , on average , reduced in both the stable and relapse groups . When excluding the nose in the soft tissue profile evaluation , the facial profile convexity was , on average , reduced in the stable group while it remained unchanged in the relapse group . When including the nose in the evaluation , an average increase in the profile convexity occurred in both examination groups . Furthermore , the upper and lower lips became retrusive in both groups . For all the variables , however , large individual variations existed . In conclusion , it can be said that the Herbst appliance improves the facial hard and soft tissue profiles . Due to post-treatment growth changes the long-term effects of therapy are , however , variable and unpredictable The aim of this study was to determine the change in profile attractiveness in children with Class II Division 1 malocclusion after 18 months ' treatment with functional appliances . Changes in profile attractiveness were assessed by panels of art students , dental students , and parents of orthodontic patients . Each panel consisted of an equal number of male and female raters . The raters first decided whether the initial or 18-month profile silhouette was more attractive , and then scored the degree to which it was more attractive on an unmarked visual analog scale . There were no significant differences between either male and female raters or among panels in their assessment s of the change in profile attractiveness in the whole sample . Neither were there significant differences between the change in profile attractiveness of the untreated subjects and the subjects treated with either Fränkel function regulators or Harvold activators . It is concluded that treatment with functional appliances does not lead to more attractive profiles than nontreatment A prospect i ve clinical study with a r and om allocation of 47 patients to three different functional appliance groups was established and compared with a slightly younger control group over a 9-month period . The cephalometric hard tissue changes were assessed in relation to the soft tissue changes produced and the patients were also assessed by three-dimensional ( 3D ) laser scanning of the facial soft tissues . Each ' averaged ' appliance group scan was compared with the ' averaged ' control group face . Statistically and clinical ly significant changes occurred in the group treated with the Twin Block appliance , and to a lesser extent in the group treated with the Bionator appliance . No statistically significant facial soft tissue changes could be demonstrated in the Bass appliance group . Upper lip position remained stable despite the significant overjet reduction attained in the three appliance groups . Lower lip protrusion ( up to 3.8 mm ) , lower lip length ( up to 4.0 mm ) , and soft tissue lower and total face height increased significantly in all appliance groups by varying amounts . The long-term effect of these changes needs to be fully evaluated . The laser scanning system was found to be a sensitive and accurate method of quantitatively assessing small changes in the soft tissue facial form . Significant changes of the facial tissues in the transverse plane were highlighted by this technique The aim of this study was to evaluate the effect of different functional appliances on the soft tissues as assessed by cephalometry and optical surface scanning . Forty-two patients were r and omly allocated to Bass , Twin Block ( TB ) , and Twin Block + Headgear ( TB + Hg ) groups . Lateral cephalograms and optical surface scans were recorded before and after the 10-month study period . ANOVA was used to test the cephalometric variables for differences at the 5 per cent level . The optical surface scanning and cephalometric results were consistent in the sagittal dimension . In the vertical dimension , however , the optical surface scans consistently recorded a greater increase compared with cephalometric values . No differences were detected with regard to cephalometric values at the 5 per cent level . However , the Bass appliance produced greater forward positioning of soft tissue pogonion as assessed by optical surface scanning |
889 | 29,937,732 | Conclusion : This systematic review found that moderate physical exercise improves cognition | Background : Physical exercise is a systematic sequence of movements executed with a predefined purpose .
This muscular activity impacts not only on circulatory adaptations , but also neuronal integration with the potential to influence cognition .
The aim of this review was to determine whether the literature supports the idea that physical exercise promotes cognitive benefits in healthy adults . | Background Recent research has suggested an important role of lateral prefrontal cortex ( lPFC ) in consistent implementation of positive health behaviors and avoidance of negative health behaviors . Methods We examined whether gray matter volume in the lPFC prospect ively predicts exercise class attendance among older women ( n = 122 ) who underwent either a 52-week or 26-week exercise training intervention . Structural magnetic resonance imaging determined gray matter volume at baseline . Results Independent of intracranial volume , age , education , body composition , mobility , depressive symptoms , and general cognitive functioning , larger lPFC volume predicted greater exercise class attendance ( all p values < .05 ) . Follow-up whole-brain analyses further confirmed that regions in the lPFC-especially the left middle frontal gyrus ( p < .005)-predicted future exercise adherence as well as identified other regions , especially in the insula and temporal cortex , that predicted exercise adherence . Conclusions These findings suggest that sustained engagement in exercise training might rely in part on functions of the lPFC and that lPFC volume might be a reasonable proxy for such functions The combined effects of hyperventilation and arterial desaturation on cerebral oxygenation ( [ Formula : see text ] ) were determined using near-infrared spectroscopy . Eleven competitive oarsmen were evaluated during a 6-min maximal ergometer row . The study was r and omized in a double-blind fashion with an inspired O2 fraction of 0.21 or 0.30 in a crossover design . During exercise with an inspired O2 fraction of 0.21 , the arterial CO2 pressure ( 35 ± 1 mmHg ; mean ± SE ) and O2 pressure ( 77 ± 2 mmHg ) as well as the hemoglobin saturation ( 91.9 ± 0.7 % ) were reduced ( P < 0.05).[Formula : see text ] was reduced from 80 ± 2 to 63 ± 2 % ( P < 0.05 ) , and the near-infrared spectroscopy-determined concentration changes in deoxy- ( ΔHb ) and oxyhemoglobin ( ΔHbO2 ) of the vastus lateralis muscle increased 22 ± 3 μM and decreased 14 ± 3 μM , respectively ( P < 0.05 ) . Increasing the inspired O2fraction to 0.30 did not affect ventilation ( 174 ± 4 l/min ) , but arterial CO2 pressure ( 37 ± 2 mmHg ) , O2 pressure ( 165 ± 5 mmHg ) , and hemoglobin O2saturation ( 99 ± 0.1 % ) increased ( P < 0.05).[Formula : see text ] remained close to the resting level during exercise ( 79 ± 2 vs. 81 ± 2 % ) , and although the muscle ΔHb ( 18 ± 2 μM ) and ΔHbO2 ( -12 ± 3 μM ) were similar to those established without O2 supplementation , work capacity increased from 389 ± 11 to 413 ± 10 W ( P < 0.05 ) . These results indicate that an elevated inspiratory O2fraction increases exercise performance related to maintained cerebral oxygenation rather than to an effect on the working muscles Background Dementia is more common in older than in younger people , and as a result of the ageing of the population in developed countries , it is becoming more prevalent . Drug treatments for dementia are limited , and the main support offered to people with dementia and their families is generally services to mitigate against loss of function . Physical exercise is a c and i date non-pharmacological treatment for dementia . Methods / Design DAPA is a r and omised controlled trial funded by the National Institute for Health Research Health Technology Assessment programme to estimate the effect of a 4-month , moderate- to hard-intensity exercise training programme and subsequent advice to remain active , on cognition ( primary outcome ) at 12 months in people with mild to moderate dementia . Community-dwelling participants ( with their carers where possible ) , who are able to walk 3 metres without human assistance , able to undertake an exercise programme and do not have any unstable or terminal illness are recruited . Participants are then r and omised by an independent statistician using a computerised r and om number generator to usual care or exercise at a 2:1 ratio in favour of exercise . The exercise intervention comprises 29 , 1-hour-long exercise classes , run twice weekly at suitable venues such as leisure centres , which include aerobic exercise ( on static bikes ) and resistance exercise ( using weights ) . Goals for independent exercise are set while the classes are still running , and supported thereafter with phone calls . The primary outcome is measured using ADAS-cog . Secondary outcome measures include behavioural symptoms , functional ability , quality of life and carer burden . Primary and secondary outcomes will be measured at baseline and at 6 and 12 months after r and omisation , by research ers masked to participant r and omisation in the participants ’ own homes . An economic evaluation will be carried out in parallel to the RCT , as will a qualitative study capturing the experiences of participants , carers and staff delivering the intervention . Discussion The DAPA study will be the first large , r and omised trial of the cognitive effects of exercise on people with dementia . The intervention is design ed to be capable of being delivered within the constraints of NHS service provision , and the economic evaluation will allow assessment of its cost-effectiveness . Trial registration DAPA was registered with the IS RCT N data base on 29 July 2011 , registration number IS RCT N32612072 BACKGROUND Over half of stroke survivors have cognitive impairment , which impedes rehabilitation and functional recovery . Evidence suggests a single session of aerobic exercise improves cognitive functions among healthy adults . Whether this holds true for stroke survivors is unclear . The objective of this study was to examine whether one session of moderate-intensity aerobic exercise improves the cognitive control and attention of stroke survivors . METHODS Nine people with chronic stroke ( ≥6 months poststroke ) performed a modified Eriksen Flanker task with concurrent electroencephalography ( EEG ) before and immediately , 20 minutes , and 40 minutes after 20 minutes of moderate-intensity exercise and after 20 minutes of rest . The sessions were in r and omized order . Accuracy and response time were recorded for congruent and incongruent stimuli . Differences in accuracy , response time , and event-related potentials ( P300 , reflective of decision making ) were analyzed using repeated measures analysis of variance . RESULTS Improvements in EEG measures were noted after exercise . P300 amplitude at Fz was greater 40 minutes after exercise compared with after rest ( P = .007 ) . P300 latency was also shorter at 20 minutes after exercise compared with after rest for both congruent ( 465.8 milliseconds versus 500.0 milliseconds ; P = .02 ) and incongruent ( 468.0 milliseconds versus 532.0 milliseconds ; P = .003 ) conditions at the central electrode on the lesional side . Differences in behavioral performance after exercise were not significant . CONCLUSIONS Preliminary results suggest that aerobic exercise improves cortical processes underlying cognitive control and attention 20 - 40 minutes postexercise . Future research should confirm results in a larger sample and examine whether attention-dem and ing rehabilitation in this window has improved outcomes UNLABELLED Repeated maximal-intensity short- duration exercise ( sprint interval training , SIT ) can produce muscle adaptations similar to endurance training ( ET ) despite a much reduced training volume . However , most SIT data use cycling , and little is known about its effects on body composition or maximal cardiac output ( Qmax ) . PURPOSE The purpose of this study was to assess body composition , 2000-m run time trial , VO(2max ) , and Q(max ) effects of run SIT versus ET . METHODS Men and women ( n = 10 per group ; mean ± SD : age = 24 ± 3 yr ) trained three times per week for 6 wk with SIT , 30-s all-out run sprints ( manually driven treadmill ) , four to six bouts per session , 4-min recovery per bout , versus ET , 65 % VO(2max ) for 30 to 60 min·d(-1 ) . RESULTS Training improved ( P < 0.05 ) body composition , 2000-m run time trial performance , and VO(2max ) in both groups . Fat mass decreased 12.4 % with SIT ( mean ± SEM ; 13.7 ± 1.6 to 12.0 ± 1.6 kg ) and 5.8 % with ET ( 13.9 ± 1.7 to 13.1 ± 1.6 kg ) . Lean mass increased 1 % in both groups . Time trial performance improved 4.6 % with SIT ( -25.6 ± 8.1 s ) and 5.9 % with ET ( -31.9 ± 6.3 s ) . VO(2max ) increased 11.5 % with SIT ( 46.8 ± 1.6 to 52.2 ± 2.0 mL·kg·(-1)·min(-1 ) ) and 12.5 % with ET ( 44.0 ± 2.0 to 49.5 ± 2.6 mL·kg·(-1)·min(-1 ) ) . None of these improvements differed between groups . In contrast , Q(max ) increased by 9.5 % with ET only ( 22.2 ± 2.0 to 24.3 ± 1.6 L·min(-1 ) ) . CONCLUSIONS Despite a fraction of the time commitment , run SIT induces similar body composition , VO(2max ) , and performance adaptations as ET , but with no effect on Q(max ) . These data suggest that adaptations with ET are of central origin primarily , whereas those with SIT are more 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 Brain-derived neurotrophic factor ( BDNF ) plays a role in the maintenance and function of neurons . Although persons with Alzheimer ’s disease have lower cortical levels of BDNF , evidence regarding the association between circulating BDNF and cognitive function is conflicting . We sought to determine the correlates of BDNF level and whether BDNF level was prospect ively associated with cognitive decline in healthy older adults . We measured serum BDNF near baseline in 912 individuals . Cognitive status was assessed repeatedly with the modified Mini-Mental Status Examination and the Digit Symbol Substitution test over the next 10 years . We evaluated the association between BDNF and cognitive decline with longitudinal models . We also assessed the association between BDNF level and demographics , comorbidities and health behaviors . We found an association between serum BDNF and several characteristics that are also associated with dementia ( race and depression ) , suggesting that future studies should control for these potential confounders . We did not find evidence of a longitudinal association between serum BDNF and subsequent cognitive test trajectories in older adults , although we did identify a potential trend toward a cross-sectional association . Our results suggest that serum BDNF may have limited utility as a biomarker of prospect i ve cognitive decline Brain blood vessels contain muscarinic receptors that are important for cerebral blood flow ( CBF ) regulation , but whether a cholinergic receptor mechanism is involved in the exercise-induced increase in cerebral perfusion or affects cerebral metabolism remains unknown . We evaluated CBF and cerebral metabolism ( from arterial and internal jugular venous O(2 ) , glucose and lactate differences ) , as well as the middle cerebral artery mean blood velocity ( MCA V(mean ) ; transcranial Doppler ultrasound ) during a sustained static h and grip contraction at 40 % of maximal voluntary contraction ( n = 9 ) and the MCA V(mean ) during ergometer cycling ( n = 8) . Separate , r and omized and counterbalanced trials were performed in control ( no drug ) conditions and following muscarinic cholinergic receptor blockade by glycopyrrolate . Glycopyrrolate increased resting heart rate from approximately 60 to approximately 110 beats min(-1 ) ( P < 0.01 ) and cardiac output by approximately 40 % ( P < 0.05 ) , but did not affect mean arterial pressure . The central cardiovascular responses to exercise with glycopyrrolate were similar to the control responses , except that cardiac output did not increase during static h and grip with glycopyrrolate . Glycopyrrolate did not significantly affect cerebral metabolism during static h and grip , but a parallel increase in MCA V(mean ) ( approximately 16 % ; P < 0.01 ) and CBF ( approximately 12 % ; P < 0.01 ) during static h and grip , as well as the increase in MCA V(mean ) during cycling ( approximately 15 % ; P < 0.01 ) , were abolished by glycopyrrolate ( P < 0.05 ) . Thus , during both cycling and static h and grip , a cholinergic receptor mechanism is important for the exercise-induced increase in cerebral perfusion without affecting the cerebral metabolic rate for oxygen The new and recent advances in neuroelectric and neuroimaging technologies provide a new era for further exploring and underst and ing how brain and cognition function can be stimulated by environmental factors , such as exercise , and particularly to study whether physical exercise influences brain development in early ages . The present study , namely the ActiveBrains project , aims to examine the effects of a physical exercise programme on brain and cognition , as well as on selected physical and mental health outcomes in overweight/obese children . A total of 100 participants aged 8 to 11 years are r and omized into an exercise group ( N=50 ) or a control group ( N=50 ) . The intervention lasts 20-weeks , with 3 - 5 sessions per week of 90 min each , and is mainly focused on high-intensity aerobic exercise yet also includes muscle-strengthening exercises . The extent to what the intervention effect remains 8-months after the exercise programme finishes is also studied in a sub sample . Brain structure and function and cognitive performance are assessed using structural and functional magnetic resonance imaging and electroencephalographic recordings . Secondary outcomes include physical health outcomes ( e.g. physical fitness , body fatness , bone mass and lipid-metabolic factors ) and mental health outcomes ( e.g. chronic stress indicators and overall behavioural and personality measurements such as anxiety or depression ) . This project will substantially contribute to the existing knowledge and will have an impact on societies , since early stimulation of brain development might have long lasting consequences on cognitive performance , academic achievement and in the prevention of behavioural problems and the promotion of psychological adjustment and mental health . Clinical trials . Gov identifier : NCT02295072 We conducted two studies of circadian misalignment in non-Hispanic African and European-Americans . In the first , the sleep/wake ( light/dark ) schedule was advanced 9 h , similar to flying east , and in the second these schedules were delayed 9 h , similar to flying west or sleeping during the day after night work . We confirmed that the free-running circadian period is shorter in African-Americans compared to European-Americans , and found differences in the magnitude and direction of circadian rhythm phase shifts which were related to the circadian period . The sleep and cognitive performance data from the first study ( published in this journal ) documented the impairment in both ancestry groups due to this extreme circadian misalignment . African-Americans slept less and performed slightly worse during advanced/misaligned days than European-Americans . The current analysis is of sleep and cognitive performance from the second study . Participants were 23 African-Americans and 22 European-Americans ( aged 18–44 years ) . Following four baseline days ( 8 h time in bed , based on habitual sleep ) , the sleep/wake schedule was delayed by 9 h for three days . Sleep was monitored using actigraphy . During the last two baseline/aligned days and the first two delayed/misaligned days , beginning 2 h after waking , cognitive performance was assessed every 3 h using the Automated Neuropsychological Assessment Metrics ( ANAM ) battery . Mixed model ANOVAs assessed the effects of ancestry ( African-American or European-American ) and condition ( baseline/aligned or delayed/misaligned ) on sleep and performance . There was decreased sleep and impaired cognitive performance in both ancestry groups during the two delayed/misaligned days relative to baseline/aligned days . Sleep and cognitive performance did not differ between African-Americans and European-Americans during either baseline/aligned or delayed/misaligned days . While our previous work showed that an advance in the sleep/wake schedule impaired the sleep of African-Americans more than European-Americans , delaying the sleep/wake schedule impaired the sleep and cognitive performance of African-Americans and European-Americans equally Background : Because of specific method ological difficulties in conducting r and omized trials , surgical research remains dependent predominantly on observational or non‐r and omized studies . Few vali date d instruments are available to determine the method ological quality of such studies either from the reader 's perspective or for the purpose of meta‐ analysis . The aim of the present study was to develop and vali date such an instrument Recent studies indicate that a single bout of physical exercise can have immediate positive effects on cognitive performance of children and adolescents . However , the type of exercise that affects cognitive performance the most in young adolescents is not fully understood . Therefore , this controlled study examined the acute effects of three types of 12-min classroom-based exercise sessions on information processing speed and selective attention . The three conditions consisted of aerobic , coordination , and strength exercises , respectively . In particular , this study focused on the feasibility and efficiency of introducing short bouts of exercise in the classroom . One hundred and ninety five students ( 5th and 6th grade ; 10–13 years old ) participated in a double baseline within-subjects design , with students acting as their own control . Exercise type was r and omly assigned to each class and acted as between-subject factor . Before and immediately after both the control and the exercise session , students performed two cognitive tests that measured information processing speed ( Letter Digit Substitution Test ) and selective attention ( d2 Test of Attention ) . The results revealed that exercising at low to moderate intensity does not have an effect on the cognitive parameters tested in young adolescents . Furthermore , there were no differential effects of exercise type . The results of this study are discussed in terms of the caution which should be taken when conducting exercise sessions in a classroom setting aim ed at improving cognitive performance Excess postexercise oxygen consumption ( EPOC ) may describe the impact of previous exercise on energy metabolism . Ten males completed Resistance Only , Run Only , Resistance-Run , and Run-Resistance experimental conditions . Resistance exercise consisted of 7 lifts . Running consisted of 25 minutes of treadmill exercise . VO2 was determined during tread-mill exercise and after each exercise treatment . Our findings indicated that treadmill exercise VO2 was significantly higher for Resistance-Run compared with Run-Resistance and Resistance Only at all time intervals . At 10 minutes postexercise , VO2 was greater for Resistance Only and Run-Resistance than for Resistance-Run . At 20 and 30 minutes , VO2 following Resistance Only was significantly greater than following Run Only . In conclusion , EPOC is greatest following Run-Resistance ; however , treadmill exercise is more physiologically difficult following resistance exercise . Furthermore , the sequence of resistance and treadmill exercise influences EPOC , primarily because of the effects of resistance exercise rather than the exercise combination . We recommend performing aerobic exercise before resistance exercise when combining them into 1 exercise session At the end of a long week in the office , you sink back into your chair , reflecting on some of the more memorable patients you cared for and counseled . Through gentle history taking , you discovered that urinary incontinence is the underlying cause of an elderly patient 's increasing social isolation . During a careful physical examination , you detected bruising on the torso of a woman with chronic headaches and began to explore the longst and ing abusive relationship between the woman and her alcoholic partner . You discontinued procainamide therapy in a 72-year-old man who had asymptomatic premature ventricular contractions after myocardial infa rct ion . To prevent bleeding from esophageal varices , you started -blocker therapy in a woman with long-st and ing cryptogenic cirrhosis and portal hypertension . In couples ' therapy , discussing the future quality of life of a middle-aged gay man with human immunodeficiency virus infection , you journeyed through emotionally intense dialogue about advance directives . You presented the risk factors for major and minor bleeding to a 39-year-old woman who was considering warfarin therapy because of recently diagnosed atrial fibrillation and valvular heart disease . You listened to , made diagnoses for , treated , advised , and comforted many patients . Yet there were some hiccoughs in your practice along the way . You stumbled while debating the pros and cons of breast cancer screening with a healthy 48-year-old woman who has been staying current with information on the Internet . You question ed the merits of a personalized walking program suggested to you by a motivated 66-year-old man with severe claudication . Explaining that you wanted to review the best current evidence on these issues , you resolved to address your uncertainties before these patients made their next office visits , in a week 's time . Sighing deeply , you acknowledge that you have little time to read . You subscribe to three journals , which you browse months after they arrive-either when your journal stack becomes precariously high or when your guilt is sufficiently motivational . You sometimes find the conclusions of individual articles conflicting or confusing . You know that some of the decisions and suggestions you made this week , specifically your decisions about stopping procainamide therapy and starting -blocker therapy and your advice about bleeding risks from anticoagulant therapy , were based on the best current research evidence [ 1 - 3 ] . On the other h and , your patients ' inquiries about breast cancer screening and exercise treatment for claudication highlight your need for a concise , current , rigorous synthesis of the best available evidence on each of these topics : in brief , a systematic review [ 4 , 5 ] . Incorporating Research Evidence into Clinical Decision Making The foregoing scenario is familiar to practitioners . In a typical week , we encounter patients with diverse problems ; exercise numerous clinical , interpersonal , and technical skills ; and make many decisions . The factors that affect these decisions and their outcomes are complex . For instance , each patient has unique sociodemographic characteristics , cultural circumstances , and personal preferences . Each physician has unique knowledge , experiences , and values . Moreover , practitioners and their patients make decisions within the context of a rapidly changing health care system that influences the availability , accessibility , and cost of diagnostic tests and therapies [ 6 ] . Timely , useful evidence from the biomedical literature should be an integral component of clinical decision making . If one treatment has been shown to be better than another , we need to know , so that we can recommend the treatment to the appropriate patients . The worldwide effort to develop new tests and treatments , and to determine their usefulness , has never been stronger , and our patients and their families expect us to be fonts of the knowledge that results from this effort [ 7 ] . Unfortunately , it is easy for current best research evidence to pass us by [ 8 ] . We may lack the time , motivation , and basic skills needed to find , critically appraise , and synthesize information , all of which we must do if we are to integrate the results of original studies into our practice . Fortunately , several potent methods are emerging that can greatly enhance our ability to interpret and apply research evidence ; foremost among them is the systematic review . This article begins a series in Annals that will examine systematic review s in detail and explore their many applications . Systematic review s represent the best chance that most practitioners will have to underst and and accurately apply the key signals arising from the robust and increasingly productive search for solutions to medical problems . A properly conducted systematic review faithfully summarizes the evidence from all relevant studies on the topic of interest , and it does so concisely and transparently . What Is a Systematic Review ? Systematic review s are scientific investigations in themselves , with pre-planned methods and an assembly of original studies as their subjects . They synthesize the results of multiple primary investigations by using strategies that limit bias and r and om error [ 9 , 10 ] . These strategies include a comprehensive search of all potentially relevant articles and the use of explicit , reproducible criteria in the selection of articles for review . Primary research design s and study characteristics are appraised , data are synthesized , and results are interpreted . When the results of primary studies are summarized but not statistically combined , the review may be called a qualitative systematic review . A quantitative systematic review , or meta- analysis , is a systematic review that uses statistical methods to combine the results of two or more studies . The term overview is sometimes used to denote a systematic review , whether quantitative or qualitative . Summaries of research that lack explicit descriptions of systematic methods are often called narrative review s. Review articles are one type of integrative publication ; practice guidelines , economic evaluations , and clinical decision analyses are others . These other types of integrative articles often incorporate the results of systematic review s. For example , practice guidelines are systematic ally developed statements intended to assist practitioners and patients with decisions about appropriate health care for specific clinical circumstances [ 11 ] . Evidence -based practice guidelines are based on systematic review s of the literature , appropriately adapted to local circumstances and values . Economic evaluations compare both the costs and the consequences of different courses of action ; the knowledge of consequences that are considered in these evaluations is often generated by systematic review s of primary studies . Decision analyses quantify both the likelihood and the valuation of the expected outcomes associated with competing alternatives . Differences between Systematic and Narrative Review s All review s , narrative and systematic alike , are retrospective , observational research studies and are therefore subject to systematic and r and om error . Accordingly , the quality of a review - and thus its worth-depends on the extent to which scientific review methods have been used to minimize error and bias . This is the key feature that distinguishes traditional narrative review s from systematic review s ( Table 1 ) . If a review is prepared according to the steps outlined in the right column of Table 1 , it is more likely to be systematic and to provide unbiased conclusions . If review methods approximate those found in the middle column of Table 1 , the article is more likely to be a narrative review , and the conclusions are less likely to be based on an unbiased summary of all relevant evidence . Table 1 . Differences between Narrative Review s and Systematic Review s Systematic review s are generated to answer specific , often narrow , clinical questions in depth . These questions can be formulated explicitly according to four variables : a specific population and setting ( such as elderly out patients ) , the condition of interest ( for example , hypertension ) , an exposure to a test or treatment ( such as pharmacologic management ) , and one or more specific outcomes ( such as cardiovascular and cerebrovascular events and mortality ) [ 12 ] . Thus , an example of a well-formulated , clinical ly relevant question is , Does pharmacologic treatment of hypertension in the elderly prevent strokes and myocardial infa rct ions or delay death ? If the question that is driving the review is not clear from the title , abstract , or introduction , or if no methods section is included , the paper is more likely to be a narrative review than a systematic review [ 13 ] . Most narrative review articles deal with a broad range of issues related to a given topic rather than addressing a particular issue in depth [ 9 ] . For example , a narrative review on diabetes ( such as that which might be found in a textbook chapter ) might include sections on the physiology and pathophysiology of carbohydrate , lipid , and protein metabolism ; the epidemiology of and prognosis associated with diabetes ; diagnostic and screening approaches ; and preventive , therapeutic , rehabilitative , and palliative interventions . Thus , narrative review s may be most useful for obtaining a broad perspective on a topic ; they are less often useful in furnishing quantitative answers to specific clinical questions . Narrative review s are appropriate for describing the history or development of a problem and its management . Narrative review s may better describe cutting-edge developments if research is scant or preliminary or if studies are very limited by flawed design or execution [ 13 ] . They may be particularly useful for discussing data in light of underlying theory and context . Narrative review s can draw analogies and can conceptually integrate two independent fields of research , such as Psychological changes associated with 16-wk moderate and low intensity exercise training programs , two of which possessed a cognitive component , were evaluated . Subjects were healthy , sedentary adults , 69 women ( mean age = 54.8 + /- 8.3 yr ) and 66 men ( mean age = 50.6 + /- 8.0 yr ) . Participants were r and omly assigned to a control group ( C ) , moderate intensity walking group ( MW ) , low intensity walking group ( LW ) , low intensity walking plus relaxation response group ( LWR ) , or mindful exercise ( ME ) group-a Tai Chi type program . Women in the ME group experienced reductions in mood disturbance ( tension , P < 0.01 ; depression , P < 0.05 ; anger , P < 0.008 ; confusion , P < 0.02 ; and total mood disturbance , P < 0.006 ) and an improvement in general mood ( P < 0.04 ) . Women in the MW group noted greater satisfaction with physical attributes ( body cathexis , P < 0.03 ) , and men in MW reported increased positive affect ( P < 0.006 ) . No other differences were observed between groups on measures of mood , self-esteem , personality , or life satisfaction . Equivocal support is provided for the hypothesis that exercise plus cognitive strategy training programs are more effective than exercise programs lacking a structured cognitive component in promoting psychological benefits |
890 | 30,245,988 | The results of the studies showed some cases of pulmonary embolism , deep vein thrombosis , and bleeding ; even then , the NOACs were effective in preventing thromboembolic events .
There is no consensus regarding the prophylaxis method for these events , which is why the challenge is to obtain high levels of prevention while minimizing the adverse effects . | Oral anticoagulants are being used in the postoperative period of hip arthroplasty to prevent of thromboembolic events , create doubts as to the effectiveness of thromboprophylaxis and reduce the risk of hemorrhage .
This systematic revision is aim ed at evaluating the use of oral anticoagulants in the prevention of thromboembolic events in the postoperative period of patients undergoing hip arthroplasty . | INTRODUCTION Perioperative blood loss is a frequent cause of complications in total hip replacement ( THR ) . The present prospect i ve study assessed the efficacy of tranexamic acid ( Exacyl ( ® ) ) in reducing blood loss in primary THR associated to rivaroxaban ( Xarelto ( ® ) ) thromboprophylaxis . HYPOTHESIS Tranexamic acid associated to rivaroxaban reduces blood loss . MATERIAL AND METHOD A prospect i ve case-control study included 70 primary cementless THRs performed by a single surgeon on a st and ardized technique , between September 2009 and September 2010 . Thirty-seven patients received perioperative tranexamic acid ; all patients received rivaroxaban thromboprophylaxis . RESULTS There was no significant difference between the two groups in terms of peroperative blood-loss volume or rates of thromboembolic or ischemic events or hematoma . Postoperative blood loss , D0 - 5 differential hemoglobinemia and real blood loss ( in mL 100 % hematocrit ) were significantly lower in the tranexamic acid group . No transfusions were required in the tranexamic acid group , versus four in the control group . DISCUSSION Tranexamic acid associated to direct anti-Xa ( antithrombin-independent ) oral anticoagulants was effective in reducing postoperative blood loss , improving hemoglobinemia at 5 days and reducing transfusion rates . The results also confirmed the efficacy of and tolerance for rivaroxaban thromboprophylaxis in primary THR , with no clinical thrombotic events induced by the association of tranexamic acid with rivaroxaban . CONCLUSIONS Tranexamic acid is a simple means of reducing postoperative blood loss in THR , without increased risk of thromboembolism when associated to rivaroxaban thromboprophylaxis . LEVEL OF EVIDENCE Level III prospect i ve case-control study OBJECTIVE Prevention of deep venous thrombosis ( DVT ) and associated pulmonary embolism following major orthopedic surgeries is challenging , and there is an increased interest in developing new treatment strategies . We compared 2 switch-therapy modalities-enoxaparin to rivaroxaban and enoxaparin to dabigatran- and enoxaparin monotherapy for preventing DVT after total knee arthroplasty ( TKA ) and total hip arthroplasty ( THA ) . METHODS This was a prospect i ve , non-blinded , r and omized controlled study . We selected 180 eligible patients out of 247 patients undergoing TKA or THA . During the preoperative checkup , patients were r and omized to receive either enoxaparin ( enoxaparin group ) or switch-therapy regimens , comprising enoxaparin during hospitalization and rivaroxaban ( rivaroxaban group ) or dabigatran ( dabigatran group ) during the outpatient period . All patients were evaluated for DVT using Doppler ultrasonography ( USG ) 6 weeks postoperatively . The primary efficacy outcome was the prevention of symptomatic or Doppler ultrasonography (USG)-proven DVT , whereas the primary safety outcome was the incidence of bleeding during the DVT-prophylaxis period . RESULTS Doppler USG at 6 weeks after surgery revealed no signs of DVT in any patient . During the hospitalization period , only 2 major bleeding events were reported ( 1 [ 1.6 % ] in the enoxaparin group and 1 [ 1.6 % ] in the dabigatran group ) . No major bleeding events were reported during the outpatient follow-up period in any group . Differences among the 3 groups regarding bleeding events were not statistically significant ( p>0.05 ) . CONCLUSION When using switch-therapy modalities , clinicians can take advantage of the safety of enoxaparin during the hospitalization period and ease of use of new oral anticoagulant drugs during the outpatient period Objective To examine the duration and magnitude of increased risk of venous thromboembolism after different types of surgery . Design Prospect i ve cohort study ( Million Women Study ) . Setting Question naire data from the Million Women Study linked with hospital admission and death records . Participants 947 454 middle aged women in the United Kingdom recruited in 1996 - 2001 and followed by record linkage to routinely collected NHS data on hospital admissions and deaths . During follow-up 239 614 admissions were for surgery ; 5419 women were admitted , and a further 270 died , from venous thromboembolism . Main outcome measures Adjusted relative risks and st and ardised incidence rates for hospital admission or death from venous thromboembolism ( pulmonary embolism or deep vein thrombosis ) , by time since and type of surgery . Results Compared with not having surgery , women were 70 times more likely to be admitted with venous thromboembolism in the first six weeks after an inpatient operation ( relative risk 69.1 , 95 % confidence interval 63.1 to 75.6 ) and 10 times more likely after a day case operation ( 9.6 , 8.0 to 11.5 ) . The risks were lower but still substantially increased 7 - 12 weeks after surgery ( 19.6 , 16.6 to 23.1 and 5.5 , 4.3 to 7.0 , respectively ) . This pattern of risk was similar for pulmonary embolism ( n=2487 ) and deep venous thrombosis ( n=3529 ) . The postoperative risks of venous thromboembolism varied considerably by surgery type , with highest relative risks after inpatient surgery for hip or knee replacement and for cancer—1 - 6 weeks after surgery the relative risks were , respectively , 220.6 ( 187.8 to 259.2 ) and 91.6 ( 73.9 to 113.4 ) . Conclusion The risk of deep vein thrombosis and pulmonary embolism after surgery is substantially increased in the first 12 postoperative weeks , and varies considerably by type of surgery . An estimated 1 in 140 middle aged women undergoing inpatient surgery in the UK will be admitted with venous thromboembolism during the 12 weeks after surgery ( 1 in 45 after hip or knee replacement and 1 in 85 after surgery for cancer ) , compared with 1 in 815 after day case surgery and only 1 in 6200 women during a 12 week period without surgery BACKGROUND This phase 3 trial compared the efficacy and safety of rivaroxaban , an oral direct inhibitor of factor Xa , with those of enoxaparin for extended thromboprophylaxis in patients undergoing total hip arthroplasty . METHODS In this r and omized , double-blind study , we assigned 4541 patients to receive either 10 mg of oral rivaroxaban once daily , beginning after surgery , or 40 mg of enoxaparin subcutaneously once daily , beginning the evening before surgery , plus a placebo tablet or injection . The primary efficacy outcome was the composite of deep-vein thrombosis ( either symptomatic or detected by bilateral venography if the patient was asymptomatic ) , nonfatal pulmonary embolism , or death from any cause at 36 days ( range , 30 to 42 ) . The main secondary efficacy outcome was major venous thromboembolism ( proximal deep-vein thrombosis , nonfatal pulmonary embolism , or death from venous thromboembolism ) . The primary safety outcome was major bleeding . RESULTS A total of 3153 patients were included in the superiority analysis ( after 1388 exclusions ) , and 4433 were included in the safety analysis ( after 108 exclusions ) . The primary efficacy outcome occurred in 18 of 1595 patients ( 1.1 % ) in the rivaroxaban group and in 58 of 1558 patients ( 3.7 % ) in the enoxaparin group ( absolute risk reduction , 2.6 % ; 95 % confidence interval [ CI ] , 1.5 to 3.7 ; P<0.001 ) . Major venous thromboembolism occurred in 4 of 1686 patients ( 0.2 % ) in the rivaroxaban group and in 33 of 1678 patients ( 2.0 % ) in the enoxaparin group ( absolute risk reduction , 1.7 % ; 95 % CI , 1.0 to 2.5 ; P<0.001 ) . Major bleeding occurred in 6 of 2209 patients ( 0.3 % ) in the rivaroxaban group and in 2 of 2224 patients ( 0.1 % ) in the enoxaparin group ( P=0.18 ) . CONCLUSIONS A once-daily , 10-mg oral dose of rivaroxaban was significantly more effective for extended thromboprophylaxis than a once-daily , 40-mg subcutaneous dose of enoxaparin in patients undergoing elective total hip arthroplasty . The two drugs had similar safety profiles . ( Clinical Trials.gov number , NCT00329628 . BACKGROUND The 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 Rivaroxaban demonstrated superior efficacy and a similar safety profile to enoxaparin for the prevention of venous thromboembolism in the phase III RECORD programme in patients undergoing elective hip or knee replacement surgery . The XAMOS study investigated adverse events , including bleeding and thromboembolic events , in patients receiving rivaroxaban for thromboprophylaxis in routine clinical practice . XAMOS was a non-interventional , open-label cohort study in patients undergoing major orthopaedic surgery of the hip or knee ( predominantly elective arthroplasty ) , in which rivaroxaban was compared with other pharmacological thromboprophylaxis . All adverse events were documented , including symptomatic thromboembolic and bleeding events . Crude and adjusted incidences based on propensity score subclasses were calculated and compared between the rivaroxaban and st and ard-of-care groups . A total of 17,701 patients were enrolled from 252 centres in 37 countries . Crude incidences of symptomatic thromboembolic events three months after surgery in the safety population were 0.89 % in the rivaroxaban group ( n=8,778 ) and 1.35 % in the st and ard-of-care group ( n=8,635 ; odds ratio [ OR ] 0.65 ; 95 % confidence interval [ CI ] 0.49 - 0.87 ) , and 0.91 % and 1.31 % ( weighted ) in the propensity score-adjusted analysis ( OR 0.69 ; 95 % CI 0.56 - 0.85 ) , respectively . Treatment-emergent major bleeding events ( as defined in the RECORD studies ) occurred in 0.40 % and 0.34 % of patients in the rivaroxaban and st and ard-of-care groups in the safety population ( OR 1.19 ; 95 % CI 0.73 - 1.95 ) , and in 0.44 % versus 0.33 % ( weighted ) in the propensity score-adjusted analysis ( OR 1.35 ; 95 % CI 0.94 - 1.93 ) , respectively . This study in unselected patients confirmed the favourable benefit-risk profile of rivaroxaban seen in the RECORD programme |
891 | 21,392,207 | Sub-group analyses indicated that prostate cancer-specific mortality was not affected by age at which participants were screened .
•Harms of screening included high rates of false-positive results for the PSA test , over-diagnosis and adverse events associated with transrectal ultrasonography guided biopsies such as infection , bleeding and pain .
•Any benefits from prostate cancer screening may take > 10 years to accrue ; therefore , men who have a life expectancy of < 10 - 15 years should be informed that screening for prostate cancer is not beneficial and has harms | OBJECTIVE •To determine whether screening for prostate cancer reduces prostate cancer-specific mortality , impact on all-cause mortality and patient health-related quality of life . | The objectives of the Prostate , Lung , Colorectal and Ovarian Cancer Screening Trial are to determine in screenees ages 55 - 74 at entry whether screening with flexible sigmoidoscopy ( 60-cm sigmoidoscope ) can reduce mortality from colorectal cancer , whether screening with chest X-ray can reduce mortality from lung cancer , whether screening men with digital rectal examination ( DRE ) plus serum prostate-specific antigen ( PSA ) can reduce mortality from prostate cancer , and whether screening women with CA125 and transvaginal ultrasound ( TVU ) can reduce mortality from ovarian cancer . Secondary objectives are to assess screening variables other than mortality for each of the interventions including sensitivity , specificity , and positive predictive value ; to assess incidence , stage , and survival of cancer cases ; and to investigate biologic and /or prognostic characterizations of tumor tissue and biochemical products as intermediate endpoints . The design is a multicenter , two-armed , r and omized trial with 37,000 females and 37,000 males in each of the two arms . In the intervention arm , the PSA and CA125 tests are performed at entry , then annually for 5 years . The DRE , TVU , and chest X-ray exams are performed at entry and then annually for 3 years . Sigmoidoscopy is performed at entry and then at the 5-year point . Participants in the control arm follow their usual medical care practice s. Participants will be followed for at least 13 years from r and omization to ascertain all cancers of the prostate , lung , colorectum , and ovary , as well as deaths from all causes . A pilot phase was undertaken to assess the r and omization , screening , and data collection procedures of the trial and to estimate design parameters such as compliance and contamination levels . This paper describes eligibility , consent , and other design features of the trial , r and omization and screening procedures , and an outline of the follow-up procedures . Sample -size calculations are reported , and a data analysis plan is presented BACKGROUND Prostate cancer is one of the leading causes of death from malignant disease among men in the developed world . One strategy to decrease the risk of death from this disease is screening with prostate-specific antigen ( PSA ) ; however , the extent of benefit and harm with such screening is under continuous debate . METHODS In December , 1994 , 20,000 men born between 1930 and 1944 , r and omly sample d from the population register , were r and omised by computer in a 1:1 ratio to either a screening group invited for PSA testing every 2 years ( n=10,000 ) or to a control group not invited ( n=10,000 ) . Men in the screening group were invited up to the upper age limit ( median 69 , range 67 - 71 years ) and only men with raised PSA concentrations were offered additional tests such as digital rectal examination and prostate biopsies . The primary endpoint was prostate-cancer specific mortality , analysed according to the intention-to-screen principle . The study is ongoing , with men who have not reached the upper age limit invited for PSA testing . This is the first planned report on cumulative prostate-cancer incidence and mortality calculated up to Dec 31 , 2008 . This study is registered as an International St and ard R and omised Controlled Trial IS RCT N54449243 . FINDINGS In each group , 48 men were excluded from the analysis because of death or emigration before the r and omisation date , or prevalent prostate cancer . In men r and omised to screening , 7578 ( 76 % ) of 9952 attended at least once . During a median follow-up of 14 years , 1138 men in the screening group and 718 in the control group were diagnosed with prostate cancer , result ing in a cumulative prostate-cancer incidence of 12.7 % in the screening group and 8.2 % in the control group ( hazard ratio 1.64 ; 95 % CI 1.50 - 1.80 ; p<0.0001 ) . The absolute cumulative risk reduction of death from prostate cancer at 14 years was 0.40 % ( 95 % CI 0.17 - 0.64 ) , from 0.90 % in the control group to 0.50 % in the screening group . The rate ratio for death from prostate cancer was 0.56 ( 95 % CI 0.39 - 0.82 ; p=0.002 ) in the screening compared with the control group . The rate ratio of death from prostate cancer for attendees compared with the control group was 0.44 ( 95 % CI 0.28 - 0.68 ; p=0.0002 ) . Overall , 293 ( 95 % CI 177 - 799 ) men needed to be invited for screening and 12 to be diagnosed to prevent one prostate cancer death . INTERPRETATION This study shows that prostate cancer mortality was reduced almost by half over 14 years . However , the risk of over-diagnosis is substantial and the number needed to treat is at least as high as in breast-cancer screening programmes . The benefit of prostate-cancer screening compares favourably to other cancer screening programs . FUNDING The Swedish Cancer Society , the Swedish Research Council , and the National Cancer Institute BACKGROUND The effect of screening with prostate-specific-antigen ( PSA ) testing and digital rectal examination on the rate of death from prostate cancer is unknown . This is the first report from the Prostate , Lung , Colorectal , and Ovarian ( PLCO ) Cancer Screening Trial on prostate-cancer mortality . METHODS From 1993 through 2001 , we r and omly assigned 76,693 men at 10 U.S. study centers to receive either annual screening ( 38,343 subjects ) or usual care as the control ( 38,350 subjects ) . Men in the screening group were offered annual PSA testing for 6 years and digital rectal examination for 4 years . The subjects and health care providers received the results and decided on the type of follow-up evaluation . Usual care sometimes included screening , as some organizations have recommended . The numbers of all cancers and deaths and causes of death were ascertained . RESULTS In the screening group , rates of compliance were 85 % for PSA testing and 86 % for digital rectal examination . Rates of screening in the control group increased from 40 % in the first year to 52 % in the sixth year for PSA testing and ranged from 41 to 46 % for digital rectal examination . After 7 years of follow-up , the incidence of prostate cancer per 10,000 person-years was 116 ( 2820 cancers ) in the screening group and 95 ( 2322 cancers ) in the control group ( rate ratio , 1.22 ; 95 % confidence interval [ CI ] , 1.16 to 1.29 ) . The incidence of death per 10,000 person-years was 2.0 ( 50 deaths ) in the screening group and 1.7 ( 44 deaths ) in the control group ( rate ratio , 1.13 ; 95 % CI , 0.75 to 1.70 ) . The data at 10 years were 67 % complete and consistent with these overall findings . CONCLUSIONS After 7 to 10 years of follow-up , the rate of death from prostate cancer was very low and did not differ significantly between the two study groups . ( Clinical Trials.gov number , NCT00002540 . BACKGROUND Screening for prostate cancer advances the time of diagnosis ( lead time ) and detects cancers that would not have been diagnosed in the absence of screening ( overdetection ) . Both consequences have considerable impact on the net benefits of screening . METHODS We developed simulation models based on results of the Rotterdam section of the European R and omized Study of Screening for Prostate Cancer ( ERSPC ) , which enrolled 42,376 men and in which 1498 cases of prostate cancer were identified , and on baseline prostate cancer incidence and stage distribution data . The models were used to predict mean lead times , overdetection rates , and ranges ( corresponding to approximate 95 % confidence intervals ) associated with different screening programs . RESULTS Mean lead times and rates of overdetection depended on a man 's age at screening . For a single screening test at age 55 , the estimated mean lead time was 12.3 years ( range = 11.6 - 14.1 years ) and the overdetection rate was 27 % ( range = 24%-37 % ) ; at age 75 , the estimates were 6.0 years ( range = 5.8 - 6.3 years ) and 56 % ( range = 53%-61 % ) , respectively . For a screening program with a 4-year screening interval from age 55 to 67 , the estimated mean lead time was 11.2 years ( range = 10.8 - 12.1 years ) , and the overdetection rate was 48 % ( range = 44%-55 % ) . This screening program raised the lifetime risk of a prostate cancer diagnosis from 6.4 % to 10.6 % , a relative increase of 65 % ( range = 56%-87 % ) . In annual screening from age 55 to 67 , the estimated overdetection rate was 50 % ( range = 46%-57 % ) and the lifetime prostate cancer risk was increased by 80 % ( range = 69%-116 % ) . Extending annual or quadrennial screening to the age of 75 would result in at least two cases of overdetection for every clinical ly relevant cancer detected . CONCLUSIONS These model-based lead-time estimates support a prostate cancer screening interval of more than 1 year BACKGROUND In 2008 , we reported that radical prostatectomy , as compared with watchful waiting , reduces the rate of death from prostate cancer . After an additional 3 years of follow-up , we now report estimated 15-year results . METHODS From October 1989 through February 1999 , we r and omly assigned 695 men with early prostate cancer to watchful waiting or radical prostatectomy . Follow-up was complete through December 2009 , with histopathological review of biopsy and radical-prostatectomy specimens and blinded evaluation of causes of death . Relative risks , with 95 % confidence intervals , were estimated with the use of a Cox proportional-hazards model . RESULTS During a median of 12.8 years , 166 of the 347 men in the radical-prostatectomy group and 201 of the 348 in the watchful-waiting group died ( P=0.007 ) . In the case of 55 men assigned to surgery and 81 men assigned to watchful waiting , death was due to prostate cancer . This yielded a cumulative incidence of death from prostate cancer at 15 years of 14.6 % and 20.7 % , respectively ( a difference of 6.1 percentage points ; 95 % confidence interval [ CI ] , 0.2 to 12.0 ) , and a relative risk with surgery of 0.62 ( 95 % CI , 0.44 to 0.87 ; P=0.01 ) . The survival benefit was similar before and after 9 years of follow-up , was observed also among men with low-risk prostate cancer , and was confined to men younger than 65 years of age . The number needed to treat to avert one death was 15 overall and 7 for men younger than 65 years of age . Among men who underwent radical prostatectomy , those with extracapsular tumor growth had a risk of death from prostate cancer that was 7 times that of men without extracapsular tumor growth ( relative risk , 6.9 ; 95 % CI , 2.6 to 18.4 ) . CONCLUSIONS Radical prostatectomy was associated with a reduction in the rate of death from prostate cancer . Men with extracapsular tumor growth may benefit from adjuvant local or systemic treatment . ( Funded by the Swedish Cancer Society and the National Institutes of Health . ) PURPOSE This clinical trial is aim ed at evaluating the impact of prostate cancer screening on cancer-specific mortality . SUBJECTS AND METHODS Forty-six thous and four hundred and eighty-six ( 46,486 ) men aged 45 - 80 years registered in the electoral roll of the Quebec city area were r and omized in 1988 between screening and no screening . Screening included measurement of serum prostatic specific antigen ( PSA ) using 3.0 ng/ml as upper limit of normal and digital rectal examination ( DRE ) at first visit . At follow-up visits , serum PSA only was used . RESULTS Seventy-four ( 74 ) deaths from prostate cancer occurred in the 14,231 unscreened controls while 10 deaths were observed in the screened group of 7,348 men during the first 11 years following r and omization . Median follow-up of screened men was 7.93 years . A Cox proportional hazards model of the age at death from prostate cancer shows a 62 % reduction ( P < 0.002 , Fisher 's exact test ) of cause-specific mortality in the screened men ( P = 0.005 ) . These results are in agreement with the continuous decrease of prostate cancer mortality observed in North America Of 9,026 males aged 50 - 69 years , 1,494 were r and omly selected and invited to participate in a programme including two screenings for carcinoma of the prostate by digital rectal examination performed in 1987 and 1990 . The remaining 7,532 served as a control group . Of the selected persons , 78 % accepted the invitation to the first screening round and 70 % to the second one . Carcinoma of the prostate was suspected in 45 of 1,163 men examined at the first screening round and in 42 of 953 at the second round . Carcinoma was confirmed by fine-needle aspiration biopsy in 13 cases from the first and in 7 from the second round . In the study group , 17.4 carcinomas were diagnosed per 1,000 men and in the control group 8.6 per 1,000 men . The screening cost was 1,640 pounds per detected cancer and 2,343 pounds per detected and potentially cured cancer . Screening for carcinoma of the prostate by digital rectal examination can be organised with a high population acceptance , and at a reasonable cost . The impact of screening on mortality in prostatic cancer remains uncertain PURPOSE The current study was undertaken within the framework of a screening trial to compare the health-related quality -of-life ( HRQOL ) outcomes of two primary treatment modalities for localized prostate cancer : radical prostatectomy and external-beam radiotherapy . PATIENTS AND METHODS We conducted a prospect i ve longitudinal cohort study among 278 patients with early screen-detected ( 59 % ) or clinical ly diagnosed ( 41 % ) prostate cancer using both generic and disease-specific HRQOL measures ( SF-36 , UCLA Prostate Cancer Index [ urinary and bowel modules ] and items relating to sexual functioning ) at three points in time : t1 ( baseline ) , t2 ( 6 months later ) , and t3 ( 12 months after t1 ) . RESULTS Question naires were completed by 88 % to 93 % of all initially enrolled patients . Patients referred for primary radiotherapy were significantly older than prostatectomy patients ( 63 v 68 years , P < .01 ) . Analyses ( adjusted for age and pretreatment level of functioning ) revealed poorer levels of generic HRQOL after radiotherapy . Prostatectomy patients reported significantly higher ( P < .01 ) posttreatment incidences of urinary incontinence ( 39 % to 49 % ) and erectile dysfunction ( 80 % to 91 % ) than radiotherapy patients ( respectively , 6 % to 7 % and 41 % to 55 % ) . Bowel problems ( urgency ) affected 30 % to 35 % of the radiotherapy group versus 6 % to 7 % of the prostatectomy group ( P < .01 ) . Patients with screen-detected and clinical ly diagnosed cancer reported similar posttreatment HRQOL . CONCLUSION Prostatectomy and radiotherapy differed in the type of HRQOL impairment . Because the HRQOL effects may be valued differently at the individual level , patients should be made fully aware of the potential benefits and adverse consequences of therapies for early prostate cancer . Differences in posttreatment HRQOL were not related to the method of cancer detection BACKGROUND Quality -of-life outcomes are important in the choice of treatment strategy for men with localized prostate cancer . OBJECTIVE To evaluate how follow-up time , number of physical symptoms , and presence of and rogen deprivation affected quality of life among men r and omized to radical prostatectomy or watchful waiting . DESIGN , SETTING , AND PARTICIPANTS The study group was composed of all 376 living men included in the Swedish part of the Sc and inavian Prostate Cancer Group Study Number 4 ( SPCG-4 ) between January 1 , 1989 , and February 29 , 1996 . Quality -of-life data were collected after a mean follow-up time of 4.1 yr . INTERVENTION All patients were r and omly assigned to radical prostatectomy or watchful waiting . Forty-five men were and rogen deprived . MEASUREMENTS Data of specific symptoms , symptom-induced stress , sense of well-being , and self-assessed quality of life were obtained by means of a question naire . Psychological symptoms were assessed using seven-point visual digital scales . RESULTS AND LIMITATIONS In analyses stratified on the basis of the numbers of physical symptoms , anxiety and depressed mood were less common , and sense of well-being and self-assessed quality of life were better throughout in the radical prostatectomy group than in the watchful waiting group . As the number of physical symptoms increased , all psychological variables became worse and more prominent in the watchful waiting group . After a follow-up time of 6 - 8 yr , a significant decrease in quality of life ( p=0.03 ) was seen in the watchful waiting group . Twenty-four percent of and rogen-deprived patients assigned to watchful waiting reported high self-assessed quality of life compared with 60 % in the radical prostatectomy group . Eighty-eight percent of patients had clinical ly detected tumors . CONCLUSIONS And rogen deprivation negatively affected self-assessed quality of life in men assigned to watchful waiting . The number of physical symptoms was associated with the level of quality of life . Quality of life was lower with longer follow-up time in both groups and was statistically significant in the watchful waiting group ( p=0.03 ) BACKGROUND The benefit of radical prostatectomy in patients with early prostate cancer has been assessed in only one r and omized trial . In 2005 , we reported that radical prostatectomy improved prostate cancer survival compared with watchful waiting after a median of 8.2 years of follow-up . We now report results after 3 more years of follow-up . METHODS From October 1 , 1989 , through February 28 , 1999 , 695 men with clinical ly localized prostate cancer were r and omly assigned to radical prostatectomy ( n = 347 ) or watchful waiting ( n = 348 ) . Follow-up was complete through December 31 , 2006 , with histopathologic review and blinded evaluation of causes of death . Relative risks ( RRs ) were estimated using the Cox proportional hazards model . Statistical tests were two-sided . RESULTS During a median of 10.8 years of follow-up ( range = 3 weeks to 17.2 years ) , 137 men in the surgery group and 156 in the watchful waiting group died ( P = .09 ) . For 47 of the 347 men ( 13.5 % ) who were r and omly assigned to surgery and 68 of the 348 men ( 19.5 % ) who were not , death was due to prostate cancer . The difference in cumulative incidence of death due to prostate cancer remained stable after about 10 years of follow-up . At 12 years , 12.5 % of the surgery group and 17.9 % of the watchful waiting group had died of prostate cancer ( difference = 5.4 % , 95 % confidence interval [ CI ] = 0.2 to 11.1 % ) , for a relative risk of 0.65 ( 95 % CI = 0.45 to 0.94 ; P = .03 ) . The difference in cumulative incidence of distant metastases did not increase beyond 10 years of follow-up . At 12 years , 19.3 % of men in the surgery group and 26 % of men in the watchful waiting group had been diagnosed with distant metastases ( difference = 6.7 % , 95 % CI = 0.2 to 13.2 % ) , for a relative risk of 0.65 ( 95 % CI = 0.47 to 0.88 ; P = .006 ) . Among men who underwent radical prostatectomy , those with extracapsular tumor growth had 14 times the risk of prostate cancer death as those without it ( RR = 14.2 , 95 % CI = 3.3 to 61.8 ; P < .001 ) . CONCLUSION Radical prostatectomy reduces prostate cancer mortality and risk of metastases with little or no further increase in benefit 10 or more years after surgery OBJECTIVE To test the feasibility of a population -based prostate cancer screening programme in general practice and explore the outcome after a 15-year follow-up period . METHODS From the total population of men aged 50 - 69 years in Norrköping ( n = 9026 ) every sixth man ( n = 1494 ) was r and omly selected to be screened for prostate cancer every third year over a 12-year period . The remaining 7532 men were treated as controls . In 1987 and 1990 only digital rectal examination ( DRE ) was performed , in 1993 and 1996 DRE was combined with a test for Prostate-Specific Antigen ( PSA ) . TNM categories , grade of malignancy , management and cause of death were recorded in the South-East Region Prostate Cancer Register . RESULTS There were 85 ( 5.7 % ) cancers detected in the screened group ( SG ) , 42 of these in the interval between screenings , and 292 ( 3.8 % ) in the unscreened group ( UG ) . In the SG 48 ( 56.5 % ) of the tumours and in the UG 78 ( 26.7 % ) were localised at diagnosis ( p < 0.001 ) . In the SG 21 ( 25 % ) and in the UG 41 ( 14 % ) received curative treatment . There was no significant difference in total or prostate cancer-specific survival between the groups . CONCLUSIONS Although PSA had not been introduced in the clinical practice at the start of the study , we were still able to show that it is possible to perform a long-term population -based r and omised controlled study with st and ardised management and that screening in general practice is an efficient way of detecting prostate cancer whilst it is localised . Complete data on stage , treatment and mortality for both groups was obtained from a vali date d cancer register , which is a fundamental prerequisite when assessing screening programmes PURPOSE We evaluated long-term survival in attendees and nonattendees of a 1-time screening for prostate cancer . MATERIAL S AND METHODS A total of 2,400 men 55 to 70 years old in 1988 were r and omly selected and invited to a screening for prostate cancer . Of the invited men 1,782 ( 74 % ) attended . Screening attendees were examined with digital rectal examination , transrectal ultrasound and prostate specific antigen analysis . When cancer was suspected , prostate biopsies were taken . A total of 65 men with prostate cancer were detected by this procedure . The entire source population comprising 27,204 men , including 618 nonattendees ( 26 % ) , was followed for prostate cancer diagnosis and survival for 15 years . RESULTS Incidence rate ratios were calculated using Poisson regression models . We found no effect of this screening procedure on the risk of death from prostate cancer and other causes of death ( incidence rate ratio 1.10 , 95 % CI 0.83 - 1.46 and 0.98 , 95 % CI 0.92 - 1.05 , respectively ) when comparing all invited men with the source population . However , attending the screening program was associated with a significantly decreased risk of death from causes other than prostate cancer ( vs source population incidence rate ratio 0.82 , 95 % CI 0.76 - 0.90 ) . In contrast , the corresponding incidence rate ratio in nonattendees was 1.53 ( 95 % CI 1.37 - 1.71 ) . CONCLUSIONS We found no evidence of a beneficial effect of this specific screening procedure but strong evidence of a difference in overall survival in screening attendees and nonattendees . These findings should be considered when interpreting previous and upcoming studies of the effect of screening programs Five r and omized pilot studies of screening for prostate cancer ( PC ) have been conducted in the area of Rotterdam from 1991 to 1994 . The purpose of these studies was to establish the feasibility of a r and omized screening protocol with PC mortality as the major end point in The Netherl and s and at a European level . All procedures related to recruitment of participants , to application of the screening tests and to data collection were evaluated . Men ( 7,200 ) aged 55 - 74 years were invited through the Rotterdam Population Registry . The recruitment rate over the 5 pilot studies averaged 38.2 % ( 2,747 men ) . Recruitment procedures proved to be relevant for establishing higher participation rates ( invitation and consent by mail ) . The screening tests were well accepted and tolerated . The general population -based character of the sample was confirmed by study ing symptoms of prostatic disease in participants and in men who refused participation . Data based on one PSA serum determination , rectal examination and transrectal ultrasonography are presented ; 204/1,403 men ( 14.5 % ) had a positive screening result by either test combination and underwent biopsy . Forty-nine cancers were found in 1,403 men ( 3.5 % ) ; 65 % of prostate cancers ( 17/26 ) identified in men who eventually underwent radical prostatectomy proved to be locally confined . From the pilot studies , we conclude that a large contribution to a European R and omized Study of Screening for Prostate Cancer ( ERSPC ) can be made by recruiting about 40,000 men in the area of Rotterdam . The preliminary data suggest that after confirmation of the present data during the first years in the European study , DRE and TRUS can be withheld depending on the PSA result in a large proportion of the screening population |
892 | 31,354,538 | Results : Collectively , the literature and original data showed that : 1 ) raised serum levels of pro-inflammatory compounds ( in particular of CRP/IL-6 ) characterize an inflammatory form of MDD with poor responsiveness to predominately serotonergic agents , but a better responsiveness to antidepressant regimens with a ) ( add-on ) noradrenergic , dopaminergic , or glutamatergic action or b ) ( add-on ) anti-inflammatory agents such as infliximab , minocycline , or eicosapentaenoic acid , showing — next to anti-inflammatory — dopaminergic or lipid corrective action ; 2 ) these successful anti-inflammatory ( add-on ) agents , when used in patients with low serum levels of CRP/IL-6 , decreased response rates in comparison to placebo .
Add-on aspirin , in contrast , improved responsiveness in such “ non-inflammatory ” patients ; 3 ) patients with increased inflammatory gene expression in circulating leukocytes had a poor responsiveness to serotonergic/noradrenergic agents .
However , at present , insufficient data exist to design protocol s with reliable inflammation parameter cutoff points to guide such therapies , the more since detrimental outcomes are possible of anti-inflammatory agents in “ non-inflamed ” patients | Low- grade inflammation plays a role not only in the pathogenesis of major depressive disorder ( MDD ) but probably also in the poor responsiveness to regular antidepressants .
There are also indications that anti-inflammatory agents improve the outcomes of antidepressants .
Aim : To study whether the presence of low- grade inflammation predicts the outcome of antidepressants , anti-inflammatory agents , or combinations thereof . | OBJECTIVE This study aim ed to explore effects of adjunctive N-acetylcysteine ( NAC ) treatment on inflammatory and neurogenesis markers in unipolar depression . METHODS We embarked on a 12-week clinical trial of NAC ( 2000 mg/day compared with placebo ) as an adjunctive treatment for unipolar depression . A follow-up visit was conducted 4 weeks following the completion of treatment . We collected serum sample s at baseline and the end of the treatment phase ( week 12 ) to determine changes in interleukin-6 ( IL6 ) , C-reactive protein ( CRP ) and brain-derived neurotrophic factor ( BDNF ) following NAC treatment . RESULTS NAC treatment significantly improved depressive symptoms on the Montgomery-Asberg Depression Rating Scale ( MADRS ) over 16 weeks of the trial . Serum levels of IL6 were associated with reductions of MADRS scores independent of treatment response . However , we found no significant changes in IL6 , CRP and BDNF levels following NAC treatment . CONCLUSION Overall , this suggests that our results failed to support the hypothesis that IL6 , CRP and BDNF are directly involved in the therapeutic mechanism of NAC in depression . IL6 may be a useful marker for future exploration of treatment response Given evidence of chronic inflammation in bipolar disorder ( BD ) , we tested the efficacy of aspirin and minocycline as augmentation therapy for bipolar depression . Ninety-nine depressed out patients with BD were enrolled in a 6 week , double-blind , placebo-controlled trial , and r and omized to one of four groups : active minocycline ( 100 mg b.i.d . ) + active aspirin ( 81 mg b.i.d . ) ( M + A ) ; active minocycline + placebo aspirin ( M + P ) ; placebo-minocycline + active aspirin ( A + P ) ; and placebo-minocycline + placebo aspirin ( P + P ) . A blinded interim analysis mid-way through the study led to the dropping of the M + P and A + P arms from further enrollment giving numbers per group who were included in the final analysis of : 30 ( M + A ) , 18 ( M + P ) , 19 ( A + P ) , and 28 ( P + P ) . When the study started , there were three primary outcome measures . Based on the results of the interim analysis , the primary outcome variable , response to treatment as defined by > 50 % decrease in Montgomery – Äsberg Depression Rating Scale ( MADRS ) score was maintained . The other two ( i.e. , the change in mean MADRS score from baseline to end of study and the remission rate , with remission being defined as a score of < 11 on the MADRS ) were reduced to exploratory outcome measures because the interim analysis indicated that the study was adequately powered to test differences in response rate but not the mean change in MADRS scores or remission rates . CRP and IL-6 were assayed to measure inflammation . Urinary thromboxane B2 ( 11-D-TXB2 ) concentrations , which were significantly increased at baseline in the combined BD sample ( n = 90 ) vs. a healthy control group ( n = 27 ) , served as an indirect marker of cyclooxygenase ( COX ) activity . In a two-group analysis , the M + A group showed a greater response rate than the P + P group ( p(one-tailed ) = 0.034 , OR = 2.93 , NNT = 4.7 ) . When all four arms were included in the analysis , there was a main effect of aspirin on treatment response that was driven by both the M + A and the A + P groups ( p(two-tailed ) = 0.019 , OR = 3.67 , NNT = 4.0 ) . Additionally , there was a significant 3-way interaction between aspirin , minocycline , and IL-6 , indicating that response to minocycline was significantly greater in participants in the M + P group with higher IL-6 concentrations . Further , participants in the M + P group who responded to treatment had significantly greater decreases in IL-6 levels between baseline and visit 7 vs. non-responders . Regarding the exploratory outcomes , there was a main effect for aspirin on the remission rate ( χ12 = 4.14 , p(2 t ) = 0.04 , OR = 2.52 , NNT = 8.0 ) . There was no significant main effect of aspirin or minocycline on the mean change in MADRS score across visits . Aspirin and minocycline may be efficacious adjunctive treatments for bipolar depression . Given their potential import , additional studies to confirm and extend these findings are warranted Background : Evidence suggests that anti-inflammatory medication may be effective in the treatment of depressive symptoms . In this study , we aim ed to investigate whether minocycline added to treatment as usual ( TAU ) for 3 months in patients with treatment-resistant depression will lead to an improvement in depressive symptoms . Methods : Multi-site , 12-week , double-blind , placebo-controlled , pilot trial of minocycline added to TAU for patients suffering from DSM-5 major depressive disorder , whose current episode has failed to respond to at least two antidepressants . The primary outcome measure was mean change in Hamilton Depression Rating Scale ( HAMD-17 ) scores from baseline to week 12 . Secondary measures were the Clinical Global Impression scale ( CGI ) , Patient Health Question naire-9 ( PHQ-9 ) , the Generalised Anxiety Disorder scale ( GAD-7 ) and EuroQoL ( EQ-5D ) quality -of-life question naire . Side-effect checklists were also used . Minocycline was started at 100 mg once daily ( OD ) and increased to 200 mg after 2 weeks . Results : A total of 41 participants were r and omised , with 21 in the minocycline group and 20 in the placebo group . A large decrease in HAMD scores was observed in the minocycline group compared to the placebo group ( st and ardised effect size ( ES ) –1.21 , p < 0.001 ) . CGI scores in the minocycline group also showed a large improvement compared with placebo ( odds ratio ( OR ) : 17.6 , p < 0.001 ) . PHQ-9 , GAD-7 and EQ-5D total showed more moderate improvements ( ES ~ 0.4–0.5 ) . Conclusion : The findings indicate that adjunctive minocycline leads to improvement in symptoms of treatment-resistant depression . However , our findings require replication in a larger sample . Trial Registration : Clinical Trials.gov identifier : NCT02263872 , registered October 2014 There is increasing evidence that both immune and neurochemical alterations are involved in the pathogenesis of bipolar disorder ; however , their precise role remains unclear . In this study , we aim ed to evaluate neuro‐immune changes in a prospect i ve study on children of patients with bipolar disorder Major depressive disorder ( MDD ) in general , and anxious-depression in particular , are characterized by poor rates of remission with first-line treatments , contributing to the chronic illness burden suffered by many patients . Prospect i ve research is needed to identify the biomarkers predicting nonremission prior to treatment initiation . We collected blood sample s from a discovery cohort of 34 adult MDD patients with co-occurring anxiety and 33 matched , nondepressed controls at baseline and after 12 weeks ( of citalopram plus psychotherapy treatment for the depressed cohort ) . Sample s were processed on gene arrays and group differences in gene expression were investigated . Exploratory analyses suggest that at pretreatment baseline , nonremitting patients differ from controls with gene function and transcription factor analyses potentially related to elevated inflammation and immune activation . In a second phase , we applied an unbiased machine learning prediction model and corrected for model- selection bias . Results show that baseline gene expression predicted nonremission with 79.4 % corrected accuracy with a 13-gene model . The same gene-only model predicted nonremission after 8 weeks of citalopram treatment with 76 % corrected accuracy in an independent validation cohort of 63 MDD patients treated with citalopram at another institution . Together , these results demonstrate the potential , but also the limitations , of baseline peripheral blood-based gene expression to predict nonremission after citalopram treatment . These results not only support their use in future prediction tools but also suggest that increased accuracy may be obtained with the inclusion of additional predictors ( eg , genetics and clinical scales ) OBJECTIVE Major depressive disorder has been linked with inflammatory processes , but it is unclear whether individual differences in levels of inflammatory biomarkers could help match patients to treatments that are most likely to be beneficial . The authors tested the hypothesis that C-reactive protein ( CRP ) , a commonly available marker of systemic inflammation , predicts differential response to escitalopram ( a serotonin reuptake inhibitor ) and nortriptyline ( a norepinephrine reuptake inhibitor ) . METHOD The hypothesis was tested in the Genome-Based Therapeutic Drugs for Depression ( GENDEP ) study , a multicenter open-label r and omized clinical trial . CRP was measured with a high-sensitivity method in serum sample s from 241 adult men and women with major depressive disorder r and omly allocated to 12-week treatment with escitalopram ( N=115 ) or nortriptyline ( N=126 ) . The primary outcome measure was the score on the Montgomery-Åsberg Depression Rating Scale ( MADRS ) , administered weekly . RESULTS CRP level at baseline differentially predicted treatment outcome with the two antidepressants ( CRP-drug interaction : β=3.27 , 95 % CI=1.65 , 4.89 ) . For patients with low levels of CRP ( < 1 mg/L ) , improvement on the MADRS score was 3 points higher with escitalopram than with nortriptyline . For patients with higher CRP levels , improvement on the MADRS score was 3 points higher with nortriptyline than with escitalopram . CRP and its interaction with medication explained more than 10 % of individual-level variance in treatment outcome . CONCLUSIONS An easily accessible peripheral blood biomarker may contribute to improvement in outcomes of major depressive disorder by personalizing treatment choice Although stress-induced increases in inflammation have been implicated in several major disorders , including cardiovascular disease and depression , the neurocognitive pathways that underlie inflammatory responses to stress remain largely unknown . To examine these processes , we recruited 124 healthy young adult participants to complete a laboratory-based social stressor while markers of inflammatory activity were obtained from oral fluids . A subset of participants ( n = 31 ) later completed an fMRI session in which their neural responses to social rejection were assessed . As predicted , exposure to the laboratory-based social stressor was associated with significant increases in two markers of inflammatory activity , namely a soluble receptor for tumor necrosis factor-α ( sTNFαRII ) and interleukin-6 ( IL-6 ) . In the neuroimaging sub sample , greater increases in sTNFαRII ( but not IL-6 ) were associated with greater activity in the dorsal anterior cingulate cortex and anterior insula , brain regions that have previously been associated with processing rejection-related distress and negative affect . These data thus eluci date a neurocognitive pathway that may be involved in potentiated inflammatory responses to acute social stress . As such , they have implication s for underst and ing how social stressors may promote susceptibility to diseases with an inflammatory component OBJECTIVE To compare the efficacy of plasma level-targeted dose imipramine and high-dose venlafaxine in depressed in patients in a r and omized double-blind study . METHODS The study included 85 patients with a diagnosis of major depressive episode according to the DSM IV criteria and a 17-item Hamilton Rating Scale for Depression ( HAM-D ) score ≥ 17 . Patients were r and omized to imipramine or venlafaxine . The dose of imipramine was adjusted for each patient to a predefined blood level of 200 - 300 ng/ml . The dose of venlafaxine was increased gradually to 300 - 375 mg/day . Efficacy was evaluated after 7 weeks of treatment . RESULTS The mean age of the study group was 54.5 ( range 29 - 82 ) years . There was no significant difference according to the primary outcome criterion of a ≥50 % reduction on the HAM-D score : 17 of 43 ( 39.5 % ) patients on imipramine were responders compared to 21 of 42 ( 50 % ) patients on venlafaxine . When considering remission as outcome criterion ( HAM-D score ≤ 7 ) , 10 of 43 ( 23.3 % ) patients on imipramine were remitters compared to 15 of 42 ( 35.7 % ) patients on venlafaxine ; again , no significant difference . When analysing a sub population of patients without psychotic features , with remission as outcome criterion , a significant difference was found : 5 of 34 ( 14.7 % ) patients on imipramine were remitters compared to 12 of 31 ( 38.7 % ) patients on venlafaxine . CONCLUSIONS The present study used optimal doses in depressed in patients and showed that venlafaxine is at least equal in efficacy to imipramine . The results in the subgroup without psychotic features indicate a possible superiority of venlafaxine Background Research ers turn to citation tracking to find the most influential articles for a particular topic and to see how often their own published papers are cited . For years research ers looking for this type of information had only one re source to consult : the Web of Science from Thomson Scientific . In 2004 two competitors emerged – Scopus from Elsevier and Google Scholar from Google . The research reported here uses citation analysis in an observational study examining these three data bases ; comparing citation counts for articles from two disciplines ( oncology and condensed matter physics ) and two years ( 1993 and 2003 ) to test the hypothesis that the different scholarly publication coverage provided by the three search tools will lead to different citation counts from each . Methods Eleven journal titles with varying impact factors were selected from each discipline ( oncology and condensed matter physics ) using the Journal Citation Reports ( JCR ) . All articles published in the selected titles were retrieved for the years 1993 and 2003 , and a stratified r and om sample of articles was chosen , result ing in four sets of articles . During the week of November 7–12 , 2005 , the citation counts for each research article were extracted from the three sources . The actual citing references for a subset of the articles published in 2003 were also gathered from each of the three sources . Results For oncology 1993 Web of Science returned the highest average number of citations , 45.3 . Scopus returned the highest average number of citations ( 8.9 ) for oncology 2003 . Web of Science returned the highest number of citations for condensed matter physics 1993 and 2003 ( 22.5 and 3.9 respectively ) . The data showed a significant difference in the mean citation rates between all pairs of re sources except between Google Scholar and Scopus for condensed matter physics 2003 . For articles published in 2003 Google Scholar returned the largest amount of unique citing material for oncology and Web of Science returned the most for condensed matter physics . Conclusion This study did not identify any one of these three re sources as the answer to all citation tracking needs . Scopus showed strength in providing citing literature for current ( 2003 ) oncology articles , while Web of Science produced more citing material for 2003 and 1993 condensed matter physics , and 1993 oncology articles . All three tools returned some unique material . Our data indicate that the question of which tool provides the most complete set of citing literature may depend on the subject and publication year of a given article Background : Increased levels of inflammation have been associated with a poorer response to antidepressants in several clinical sample s , but these findings have had been limited by low reproducibility of biomarker assays across laboratories , difficulty in predicting response probability on an individual basis , and unclear molecular mechanisms . Methods : Here we measured absolute mRNA values ( a reliable quantitation of number of molecules ) of Macrophage Migration Inhibitory Factor and interleukin-1β in a previously published sample from a r and omized controlled trial comparing escitalopram vs nortriptyline ( GENDEP ) as well as in an independent , naturalistic replication sample . We then used linear discriminant analysis to calculate mRNA values cutoffs that best discriminated between responders and nonresponders after 12 weeks of antidepressants . As Macrophage Migration Inhibitory Factor and interleukin-1β might be involved in different pathways , we constructed a protein-protein interaction network by the Search Tool for the Retrieval of Interacting Genes/Proteins . Results : We identified cutoff values for the absolute mRNA measures that accurately predicted response probability on an individual basis , with positive predictive values and specificity for nonresponders of 100 % in both sample s ( negative predictive value=82 % to 85 % , sensitivity=52 % to 61 % ) . Using network analysis , we identified different clusters of targets for these 2 cytokines , with Macrophage Migration Inhibitory Factor interacting predominantly with pathways involved in neurogenesis , neuroplasticity , and cell proliferation , and interleukin-1β interacting predominantly with pathways involved in the inflammasome complex , oxidative stress , and neurodegeneration . Conclusion : We believe that these data provide a clinical ly suitable approach to the personalization of antidepressant therapy : patients who have absolute mRNA values above the suggested cutoffs could be directed toward earlier access to more assertive antidepressant strategies , including the addition of other antidepressants or antiinflammatory drugs This study explores whether inflammatory biomarkers act as moderators of clinical response to omega-3 ( n-3 ) fatty acids in subjects with major depressive disorder ( MDD ) . One hundred fifty-five subjects with Diagnostic and Statistical Manual of Mental Disorders , 4th Edition ( DSM-IV ) MDD , a baseline 17-item Hamilton Depression Rating Scale ( HAM-D-17 ) score ⩾15 and baseline biomarker data ( interleukin (IL)-1ra , IL-6 , high-sensitivity C-reactive protein ( hs-CRP ) , leptin and adiponectin ) were r and omized between 18 May 2006 and 30 June 2011 to 8 weeks of double-blind treatment with eicosapentaenoic acid (EPA)-enriched n-3 1060 mg day−1 , docosahexaenoic acid (DHA)-enriched n-3 900 mg day−1 or placebo . Outcomes were determined using mixed model repeated measures analysis for ‘ high ’ and ‘ low ’ inflammation groups based on individual and combined biomarkers . Results are presented in terms of st and ardized treatment effect size ( ES ) for change in HAM-D-17 from baseline to treatment week 8 . Although overall treatment group differences were negligible ( ES=−0.13 to + 0.04 ) , subjects with any ‘ high ’ inflammation improved more on EPA than placebo ( ES=−0.39 ) or DHA ( ES=−0.60 ) and less on DHA than placebo ( ES=+0.21 ) ; furthermore , EPA-placebo separation increased with increasing numbers of markers of high inflammation . Subjects r and omized to EPA with ‘ high ’ IL-1ra or hs-CRP or low adiponectin ( ‘ high ’ inflammation ) had medium ES decreases in HAM-D-17 scores vs subjects ‘ low ’ on these biomarkers . Subjects with ‘ high ’ hs-CRP , IL-6 or leptin were less placebo-responsive than subjects with low levels of these biomarkers ( medium to large ES differences ) . Employing multiple markers of inflammation facilitated identification of a more homogeneous cohort of subjects with MDD responding to EPA vs placebo in our cohort . Studies are needed to replicate and extend this proof-of-concept work OBJECTIVE Currently , no valid measures inform treatment selection for depressed patients . Whether C-reactive protein ( CRP ) in particular and two other acute phase reactants ( inflammatory markers ) could differentiate between patients responding to either of two treatments with different mechanisms of action was assessed . METHOD Subjects included Combining Medications to Enhance Depression Outcomes ( CO-MED ) trial participants r and omly assigned to either escitalopram plus placebo ( SSRI monotherapy , n=51 ) or bupropion plus escitalopram combination ( bupropion-SSRI combination , n=55 ) with baseline plasma sample s. CRP , serum amyloid P component , and alpha-2-macroglobulin were measured using the Bioplex Pro ™ human acute-phase 4-plex panel . We conducted mixed model analyses of depressive symptom ( Quick Inventory of Depressive Symptomatology Self-Report ) and side-effect burden ( Frequency , Intensity , and Burden of Side-Effects Rating Scale ) obtained weekly or every other week over the 12-week acute-phase of CO-MED trial to evaluate the relationship between these outcomes and baseline CRP and other acute-phase reactants . RESULTS The treatment arms did not differ in depressive symptom or side effect outcomes . Most participants ( 69.8 % , 74/106 ) had baseline CRP levels greater than 1mg/L ( indicative of systemic inflammatory activity ) . Higher baseline CRP levels were associated lower depression severity ( correlation coefficient=-0.63 ) with bupropion-SSRI combination but not with SSRI monotherapy ( correlation coefficient=0.40 ) . The overall remission rate was 41.5 % . The estimated remission rate with CRP threshold based assignment ( SSRI monotherapy for < 1mg/L and Bupropion-SSRI for ≥1mg/L ) was 53.1 % , with a number needed to treat of 8.6 . Side effect burden was unrelated to any baseline inflammatory marker . CONCLUSIONS Baseline CRP levels relate differentially to antidepressant treatment outcomes in persons with major depressive disorder . Clinical trials.gov identifier : NCT00590863 OBJECTIVE This study aim ed to explore effects of adjunctive treatment with N-acetyl cysteine ( NAC ) on markers of inflammation and neurogenesis in bipolar depression . METHODS This is a secondary analysis of a placebo-controlled r and omised trial . Serum sample s were collected at baseline , week 8 , and week 32 of the open-label and maintenance phases of the clinical trial to determine changes in interleukin (IL)-6 , IL-8 , IL-10 , tumour necrosis factor-α ( TNF-α ) , C-reactive protein ( CRP ) and brain-derived neurotrophic factor ( BDNF ) following adjunctive NAC treatment , and to explore mediation and moderator effects of the listed markers . RESULTS Levels of brain-derived neurotrophic factor ( BDNF ) , tumour necrosis factor-α ( TNF-α ) , C-reactive protein ( CRP ) , interleukins ( IL ) -6 , 8 , or 10 were not significantly changed during the course of the trial or specifically in the open-label and maintenance phases . There were no mediation or moderation effects of the biological factors on the clinical parameters . CONCLUSION The results suggest that these particular biological parameters may not be directly involved in the therapeutic mechanism of action of adjunctive NAC in bipolar depression |
893 | 21,385,300 | 6 Gimeno-Garcı́a AZ , Ramı́rez F , Gonzalo V , Belaguer F , Petit A , Pellisé M , Llach J , Bordas JM , Piqué JM , Castells A. High- grade dysplasia as a risk factor of metachronous advanced neoplasms in patients with advanced adenomas .
Ongoing colorectal cancer risk despite surveillance colonoscopy : the Polyp Prevention Trial Continued Follow-up Study . | 2 Neugut AI , Jacobson JS , Ahsan H , Santos J , Garbowski GC , Forde KA , Treat MR , Waye J. Incidence and recurrence rates of colorectal adenomas : a prospect i ve study .
3 Laiyemo AO , Murphy G , Albert PS et al. Postpolypectomy colonoscopy surveillance guidelines : predictive accuracy for advanced adenoma at 4 years .
8 Saini SD , Kim HM , Schoenfeld P. Incidence of advanced adenomas at surveillance colonoscopy in patients with a personal history of colon adenomas : a meta- analysis and systematic review .
9 Loeve F , van Ballegooijen M , Boer R , Kuipers EJ , Habbema JD .
Colorectal cancer risk in adenoma patients : a nationwide study .
11 Yang G , Zheng W , Sun QR , Shu XO , Li WD , Yu H , Shen GF , Shen YZ , Potter JD , Zheng S. Pathologic features of initial adenomas as predictors for metachronous adenomas of the rectum .
12 Nusko G , Hahn EG , Mansmann U. Risk of advanced metachronous colorectal adenoma during long-term follow up .
13 Rex DK , Goldblum JR , Appelman HD , Odze R. Should HGD or degree of villous change in colon polyps be reported ?
16 Schlemper RJ , Itabashi M , Kato Y , Lewin KJ , Riddell RH , Shimoda T , Sipponen P , Stolte M , Watanabe H. Differences in the diagnostic criteria used by Japanese and Western pathologists to diagnose colorectal carcinoma .
17 Schlemper RJ , Riddell RH , Kato Y et al. The Vienna classification of gastrointestinal epithelial neoplasia .
18 Zauber AG , Winawer SJ .
Initial management and follow-up surveillance of patients with colorectal adenomas .
Colorectal adenoma characteristics as predictors of recurrence . | BACKGROUND / AIMS The frequency of colorectal adenomas , the precursor lesions for most cases of colorectal carcinoma , has been generally measured as prevalence rates of adenomas at autopsy or colonoscopy . The aim of this study was to estimate the incidence rate of adenomas and compare it with the adenoma recurrence rate . METHODS Data on colonoscopies performed in three New York City practice s were collected prospect ively . The cumulative rate of adenoma diagnosis on repeat colonoscopy was calculated for patients with no abnormalities on index colonoscopy ( " incidence " rate ) and for patients with adenomas on the index colonoscopy ( " recurrence " rate ) . RESULTS The cumulative incidence rate of adenomas at 36 months was 16 % , and the cumulative recurrence rate at 36 months was 42 % ( P < 0.004 ) . The recurrence rate was higher in patients with multiple adenomas than in those with a single adenoma on index colonoscopy , although the increase was not statistically significant . CONCLUSIONS Although the recurrence rate has always been assumed to be elevated , this study is the first to compare the recurrence rate of adenomas with the incidence rate directly and to show that the recurrence rate is indeed elevated The National Polyp Study ( NPS ) , a r and omized clinical trial to evaluate effective surveillance of patients discovered to have one or more colorectal adenomas , was the framework for this statistical analysis which used a multiple logistic model to assess the independent risk factors of patient and polyp characteristics associated with high- grade dysplasia in adenomas . The data base included 3371 adenomas from 1867 patients . Adenoma size and the extent of the villous component were found to be the major independent polyp risk factors associated with high- grade dysplasia ( p less than 0.0001 ) . The adjusted odds ratios were 3.3 for medium-sized adenomas and 7.7 for large adenomas relative to small adenomas and 2.7 for villous A adenomas , 3.4 for villous B adenomas , and 8.1 for villous C and D adenomas relative to tubular adenomas . Increased frequency of high- grade dysplasia in adenomas located distal to the splenic flexure was attributable mainly to increased size and villous component rather than to location per se . The adjusted odds ratio was 1.4 ( p less than 0.11 ) for left-sided location . Multiplicity of adenomas affected the risk for high- grade dysplasia in patients but was dependent on adenoma size and villous component and was not an independent factor . The adjusted odds ratio was 1.3 ( p less than 0.17 ) for multiplicity . Increasing age was associated with risk for high- grade dysplasia in patients , and this effect was independent of the effect of adenoma size and histological type . The adjusted odds ratio was 1.8 ( p less than 0.0016 ) for age greater than or equal to 60 yr . Gender was not associated with high- grade dysplasia . The adjusted odds ratio was 1.0 ( p less than 0.95 ) for men . The size of the patient series , the prospect i ve nature of the data collection , the completeness of information on all patients , the requirements of complete examination of the entire colon and pathological examination of all lesions encountered , and the exclusion of patients with previously diagnosed adenomas are , collectively , features unique to this study . The detailed model provided by the analysis integrates multiple patient and adenoma factors associated with high- grade dysplasia in colorectal adenomas BACKGROUND & AIMS Outcomes of colon surveillance after colorectal cancer screening with colonoscopy are uncertain . We conducted a prospect i ve study to measure incidence of advanced neoplasia in patients within 5.5 years of screening colonoscopy . METHODS Three thous and one hundred twenty-one asymptomatic subjects , age 50 to 75 years , had screening colonoscopy between 1994 and 1997 in the Department of Veterans Affairs . One thous and one hundred seventy-one subjects with neoplasia and 501 neoplasia-free controls were assigned to colonoscopic surveillance over 5 years . Cohorts were defined by baseline findings . Relative risks for advanced neoplasia within 5.5 years were calculated . Advanced neoplasia was defined as tubular adenoma greater than > or = 10 mm , adenoma with villous histology , adenoma with high- grade dysplasia , or invasive cancer . RESULTS Eight hundred ninety-five ( 76.4 % ) patients with neoplasia and 298 subjects ( 59.5 % ) without neoplasia at baseline had colonoscopy within 5.5 years ; 2.4 % of patients with no neoplasia had interval advanced neoplasia . The relative risk in patients with baseline neoplasia was 1.92 ( 95 % CI : 0.83 - 4.42 ) with 1 or 2 tubular adenomas < 10 mm , 5.01 ( 95 % CI : 2.10 - 11.96 ) with 3 or more tubular adenomas < 10 mm , 6.40 ( 95 % CI : 2.74 - 14.94 ) with tubular adenoma > or = 10 mm , 6.05 ( 95 % CI : 2.48 - 14.71 ) for villous adenoma , and 6.87 ( 95 % CI : 2.61 - 18.07 ) for adenoma with high- grade dysplasia . CONCLUSIONS There is a strong association between results of baseline screening colonoscopy and rate of serious incident lesions during 5.5 years of surveillance . Patients with 1 or 2 tubular adenomas less than 10 mm represent a low-risk group compared with other patients with colon neoplasia |
894 | 27,328,133 | The clinical studies considered for this review suggest that a two-step impression procedure may not be m and atory for the success of conventional complete denture fabrication regarding a variety of clinical aspects of denture quality and patients ' perceptions of the treatment | The literature has question ed the real need for some clinical and laboratory procedures considered essential for achieving better results for complete denture fabrication .
The aim of this study was to review the current literature concerning the relevance of a two-step impression procedure to achieve better clinical results in fabricating conventional complete dentures . | PURPOSE This study aim ed to quantify the costs of complete denture fabrication by a simplified method compared with a conventional protocol . MATERIAL S AND METHODS A sample of edentulous patients needing conventional maxillary and m and ibular complete dentures was r and omly divided into group S , which received dentures fabricated by a simplified method , and group C , which received conventionally fabricated dentures . We calculated direct and indirect costs for each participant including unscheduled procedures . This study assessed 19 and 20 participants allocated into groups S and C , respectively , and comparisons between groups were conducted by the Mann-Whitney and Student 's t-test ( α = 0.05 ) . RESULTS Complete denture fabrication dem and ed median time periods of 173.2 and 284.5 minutes from the operator for groups S and C respectively , and 46.6 and 61.7 minutes from the dental assistant ( significant differences , p < 0.05 ) . There was no difference between groups regarding postinsertion adjustments . Group S showed lower values for costs with material s and time spent by patients than group C during the fabrication stage , but not during adjustments . CONCLUSIONS The median direct cost of complete denture treatment was 34.9 % lower for the simplified method . It can be concluded that the simplified method is less costly for patients and the health system when compared with a conventional protocol for the rehabilitation of edentulous patients 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 Previous papers in this series on evidence -based dentistry have discussed the first 2 steps in seeking answers to clinical problems formulating a clear question and strategically search ing for evidence . The next step , critical appraisal of the evidence , is made easier if one underst and s the basic concepts of clinical research design . The strongest design , especially for questions related to therapeutic or preventive interventions , is the r and omized , controlled trial . Questions relating to diagnosis , prognosis and causation are often studied with observational , rather than experimental , research design s. The strongest study design should be used whenever possible . Rules have been established to grade research evidence . This paper , the fourth in the series , presents an overview of research methodology most commonly used in the dental literature OBJECTIVES To compare subjective and objective outcomes of complete dentures fabricated with st and ard clinical protocol s , but omitted selected steps during the laboratory phase . MATERIAL S AND METHODS Forty-three edentulous patients ( mean age 58.1 years , SD 9.9 , range 35 - 78 ) , were consecutively recruited and r and omly assigned to one of four groups according to selected variations of laboratory steps : Group 1 ( n=10 ) , omission of secondary casts obtained from impressions in border moulded custom trays ; Group 2 ( n=10 ) , omission of secondary casts and face-bow articulator mounting ; Group 3 ( n=10 ) , omission of face-bow mounting ; Group 4 ( n=13 ) , no steps omitted ( control ) . Clinical procedures for all groups were identical , and performed by senior dental students under supervision of prosthodontists , all of whom were blinded to the Group . At 1- , 4- and 12-weeks after delivery , patients rated their overall satisfaction , as well as a range of functional factors using visual analogue scales . An independent blinded prosthodontist similarly rated four domains of denture quality at the 1-week follow-up . RESULTS No significant differences were noted among the groups in all aspects of patients ' assessment s at all the time points ( P>0.1 ) . There were no significant differences in prosthodontists ' ratings of denture quality in any of the domains examined ( P>0.1 ) . CONCLUSION Selected omissions of steps ( face-bow mounting and /or secondary casts ) during the laboratory phase of complete denture fabrication has only a minor role , if any , in subjective and objective outcomes , contrasting with the common belief that such omissions will adversely affect outcomes . CLINICAL SIGNIFICANCE General practitioners provide most complete dentures . Many do not follow all the procedures they were taught at dental school . Our finding that omitting frequently advocated steps made no difference to patient satisfaction or to denture quality suggests that cost-effectiveness through simplifications be considered in practice and in education OBJECTIVES To compare a simplified method to a conventional protocol for complete denture fabrication regarding masticatory performance and ability . METHODS A sample was formed by edentulous patients requesting treatment with maxillary and m and ibular complete dentures . Participants were r and omly divided into two groups : Group S , which received dentures fabricated by a simplified method , and Group C ( n=21 each ) , which received conventionally fabricated dentures . After three months following insertion , masticatory performance was evaluated by a colorimetric assay based on chewing two capsules as test food during twenty and forty cycles . Masticatory ability was assessed by a question naire with binary answers and a single question answered by means of a 0 - 10 scale . A third group ( DN ) formed by seventeen dentate volunteers served as an external comparator . Groups were compared by statistical tests suitable for data distribution ( α=0.05 ) . RESULTS Thirty-nine participants were assessed for three months ( twenty from Group C and nineteen from Group S ) . Groups C and S presented similar masticatory performance which corresponded to approximately 30 % of Group DN . Results for masticatory ability showed similarity between S and C , regardless of the assessment method , although an isolate question naire item showed more favourable results for the first group . CONCLUSIONS The simplified method for complete denture fabrication is able to restore masticatory function to a level comparable to a conventional protocol , both physiologically and according to patient 's perceptions . CLINICAL SIGNIFICANCE Although masticatory function is impaired by the loss of natural teeth and dentures can restore only a fraction of such function , patients can benefit from a simplified protocol for complete denture fabrication to the same extent they would by conventional techniques PURPOSE Conventional dentures will remain the only treatment available to most edentulous people for the foreseeable future . In this study , we compared the efficiency of two methods of making complete conventional dentures-the traditional academic st and ard ( T ) and a simplified technique ( S ) used in private practice . We have previously shown that they produce similar levels of patient satisfaction and denture quality . MATERIAL S AND METHODS Data were gathered during a r and omized controlled clinical trial of 122 subjects from initial examination until 6-month follow-up . For this report , the direct costs of providing one set of conventional complete dentures by T or S techniques were estimated . All material s used were recorded and their cost was calculated in Canadian dollars ( CAN$ ) . The costs of fabrication in an outside laboratory were added . Clinician 's labor time was recorded for every procedure . Between-group comparisons for each clinical procedure were carried out with independent t-tests . The number of patients in each group who needed postdelivery treatment was compared with Chi-square tests . The effect of group assignment and of treatment difficulty on outcomes was analyzed with multiple regression analysis . RESULTS The mean total cost of the T method was significantly greater than S ( CAN$166.3 ; p < 0.001 ) , and clinicians spent 90 minutes longer ( p < 0.001 ) on clinical care . The difficulty of the case had no significant influence on outcomes . CONCLUSIONS The results indicate that the S method is the more cost-efficient method and that there are no negative consequences that detract from the cost savings OBJECTIVES The objective of this r and omised controlled clinical trial study was to compare the effectiveness of a traditional and a simplified protocol for construction of conventional CD . BACKGROUND The replacement of conventional dentures can result in potential functional and aesthetic benefits to the patient . Previous studies suggest that simplified procedures for complete dentures ( CD ) construction achieve results similar to the traditional methods . MATERIAL S AND METHODS Fifty patients were r and omly divided into two equal groups , traditional protocol ( T group ) and simplified protocol ( S group ) . Treatment outcomes were assessed before the insertion of the new dentures and 30 days and 6 months after the last adjustment . It included measurements of quality of life related to oral conditions measured by the Brazilian version of OHIP-Edentulous scale and patients ' satisfaction with the upper and lower dentures using a visual analogue scale ( VAS ) , which combines the patient 's perception in relation to overall satisfaction with the comfort , stability , ability to chew , ability to talk and aesthetics . RESULTS The results showed significant reduction in negative impacts of oral conditions on quality of life and improved satisfaction with the upper and lower dentures ( p < 0.001 ) at the 30-day and 6-month follow-up . Quality of life improvement occurred in all dimensions of the OHIP-Edentulous ( p < 0.001 ) . Despite the significant reduction in quality of life impacts and significant increase in patients ' satisfaction with the dentures , there were no differences between the traditional and simplified protocol s ( p > 0.05 ) . CONCLUSIONS It was concluded that the simplified protocol results in patent 's perception of treatment outcomes similar to the traditional protocol OBJECTIVES To compare the quality of conventional complete dentures fabricated with two different techniques . A r and omized controlled clinical trial was conducted to compare traditional ( T ) and simplified ( S ) methods of making complete conventional dentures on patients ' ratings of satisfaction , comfort and function at 3 and 6 months following delivery . The quality of the prostheses was rated by prosthodontists at 6 months . MATERIAL S AND METHODS One hundred twenty-two male and female edentulous individuals , aged 45 - 75 years , were r and omly allocated into groups that received dentures made with either T or S methods . Following delivery , patients ' ratings of several denture-related factors were measured using 100 mm visual analogue scales , and denture quality was assessed by blinded prosthodontists using ratings on a vali date d quantitative scale . RESULTS There were no significant differences between the two groups in patient ratings for overall satisfaction ( 3 months : mean T = 83 mm , mean S = 83 mm , P = 0.97 ; 6 months : mean T = 79 mm , mean S = 79 mm , P = 0.96 ) or in prosthodontists ' ratings of denture quality ( T = 66 , S = 63 ; P = 0.38 ) . CONCLUSION These results show that the quality of complete dentures does not suffer when manufacturing techniques are simplified to save time and material s. Dental educators should consider these findings when re- design ing prosthodontic training programs |
895 | 17,692,084 | Laparoscopy is associated with a reduction in the following : febrile morbidity , urinary tract infection , postoperative complications , postoperative pain , days in hospital , and total cost . | To determine the efficacy , safety , and cost of laparoscopic surgery compared with laparotomy in women with ovarian tumors assumed to be benign .
This study is a systematic review . | OBJECTIVE To compare the surgical management and follow-up of patients with endometriomas managed by endoscopic surgery versus laparotomy using a retrospective case control format . DESIGN Endoscopic oophorocystectomies were performed on 36 patients . Chart review of laparotomy oophorocystectomies from 21 patients was conducted . Six-week and 12-month follow-up for evaluation of symptoms , evidence of recurrence , and fertility was available on all subjects . RESULTS In the endoscopy group , 39 patients had screening laparoscopy for possible endoscopic surgery . Three of this group required laparotomy and 36 patients underwent endoscopic surgery . Chart review identified 21 patients who had undergone primary laparotomy for endometriomas . Patient groups were matched for age , severity of disease , presence of other infertility factors , and absence of perioperative medical suppression . Outcome parameters for each group were : operating time -- endoscopy 2.8 hours ( + /- 1.2 ) , laparotomy 3.1 hours ( + /- 1.8 ) ; estimated blood loss -- endoscopy 40 cc ( + /- 45 ) ; laparotomy , 240 cc ( + /- 107 ) ; recovery time -- endoscopy , 6.2 days ( + /- 2.5 ) , laparotomy 30 days ( + /- 6.8 ) ; endometrioma recurrence rate -- endoscopy 11.1 % , laparotomy 19 % ; and pregnancy rate -- endoscopy 42.8 % , laparotomy 46.6 % . CONCLUSION A high percentage of patients with endometriomas associated with advanced endometriosis can be managed effectively by endoscopic surgery OBJECTIVE To evaluate the efficacy of laparoscopic ovarian cystectomy and to compare the surgical course , post-surgical course and particularly post-surgical pain of the laparoscopic and laparotomic methods . STUDY DESIGN We conducted a surgical study on dermoid cysts at the Gynecology Department of Siena University between 1 January 1992 and 31 December 1996 . The selected cases were r and omized into two groups based on surgical approach : via laparotomy ( n=22 ) or laparoscopy ( n=22 ) . Surgical times , estimated blood loss , post-surgical pain , time in hospital , speed of recovery and complications were compared . RESULTS Mean blood loss was significantly less for laparoscopy ( 58.64+/-30.17 ml versus 103.84+/-38.45 ml , P<0.05 ) . Mean hospitalization was 6.32+/-1.09 days for laparotomy and 3.18+/-0.39 days for laparoscopy ( P<0.05 ) . Post-surgical pain was significantly less in laparoscopy patients ( P<0.05 ) . The laparoscopic technique had fewer post-surgical complications . CONCLUSIONS The laparoscopic approach had many advantages . Laparoscopy should be the elective treatment for women with dermoid cysts , because it has many advantages for the patient and lower costs for the national health system OBJECTIVES Our purpose was to evaluate the efficacy of laparoscopic ovarian dermoid cystectomy and to compare the operative course , postoperative course , and complications between the laparoscopy and the laparotomy techniques . STUDY DESIGN The safety and efficacy of laparoscopic ovarian dermoid cystectomy were evaluated in 40 women . Twenty-nine of 40 patients underwent laparoscopic excision of a solitary dermoid cyst without any additional procedure . The operative course , the postoperative course , and complications among these 29 women were compared with those of 26 other women who underwent a similar procedure by laparotomy . RESULTS Spillage of the cyst 's content did not lead to any complication . The operating time in the laparoscopy group was 73.5 + /- 4.7 minutes and in the laparotomy group it was 41.4 + /- 2.9 minutes . The duration of hospitalization was significantly shorter in the laparoscopy group ( 0.7 + /- 0.2 days ) than in the laparotomy group ( 3.8 + /- 0.1 days ) . CONCLUSIONS Although ovarian dermoid cystectomy by laparoscopy is associated with a longer operating time than by laparotomy , the duration of hospitalization is shorter and recovery is faster . Spillage of the contents of the dermoid cyst does not lead to any complication ; perhaps this is due to the liberal irrigation of the peritoneal cavity STUDY OBJECTIVE To compare the outcome of laparoscopic treatment of adnexal masses with treatment by laparotomy . The procedures , their duration , and associated complications also were evaluated . DESIGN Women were r and omized to undergo either procedure based on the ward to which they were admitted . SETTING A university teaching hospital . PATIENTS The 192 patients were admitted with a preoperative diagnosis of adnexal mass . INTERVENTIONS Surgical procedures were cystectomy , salpingectomy , oophorectomy , and unilateral or bilateral salpingo-oophorectomy . Organ-preserving techniques were used wherever possible . All tissue specimens were examined histologically . MEASUREMENTS AND MAIN RESULTS The mean duration of surgery was statistically not significantly different between the groups , 96.8 minutes for minimally invasive surgery , and 116 minutes for laparotomy . Organ preservation did reach statistical significance at 65.7 % and 17.2 % respectively ( p < 0.001 ) . Postoperative morbidity was statistically lower in patients undergoing minimally invasive procedures . Preoperative tumor marker levels did not correlate well with postoperative histology . One woman in the laparotomy group had histologically proved ovarian cancer . Minimally invasive surgery was converted to laparotomy in three patients in whom malignancy was suspected at the start of operation . CONCLUSIONS Laparoscopic management of adnexal masses has definite advantages over laparotomy , for example , lower postoperative morbidity . In addition , intraoperative endoscopic diagnosis is highly accurate , and the frequency of unnecessary procedures is lower OBJECTIVE To analyze clinical results and financial costs of salpingo-oophorectomy performed by laparoscopy versus laparotomy . STUDY DESIGN Comparison of laparoscopic salpingo-oophorectomy with procedures performed by laparotomy . SETTING St. Vincent 's Hospital and Fallon Clinic in Worcester , Massachusetts . PATIENTS Twenty women in both groups . INTERVENTIONS Salpingo-oophorectomies performed by laparoscopy and laparotomy . MEASUREMENTS AND MAIN RESULTS Women undergoing laparotomy had a 25 % rate of postoperative complications compared with 0 % of those having laparoscopy . The duration of the procedures and hospital charges were similar for both groups . Length of hospital stay and time to return to work were significantly less after laparoscopy than laparotomy . CONCLUSIONS Laparoscopic salpingo-oophorectomy was associated with significantly fewer complications than the operations performed by laparotomy . Although women in the laparoscopy group had a shorter hospital stay , their higher charges were attributed to costly disposable instruments . Patients benefit from early return to work and other activities after laparoscopy OBJECTIVE Our purpose was to compare the newer technique of laparoscopic adnexal excision with conventional laparotomy . DESIGN With the same entry criteria , a retrospective , consecutive series of 26 women who underwent adnexectomy by laparotomy was compared with a later prospect i ve consecutive series of 64 women who had laparoscopic adnexectomy in a university referral practice . The two groups were similar in all characteristics examined . The ages of the women ranged from 18 to 70 years , but only two women were postmenopausal . Pelvic pain with or without an ovarian cystic mass was the surgical indication in 91 % to 92 % of the women . Seven women had a persistent adnexal cystic mass and one woman had a unilateral and rogen-secreting ovary . Bipolar coagulation was the laparoscopic method used . RESULTS Median operating time ( 88 vs 107 minutes ) , blood loss ( 72 vs 222 ml ) , days in the hospital ( 1 day vs 3 days ) , total costs ( $ 4573 vs $ 6044 ) , and recovery time ( 1 week vs 4 weeks ) were significantly less with laparoscopic adnexectomy . There were no differences between the two techniques in major complications ( one in each group ) , blood transfusions , adhesion formation , or the proportion of women noting improvement of pain symptoms . CONCLUSION In this preliminary assessment of laparoscopic adnexectomy , this surgical procedure offers significant advantages to laparotomy in selected patients when performed by a laparoscopist experienced in advanced techniques The aim of our study was to compare laparoscopy with laparotomy for the removal of ovarian dermoid cysts . Thirty-eight women with benign ovarian dermoid cyst were allocated for either laparoscopy ( 18 patients ) or laparotomy ( 20 patients ) . The two groups were compared for operative and hospitalization times and postoperative course . Operating time was longer ( 93.6 + /- 23.8 min ) and hospitalization time significantly shorter ( 22.4 + /- 6.6 h ) in the laparoscopy group . No complications were reported in either group . We conclude that operative laparoscopy is a safe procedure for the removal of dermoid ovarian cysts and is as effective as laparotomy OBJECTIVES The aim of the study is to specify the place , modalities and results of operative laparoscopy when adnexectomy is indicated in a patient presenting with an adnexal mass . STUDY DESIGN A retrospective analysis of the 186 patients who underwent adnexectomy for an adnexal mass between January 1 , 1989 and December 31 , 1994 . RESULTS The operation took place via laparotomy in 34.9 % of cases ( 65 patients ) and by laparoscopic surgery in 65.1 % of cases ( 121 patients ) . All the patients presenting a malignant ovarian lesion ( 15 cases ) were operated by laparotomy . For these patients the laparotomy was decided from the outset in 7 cases and there was a conversion to laparotomy decided during the diagnostic phase of laparoscopy in 8 cases . The preoperative workup ( clinical examination , study of past history , trans vaginal ultrasonography , doppler , tumoral markers etc . ) together with the diagnostic phase of laparoscopy provide 100 % sensitivity , a positive predictive value of 50 % and a negative predictive value of 100 % for diagnosis of malignancy . CONCLUSION These results demonstrate that provided a strict selection system is used , it is possible to carry out adnexectomy using laparoscopic surgery in 70.8 % of cases ( 121/171 ) for patients with benign adnexal mass OBJECTIVE Our purpose was to compare the results of laparoscopy with laparotomy in the management of ovarian masses not suspected to be malignant . STUDY DESIGN In a prospect i ve r and omized study 102 patients requiring surgical management of ovarian masses were r and omly assigned to laparoscopy ( 52 ) or laparotomy ( 50 ) in a teaching hospital from July 1994 to September 1995 . Inclusion criteria was tumor not suspected to be malignant with a diameter of < or = 10 cm as measured by ultrasonography . All operations were performed by trainees under the supervision of an experienced surgeon . Statistical analysis included t tests and chi2 tests . RESULTS There were no differences in demographic characteristics between the two groups nor any difference in the size of ovarian masses , adnexal adhesion score , or frequency of bilateral disease . All the ovarian masses were benign . Endometriotic cysts and dermoid cysts were the most common disorder in the two groups . Cystectomy was performed in > 70 % of cases in each group . Operating time was not increased with the laparoscopic approach , and the frequency of inadvertent rupture of the ovarian masses was just as high as in laparotomy . The laparoscopic approach was associated with a significant reduction in operative morbidity ( odds ratio 0.34 , 95 % confidence interval 0.13 to 0.88 ) , postoperative pain and analgesic requirement , hospital stay , and recovery period . Patients in general were satisfied with the operation , but significantly more patients were satisfied with the laparoscopy scar . CONCLUSION Operative laparoscopy should replace laparotomy in the management of benign ovarian masses Objective To compare laparoscopy and laparotomy in the management of benign adnexal cysts , with particular attention to postoperative convalescence . Methods Forty premenopausal , nonpregnant women , 18–40 years of age and without acute pelvic symptoms , were scheduled to undergo surgical management of anechoic , unilateral , unilocular , persistent adnexal cysts from January 1993 through June 1994 at the Department of Obstetrics and Gynecology of the University of Cagliari , Cagliari , Italy . After ultrasonographic examination , followed by the completion of 6 months ' expectant management with repeat ultrasonographic evaluations , subjects were r and omized to undergo operative laparoscopy ( n = 20 ) or laparotomy ( n = 20 ) . The patients were review ed postoperatively at the outpatient clinic at 15 , 30 , 90 , and 180 days . The intensity of pain was assessed by completion of a visual analogue scale on the day of surgery and 1 , 2 , and 3 days postoperatively , and the results of the two groups were compared . We also compared the proportions of patients who were analgesic-free on day 2 , discharged from hospital within 3 days , and feeling fully recuperated on day 15 . Results The intensity of postoperative pain was significantly lower ( P < .05 ) in the operative laparoscopy group than in the laparotomy group . A significantly higher ( P < .05 ) proportion of the laparoscopy patients was analgesicfree on day 2 , discharged from the hospital within 3 days , and feeling fully recuperated on postoperative day 15 . Conclusion After careful patient evaluation , management of anechoic , unilocular adnexal cysts by operative laparoscopy significantly reduces both the intensity of postoperative pain and the length of convalescence compared with laparotomy OBJECTIVE Women with ectopic pregnancy ( EP ) who have been operated on by laparoscopy are thought to have improved subsequent fertility , probably because of less adhesion formation . We aim ed to evaluate the adhesion formation after laparoscopy as compared with laparotomy in a r and omized trial . DESIGN One hundred five patients with tubal pregnancy were stratified with regard to age and risk factors and r and omized to surgery by laparoscopy or laparotomy . To evaluate adhesion formation and tubal status , 73 patients with strong desire of pregnancy underwent a second-look laparoscopy . The adhesion status at the ipsilateral and contralateral side at primary surgery was compared with the status at second-look laparoscopy . RESULTS Patients operated on by laparotomy developed significantly more adhesions at the operated side than patients operated on by laparoscopy ( P less than 0.001 ) . Substantially more patients in the laparotomy group underwent adhesiolysis at second-look laparoscopy than did patients in the laparoscopy group . Tubal patency did not differ between the groups . CONCLUSIONS Laparoscopic treatment of EP results in less impairment of the pelvic status compared with conventional conservative surgery |
896 | 22,188,875 | None of the studies established a conclusive relationship between mask/respirator use and protection against influenza infection .
Some evidence suggests that mask use is best undertaken as part of a package of personal protection especially h and hygiene .
The effectiveness of masks and respirators is likely linked to early , consistent and correct usage | There are limited data on the use of masks and respirators to reduce transmission of influenza .
A systematic review was undertaken to help inform p and emic influenza guidance in the United Kingdom . | Please cite this paper as : MacIntyre et al. ( 2011 ) A cluster r and omized clinical trial comparing fit‐tested and non‐fit‐tested N95 respirators to medical masks to prevent respiratory virus infection in health care workers . Influenza and Other Respiratory Viruses DOI : 10.1111/j.1750‐2659.2010.00198.x . Background We compared the efficacy of medical masks , N95 respirators ( fit tested and non fit tested ) , in health care workers ( HCWs ) . Methods A cluster r and omized clinical trial ( RCT ) of 1441 HCWs in 15 Beijing hospitals was performed during the 2008/2009 winter . Participants wore masks or respirators during the entire work shift for 4 weeks . Outcomes included clinical respiratory illness ( CRI ) , influenza‐like illness ( ILI ) , laboratory‐confirmed respiratory virus infection and influenza . A convenience no‐mask/respirator group of 481 health workers from nine hospitals was compared . Findings The rates of CRI ( 3·9 % versus 6·7 % ) , ILI ( 0·3 % versus 0·6 % ) , laboratory‐confirmed respiratory virus ( 1·4 % versus 2·6 % ) and influenza ( 0·3 % versus 1 % ) infection were consistently lower for the N95 group compared to medical masks . By intention‐to‐treat analysis , when P values were adjusted for clustering , non‐fit‐tested N95 respirators were significantly more protective than medical masks against CRI , but no other outcomes were significant . The rates of all outcomes were higher in the convenience no‐mask group compared to the intervention arms . There was no significant difference in outcomes between the N95 arms with and without fit testing . Rates of fit test failure were low . In a post hoc analysis adjusted for potential confounders , N95 masks and hospital level were significant , but medical masks , vaccination , h and washing and high‐risk procedures were not . Interpretation Rates of infection in the medical mask group were double that in the N95 group . A benefit of respirators is suggested but would need to be confirmed by a larger trial , as this study may have been underpowered . The finding on fit testing is specific to the type of respirator used in the study and can not be generalized to other respirators . Trial registration Australian New Zeal and Clinical Trials Registry ( ANZCTR ) , ACTRN : ACTRN12609000257268 ( http://www.anzctr.org.au ) BACKGROUND During the influenza A(H1N1 ) p and emic , antiviral prescribing was limited , vaccines were not available early , and the effectiveness of nonpharmaceutical interventions ( NPIs ) was uncertain . Our study examined whether use of face masks and h and hygiene reduced the incidence of influenza-like illness ( ILI ) . METHODS A r and omized intervention trial involving 1437 young adults living in university residence halls during the 2006 - 2007 influenza season was design ed . Residence halls were r and omly assigned to 1 of 3 groups-face mask use , face masks with h and hygiene , or control- for 6 weeks . Generalized models estimated rate ratios for clinical ly diagnosed or survey-reported ILI weekly and cumulatively . RESULTS We observed significant reductions in ILI during weeks 4 - 6 in the mask and h and hygiene group , compared with the control group , ranging from 35 % ( confidence interval [ CI ] , 9%-53 % ) to 51 % ( CI , 13%-73 % ) , after adjusting for vaccination and other covariates . Face mask use alone showed a similar reduction in ILI compared with the control group , but adjusted estimates were not statistically significant . Neither face mask use and h and hygiene nor face mask use alone was associated with a significant reduction in the rate of ILI cumulatively . CONCLUSIONS These findings suggest that face masks and h and hygiene may reduce respiratory illnesses in shared living setting s and mitigate the impact of the influenza A(H1N1 ) p and emic . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT00490633 BACKGROUND Health care workers outside surgical suites in Asia use surgical-type face masks commonly . Prevention of upper respiratory infection is one reason given , although evidence of effectiveness is lacking . METHODS Health care workers in a tertiary care hospital in Japan were r and omized into 2 groups : 1 that wore face masks and 1 that did not . They provided information about demographics , health habits , and quality of life . Participants recorded symptoms daily for 77 consecutive days , starting in January 2008 . Presence of a cold was determined based on a previously vali date d measure of self-reported symptoms . The number of colds between groups was compared , as were risk factors for experiencing cold symptoms . RESULTS Thirty-two health care workers completed the study , result ing in 2464 subject days . There were 2 colds during this time period , 1 in each group . Of the 8 symptoms recorded daily , subjects in the mask group were significantly more likely to experience headache during the study period ( P < .05 ) . Subjects living with children were more likely to have high cold severity scores over the course of the study . CONCLUSION Face mask use in health care workers has not been demonstrated to provide benefit in terms of cold symptoms or getting colds . A larger study is needed to definitively establish noninferiority of no mask use Background There are sparse data on whether non-pharmaceutical interventions can reduce the spread of influenza . We implemented a study of the feasibility and efficacy of face masks and h and hygiene to reduce influenza transmission among Hong Kong household members . Methodology /Principal Findings We conducted a cluster r and omized controlled trial of households ( composed of at least 3 members ) where an index subject presented with influenza-like-illness of < 48 hours duration . After influenza was confirmed in an index case by the QuickVue Influenza A+B rapid test , the household of the index subject was r and omized to 1 ) control or 2 ) surgical face masks or 3 ) h and hygiene . Households were visited within 36 hours , and 3 , 6 and 9 days later . Nose and throat swabs were collected from index subjects and all household contacts at each home visit and tested by viral culture . The primary outcome measure was laboratory culture confirmed influenza in a household contact ; the secondary outcome was clinical ly diagnosed influenza ( by self-reported symptoms ) . We r and omized 198 households and completed follow up home visits in 128 ; the index cases in 122 of those households had laboratory-confirmed influenza . There were 21 household contacts with laboratory confirmed influenza corresponding to a secondary attack ratio of 6 % . Clinical secondary attack ratios varied from 5 % to 18 % depending on case definitions . The laboratory-based or clinical secondary attack ratios did not significantly differ across the intervention arms . Adherence to interventions was variable . Conclusions / Significance The secondary attack ratios were lower than anticipated , and lower than reported in other countries , perhaps due to differing patterns of susceptibility , lack of significant antigenic drift in circulating influenza virus strains recently , and /or issues related to the symptomatic recruitment design . Lessons learnt from this pilot have informed changes for the main study in 2008 . Trial Registration Clinical Trials.gov NCT00425893 HK Clinical Trials.com CONTEXT Data about the effectiveness of the surgical mask compared with the N95 respirator for protecting health care workers against influenza are sparse . Given the likelihood that N95 respirators will be in short supply during a p and emic and not available in many countries , knowing the effectiveness of the surgical mask is of public health importance . OBJECTIVE To compare the surgical mask with the N95 respirator in protecting health care workers against influenza . DESIGN , SETTING , AND PARTICIPANTS Noninferiority r and omized controlled trial of 446 nurses in emergency departments , medical units , and pediatric units in 8 tertiary care Ontario hospitals . INTERVENTION Assignment to either a fit-tested N95 respirator or a surgical mask when providing care to patients with febrile respiratory illness during the 2008 - 2009 influenza season . MAIN OUTCOME MEASURES The primary outcome was laboratory-confirmed influenza measured by polymerase chain reaction or a 4-fold rise in hemagglutinin titers . Effectiveness of the surgical mask was assessed as noninferiority of the surgical mask compared with the N95 respirator . The criterion for noninferiority was met if the lower limit of the 95 % confidence interval ( CI ) for the reduction in incidence ( N95 respirator minus surgical group ) was greater than -9 % . RESULTS Between September 23 , 2008 , and December 8 , 2008 , 478 nurses were assessed for eligibility and 446 nurses were enrolled and r and omly assigned the intervention ; 225 were allocated to receive surgical masks and 221 to N95 respirators . Influenza infection occurred in 50 nurses ( 23.6 % ) in the surgical mask group and in 48 ( 22.9 % ) in the N95 respirator group ( absolute risk difference , -0.73 % ; 95 % CI , -8.8 % to 7.3 % ; P = .86 ) , the lower confidence limit being inside the noninferiority limit of -9 % . CONCLUSION Among nurses in Ontario tertiary care hospitals , use of a surgical mask compared with an N95 respirator result ed in noninferior rates of laboratory-confirmed influenza . TRIAL REGISTRATION clinical trials.gov Identifier : |
897 | 24,588,438 | Discussion s regarding LOMT were frequently performed more commonly than resuscitation interventions such as endotracheal intubation . | BACKGROUND The medical emergency team ( MET ) is now common in many hospitals .
Apart from early identification and management of patients who are potentially unwell on the ward , the MET may also be involved in end-of-life ( EOL ) care .
It is not known how often METs perform EOL interventions .
METHODS We performed a systematic review to identify the frequency of EOL interventions in comparison with other commonly performed interventions during MET calls . | Abstract Objectives : To determine whether earlier clinical intervention by a medical emergency team prompted by clinical instability in a patient could reduce the incidence of and mortality from unexpected cardiac arrest in hospital . Design : A non-r and omised , population based study before ( 1996 ) and after ( 1999 ) introduction of the medical emergency team . Setting : 300 bed tertiary referral teaching hospital . Participants : All patients admitted to the hospital in 1996 ( n=19 317 ) and 1999 ( n=22 847 ) . Interventions : Medical emergency team ( two doctors and one senior intensive care nurse ) attended clinical ly unstable patients immediately with resuscitation drugs , fluid , and equipment . Response activated by the bedside nurse or doctor according to predefined criteria . Main outcome measures : Incidence and outcome of unexpected cardiac arrest . Results : The incidence of unexpected cardiac arrest was 3.77 per 1000 hospital admissions ( 73 cases ) in 1996 ( before intervention ) and 2.05 per 1000 admissions ( 47 cases ) in 1999 ( after intervention ) , with mortality being 77 % ( 56 patients ) and 55 % ( 26 patients ) , respectively . After adjustment for case mix the intervention was associated with a 50 % reduction in the incidence of unexpected cardiac arrest ( odds ratio 0.50 , 95 % confidence interval 0.35 to 0.73 ) . Conclusions : In clinical ly unstable in patients early intervention by a medical emergency team significantly reduces the incidence of and mortality from unexpected cardiac arrest in hospital . What is already known on this topic In most studies mortality from unexpected cardiac arrest in hospital exceeds 50 % Such events are usually preceded by signs of clinical deterioration in the hours before cardiac arrest What this paper adds Early intervention by a medical emergency team significantly reduced the incidence of and mortality from unexpected cardiac arrest in BACKGROUND Patients with cardiac arrests or who die in general wards have often received delayed or inadequate care . We investigated whether the medical emergency team ( MET ) system could reduce the incidence of cardiac arrests , unplanned admissions to intensive care units ( ICU ) , and deaths . METHODS We r and omised 23 hospitals in Australia to continue functioning as usual ( n=11 ) or to introduce a MET system ( n=12 ) . The primary outcome was the composite of cardiac arrest , unexpected death , or unplanned ICU admission during the 6-month study period after MET activation . Analysis was by intention to treat . FINDINGS Introduction of the MET increased the overall calling incidence for an emergency team ( 3.1 vs 8.7 per 1000 admissions , p=0.0001 ) . The MET was called to 30 % of patients who fulfilled the calling criteria and who were subsequently admitted to the ICU . During the study , we recorded similar incidence of the composite primary outcome in the control and MET hospitals ( 5.86 vs 5.31 per 1000 admissions , p=0.640 ) , as well as of the individual secondary outcomes ( cardiac arrests , 1.64 vs 1.31 , p=0.736 ; unplanned ICU admissions , 4.68 vs 4.19 , p=0.599 ; and unexpected deaths , 1.18 vs 1.06 , p=0.752 ) . A reduction in the rate of cardiac arrests ( p=0.003 ) and unexpected deaths ( p=0.01 ) was seen from baseline to the study period for both groups combined . INTERPRETATION The MET system greatly increases emergency team calling , but does not substantially affect the incidence of cardiac arrest , unplanned ICU admissions , or unexpected death Objective To determine whether the introduction of an intensive care unit-based medical emergency team , responding to hospital-wide preset criteria of physiologic instability , would decrease the rate of predefined adverse outcomes in patients having major surgery . Design Prospect i ve , controlled before- and -after trial . Setting University-affiliated hospital . Patients Consecutive patients admitted to hospital for major surgery during a 4-month control phase and during a 4-month intervention phase . Interventions Introduction of a hospital-wide intensive care unit-based medical emergency team to evaluate and treat in- patients deemed at risk of developing an adverse outcome by nursing , paramedical , and /or medical staff . Measurements and Main Results We measured incidence of serious adverse events , mortality after major surgery , and mean duration of hospital stay . There were 1,369 operations in 1,116 patients during the control period and 1,313 in 1,067 patients during the medical emergency team intervention period . In the control period , there were 336 adverse outcomes in 190 patients ( 301 outcomes /1,000 surgical admissions ) , which decreased to 136 in 105 patients ( 127 outcomes /1,000 surgical admissions ) during the intervention period ( relative risk reduction , 57.8 % ; p < .0001 ) . These changes were due to significant decreases in the number of cases of respiratory failure ( relative risk reduction , 79.1 % ; p < .0001 ) , stroke ( relative risk reduction , 78.2 % ; p = .0026 ) , severe sepsis ( relative risk reduction , 74.3 % ; p = .0044 ) , and acute renal failure requiring renal replacement therapy ( relative risk reduction , 88.5 % ; p < .0001 ) . Emergency intensive care unit admissions were also reduced ( relative risk reduction , 44.4 % ; p = .001 ) . The introduction of the medical emergency team was also associated with a significant decrease in the number of postoperative deaths ( relative risk reduction , 36.6 % ; p = .0178 ) . Duration of hospital stay after major surgery decreased from a mean of 23.8 days to 19.8 days ( p = .0092 ) . Conclusions The introduction of an intensive care unit-based medical emergency team in a teaching hospital was associated with a reduced incidence of postoperative adverse outcomes , postoperative mortality rate , and mean duration of hospital stay INTRODUCTION Atrial fibrillation ( AF ) in hospitalized patients may lead to activation of the medical emergency team ( MET ) . We sought to assess the baseline characteristics and outcomes of the patients presenting AF as a cause of MET call activation . METHODS Using a prospect ively constructed MET data base , we retrospectively review ed all patients with AF as a trigger for MET activation between August 2005 and April 2010 . Demographics , principal diagnostic and outcome of these patients were compared with those of a control group of patients matched for age , sex and ward of origin , r and omly selected from the data base . RESULTS We studied 5431 MET calls of which 557 ( 10.3 % ) , in 458 patients were triggered by AF . Mean age for AF patients was 74.8 years , 230 ( 50.2 % ) were female and 271 ( 59.1 % ) were in a surgical ward . 92 ( 20.1 % ) AF patients died in hospital compared with 131 ( 28.6 % ) in the control group . Among the 336 patients without limitations of medical therapy ( LOMT ) , 46 ( 13.7 % ) died in hospital . In total , 46 ( 13.7 % ) patients were transferred to a higher level care ward while 290 ( 86.3 % ) remained on the ward . Only 2 ( 4.3 % ) of these patients died compared with 44 ( 15.2 % ) among those who remained in the general ward ( p=0.03 ) . CONCLUSIONS In our hospital , AF triggers one tenth of MET activations and mortality associated with it is high even when issues of LOMT are excluded . The decreased mortality among patients admitted to a higher level ward suggests that some of these deaths may be avoidable OBJECTIVE To examine NFR orders in relation to adverse events and emergency team calls in hospitals with or without a Medical Emergency Team ( MET ) system during the MERIT study . METHOD Within a cluster r and omized controlled trial ( the MERIT study ) , examining the effect of introducing a MET system , we recorded NFR orders in relation to adverse events and emergency team calls . We compared the proportion and rate of NFR orders issued in relation to " adverse events " and " adverse event-free emergency team calls " in hospitals with or without a MET system . RESULTS Information on NFR orders was available for 3650 patients who died , 1466 patients who had an unplanned ICU admission , 574 patients who suffered a cardiac arrest and 1529 patients who had a adverse event-free emergency team call . Close to 90 % of deaths occurred in patients with a previously documented NFR order . Only approximately 4 % of cardiac arrests had a previously documented NFR order . In patients with unplanned ICU admission , NFR orders were present in approximately 3 % of cases . An NFR order was issued at the time of an " event " in 3.85 % of cases in MET hospitals compared with 1.72 % in control hospitals ( OR=2.29 ; 95 % CI : 1.31 - 4.01 ; p=0.005 ) . This difference was mostly due to a greater proportion of patients being made NFR in MET hospitals at the time of a " adverse event-free " emergency team call ( 7.96 % vs. 3.05 % ; OR=2.75 ; 95 % CI : 0.97 - 7.80 ; p=0.048 ) . The number of NFR orders issued at the time of a serious adverse event-free emergency team call was 10 times higher in MET hospitals ( 0.398 vs. 0.041 per 1000 admissions ; weighted absolute risk difference : 0.49 ( 95 % CI : 0.20 - 0.78 ; p=0.002 ) . Multivariate models could only account for less than 50 % of the variance in the issuing of NFR orders . CONCLUSIONS In a cohort of Australian hospitals , most deaths occurred in patients with a previously documented NFR order but NFR orders were uncommon before cardiac arrest calls or unplanned ICU admissions . During the conduct of a cluster r and omised controlled trial , more NFR orders were issued by emergency teams in those hospitals that implemented a MET system than in control hospitals . MET allocation , teaching hospital status , number of hospital beds and metropolitan location could only explain less than 50 % of variance in NFR orders CONTEXT Rapid response teams have been shown in adult in patients to decrease cardiopulmonary arrest ( code ) rates outside of the intensive care unit ( ICU ) . Because a primary action of rapid response teams is to transfer patients to the ICU , their ability to reduce hospital-wide code rates and mortality remains unknown . OBJECTIVE To determine rates of hospital-wide codes and mortality before and after implementation of a long-term rapid response team intervention . DESIGN , SETTING , AND PATIENTS A prospect i ve cohort design of adult in patients admitted between January 1 , 2004 , and August 31 , 2007 , at Saint Luke 's Hospital , a 404-bed tertiary care academic hospital in Kansas City , Missouri . Rapid response team education and program rollout occurred from September 1 to December 31 , 2005 . A total of 24 193 patient admissions were evaluated prior to the intervention ( January 1 , 2004 , to August 31 , 2005 ) , and 24 978 admissions were evaluated after the intervention ( January 1 , 2006 , to August 31 , 2007 ) . INTERVENTION Using st and ard activation criteria , a 3-member rapid response team composed of experienced ICU staff and a respiratory therapist performed the evaluation , treatment , and triage of in patients with evidence of acute physiological decline . MAIN OUTCOME MEASURES Hospital-wide code rates and mortality , adjusted for preintervention trends . RESULTS There were a total of 376 rapid response team activations . After rapid response team implementation , mean hospital-wide code rates decreased from 11.2 to 7.5 per 1000 admissions . This was not associated with a reduction in the primary end point of hospital-wide code rates ( adjusted odds ratio [ AOR ] , 0.76 [ 95 % confidence interval { CI } , 0.57 - 1.01 ] ; P = .06 ) , although lower rates of non-ICU codes were observed ( non-ICU AOR , 0.59 [ 95 % CI , 0.40 - 0.89 ] vs ICU AOR , 0.95 [ 95 % CI , 0.64 - 1.43 ] ; P = .03 for interaction ) . Similarly , hospital-wide mortality did not differ between the preintervention and postintervention periods ( 3.22 vs 3.09 per 100 admissions ; AOR , 0.95 [ 95 % CI , 0.81 - 1.11 ] ; P = .52 ) . Secondary analyses revealed few instances of rapid response team undertreatment or underuse that may have affected the mortality findings . CONCLUSION In this large single-institution study , rapid response team implementation was not associated with reductions in hospital-wide code rates or mortality Problem : Advance cardiac life support ( ACLS ) training does not address coordination of team re sources to improve the ability of teams to deliver needed treatments reliably and rapidly . Our objective was to use a human simulation training educational environment to develop multidisciplinary team skills and improve medical emergency team ( MET ) performance . We report findings of a crisis team training course that is focused on organization . Setting : Large center for human simulation training at a university affiliated tertiary care hospital . Participants : Ten courses were delivered and 138 clinical ly experienced individuals were trained ( 69 critical care nurses , 48 physicians , and 21 respiratory therapists ) . All participants were ACLS trained and experienced in responding to cardiac arrest situations . Course design : Each course had four components : ( 1 ) a web based presentation and pretest before the course ; ( 2 ) a brief reinforcing didactic session on the day of the course ; ( 3 ) three of five different simulated scenarios ; each followed by ( 4 ) debriefing and analysis with the team . Three of five simulator scenarios were used ; scenario selection and order was r and om . Trainees did not repeat any scenario or role during the training . Participants were video recorded to assist debriefing . Debriefing focused on reinforcing organizational aspects of team performance : assuming design ated roles independently , completing goals ( tasks ) assigned to each role , and directed communication . Measures for improvement : Participants grade d their performance of specific organizational and treatment tasks within specified time intervals by consensus . Simulator “ survival ” depended on supporting oxygenation , ventilation , circulation within 60 seconds , and delivering the definitive treatment within 3 minutes . Effects of change : Simulated survival ( following predetermined criteria for death ) increased from 0 % to 89 % . The initial team task completion rate was 10–45 % and rose to 80–95 % during the third session . Lessons learnt : Training multidisciplinary teams to organize using simulation technology is feasible . This preliminary report warrants more detailed inquiry Purpose To prospect ively evaluate the implementation of a rapid response team in the form of a medical emergency team ( MET ) with regard to cardiac arrests and hospital mortality . Methods Prospect i ve before- and -after trial of implementation of a MET at the Karolinska University Hospital , Stockholm , Sweden . All adult patients , apart from cardiothoracic , admitted to the hospital were regarded as participants in the study . A control period of 5 years and 203,892 patients preceded the 2-year intervention period of 73,825 patients .Main results Number of MET calls was 9.3 per 1,000 hospital admissions . Cardiac arrests per 1,000 admissions decreased from 1.12 to 0.83 , OR 0.74 ( 95 % CI 0.55–0.98 , p = 0.035 ) . Adjusted for age , sex , hospital length of stay , acute/elective admission as well as co-morbidities , MET implementation was associated with a reduction in total hospital mortality by 10 % , OR 0.90 ( 95 % CI 0.84–0.97 ) , p = 0.003 . Hospital mortality was also reduced for medical patients by 12 % , OR 0.88 ( 95 % CI 0.81–0.96 , p = 0.002 ) and for surgical patients not operated upon by 28 % , OR 0.72 ( 95 % CI 0.56–0.92 , p = 0.008).For patients fulfilling the MET criteria Thirty-day mortality pre-MET was 25 % versus 7.9 % following MET compared with historical controls . Similarly , 180-day mortality was 37.5 % versus 15.8 % , respectively . Conclusions Implementing the MET team was associated with significant improvement in both cardiac arrest rate and overall adjusted hospital mortality . Significant reductions in hospital mortality for un-operated surgical patients as well as for medical patients were also seen . Thus , introduction of the MET seemed to improve outcome for hospitalized patients AIM To evaluate the activity and impact of a Medical Emergency Team ( MET ) one year after implementation . SETTING AND POPULATION A 700-bed District General Hospital ( DGH ) in Southeast Engl and with approximately 53,500 adult admissions per annum . The population studied included all adult admissions receiving intervention by the MET during a 12-month period between 1 October 2000 and 30 September 2001 . METHODS Analysis of the activation of the MET using both prospect i ve and retrospectively acquired data . Routinely collected hospital data for admissions , discharges and deaths was used to compare outcomes for the 12 months before and after the introduction of the MET . RESULTS There were 136 activations of MET over 1-year . Six cases were excluded . Mean age of patients was 73 years ( range 20 - 97 years ) . 40 % ( 52/130 ) survived to discharge following MET intervention . Of those who died 22 % ( 28/130 ) were design ated ' not for resuscitation ' . Patients that died were more likely to have three or more physiological abnormalities present ( odds ratio , OR 6.2 , Chi-square ( chi(2 ) ) P = 0.004 ) and had higher MET scores ( P = 0.004 ) . Commonest interventions by the MET were initiation or increase of oxygen therapy or ventilatory support ( 80 % ) , with or without the administration of intravenous fluids or medications . In 10 % of cases , oxygen therapy was the sole intervention . One year after implementation of the MET a reduction in cardiac arrest rate and overall mortality was noted but this was not statistically significant . CONCLUSION Often only simple interventions are only required to reverse deterioration . Initiating ' do not attempt resuscitation ' ( DNAR ) decisions is a key part of MET activity . Multiple physiological abnormalities are associated with increased mortality and therefore wider and earlier application of the MET to the hospital population may save lives or expedite DNAR decisions . New systems need time to develop ( " bed in " ) and further research is needed to observe significant reductions in cardiac arrests and overall mortality Introduction Introducing an intensive care unit (ICU)-based medical emergency team ( MET ) into our hospital was associated with decreased postoperative in-hospital mortality after major surgery . The purpose of the present study was to assess the effect of the MET and other variables on long-term mortality in this patient population . Methods We conducted a prospect i ve , controlled , before- and -after trial in a University-affiliated hospital . Participants included consecutive patients admitted for major surgery ( surgery requiring hospital stay > 48 hours ) during a four month control phase and a four month MET phase . The intervention involved the introduction of a hospital-wide ICU-based MET service to evaluate and treat ward patients with acutely deranged vital signs . Information on long-term mortality was obtained from the Australian death registry . The main outcome measure was patient mortality at 1500 days . Data on patient demographics , surgery undertaken and whether the surgery was scheduled or unscheduled was obtained from the hospital electronic data base . Multivariable analysis was conducted to determine independent predictors of 1500-day mortality . Results There were 1,369 major operations in 1,116 patients during the control period and 1,313 operations in 1,067 patients during the MET ( intervention ) period . Overall survival at 1500 days was 65.8 % in the control period and 71.6 % during the MET period ( P = 0.001 ) . Patients in the control phase were statistically less likely to be admitted under orthopaedic surgery , urology and faciomaxillary surgery units , but more likely to be admitted under cardiac surgery or neurosurgery units . Patients in the MET period were less likely to undergo unscheduled surgery . Multivariable analysis revealed that age , unscheduled surgery and admission under thoracic surgery , neurosurgery , oncology and general medicine were independent predictors of increased 1500-day mortality . Admission during the MET period was also an independent predictor of decreased 1500-day mortality ( odds ratio 0.74 ; P = 0.005 ) . Conclusion Introduction of a MET service in a teaching hospital was associated with increased long-term survival even after adjusting for other factors that contribute to long-term surgical mortality BACKGROUND : We sought to determine the impact of a rapid response system on cardiac arrest rates and mortality in a United States veteran population . METHODS : We describe a prospect i ve analysis of cardiac arrests in 9 months before and 27 months after institution of a rapid response system , and retrospective analysis of mortality 3.5 years before the intervention and 27 months after the intervention . The study included all in patients from a university-affiliated United States Veterans Affairs Medical Center , before and after implementation of a rapid response system , including an educational program , patient calling criteria , and a physician-led medical emergency team . Primary end points were hospital-wide cardiac arrests and mortality rates normalized to hospital discharges . Comparisons of event rates between various time points during the implementation process were made by analysis of variance . RESULTS : Three hundred seventy-eight calls were made to the medical emergency team in the time period studied . Compared with preintervention time points , cardiac arrests were reduced by 57 % , amounting to a reduction of 5.6 cardiac arrests per 1000 hospital discharges ( P < 0.01 ) . Mortality was reduced during the intervention , but this was attributable to a natural decrease occurring over all phases of the study . CONCLUSIONS : A significant reduction in the rate of cardiac arrests was realized with this intervention , as well as a trend toward lower mortality . We estimate that 51 arrests were prevented in the timeframe studied . Our results suggest that further reductions in morbidity can be realized by expansion of rapid response systems throughout the Veterans Affairs network Objective : To determine the effect of a rapid response system composed primarily of a rapid response team led by physician assistants on the rates of in-hospital cardiac arrests , total and unplanned intensive care unit admissions , and hospital mortality . Design : Prospect i ve , controlled , before and after trial . Setting : A 350-bed nonteaching community hospital . Patients : All adult patients admitted to the hospital from May 1 , 2005 , to October 1 , 2006 . Interventions : We introduced a hospital-wide rapid response system that included a rapid response team ( RRT ) led by physician assistants with specialized critical care training . Measurements and Main Results : We measured the incidence of cardiac arrests that occurred outside of the intensive care unit , total intensive care unit admissions , unplanned intensive care unit admissions , intensive care unit length of stay , and the total hospital mortality rate occurring over the study period . There were 344 RRT calls during the study period . In the 5 months before the rapid response system began , there were an average of 7.6 cardiac arrests per 1,000 discharges per month . In the subsequent 13 months , that figure decreased to 3.0 cardiac arrests per 1,000 discharges per month . Overall hospital mortality the year before the rapid response system was 2.82 % and decreased to 2.35 % by the end of the RRT year . The percentage of intensive care unit admissions that were unplanned decreased from 45 % to 29 % . Linear regression analysis of key outcome variables showed strong associations with the implementation of the rapid response system , as did analysis of variables over time . Physician assistants successfully managed emergency airway situations without assistance in the majority of cases . Conclusions : The deployment of an RRT led by physician assistants with specialized skills was associated with significant decreases in rates of in-hospital cardiac arrest and unplanned intensive care unit admissions OBJECTIVE Hospitalized patients are at risk for adverse events such as unexpected cardiac arrest or admission to an Intensive Care Unit ( ICU ) . Prior to these adverse events these patients often have derangements in vital signs that are not recognized and treated adequately . To identify and treat those patients at risk , our hospital implemented a rapid response system in 2004 . The purpose of this paper is to describe implementation and results of our rapid response system . DESIGN Prospect i ve cohort study . METHOD The implementation of the rapid response system started by training all doctors and nurses to score vital signs using a dedicated score card . If a patient scores 3 or more points , the patients ' treating physician has to see the patient and - if necessary - call the medical emergency team ( MET ) , consisting of an ICU physician and an ICU nurse . We analyzed all consecutive MET calls in the period January 2005-December 2009 . RESULTS A total of 1058 MET calls for 981 patients were analyzed . In 606 patients ( 57.3 % ) it was decided to transfer the patient to a higher dependency unit , in most cases the ICU . In 353 patients ( 33.4 % ) treatment could be continued on the ward . In 88 patients ( 8.4 % ) it was decided that ICU treatment would not be beneficial and limits on treatment were put in place . Of the 981 patients , 255 ( 26.0 % ) died in hospital . CONCLUSION In our hospital the rapid response system has developed into an important tool for the early identification and treatment of patients at risk . However , our data can not prove the efficacy of the rapid response system in terms of reducing hospital mortality AIM We used the Utstein template , with special reference to patients having automated patient monitoring , and studied the factors which are associated with delayed medical emergency team ( MET ) activation and increased hospital mortality . DESIGN AND SETTING A prospect i ve observational study in a tertiary hospital with 45 of 769 general ward beds ( 5.9 % ) equipped with automated monitoring . COHORT 569 MET review s for 458 patients . RESULTS Basic MET review characteristics were comparable to literature . We found that 41 % of the review s concerned monitored ward patients . These patients ' vitals had been more frequently documented during the 6h period preceding MET activation compared to patients in normal ward areas ( 96 % vs. 74 % , p<0.001 ) , but even when adjusted to the documentation frequency of vitals , afferent limb failure ( ALF ) occurred more often among monitored ward patients ( 81 % vs. 53 % , p<0.001 ) . In MET population , factors associated with increased hospital mortality were non-elective hospital admission ( OR 6.25 , 95 % CI 2.77 - 14.11 ) , not-for-resuscitation order ( 3.34 , 1.78 - 6.35 ) , ICD XIV genitourinary diseases ( 2.42 , 1.16 - 5.06 ) , ICD II neoplasms ( 2.80 , 1.59 - 4.91 ) , age ( 1.02 , 1.00 - 1.04 ) , preceding length of hospital stay ( 1.04 , 1.01 - 1.07 ) , ALF ( 1.67 , 1.02 - 2.72 ) and transfer to intensive care ( 1.85 , 1.05 - 3.27 ) . CONCLUSIONS Documentation of vital signs before MET activation is suboptimal . Documentation frequency seems to increase if automated monitors are implemented , but our results suggest that benefits of intense monitoring are lost without appropriate and timely interventions , as afferent limb failure , delay to call MET when predefined criteria are fulfilled , was independently associated to increased hospital mortality OBJECTIVES To improve the documentation of events surrounding medical emergency team ( MET ) calls and to audit the incidence of MET calls and subsequent patient outcomes . METHODS Prospect i ve audit and patient chart review before and after three simultaneous interventions : medical team education , addition of intensive care personnel to the MET and introduction of a dedicated medical documentation pro forma . Data collected included patient demographics ( including outcomes ) , features of each MET call ( criteria , timing and treatment ) and the completeness of medical documentation using nine predetermined criteria . Baseline data were collected over 5 months , April to August 2005 . Following a 2-week education period , data were collected for a further 4 months , September to December 2005 . Apart from the principal investigators , medical and nursing staff were not aware of this research during either data collection period . RESULTS There were 94 MET calls ( 10.3 per 1000 admissions ) during the baseline period and 101 ( 14.2 per 1000 admissions ) after the interventions . MET calls were more common in medical than surgical patients ( 34.9 v 12.9 calls per 1000 admissions ; P < 0.001 ) . Sixty of the 195 calls ( 30.7 % ) result ed in patients being transferred to a critical care area , and the overall in-hospital mortality following a MET call was 31.8 % . The interventions result ed in a significant increase in the overall quantity and quality of medical documentation ( in seven out of the nine criteria ) . The interventions were not associated with an increase in hospital re source utilisation , in particular hospital bed days or admissions to critical care areas . CONCLUSIONS Critical-care re source utilisation and inhospital mortality risk following a MET call at our institution is high . Three simple interventions improved the quality of medical documentation but did not significantly increase overall re source utilisation or improve patient outcomes PURPOSE The objective of this study was to further our underst and ing of the decision-making process near the end of life . Specifically , we ascertained the seriously ill patients ' preferred role in the decision-making process , what factors were associated with this role , and how this stated preference related to physicians ' perception of preferred role . MATERIAL S AND METHODS Prospect i ve cohort study of hospitalized patients with end-stage congestive heart disease , chronic pulmonary disease , cirrhosis , or metastatic cancer . Eligible patients were interviewed to ascertain their personal views on end-of-life decision making , desired role , and level of symptoms experienced . RESULTS A total of 135 patients were enrolled in this study . The majority of patients ( 103 , 76 % ) had thought about end-of-life issues although only 48 ( 36 % ) had discussed them with their doctor in the hospital . With respect to preferred role in decision making , in the scenario of a competent patient , 14 ( 10 % ) preferred to leave all decisions to the doctor , 12 ( 9 % ) preferred that the doctor make the final decision after considering their opinion , 43 ( 32 % ) preferred that the doctor shared responsibility with them to make the decision , 32 ( 24 % ) patients preferred to make the final decision after considering the doctor 's opinion , 21 ( 16 % ) preferred to make the treatment decision alone , and 13 ( 10 % ) did not answer . Physicians were not able to accurately predict patient 's preferred role nor could the variability in patient choice be accounted for by demographic or symptom covariates . CONCLUSION Seriously ill hospitalized patients desire to discuss end-of-life issues with their physicians but their preferred role in decision making is variable and difficult to predict Objective To identify factors that predict outcome in patients receiving a Medical Emergency Team review . Design Prospect i ve observational study . Setting Tertiary hospital . Patients Cohort of 228 patients receiving one or more Medical Emergency Team review s during daytime hours over a 1-year-period . Control cohort of all patients ( n = 900 ) receiving a Medical Emergency Team review in the same period . Measurements and results We prospect ively collected information from patients receiving a Medical Emergency Team review during daytime hours from Monday to Friday ( audit group ) including the clinical cause of deterioration and timing of call in relation to the first documented Medical Emergency Team call criterion ( activation delay ) . We also collected information from the hospital Medical Emergency Team data base regarding all patients visited by the Medical Emergency Team during the same period ( complete cohort ) . Audit group patients had several similar characteristics to complete cohort patients but were less likely to be not-for-resuscitation before Medical Emergency Team review and more likely to receive a Medical Emergency Team review because of hypotension , change in neurological status and oliguria . Delayed Medical Emergency Team activation and not-for resuscitation orders were the only factors to show an independent statistical association with mortality ( OR 2.53 , 95 % CI : 1.2–5.31 , P = 0.01 and OR 5.63 , 95 % CI : 2.81–11.28 , P < 0.01 , respectively ) . Conclusion Delayed Medical Emergency Team activation and NFR orders are the strongest independent predictors of mortality in patients receiving a Medical Emergency Team review . Avoidance of delayed Medical Emergency Team activation should be a priority for hospitals operating rapid response systems AIM This study assessed the level of agreement on CPR decisions among intensive care doctors and specialist physicians and surgeons , and the barriers to documenting do not attempt resuscitation ( DNAR ) orders for ward patients during Medical Emergency Team ( MET ) calls . METHODS We prospect ively assessed all patients having MET calls for 11 months . If the intensive care doctor on the MET considered a DNAR order appropriate for the patient , the primary care clinician was contacted to : ( 1 ) confirm agreement or disagreement with a DNAR order and ( 2 ) give reasons as to why a DNAR order was not considered or documented prior to the MET call . RESULTS In the study period , the MET attended 1458 patients . A DNAR order was considered appropriate in 129 cases . In 116 ( 90 % ) , the primary care clinician agreed with a DNAR order at the time of the MET . Common reasons given by primary care clinicians for not documenting DNAR orders included acute or unexpected deterioration ( 22.5 % ) , awaiting family discussion ( 22.5 % ) , actively treating the patient for a reversible condition ( 17.1 % ) , not knowing the patient well enough ( 10.9 % ) and resuscitation status not yet discussed by team ( 10.9 % ) . CONCLUSIONS This study shows a high level of agreement on DNAR orders among intensive care doctors , physicians and surgeons for deteriorating ward patients . Barriers to timely documentation need to be addressed . Delay in documentation and communication of DNAR orders is common . The MET system provides an opportunity to identify patients for whom a DNAR order should be considered Objective : To investigate the role of medical emergency teams in end-of-life care planning . Design : One month prospect i ve audit of medical emergency team calls . Setting : Seven university-affiliated hospitals in Australia , Canada , and Sweden . Patients : Five hundred eighteen patients who received a medical emergency team call over 1 month . Interventions : None . Measurements and Main Results : There were 652 medical emergency team calls in 518 patients , with multiple calls in 99 ( 19.1 % ) patients . There were 161 ( 31.1 % ) patients with limitations of medical therapy during the study period . The limitation of medical therapy was instituted in 105 ( 20.3 % ) and 56 ( 10.8 % ) patients before and after the medical emergency team call , respectively . In 78 patients who died with a limitation of medical therapy in place , the last medical emergency team review was on the day of death in 29.5 % of patients , and within 2 days in another 28.2%.Compared with patients who did not have a limitation of medical therapy , those with a limitation of medical therapy were older ( 80 vs. 66 yrs ; p < .001 ) , less likely to be male ( 44.1 % vs. 55.7 % ; p = .014 ) , more likely to be medical admissions ( 70.8 % vs. 51.3 % ; p < .001 ) , and less likely to be admitted from home ( 74.5 % vs. 92.2 % , p < .001 ) . In addition , those with a limitation of medical therapy were less likely to be discharged home ( 22.4 % vs. 63.6 % ; p < .001 ) and more likely to die in hospital ( 48.4 % vs. 12.3 % ; p < .001 ) . There was a trend for increased likelihood of calls associated with limitations of medical therapy to occur out of hours ( 51.0 % vs. 43.8 % , p = .089 ) . Conclusions : Issues around end-of-life care and limitations of medical therapy arose in approximately one-third of calls , suggesting a mismatch between patient needs for end-of-life care and re sources at participating hospitals . These calls frequently occur in elderly medical patients and out of hours . Many such patients do not return home , and half die in hospital . There is a need for improved advanced care planning in our hospitals , and to confirm our findings in other organizations OBJECTIVE To determine whether the introduction of the Medical Emergency Team ( MET ) system design ed to provide immediate help for seriously ill patients : ( i ) changed the pattern of ICU patient transfers from the wards ; and ( ii ) improved hospital survival rates . METHODS Prospect i ve information on MET calls and unanticipated ICU transfers was collected for 3 years in a suburban metropolitan hospital . RESULTS A 3-year review of MET showed the number of MET calls doubled in the second and third year and the team was activated for more than just the most extremely ill patients . Whilst the frequency of calls for cardiopulmonary arrest remained constant ( n = 16 ) , increased use of the MET result ed in the proportion of calls for cardiopulmonary arrest dropping from 30 % in year 1 to 13 % in year 3 . A slight decrease in the percentage of in-hospital deaths ( 0.74 % in year 1 to 0.65 % in year 3 ) was also demonstrated . The incidence of cardiopulmonary arrest per hospital admission also decreased slightly ( 0.08 - 0.07 % ) . Although the overall number of ICU transfers remained constant , more seriously ill patients were transferred to ICU via the MET system . This was accompanied by a significant fall in unanticipated ICU transfers . Whilst the reduction in hospital deaths was encouraging , this study could not demonstrate whether the slight improvement in hospital survival rate over the 3 years was due to the MET system . CONCLUSION More information is needed to demonstrate that the MET system improves patient survival . The study also highlights the importance of taking proactive measures , which should include providing in-service education on the benefits of early identification and treatment of patients who are at risk of acute deterioration , raising awareness and changing attitudes in hospitals when introducing system such as the MET CONTEXT In-hospital cardiac arrests are commonly associated with poor outcomes and preceded by observable signs of clinical deterioration . Medical emergency teams ( METs ) have emerged to provide early specialist care intervention to critically ill patients . OBJECTIVE To determine the effect of MET implementation on hospital-wide mortality rates , cardiopulmonary arrests and admissions to the intensive care unit ( ICU ) in a regional Queensl and hospital . METHOD A prospect i ve cohort before and after interventional trial was conducted on adult and paediatric in patients admitted in 2004 - 2008 at a 150 bed regional teaching hospital in Australia . MET was introduced in 2006 and attended clinical ly unstable patients . Response was activated by the bedside nurse or doctor according to predefined criteria . RESULTS There were a total of 296 MET activations . After MET implementation , mean hospital-wide mortality rates decreased from 9.9 to 7.5 per 1000 admissions ( relative risk reduction , RRR : 24.2 % ; p = 0.003 ) . Similarly , ICU admissions decreased from 22.4 to 17.6 per 1000 admissions ( RRR : 21.4 % ; p < 0.0001 ) . There was also a significant decline in hospital-wide cardiopulmonary arrests post intervention ( 77 versus 42 , RRR : 45.5 % ; p = 0.0025 ) however this may be explained by the increase in the number of patients deemed not for resuscitation by the MET . Secondary analysis revealed evidence of MET underuse that may have affected the mortality findings . CONCLUSION Implementation of the MET in a regional hospital was associated with statistically significant reductions in hospital-wide mortality rates , ICU admissions and cardiopulmonary arrests BACKGROUND AND OBJECTIVES There is no information on the clinical features and outcome of patients receiving multiple Medical Emergency Team ( MET ) review s. Accordingly , we studied the characteristics and outcome of patients receiving one MET call and compared them with those receiving multiple MET review s. DESIGN Retrospective observational study using prospect ively collected data . SETTING Tertiary hospital . PATIENTS Cohort of 1664 patients receiving 2237 MET review s over a 2-year period . MEASUREMENTS AND MAIN RESULTS We retrieved information about patient demographics , reasons for MET review , procedures performed by the MET and hospital outcome . We found that 1290 ( 77.5 % ) patients received a single MET review and 374 ( 22.5 % ) received multiple MET review s ( mean 2.5 review s , median 2.0 ) . Multiple MET review s were more likely to be in surgical patients ( p < 0.001 ) and to be due to arrhythmias ( p = 0.016 ) . Multiple MET review patients were more likely to be admitted for gastrointestinal diseases ( p < 0.001 ) , had a 50 % longer hospital stay ( p < 0.001 ) and a 34.6 % increase in hospital mortality ( p < 0.001 ) compared to single MET review patients . Their odds ratio ( OR ) for mortality was 2.14 ( 95 % C.I. : 1.62 - 2.83 ; p < 0.001 ) . After exclusion of patients with not for resuscitation ( NFR ) orders , the OR for mortality was 2.92 ( 95 % C.I. : 2.10 - 4.06 ; p < 0.001 ) . The in-hospital mortality of patients subject to multiple MET review s who were not design ated NFR was 34.1 % , but only 9.7 % of these deaths occurred within 48 h of the initial MET review . CONCLUSION In our hospital , one fifth of patients receiving MET calls are subject to multiple MET calls . Such patients have identifiable features and have an increased risk of morbidity and mortality . Within any rapid response system , such patients should be recognized as a higher risk group and receive specific additional attention |
898 | 18,407,412 | These data suggest that recovery occurs for a substantial proportion of subjects in the initial 3 months after the accident but after this time recovery rates level off .
Pain and disability symptoms also reduce rapidly in the initial months after the accident but show little improvement after 3 months have elapsed . | We conducted a systematic review and meta- analysis of prospect i ve cohort studies of subjects with acute whiplash injuries .
The aim was to describe the course of recovery , pain and disability symptoms and also to assess the influence of different prognostic factors on outcome . | A retrospective analysis of insurance data was made of 600 individuals cl aim ing compensation for whiplash following motor vehicle accidents . Three hundred r and omly selected cl aim ants who had settled their injury cl aims within 9 months of the accident were compared with 300 who had settled more than 24 months after the accident . We compared the two groups to identify possible risk factors for prolonged recovery , for which settlement time greater than 24 months was a marker . Variables considered included demographic factors , type of collision , degree of vehicle damage , workers compensation , prior cl aim or neck disability , treatment and time to settlement . Consulting a solicitor was associated with a highly significant , four-fold increase of late settlement of the cl aim . A concurrent workers ’ compensation cl aim , prior neck disability and undergoing physiotherapy or chiropractic treatment were weakly associated with late settlement . The degree of damage to the vehicle ( as indicated by cost of repairs ) was not a significant predictor of late settlement . Late settlement may be the direct effect of legal intervention , independent of the severity of the injury . Whilst the financial benefit to the cl aim ant of consulting a solicitor is apparent , the benefit of prolonged disability is not . It may be to the advantage of both insurers and cl aim ants if those likely to proceed to late settlement could be recognised early and their cl aims settled expeditiously We performed a prospect i ve study of patients with a whiplash trauma to the cervical spine to describe the incidence of these injuries and to evaluate prognostic factors for disability and recovery . A total of 356 patients were enrolled in the study . All the patients received a comprehensive question naire after the injury , and 296 cases responded to the follow-up protocol more than 1 year after the accident . Disability related to the whiplash trauma was used as the outcome variable for the assessment of prognostic factors . The annual incidence of acute whiplash trauma in the catchment area was 4.2 per 1,000 inhabitants and 3.2 per 1,000 for whiplash-associated disorder grade s 1–3 . Thirty-two percent reported persisting disability at follow-up . The following factors were significantly associated with a poor prognosis : pretraumatic neck pain , low educational level , female gender , and whiplash-associated disorder grade s 2–3 Ninety-three cases with a car-accident soft-tissue injury of the cervical spine were studied prospect ively . Neck pain and stiffness were the main initial symptoms , while 4 cases had abnormal neurologic signs . At follow-up , on an average 2 years after the accident , 42 percent had recovered completely , 15 percent had minor discomfort , and 43 percent had discomfort sufficient to interfere with their capacity for work . The statistical analysis of 17 factors , including acute symptoms and physical findings , as well as the forces and directions of impact , head rests , radiographs , length , and sex , did not reveal any factor of prognostic importance Hypersensitivity to a variety of sensory stimuli is a feature of persistent whiplash associated disorders ( WAD ) . However , little is known about sensory disturbances from the time of injury until transition to either recovery or symptom persistence . Quantitative sensory testing ( pressure and thermal pain thresholds , the brachial plexus provocation test ) , the sympathetic vasoconstrictor reflex and psychological distress ( GHQ‐28 ) were prospect ively measured in 76 whiplash subjects within 1 month of injury and then 2 , 3 and 6 months post‐injury . Subjects were classified at 6 months post‐injury using scores on the Neck Disability Index : recovered ( < 8 ) , mild pain and disability ( 10–28 ) or moderate/severe pain and disability ( > 30 ) . Sensory and sympathetic nervous system tests were also measured in 20 control subjects . All whiplash groups demonstrated local mechanical hyperalgesia in the cervical spine at 1 month post‐injury . This hyperalgesia persisted in those with moderate/severe symptoms at 6 months but resolved by 2 months in those who had recovered or reported persistent mild symptoms . Only those with persistent moderate/severe symptoms at 6 months demonstrated generalised hypersensitivity to all sensory tests . These changes occurred within 1 month of injury and remained unchanged throughout the study period . Whilst no significant group differences were evident for the sympathetic vasoconstrictor response , the moderate/severe group showed a tendency for diminished sympathetic reactivity . GHQ‐28 scores of the moderate/severe group were higher than those of the other two groups . The differences in GHQ‐28 did not impact on any of the sensory measures . These findings suggest that those with persistent moderate/severe symptoms at 6 months display , soon after injury , generalised hypersensitivity suggestive of changes in central pain processing mechanisms . This phenomenon did not occur in those who recover or those with persistent mild symptoms The present study aim ed to establish criteria for delayed recovery after whiplash injury using a 1-year prospect i ve cohort study . 117 whiplash patients referred from primary care and 16 whiplash patients recruited from the insurance company . At baseline all patients underwent neurological , radiological and psychosocial factors assessment and testing of personality traits , well-being , cognitive ability and cognitive functioning . According to the logistic regression in patients referred from primary care the following initial variables are in significant relationship with poor outcome at 1 year : impaired neck movement , history of pretraumatic headache , history of head trauma , higher age , initial neck pain intensity , initial headache intensity , nervousness score , neuroticism score and test score on focused attention . Employing these variables , correct prediction of outcome at 1 year was found in 88 % of patients recruited from the insurance company . Authors conclude that a comprehensive assessment of whiplash patients early after trauma enables physicians to identify patients at risk of delayed recovery & NA ; Dysfunction in the motor system is a feature of persistent whiplash associated disorders . Little is known about motor dysfunction in the early stages following injury and of its progress in those persons who recover and those who develop persistent symptoms . This study measured prospect ively , motor system function ( cervical range of movement ( ROM ) , joint position error ( JPE ) and activity of the superficial neck flexors ( EMG ) during a test of cranio‐cervical flexion ) as well as a measure of fear of re‐injury ( TAMPA ) in 66 whiplash subjects within 1 month of injury and then 2 and 3 months post injury . Subjects were classified at 3 months post injury using scores on the neck disability index : recovered ( < 8 ) , mild pain and disability ( 10–28 ) or moderate/severe pain and disability ( > 30 ) . Motor system function was also measured in 20 control subjects . All whiplash groups demonstrated decreased ROM and increased EMG ( compared to controls ) at 1 month post injury . This deficit persisted in the group with moderate/severe symptoms but returned to within normal limits in those who had recovered or reported persistent mild pain at 3 months . Increased EMG persisted for 3 months in all whiplash groups . Only the moderate/severe group showed greater JPE , within 1 month of injury , which remained unchanged at 3 months . TAMPA scores of the moderate/severe group were higher than those of the other two groups . The differences in TAMPA did not impact on ROM , EMG or JPE . This study identifies , for the first time , deficits in the motor system , as early as 1 month post whiplash injury , that persisted not only in those reporting moderate/severe symptoms at 3 months but also in subjects who recovered and those with persistent mild symptoms Abstract . Outcome following whiplash injury of the cervical spine is variable , and the pathology of those with prolonged symptoms is uncertain . We undertook a prospect i ve study in 25 patients to identify whether those with prolonged symptoms following whiplash injury exhibit a rise in serum creatine kinase consistent with significant muscle damage at the time of injury . Transient rise in creatine kinase level was seen in only 2 of 25 patients , neither of whom complained of prolonged symptoms . Of the 8 patients who developed chronic symptoms following whiplash injury , none demonstrated a serum creatine kinase rise . Prolonged symptoms following whiplash injury can not be explained by biochemically measurable muscle damage OBJECTIVE An earlier pilot study suggested that the late whiplash syndrome is uncommon in Greece . The purpose of the present study is to extend the evaluation to a larger sample , and include the prevalence of specific symptoms in the evaluation . METHODS In a prospect i ve , cohort study , a total of 180 accident victims were consecutively recruited following Emergency ward presentation . A st and ard question naire asked about neck pain , headache , shoulder pain , limb numbness or pain , and dizziness . Accident victims were followed for 6 months . RESULTS In the initial 4 weeks after the accident , accident victims reported neck pain , headache , shoulder pain , arm numbness or pain , and dizziness , but at 4 weeks more than 90 % had recovered from these , the remainder of the subjects having minor symptoms ( not requiring therapy ) , and returning to their pre-accident state of health ( which included minor symptoms ) . There were no cases of chronic disability . CONCLUSION In Greece , symptoms after an acute whiplash injury are self-limiting , brief , and do not appear to evolve into the so-called late whiplash syndrome One hundred and seventeen r and omly selected patients were assessed for different psychological variables ( personality traits , wellbeing , and cognitive ability ) in relation to somatic symptoms after common whiplash . Patients were investigated at an average of 7.4 ( SD 4.2 ) days after trauma and again at three and six months . The course of recovery could not be explained by the patients ' disposition . The results indicated that improvement in wellbeing was associated with recovery from somatic symptoms . There was , however , cognitive impairment in patients who suffered from symptoms . These findings support the view that the psychological and cognitive problems of patients with common whiplash are mainly related to somatic symptoms It is generally accepted that the incidence of whiplash associated disorders is increasing in all industrialised countries , despite the almost universal fitment of head restraints in at least the front seats of cars . This is usually attributed to the fact that few people can be observed to follow the st and ard recommendations as regards head restraint positioning , that is , level with the head vertically and as close to the head as possible horizontally . This study set out to determine whether any other factors , in addition to head restraint adjustment , could be found which would influence the severity of whiplash injury . This was done by linking medical assessment of real-world accident victims with engineering assessment of the accident vehicles . A r and om sample of road accident victims suffering from whiplash associated disorder was studied . The vehicles they had been travelling in were examined to assess impact severity and , where possible , measurements were made of seat and head restraint adjustment with the subject sitting in the vehicle . All subjects were interviewed to assess the disability result ing from their injuries , and their progress was followed for 12 months . The results were subjected to statistical analysis to try to determine relationships between severity of injury ( as measured by result ant disability ) and a number of occupant- and vehicle-related factors . A significant proportion of the sample had suffered lumbar strain injury in addition to whiplash , and these were excluded from the present analysis . Frontal impact victims suffered symptoms indistinguishable from those of rear impact victims . The beneficial effects of good head restraint adjustment could not be clearly demonstrated , and some trends , especially in rear impacts , where the benefits of a well-adjusted restraint should have been very clear , indicated that larger distances from head to restraint were associated with lower disability . The paper discusses these counter-intuitive results and their implication Background : Exposure to a whiplash injury implies a risk for development of chronic disability and h and icap , with reported frequencies ranging from 0 % to 50 % in follow-up studies . The exact risk for development of chronic whiplash syndrome is not known . Objective : To prospect ively determine the sensitivity and specificity of five possible predictors for h and icap following a whiplash injury . Methods : In a 1-year prospect i ve study of persons with acute whiplash injury ( n = 141 ) and control subjects who had acute ankle distortion ( n = 40 ) , pain intensity , number of nonpainful neurologic complaints , cervical mobility , workload during extension and flexion of the neck , and results of psychometric assessment were recorded . The consecutively sample d injured persons were assessed with structured and semistructured question naires , and underwent neurologic examination after 1 week and 1 , 3 , 6 , and 12 months . After 3 to 4 years , participants with whiplash injury were question ed about legal issues . Results : After 1 year , 11 ( 7.8 % ) persons with whiplash injury had not returned to usual level of activity or work . The best single estimator of h and icap was the cervical range-of-motion test , which had a sensitivity of 73 % and a specificity of 91 % ( p < 0.01 , Cox regression analysis ) . Accuracy and specificity increased to 94 % and 99 % when combined with pain intensity and other complaints . This increase was gained at the expense of a reduced sensitivity . Initiation of lawsuit within first month after injury did not influence recovery . Conclusion : The cervical range-of-motion test has a high sensitivity in prediction of h and icap after acute whiplash injury . The value of cervical range-of-motion test is further improved by additional recording of symptoms and pain intensity & NA ; Psychological distress is a feature of chronic whiplash‐associated disorders , but little is known of psychological changes from soon after injury to either recovery or symptom persistence . This study prospect ively measured psychological distress ( General Health Question naire 28 , GHQ‐28 ) , fear of movement/re‐injury ( TAMPA Scale of Kinesphobia , TSK ) , acute post‐traumatic stress ( Impact of Events Scale , IES ) and general health and well being ( Short Form 36 , SF‐36 ) in 76 whiplash subjects within 1 month of injury and then 2 , 3 and 6 months post‐injury . Subjects were classified at 6 months post‐injury using scores on the Neck Disability Index : recovered ( < 8 ) , mild pain and disability ( 10–28 ) or moderate/severe pain and disability ( > 30 ) . All whiplash groups demonstrated psychological distress ( GHQ‐28 , SF‐36 ) to some extent at 1 month post‐injury . Scores of the recovered group and those with persistent mild symptoms returned to levels regarded as normal by 2 months post‐injury , parallelling a decrease in reported pain and disability . Scores on both these tests remained above threshold levels in those with ongoing moderate/severe symptoms . The moderate/severe and mild groups showed elevated TSK scores at 1 month post‐injury . TSK scores decreased by 2 months in the group with residual mild symptoms and by 6 months in those with persistent moderate/severe symptoms . Elevated IES scores , indicative of a moderate post‐traumatic stress reaction , were unique to the group with moderate/severe symptoms . The results of this study demonstrated that all those experiencing whiplash injury display initial psychological distress that decreased in those whose symptoms subside . Whiplash participants who reported persistent moderate/severe symptoms at 6 months continue to be psychologically distressed and are also characterised by a moderate post‐traumatic stress reaction & NA ; Predictors of outcome following whiplash injury are limited to socio‐demographic and symptomatic factors , which are not readily amenable to secondary and tertiary intervention . This prospect i ve study investigated the predictive capacity of early measures of physical and psychological impairment on pain and disability 6 months following whiplash injury . Motor function ( ROM ; kinaesthetic sense ; activity of the superficial neck flexors ( EMG ) during cranio‐cervical flexion ) , quantitative sensory testing ( pressure , thermal pain thresholds , brachial plexus provocation test ) , sympathetic vasoconstrictor responses and psychological distress ( GHQ‐28 , TSK , IES ) were measured in 76 acute whiplash participants . The outcome measure was Neck Disability Index scores at 6 months . Stepwise regression analysis was used to predict the final NDI score . Logistic regression analyses predicted membership to one of the three groups based on final NDI scores ( < 8 recovered , 10–28 mild pain and disability , > 30 moderate/severe pain and disability ) . Higher initial NDI score ( 1.007–1.12 ) , older age ( 1.03–1.23 ) , cold hyperalgesia ( 1.05–1.58 ) , and acute post‐traumatic stress ( 1.03–1.2 ) predicted membership to the moderate/severe group . Additional variables associated with higher NDI scores at 6 months on stepwise regression analysis were : ROM loss and diminished sympathetic reactivity . Higher initial NDI score ( 1.03–1.28 ) , greater psychological distress ( GHQ‐28 ) ( 1.04–1.28 ) and decreased ROM ( 1.03–1.25 ) predicted subjects with persistent milder symptoms from those who fully recovered . These results demonstrate that both physical and psychological factors play a role in recovery or non‐recovery from whiplash injury . This may assist in the development of more relevant treatment methods for acute whiplash Abstract Higher initial levels of pain and disability , older age , cold hyperalgesia , impaired sympathetic vasoconstriction and moderate post‐traumatic stress symptoms have been shown to be associated with poor outcome 6 months following whiplash injury . This study prospect ively investigated the predictive capacity of these variables at a long‐term follow‐up . Sixty‐five of an initial cohort of 76 acutely injured whiplash participants were followed to 2–3 years post‐accident . Motor function ( ROM ; kinaesthetic sense ; activity of the superficial neck flexors ( EMG ) during cranio‐cervical flexion ) , quantitative sensory testing ( pressure , thermal pain thresholds and brachial plexus provocation test ) , sympathetic vasoconstrictor responses and psychological distress ( GHQ‐28 , TSK and IES ) were measured . The outcome measure was Neck Disability Index ( NDI ) scores . Participants with ongoing moderate/severe symptoms at 2–3 years continued to manifest decreased ROM , increased EMG during cranio‐cervical flexion , sensory hypersensitivity and elevated levels of psychological distress when compared to recovered participants and those with milder symptoms . The latter two groups showed only persistent deficits in cervical muscle recruitment patterns . Higher initial NDI scores ( OR 1.00–1.1 ) , older age ( OR 1.00–1.13 ) , cold hyperalgesia ( OR 1.1–1.13 ) and post‐traumatic stress symptoms ( OR 1.03–1.2 ) remained significant predictors of poor outcome at long‐term follow‐up ( r2 = 0.56 ) . The robustness of these physical and psychological factors suggests that their assessment in the acute stage following whiplash injury will be important STUDY DESIGN This study was used to evaluate the relationship between magnetic resonance imaging findings and clinical findings after whiplash injury . OBJECTIVES To identify initial soft-tissue damage after whiplash injury , the development of disc pathology , and the relationship of disc pathology to clinical findings . SUMMARY OF BACKGROUND DATA Although a few studies have reported pathological magnetic resonance imaging findings after whiplash injuries , there is no prospect i ve study published to our knowledge . METHODS Thirty-nine patients , 20 women and 19 men with a mean age of 32 years , were treated for whiplash injury . Magnetic resonance imaging and clinical examination were performed in a blinded manner at a mean of 11 days after trauma . The procedure was repeated at a 2-year follow-up visit . Two patients could not be examined with the second magnetic resonance imaging because of claustrophobia and pregnancy , respectively . RESULTS The authors found 13 patients ( 33 % ) with disc herniations with medullary ( six cases ) or dura ( seven cases ) impingement over the 2-year follow-up period . At the follow-up examination all patients with medullary impingement had persistent or increased symptoms , and three of 27 patients ( 11 % ) with no or slight changes on magnetic resonance imaging had persistent symptoms . No ligament injuries were diagnosed . CONCLUSION Although disc pathology seems to be one contributing factor in the development of chronic symptoms after whiplash injury , it may be unnecessary to examine these patients in the acute phase with magnetic resonance imaging ; correlating initial symptoms and signs to magnetic resonance imaging findings is difficult because of the relatively high proportion of false-positive results . Magnetic resonance imaging is indicated later in the course of treatment in patients with persistent arm pain , neurologic deficits or clinical signs of nerve root compression to diagnose disc herniations requiring surgery Summary Fifty consecutive patients with soft-tissue neck injuries following rear end collisions were studied prospect ively to assess their rate of recovery . Patients were seen within 5 days of the accident , after 3 months , 1 year and 2 years , and their symptoms were classified into one of four groups ( A , asymptomatic ; B , nuisance ; C , intrusive ; D , disabling ) . Fourteen of 15 patients ( 93 % ) who were asymptomatic after 3 months remained symptom-free after 2 years . Of 35 patients with symptoms after 3 months , 30 ( 86 % ) remained symptomatic after 2 years . After 1 year , 26 ( 52 % ) stated that they had recovered completely , but after 2 years this had fallen to 19 ( 38 % ) . Nine of the 15 patients who had improved between 3 months and 1 year deteriorated to their previous status , or worse , between 1 and 2 years . In asymptomatic cases , a prognosis that is 93 % accurate after 2 years can be given after 3 months , and 86 % of patients who are symptomatic after 3 months will remain so after 2 years . However , the severity of their symptoms will change during this period and will be at the same degree of severity in less than 50 % UNLABELLED Whiplash injury and chronic whiplash syndrome represent major health problems in certain western communities , pain being the main symptom . Sensitization of the nociceptive system may play a role for non-recovery after whiplash injury . AIMS This study examined if tolerance to endure pain stimuli may predict outcome in whiplash injury . In a prospect i ve fashion , 141 acute whiplash patients exposed to rear-end car collision ( WAD grade 1 - 3 ) and 40 ankle-injured controls were followed and exposed to a cold pressor test , respectively , 1 week , 1 , 3 , 6 and 12 months after the injury . VAS score of pain and discomfort was obtained before , during and after immersion of the dominant h and into cold water for 2 min . The McGill Pain Question naire showed that ankle-injured controls had higher initial pain scores than the corresponding whiplash group , while whiplash-injured subjects had higher scores at 6 months ; pain scores being similar at other time points . No difference was found in cold pressor pain between recovered whiplash patients and ankle-injured subjects . Non-recovery was only encountered in whiplash injury . Eleven non-recovered whiplash patients ( defined as : h and icap after 1 year ) showed reduced time to peak pain from 1 week to 3 months ( P<0.001 ) , 6 months ( P<0.01 ) , but not 12 months after the injury . A larger pain area was seen in non-recovered vs. recovered whiplash-injured subjects during the entire observation period ( P<0.001 ) . Non-recovery after whiplash was associated with initially reduced cold pressor pain endurance and increased peak pain , suggesting that dysfunction of central pain modulating control systems plays a role in chronic pain after acute whiplash injury Objective : To describe the coping process over time for patients with whiplash-associated disorders ( WAD ) . Design : The study was conducted by following patients prospect ively for 12 months . Setting s : The orthopaedic clinic at a university hospital . Subjects : Fifty-three patients out of 59 had complete data -sets . Main outcome measures : Two measures were used : the Pain Disability Index ( PDI ) and the Coping Strategies Question naire ( CSQ ) . Results : The results showed that the proportion of variance in disability shared with coping increased over time . Conclusion : The importance of coping as an explanatory factor for disability increased during the one year follow-up . Thus , coping has a crucial role for disability . The possibility of a positive long-term outcome could therefore be improved by teaching patients to use active and adaptive coping strategies shortly after an accident The relationship between psychosocial stress , cognitive performance and disability was assessed in 97 r and omly selected common whiplash patients . Patients were investigated early after injury ( mean 7.2 days , SD = 3.8 ) and again at 6 months . Assessment included different aspects of psychosocial stress , negative affectivity , personality traits and attentional functioning . At 6 months six patients ( 7 % ) showed partial or complete disability ( disabled group ) while 91 patients went back to work at pre-injury levels ( non-disabled group ) . However , 26 patients from the latter group at 6 months were still symptomatic . The disabled and non-disabled groups did not differ with respect to psychosocial stress , negative affectivity and personality traits as assessed at baseline . At 6 months no significant differences were found between the disabled group and 26 symptomatic patients from the non-disabled group with respect to any of the assessed factors . The disabled group showed a combination of the following variables as assessed at baseline : greater age , initial neck pain intensity , initial back pain , blurred vision , and anxiety but less dizziness , sensitivity to noise and neurotic or behavioural problems in childhood Objective To investigate the predictive capacity of the West Haven – Yale Multidimensional Pain Inventory ( MPI ) with regard to prolonged pain , using car occupants who had sustained a neck sprain in a traffic accident . Design A prospect i ve cohort study including a one-year follow-up . Patients One hundred thirty adults were examined by a specialized neck-injury team after a first visit to an accident and emergency department . The subjects answered the MPI question naire within one month of the accident . Outcome Measures One year later , the patients answered a question naire about residual neck pain . The main outcome was determined by the question , “ Do you have residual pain which you relate to the accident ? ” Results One hundred twenty-three ( 95 % ) of the subjects completed the study . Ninety-seven reported pain of some degree that they related to the accident . All but one of the MPI variables differed significantly between the group with residual pain and the group without pain . The variable interference had the strongest correlation with the outcome . Its discriminative capacity was 81 % for those with pain and 94 % for those without pain one year later . Conclusions The MPI may be used at an early stage to identify patients who may develop chronic neck-pain after a traffic accident , at least in those who want a follow-up session after an initial visit to an accident and emergency department Abstract Pain coping strategies are associated with pain severity , psychological distress and physical functioning in population s with persistent pain . However , there is little evidence regarding the relationship between coping styles and recovery from recent musculoskeletal injuries . We performed a large , population ‐based prospect i ve cohort study of traffic injuries to assess the relationship between pain coping strategies and recovery from whiplash injuries . Subjects were initially assessed within 6 weeks of the injury , with structured telephone interview follow‐up at 6 weeks , and 3 , 6 , 9 and 12 months post‐injury . Coping was measured at 6 weeks using the Pain Management Inventory and recovery was assessed at each subsequent follow‐up period , using a global self‐report question . Multivariable Cox proportional hazards models showed that early use of passive coping strategies was independently associated with slower recovery . Depressive symptomatology ( CES‐D ) was an effect modifier of this relationship . Without depressive symptomatology , those using high levels of passive coping recovered 37 % slower than those using low levels of passive coping ( HRR = 0.63 ; 95 % CI 0.44–0.91 ) . However , in the presence of depressive symptomatology , those using high levels of passive coping recovered 75 % more slowly than those who coped less passively ( HRR = 0.25 ; 95 % CI 0.17–0.39 ) . In other words , those with depressive symptoms but who used few passive coping strategies recovered four times more quickly than those with depressive symptoms who used high levels of passive coping . Active coping showed no independent association with recovery . These findings highlight the importance of early assessment of both coping behaviors and depressive symptomatology The present study was undertaken to evaluate if MRI within 2 days of a motor vehicle accident could reveal pathology of importance for underst and ing long-term disability after whiplash neck-sprain injuries . As part of a prospect i ve study cervical and cerebral MRI was performed on 40 neck sprain patients with whiplash injury after car accidents . The imaging was done within 2 days of the injury to make sure that any neck muscle bleeding , oedema or other soft tissue injuries could be detected . The MRI findings from the patients were both correlated to reported symptoms 6 months after the accident and compared to a control group of 20 volunteers . The MRI of both brain and neck revealed no significant differences between the patients and the control group . When the patients were grouped according to the main MRI findings at intake and compared according to the development of subjective symptoms reported by the patients , the only significant difference was more headaches at 6 months in the groups with disk pathology or spondylosis when compared to the group with no pathology . In conclusion , MRI within 2 days of the whiplash neck-sprain injury could not detect pathology connected to the injury nor predict symptom development and outcome It is widely accepted that psychosocial factors are related to illness behaviour and there is some evidence that they may influence the rate of recovery from post-traumatic disorders . The abilities of psychosocial stress , somatic symptoms , and subjectively assessed cognitive impairment to predict delayed recovery from common whiplash were investigated in a follow-up study . 78 consecutive patients referred 7.2 ( SD 4.5 ) days after they had sustained common whiplash in car accidents were assessed for psychosocial stress , negative affectivity , personality traits , somatic complaints , and cognitive impairment by semistructured interview and by several st and ardised tests . On examination 6 months later 57 patients were fully recovered and 21 had persisting symptoms . The groups ' scores for the independent variables assessed at the baseline examination were compared . Stepwise regression analysis showed that psychosocial factors , negative affectivity , and personality traits were not significant in predicting the outcome . However , initial neck pain intensity , injury-related cognitive impairment , and age were significant factors predicting illness behaviour . This study , which was based on a r and om sample and which considered many other possible predictive factors as well as psychosocial status , does not support previous findings that psychosocial factors predict illness behaviour in post-trauma patients This is a 1-year prospect i ve study to investigate the prognostic value of coping strategies such as catastrophising for persistent pain after a whiplash injury . A consecutive series of 96 patients who were seen in the emergency room in the acute phase after the injury were followed prospect ively for 1 year . Age , gender and whether or not pain in the neck preceded the accident was recorded . Cases involving fractures or dislocations of the cervical spine , head trauma or pre-existing neurological disorders were not included . The mean interval between the accident and the initial examination was 3+/-2(S.D. ) days . Coping was measured using the Coping Strategies Question naire ( CSQ ) . The outcome parameter was self-reported neck pain at 1 year after the motor vehicle accident . At 1 year , 34 % of the patients had neck pain . Women developed chronic neck pain more often than men ( 71 % versus 29 % ) ; they also had significantly higher coping activity , such as diverting attention , praying or hoping ( p<0.05 ) , catastrophising and increasing behavioural activities ( p<0.0001 ) . Women reported pain in the neck or shoulder more often before the accident and this was the only statistically significant predictor of chronic symptoms when analysed by logistic regression ( odds ratio 4.5 ) . To conclude , we found no evidence that the different coping patterns during the early phase after a whiplash injury influenced the prognosis Objective : To establish the aetiological influences of persistent neck pain following a motor vehicle collision and to construct a model for use in the emergency department for identifying patients at high risk of persistent symptoms . Design : Prospect i ve cohort study . Patients recruited from hospital emergency departments were sent a question naire to gather information on various exposures . They were followed up at 1 , 3 , and 12 months to identify those with persistent symptoms . Main outcome measure : Persistent neck pain ( pain at 1 , 3 , and 12 months after collision ) . Results : The baseline survey included 765 patients . Subsequently , 480 completed a question naire at each follow up time point , of whom 128 ( 27 % ) reported neck pain on each occasion . Few collision specific factors predicted persistent neck pain . In contrast , a high level of general psychological distress , pre-collision history of widespread body pain , type of vehicle , whiplash associated symptoms , and initial neck disability best predicted the persistence of symptoms . Furthermore , these factors , in combination , accounted for more than a fivefold increase in the risk of persistent neck pain . Conclusion : The greatest predictors of persistent neck pain following a motor vehicle collision relate to psychological distress and aspects of pre-collision health rather than to various attributes of the collision itself . With these factors , and those relating to initial injury severity , it is possible to identify a subgroup of patients presenting with neck pain with the highest risk of persistent symptoms . Thus , it is possible to identify whiplash patients with a poor prognosis and to provide closer follow up and specific attention to management in these individuals Objective : To prospect ively examine the course of pain and other neurologic complaints in patients with acute whiplash injury and in controls with acute ankle injury . Methods : Patients with acute whiplash ( n = 141 ) and ankle-injured controls ( n = 40 ) were consecutively sample d , and underwent interview and examination after 1 week and 1 , 3 , 6 , and 12 months . Outcome measures were pain intensity , pain frequency , and associated symptoms . Results : Initial overall pain intensity above lower extremities ( pain in neck , head , shoulder-arm , and low back ) was similar in patients with whiplash ( median Visual Analogue Scale [VAS]0–100 of 20 [ 25th and 75th percentile , 4 , 39 ] ) and ankle-injured controls ( median VAS0–100 of 15 [ 5 , 34 ] ) . Whiplash-injured patients reported median overall VAS0–100 pain intensity above lower extremities of 23 ( 12 , 40 ) after 11 days and 14 ( 12 , 40 ) after 1 year . Controls reported pain intensity of 0 ( 0 , 4 ) after 12 days and 0 ( 0 , 9 ) after 1 year . Reported overall pain frequency above lower extremities was 96 % after 11 days and 74 % after 1 year in whiplash-injured patients and 33 % after 12 days and 47 % after 1 year in controls . Associated neurologic symptoms were two to three times more common after whiplash injury . Correlation was found between pain intensity and associated symptoms in whiplash-injured patients but not controls . Conclusion : Pain occurs with high frequency but low intensity after whiplash and ankle injury . Associated neurologic symptoms were not correlated to pain in ankle-injured controls , but were correlated to pain in patients with whiplash injury . Persistent symptoms in whiplash-injured patients may be caused by both specific neck injury – related factors and nonspecific post-traumatic reactions . Disability was only encountered in the whiplash group Study Design . Population -based , incidence cohort . Objectives . To evaluate a government policy of funding community and hospital-based fitness training and multidisciplinary rehabilitation for whiplash . Summary of Background Data . Although insurance benefits commonly include rehabilitation for whiplash , its effectiveness is unknown . Methods . All Saskatchewan adults treated for whiplash ( n = 6,021 ) over a 2-year period were followed up at 6 weeks , 3 , 6 , 9 , and 12 months . Recovery was defined by self-report of improvement . Recovery times were compared between those attending fitness training at health clubs ( n = 833 ) , multidisciplinary outpatient rehabilitation ( n = 468 ) , and multidisciplinary inpatient rehabilitation ( n = 135 ) to those receiving usual insured individual care . Results . Recovery was 32 % slower in those receiving fitness training within 69 days of injury ( P = 0.001 ) and 19 % slower when received within 119 days of injury ( P = 0.041 ) . Recovery was 50 % slower in those receiving outpatient rehabilitation within 119 days of injury ( P = 0.001 ) . Attending inpatient rehabilitation did not influence recovery rates during the follow up ( P = 0.131 ) . Multivariable adjustment for important prognostic factors did not change these results . Conclusions . We found no evidence to support the effectiveness of a population -based program of fitness training and multidisciplinary rehabilitation for whiplash . Rehabilitation programs should be tested in r and omized trials before being recommended to injured population Introduction – In a prospect i ve study 29 patients fulfilled the criteria of Whiplash‐Associated Disorders grade III in the Quebec classification . Material and methods – One month postinjury , computerized neuropsychological tests , a clinical interview and the symptom checklist SCL‐90‐R were administered . Three whiplash scales were extrapolated from SCL‐90‐R : pain , subjective cognitive difficulties and sleep disorders . SCL‐90‐R was repeated 6 months later . Results – One month after the accident , 85 % of the patients had resumed work . Subjective cognitive disturbances , however , were frequent but unrelated to test performances , which were within the normal range . Patients reporting stressful life events unrelated to the injury had more symptoms and elevated levels of distress on all SCL‐90‐R syndrome scales . At follow‐up their distress was unchanged , and subjective cognitive function had deteriorated . Conclusion – Stressful life events unrelated to the accident and a high level of distress 1 month postinjury may augment the risk of “ late whiplash syndrome ” . Re assessment 3–6 weeks postinjury as recommended by the Quebec Task Force should include assessment of complicating social factors and a psychological symptom checklist & NA ; The objective of our prospect i ve inception cohort study was to identify prognostic factors for poor recovery in patients with whiplash‐associated disorders grade 1 or 2 who still had neck pain and accompanying complaints 2 weeks after the accident . The study was carried out in a primary health care setting in The Netherl and s and included 125 patients . The primary outcome measure was functional recovery defined in terms of neck pain intensity or work disability without medication use . The secondary outcome measures included neck pain intensity , work disability and sick leave . The outcomes were assessed at 4 , 12 and 52 weeks after the accident . Prognostic factors were identified by logistic regression analyses . One year after the injury , 64 % of the patients were recovered . Factors related to poor recovery were female gender , a low level of education , high initial neck pain , more severe disability , higher levels of somatisation and sleep difficulties . Neck pain intensity and work disability proved to be the most consistent predictors for poor recovery . The accuracy of the predictions of the prognostic models was high , meaning that the models adequately distinguished patients with poor recovery from those regarded as recovered . These findings add to the growing body of evidence , indicating that socio‐demographic , physical and psychological factors affect short‐ and long‐term outcome after whiplash injury . Our findings also indicate that care providers can easily identify patients at risk for poor recovery with a visual analogue scale for initial pain intensity and work‐related activities OBJECTIVES In Lithuania , there is little awareness of the notion that chronic symptoms may result from rear end collisions via the so-called whiplash injury . After most such collisions no contact with the health service is established . An opportunity therefore exists to study post-traumatic pain without the confounding factors present in western societies . METHODS In a prospect i ve , controlled inception cohort study , 210 victims of a rear end collision were consecutively identified from the daily records of the Kaunas traffic police . Neck pain and headache were evaluated by mailed question naires shortly after the accident , after 2 months , and after 1 year . As controls , 210 sex and age matched subjects were r and omly taken from the population register of the same geographical area and evaluated for the same symptoms immediately after their identification and after 1 year . RESULTS Initial pain was reported by 47 % of accident victims ; 10 % had neck pain alone , 18 % had neck pain together with headache , and 19 % had headache alone . The median duration of the initial neck pain was 3 days and maximal duration 17 days . The median duration of headache was 4.5 hours and the maximum duration was 20 days . After 1 year , there were no significant differences between the accident victims and the control group concerning frequency and intensity of these symptoms . CONCLUSIONS In a country were there is no preconceived notion of chronic pain arising from rear end collisions , and thus no fear of long term disability , and usually no involvement of the therapeutic community , insurance companies , or litigation , symptoms after an acute whiplash injury are self limiting , brief , and do not seem to evolve to the so-called late whiplash syndrome & NA ; This study evaluated the course of psychological variables during a 2‐year follow‐up in patients after common whiplash of the cervical spine . From a sample of 117 non‐selected patients with common whiplash ( investigated on average 7.2 ± 4.2 days after trauma ) a total of 21 suffered trauma‐related symptoms over 2 years following initial injury . These patients ( symptomatic group ) were compared with 21 age , gender and education pair‐matched patients , who showed complete recovery from trauma‐related symptoms during the 2‐year follow‐up ( asymptomatic group ) . Both groups underwent st and ardised testing procedures ( i.e. , Freiburg Personality Inventory and Well‐Being Scale ) at referal , and at 3 , 6 and 24 months . In the symptomatic group during follow‐up no significant changes in ratings of neck pain or headache were found . Significant differences between the groups and significant deviation of scores over time were found on the Well‐Being and Nervousness Scales . There was a lack of significant difference between the groups on the Depression Scale , indicating a possible somatic basis for changes in psychological functioning in the investigated sample . With regard to scales of Extraversion or Neuroticism , there were neither significant differences between the groups nor significant deviation over time . These results highlight that patients ' psychological problems are rather a consequence than a cause ; of somatic symptoms in whiplash Objective : To compare two different home exercise programmes for patients with acute whiplash-associated disorders ( WAD ) . A further aim was to describe the initial prognostic variables related to self-reported pain at six months follow-up . Design : A r and omized treatment study with a follow-up period of six months . Setting s : The study was undertaken in an orthopaedic clinic at a university hospital . Subjects : A total of 59 symptomatic ( neck pain , stiffness , etc . ) patients with acute whiplash injury . Interventions : Patients were r and omized to a regular treatment group ( RT group ) and an additional-exercise treatment group ( AT group ) . Main outcome measures : Pain Disability Index ( PDI ) , Self-Efficacy Scale ( SES ) , Coping Strategies Question naire ( CSQ ) , neck range of motion ( ROM ) , head posture , kinaesthetic sensibility , visual analogue scale ( VAS ) . Results : Patients given an additional exercise did not improve more than patients with regular treatment . Only one CSQ item , ‘ Ability to decrease pain ' , showed a significant difference between the groups in its pattern of change over time : the AT group had a significant increase between three and six months whilst values in the RT group decreased . Nonsymptomatic patients at six months follow-up were characterized by initially better self-efficacy , lower disability and significantly different patterns in the use of ‘ behavioural coping strategies ' when compared with symptomatic patients . The nonsymptomatic patients also reported more frequent training than symptomatic patients , i.e. they complied better with the treatment regime . Conclusion : This home exercise programme , including training of neck and shoulder ROM , relaxation and general advice seems to be sufficient treatment for acute WAD patients when used on a daily basis . Additionally , patients reporting low self-efficacy and high disability levels may profit from more attention initially , as these psychological factors are significant predictors of pain at long-term follow-up BACKGROUND Shoulder pain is common in primary health care . Nevertheless , information on the outcome of shoulder disorders is scarce , especially for patients encountered in general practice . AIM To study the course of shoulder disorders in general practice and to determine prognostic indicators of outcome . METHOD For this prospect i ve follow-up study , 11 Dutch general practitioners recruited 349 patients with new episodes of shoulder pain . The participants filled out a question naire at presentation and further ones after 1 , 3 , 6 and 12 months ; these contained questions on the nature , severity and course of the shoulder complaints . The association between potential prognostic indicators and the status of shoulder complaints ( absence or presence of symptoms ) was evaluated after one and 12 months of follow-up . RESULTS After one month , 23 % of all patients showed complete recovery ; this figure increased to 59 % after one year . A speedy recovery seemed to be related to preceding overuse or slight trauma and early presentation . A high risk of persistent or recurrent complaints was found for patients with concomitant neck pain and severe pain during the day at presentation . CONCLUSION A considerable number of patients ( 41 % ) showed persistent symptoms after 12 months . It may be possible to distinguish patients who will show a speedy recovery from those with a high risk of long-st and ing complaints by determining whether there is a history of slight trauma or overuse , an early presentation or an absence of concomitant neck pain A r and om sample of 98 patients with common whiplash was examined early after trauma ( mean + /- SD , 7.3 + /- 3.9 days ) and again 6 months later . Cognitive functioning was assessed in conjunction with complaints , pain intensity , well-being , subjective cognitive impairment , neuroticism , and medication . At 6 months , 67 patients had fully recovered ( asymptomatic group ) , while 31 were still symptomatic ( symptomatic group ) . Symptomatic patients who were older at baseline , had a greater variety of symptoms , higher neck pain intensity , and greater subjective cognitive impairment . At baseline , both groups scored poorly on tests requiring complex attentional processing . All neuropsychological functions improved to normal at 6 months in both groups . This improvement can not be explained by a practice effect , as shown by the results of normal volunteers . The symptomatic group showed delayed recovery regarding complex attentional functioning , which may be related to adverse effects of medication Whiplash injuries were studied prospect ively in 151 patients . Patterns of injury and recovery were found not to depend on the type of accident . Clinical and radiological findings were correlated with the possible pathological bases for the symptoms and signs ; some of these were found to be unlikely to be contributors to the clinical picture . The factors which might contribute to a delay in recovery were review ed , and compensation cl aims were found not to affect outcome significantly . It is suggested that many patients have sustained an important injury , the exact nature of which remains unclear Psychological factors have been alleged to be important in the course and outcome of ' whiplash ' neck injury but there is little quantitative evidence . This study uses quantitative methods involving a prospect i ve interview assessment to describe psychological and quality of life predictors , and 3 and 12 month outcome . Consecutive attenders to the Accident and Emergency department of a teaching district hospital with a clinical diagnosis of ' whiplash ' neck injury were included and there were follow-up interviews at home . Neck symptoms were recorded , and there was a st and ard mental-state interview with added questions about post-traumatic symptoms and a semi-structured interview for disability and consequences for quality of life . There was a wide individual variation in course and outcome ; the majority of subjects complained of persistent neck symptoms and a sizeable minority reported specific post-traumatic psychological symptoms ( intrusive memory , phobic travel anxiety ) , similar to those described by patients suffering multiple injuries . Social impairment , including effects on travel , were considerable in one-quarter . Reports of persistent neck symptoms were not associated with any baseline psychological variables or with compensation proceedings ; psychological factors appeared to be more important in determining the extent of social impairment . We conclude that travel , social and psychological morbidity is substantially greater than previously recognized Study Design . A prospect i ve study of 135 patients with whiplash injury . Objectives . To identify factors predictive of prolonged disability following whiplash injury . Summary of Background Data . Although patients with whiplash associated disorders lack demonstrable physical injury , many exhibit prolonged disability . Disability appears unrelated to the severity of the collision . Methods . A total of 147 patients with recent whiplash injury were interviewed for putative risk factors for disability , and 135 were reinterviewed 12 months later to assess degree and duration of disability . Bivariate and multivariate analyses were undertaken to measure the association between putative risk factors and measures of outcome ( change in Neck Pain Outcome Score [ NPOS ] and visual analogue pain score [ VAPS ] , return to work , still requiring treatment , settlement of cl aim ) . Results . The bodily pain score and role emotional scores of the Short Form-36 health question naire showed a consistent significant positive association with better outcomes . After adjustment for bodily pain score and role emotional scores , consulting a lawyer was associated with less improvement in NPOS ( P < 0.05 ) , but there was no association with change in VAPS . Consulting a lawyer was associated with a lesser chance of cl aim settlement ( P < 0.01 ) and a greater chance of still having treatment ( P < 0.01 ) after 1 year , but there was no significant association with a return to work . The degree of damage to the vehicle was not a predictor of outcome . Conclusions . Short Form-36 scores for bodily pain and role emotional are useful means of identifying patients at risk of prolonged disability . The findings support the implementation of an insurance system design ed to minimize litigation |
899 | 28,470,696 | TSA of long-term all-cause mortality , long-term cardiovascular mortality , and long-term non-fatal myocardial infa rct ion showed that more RCTs are needed to reach more conclusive results on these outcomes .
Regarding long-term repeat revascularisation more RCTs may not change our present result .
TSA also supports the need for more RCTs in order to draw stronger conclusions regarding the effects of complete revascularisation on long-term all-cause mortality , long-term cardiovascular mortality , and long-term non-fatal myocardial infa rct ion | BACKGROUND Multi-vessel coronary disease in people with ST elevation myocardial infa rct ion ( STEMI ) is common and is associated with worse prognosis after STEMI .
Based on limited evidence , international guidelines recommend intervention on only the culprit vessel during STEMI .
This , in turn , leaves other significantly stenosed coronary arteries for medical therapy or revascularisation based on inducible ischaemia on provocative testing .
Newer data suggest that intervention on both the culprit and non-culprit stenotic coronary arteries ( complete intervention ) may yield better results compared with culprit-only intervention .
OBJECTIVES To assess the effects of early complete revascularisation compared with culprit vessel only intervention strategy in people with STEMI and multi-vessel coronary disease . | BACKGROUND Recent r and omized trials and meta-analyses demonstrated that a complete revascularization of significant non culprit lesions in patients with ST elevation myocardial infa rct ion ( STEMI ) is superior to a culprit only revascularization approach in reducing major adverse cardiac events ( MACE ) , however the proportion of diabetic patients was low in these trials . OBJECTIVES To investigate whether a complete revascularization approach is associated with better outcomes in diabetic patients with STEMI and multi-vessel disease . METHODS One hundred diabetic patients with acute STEMI with at least one non-culprit lesion were r and omized to either complete revascularization ( n = 50 ) or culprit-only treatment ( n = 50 ) . Complete revascularization was performed either at the time of primary percutaneous coronary intervention ( PCI ) or within 72 hours during hospitalization . The primary endpoint was the composite of all-cause mortality , recurrent MI , and ischemia-driven revascularization at 6 months . RESULTS A complete revascularization approach was significantly associated with a reduction in the primary outcome ( 6 % vs. 24 % , P = 0.01 ) , primarily due to reduction in ischemia driven revascularization in the complete revascularization group ( 2 % vs. 12 % ; P = 0.047 ) . There was no significant reduction in death or MI ( 2 % vs. 8 % ; P = 0.17 ) and ( 2 % vs. 4 % ; P = 0.56 ) respectively , or in the safety endpoints of major or minor bleeding , contrast-induced nephropathy , or stroke between the groups . CONCLUSIONS In diabetic patients with multi-vessel coronary artery disease undergoing PPCI , complete revascularization is associated with significantly reduced risk of adverse cardiovascular events , as compared with culprit vessel only PCI . ( J Interven Cardiol 2016;29:241 - 247 ) Background There are conflicting data regarding optimal treatment of non-culprit lesions detected during primary percutaneous coronary intervention ( PCI ) in patients with ST-elevation myocardial infa rct ion ( STEMI ) and multi-vessel disease ( MVD ) . We aim ed to investigate whether ischaemia-driven early invasive treatment improves the long-term outcome and prevents major adverse cardiac events ( MACE ) . Methods 121 patients with at least one non-culprit lesion were r and omised in a 2:1 manner , 80 were r and omised to early fractional flow reserve (FFR)-guided PCI ( invasive group ) , and 41 to medical treatment ( conservative group ) . The primary endpoint was MACE at 3 years . Results Three-year follow-up was available in 119 patients ( 98.3 % ) . There was no significant difference in all-cause mortality between the invasive and conservative strategy , 4 patients ( 3.4 % ) died , all in the invasive group ( P = 0.29 ) . Re-infa rct ion occurred in 14 patients ( 11.8 % ) in the invasive group versus none in the conservative group ( p = 0.002 ) . Re-PCI was performed in 7 patients ( 8.9 % ) in the invasive group and in 13 patients ( 32.5 % ) in the conservative group ( P = 0.001 ) . There was no difference in MACE between these two strategies ( 35.4 vs 35.0 % , p = 0.96 ) . Conclusions In STEMI patients with MVD , early FFR-guided additional revascularisation of the non-culprit lesion did not reduce MACE at three-year follow-up compared with a more conservative strategy . The rate of MACE in the invasive group was predominantly driven by death and re-infa rct ion , whereas in the conservative group the rate of MACE was only driven by repeat interventions Results of recent studies have suggested that routine cardiac catheterization may be unnecessary after reperfusion therapy for acute myocardial infa rct ion . Therefore to better define the short-term prognostic value of early coronary angiography , and specifically the prognostic significance of multivessel coronary artery disease , the angiographic findings of 855 patients consecutively enrolled in five phases of the TAMI study were correlated with their in-hospital outcome . All patients received intravenous thrombolytic therapy ( tissue plasminogen activator , urokinase , or both agents ) and underwent cardiac catheterization within 90 minutes of the initiation of therapy . Multivessel disease , defined as the presence of greater than or equal to 75 % luminal diameter stenosis in two or more major epicardial arteries , was documented in 236 patients . When compared with the group of patients without multivessel disease , this group had a higher prevalence of coronary risk factors and more frequently had a history of antecedent ischemic chest pain . Although the severity of the infa rct zone dysfunction was similar in the two groups ( -2.77 + /- 1.00 vs -2.50 + /- 1.09 SD/chord , p = NS ) , global left ventricular ejection fraction was lower in the group with multivessel disease ( 48.6 + /- 12.4 % vs 51.8 + /- 10.6 % , p less than 0.01 ) . This was associated with a significant difference in the function of the noninfa rct zone . Whereas this region was hyperkinetic in the group with minimal or single-vessel disease , it was hypocontractile or dyskinetic in those with multivessel disease ( + 0.66 + /- 1.53 vs -0.52 + /- 1.73 SD/chord , p = 0.0001 ) . ( ABSTRACT TRUNCATED AT 250 WORDS Background : In the Preventive Angioplasty in Myocardial Infa rct ion trial ( PRAMI ; IS RCT N73028481 ) , immediate multivessel PCI ( MV-PCI ) of non-IRA ( infa rct related artery ) lesions in patients with acute ST elevation myocardial infa rct ion ( STEMI ) and multivessel coronary disease ( MVD ) improved long term prognosis . We assessed infa rct distribution and size in a pre-specified cardiac magnetic resonance ( CMR ) sub- study . Methods : In this single centre prospect i ve sub- study , PRAMI participants were invited to undergo 1.5 Tesla CMR 1 week and 1 year after primary PCI . The CMR scans were analysed using semi-automated software by a clinician blinded to treatment group assignment and clinical outcomes . The presence and extent of infa rct ion were assessed quantitatively with late gadolinium enhancement ( LGE ) imaging ( Gadovist , 0.1 mmol/kg ) . The infa rct was delineated as an area of myocardial enhancement ( cm2 ) using a signal intensity threshold of > 5SDs above a remote region , and expressed as a % of total LV mass . The incidence of new LGE in non-infa rct related artery territories at baseline and 1 year were assessed . Data were analysed by an independent statistician . Results : Of 465 r and omised trial participants in 6 UK hospitals , 138 ( 30 % ) were enrolled in Glasgow . Of these 80 patients underwent CMR 1 week post primary PCI of whom 41 ( 51 % ) were in the multi-vessel PCI group and 39 ( 49 % ) were in the IRA-only group . At 1 year , 69 ( 86 % ) patients had a follow up CMR scan . Infa rct size and distribution are described in Table 1 BACKGROUND In patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infa rct ion , ischemic postconditioning has been shown to reduce infa rct size , but the effect on clinical outcome has not been tested in a large r and omized trial . In addition , deferring stent implantation in the infa rct -related lesion 1 to 3 days after acute opening of the infa rct -related artery could have protective effects , by reducing the risk of injury caused by distal embolization and microvascular obstruction . Finally , a considerable fraction of patients present with lesions in other coronary artery branches than the infa rct -related artery . Whether a strategy of complete or partial revascularization of these patients should be preferred remains uncertain . STUDY DESIGN The DANAMI 3 trial program was design ed to investigate 3 different r and omized treatment strategies in patients with ST-segment elevation myocardial infa rct ion : ( 1 ) ischemic postconditioning versus conventional treatment with a primary end point of death and hospitalization for heart failure ; ( 2 ) deferring stent implantation in the infa rct -related lesion versus conventional treatment with a primary end point of death , hospitalization for heart failure , reinfa rct ion , and repeat revascularization ; and ( 3 ) treatment of the culprit lesion only versus fractional flow reserve-guided complete revascularization in patients with multivessel disease , with a primary end point of death , reinfa rct ion , and repeat revascularization . SUMMARY The DANAMI 3 trial program will determine whether either of 2 approaches to reduce reperfusion injury and distal microvascular obstruction with postconditioning or deferred stent implantation will translate into improved clinical outcome and whether patients with multivessel disease undergoing primary percutaneous coronary intervention will benefit from a strategy of complete or partial revascularization Background Few reports described outcomes of complete compared with infa rct -related artery (IRA)-only revascularisation in patients with ST-elevation myocardial infa rct ion ( STEMI ) and multivessel coronary artery disease ( CAD ) . Moreover , no studies have compared the simultaneous treatment of non-IRA with the IRA treatment followed by an elective procedure for the other lesions ( staged revascularisation ) . Methods The outcomes of 214 consecutive patients with STEMI and multivessel CAD undergoing primary angioplasty were studied . Before the first angioplasty patients were r and omly assigned to three different strategies : culprit vessel angioplasty-only ( COR group ) ; staged revascularisation ( SR group ) and simultaneous treatment of non-IRA ( CR group ) . Results During a mean follow-up of 2.5 years , 42 ( 50.0 % ) patients in the COR group experienced at least one major adverse cardiac event ( MACE ) , 13 ( 20.0 % ) in the SR group and 15 ( 23.1 % ) in the CR group , p<0.001 . Inhospital death , repeat revascularisation and re-hospitalisation occurred more frequently in the COR group ( all p<0.05 ) , whereas there was no significant difference in re-infa rct ion among the three groups . Survival free of MACE was significantly reduced in the COR group but was similar in the CR and SR groups . Conclusions Culprit vessel-only angioplasty was associated with the highest rate of long-term MACE compared with multivessel treatment . Patients scheduled for staged revascularisation experienced a similar rate of MACE to patients undergoing complete simultaneous treatment of non-IRA AIMS To examine the incidence of and propensity for non-culprit interventions performed at the time of the primary percutaneous coronary intervention ( PCI ) and its association with 90-day outcomes . METHODS AND RESULTS We examined the incidence , propensity for , and associated 90-day outcomes following non-culprit interventions performed at the time of primary PCI among ST-elevation myocardial infa rct ion patients with multi-vessel coronary artery disease ( MVD ) . Of the 5373 patients who underwent primary PCI in the APEX-AMI trial , 2201 had MVD . Of those , 217 ( 9.9 % ) underwent non-infa rct -related arteries ( IRA ) PCI , whereas 1984 ( 90.1 % ) underwent PCI of the IRA alone . Ninety-day death and death/CHF/shock were higher in the non-IRA group compared with the IRA-only PCI group ( 12.5 vs. 5.6 % , P ( log-rank ) < 0.001 and 17.4 vs. 12.0 % , P ( log-rank ) = 0.020 , respectively ) . After adjusting for patient and procedural characteristics as well as propensity for performing non-IRA PCI , this procedure remained independently associated with an increased hazard of 90-day mortality [ adjusted hazard ratio 2.44 , 95 % CI ( 1.55 - 3.83 ) , P < 0.001 ] . CONCLUSION Non-culprit coronary interventions were performed at the time of primary PCI in 10 % of MVD patients and were significantly associated with increased mortality . Our data support current guideline recommendations discouraging the performance of such procedures in stable primary PCI patients . Prospect i ve r and omized study of this issue may be warranted BACKGROUND Rapid recanalization of infa rct -related artery ( IRA ) has become the major target during primary percutaneous coronary intervention ( PCI ) for patients with ST-elevation myocardial infa rct ion ( MI ) , but strategy for treatment of non-IRA lesions in this setting remains unclear . This study aim ed to compare long-term effects between PCI for IRA only and that for both IRA and non-IRA in ST-elevation MI patients with multi-vessel disease . METHODS A total of 242 eligible patients with ST-elevation MI and at least two diseased coronary arteries ( luminal narrowing > or = 70 % ) undergoing primary PCI were included . Of them , 149 patients underwent primary PCI for IRA only ( group 1 ) , and 93 received primary PCI for IRA followed by elective PCI for non-IRA 7 to 15 days after acute myocardial infa rct ion ( AMI ) ( group 2 ) . Drug-eluting stents ( DESs ) were deployed in more than 90 % of the patients . RESULTS The two groups did not differ with respect to baseline clinical and angiographic characteristics . No significant differences were observed in 12-month clinical follow-up results regarding major adverse cardiac events ( 11.5 % vs 15.1 % , P > 0.05 ) and target lesion revascularization ( 8.1 % vs 7.6 % , P > 0.05 ) between the two groups . However , patients in group 1 had higher rates of recurrent angina ( 10.1 % vs 2.1 % , P < 0.05 ) and depressed left ventricular ejection fraction evaluated by echocardiography ( 0.56 + /- 0.22 vs 0.63 + /- 0.25 , P < 0.05 ) . CONCLUSION With the use of DESs , complete revascularization with elective PCI for non-IRA after primary PCI may exert a beneficial effect on long-term symptomatology and left ventricular function in patients with ST-elevation MI and multi-vessel disease BACKGROUND The purpose of this study was to compare the safety , efficacy , and costs of complete versus " culprit " vessel revascularization in multivessel coronary artery disease treated with percutaneous coronary interventions ( PCI ) . METHODS Patients with multivessel disease and an identified culprit vessel were r and omly assigned to complete revascularization of vessels > or = 50 % stenoses ( n = 108 ) versus revascularization limited to the culprit vessel ( n = 111 ) . The primary end point , major adverse cardiac events ( MACE ) , were defined as cardiac or noncardiac death , myocardial infa rct ion , need for coronary artery bypass graft surgery , and repeat PCI up to 1 year . RESULTS Despite equal MACE at 24 hours ( 6.3 % vs 7.4 % ) , strategy success was higher in the culprit vessel than in the complete revascularization group ( 93.7 % vs 81.5 % , P = .007 ) . MACE rates at 1 month ( 14.4 % vs 9.3 % ) , 1 year ( 32.4 % vs 26.9 % ) , and 4.6 + /- 1.2 years ( 40.4 % vs 34.6 % ) were similar in both groups . Repeat PCI was performed more often in the culprit vessel group ( 31.2 % vs 21.2 % , P = .06 ) . A lower consumption of medical material was associated with lower procedural costs in the culprit vessel group ( 5784 vs 7315 Euros ; P < .001 ) . However , between 1 year and the end of follow-up , costs had equalized in both groups . CONCLUSIONS Complete versus culprit vessel revascularization in multivessel coronary disease treated with PCI was associated with a lower strategy success rate , similar MACE rates , and initially higher costs . However , over the long term , more repeat PCIs were conducted in patients treated by culprit revascularization only , mostly because of the need to treat lesions initially left untreated . As a consequence , incremental costs had equalized within 1 year . The decision of whether to perform culprit vessel or complete revascularization can be made on an individual basis OBJECTIVES We sought to develop a simple risk score for predicting mortality after primary percutaneous coronary intervention ( PCI ) for acute myocardial infa rct ion ( AMI ) . BACKGROUND Accurate risk stratification after primary PCI is important . Previous risk scores after reperfusion therapy have incorporated clinical + /- angiographic variables but have not considered baseline left ventricular function . Moreover , prior studies have not been vali date d against independent data bases or studies . METHODS The data bases from the two largest multicenter , r and omized AMI trials of primary PCI were utilized for score derivation ( the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications [ CADILLAC ] trial , n = 2,082 ) and subsequent validation ( the Stent- Primary Angioplasty in Myocardial Infa rct ion [ Stent-PAMI ] trial , n = 900 ) . Logistic regression and the jackknife procedure were used to select correlates of one-year mortality that were subsequently weighted and integrated into an integer scoring system . RESULTS Seven variables selected from the initial multivariate model were weighted proportionally to their respective odds ratio for one-year mortality ( age > 65 years [ 2 points ] , Killip class 2/3 [ 3 points ] , baseline left ventricular ejection fraction < 40 % [ 4 points ] , anemia [ 2 points ] , renal insufficiency [ 3 points ] , triple-vessel disease [ 2 points ] , and post-procedural Thrombolysis In Myocardial Infa rct ion flow grade [ 2 points ] ) . Three strata of risk were defined ( low risk , score 0 to 2 ; intermediate risk , score 3 to 5 ; and high risk , score > /=6 ) with excellent prognostic accuracy for survival in the derivation and validation sets ( c statistics = 0.83 and 0.81 for 30-day mortality and 0.79 and 0.78 for 1-year mortality , respectively ) . CONCLUSIONS In AMI patients treated with primary PCI , seven risk factors readily available at the time of intervention accurately predict short- and long-term mortality . Of note , measurement of baseline left ventricular function is the single most powerful predictor of survival and should be incorporated into risk score models BACKGROUND Patients with acute ST-segment elevation myocardial infa rct ion ( STEMI ) and multivessel coronary disease have a worse prognosis compared with individuals with single-vessel disease . We aim ed to study the clinical outcome of patients with STEMI treated with fractional flow reserve (FFR)-guided complete revascularisation versus treatment of the infa rct -related artery only . METHODS We undertook an open-label , r and omised controlled trial at two university hospitals in Denmark . Patients presenting with STEMI who had one or more clinical ly significant coronary stenosis in addition to the lesion in the infa rct -related artery were included . After successful percutaneous coronary intervention ( PCI ) of the infa rct -related artery , patients were r and omly allocated ( in a 1:1 ratio ) either no further invasive treatment or complete FFR-guided revascularisation before discharge . R and omisation was done electronically via a web-based system in permuted blocks of varying size by the clinician who did the primary PCI . All patients received best medical treatment . The primary endpoint was a composite of all-cause mortality , non-fatal reinfa rct ion , and ischaemia-driven revascularization of lesions in non-infa rct -related arteries and was assessed when the last enrolled patient had been followed up for 1 year . Analysis was on an intention-to-treat basis . This trial is registered with Clinical Trials.gov , number NCT01960933 . FINDINGS From March , 2011 , to February , 2014 , we enrolled 627 patients to the trial ; 313 were allocated no further invasive treatment after primary PCI of the infa rct -related artery only and 314 were assigned complete revascularization guided by FFR values . Median follow-up was 27 months ( range 12–44 months ) . Events comprising the primary endpoint were recorded in 68 ( 22 % ) patients who had PCI of the infa rct -related artery only and in 40 ( 13 % ) patients who had complete revascularisation ( hazard ratio 0∙56 , 95 % CI 0∙38–0∙83 ; p=0∙004 ) . INTERPRETATION In patients with STEMI and multivessel disease , complete revascularisation guided by FFR measurements significantly reduces the risk of future events compared with no further invasive intervention after primary PCI . This effect is driven by significantly fewer repeat revascularisations , because all-cause mortality and non-fatal reinfa rct ion did not differ between groups . Thus , to avoid repeat revascularisation , patients can safely have all their lesions treated during the index admission . Future studies should clarify whether complete revascularization should be done acutely during the index procedure or at later time and whether it has an effect on hard endpoints . FUNDING Danish Agency for Science , Technology and Innovation and Danish Council for Strategic Research OBJECTIVE The ability to accurately identify articles about therapy in large bibliographic data bases such as EMBASE is important for research ers and clinicians . Our study aim ed to develop optimal search strategies for detecting sound treatment studies in EMBASE in the year 2000 . METHODS H and search es of journals were compared with retrievals from EMBASE for c and i date search strategies . Six trained research assistants review ed fifty-five journals indexed in EMBASE and rated articles using purpose and quality indicators . C and i date search strategies were developed for identifying treatment articles and then tested , and the retrievals were compared with the h and - search data . The operating characteristics of the strategies were calculated . RESULTS Three thous and eight hundred fifty articles were original studies on treatment , of which 1,256 ( 32.6 % ) were method ologically sound . Combining search terms revealed a top performing strategy ( r and om:.tw . OR clinical trial:.mp . OR exp health care quality ) with sensitivity of 98.9 % and specificity of 72.0 % . Maximizing specificity , a top performing strategy ( double-blind:.mp . OR placebo:.tw . OR blind : .tw . ) achieved a value over 96.0 % , but with compromised sensitivity at 51.7 % . A 3-term strategy achieved the best optimization of sensitivity and specificity ( r and om:.tw . OR placebo:.mp . OR double-blind:.tw . ) , with both these values over 92.0 % . CONCLUSION Search strategies can achieve high performance for retrieving sound treatment studies in EMBASE AIMS The aim of this study was to evaluate whether a staged in-hospital complete revascularisation strategy increases the risk of serious bleeding events in patients with ST-segment elevation myocardial infa rct ion ( STEMI ) and multivessel disease . METHODS AND RESULTS The DANAMI-3-PRIMULTI trial investigated whether a staged in-hospital complete revascularisation strategy improved outcome in patients with STEMI and multivessel disease . In this sub study , we investigated potential bleeding complications related to a second in-hospital procedure . Bleedings were assessed using BARC and TIMI criteria . Six hundred and twenty-seven ( 627 ) patients were r and omised 1:1 to either PCI of the infa rct -related artery ( IRA ) only ( n=313 ) or complete revascularisation during a staged procedure before discharge ( n=314 ) . We found no significant difference in TIMI major+minor bleedings related to the primary PCI . There were neither major nor minor bleedings in relation to the second procedure in the complete revascularisation arm . There were significantly more in-hospital minimal+medical attention bleedings in the group r and omised to complete revascularisation ( 61.5 % vs. 49.5 % in the IRA-PCI only group , p=0.003 ) , but no difference in admission time or one-year mortality ( 2.2 % complete revascularisation-group vs. 2.6 % IRA-PCI only group , p=0.8 ) . CONCLUSIONS In multivessel diseased STEMI patients , a staged complete in-hospital revascularisation strategy or any second in-hospital procedure did not result in an increase in serious bleeding events BACKGROUND In acute ST-segment elevation myocardial infa rct ion ( STEMI ) , the use of percutaneous coronary intervention ( PCI ) to treat the artery responsible for the infa rct ( infa rct , or culprit , artery ) improves prognosis . The value of PCI in noninfa rct coronary arteries with major stenoses ( preventive PCI ) is unknown . METHODS From 2008 through 2013 , at five centers in the United Kingdom , we enrolled 465 patients with acute STEMI ( including 3 patients with left bundle-branch block ) who were undergoing infa rct -artery PCI and r and omly assigned them to either preventive PCI ( 234 patients ) or no preventive PCI ( 231 patients ) . Subsequent PCI for angina was recommended only for refractory angina with objective evidence of ischemia . The primary outcome was a composite of death from cardiac causes , nonfatal myocardial infa rct ion , or refractory angina . An intention-to-treat analysis was used . RESULTS By January 2013 , the results were considered conclusive by the data and safety monitoring committee , which recommended that the trial be stopped early . During a mean follow-up of 23 months , the primary outcome occurred in 21 patients assigned to preventive PCI and in 53 patients assigned to no preventive PCI ( infa rct -artery-only PCI ) , which translated into rates of 9 events per 100 patients and 23 per 100 , respectively ( hazard ratio in the preventive-PCI group , 0.35 ; 95 % confidence interval [ CI ] , 0.21 to 0.58 ; P<0.001 ) . Hazard ratios for the three components of the primary outcome were 0.34 ( 95 % CI , 0.11 to 1.08 ) for death from cardiac causes , 0.32 ( 95 % CI , 0.13 to 0.75 ) for nonfatal myocardial infa rct ion , and 0.35 ( 95 % CI , 0.18 to 0.69 ) for refractory angina . CONCLUSIONS In patients with STEMI and multivessel coronary artery disease undergoing infa rct -artery PCI , preventive PCI in noninfa rct coronary arteries with major stenoses significantly reduced the risk of adverse cardiovascular events , as compared with PCI limited to the infa rct artery . ( Funded by Barts and the London Charity ; PRAMI Current Controlled Trials number , IS RCT N73028481 . ) Background Recanalization of the culprit lesion is the main goal of primary angioplasty for acute ST-segment elevation myocardial infa rct ion ( STEMI ) . Patients presenting with acute myocardial infa rct ion and multivessel disease are , therefore , usually subjected to staged procedures , with the primary percutaneous coronary intervention ( PCI ) confined to recanalization of the infa rct -related artery ( IRA ) . Theoretically at least , early relief of stenoses of non-infa rct related arteries could promote collateral circulation , which could help to limit the infa rct size . However , the safety and feasibility of such an approach has not been adequately established . Methods In this single-center prospect i ve study we examined 73 consecutive patients who had an acute STEMI and at least one or more lesions ≥ 70 % in a major epicardial vessel other than the infa rct related artery . In the first 28 patients , forming the multi-vessel ( MV ) PCI group , all lesions were treated during the primary procedure . In the following 45 patients , forming the culprit-only ( CO ) PCI group , only the culprit lesion was treated during the initial procedure , followed by either planned-staged or ischemiadriven revascularization of the non-culprit lesions . Fluoroscopy time and contrast dye amount were compared between both groups , and patients were followed up for one year for major adverse cardiac events ( MACE ) and other significant clinical events . Results The two groups were well balanced in terms of clinical characteristics , number of diseased vessels and angiographic characteristics of the culprit lesion . In the MV-PCI group , 2.51 lesions per patient were treated using 2.96 ± 1.34 stents ( 1.00 lesions and 1.76 ± 1.17 stents in the CO-PCI group , both p < 0.001 ) . The fluoroscopy time increased from 10.3 ( 7.2–16.9 ) min in the CO-PCI group to 12.5 ( 8.5–19.3 ) min in the MV-PCI group ( p = 0.22 ) , and the amount of contrast used from 200 ( 180–250 ) ml to 250 ( 200–300 ) ml , respectively ( p = 0.16 ) . Peak CK and CK-MB were significantly lower in patients of the MV-PCI group ( 843 ± 845 and 135 ± 125 vs 1652 ± 1550 and 207 ± 155 U/l , p < 0.001 and 0.01 , respectively ) . Similar rates of major adverse cardiac events at one year were observed in the two groups ( 24 % and 28 % in multi-vessel and culprit treatment groups , p = 0.73 ) . The incidence of new revascularization in both infa rct - and noninfa rct -related arteries was also similar ( 24 % and 28 % , respectively , p = 0.73 ) . Conclusion We may state from this limited experience that a multi-vessel stenting approach for patients with acute STEMI and multi-vessel disease is feasible and probably safe during routine clinical practice . Our data suggest that this approach may help to limit the infa rct size . However , larger studies , perhaps using drug-eluting stents , are still needed to further evaluate the safety and efficiency of this procedure , and whether it is associated with a lower need of subsequent revascularization and lower costs Background In the R and omized Trial of Preventive Angioplasty in Myocardial Infa rct ion ( PRAMI ; IS RCT N73028481 ) , compared with infa rct -related artery (IRA)-only PCI , additional immediate multivessel PCI ( MV-PCI ) of nonIRA lesions in patients with acute ST elevation myocardial infa rct ion ( STEMI ) and multivessel coronary disease ( MVD ) improved long term prognosis . We studied left ventricular ( LV ) outcomes in a pre-specified cardiac magnetic resonance ( CMR ) sub- study AIMS Primary percutaneous coronary intervention ( PPCI ) is the preferred strategy for acute ST-segment elevation myocardial infa rct ion ( STEMI ) , with evidence of improved clinical outcomes compared to fibrinolytic therapy . However , there is no consensus on how best to manage multivessel coronary disease detected at the time of PPCI , with little robust data on best management of angiographically significant stenoses detected in non-infa rct -related ( N-IRA ) coronary arteries . CVLPRIT will determine the optimal management of N-IRA lesions detected during PPCI . METHODS AND RESULTS CVLPRIT ( Complete Versus culprit-Lesion only PRimary PCI Trial ) is an open-label , prospect i ve , r and omised , multicentre trial . STEMI patients undergo verbal " assent " on presentation . Patients are included when angiographic MVD has been detected , and r and omised to culprit (IRA)-only PCI ( n=150 ) or in-patient complete multivessel PCI ( n=150 ) . Cumulative major adverse cardiac events ( MACE ) - all-cause mortality , recurrent MI , heart failure , need for revascularisation ( PCI or CABG ) will be recorded at 12 months . Secondary endpoints include safety endpoints of confirmed ischaemic stroke , intracranial haemorrhage , major non-intracranial bleeding , and repair of vascular complications . A cardiac magnetic resonance ( CMR ) sub study will provide mechanistic data on infa rct size , myocardial salvage index and microvascular obstruction . A cost efficacy analysis will be undertaken . CONCLUSIONS The management of multivessel coronary artery disease in the setting of PPCI for STEMI , including the timing of when to perform non-culprit-artery revascularisation if undertaken , remains unresolved . CVLPRIT will yield mechanistic insights into the myocardial consequence of N-IRA intervention undertaken during the peri-infa rct period DESIGN : Prospect i ve r and omized , multicentre study . RATIONALE : Recanalisation of the culprit lesion is the main goal of primary angioplasty for acute myocardial infa rct ion . With the exception of cardiogenic shock , staged procedures are performed in the presence of multivessel disease . The study hypothesis is that with modern non-thrombogenic stents ( heparin coated ) complete revascularization with multivessel treatment can be safely achieved during the primary angioplasty procedure with a lower need of subsequent revascularization procedures and at a lower cost . ENDPOINTS : PRIMARY : 12-month incidence of repeat revascularization ( any revascularization , infa rct related artery as well as non-infa rct -related artery ) . SECONDARY : ( 1 ) in hospital repeat revascularization , reinfa rct ion and death ; ( 2 ) total hospital cost ( including a 12 months follow-up period ) . METHODS : 69 patients with ST elevation Acute Myocardial Infa rct ion ( AMI ) , < 12 hours after symptoms onset , undergoing primary angioplasty , with documented multivessel disease and both culprit lesion and 1 to 3 other lesions suitable for stent implantation . Unbalanced r and omization between culprit lesion treatment only ( n = 17 ) and complete multivessel treatment ( n = 52 , with 71 additional lesions treated ) . RESULTS : The two groups were well balanced in terms of clinical characteristics , number of diseased vessels and angiographic characteristics of the culprit lesion . In the complete multivessel treatment group 2.36 ± 0.64 lesions per patient were treated using 2.73 ± 0.78 heparin coated stents ( 1.00 lesions and 1.29 ± 0.61 stents in the culprit treatment group , bothp < 0.001 ) . The duration of the procedure increased from 53 ± 21 min ( culprit treatment group ) to 69 ± 32 min ( p = 0.032 ) and the amount of contrast used from 242 ± 102 ml ( culprit treatment group ) to 341 ± 163 ml ( multivessel complete treatment),p = 0.025 . A similar low incidence of in-hospital major adverse cardiac events was observed in the 2 groups ( 0 and 3.8 % in culprit and multivessel treatment groups , p = 0.164 ) . The increase in the incidence of new revascularisation in the culprit treatment group at 12 month follow-up was not significant ( 35 vs 17%,p = 0.247 ) but was sufficient to compensate the initial higher in-hospital cost , with a similar 12 month hospital cost in the 2 groups ( € 22 330 ± € 13 653 vs € 20 382 ± € 11 671,p = 0.231 ) . CONCLUSION : Multivessel treatment during primary PTCA was safe in this controlled trial . However , when only the culprit lesion was initially treated , the need for subsequent clinical ly driven revascularization remained low and no clinical or economical advantages were obtainable with a more aggressive initial approach . In clinical practice , a staged approach to multivessel treatment during primary angioplasty avoids to treat unnecessarily non clinical ly relevant lesions . ( Int J Cardiovasc Intervent 2004 ; 6 : 128 - 133 OBJECTIVE To investigate the effect and medical cost of different revascularization strategies for acute myocardial infa rct ion ( AMI ) patients with multi-vessel disease ( MVD ) . METHODS A prospect i ve r and omized controlled trial ( RCT ) was conducted . From January 2009 to June 2012 , patients with AMI and MVD undergoing primary percutaneous coronary intervention ( PCI ) were enrolled . They were r and omly assigned to group A [ staged PCI for non-infa rct ion related artery ( non-IRA ) within 7 - 10 days after AMI ] and group B ( subsequent PCI for non-IRA recommended only for those with evidence of ischemia ) . All of patients were given optimized medical therapy according to clinical guideline , and they were followed up for 24 months at regular intervals . Major adverse cardiovascular events ( MACE ) including recurrence of myocardial infa rct ion and death due to cardiac ailments were recorded . Meanwhile , re-hospitalization from cardiac causes , recurrence of angina , heart failure , and re-PCI , number of stents , total hospital stay days , and total medical expenditure were recorded . RESULTS A total of 428 patients accomplished the 24-month follow up . All the patients underwent PCI for non-IRA in group A ( 215 patients ) , while 62 patients in group B ( 213 patients ) undergone PCI for myocardial ischemia , and 51 patients received non-IRA treatment . There was no significant difference in MACE incidence between group A and group B [ 8.4 % ( 18/215 ) vs. 10.8 % ( 23/213 ) , χ² = 0.727 , P = 0.394 ] . The difference of death rate due to cardiac causes ( 5.1 % vs. 6.6 % ) , recurrence of myocardial infa rct ion ( 4.2 % vs. 6.6 % ) , and heart failure ( 4.2 % vs. 7.0 % ) were not significantly different between groups A and B ( all P > 0.05 ) . The rate of recurrence of angina ( 14.4 % vs. 32.9 % ) , re-hospitalization from cardiac causes ( 14.4 % vs. 33.8 % ) , and re-treatment of implanting stents ( 12.6 % vs. 29.1 % ) were significantly lower in group A than group B ( all P < 0.01 ) , and the rate of revascularization was significantly higher in group A than group B ( 10.7 % vs. 5.2 % , P < 0.05 ) . The total number of stents ( 610 vs. 366 ) , mean number of stents per patient ( 2.83 ± 0.91 vs. 1.72 ± 0.91 , t = 12.725 , P = 0.000 ) , and total cost per patient ( kRMB : 63.7 ± 12.6 vs. 51.5 ± 1 2.3 , t = 10.107 , P = 0.000 ) in group A were significantly higher than those in group B. Total hospital stay days in group A was significantly less than group B ( days : 8.21 ± 2.45 vs. 9.89 ± .23 , t = 6.071 , P = 0.000 ) . Because non-IRA-vascular reconstruction rate was low in group B , the rate of using β-blocker and anti-anginal agents during the 24-month follow up in group B was significantly higher than group A [ 59.2 % ( 126/213 ) vs. 47.0 % ( 101/215 ) , χ² = 6.371 , P = 0.012 ; 56.3 % ( 112/213 ) vs. 17.6 % ( 36/215 ) , χ² = 64.704 , P = 0.000 ] . CONCLUSIONS In patients with AMI and MVD undergone emergency PCI , staged PCI within 7 - 10 days for non-IRA can not decrease the incidence of myocardial infa rct ion and death due to cardiac causes , recurrence of angina and rehospitalization for cardiac causes was diminished , and it may increase the number of stents and medical cost significantly Background The optimal management of patients found to have multivessel disease while undergoing primary percutaneous coronary intervention ( P-PCI ) for ST-segment elevation myocardial infa rct ion is uncertain . Objectives CvLPRIT ( Complete versus Lesion-only Primary PCI trial ) is a U.K. open-label r and omized study comparing complete revascularization at index admission with treatment of the infa rct -related artery ( IRA ) only . Methods After they provided verbal assent and underwent coronary angiography , 296 patients in 7 U.K. centers were r and omized through an interactive voice-response program to either in-hospital complete revascularization ( n = 150 ) or IRA-only revascularization ( n = 146 ) . Complete revascularization was performed either at the time of P-PCI or before hospital discharge . R and omization was stratified by infa rct location ( anterior/nonanterior ) and symptom onset ( ≤3 h or > 3 h ) . The primary endpoint was a composite of all-cause death , recurrent myocardial infa rct ion ( MI ) , heart failure , and ischemia-driven revascularization within 12 months . Results Patient groups were well matched for baseline clinical characteristics . The primary endpoint occurred in 10.0 % of the complete revascularization group versus 21.2 % in the IRA-only revascularization group ( hazard ratio : 0.45 ; 95 % confidence interval : 0.24 to 0.84 ; p = 0.009 ) . A trend toward benefit was seen early after complete revascularization ( p = 0.055 at 30 days ) . Although there was no significant reduction in death or MI , a nonsignificant reduction in all primary endpoint components was seen . There was no reduction in ischemic burden on myocardial perfusion scintigraphy or in the safety endpoints of major bleeding , contrast-induced nephropathy , or stroke between the groups . Conclusions In patients presenting for P-PCI with multivessel disease , index admission complete revascularization significantly lowered the rate of the composite primary endpoint at 12 months compared with treating only the IRA . In such patients , inpatient total revascularization may be considered , but larger clinical trials are required to confirm this result and specifically address whether this strategy is associated with improved survival . ( Complete Versus Lesion-only Primary PCI Pilot Study [ CvLPRIT ] ; IS RCT N70913605 Recent r and omized trials and meta-analyses demonstrated that a complete revascularization of significant non culprit lesions in patients with ST elevation myocardial infa rct ion ( STEMI ) is superior to a culprit only revascularization approach in reducing major adverse cardiac events ( MACE ) , |
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